BASIC AND TRANSLATIONAL MEDICINE
BASIC RESEARCH OF CARDIOVASCULAR DISEASE
GW35-e0016
Xiumeng Hua
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Anthracyclines are chemotherapeutic drugs used for solid tumors and hematologic malignancies. Overall, the effects of tumor inhibition are satisfactory. However, the life-threatening cardiotoxicity, which involves cardiac dilation and heart failure, is a weakness, but the exact mechanism is unknown.
METHODS Using a combination of in vivo (4 weekly injections of doxorubicin 10 mg · kg−1) in C57/BL6J mice for single cell/nucleus RNA sequencing and in vitro approaches (cardiomyocyte cells: H9c2/HL-1 cells and human induced pluripotent stem cell-derived cardiomyocytes, non-cardiomyocyte cells such as NIH3T3, RCF, HUVEC, and Raw246.7, and cancer cell lines such as MCF-7 and HeLa cells) for insights into mechanism. Genetic depletion and pharmacological blocking peptide on Picalm were performed to evaluate the role of PICALM on doxorubicin-induced cardiotoxicity in vivo. Human heart tissue samples were applied for verification.
RESULTS End-stage heart failure patients with chemotherapy-induced cardiotoxicity showed a thinner cell membrane compared to healthy controls. By using the doxorubicin-induced cardiotoxicity mice model, it is possible to replicate the corresponding phenotype of patients. Cellular changes in doxorubicin-induced cardiotoxicity in mice were identified, especially in cardiomyocytes, using single cell/nucleus RNA sequencing. Picalm expression was upregulated only in cardiomyocytes associated with doxorubicin-induced cardiotoxicity. Amyloid β-peptide production was also increased after doxorubicin treatment, which led to a higher increase in membrane permeability of cardiomyocytes. Genetic depletion and pharmacological blocking peptides on Picalm reduced the generation of amyloid β-peptide, which alleviated the doxorubicin-induced cardiotoxicity in vitro and in vivo, respectively. In human heart tissue samples of patients with chemotherapy-induced cardiotoxicity, PICALM and amyloid β-peptide were elevated as well.
CONCLUSIONS Our study demonstrated a comprehensive cellular change in doxorubicin-induced cardiotoxicity, mainly in cardiomyocytes. Picalm was identified as a hallmark gene responsible for the generation of amyloid β-peptide in cardiomyocytes of both human patients and mice models. Preventing cardiotoxicity from anthracycline-induced generation of amyloid β-peptide could be achieved by inhibiting PICALM.
GW35-e0026
Mingrui Ma1,2, Yingqian Zhang2, Yundai Chen2
1Medical School of Chinese PLA, No. 28 Fuxing Road, Beijing 100853, China
2The Senior Department of Cardiology, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
OBJECTIVES Atherosclerosis is the primary pathophysiological process responsible for cardiovascular disease (CVD). However, the gold standard method for revealing plaque composition and staging is pathology, which includes the limitations such as prolonged staining and fluorescence quenching. Hence, we aim to quantitatively characterize atherosclerotic plaque utilizing two novel imaging techniques called two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) imaging, which features label-free analysis, high signal-to-noise ratio, and high resolution.
METHODS This study included rabbits that were fed a high-fat diet (HFD) for 0, 4, 6, and 12 weeks. The sections of their carotid were imaged by TPEF/SHG and Masson staining sequentially. The consistency between TPEF/SHG images and pathological images in reflecting atherosclerotic plaque characteristics was assessed by the simple linear regression. Additionally, the fluorescence density and gray-level co-occurrence matrix (GLCM) texture feature parameters were separately utilized to quantify the changes in fiber content and arrangement of atherosclerotic lesions with their progression.
RESULTS The TPEF/SHG could clearly visualized the foam cells, collagen and elastic fibers, internal and external elastic membranes (IEM, EEM), and neovascularization within carotid atherosclerosis lesions at different stages. Furthermore, the TPEF/SHG imaging exhibited a high consistency with the pathological sections staining. The simple linear regression demonstrated a significant agreement between the TPEF/SHG image and the pathological image in reflecting plaque area, foam cell ratio, intima/media ratio, and other characteristics as the lesions progressed (R2 = 0.9770, 0.9913, 0.9798, respectively; P < 0.0001). The content ratio of elastic fibers to collagen fibers within the intima (32.64 ± 14.69, 215.20 ± 149.90, 74.56 ± 32.97, respectively), media (31.58 ± 9.18, 42.89 ± 13.00, 159.40 ± 52.84, 99.14 ± 22.94, respectively) and adventitia (0.1136 ± 0.0230, 0.2653 ± 0.0400, 4.959 ± 2.5850, 1.596 ± 0.7769, respectively) also showed an initial increase followed by a subsequent decrease. Furthermore, the texture attributes revealed that as the lesions advanced, there was an escalation in the unevenness of fiber arrangement within the plaque (correlation: 0.8322 ± 0.01731, 0.8607 ± 0.01920, 0.9260 ± 0.02028, respectively). Additionally, the unevenness of the media (contrast: 0.0003571 ± 0.001092, 0.0004429 ± 0.0001902, 0.04040 ± 0.01328, 0.009114 ± 0.007033) initially increased and subsequently decreased.
CONCLUSIONS The TPEF/SHG imaging technique has the capability to unveil the characteristics of atherosclerotic lesions at different stages in progression rapidly and label-freely, showing high consistent with pathology. Additionally, it enables the quantitative analysis of the structure and fiber components associated with the plaque progression, which constitutes a complement to histopathology.
GW35-e0035
Wang Danning
The Fifth Affiliated Hospital of Sun Yat-sen University
OBJECTIVES Exosomes (exo) play an important role in intercellular signal transduction, substance transport and possess regulatory function by carrying bioactive substances. Bone marrow mesenchymal stem cells (BMSCs) exert powerful ability to secrete exosomes. The current research aimed to investigate the function of BMSCs-produced-exo miR-140-3p on cardiomyocyte apoptosis induced by ischemia/reperfusion (I/R) injury and to explore the underlying mechanism.
METHODS Exosomes were isolated from culture medium by ultracentrifugation and identified through transmission electron and Western blot. MiR-140-3p and apoptosis-related gene expression was detected by qRT-PCR and Western blot, respectively. The interaction between miR-140-3p and MKK6 was confirmed by dual luciferase activity assay and RNA binding protein immunoprecipitation (RIP) assay. Cell viability was measured by LDH release assay and CCK-8 assay. Cell apoptosis was detected using Annexin-V/PI stain and caspase-3 activity kit. Myocardial ischemia was established by neonatal rat cardiomyocytes (NRCM) cells hypoxia/reoxygenation (H/R) model and mice ischemia/reperfusion (I/R) model.
RESULTS Isolated BMSCs-exo exerted protective functions in cardiomyocytes I/R injury both in vivo and in vitro. BMSCs-exo contained a higher level of miR-140-3p than BMSCs, and miR-140-3p was decreased after I/R injury, indicating that miR-140-3p might play a beneficial role in this process. Furthermore, miR-140-3p directly targeting MMK6 and down-regulated the MMK6 expression, inactivated the p38MAPK signaling pathway, so as to protected cardiomyocytes from cell apoptosis induced by I/R injury. This protective effect could be partial attenuated by overexpression of MKK6.
CONCLUSIONS BMSCs-exo transferred miR-140-3p into damaged cardiomyocytes, attenuating excessive apoptosis by targeting MKK6, which highlighted the potential of BMSCs-exo-miR-140-3p as a new biotherapy for I/R injury in the future.
GW35-e0037
Guangwei Huang
Kunming Yan’an Hospital
OBJECTIVES S100A4 plays a pivotal role in myocardial ischemia-reperfusion injury (MIRI), shaping the interplay between autophagy and inflammation, yet the precise mechanisms by which S100A4 impacts these processes remain elusive.
METHODS In a mouse model, ischemia-reperfusion (I/R) was induced, followed by 2-day reperfusion period post 2 hours of ischemia. S100A4 was silenced using short hairpin RNA (shRNA) in the I/R+S100A4-shRNA group. Diagnostic evaluations, including electrocardiograms, cardiac function and enzyme analyses, and 2,3,5-triphenyl tetrazolium chloride (TTC) staining, assessed myocardial injury. Hematoxylin-eosin (HE) and Immunohistochemistry staining examined IL-1 and TNF-a expression, cardiomyocyte morphology. Protein blotting analyzed autophagy-related proteins and Bnip3 signaling.
RESULTS An ischemia-reperfusion (I/R) model was established in mice. The optimal timing for inducing reperfusion injury was determined, and mice were divided into sham and experimental groups. The experimental group underwent 2 hours of ischemia/reperfusion injury followed by a 2-day reperfusion period. In the I/R+S100A4-shRNA group, S100A4 silencing was achieved through the injection of short hairpin RNA (shRNA). Myocardial ischemia was induced by occluding the left anterior descending branch (LAD) of the coronary artery. Diagnostic procedures, including electrocardiogram assessments, cardiac function testing, cardiac enzyme analyses, and 2,3,5-triphenyl tetrazolium chloride (TTC) staining, were performed to assess myocardial injury. Immunohistochemistry, immunofluorescence staining, hematoxylin-eosin (HE) staining, and Masson trichrome staining were used to evaluate the expression levels of IL-1, TNF-a, morphological changes in cardiomyocytes, and cardiac fibrosis. Protein blotting was conducted to examine autophagy-related proteins and Bnip3 signaling-related proteins.
CONCLUSIONS S100A4-shRNA reduces the activity of the BNIP3 autophagy pathway, thereby reducing inflammation, improving the severity of MIRI, and promoting improvement in cardiac function.
GW35-e0038
Guangwei Huang
Kunming Yan’an Hospital
OBJECTIVES Progressive cardiac fibrosis, culminating in ventricular wall stiffening and impaired cardiac function, is a hallmark of heart failure. Despite its widespread expression in various tissues, including the heart, the specific role of PCSK9 in cardiac fibrosis remains unclear. This study aims to unravel the potential involvement and underlying mechanisms of PCSK9 in the pathogenesis of cardiac fibrosis.
METHODS PCSK9 inhibitors were used to determine the role of PCSK9 in cardiac fibrosis in rats following I/R surgery. Subsequently, a series of analyses, including immunohistochemistry, immunofluorescence, TTC staining, Western blot, and cardiac ultrasound, were conducted to explore the potential mechanisms of PCSK9-induced activation of the TGF-β1/Smad3 pathway and inflammatory response.
RESULTS The study revealed elevated levels of PCSK9, TGF-β1, and Smad3 in cardiac tissues of rats undergoing fibrosis post-reperfusion injury. Treatment with a PCSK9 inhibitor resulted in a reduction in the expression of pro-fibrotic proteins in response to TGF-β1 stimulation, protecting the heart and alleviating the damage and subsequent fibrosis induced by I/R. Additionally, PCSK9 inhibition improved I/R-induced cardiac inflammation. Finally, the addition of a PCSK9 inhibitor resulted in a reduction in the infarct size post-myocardial infarction, improving cardiac function, and contributing to the slowing of the progression of heart failure.
CONCLUSIONS PCSK9 inhibitors significantly inhibit I/R-induced activation of the TGF-β1/Smad3 pathway, inflammation, and injury in the heart. Consequently, this leads to a reduced infarct size, delayed fibrosis, and improved cardiac function, providing a novel therapeutic strategy for myocardial fibrosis after ischemia-reperfusion injury.
GW35-e0041
Chen Mingxian, Zhou Shenghua
The Second Xiangya Hospital of Central South University
OBJECTIVES Subarachnoid hemorrhage (SAH) is one of the causes of sudden cardiac death (SCD). However, the time course of ventricular arrhythmias and potential mechanisms responsible for this effect after SAH remain unknown. This study aims to investigate the effect of SAH on ventricular electrophysiological changes and its potential mechanisms in long-term phase.
METHODS We examined the ventricular electrophysiological remodeling and potential mechanisms in a Sprague Dawley rat model of SAH at six time points (baseline, and Days 1, 3, 7, 14 and 28) and explored the potential mechanisms. We measured the ventricular effective refractory period (ERP), ventricular fibrillation threshold (VFT) and left stellate ganglion (LSG) activity at different time points before and after SAH. We also detected neuropeptide Y (NPY) levels in plasma and myocardial tissues by enzyme-linked immunosorbent assay, and quantified NPY 1 receptor (NPY1R) protein and mRNA expression levels by western blotting and quantitative real-time reverse transcription-polymerase chain reaction, respectively.
RESULTS Subarachnoid hemorrhage gradually prolonged QTc intervals, shortened ventricular ERP and reduced VFT during the acute phase, peaking at Day 3. However, no significant changes were observed from Days 14 to 28 compared to Day 0. Subarachnoid hemorrhage gradually increased LSG activity, increased NPY concentrations and up-regulated NPY1R expression in the acute phase of SAH, peaking at Day 3. However, no significant variations were found from Days 14 to 28 compared to Day 0.
CONCLUSIONS Subarachnoid hemorrhage increases the transient susceptibility of VAs in the acute phase, and the underlying mechanisms for this response included increased sympathetic activity and up-regulated NPY1R expression.
GW35-e0048
Chunyan Li1,2, Shangqi Yin1
1Beijing Jishuitan Hospital, Capital Medical University, Xicheng District, Beijing 100035, China
2Department of Laboratory Medicine, Peking University Fourth School of Clinical Medicine, Beijing Jishuitan Hospital, Xicheng District, Beijing 100035, China
OBJECTIVES Left ventricular noncompaction (LVNC) is a congenital cardiomyopathy characterized by hypertrabeculation of the left ventricle. Some studies have shown that apoptosis of cardiomyocytes leads to impaired development and densification, resulting in LVNC formation. The applicant’s previous results showed that CARF protein was specifically down-regulated in myocardial tissue of LVNC disease, and the pathway specifically enriched in LVNC was the p53 apoptosis pathway, and CARF was enriched in the p53 apoptosis pathway.
METHODS Comparative proteomic analysis by iTRAQ-2DLC-MS/MS was used to screen differentially expressed proteins in heart samples obtained from heart transplantation patients diagnosed with LVNC, ARVC, and HCM in comparison to normal heart samples. Decreasing expressed CARF in heart samples from LVNC was further confirmed by Western blot. Immunofluorescence, western blots were used to study the effects of knock out CARF on the structure and function of HL1 cardiomyocytes. Functional and morphological changes were observed by TUNEL staining in cardiomyocytes whose left ventricle knock out CARF.
RESULTS In our study, CARF protein is specifically down-regulated in myocardial tissue of LVNC disease. The pathway specifically enriched in LVNC is the p53 apoptosis pathway, and CARF is enriched in the p53 apoptosis pathway. We hypothesized that CARF interacts with p53 to influence apoptotic pathway activity resulting in LVNC. In view of the localization and function of CARF in the heart, we hypothesized that knock out the CARF might be involved in the apoptosis pathway and participated in the molecular mechanism of LVNC.
CONCLUSIONS Myocardial CARF phosphorylation participate in the apoptosis pathway which result in cardiomyocytes apoptosis. Our findings suggest that decreased myocardial CARF might be involved in the molecular mechanism of LVNC. CARF participates in the occurrence and development of LVNC by mediating the p53 pathway, so as to develop new therapeutic targets for LVNC.
GW35-e0053
Yuwu Chen1,2, Biyi Xu1,2, Haibo Jia1,2
1The 2nd Affiliated Hospital of Harbin Medical University
2The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin
OBJECTIVES Patients with diabetes mellitus (DM) frequently experience comorbidities such as heart failure and renal failure. Renal failure leads to elevated levels of blood parathyroid hormone (PTH). Rats with Type 2 diabetes mellitus exhibit elevated levels of blood parathyroid hormone compared to healthy rats. The Calcium sensing receptor (CaSR), a member of the superfamily of G protein-coupled receptors (GPCRs), is implicated in various cellular biology processes. Recent research has linked CaSR to several cardiovascular conditions, such as myocardial ischemia-reperfusion injury, heart failure, and vascular calcification. It has been reported that parathyroid hormone has deleterious effects on cardiomyocytes via increasing intracellular and extracellular calcium levels. Cardiomyocytes in diabetic rats demonstrate heightened expression of CaSR. The objective of this study is to investigate the impact of parathyroid hormone (PTH) on the expression of calcium-sensitive receptors and myocardial injury in diabetic rats, as well as to further elucidate its potential underlying mechanism.
METHODS The study involved treating cells with various concentrations of parathyroid hormone (PTH) for 24 hours, with phosphate-buffered saline (PBS) used as a control. Reverse transcription-polymerase chain reaction (RT-PCR) was utilized to assess the expression of the calcium-sensing receptor (CaSR). Additionally, cells were treated with both PTH and a CaSR antagonist, as well as with the antagonist alone. RT-PCR was employed to quantify CaSR expression, while Western blot analysis was conducted to measure the levels of CaSR, JNK, P38, ERK, and P53 proteins. Intracellular calcium levels were examined by using a confocal laser scanning microscope, and cell viability was assessed by using a CCK8 kit.
RESULTS The PTH treatment group exhibited a higher cell mortality rate compared to the control group in a concentration-dependent manner (P < 0.05). Additionally, the mRNA and protein expression levels of CaSR were significantly higher in the PTH treatment group than in the control group (P < 0.001). There were no significant differences in the expression levels of P38 and ERK between the PTH treatment and control groups; However, the PTH treatment group showed higher expression levels of JNK, P53, p-P53, and intracellular calcium concentration compared to the control group (P < 0.05). These effects could be attenuated by the administration of a CaSR antagonist (P < 0.05).
CONCLUSIONS PTH induce apoptosis in cardiomyocytes via increasing the expression of the CaSR. This process is linked to the activation of the JNK-P53 signaling pathway, rather than the ERK and P38 pathways, and exacerbates intracellular calcium accumulation.
GW35-e0061
Dingqian Liu
Zhongshan Hospital, Fudan University
OBJECTIVES Aortic dissection (AD) is one of the more common and most complex and dangerous cardiovascular diseases. Previous studies have reported that mortality and complications remain high after open surgery for acute type A AD, which are associated with coagulation disorders. Besides, platelets play an important role in coagulation. However, mendelian randomisation (MR) analysis of platelet count and AD has not been reported.
METHODS The AD (finn-b-I9_AORTDIS) dataset and platelet count (ieu-a-1008) dataset were screened from IEU OpenGWAS database for bidirectional MR analysis. The forward MR analysis was performed to analyze the relationship between platelet count and AD by five methods (MR-Egger, weighted mediam, inverse variance weighted (IVW), simple mode, and weighted mode), of which IVW was the predominant method. To assess the reliability of the MR results, the heterogeneity test, horizontal pleiotropy test and Leave-One-Out (LOO) method were applied. Similarly, the method of reverse MR analysis of platelet counts (outcoms) and AD (exposure factors) was consistent with forward MR analysis.
RESULTS In the forward MR Analysis, 38 single nucleotide polymorphisms (SNPs) related to platelet count were identified as instrumental variables (IVs). The results suggested that platelet count was causally associated with AD (P = 0.005) and platelet count was a risk factor for AD (Odd Ratio (OR) = 1.01). The reliability of the forward MR results was verified through sensitivity analysis. However, 5 SNPs related to AD were used for reverse MR analysis, and there was no causal relationship between AD as an exposure factor and platelet count as an outcome (P = 0.156, OR = 2.095).
CONCLUSIONS In forward MR analysis, platelet count was causally associated with AD, and platelet count was a risk factor for AD. In contrast, there was no causal relationship between AD and platelet count in reverse MR analysis. This study laid the groundwork for the treatment of AD.
GW35-e0084
Yulong Ge
Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES Heart failure is the end-stage manifestation of various cardiovascular diseases, among which heart failure caused by coronary atherosclerotic heart disease is the main cause of clinical heart failure. Coronary heart disease, especially myocardial infarction, leads to massive myocardial cell necrosis, immune cell infiltration, scar formation, and ventricular remodeling. Therefore, an in-depth exploration of the pathophysiological processes and key molecular mechanisms underlying the development of post-infarction ventricular remodeling and heart failure is of great clinical significance in delaying or reversing the development of post-infarction heart failure and improving the poor prognosis of patients with myocardial infarction.
METHODS Therefore, we used immunofluorescence staining, western blot, RNA-sequencing, and other experiments to explore the function and specific mechanism of DDX3X in the process of ventricular fibrosis and remodeling after myocardial infarction.
RESULTS By analyzing RNA-sequencing data from heart failure patients, DDX3X expression was significantly down-regulated in the heart tissues of hypertrophic cardiomyopathy and dilated cardiomyopathy compared with the healthy heart tissues. Meanwhile, both in vitro and in vivo experiments confirmed that DDX3X expression was down-regulated after myocardial infarction. Further exploring the reasons for the downregulation of DDX3X expression induced by heart failure, it was found that miR-322-5p expression was significantly up-regulated in both heart failure and myocardial infarction, which could directly target DDX3X and down-regulate its RNA and protein levels. Functionally, overexpression of DDX3X significantly reduced the incidence of cardiac insufficiency post-myocardial infarction, increased left ventricular ejection fraction (LVEF), left ventricular short-axis constriction rate (LVFS), decreased left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV). Combined with RNA-sequencing data, the specific mechanism of DDX3X regulation on ventricular remodeling after myocardial infarction was explored. It was found that DDX3X overexpression regulated collagen synthesis in fibroblasts by activating FOXO1, thus promoting collagen fiber synthesis and granulation tissue formation at the infarct site after myocardial infarction, contributing to maintaining the integrity of the heart and alleviating the incidence of cardiac insufficiency after myocardial infarction. miR-322-5p antagomir was further used to inhibit miR-322-5p expression in heart tissue, and it was found to significantly improve ventricular remodeling and the occurrence of heart failure after myocardial infarction.
CONCLUSIONS In conclusion, miR-322-5p-DDX3X regulates fibroblast activation and ventricular fibrosis through FOXO1 signaling, maintaining cardiac integrity after myocardial infarction, and ultimately alleviating the occurrence and development of heart failure after myocardial infarction.
GW35-e0086
Tiankai Shan, Liansheng Wang
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES Circular RNAs (circRNAs) have emerged as potential biomarkers for diagnosis and promising therapeutic targets. Yet, their roles in endogenous cardiac regeneration and myocardial renewal remain largely unexplored. This study aimed to investigate the function of circIGF1R and its mechanistic pathways in cardiac regeneration.
METHODS Through circular RNA profiling using genome-wide RNA sequencing data from neonatal and adult cardiomyocytes, we identified circRNAs associated with regeneration. Quantitative polymerase chain reaction (qPCR) and in situ hybridization were utilized to examine circRNA expression patterns in cardiac tissues. We performed gain- and loss-of-function experiments to assess the role of the identified circRNA in cardiac regeneration post-injury, employing both in vitro and in vivo models. RNA pull-down and RNA immunoprecipitation (RIP) assays elucidated circRNA-protein interactions, while coimmunoprecipitation (Co-IP) assays were conducted to explore protein-protein interactions.
RESULTS Expression of circIGF1R was markedly elevated in neonatal hearts, subsequently declining with postnatal maturation, and was re-upregulated in response to pro-regenerative injuries, such as apical resection. In patients diagnosed with acute myocardial infarction (AMI) within one week, analyses of plasma samples revealed a generalized upregulation of circIGF1R. Utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and murine models, we observed that circIGF1R overexpression promoted cardiomyocyte proliferation, inhibited apoptosis, and ameliorated cardiac dysfunction and fibrosis following myocardial infarction (MI). Conversely, suppression of circIGF1R impeded endogenous cardiac renewal. Mechanistically, circIGF1R directly bound to DEAD-box helicase 5 (DDX5), augmenting its protein levels. This subsequently enhanced the interaction between DDX5 and β-catenin, thereby inducing nuclear localization of β-catenin and transcriptionally activating c-Myc and cyclin D1 to foster cardiac regeneration and myocardial repair.
CONCLUSIONS Our findings highlight the pivotal role of circIGF1R in facilitating endogenous cardiac regeneration and repair. The circIGF1R/DDX5/β-catenin axis emerges as a novel therapeutic target for enhancing myocardial repair post-MI, offering promising avenues for the development of regenerative therapies.
GW35-e0090
Buchun Zhang
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
OBJECTIVES Vascular smooth muscle cell (VSMC) proliferation and neointima formation are of importance in the pathogenesis of vascular diseases such as restenosis or atherosclerosis. Studies have shown that colchicine can effectively treat cardiovascular diseases. However, its effect on vascular neointima formation is still unknown.
METHODS C57BL/6J mice were subjected to carotid artery ligation to evaluate the effects of colchicine during neointimal hyperplasia in vivo. Primary mouse aortic VSMCs were exposed to platelet-derived growth factor-BB (PDGF-BB) with or without colchicine treatment. The effect of colchicine in rat VSMC proliferation and migration was examined in vivo and vitro. MTT assay for measuring cell proliferation, Cell scratch wound assay for measuring cell migration. Then, the targets of colchicine were identified by RNA-seq. Finally, the expression levels of proteins in the FOXO3a-MSX1/2 pathway were measured by western blot.
RESULTS Colchicine greatly inhibited neointima formation and prevented VSMC from switching to a synthetic phenotype in vivo. Furthermore, PDGF-BB promoted VSMC proliferation and migration and transformed VSMCs to the synthetic phenotype, which was reversed with colchicine treatment. Mechanistically, we discovered that FOXO3a is a direct target of colchicine. Furthermore, an analysis of the signaling events revealed that colchicine inhibited the transformation of VSMC from contractile to synthetic phenotype via the FOXO3a-MSX1/2 mediated autophagy pathway.
CONCLUSIONS Colchicine attenuated neointima formation in the mouse model of common carotid-artery ligation injury. Colchicine protection may be mediated by maintaining a VSMC contractile phenotype via the FOXO3a-MSX1/2 mediated autophagy pathway.
GW35-e0091
Buchun Zhang
Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine
OBJECTIVES Colchicine has a wide range of anti-inflammatory, immunosuppressive and antifibrotic effects. Studies have shown that colchicine can effectively treat cardiovascular diseases. However, its effect on vascular calcification is still unknown. This study aims to investigate the role of colchicine in vascular calcification and the molecular mechanisms involved.
METHODS In this study, we used C57BL/6J male mice to construct calcification mouse model by nicotine and vitamin D3 (VD3). Mice were divided into three groups (control, model, and colchicine treatment groups). At the end of experiment, mice were euthanized and whole aorta was collected. In vitro, human aortic smooth muscle cells (HASMCs) and aortic rings was treated in high phosphate medium to induce calcification.
RESULTS The results of Alizarin red S staining showed that colchicine treatment markedly decreased calcification-positive areas in lesion areas of the whole aorta and aortic root in vivo. In vitro, we found that colchicine treatment effectively reduced calcification in aortic rings and HASMCs. At molecular levels, our results showed that colchicine reduced transcriptional factor in osteogenic differentiation runt-related transcription factor 2 (RUNX2), and downstream targets alkaline phosphatase (ALPL) and bone morphogenetic protein 2 (BMP2) in HASMCs at both protein and mRNA levels. Moreover, we further revealed that colchicine attenuates aerobic glycolysis in HASMCs associated with regulating the nuclear localization of PKM2.
CONCLUSIONS These results indicate that colchicine can effectively inhibit vascular calcification via aerobic glycolysis pathway, providing a potential drug target and strategy for the clinical treatment of vascular calcification.
GW35-e0092
Buchun Zhang
Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
OBJECTIVES Macrophage apoptosis plays an important role in the pathogenesis of atherosclerosis progression. Apoptosis-inducing factor mitochondria-associated 2(AIFM2) is upregulated in macrophages of patients with atherosclerotic coronary artery disease. However, the role of AIFM2 in the setting of atherosclerosis remains to be defined. This study aims to investigate whether AIFM2 promotes macrophage apoptosis and atherosclerosis progression based on bioinformatics analysis and experimental verification.
METHODS The atherosclerosis datasets GSE28829, GSE100927, GSE41571, and GSE57691 were obtained from the Gene Expression Omnibus (GEO) database. Functional enrichment, and immunoinfiltration analyses were performed in R software. The role of AIFM2 in apoptosis, and inflammation was analyzed using western blot, immunofluorescence staining, and flow cytometry, respectively.
RESULTS A total of 362 differentially expressed genes (DEGs) were screened from the GEO database. Functional enrichment analysis results primarily indicated enrichment in the apoptosis-related pathway, oxidative stress and inflammation, cholesterol metabolism, so on. Two common DEGs overlapped among the four datasets. The PPI network revealed that AIFM2 was the core gene. Immune cell infiltration analysis showed that AIFM2 expression was significantly correlated with macrophages, B cells, active dendritic cells, and interstitial dendritic cells (iDC). As compared with the ApoE−/− mice, ApoE and AIFM2 dual deficiency (AIFM2−/−/ApoE−/−) mice show a reduction of atherosclerotic lesion area and inflammatory response when induced with a high-fat diet. Single-cell transcriptome analysis demonstrates that AIFM2 is mainly expressed in macrophages. In vitro, oxidized low-density lipoprotein (ox-LDL) induces AIFM2 expression in macrophages. Mechanistically, ablation of AIFM2 in macrophages represses ox-LDL-induced inflammation and macrophage apoptosis. Moreover, the serum AIFM2 levels of acute coronary disease patients were significantly higher than that of healthy volunteers.
CONCLUSIONS This study indicated that AIFM2-mediated apoptosis aggravates the progression of atherosclerosis and AIFM2 could be a potential therapeutic approach for atherosclerosis.
GW35-e0109
Ziyu Guo1,2, Yonghui Xu1, Jingjing Xu1, Wei Kong2, Yanxiang Gao1, Jingang Zheng1,2
1China-Japan Friendship Hospital
2Peking University
OBJECTIVES Heart failure with preserved ejection fraction (HFpEF) is a complex, heterogeneous disease characterized by autonomic imbalance, cardiac remodeling, and diastolic dysfunction. the emerging “microvascular hypothesis” of HFpEF proposes that macrovascular and microvascular dysfunction are strongly implicated in the pathogenesis of HFpEF. Despite this, characteristics of microcirculation pathological changes in HFpEF are not completely known.
METHODS Eight-week-old male C57BL/6 N mice were treated concurrently with high-fat diet and Nω-nitro-L-arginine methyl-ester (L-NAME) via drinking water for 5 weeks. Body weight, fasting blood glucose and blood pressure were observed. Cardiac function were monitored using echocardiography. Hematoxylin-eosin (HE) and wheat germ agglutinin (WGA) were performed to evaluate cardiomyocytes, and picrosirius red staining was performed to evaluate myocardial fibrosis. The coronary microvascular structure and distribution of cardiac pericytes were observed using immunofluorescence staining.
RESULTS HFpEF was evident by significantly elevated E/e’ and reduced exercise capacity in mice treated with NG-Nitroarginine methyl ester hydrochloride (L-NAME) and high fat diet (HFD). The left ventricular ejection fraction and fractional shortening were not significantly different between the two group. Cardiomyocyte hypertrophy and peri-vascular fibrosis were observed in the HFpEF group. No significant differences were found in coronary flow reserve (CFR) but the number of capillaries was decreased in HFpEF group, accompanied by increased capillary diameter and tortuosity. Moreover, the number and microvascular coverage of cardiac pericytes were reduced in HFpEF group.
CONCLUSIONS This study detected pathological changes of heart during HFpEF, suggesting a pathogenic role for capillary and pericytes pathological changes in the development and progression of HFpEF.
GW35-e0142
Hongwei Li1,2, Kexin Wen1,2, Ling Zeng2, Juanzhang Liu1, Yuan Jiang2, Qiaofei Chen1, Jinjin Chen2, Yuling Zhang1, Baixing Wu2
1Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, RNA Biomedical Institute, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
OBJECTIVES Proprotein convertase subtilisin kexin/type 9 (PCSK9) is a safe cardiovascular target for alleviating hypercholesterolemia. A more potent and long-term PCSK9 gene silencing effect can be achieved by circular RNA sponged small-interfering RNA (circ-siRNA) with multiple antisense strand binding sites than traditional linear siRNA.
METHODS CircRNAs containing quadruple sense strand tandem repeats were circularized by Anabaena group I intron. Circular sense strands were expressed in E. coli by lactose analogue induction. Linear antisense strands and sense strands were synthesized by in vitro transcription (IVT). Both circRNA and linear RNA were gel-purified, and circular sense strands were annealed with linear antisense strands. The gene silencing effect and immunogenicity of circ-siRNA and siRNA were compared by qRT-PCR, and the off-target effect was evaluated by transcriptomic analyses.
RESULTS Circ-siRNA revealed a stronger reduction in exogenous CopGFP expression and endogenous expression than traditional linear siRNA. Moreover, circ-siRNA kept the strong inhibitory effect of PCSK9 for 7 days with low immunogenicity in HepG2 hepatocytes. Both circ-siPCSK9 and linear siPCSK9 only affected <7% change of transcriptomic entropy, and their potential off-target effect were reversed with 7 days. A liver-targeting lipid nanoparticle (LNP) successfully delivered circ-siPcsk9 for lowering serum PCSK9 concentrations, serum low-density lipoprotein-cholesterol (LDL-C), and atherosclerotic plaque burden, and the anti-atherogenic effect was stronger than LNP/siPcsk9 with no significant organ damages.
CONCLUSIONS An engineered circ-siRNA system with multiple antisense strand binding sites is developed for robust and long-acting gene inhibition, which may be a novel therapeutic platform for cardiovascular diseases and other diseases.
GW35-e0143
Sidong Cai
The University of Hong Kong-Shenzhen Hospital
OBJECTIVES Diabetic cardiomyopathy is diabetes mellitus (DM)-induced pathophysiological condition that can result in heart failure. ATP shortage caused by the dysfunction of Complex I in electron transport chain is a pivotal mechanism of diabetic cardiomyopathy. Similarly, protein arginine methyltransferase 5 (PRMT5) is also plays an essential role in the progression of cardiovascular diseases. However, the potential role of PRMT5 on the activity of Complex I remains unrevealed.
METHODS In the present study, we concentrated on clarifying the function of PRMT5 in diabetic cardiomyopathy by knockdown and overexpression of PRMT5 in cardiomyocytes, screening and validating the substrates of PRMT5 by immunoprecipitation and mass spectrometry (IP-MS) sequencing, as well as exploring the underlying mechanisms of PRMT5 in maintaining the activity of Complex I by western blotting, immunoprecipitation and enzymatic validation.
RESULTS We found that overexpression of PRMT5 in cardiomyocytes protected against diabetic cardiomyopathy in culture medium with hyperglycemia, whereas knockdown of PRMT5 or suppression of its enzymatic activity provoked diabetic cardiomyopathy. Besides, we confirmed that NADH dehydrogenase [ubiquinone] iron-sulfur protein 2 (Ndufs2), a catalytic subunit of Complex I, was the key substrates of PRMT5. Mechanistically, PRMT5 protected against diabetic cardiomyopathy by promoting symmetric di-methylation of R118 on Ndufs2, resulted in suppressing ubiquitin protein degradation system-induced downregulation of Ndufs2 and maintaining the activity of Complex I.
CONCLUSIONS Taken together, PRMT5 played a protective role in diabetic cardiomyopathy via preventing degradation of Ndufs2 in a methylation-ubiquitination crosstalk, suggesting PRMT5/Ndufs2 axis and R118 in Ndufs2 may function as potential therapeutic targets for diabetic cardiomyopathy.
GW35-e0171
Chunyu He
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Preeclampsia is a pregnancy-specific disease that poses a serious health risk to both mother and child. Angiotensin II type 1 receptor autoantibodies (AT1-AA), a pathologic autoantibody first identified in the serum of patients with preeclampsia, cause structural and functional abnormalities in blood vessels, but the mechanism is unclear. AT1-AA was found to inhibit the activity of the big conductance calcium-activated potassium channels (BKCa), which are involved in the regulation of vascular tone, in vascular smooth muscle cells at the ex vivo level. Therefore, the study was designed to observe the effect of AT1-AA on the expression of BKCa channels on placental vasculature and the mechanism of vascular remodeling caused by AT1-AA through BKCa channels using a pregnant rat model.
METHODS AT1-AA was prepared by active immunization and affinity purification; AT1-AA activity and titer were measured by myocardial beating assay and ELISA in suckling rat; Masson staining and immunohistochemistry were used to investigate vascular remodeling induced by AT1-AA; vascular tone was measured by vascular ring assay; immunofluorescence assay was used to identify isolated and cultured placental vascular smooth muscle cells; protein expression was measured by Western blot; transcriptome sequencing for screening differential genes and signaling pathways.
RESULTS The prepared AT1-AA had high purity and good biological activity; the administration of AT1-AA to pregnant rats caused preeclampsia-like lesions; AT1-AA caused abnormal fetal and placental growth and development, placental vascular collagen deposition, and decreased expression of contractile proteins and BKCa channels in pregnant rats. AT1-AA-induced increase in vascular tone can be reversed by BKCa channel agonists, and BKCa channel knockout rats showed increased vascular tone and vascular remodeling compared with wild-type rats, suggesting that BKCa channels play an important role in AT1-AA-induced vascular remodeling. At the cellular level, we successfully established an original method for isolation and culture of rat placental vascular smooth muscle cells, and found that AT1-AA caused a decrease in the expression of contractile proteins and a decrease in the expression and activity of BKCa channels in placental vascular smooth muscle cells, and the addition of a BKCa channel agonist reversed the AT1-AA-induced phenotypic transformation of placental vascular smooth muscle cells. RNA-Seq results showed differential gene enrichment in vascular remodeling and TGF β signaling pathways.
CONCLUSIONS Prolonged action of AT1-AA reduced the protein expression and activity of BKCa channels in the placenta of pregnant rats and affected the TGF β signaling pathway, which in turn induced vascular remodeling, which may be one of the molecular mechanisms underlying the placental vascular injury and the abnormal development of the fetus and placenta caused by AT1-AA.
GW35-e0185
Yanpeng Li, Dilara Adi, Yitong Ma
Department of Cardiology Heart disease, The First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES Lysophosphatidylcholine (LPC) is one of the most common lysoglycerophosphates, which is involved in many important biological effects such as inflammation, immunity, cell proliferation, apoptosis and aging, and plays a key role in the pathophysiological process. The purpose of this study is to explore the function and mechanism of LPC metabolism-mediated apoptosis in dilated cardiomyopathy (DCM).
METHODS (1) The DCM model of SD rats was established induced by doxorubicin (DOX), and the experimental animals were divided into control group, DCM group, and intervention group. The DCM group was established by intraperitoneal injection of low-dose DOX for a long time, and the intervention group was given intraperitoneal injection of LPC on the basis of DCM model. The changes of myocardial structure and function were compared with in each group, and the influence of LPC on myocardial apoptosis were explored. TUNEL staining was used to detect myocardial apoptosis, and Western Blot and qPCR were used to detect the protein and mRNA expression of apoptotic proteins Bax, Bcl-2, and caspase-3 in myocardial cells. The detection of PI3K/Akt-OPN signal pathway was also detected by Western Blot. (2) H9c2 cells of rat myocardium were selected and given exogenous intervention of DOX and LPC with different concentrations and different time. CCK8 was used to detect the optimal concentration and time of DOX and LPC intervention. A cell model intervened by DOX and LPC was constructed. Cell apoptosis and reactive oxygen species (ROS) were detected by PE/Annexin V apoptosis detection box and Western Blot was used to detect the expression of PI3K/Akt signaling pathway protein and downstream target protein OPN in H9c2. LPAR-specific inhibitors and PI3K-specific inhibitors were given to the cell model intervened by LPC, and their effects on apoptosis function were detected.
RESULTS (1) Compared with the control group, the heart of SD rats in DCM group was obviously enlarged, the myocardial function was weakened, the expressions of apoptosis-related proteins Bax/Bcl-2 and caspase-3 were increased, and the myocardial apoptosis was significantly increased. After LPC intervention, the expression of apoptosis proteins Bax/Bcl-2 and caspase-3 in DCM group decreased, while the expression of PI3K/Akt-OPN signaling pathway related proteins PI3K and p-Akt/Akt increased, and the apoptosis decreased, and the myocardial function improved. (2) In H9c2 cells induced by DOX, the apoptosis was obviously reduced after the intervention of LPC with appropriate concentration. In this process, the protective function of apoptosis was inhibited by LPAR2 specific inhibitor. Under the action of PI3K inhibitor, the expression of OPN and apoptosis-related proteins downstream of signal pathway in cells was inhibited.
CONCLUSIONS High-level LPC activates PI3K/Akt-OPN signaling pathway in cardiomyocytes through LPAR2, and inhibits the expression of apoptosis factors in cardiomyocytes, thus inhibiting apoptosis and the progress of DCM.
GW35-e0190
Hongyan Yang, Jiaheng Zhou, Xing Zhang, Jia Li, Feng Gao
Key Laboratory of Aerospace Medicine of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, 169 Changlexi Road, Xi’an 710032, China
OBJECTIVES Aging is characterized by chronic inflammation, known as inflammaging. Mitochondrial DNA (mtDNA) inducing inflammation and promoting the generation of senescence-associated secretory phenotype. Multi-omics databases in the population has indicated elevated expression of insulin receptors on monocytes in centenarians, potentially contributing to their prolonged healthspan. However, the relationship among insulin receptor signaling, macrophage clearance, and inflammaging is still unclear.
METHODS Mice with macrophage-specific insulin receptor knockout (MΦ-InsR-KO) was constructed and compared with a wild-type control (WT). Various parameters were assessed, including activity performances, cardiovascular function, aging marker. Bone marrow cells from mice with leukocytes expressing CD45.2 (MΦ-InsR-KO group and WT group) were transplanted into mice with leukocytes expressing CD45.1. The phagocytosis and clearance of mtDNA and the plasma content mtDNA, as well as the expression of proteins was assessed.
RESULTS Transcriptomic analysis of mouse macrophages showed that differential genes were enriched in PI3K-Akt and Ras-MAPK, two classical downstream signaling pathways of insulin. At 12 months of age, InsR expression in macrophage decreased, while InsR in skeletal muscle did not change significantly. These results suggest a decline in macrophage insulin receptor expression and gradual weakening of insulin signaling during aging process in mice. Compared with WT group, 8-month-old MΦ-InsR-KO mice exhibited a significant decrease in the activity, coordination, endurance, gripping power and muscle weight of group, accompanied with increased infiltration of inflammatory cell in gastrocnemius, and the expression of aging markers. MΦ-InsR-KO mice at 16 months of age had obvious hair loss and increased spinal curvature. The survival rate of mice in MΦ-InsR-KO group was decreased. These results suggest that macrophage-specific insulin receptor knockout accelerates aging in mice. BMDM cells of MΦ-InsR-KO mice exhibited significantly diminished phagocytic clearance ability of mtDNA, resulting in and elevated mtDNA content in plasma of MΦ-InsR-KO mice, and an increased accumulation of mitochondrial outside skeletal muscle cells. Moreover, the results from bone marrow transplantation experiment showed that the phagocytosis and clearance of mtDNA in bone marrow cells with InsR knockout decreased, and the content of mtDNA in plasma increased significantly. These results suggest that reduced expression of macrophage insulin receptor result in the decreased ability to phagocytose and clear mtDNA. Lamtor1 expression in BMDM cells decreased significantly after InsR knockout. Insulin enhanced the ability of macrophages to phagocytose and clear mtDNA, which was blunted by LAMTOR1 knockdown. Database analysis showed that transcription factor Srebf1 is both a downstream molecule of insulin signaling pathway and a transcriptional regulator of LAMTOR1. The transcription factor Srebf1 bound to the LAMTOR1 promoter region. Insulin enhanced LAMTOR1 expression in macrophages, which was blunted by Srebf1 knockdown. These results suggest that insulin receptors regulate LAMTOR1 expression through the downstream transcription factor Srebf1 to modulate the phagocytosis and clearance of mtDNA in macrophages.
CONCLUSIONS The decrease in insulin receptor expression in macrophages is an important factor that accelerates aging, with the underlying mechanism related to the regulation of LAMTOR1 expression and clearance ability of macrophages through insulin receptor signaling involving the downstream transcription factor Srebf1.
GW35-e0201
Meiqi Miao
The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine
OBJECTIVES Cardiovascular disease (CVD) is a leading cause of global mortality, with atherosclerosis (AS) serving as its pathological basis. Inflammation plays a critical role in the pathophysiological process of AS, and the NLRP3 inflammasome has been extensively studied in this context. This study aims to analyze the research status of the NLRP3 inflammasome in cardiovascular disease and provide research directions for further exploration in this field.
METHODS Using the “Bibliometrix” and “CiteSpace” software, a total of 516 articles from the Web of Science (WoS) database between 2012 and 2023 were retrieved using the keywords “[“CVD” OR “cardiovascular disease”] AND [“NLRP3 inflammasome” OR “NLRP3”].” Visual analysis was performed on authors, countries, institutions, journal sources, keywords, references, and future trends.
RESULTS A total of 516 English articles were retrieved, showing an overall upward trend in annual publication volume with slight fluctuations. China, the United States, and Europe were the countries and regions with the highest number of published articles. Among them, China had the highest article count (170), the United States had the highest citation count (18,664), centrality (0.43), and h-index (90). These countries also possessed elite institutions, professional researchers, and high-impact journals, making them leading contributors in this field. The main pathogenic mechanisms of the NLRP3 inflammasome in CVD were identified as “oxidative stress,” “pyroptosis,” and “inflammation.” The most frequently studied signaling pathways included “NF-kB,” “IL-1,” and “C-reactive protein.” The most studied disease types were coronary heart disease, atherosclerosis, metabolic syndrome, and myocardial infarction. Additionally, recent research has shown a growing interest in the correlation between cholesterol markers and inflammatory indicators associated with NLRP3 inflammasome in CVD risk assessment, with the main mechanism being NLRP3/IL-6/hs-CRP, and cholesterol lipoproteins emerging as key keywords in this context.
CONCLUSIONS This study provides valuable insights into the research hotspots and emerging trends of the NLRP3 inflammasome in cardiovascular disease. The findings offer guidance for researchers and scholars in this field and facilitate the exploration of new research directions.
GW35-e0210
Ying Wang, Yan Li, Lang Hu
Department of Cardiology, Tangdu Hospital, Airforce Medical University
OBJECTIVES Lipid overload-induced cardiac injury is characterized by mitochondrial dysfunction, leading to energy metabolic disorders and compromised contractility. Prolonged lipid overload creates an intracellular environment that induced protein acetylation. However, the mechanism by which protein acetylation was involved in cardiac metabolic disorders in the lipid overload heart remains poorly understood.
METHODS Mice was fed with high-fat diet (HFD) for 20 weeks to induce lipid overload-induced cardiac dysfunction. Cardiac structure and function were detected using echocardiography and histological staining. Multiple approaches including acetylation proteomics, mitochondrial respiratory function, and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis were performed in-vivo and in-vitro to investigate the potential underlying mechanisms.
RESULTS Mice fed a HFD developed signs of cardiac dysfunction and heart hypertrophy. Lipid overload heart also exhibited significant mitochondrial respiratory function impairment, fatty acid oxidation inhibition and aberrant cardiac lipid accumulation. Furthermore, HFD increased intracellular acetyl-CoA level while decreased NAD+ concentration. The acetylation proteomics revealed that the majority of HFD-induced hyperacetylated proteins located in mitochondria and concentrated in fatty acid oxidation pathway. Activation of deacetylases by NAD+ supplementation prevented mitochondrial protein hyperacetylation, restored mitochondrial respiratory function and rescued cardiac function in HFD-fed mice. Proteomics analysis and in vitro screening revealed that DLAT, a subunits of dehydrogenase complex, was responsible for the HFD-induced mitochondrial protein hyperacetylation. Cardiac-specific silence of DLAT attenuated mitochondrial functional impairment in both HFD heart and palmitate-cultured cardiomyocytes. Moreover, we further identified Mfn2 as a target protein which was involved in mitochondrial dynamics, mitochondrial respiration and mitochondria related organelle interaction. Mfn2 overexpression partly reversed DLAT-induced mitochondrial injury and cardiac dysfunction in lipid overload heart.
CONCLUSIONS These findings uncover a novel mechanism by which protein acetylation contributes to lipid overload-induced cardiac metabolic disorder and dysfunction. DLAT activation combined with intracellular hyper-acetyl-CoA environment facilitated mitochondrial protein acetylation, which, in turn, induced mitochondrial dysfunction and resulted in cardiac injury. Thus, DLAT may be a critical target for manipulating protein hyperacetylation and restoring mitochondrial energy metabolism and cardiac function in lipid overload heart.
GW35-e0218
Jinyao Liu1, Yumiko Oba1, Seiko Yamano2
1Yamaguchi University Graduate School of Medicine, Ube, Japan
2Advanced Medical Research Academic-Course, Yamaguchi University Graduate School of Medicine, Ube, Japan
OBJECTIVES This study focuses on the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and increased cardiovascular-related mortality, particularly in apolipoprotein E/low-density lipoprotein receptor double-knockout (AL) mice. Combining alcohol with a low-carbohydrate-high-protein-high-fat atherogenic diet (AD) in these mice leads to a higher incidence of lethal arrhythmia and upregulation of left ventricular (LV) gap junctional protein alpha 1 (Gja1, or Cx43) mRNA expression. Gap junctional remodeling and interstitial fibrosis, known to impair electrical conduction velocity, are linked to the increased risk of lethal arrhythmias. The study investigates the impact of LV myocardial interstitial fibrosis (MIF) on lethal arrhythmogenicity during the progression of metabolic dysfunction-associated steatohepatitis (MASH) in AL mice.
METHODS Male AL mice were fed an AD diet with or without ethanol for 16 weeks, while age-matched male AL and wild-type mice served as controls. Analysis of liver and cardiac tissues, along with susceptibility to lethal arrhythmia, was conducted using various techniques including histopathological and fluorescence immunohistochemical examination, RNA-seq analysis, RT-PCR, and lethal arrhythmia-evoked test (an acute restraint stress (ARS) test with intraperitoneal epinephrine infusion).
RESULTS Co-diet ethanol with AD induces significant LV MIF in AL mice with MASH, characterized by the increased fibrosis-related gene expression, Sirius-Red content, and collagen 1a1 and collagen 3a1 mRNA expressions, along with the highest incidence of lethal arrhythmia during the lethal arrhythmia-evoked test. Additionally, cardiac myofibroblasts, exhibiting sympathetic activation, activated and produced more fibrosis factors (transforming growth factor β1).
CONCLUSIONS Cardiac myofibroblasts, exhibiting sympathetic activation, play a role in the initiation and progression of LV MIF during MASH progression, thereby contributing to the increased susceptibility to lethal arrhythmia in AL mice fed a co-diet of ethanol and AD.
GW35-e0250
Wenting Wang, Lulu Zhu, Miaomiao Qi, Jing Yu
Lanzhou University Second Hospital
OBJECTIVES The estrogen level of postmenopausal women decreased sharply, while the androgen level did not decrease significantly, which was characterized by the inversion of estrogen/androgen ratio. Therefore, it could be observed that relative excess androgen in the circulation of postmenopausal women, which may be one of the reasons for the increase of cardiovascular disease in postmenopausal women. In this study, the model of postmenopausal hypertension was established by bilateral ovariectomy in spontaneously hypertensive rats (SHR), and the specific mechanism of testosterone-induced myocardial hypertrophy in ovariectomized SHR was explored.
METHODS Twenty four SHR were randomly divided into four groups: WKY group (n = 6), sham operation group (Sham group, n = 6), bilateral ovariectomized group (OVX group, n = 6) and testosterone propionate intervention group (OVX+T group, 6 mg/kg/Weekly, im for 4 weeks, n = 6). Western Blot was used to detect the protein expression of β-MHC, ANP, Androgen receptor, Akt, p-Akt, mTORC2 and its subunits Rictor. Moreover, the expression of autophagy-related proteins LC3 was observed.
RESULTS (1) Testosterone-induced cardiac hypertrophy in ovariectomized SHR: The study revealed that the expression of β-MHC and ANP was significantly increased in both the OVX and OVX+T groups when compared to the WKY and Sham groups. Remarkably, testosterone induced a more significant cardiac hypertrophy response than observed in the OVX group alone. Additionally, the expression of androgen receptors was markedly upregulated in both the OVX and OVX+T groups. These findings strongly suggest that testosterone primarily induces myocardial hypertrophy in SHR after ovariectomy through androgen receptors. (2) Testosterone activation of mTORC2 expression in myocardial tissue: Although no significant difference in mTORC2 expression was noted between the WKY, Sham, and OVX groups, testosterone exhibited a notable capacity to activate mTORC2 expression and the p-Rictor subunit in the OVX+T group. (3) Testosterone can activate mitophagy in myocardial tissue: The expression of LC3II/LC3I and mitochondrial fission protein DRP1 were increased in the OVX+T group when compared to the WKY, Sham, and OVX groups. While the expression of MFN2 in the four groups shows no significant difference. Meanwhile, the expression of Atg9a was increased in OVX+T group. The results indicate that testosterone might activate mitophagy via inducing the expression of Atg9a.
CONCLUSIONS In bilateral ovariectomized SHR, testosterone has the potential to activate mitophagy by activating the mTORC2/Atg9a pathway, which, in turn, leads to cardiac hypertrophy
GW35-e0251
Xing Yu1, Zhijian Wang2, Liangdi Xie1
1Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
2Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
OBJECTIVES Sacubitril/valsartan (LCZ696) is an effective medication for the treatment of heart failure, and its active metabolite, LBQ657, has been found to improve the aging of myocardial cells. This study aims to establish a mouse model of myocardial cell aging and investigate the effects and mechanisms of LBQ657 on myocardial cell aging by analyzing the expression profiles of IncRNAs and mRNAs using high-throughput sequencing.
METHODS HL-1 myocardial cells were divided into three groups: the control group (N group) with normal culture conditions, the aging model group (A group) induced by D-galactose, and the LBQ657 treatment group (L group) receiving LBQ657 treatment during the aging induction. Cell aging rate was evaluated using β-galactosidase staining, and the levels of SOD and MDA were measured to assess changes in anti-oxidative stress capacity. qPCR was used to detect the mRNA expression levels of MYH-7, ACTA-1, MYH-6, and SERCA-2 to analyze changes in myocardial cell aging and dysfunction. High-throughput sequencing was employed to detect differential expression of IncRNAs and mRNAs, followed by GO and KEGG functional enrichment analysis and the construction of an IncRNA-mRNA co-expression network.
RESULTS Compared with the control group, the aging model group showed significantly increased rates of myocardial cell aging, MDA levels, MYH-7, andACTA-1 mRNA expression, as well as decreased SOD, MYH-6, and SERCA-2mRNA expression (P < 0.05). In the LBQ657 treatment group, the rates of myocardial cell aging, MDA levels, MYH-7, and ACTA-1 mRNA expression were decreased, while SOD, MYH-6, and SERCA-2 mRNA levels were increased (P < 0.05). The aging model group and the treatment group exhibited 1294 and 811 differentially expressed IncRNAs and 7491 and 2950 differentially expressed mRNAs, respectively. GO and KEGG analysis revealed significant enrichment of functions related to metabolism, cellular apoptosis, and other processes. Cluster heat maps and co-expression network analysis showed up-regulation of Cdkn1b and Bbc3 gene expression (P < 0.05) in the model group, which was down-regulated (P < 0.05) in the treatment group, along with five co-expressed IncRNAs in each group.
CONCLUSIONS LBQ657 can delay myocardial cell aging in HL-1 cardiomyocytes possibly through the involvement of mRNA and IncRNA, including Cdkn1b andBbc3.
GW35-e0260
Yunhao Li
General Hospital of Northern Theatre Command
OBJECTIVES The cardiac conduction system comprises specialized cardiomyocytes that regulate the coordinated activity of the heart. Originating from the ventricular base, Purkinje fibres form a series of bundles in the subendocardial layer that gradually converge and cross to extend towards the apical region of the heart. These bundles intertwine to form a network within the subendocardium extending perpendicularly to the endocardial surface between the myocardium and the working cells. Studies have suggested that the development and persistence of certain ventricular tachycardias may be related to structural or functional abnormalities within the Purkinje fiber network. Purkinje fibres carry faster conduction and shorter action potential durations compared to ventricular myocytes and play a fundamental role in enabling the ventricular myocardium to contract in a coordinated manner as a functional syncytium. The aim of this study was to provide an overview of the anatomical features of Purkinje fibres in the canine left ventricle by gross and microscopic observations, with the aim of guiding experimental and catheter ablation interventions for Purkinje associated ventricular arrhythmias.
METHODS Lugol’s solution was used to stain the endocardial surface of fresh canine hearts for gross observation of the left bundle branch and Purkinje fiber pathways. Histological examination using HE staining, Masson’s trichrome staining, and CX40 immunohistochemistry was performed for microscopic observation of the distribution of bundle branches and Purkinje fibers. The main methods used to visualize the intracardiac conduction system are gross dissection and staining. Gross dissection is particularly suitable for examining larger intracardiac structures such as the sinus node. Conversely, staining techniques are more appropriate for visualizing smaller conduction systems, such as the Purkinje fibres. Various staining techniques are available, including dye perfusion staining, iodine solution staining and iodine gas staining. Our study opted for Lugol’s iodine staining, which takes advantage of the difference in glycogen content between the Purkinje fibres and the endocardial surface to produce different colors.
RESULTS The study successfully obtained 12 beagle canines (age 2.90 ± 0.56 years, weight 21.50 ± 3.32 kg) for ex vivo heart examination, revealing the transverse characteristics of different levels of conduction bundles and Purkinje fibers in the left ventricular endocardium using Lugol’s solution, and microscopic observation showed the longitudinal layered distribution of Purkinje fibers.
CONCLUSIONS The Purkinje fibers in the left ventricle of canines exhibit graded, layered, and networked distribution characteristics, which can guide experimental and ablation treatments for Purkinje-related ventricular arrhythmias. In cases of ventricular chamber dilatation due to various physiological and pathological causes, certain ventricular arrhythmias may be related to the deformation and mechanical stress experienced by the false tendons. Studies have suggested that the region of the endocardium where the false tendons attach may be more susceptible to mechanical stretch, particularly due to the denser connective tissue sheath in the mid-segment of the false tendons. Therefore, ablation at the junction between the false tendons and the endocardium has been suggested as a potentially effective treatment.
GW35-e0267
Xin Fan, Jing Yu
Lanzhou University Second Hospital
OBJECTIVES Hypertension is one of the common causes of cardiovascular diseases. Long-term hypertension can lead to structural and functional impairment of the heart. Therefore, active treatment of hypertension is highly significant in preventing target organ damage. Angiotensin II (AngII) plays a crucial role in hypertension-induced cardiac hypertrophy. Reportedly, TRV027, an AngII type 1 receptor (AT1R) biased agonist, can competitively bind to AT1R and inhibit the AngII-induced damage. Whether TRV027 could lower blood pressure and treat hypertensive cardiac hypertrophy remains unknown.
METHODS Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were selected, and some of the SHRs were administered with TRV027. H9C2 cells were utilized for in vitro study to explore the underlying mechanism of TRV027. A multidisciplinary approach combining pathology and molecular techniques was used to explore the role and mechanism of TRV027 in reducing blood pressure and restoring ventricular hypertrophy.
RESULTS Our studies revealed that TRV027 reduced blood pressure and restored hypertension-induced ventricular hypertrophy in SHRs. Moreover, the modulated expression of Connexin43 (Cx43) and phosphorylation of the MAPK/ERK pathway were normalized by TRV027. After the inhibition of Cx43 expression, cardiomyocytes recovered from hypertrophy and damage, followed by the modulation of phosphorylation of the MAPK/ERK pathway.
CONCLUSIONS Our studies revealed that TRV027 reduced blood pressure and restored hypertension-induced ventricular hypertrophy in SHRs. Moreover, the modulated expression of Connexin43 (Cx43) and phosphorylation of the MAPK/ERK pathway were normalized by TRV027. After the inhibition of Cx43 expression, cardiomyocytes recovered from hypertrophy and damage, followed by the modulation of phosphorylation of the MAPK/ERK pathway.
GW35-e0268
Zhu Mei, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES The cardioprotective effect of AMPK in the progression of MI are attributed to phosphorylation of the α subunit at Thr172. However, whether the AMPKγ2 subunit plays an important role in MI remains unclear.
METHODS AMPKγ2 plasma levels in patients with MI were tested using ELISA. LAD surgery was performed to establish a mouse MI model. Transwell and scratch assays were performed to evaluate the macrophage migration ability. Lyz2-cre AMPKγ2 and adeno-associated virus carrying the F4/80 promoter for macrophage-specific overexpression AMPKγ2 mice were employed to investigate the role of AMPKγ2 in macrophages derived from MI in vivo.
RESULTS AMPKγ2 is highly expressed in macrophages. AMPKγ2 levels were decreased in monocytes of myocardial infarction patients and downregulated by inflammatory stimuli of IFN-γ in RAW264.7 cells and in bone marrow-derived macrophages (BMDM) extracted from mice subjected to MI. Lyz2-cre AMPKγ2 mice developed worse cardiac dysfunction post MI by boosting macrophage infiltration. Overexpression of AMPKγ2 repressed macrophage migration and inflammation in vivo and in vitro. The CXCL16 was a key contributor to macrophage migration and inflammation, which was alleviated by AMPKγ2 administration via transcriptional regulation. Moreover, the CXCL16/CXCR6 and NF-κB-MCP1/IL-6 pathways jointly formed a positive feedback loop. AMPKγ2 repressed the CXCL16/CXCR6 axis by restraining YY1 expression to rescue cardiac dysfunction after MI and restrain macrophage infiltration dependent on AMPKα1 subunit-mediated AMPK activity. A769662, but not the classic AMPK agonist metformin can rescue deficiency of AMPKγ2 induced-the myocardial dysfunction. AMPKγ2 phosphorylated smurf2S384 to promote YY1 degradation via the ubiquitin proteasome pathway. Finally, IFN-γ downregulated HOXA5 to repress AMPKγ2 transcriptional activity and protein expression in vitro and in vivo.
CONCLUSIONS AMPKγ2 inhibits the YY1-CXCL16-CXCR6 pathway, which plays an important role in cardiac dysfunction following MI, and may be a potential therapeutic target for myocardial remodeling after MI.
GW35-e0274
Xuewei Xia
Army Medical Center of PLA
OBJECTIVES Stem cell transplantation in the treatment of myocardial infarction has achieved limited success. However, the hypoxic-ischemic microenvironment following myocardial infarction is not conducive to stem cell survival, leading to significant apoptosis of transplanted stem cells and severely limiting its therapeutic efficacy. Studies have demonstrated that MG53 exerts a protective effect on cardiac injury by enhancing cardiomyocyte viability, suppressing inflammation, and inhibiting apoptosis.
METHODS The bone marrow mesenchymal stem cells were transfected with lentivirus carrying either MG53 overexpression or an empty vector. In vitro, apoptosis of BMSC was observed following H2O2 stimulation. Subsequently, the MG53-overexpressing or control BMSCs were transplanted into mice after myocardial infarction to evaluate their efficacy.
RESULTS Apoptosis in both BMSCs and myocardium transplanted with BMSCs exhibited significantly reduced apoptosis compared to the control group. Scar size was limited, while cardiac function improved following transplantation of MG53-overexpressing BMSCs. Hypoxia treatment increased PHD3 expression but this was reduced by MG53 overexpression. Furthermore, MG53 bound to PHD3, promoting its ubiquitination and degradation, resulting in increased Hif2α levels and decreased apoptosis of BMSCs. Additionally, paracrine effects of BMSCs were enhanced by MG53 overexpression, particularly for factors such as higher levels of MG53. Moreover, culture supernatant from MG53-overexpressing BMSC also demonstrated a protective effect on myocardial infarction which weakened after neutralization of MG53.
CONCLUSIONS Transfection of MG53 can promote the survival of BMSCs, enhance their paracrine secretion, and protect myocardial cell function in mice with myocardial infarction. The degradation of PHD3 by MG53 promotes the survival of BMSC by increasing the expression of Hif2α. Overexpression of MG53 in stem cells may be a novel strategy to enhance the efficacy of stem cell therapy after myocardial infarction.
GW35-e0282
Lingbing Meng1,2, Jiapei Xu2, Gaifeng Hu3
1Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University
2Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences
3Department of Cardiology, Anzhen Hospital, Capital Medical University
OBJECTIVES Chronic stress can lead to prolonged activation of the body’s stress response systems. This long-term activation may contribute to the instability of atherosclerotic plaques. However, the molecular mechanisms underlying this process remain unclear.
METHODS Bioinformatics was used to screen the hub molecular myosin heavy chain 10 (MYH10) and signaling pathway. Cell experiment was performed to explore the molecular mechanism of chronic stress and atherosclerosis. MYH10 molecule is knocked out by siRNA on aortic smooth muscle cells, and the PINK1/Parkin mitochondrial autophagy signaling pathway was tested to analyze the influence of chronic stress on the atherosclerotic plaques. Male SPF C57BL/6 mice aged 6–8 weeks were used to construct the chronic stress model and atherosclerotic model. And the all animals were classified to: Control group, CS group, HFD (high fat diet) + Apoe−/− group, HFD + CS group, HFD + TPM2+/− group, HFD + CS + TPM2+/− group, HFD+MYH10+/− group, HFD + CS + MYH10+/− group. Furthermore, a total of 34 clinical samples are obtained to verify the function of MYH10 in the chronic tress and atherosclerosis in this study, including 17 samples with atherosclerosis and 17 samples without atherosclerosis.
RESULTS Chronic stress affects the atherosclerosis mainly through the hypothalamic-pituitary-adrenal axis via GNG4 and calcium channel regulation. Chronic stress affects energy metabolism through the TAC cycle via OGDH and citrate synthase to aggravate the atherosclerosis. Using public database of selected atherosclerotic and non-atherosclerotic specimens, we identified the key molecules in the development of atherosclerosis: MYH10 and PINK1/Parkin mitochondrial autophagy signaling pathway. Under chronic stress, the expression of MYH10 decreases, inhibiting mitochondrial autophagy. Mitochondrial fusion decreases while fission increases, leading to the accumulation of dysfunctional mitochondria. This results in increased apoptosis, enhanced oxidative stress, subsequent phenotypic transition of smooth muscle cells, and migration to the vascular intima, contributing to the formation of atherosclerotic (AS) plaques. These cells transform into macrophages and phagocytize ineffective low-density lipoproteins, necrotic components, or apoptotic cells, thereby forming numerous foam cells, leading to the development of AS and unstable plaque formation.
CONCLUSIONS Chronic stress may increase the instability of atherosclerotic plaques by downregulating MYH10, thereby inhibiting the PINK1/Parkin mitochondrial autophagy signaling pathway.
GW35-e0293
Xinyu Yang, Yong Sun, Jian Wu
Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University
OBJECTIVES Heart failure with preserved ejection fraction (HFpEF) poses a significant challenge in the cardiovascular field due to its high prevalence, poor prognosis, and the lack of effective diagnostic and treatment strategies. Notably, aberrant lipid metabolism stands out as a pivotal contributor to the onset and progression of HFpEF. Presently, our understanding of the regulatory mechanisms governing abnormal myocardial lipid metabolism in HFpEF remains nascent, with hub genes and targets remaining elusive. Therefore, elucidating the pivotal genes dictating lipid metabolism and undertaking comprehensive investigations will deepen our comprehension of HFpEF pathogenesis.
METHODS (1) 5 bulk RNA-seq datasets of HFpEF mice were obtained from the GEO database. Differential gene expression analysis was conducted using the DESeq2 package. The hub genes related to lipid metabolism pathway were determined by enrichment analysis and construction of a protein-protein interaction network. (2) An HFpEF mouse model was created by administering a HFD and L-NAME for seven weeks, qRT-PCR was employed to measure the expression of hub lipid metabolism genes in the ventricular tissue of HFpEF mice. (3) scRNA-seq data from the ventricular tissue of HFpEF mice were used to create a single-cell atlas using the Seurat package. The proportion of each cell type in the ventricular tissue was defined. Differences in the expression of hub lipid metabolism genes among heart cell groups in HFpEF mice were examined. (4) Cardiac macrophage subsets in HFpEF mice were further analyzed. A pseudo-temporal trajectory was constructed using monocle3 to investigate changes in the expression of hub lipid metabolism genes over time.
RESULTS (1) Using bioinformatics methods, we identified Pparg, Ppargc1a, Scd1, Il1b, Ptgs2, Pdk4, Angptl4, Ucp3, Elovl6 and Fabp5 as hub lipid metabolism genes potentially regulating the HFpEF process. Among these, Il1b, Ucp3, Angptl4, Fabp5 and Pparg were significantly upregulated in the ventricular tissue of HFpEF mice. (2) The single-cell atlas of HFpEF mice revealed increased proportions of fibroblasts (64.09% vs. 52.91%), macrophages (4.56% vs. 2.51%), B cells (3.81% vs. 2.35%), and T cells (2.51% vs. 1.36%). Among these, hub genes were significantly different mainly in fibroblasts (Il1b, Scd1, Ptgs2, Fabp5, Elovl6, Angptl4), macrophages (Il1b, Scd1, Pparg, Ptgs2, Fabp5), smooth muscle cell (Scd1, Ptgs2, Ppargc1a, Angptl4, Pdk4), endothelial cells (Angptl4, Fabp5, Pdk4), and neutrophils (Il1b, Ptgs2, Fabp5). (3) In HFpEF mice, there was an increase in Ccr2+MHC-IIhi macrophages, GSEA analysis showed that Ccr2+MHC-IIhi macrophages were enriched in both lipid metabolism and inflammation pathways. (4) Pseudotime analysis revealed significant expression changes of Fabp5 and Il1b along the pseudotime trajectory, with a notable increase in expression in Ccr2+MHC-IIhi macrophages and the HFpEF group.
CONCLUSIONS (1) The expressions of Il1b, Ucp3, Angptl4, Fabp5 and Pparg are significantly upregulated in the ventricular tissue of HFpEF mice. The expressions of Il1b, Scd1, Ptgs2, Fabp5 and Angptl4 show significant differences across various cell types in the ventricles of HFpEF mice. These genes are key in regulating lipid metabolism in HFpEF. (2) Fabp5 and Il1b may be involved in the lipid metabolism and inflammatory processes of HFpEF through their interaction with Ccr2+MHC-IIhi macrophages.
GW35-e0311
Hongkui Chen, Ziqing Ruan, Zhijie Lin, Yansong Guo
Fujian Provincial Hospital
OBJECTIVES N7-methylguanine (m7G) had been shown to play a role in the development of many diseases, but its effect on coronary heart disease (CHD) was unclear. The aim of this study was to explore m7G related biomarkers with potential therapeutic effects on CHD.
METHODS In this study, 29 m7G-related genes (mRGs) obtained from previous literature, transcriptome data (GSE113079 and GSE179789) and single-cell sequencing data GSE121893 were retrieved from public database. The key module genes associated with score of m7G were identified by weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) were identified between CHD and normal groups in GSE113079. Moreover, differentially expressed (DE-mRGs) were obtained by taking the intersection of key module genes and DEGs. Biomarkers were identified by plotting receiver operating characteristic (ROC) curves and two algorithms (Boruta and LASSO-Logistic) and expression validation. Based on biomarkers, enrichment analysis and construction of network were performed.
RESULTS A sum of 221 DE-mRGs were obtained by screening. Next, MUC4, NCAPD3, and PTGER1 were identified as biomarkers. Among them, MUC4 and NCAPD3 were highly expressed and PTGER1 was lowly expressed in CHD. And MUC4 and NCAPD3 were significantly positively and PTGER1 was significantly negatively correlated with protein processing in the endoplasmic reticulum, etc. Finally, Ruxolitinib, methylcellulose and cyanohydrin were found to have potential therapeutic effects on CHD.
CONCLUSIONS We obtained three m7G related biomarkers (MUC4, NCAPD3, and PTGER1) associated with CHD, which laid a theoretical foundation for the treatment of CHD.
GW35-e0328
Bingjun Lu
Southwest Hospital
OBJECTIVES The regenerative capacity of mammalian cardiomyocytes significantly changes during heart development. The mechanisms regulating cardiomyocyte proliferation remain unclear. This study aims to investigate the molecular basis behind the perinatal cell cycle arrest of cardiomyocytes and explore novel targets for stimulating adult cardiomyocyte proliferation.
METHODS We gathered transcription datasets related to normal heart development from Gene Expression Omnibus. The gene co-expression network was constructed using weighted gene co-expression network analysis. GO enrichment analysis and KEGG pathway analysis were conducted using the web tool g: profiler2. Single nucleus RNA-seq (snRNA-seq) was utilized to identify the cell cycle genes with the highest expression in cardiomyocytes. The communication between cardiomyocytes and non-cardiomyocytes based on ligand and receptor interactions was analyzed. iRegulon and pseudo-temporal analysis were utilized to identify transcription factors. Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery.
RESULTS We have pinpointed three cell cycle-linked modules by analyzing 655 hearts from 39 independent datasets. Integrating bulk RNA-seq and scRNA-seq highlighted 44 down-regulated cell cycle genes in cardiomyocytes versus non-cardiomyocytes. Spearman correlation and enrichment analysis identified 49 GO terms and 76 KEGG pathways linked to cardiomyocyte proliferation. For the cellular communication between all cardiac cell types, 289 ligand/receptor interactions were discerned to be associated with proliferation among cardiomyocytes and non-cardiomyocytes. Seventy-seven transcription factors were associated with cardiomyocyte cell cycle arrest during development, among which 21 genes were found to influence cardiomyocyte proliferation in vitro. Manipulation of transcription factor Nr3c1 enhanced adult cardiomyocyte proliferation and cardiac function post-myocardial infarction in-vivo, spotlighting Nr3c1 as a novel target for stimulating adult heart regeneration.
CONCLUSIONS Our study outlined a spatiotemporal molecular framework for cardiomyocyte proliferation regulation during normal heart development, and identified a series of novel potential targets including Nr3c1 for stimulating adult cardiomyocyte proliferation.
GW35-e0341
Shitong Huang, Qiuying Wang, Liming Lei
Guangdong Provincial People’s Hospital
OBJECTIVES Marfan syndrome (MFS) is an inherited autosomal dominant disorder that affects connective tissue with an incidence of about 1 in 5000–10,000 people. Ninety percent of MFS is caused by mutations in the fibrillin-1 (fbn1) gene. We recruited a family with MFS phenotype in South China and identified a novel variant in fbn1 by whole exome sequencing (WES). The zebrafish share high genetic similarity to humans. This study aimed to generate this novel mutation in the fbn1 gene of zebrafish using the CRISPR/Cas9 technology and researched whether this variant is pathogenic.
METHODS A three-generation consanguineous family was recruited in this study, which was visited and interviewed for the clinical data and family history. Peripheral blood samples were collected from family members for DNA isolation and WES. The 3D structure of the protein was predicted by Alphafold. CRISPR/Cas9 was applied to generate an fbn1 nonsense mutation (fbn1+/− ) in zebrafish. Morphological abnormalities were assessed in F2 fbn1+/− zebrafish by comparing with the wild-type (WT) controls at different development stages. We finally identified possible pathways related to the pathogenesis of Marfan syndrome by RNA-seq analysis on zebrafish.
RESULTS Our study recruited a family with MFS phenotype in South China and identified a novel variant [NM_000138.5; c.7764C>G: p. (Y2588*)] in fbn1. Through Sanger sequencing, we found that family members III-1 and III-2 had the fbn1 variant segregated with MFS in the family. The p.Y2588* mutation resulted in the absence of 283 amino acids, thereby leading to the deficiency of 17 β-folded structures, 4 α-helix structures, and various loop structures. Compared with WT zebrafish, F2 fbn1+/− zebrafish exhibited aortic arches bleeding, abnormal angiogenesis, decreased cardiac volume, cardiac function defects, curly tail, and cartilage malformations. The RNA-Seq analysis in zebrafish embryos indicated that fbn1 mutation could affect the homeostasis of glucose and adipose by influencing the production of leptin, retinol metabolism and bile secretion, and it also could affect pathological changes in vascular endothelium by changing the process of altered cell adhesion, ECM-receptor interactions, and focal adhesions.
CONCLUSIONS A novel variant [NM_000138.5; c.7764C>G: p.(Y2588*)] was identified in fbn1 gene, which has not been reported in previous literature. The variant caused loss of function through premature protein truncation or nonsense-mediated mRNA decay. In zebrafish, we identified functional evidence of the detected nonsense mutation, which aligns with the clinical significance, suggesting a pathogenic variant of fbn1. Zebrafish as a novel, efficient tool to allow for the quick classification of unknown variants in fbn1 and improve the clinical diagnosis and treatment of MFS. It has brought the implementation of personal and precision medicine in the clinic within reach and made it possible to find patient-specific treatments. Our research offers a justification for investigating metabolic symptoms in individuals with MFS, opening the door to tailored dietary advice for this population, and ultimately enhancing their quality of life.
GW35-e0344
Bin Liu, Dinghui Wang
Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University
OBJECTIVES The role of structural remodeling in the development and persistence of atrial fibrillation atrial fibrillation (AF) is significant, although its mechanism remains unknown at present. This study aims to explore the transcriptomic mechanisms of AF structural remodeling through bioinformatics analysis.
METHODS These were acquired from the GEO database. Next, a series of bioinformatics methods were used, such as R language, DAVID, STING, and Cytoscape software, to study the DEG between AF and control samples. Then, we found genes related to ferroptosis from FerrDb database and conducted joint analysis with differentially expressed genes (DEG). In addition, we predicted several transcription factors that regulate DEG and conducted immune infiltration analysis using CIBERSORT software.
RESULTS A total of 363 up-regulated DEGs and 308 down-regulated DEGs were identified fromatrium cordis samples of 16 AF patients and 13 controls of microarrays GSE14975, GSE31821 and GSE79768. Functional changes of DEGs mainly focus on positive regulation of inflammatory response, signal transduction, inflammatory response, immune response, oxidation-reduction process and extracellular matrix organization. Eleven DE-FRGs were identified, including HSPB1, ALOX15, ETV4, ACO1, CHAC1, FH, PARP15, IFNG, ACSL1, FABP4 and IL1B and several TFs (POLE2, GATA5, CEBPA, ATF3, MEF2C) were predicted via Cytoscape software. Macrophage M2 was found to occupy the largest proportion of all the immune cells.
CONCLUSIONS The occurrence of AF may be a result of fibrosis caused by myocardial cell ferroptosis and imbalance of the immune microenvironment. Obtained DE-FRGs HSPB1, ALOX15, ETV4, ACO1, CHAC1, FH, PARP15, IFNG, ACSL1, FABP4 and IL1B and predicted TFs POLE2, GATA5, CEBPA, ATF3, MEF2C can be seen as potential targets for preventing AF.
GW35-e0358
Shuang Guo1, Zaihan Li2, Shuren Li1, Mei Zhao1
1Hebei General Hospital
2University of Chinese Academy of Sciences
OBJECTIVES This study aims to investigate the correlation between fibroblast growth factor 23 (FGF23) and atrial fibrillation (AF) mediated cardiomyopathy (AMC)
METHODS Rabbit models of AF were created through rapid atrial stimulation, with division into three groups: control (pacemakers implanted without pacing, n = 6), AF (pacing with ejection fraction decrease <10%, n = 5), and AMC (pacing with ejection fraction decrease ≥10%, n = 6). After 4 weeks, Western Blot (WB), multiplex chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) analyses were conducted. Additionally, FGF23 expression were measured in 102 patients with chronic AF and 86 with AF-related heart failure (AF-HF). ROC curves were constructed to determine the diagnostic value. Factors associated with all cause mortality of AF-HF were identified through Cox regression analysis.
RESULTS In the animal model, higher fibroblast growth factor 23 expression compared to the AF group were observed in the AMC group. In clinical observations, the area under the curve for FGF23 in diagnosing AF and AF-HF was 0.982 (0.967-0.996), with a sensitivity of 93.0% and specificity of 96.1%. In multivariate Cox analyses, FGF23 (OR 1.002, 95% CI 1.001-1.003, P < 0.001) were independently associated with all-cause mortality in patients with AF-HF.
CONCLUSIONS Our findings suggest that FGF23 has diagnostic value for AF patients to develop AF-related HF. After correcting the influencing factors, FGF23 is an independent influencing factor for all-cause mortality of AMC patients.
GW35-e0363
Chao Su1, Jinzheng Ma2, Jie Yang2, Minxin Wei1
1The University of Hong Kong-Shenzhen Hospital
2Tianjin Medical University
OBJECTIVES The neonatal mammalian heart exhibits considerable regenerative potential following injury through cardiomyocyte proliferation, whereas mature cardiomyocytes withdraw from the cell cycle and lose regenerative capacities. Therefore, investigating the mechanisms underlying neonatal cardiomyocyte proliferation and regeneration is crucial for unlocking the regenerative potential of adult mammalian heart to repair damage and restore contractile function following myocardial injury.
METHODS The Tudor staphylococcal nuclease (Tudor-SN) transgenic (TG) or cardiomyocyte-specific knockout mice (Myh6-Tudor-SN−/−) were generated to investigate the role of Tudor-SN in cardiomyocyte proliferation and heart regeneration following apical resection (AR) surgery. Primary cardiomyocytes isolated from neonatal mice were used to assess the influence of Tudor-SN on cardiomyocyte proliferation in vitro. Affinity purification and mass spectrometry were employed to elucidate the underlying mechanism. H9c2 cells and mouse myocardia with either overexpression or knockout of Tudor-SN were utilized to assess its impact on the phosphorylation of Yes-associated protein (YAP), both in vitro and in vivo.
RESULTS We previously identified Tudor-SN as a cell cycle regulator that is highly expressed in neonatal mice myocardia but downregulated in adults. Our present study demonstrates that sustained expression of Tudor-SN promotes and prolongs the proliferation of neonatal cardiomyocytes, improves cardiac function, and enhances the ability to repair the left ventricular apex resection in neonatal mice. Consistently, cardiomyocyte-specific knockout of Tudor-SN impairs cardiac function and retards recovery after injury. Tudor-SN associates with YAP, which plays important roles in heart development and regeneration, inhibiting phosphorylation at Ser 127 and Ser 397 residues by preventing the association between Large Tumor Suppressor 1 (LATS1) and YAP, correspondingly maintaining stability and promoting nuclear translocation of YAP to enhance the proliferation-related genes transcription.
CONCLUSIONS Tudor-SN regulates the phosphorylation of YAP, consequently enhancing and prolonging neonatal cardiomyocyte proliferation under physiological conditions and promoting neonatal heart regeneration after injury.
GW35-e0368
Changqing Du
Zhejiang Hospital
OBJECTIVES To investigate the role of farnesyl diphosphate synthase (FDPS) in abdominal aortic aneurysm (AAA) formation in angiotensin II-infused (Ang II) Apolipoprotein E-knockout (ApoE−/−) mice and the underlying mechanisms.
METHODS AAA was established using subcutaneous implantable osmotic pump infused with Ang II in ApoE−/− mice for 4 weeks. Mice in the AD-FDPS-RNAi group were injected with interfering adenovirus (AD-FDPS-RNAi) via tail vein every two week.
RESULTS At the end of the experiments, both the mortality rate and the AAA formation rate were significantly reduced after AD-FDPS-RNAi intervention. The ultrasound results showed that the average maximum diameter of abdominal aorta was significantly elevated in Ang II-induced aortas, but it was significantly reduced after knockdown of FDPS. Histological staining revealed that knockdown of FDPS improves aortic structural remodeling in Ang II-induced AAA mice. Furthermore, immunohistochemical staining indicated that knockdown of FDPS reduces the phenotypic switching of smooth muscle cells (SMCs). Western blotting further demonstrates that expression levels of p-P38, p-ERK1/2, p-JNK were significantly elevated in the Ang II-induced aortic tissues, and decreased after knockdown of FDPS. The activity of RhoA, Rac1, and Ras were all significantly increased in the Ang II-induced AAA model. However, after knockdown of FDPS expression, the activity of RhoA, Rac1 were significantly reduced, but there was no effect on the activity level of Ras.
CONCLUSIONS In conclusion, knockdown of FDPS may attenuate Ang II-induced AAA formation as well as vascular remodeling in AAA, which may be dependent on RhoA/MAPKs and Rac1/MAPKs pathways.
GW35-e0369
Wang Ruiyu
Sichuan Provincial People’s Hospital
OBJECTIVES Cardiac dysfunction often occurs following cardiac arrest (CA) and is a common complication associated with high mortality during post resuscitation care. However, limited medical interventions are currently available due to the complex pathophysiological processes of CA. This study aimed to investigate the role of cyclic GMP-AMP synthase (cGAS), a stimulator of interferon genes (STING) pathway in post-CA myocardial dysfunction.
METHODS In vivo, ventricular fibrillation (VF)-induced CA was induced in rats, and RU.521 (a cGAS inhibitor) was administered to inhibit cGAS activity. In vitro, H9C2 cardiomyocytes were subjected to hypoxia and reoxygenation (H/R) to mimic CA occurrence and were transfected with a specific siRNA targeting cGAS to block activation of the cGAS-STING pathway.
RESULTS We found that both in the myocardial tissues from rats after spontaneous circulation (ROSC) and in H/R-treated H9C2 cells, the protein level of cGAS was significantly upregulated, in parallel with the activation of the cGAS-STING pathway. Administration of RU.521 effectively improved cardiac function and maintained hemodynamic stability in rats after ROSC. Knockdown of cGAS with siRNA protected H9C2 cells against H/R-induced cell injury. Furthermore, inhibition of cGAS effectively mitigated CA-induced mitochondrial injury while suppressing oxidative stress and apoptosis.
CONCLUSIONS These findings suggest that the cGAS-STING pathway contributes to myocardial injury following CA, highlighting targeting cGAS as a promising therapeutic approach for improving cardiac function in patients after CA.
GW35-e0384
Ningxia Wu, Fei Li
The Affiliated Hospital of Yan’an University
OBJECTIVES To identify the genes related to acute myocardial infarction by WGCNA analysis, so as to provide a basis for the treatment of acute myocardial infarction.
METHODS The collected datasets were analyzed by using Rstudio to search for the keyword “AMI” in the GEO database, and the key genes in the key modules were screened out by introducing the “Limma package” for differentiation analysis, GO enrichment analysis and KEGG enrichment analysis were used for gene identification, and WGCNA was used for gene identification.
RESULTS After searching the GEO database GSE48060, GSE66360 the differential genes were obtained by using Rstudio to introduce relevant calculation methods, including 403 differential genes and 64 GSE48060 differential genes in the GSE66360. Subsequently, WGCNA analysis was carried out, and two key modules with different colors were obtained, a total of 276 light green modules and 1106 blue modules. GO enrichment analysis and KEGG enrichment analysis were performed on the genes of key modules, and the related metabolic pathways were analyzed and summarized. Finally, by plotting the Venn diagram, four key hub genes were obtained, namely SLPI, AQP9, MGAM and MMP9.
CONCLUSIONS WGCNA was used to study sepsis-related susceptibility modules and genes. Our study identified two modules and four key genes as important components of the etiology of acute myocardial infarction, which may improve our understanding of its molecular mechanisms.
GW35-e0385
Ningxia Wu, Fei Li
The Affiliated Hospital of Yan’an University
OBJECTIVES He differentially expressed genes (DEGs) and related drug candidates of acute myocardial infarction (AMI) were analyzed by bioinformatics methods, in order to provide targets for the drug treatment of AMI.
METHODS Download GSE66360 microarray (including myocardial tissue microarray data from 99 patients, including 50 AMI patients and 49 normal people) from the Gene Expression Database (GEO) of the National Center for Bioinformatics (NCBI). The limma software package in R language was used to screen DEGs of AMI with a differential expression fold of no less than 2 times and a corrected P value of <0.05, and the ClusterProfiler software package was used for gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The STRING online database was used to analyze and screen key genes for protein-protein interaction (PPI) networks, Metascape databases, and David databases. The Comparative Toxicology Genome Database (CTD) was used to screen drugs acting on key genes, and the Correlation Atlas (CMAP) database was used to screen small molecule compounds negatively associated with DEGs.
RESULTS A total of 24 ferroptosis-related DEGs were screened in the AMI group compared with the control group. Among them, a total of 23 DEGs were raised and 1 DEGs were downgraded. The results of GO enrichment analysis showed that the biological processes involved in these genes mainly included the negative regulation of cell response to lipopolysaccharide, cell proliferation, angiogenesis, response to xenobiotic stimulation and NF-κB transcription factor activity. KEGG results showed that these genes were mainly involved in the iron TNF signaling pathway, IL-17 signaling pathway and leishmaniasis in acute myocardial infarction. PPI network analysis showed that IL1B, JUN, PTGS2, DUSP1, EGR1, CDKN1A, TNFAIP3 and CXCL2 were the key genes, and a total of 2 MOCODES were generated, and the expression of all genes was up-regulated. Subsequently, 8 Hub genes were analyzed, and the top 10 drugs recommended for acute myocardial infarction were obtained. Resveratrol acting on IL1B was screened in the CTD database as a potential effective drug for the treatment of AMI. A total of 16 small molecule drugs negatively related to AMI were successfully screened in the CMAP database, and aspirin and resveratrol were the most promising drugs for the treatment of AMI.
CONCLUSIONS Based on GEO bioinformatics analysis, CREB5, CXCL2, EGR1, IL1B, JUN, PTGS2, ATG7 and GABARAPL1 were the key genes for the occurrence and development of AMI. Aspirin and resveratrol are potentially effective drugs for the treatment of ICM. Bioinformatics analysis revealed the potential role of ferroptosis-related genes in acute myocardial infarction, and the pivotal genes and potential drugs may become new biomarkers for prognosis and precision therapy in the future.
GW35-e0386
Wei Wang
Department of Cardiology, Daping Hospital, The Third Military Medical University (Army Medical University), Chongqing, P.R. China
OBJECTIVES Myocardial infarction (MI) and subsequent heart failure are leading causes of death worldwide. Certain species, such as zebrafish, and neonatal mammals are capable of cardiac regeneration following myocardial injury through the proliferation of pre-existing cardiomyocytes; however, regeneration of adult mammalian heart tissue after injury is difficult to achieve, leading to an increased likelihood of heart failure. Therefore, stimulating adult cardiomyocyte proliferation is a promising therapeutic strategy for treating MI. Recent studies have highlighted inflammatory cells and cytokines as key drivers of cardiac regeneration. In the context of cardiac inflammation following MI, C-C motif chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein 1 (MCP1), is one of the most significantly upregulated cytokines. CCL2 levels in plasma and heart tissue are elevated in animals and humans with MI, and cardiac over-expression of CCL2 attenuates cardiac dysfunction and enhances cardiac healing. However, it is not known if CCL2 regulates cardiomyocyte proliferation.
METHODS MI model was performed on adult C57BL/6J mice. The expression of CCL2 was assessed in mouse heart tissue and plasma after MI. Recombinant CCL2 (rCCL2) protein was administrated through myocardial injection following MI. The effect of rCCL2 on cardiomyocyte proliferation, cardiomyocyte apoptosis, cardiac function and scar size were determined in mice after MI. In vitro, primary cardiomyocytes were isolated from postnatal day 1 (P1) and postnatal day 7 (P7) neonatal mouse heart.
RESULTS MI was induced in adult mice by permanent ligation of the left anterior descending artery, we showed that the serum and cardiac CCL2 levels were significantly increased in MI mice. Intramyocardial injection of recombinant CCL2 (rCCL2, 1 μg) immediately after the surgery significantly promoted cardiomyocyte proliferation, improved survival rate and cardiac function, and diminished scar sizes in post-MI mice. Alongside these beneficial effects, we observed an increased angiogenesis and decreased cardiomyocyte apoptosis in post-MI mice. Conversely, treatment with a selective CCL2 synthesis inhibitor Bindarit (30 μM) suppressed both CCL2 expression and cardiomyocyte proliferation in P1 neonatal rat ventricle myocytes (NRVMs). We demonstrated in NRVMs that the CCL2 stimulated cardiomyocyte proliferation through STAT3 signaling: treatment with rCCL2 (100 ng/mL) significantly increased the phosphorylation levels of STAT3, whereas a STAT3 phosphorylation inhibitor Stattic (30 μM) suppressed rCCL2-induced cardiomyocyte proliferation.
CONCLUSIONS In conclusion, this study suggests that CCL2 promotes cardiac regeneration via activation of STAT3 signaling, underscoring its potential as a therapeutic agent for managing MI and associated heart failure.
GW35-e0396
Pin fang Kang1,2, Zheng yu Sun1,2, Hong yan Sun1,2, Guo qign Lu1,2, Wendi Jiang3, Lei Wang1,2, Bi Tang1,2
1Department of Cardiovascular Medicine of The First Affiliated Hospital of Bengbu Medical University
2Key Laboratory of Basic and Clinical Cardiovascular and Cerebrovascular Diseases, Bengbu Medical University
3Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Bengbu Medical University
OBJECTIVES Pulmonary hypertension (PH) is a progressive and fatal disease caused by end-stage occlusion of a distal pulmonary artery (diameter <500 μm), causing high pulmonary vascular resistance, pulmonary artery pressure, and right ventricular hypertrophy, which lead to right heart failure and death. Hypoxic pulmonary vasoconstriction (HPV) is a reflex constriction of vascular smooth muscle in the pulmonary circulation. This study aims to investigate the role of Salidroside (Sal) in pulmonary arterial dilatation and the potential mechanism of Sal regulating hypoxic pulmonary hypertension in vitro and in vivo.
METHODS A rat model of hypoxic pulmonary hypertension (HPH) was constructed using hypoxic chamber. The effect of Sal on HPH were evaluated using vascular ring, whole cell patch-clamp, WGA staining, HE staining, and Sirius Scarlet staining assays.
RESULTS Sal treatment alleviated the injury of acute hypoxia on pulmonary circulation in SD rats. Meanwhile, Sal treatment reduced the pulmonary vascular tone of acute hypoxia in a concentration-dependent manner, which was involved in the TWIK-related acid-sensitive potassium channel 1 (TASK-1) mediating diastolic effect. We found that Sal treatment significantly increased the TASK-1 current of pulmonary artery smooth muscle cells (PASMCs) in a concentration-dependent manner, as well as reversed the inhibitory effect of acute hypoxia on the TASK-1 current. Moreover, Sal treatment improved the TASK-1 current density, promoted the proliferation, and suppressed the apoptosis of PASMCs in SD rats under continuous hypoxic condition. In addition, we found that the electrophysiological remodeling and pulmonary vascular remodeling of PASMCs were improved by the treatment of Sal through the regulation of TASK-1 channel.
CONCLUSIONS Sal could alleviate HPH by restoring the function of TASK-1 channel, which may provide a novel method for the treatment of HPH.
GW35-e0397
Xinxin Zhu, Haibo Jia, Bo Yu
2nd Affiliated Hospital of Harbin Medical University
OBJECTIVES Accumulating evidence suggests that pyroptosis, especially macrophage pyroptosis, is involved in the pathogenesis of inflammatory diseases, such as atherosclerosis, ulcerative colitis and systemic lupus erythematosus. It was found that there is a large number of macrophages pyroptosis in advanced atherosclerotic plaques, and NLRP3 specific inhibitors significantly slow the progression of atherosclerosis. Furthermore, several studies showed that some drugs for inflammatory diseases, such as melatonin and statin, have also recently been found have a protective effect against macrophage pyroptosis. Taken tougher, macrophages pyroptosis could be a pharmacological target for inflammatory diseases.
Quercetin is a natural flavonoid widely distributed in vegetables and fruits with various biological activities such as anti-oxidation and anti-inflammation. Recent studies have reported that quercetin possess protective effects on inflammatory diseases, and decreases the serum inflammatory factors in osteoarthritis and atherosclerosis model. However, to the best of our knowledge, the effect of quercetin on pyroptosis has not been investigated.
METHODS LPS/ATP treatment was used to induce THP-1 macrophage pyroptosis, different concentrations of quercetin were used to pretreat THP-1 macrophages before LPS/ATP induction. Cell counting kit-8 (CCK-8) assay was used to evaluate cell viability. Scanning electron microscope (SEM) was used to detect cell morphology. Hoechst/PI staining and LDH assay were performed to evaluate the cell membrane integrity. The expression of key components and effectors of NLRP3 inflammasome were examined by real-time PCR and western blot. Immunofluorescence staining was used to analysis the reactive oxygen (ROS) level and P65 translocation.
RESULTS Our results showed that quercetin prevented THP-1 macrophage pyroptosis by attenuating the expression of NLRP3 and cleaved-caspase1, inhibiting the maturation of IL-1β and N-GSDMD. Quercetin suppressed NLRP3 inflammasome activation by inhibiting ROS overproduction. Moreover, quercetin inhibited the phosphorylation of P65 and its translocation from cytoplasm into nuclear. In addition, we found that quercetin attenuated the increase of TLR2 and p-AMPK induced by LPS/ATP, while both TLR2 and AMPK agonist alleviated the protective effect of quercetin on macrophages pyroptosis.
CONCLUSIONS In this study, we found quercetin, a natural polyphenolic compound, exerts an anti-pyroptosis effect in macrophages. Quercetin dose-dependently inhibited NLRP3 inflammasome activation, as well as mitigated the mutation of N-GSDMD and IL-1β. The results also showed that quercetin inhibited the nuclear translocation and phosphorylation of P65. Furthermore, quercetin also attenuated the ROS overproduction and suppressed the expression of NLRP3 inflammasome compounds, which suggested that quercetin prevented the activation of NLRP3 inflammation by suppressing ROS overproduction. In addition, quercetin attenuated the increase of TLR2 and p-AMPK induced by LPS/ATP, and the specific activation of TLR2 and AMPK diminished the anti-pyroptotic effect of quercetin. Generally, we found that quercetin prevented macrophage pyroptosis via TLR/Myd88/NF-κB and ROS/AMPK pathway.
GW35-e0400
Xinxin Zhu1,2, Haibo JIa1,2, Bo Yu1,2
1Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, P.R. China
2Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, P.R. China
OBJECTIVES Micheliolide (MCL), which is the active metabolite of parthenolide, has demonstrated promising clinical application potential. However, the effects and underlying mechanisms of MCL on atherosclerosis are still unclear.
METHODS ApoE−/− mice were fed with high fat diet, with or without MCL oral administration, then the plaque area, lipid deposition and collagen content were determined. In vitro, MCL was used to pretreat macrophages combined by ox-LDL, the levels of ferroptosis related proteins, NRF2 activation, mitochondrial function and oxidative stress were detected.
RESULTS MCL administration significantly attenuated atherosclerotic plaque progress, which characteristics with decreased plaque area, less lipid deposition and increased collagen. Compared with HD group, the level of GPX4 and xCT in atherosclerotic root macrophages were increased in MCL group obviously. In vitro experiment demonstrated that MCL increased GPX4 and xCT level, improved mitochondrial function, attenuated oxidative stress and inhibited lipid peroxidation to suppress macrophage ferroptosis induced with ox-LDL. Moreover, MCL inhibited KEAP1/NRF2 complex formation and enhanced NRF2 nucleus translocation, while the protective effect of MCL on macrophage ferroptosis was abolished by NRF2 inhibition. Additionally, molecular docking suggests that MCL may bind to the Arg483 site of KEAP1, which also contributes to KEAP1/NRF2 binding. Furthermore, Transfection Arg483 (KEAP1-R483S) mutant plasmid can abrogate the anti-ferroptosis and anti-oxidative effects of MC in macrophages. KEAP1-R483S mutation also limited the protective effect of MCL on atherosclerosis progress and macrophage ferroptosis in ApoE−/− mice.
CONCLUSIONS MCL suppressed atherosclerosis by inhibiting macrophage ferroptosis via activating NRF2 pathway, the related mechanism is through binding to the Arg483 site of KEAP1 competitively.
GW35-e0414
Xinpei Wang1, Jiaheng Zhou1, Lina Su2, Zihan Wei3, Jingyi Ren2, Xing Zhang1, Jia Li1, Feng Gao1
1Key Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Air Force Medical University, Xi’an, China
2Heart Failure Center, Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
3Department of Neurology, Xijing Hospital, Air Force Medical University, Xi’an, China
OBJECTIVES Recent studies have unveiled the unique role of amino acids in cardiac pathophysiology. Glutamine, the most abundant non-essential amino acid in circulation, serves as an important energy source in proliferating cells. Current clinical studies reveal that impaired glutaminolysis is associated with an increased risk of cardiovascular events but the underlying mechanism remains largely unknown. This study aims to investigate the role of glutaminolysis in regulating cardiac function at rest and under high workload and the underlying mechanism.
METHODS To investigate the role of glutaminolysis in cardiomyocytes, cardiomyocyte-specific glutaminase (GLS) conditional knockout mice (Gls-cKO) and their control littermates (Gls fl/fl) were generated, and cardiac structure, baseline cardiac function and cardiac reserve were assessed. We also isolated adult mouse cardiomyocytes of Gls fl/fl and Gls-cKO mice to evaluate single cardiomyocyte contraction amplitude under low (1 Hz electrical field stimulation) and high (40 nM Iso combined with 4 Hz electrical field stimulation) workload conditions. Transcriptomic, targeted metabolomic, 13C isotopic labeling and reactive oxygen species emission analyses were performed to investigate the underlying mechanism. To further investigate whether acute glutamine supplementation could enhance cardiac reserve in human, 30 young, healthy participants (age 22.85 ± 3.40 years, comprising 15 males and 15 females) were enrolled in a randomized, double-blind, placebo-controlled crossover study (registered at chictr.org.cn/indexEN.html under the identifier ChiCTR2400082676). Each participant underwent two exercise stress echocardiography with a 3- to 7-day interval. Prior to each test, participants randomly consumed either a placebo or Gln (10 g) beverage.
RESULTS GLS deficiency impaired cardiac reserve and exercise capacity in mice, but had no discernible effects on cardiac structure or function under baseline condition. Inhibition of glutaminolysis in cardiomyocytes did not affect cell morphology, cell survival or contractile function under low workload condition (1 Hz), but diminished contractile function and elevated oxidative stress levels of cardiomyocytes under high workload condition (Iso/4 Hz). Targeted metabolome and metabolic flux demonstrated that cardiac glutaminolysis was upregulated to enhance glutathione (GSH) production, particularly within the mitochondria, under high workload. Supplementation of GSH restored cardiac reserve of Gls-cKO mice, while specifically increasing mitochondrial GSH by heterologous expression of an engineered mitochondrial biosynthetic enzyme in cardiomyocytes improved cardiac reserve of both Gls fl/fl and Gls-cKO mice. Finally, acute glutamine supplementation increased peak systolic and diastolic cardiac function, resulting in improved peak cardiac output in healthy participants, suggesting acute glutamine supplementation could enhance cardiac reserve.
CONCLUSIONS Our findings establish the previously unrecognized role of glutaminolysis in cardiomyocytes, maintaining cardiac reserve via upregulating mitochondrial GSH levels. This suggests that targeting glutaminolysis is a potential strategy for improving cardiac reserve and managing cardiac diseases.
GW35-e0435
Chaochao Li1,2, Hao Fei1,2, Huizi Huang1,2, Jingyi Zhang1,2, Chao Luo1,2, Jiarui Xie1,2, Jinman Gao1,2, Rong Wang1,2
1Research Institute of Atherosclerotic Disease, Xi’an Jiaotong University Cardiovascular Research Center, Xi’an, Shaanxi 710061, China
2Laboratory Animal Center, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061, China
OBJECTIVES SUMOylation, an important protein post-translational modification, is greatly involved in pathological processes of atherosclerosis (AS). Protein inhibitor of activated STAT 3 (PIAS3) acts as a SUMO ligase promoting protein SUMOylation. Our previous study indicated that PIAS3 expression decreased in atherosclerotic lesions and PIAS3 deficiency promotes the phenotypic switching of vascular smooth muscle cells (VSMCs) in atherosclerotic tissues. However, the role of PIAS3-mediated SUMOylation on atherosclerosis remains unclear.
METHODS In this study, male VSMC-specific PIAS3 knockout mice with ApoE−/− background (PIAS3Δsmc/ApoE−/−) at 4 weeks of age were injected via tail vein with adeno-associated virus encoding wild-type PIAS3 (AAV-PIAS3-WT) or ligase activity-deficient PIAS3 (AAV-PIAS3-Mu). AAV-GFP injection group was also included as control. Four weeks after the intravenous administration, the mice were fed with high-fat/high-cholesterol diet (HFCD) for 12 weeks to induce atherosclerosis. Aorta tissues were collected for assessing plaque formation by Oil red O staining and H&E staining. In vitro, a VSMCs cell line (MOVAS) was transfected with plasmids of PIAS3 and PIAS3-Mu respectively. Empty vector (EV) transfection group was also included as control. RT-PCR and Western Blotting detected the expression level of VSMCs phenotypic switching marker. CCK-8 testing, wound-healing assay and transwell assay measured levels of VSMCs proliferation and migration.
RESULTS We discovered that the atherosclerotic plaques in AAV-PIAS3-WT group were obviously less than those in AAV-GFP group, while the plaques in AAV-PIAS3-Mu group were similar to those in AAV-GFP group. RT-PCR and Western blotting results showed that in comparison with the EV transfected control cells, there were lower expression levels of synthetic markers (Vim, Opn) and higher levels of contractile markers (Acta2, Cnn1) in cells with PIAS3 transfection. But the tendency was eliminated in PIAS3-Mu-transfected cells. The results of CCK-8 testing, wound-healing assay and transwell assay showed that PIAS3 significantly suppressed VSMCs proliferation and migration, nevertheless, ligase activity-deficient PIAS3 attenuated its inhibitory effect. It suggests that PIAS3 might influence the phenotypic switching of VSMCs to inhibit atherosclerosis formation by exerting its SUMO ligase activity.
CONCLUSIONS These results indicated that PIAS3-mediated SUMOylation is associated with the formation of AS, as well as playing function on regulation of VSMCs phenotypic switching. This finding improves our understanding on the pathogenesis of atherosclerosis.
GW35-e0437
Xi Zhang, Chenhui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of acute myocardial infarction (AMI) and externalization of several S100 family members. This study investigated the effects of S100A12 on NET formation and myocardial injury following AMI.
METHODS Since S100A12 is a human-specific molecule, lysozyme M promoter-driven S100A12 transgenic (TG) mice were generated to address the role of S100A12 in the heart. Left anterior descending (LAD) coronary artery ligation was conducted to induce AMI in mice. Heart function was assessed by echocardiography. Cardiomyocyte injury and NETs formation were detected in vivo and in vitro. Calcium influx was measured by Fluo-4-AM loading. Quantitative RT-PCR was used to assess changes in transcription. Protein levels were examined by western blotting. Cardiomyocyte apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Adeno-associated virus was used to silence the expression of Annexin A5 (ANXA5). Luciferase reporter assay was conducted to assess promoter activity.
RESULTS S100A12 expression increased rapidly in neutrophils and peaked on day 1 after MI, which promoted NET production and cardiomyocyte apoptosis and exacerbated myocardial injury. Further, we showed that DNase I, an inhibitor of NETs, reduced apoptosis of cardiomyocytes induced by S100A12. Mechanistically, we demonstrated that S100A12 interacted with ANXA5 to enhance the calcium influx and promoteNET formation. Blockage of ANXA5 effectively attenuated heart function impairment after MI. Additionally, we found that hypoxia-inducible factor-1α (HIF1α) directly bound to the S100A12 promoter to increase S100A12 expression. Finally, we showed that plasma S100A12 levels correlated with the concentration of dsDNA, and this correlation was associated with an increased risk of all-cause mortality during the 1-year follow-up of AMI patients.
CONCLUSIONS These findings revealed the critical role of S100A12 in regulating neutrophils activation and NET formation, resulting in aggravated myocardial injury after AMI. Therefore, the S100A12-annexin A5-calcium influx axis may represent a promising marker and a potential target for the treatment of AMI.
GW35-e0445
Jie Xu1,2, Qing Pan2, Tianyi Lu2, Rongzhen Zhang1, Ning Yang3, Yingying Wei4, Sibin Guan1, Yagang Ding5, Zhenjun Li2, Bo Yang2, Wei Han1,2
1Department of Heart failure, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
2Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
3Department of Echocardiography, The First Affiliated Hospital of Harbin Medical University, Harbin, China
4Department of Cardiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
5Department of Cardiac Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
OBJECTIVES Calcium channel α2δ2 subunit, encoded by CACNA2D2 gene, is most abundantly expressed in atrium, but its function for atrial disease is poorly understood. This study aimed to assess whether α2δ2 protein expression participates in the development of atrial fibrosis and atrial fibrillation (AF).
METHODS We have collected right atrial appendage tissues to measure the expression level of α2δ2 proteins from patients with atrial fibrillation and sinus rhythm. The expression of α2δ2 protein in right atrial appendages from AF patients was investigated by immunoblotting and immunofluorescence. Next, we transfected rats with adeno-associated virus 9 encoding α2δ2 protein via tail-vein injection to explore the incidence and duration of AF and atrial fibrosis. Additionally, the samples of fibroblasts overexpressing α2δ2 were sent to perform transcriptional sequencing to reveal signaling pathway responsible for fibroblasts activation in fibroblasts overexpressing α2δ2.
RESULTS The expression of α2δ2 protein in right atrial appendages from AF patients was significantly upregulated compared to sinus rhythm patient samples. Co-immunofluorescence staining indicated that α2δ2 proteins were significantly higher in vimentin positive fibroblasts in AF patients compared with those in SR patients. Next, α2δ2 overexpression significantly increased the incidence and duration of AF, and shortened the atrial effective refractory period. Remarkably, α2δ2 overexpression significantly induced atrial fibrosis evidenced by upregulation of TGF-β1/Smads signal pathway. Additionally, fibroblasts overexpressing α2δ2 exhibited enhanced expression of collagen I and TGF-β1. Transcriptional sequencing revealed a marked activation of the MAPK signaling pathway in fibroblasts overexpressing α2δ2, and intracellular free calcium levels were notably elevated. Importantly, treatment with SB203580, a p38 phosphorylation inhibitor, or the intracellular calcium chelator BAPTA-AM, led to significant inhibition of activation in fibroblasts overexpressing α2δ2.
CONCLUSIONS We demonstrate that elevated expression of calcium channel subunit α2δ2 may lead to atrial fibrosis and we show that α2δ2 overexpression results in fibroblast activation, which may be mediated by Ca2+/p38 signal pathway.
GW35-e0454
Qingbin Hou, Chenhui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Abdominal aortic aneurysm (AAA) is a life-threatening condition in which progressive expansion of the infrarenal aorta may lead to rupture, which is associated with high mortality. The phenotypic switching of vascular smooth muscle cells (VSMCs) serves as a significant foundation for AAA. Several studies have demonstrated that miRNAs are involved in mediating the process of AAA and circulatory miRNAs are proposed as potential diagnostic and prognostic biomarkers. miR3154, a newly identified microRNA that up-regulated in AAA model, and whether and how miR3154 regulates VSMC differentiation in AAA, the underlying mechanisms are still unclear.
METHODS AngII – induced murine AAA model was used to study VSMC phenotypic transition, proliferation and migration in vivo. RNA-seq analysis, cell migration assay, cell invasion assay, collagen gel contraction assay, protein interactome analysis, immunofluorescence, immunohistochemistry, Flourescence in situ hybridization, Molecular dynamics simulation were performed to clarify the phenotype and elucidate the molecular mechanisms.
RESULTS miR-3154 was found up-regulated in the VSMC of AngII-induced murine AAA model through miRNA expression profiles. And it found to increase in the early stage of aneurysm formation in Angiotensin II-induced AAA mice model. Moreover, miR-3154 was significantly increased in the serum of patients with AAA, which was proportional to the size of aneurysm by CT. Mechanically, miR-3154 was also demonstrated to aggravate vascular smooth muscle cells (VSMCs) phenotypic switching to promote its de-differentiated phenotype and VSMCs migration in vivo and in vitro. Tensin1 (TNS1) was identified as a direct target of miR-3154, The immunofluorescence-Fluorescence in situ hybridization shows that they are co-located, and miR-3154 was certified to interact with 3’ untranslated region of TNS1 mRNA by dual-luciferase reporter assay. More important, specific knockdown of TNS1 protein in VSMCs using adeno-associated virus can significant aggravated AngII-induced AAA formation. Further protein interactome analysis, co-immunoprecipitation, and Molecular dynamics simulation revealed that TNS1 G3 domain (amino acids 1262 – 1735) directly interacts with the G2 domain (amino acids 401 – 1580) of TLN1 particular into VSMCs phenotypic switching and migration. The average fluctuation amplitude of The RMSD curve of TLN1-TNS1 was 1.9 Å. The number of hydrogen bonds formed between TLN1 and TNS1 complexes during the simulation of 150 ns was found to be basically stable at 40 and reached 61 at the most. The most energy-contributing amino acids are: ALA1790, ARG277, PRO2230, LYS1361, THR344, GLN1356, ALA1789, ASN1507, LYS343, ARG1652, THR1428, GLY1844, GLU1362, MET319 and ALA2229. Further, miR-3154 blocks TNS1-TLN1 interaction by silencing TNS1 expression to inhibit transcriptional factor Meox1 expression, which involved into the VSMCs phenotypic switching and migration.
CONCLUSIONS miR3154 restrains the contractile phenotype of VSMCs through TNS1-TLN1 signaling in vitro and in vivo. Its modulation in the context of disease could be exploited for therapeutic purposes.
GW35-e0455
Qingbin Hou, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China.
OBJECTIVES White adipose tissue is an important endocrine organ of human body. But how its modulates vascular function and atherosclerosis through endocrine mechanisms remains poorly understood. In previous studies, it was found that CREG1, as a glycoprotein molecule, regulates homeostasis of vascular wall cells and inhibits inflammation of vascular histiocytes and macrophages, Whether it can also play an anti-atherosclerotic role in adipose tissue is unknown.
METHODS We generated APOE−/−CREGfl/fl AdipQ cre and APOE−/−CREGfl/fl, APOE−/− and APOE−/−CREGtg mice, Susceptibility to atherosclerosis was evaluated in whole aortae and cross sections of the aortic sinus in male and female mice fed a high-fat Western diet for 14 weeks, starting at 8 weeks.
RESULTS CREG1 was downregulated in white adipose cell of APOE−/− mice fed a Western diet compared with chow diet. On Western diet, APOE−/−CREGfl/fl AdipQ cre mice exhibited marked increase in atherosclerotic lesion formation, expanded immune and inflammatory cell content in aortas, and increased necrotic core content compared with APOE−/−CREGfl/fl.APOE−/−CREGtg mice compared with APOE−/− mice, Contrary to the above results. Mechanistically, we show that CREG1 loss specifically decreased the expression of AMPKγ2. Its leads to increased expression of the transcription factor SREBP1, which promotes cholesterol metabolism, and triggers an inflammatory response. We further show that ox-LDL (oxidized LDL) treatment decreased adipose cell CREG1, its promoted the degradation of AMPKγ2.
CONCLUSIONS Adipose cell CREG1 delays atherogenesis by inhibiting proinflammatory recruitment and transcriptional activation of SREBP1 in part by upregulating AMPKγ2, implicating that targeting CREG1 in white adipose cell may serve as a novel therapeutic strategy to treat atherosclerosis.
GW35-e0456
Zheming Yang1,2, Chenhui Yan1, Yaling Han1,2
1State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
2College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China
OBJECTIVES Sorafenib (Sor) is a commonly used chemotherapeutic drug for hepatocellular carcinoma, but its use is limited due to significant cardiac dysfunction as a side effect. Currently, there are no clinical drugs available to alleviate this side effect. Recent research suggests that Sor-induced cardiac dysfunction may be attributed to necroptosis, a unique type of programmed cell death. Previous studies have identified cellular repressor of E1A stimulated genes (CREG) as a crucial protein involved in maintaining the heart’s physiological and pathological processes. Interestingly, CREG was initially characterized as a tumor suppressor gene. This study aims to investigate whether CREG can mitigate Sor-induced cardiac dysfunction by interfering with necroptosis without affecting Sor’s anticancer effects. The findings from this research could potentially offer a novel approach to address the negative cardiac side effects of Sor, enhance its usage in treating hepatocellular carcinoma, and improve patient outcomes.
METHODS C57BL/6 mouse hearts were subjected to single-cell sequencing analysis after 8 weeks of oral administration of Sor. Mice with CREG knockout, CREG overexpression, and mice pretreated with recombinant 0.3 mg/kg · d CREG protein infusion were subjected to Sor treatment, and cardiac function was assessed using animal ultrasound technology. Sor-induced myocardial injury was investigated through histological analyses, quantitative RT-PCR, and western blotting. HepG2 cell lines and primary mouse cardiomyocytes were treated with Sor and various other interventions. Cardiomyocyte necroptosis was evaluated using flow cytometry, western blotting, and transmission electron microscopy (TEM). Mitochondrial Ca2+ uptake was measured using Rhod-2 probes and confocal imaging. Downstream proteins directly bound and regulated by CREG were detected using immunoprecipitation, mass spectrometry, immunofluorescence staining, and Western blotting. Molecular docking, dynamic simulation, and Western blotting were employed to identify the active fragments of CREG involved in regulating necroptosis.
RESULTS Single-cell sequencing analysis revealed that Sor treatment led to a reduction in the expression of CREG in cardiomyocytes. In vivo experiments demonstrated that Sor reduced CREG expression by downregulating the transcription factor FOXO3a. Loss-of-function studies indicated that CREG deficiency exacerbated Sor-induced cardiac dysfunction, while gain-of-function research showed that CREG overexpression had the opposite effect. In vitro experiments also revealed that CREG overexpression reduced Sor-induced necroptosis, whereas silencing CREG worsened Sor-induced necroptosis. Importantly, treatment of mice with recombinant CREG protein effectively alleviated Sor-induced cardiac dysfunction. Mechanistically, our results suggested that CREG regulated necroptosis through the modulation of TYK2. Overexpressed CREG inhibited TYK2 expression by promoting TYK2 degradation in lysosomes, thereby suppressing Sor-induced myocardial necroptosis. Moreover, we observed that CREG did not impact Sor-induced death of liver cancer cells.
CONCLUSIONS The overexpression of CREG rescued Sor-induced cardiomyocyte necroptosis without interfering with its antitumor effects. This finding suggests that CREG’s protective role in Sor-induced cardiac dysfunction may be specific to the heart, rather than exerting a general effect on Sor’s antitumor activity. CREG protein holds promise as a potential clinical application for preventing Sor-induced cardiac dysfunction.
GW35-e0457
Zheming Yang1,2, Chenhui Yan1, Yaling Han1,2
1State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
2College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China
OBJECTIVES Psoriasis is a chronic inflammatory skin disorder characterized by abnormal keratinocyte proliferation and immune system dysregulation, leading to scaly plaques. It is associated with an increased risk of comorbidities, particularly cardiovascular diseases like acute myocardial infarction (AMI), a major cause of global morbidity and mortality. Despite the known correlation between psoriasis and AMI, the molecular pathways connecting these conditions are poorly understood. Therefore, it is crucial to unravel the molecular basis of their association to improve diagnostic approaches, develop targeted therapies, and enhance disease management strategies. Achieving these goals will significantly alleviate the burden of psoriasis and AMI on individuals and healthcare systems worldwide.
METHODS We conducted bioinformatics analyses using gene expression datasets to identify differentially expressed genes (DEGs) and hub genes associated with both psoriasis and AMI. Additionally, we constructed protein-protein interaction (PPI) networks and transcription factor-DEG networks to elucidate regulatory interactions among these key genes. Furthermore, we investigated immune cell infiltration patterns and their correlation with gene expression profiles in psoriasis and AMI patients, utilizing advanced computational tools. To assess the diagnostic potential of the identified hub genes, we evaluated their expression levels in disease contexts. Moreover, we performed molecular docking simulations to investigate the binding interactions between simvastatin, a commonly used medication for cardiovascular diseases, and the key target proteins identified. Finally, to experimentally validate our findings, we utilized immunohistochemistry techniques to examine the expression of hub genes in myocardial infarction tissue samples from mice and psoriasis patient tissues.
RESULTS Our comprehensive analysis revealed 37 DEGs associated with chemotaxis and signaling pathways of inflammatory cells, shedding light on the underlying mechanisms connecting psoriasis and AMI. Through PPI network analysis, we identified 7 hub genes strongly associated with immune cells. CXCL8, IL1B, S100A9, and S100A12 stood out among these hub genes due to their remarkable diagnostic potential in distinguishing between psoriasis and AMI. These genes exhibited significantly elevated expression levels in both myocardial infarction tissue samples from mice and psoriasis patient tissues, emphasizing their relevance in the pathogenesis of both conditions. Furthermore, molecular docking simulations indicated potential interactions between simvastatin and these key target proteins, suggesting the therapeutic relevance of simvastatin in modulating the activity of CXCL8, IL1B, S100A9, and S100A12, further supporting its potential as a treatment option for individuals with psoriasis and AMI.
CONCLUSIONS Our study employing comprehensive bioinformatics analyses, uncovers shared molecular signatures and potential therapeutic targets in psoriasis and AMI. The identification of DEGs, hub genes, and immune-related pathways highlights the role of immune dysregulation in the development of both conditions. The promising diagnostic potential of CXCL8, IL1B, S100A9, and S100A12 emphasizes their importance as potential biomarkers for psoriasis and AMI. Furthermore, the potential interactions between simvastatin and these proteins suggest its utility as a therapeutic agent targeting shared pathways. These findings provide a foundation for future studies investigating common mechanisms and developing targeted therapies for psoriasis and AMI, contributing to advancements in clinical practice.
GW35-e0472
Zheming Yang1,2, Chenhui Yan1, Yaling Han1,2
1State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
2College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China
OBJECTIVES Guanxinshutong capsule (GXST), a traditional Chinese medicine, has been widely used for treating cardiovascular disease and has shown promising efficacy in improving symptoms and enhancing the quality of life for patients with heart failure (HF). However, the precise mechanisms underlying GXST’s therapeutic effects in HF remain poorly understood. To bridge this knowledge gap, we adopted an integrated approach combining network pharmacology, molecular dynamics simulations, and in vitro validations to investigate the potential targets and molecular pathways through which GXST exerts its effects against HF.
METHODS We curated active ingredients and target genes of GXST, along with relevant genes associated with HF, from various public databases. Through rigorous bioinformatics analysis, we constructed comprehensive networks that depict the intricate interactions between ingredients, disease, and targets. Furthermore, we performed functional annotations of the core targets to gain insight into their biological roles. Molecular dynamics simulations were conducted to validate the binding affinities between the identified protein-ligand complexes. In vitro evaluations, including assessments of cell proliferation, apoptosis, and protein expression, were performed on HUVEC cells treated with GXST to evaluate its pharmacodynamics.
RESULTS Our network analysis revealed 320 intersection genes and 74 active ingredients within the Herbs-ingredients-target genes-disease network. We identified key active ingredients and target genes that overlapped, providing crucial leads for further investigation. KEGG pathway analysis of the intersection genes primarily indicated enrichment in the PI3K-Akt signaling pathway and apoptosis. Noteworthy proteins in the protein-protein interaction network included AKT1, VEGFR2, and eNOS. Molecular dynamics simulations confirmed stable docking and lower binding energy between four identified ingredients (kaempferol, quercetin, (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl) chroman-4-one, and ellagic acid) and their respective core proteins (VEGFR2, eNOS, and AKT). In vitro verifications aligned with the in silico predictions, demonstrating the protective effects of GXST against H2O2-induced apoptosis in HUVEC cells, as well as the activation of the VEGFR2/AKT/eNOS signaling pathways.
CONCLUSIONS This multidisciplinary study sheds light on the underlying mechanisms responsible for the therapeutic effects of GXST in heart failure. The involvement of the VEGFR2/AKT/eNOS signaling pathways suggests their significance in further elucidating and applying GXST in the clinical treatment of heart failure. By employing a comprehensive approach, our findings contribute to a deeper understanding of GXST’s actions and support its potential as a viable treatment option for heart failure, warranting further clinical investigation and application.
GW35-e0474
Jiaqi He, Chenhui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES To unveil the dynamic transcript profiles of myocardial lymphangiogenesis post myocardial infarction.
METHODS This study integrated single-cell sequencing data and spatial transcriptome data from mouse heart tissue at different time points post-myocardial infarction (MI) from publicly available data in the ArrayExpress and gene expression omnibus (GEO) databases.
RESULTS We identified four transcriptionally distinct subtypes of lymphatic endothelial cells (LECs) and localized them in space. In early MI (D3), LEC capillary I (ca I), ca III and LEC collecting (co) were mainly distributed in the infarct zone (IZ) and border zone (BZ), with LEC ca III being significantly higher in the IZ. In contrast, LEC ca II was mainly distributed in the BZ and RZ, and was significantly reduced in the IZ. As the morphology of the infarcted area gradually became clear, on D7, LEC ca I continued to increase in the IZ region, LEC ca III was still mainly distributed in the IZ, LEC co migrated from the BZ to the IZ, and LEC ca II showed no significant spatial localization or expression differences, but were still highly expressed in the BZ and RZ. Additionally, LEC ca III may be involved in the direct regulation of myocardial injuries in infarcted zone from the perspective of metabolic stress, while LEC ca II may be related to the rapid immune inflammatory responses of the border zone in the early stage of MI. LEC ca I, as well as LEC collection mainly participate in the regulation of myocardial tissue edema resolution in the middle and late stages post-MI. Cell trajectory and Cell-Chat analyses further identified that LECs may regulate myocardial edema through Aqp1, and might affect the infiltration of macrophages through the galectin9-CD44 pathway.
CONCLUSIONS Our study revealed the dynamic transcriptional heterogeneity distribution of LECs in different regions of the infarcted heart, in detail; these LECs formed different functional subgroups, that might exhibit different bioeffects in myocardial tissue post-MI.
GW35-e0475
Haixu Song, Chenhui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES The inflammatory response and repair of myocardial tissue after myocardial infarction (MI) play an important role in the prognosis of MI; in which macrophages play an important role. In this study, we have attempted to elucidate whether CREG1, a widely expressed differentiation homeostasis regulatory protein, is involved in the repair of myocardial injury after MI by regulating macrophage function.
METHODS Western blotting, immunofluorescence, flow cytometry, and qPCR were used to study the expression profile of CREG1. The miRNA chip and transcription factor chip were used to screen CREG1 target genes. Myeloid-specific knockout mice and transgenic mice were used to verify the role of CREG1 in MI in mice. Deletion of CREG1 in macrophages led to further reduction of cardiac function after MI and increased inflammatory cell infiltration in the cardiac tissue in the early stage of MI. The cardiac function of Creg1tg mice was improved compared to that of Creg1wt/wt mice after MI. Reduced CREG1 expression led to increased expression of pro-inflammation-related genes in macrophages; conversely, increased CREG1 expression led to inactivation of macrophage-related genes.
RESULTS CREG1 can regulate the inflammation pathway via the miR-125a/99b/let-7e-5p cluster. Overexpression of miR-125a-5p in CREG1-deficient bone marrow derived macrophages (BMDMs) alleviated the excessive activation of macrophage inflammation. Conversely, inhibition of miR-125a/99b/let7e-5p activated the inflammatory pathway and increased macrophage migration in BMDMs overexpressing CREG1. We found that HOXA5 might bind to the promoter region of miR-125a/99b/let-7e-5p after CREG1 expression was increased. ETS1, as a transcription repressor, inhibits the expression of CREG1 in macrophages after MI. Meanwhile, serological studies on patients with MI suggest that the expression of miR125a-5p, HOXA5, and CREG1 are significantly correlated.
CONCLUSIONS The loss of CREG1 in macrophages causes an increase in cardiac inflammation in the acute phase of MI through downregulation of HOXA5-miR-125a-5p/99b/let7e-5p, which subsequently aggravates cardiac tissue repair and pathological ventricular remodeling.
GW35-e0476
Yuan Wu1,2, Chenghui Yan1, Yaling Han1
1State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
2Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
OBJECTIVES Myocardial infarction (MI), a prominent cause of mortality in cardiovascular diseases, involves a complex interplay of pro-inflammatory and anti-inflammatory processes. Macrophages plays a key role in the early inflammatory response after MI. Although there is currently a large amount of available data on single-cell RNA sequence (ScRNA-seq) describing the differentiation and function of different subtypes of macrophages after MI, they cannot directly reflect the protein changes in cells, and therefore it is difficult to fully elucidate the function of macrophages after myocardial infarction.
METHODS To overcome this issue, we combined scRNA-seq from ArrayExpress database and protein modification omics data done in our laboratory to conduct in-depth analysis of the impact of protein modification changes in macrophage subpopulations in early MI on their function and prognosis of MI.
RESULTS ScRNA-seq data revealed seven cell clusters in macrophages. Mφ-0 and Mφ-2 were associated with leukocyte migration, chemotaxis, and oxidative stress, peaking at 3 days post-MI. By integrating multiomics data, we obtained 128 differentially expressed proteins (DEPs) that were altered at the translational level but not at RNA level in macrophages post-MI. Our result showed that there were 44 DEPs located in Mφ-0 and Mφ-2, and those also were related to inflammation and oxidative stress. Further, we found DEPs in Mφ-0 and Mφ-2 and related to protein metabolism (Dnajb11, Ubl4a) and myocardial contraction (Tpm3, Capg, Lrrc59) showed opposite changes in protein level and Kbhb modifications.
CONCLUSIONS Taken together, PTMs play a crucial role in modulating inflammatory response and oxidative stress in the early stages of MI. This study provides a comprehensive overview of post-translational modifications in macrophages post-MI and lays the groundwork for developing targeted interventions tailored to specific cell types and time points in MI.
GW35-e0477
Jiaxin Xu, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Myocardial Infarction (MI) is one of the most serious forms of cardiovascular disease. MI occurs when coronary artery occlusion leads to ischemia and hypoxia of local cardiomyocytes, resulting in irreversible damage or death. Apoptosis is the most important Programmed Cell Death mode of cardiomyocyte hypoxic injury. The Cellular repressor of E1A-stimulated genes (CREG1) is a lysosomal associated protein that plays an important role in the regulation of differentiated tissues and cell homeostasis. It is very low expressed in embryonic tissues, but widely expressed in mature tissues and cells. To investigate the hypoxia-induced cardiomyocyte death mode and protective mechanism, and elucidate the protective mechanism of lysosomal protein CREG1 against cardiomyocyte hypoxic injury.
METHODS The hypoxia injury model of primary cardiomyocytes cultured in vitro was established by the intervention of different concentrations of Cocl2. Different cell death markers were used to detect cell death. The main death modes of hypoxic-induced cardiomyocyte death were detected by different cell death inhibitors. Western blot and RT-PCR were used to detect the expression of CREG1. Primary cardiomyocytes with CREG1 overexpression and low expression were prepared by adenovirus infection and siRNA transfection, and the regulatory effect of CREG1 on cell death was detected. Lysosome correlation assay was used to detect the changes of cellular lysosome and determine whether the regulation of cardiomyocyte death by CREG1 is related to lysosome function.
RESULTS The hypoxia injury model of primary cardiomyocytes cultured in vitro was established by the intervention of different concentrations of cobalt chloride (CoCl2). Application of different cell death inhibitors testing oxygen induced myocardial cell death of the main manner of death, found that apoptosis inhibitor Z-VAD-FMK could significantly inhibit CoCl2-induced cell death in both in vitro and in vivo studies, suggesting that apoptosis is the main mode of cardiomyocyte death caused by hypoxia. On the contrary, intervention with the Autophagy agonists Resveratrol could inhibit cardiac cell death. The results suggest that CoCl2-induced cell death is mainly apoptosis. The occurrence of apoptosis may be related to the lysosome excessive activation and spillover damage on the lysosomal enzyme, and activate cell autophagy suppresses early myocardial cell death occurred. L-Leucyl-L-Leucine methyl ester (LLOMe) hydrochloridecan induce lysosomal pathway stress to inhibit myocardial cell death. Western blot and RT-PCR detection confirmed that the protein expression of CREG1 decreased rapidly during CoCl2-induced apoptosis, while the RNA level did not change significantly.
CONCLUSIONS Apoptosis was the main cell death induced by hypoxia. CREG1 is involved in the regulation of autophagolysosomal function, reducing apoptosis and alleviating myocardial cell damage.
GW35-e0479
Ting Zhou, Haixu Song, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province 110016, China
OBJECTIVES Myocardial infarction (MI) is the leading cause of premature death among adults. Cardiomyocyte death and dysfunction of the remaining viable cardiomyocytes are the main pathological factors of heart failure after MI. Mitochondrial dysfunction and the resulting oxidative stress have been associated with the pathogenesis of MI. Thus, unveiling the mechanism of mitochondrial network regulation will provide a novel therapeutic strategy for MI and heart failure.
METHODS RNA sequencing (RNA-seq) data from the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo), real-time polymerase chain reaction (RT-PCR), and western blot, were employed to analyze the CDC20 levels in samples of hearts of mice subjected to sham or myocardial infarction (MI) surgery. Mice with CDC20 cardiac-specific overexpression and deficiency mediated by adeno-associated virus serotype 9 (AAV9) were subjected to sham or MI surgery. Mice with CDC20 cardiac-specific overexpression underwent MI surgery, followed by injected with withaferin A. Seahorse XF24 Analyzer was used to understand oxygen consumption (OCR) and extracellular acidification rate (ECAR) in cardiomyocytes and used RT-PCR as well as western blot to analyze the gene expression of mitochondrial biogenesis. MitoTracker Deep Green and JC-1 staining were utilized to analyze the mitochondrial activity of cardiomyocytes. Protein mass spectrometry analysis was utilized to screen the downstream target of CDC20. Co-immunoprecipitation was conducted to identify the ubiquitinated proteins of CDC20.
RESULTS CDC20 expression was increased in MI mice and cardiomyocytes under hypoxia conditions, and positively correlated with impaired mitochondrial biogenesis. Ectopic specifical overexpression of CDC20 aggravated mitochondrial biogenesis in MI mice, which could be rescued by withaferin A treatment. Conversely, specifical knockdown of CDC20 alleviated mitochondrial biogenesis in MI mice. ALDOA acted as a ubiquitinated protein of CDC20 and promoted mitochondrial biogenesis under hypoxia conditions by activating the p38/ERK/MAPK signaling cascade.
CONCLUSIONS These findings demonstrate that CDC20 exerts an impaired effect on mitochondrial biogenesis and holds tremendous promise to act as a target for intervention in MI and HF.
GW35-e0480
Kun Na, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES This study investigates the role and mechanisms of dapagliflozin in regulating endothelial tight junctions and improving abdominal aortic aneurysm (AAA). AAA is a life-threatening condition with a high mortality rate upon rupture, significantly higher than myocardial infarction. The mechanisms behind AAA development and progression remain poorly understood, and there are no effective early pharmacological interventions available. This research aims to explore the potential of dapagliflozin, a Sodium-glucose cotransporter 2 (SGLT2) inhibitor, in improving endothelial tight junctions and preventing AAA.
METHODS Using 8-week-old male ApoE−/− mice, an AAA model was established by subcutaneous implantation of micro-osmotic pumps delivering Angiotensin II (Ang II) at a dose of 1000 ng/kg/min. The study consisted of two main parts: (1) examining the role of endothelial tight junctions in the early stages of AAA formation induced by Ang II in ApoE−/− mice, and (2) investigating the inhibitory effects of dapagliflozin on AAA formation in Ang II-induced ApoE−/− mice. In the second part, mice were divided into four groups: ApoE−/−+Saline, ApoE−/−+Dapagliflozin, ApoE−/−+Ang II, and ApoE−/− +Ang II + Dapagliflozin. Dapagliflozin was administered orally at 10 mg/kg/day 28 days before and during Ang II treatment, and (3) SGLT2 and Tjp1-Dependent Mechanisms in AAA Inhibition by Dapagliflozin.
RESULTS Histological analysis showed significant thickening of the aortic medial layer, elastin degradation, collagen deposition, and CD68-positive cell infiltration in Ang II-treated mice. Dapagliflozin treatment significantly reduced aortic diameter and aneurysm incidence, improved aortic wall structure, and decreased inflammation markers such as CD68, neutrophils, leukocytes, and macrophages. Electron microscopy and En face staining revealed that dapagliflozin restored tight junction protein ZO-1 expression and improved endothelial barrier integrity. The study also explored the SGLT2-dependent mechanisms of dapagliflozin, SGLT2 overexpression in ApoE−/− mice exacerbated Ang II-induced AAA and endothelial damage, negating dapagliflozin’s protective effects. Tjp1 knockdown similarly increased vascular injury, suggesting a central role for SGLT2 and Tjp1 in dapagliflozin’s action. In vitro experiments showed that dapagliflozin mitigated TNF-α-induced downregulation of tight junction proteins in human umbilical vein endothelial cells (HUVECs) through the SGLT2-PRKCZ-Erk pathway and reduced JUN-mediated SGLT2 transcription.
CONCLUSIONS Dapagliflozin significantly improves endothelial barrier function and reduces AAA formation and expansion by targeting SGLT2. This study highlights the potential of dapagliflozin as a therapeutic agent for AAA by maintaining endothelial integrity and preventing vascular inflammation and damage.
GW35-e0481
Yiming LI, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Aortic dissection (AD) is a serious and life-threatening condition which allows blood to enter the vessel wall and causes aorta rapture. NETosis is a type of programmed cell death induced by neutrophils, which is characterized by the release of neutrophil extracellular traps (NETs). In this study, we attempted to elucidate whether NETs components are involved in the occurrence and development of AD and intervene in it.
METHODS Human AD tissue samples from dissecting aortic dissection and sera were collected intraoperatively from patients underwent aorta replacement. The mass spectrometry and single-cell RNA sequencing analyses were used between humanic dissected and normal aorta to screen target differentially expressed genes. Enzyme-linked immunosorbent assay, Western Blotting and immunohistochemical staining were used to exam levels of expression of target genes in AD patients. The lysozyme M promoter and S100A12 gene sequence were constructed on the transposon. The linearized transgenic vector was injected into the embryonic stem cells of C57BL/6J pseudo-pregnant females by microinjection to prepare transgenic (TG) mice. Construction of lysozyme M promoter S100A12TG/TG AD mouse model using BAPN drinking method. Ultrasound, micro-CT, and PET-CT were used to evaluate aortic remodeling and inflamation status in vivo. Exploring the mechanisms through HL-60, 293T, and PB5 cells in vitro of this study.
RESULTS Neutrophil Elastase (NE) was significant overexpressed in AD than that in non-AD human aorta. Human AD aorta underwent structural changes and a large amount of collagen deposition, indicating VSMC phenotypic transformation happened. There was a significant overexpression of S100A12 and NE in the mass spectrometry and single-cell RNA sequencing analyses of human AD than normal aortic proteins. Serological studies had found that the expression level of S100A12 in the serum of AD patients reaches its peak around 24 hours after onset, and the content was about three times that of the normal population. Using BAPN to establish AD mice model, lysozyme M promoter S100A12TG/TG mice showed higher negative vascular remodeling rate and mortality compared to C57 mice. S100A12 can promote the expression of NE through its transcription factor SPI1, while mutate of SPI1 site can reduce the expression level of NE. When co-culturing neutrophils and VSMCs, specific inhibitior of NE activity Sivelestat can save the migration, apoptosis and phenotypic transformation of VSMCs induced by NE by inhibiting the NF-κB pathway. Intraperitoneal injection of Sivelestat of the AD mice model could reduce the level of local inflammation in the aorta of mice, reduce the incidence of AD, improve vascular remodeling and prolong the survival time of mice.
CONCLUSIONS S100A12 overexpression in neutrophils promotes NE expression through the transcription factor SPI1. Specific inhibition of NE activity by Sivelestat, via inhibition of the NF-κB pathway, can mitigate the phenotype transformation of VSMCs induced by NE. In vivo experiments have demonstrated that overexpression of S100A12 in myeloid cells increases mortality and negative vascular remodeling in AD model mice, while Sivelestat can counteract these adverse effects.
GW35-e0482
Yi Fang
General Hospital of Northern Theater Command, Shenyang
OBJECTIVES To explore potential diagnostic biomarkers for aortic valve stenosis complicated with coronary artery disease (AS-CAD) patients based on bioinformatics analysis and machine learning.
METHODS Valve tissue samples were collected from AS-CAD and AS patients for proteomic analysis, identifying 244 differentially expressed genes (DEGs). Functional enrichment analysis revealed that DEGs were enriched in cell-substrate adhesion, Golgi vesicle transport, collagen-containing extracellular matrix, and other functions. Fibrinogen-like protein 1 (FGL1) was identified as a potential biomarker for AS-CAD using bioinformatics and machine learning.
RESULTS A random forest model was constructed using clinical samples for external validation, with an area under the curve of 0.993 (95% confidence interval [CI]: 0.975-0.993). Furthermore, FGL1 expression in AS-CAD valve tissues was validated using enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemical staining. The results demonstrated significant up-regulation of FGL1 in AS-CAD. Subsequently, after dichotomizing the median FGL1 levels, the results of multivariate logistic regression analysis showed that high FGL1 levels were associated with a significantly increased risk of all-cause mortality compared with the reference group, with an adjusted relative risk (aHR) of 4.556 (95% CI: 1.118–18.560), which was statistically significant (P = 0.03).
CONCLUSIONS FGL1 was identified as a diagnostic and prognosis model for AS-CAD based on bioinformatics analysis. It was externally validated using clinical data, ELISA detection of serum samples, and tissue samples.
GW35-e0484
Zhaoyu Pan1,2, Haixu Song1, Yaling Han1,2
1State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
2School of Life Science and Biochemistry, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province 110016, China
OBJECTIVES Heart failure (HF) is a terminal condition of multiple cardiovascular disorders. Cancer is a highly prevalent and deadly disease worldwide. However, the relationship between HF and cancer remains poorly understood. Therefore, there is a critical need to explore the potential mechanisms and therapeutic targets shared between HF and cancer.
METHODS The Gene Expression Omnibus (GEO) database was used to download the RNA sequencing (RNA-seq) data of 356 patients, including individuals with HF and those without HF, to establish a co-expression network using the weighted correlation network analysis (WGCNA) algorithm, to calculate the compositions of immune infiltrating cells in the CIBERSORT algorithm, and to identify candidate hub genes within the modules of individuals with HF. Pearson Correlation Analysis was employed to identify the correlation between hub genes and CD8+T-cells in HF, as well as between hub genes and both tumor mutation burden (TMB) and microsatellite instability (MSI) across cancers. Molecular biology experiments were conducted to confirm the correlation between the hub genes and HF. Finally, the NetworkAnalyst database and the CellMiner database were utilized to predict the transcription factors (TFs) and potential therapeutic drugs of hub genes, respectively.
RESULTS HF was significantly linked to immune response pathway by the analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The brown and blue modules, identified by WGCNA, were the primary modules related to CD8+T-cells. Concomitantly, we observed a positive correlation between the expression levels of the four hub genes and the infiltration of CD8+T-cells in pan-cancer. Additionally, western blotting and real-time polymerase chain reaction (RT-PCR) validated the high expression of three hub genes (GZMM, NKG7, and ZAP70) in both mice and patients with HF compared to those in the control group. Finally, the hub gene-associated TF-gene networks and 11 agents targeting the hub genes were successfully predicted.
CONCLUSIONS Our study highlights the shared pathogenesis of HF and cancer and provides valuable insights for developing novel therapeutic strategies that target shared pathways, offering new opportunities for improving the management and treatment outcomes of both HF and cancer.
GW35-e0485
Chunying Liu1,2, Haixu Song1,2, Yaling Han1,2
1State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, No. 83 Wenhua Road, Shenyang 110016, China
2Beifang Hospital of China Medical University, No. 83 Wenhua Road, Shenyang 110016, China
OBJECTIVES Ankylosing Spondylitis (AS), one of the most significant cardiovascular risk factors, often cause irreversible damage to the cardiovascular system. In this study, we aim to explore the reliable biomarkers for the diagnosis of AS-myocardial infarction (MI) and to improve diagnostic and therapeutic efficiency.
METHODS The MI dataset (GSE66360) and the AS dataset (GSE25101) were obtained for screening differentially expressed genes (DEGs). Protein-protein interaction (PPI) was employed to reveal potential genes in AS-MI. The validation of the hub genes was conducted in the two external datasets. Receiver operating characteristic (ROC) curve was carried out to assess the diagnostic accuracy of nomogram. The CIBERSORT and ssGSEA algorithm were applied to explore the immune landscape in MI and AS datasets. Finally, we performed drug prediction and molecular docking.
RESULTS We identified 10 C-DEGs and 3 hub genes (SYK, S100A12 and TLR4) were further chosen as candidate biomarkers. The validation of the hub genes in MI and AS external cohorts as well as the ROC analysis all showed high diagnostic performance for distinguishing AS-MI. Immune cell infiltration uncovered that the 3 hub genes were significantly related to immune cells. At last, Myristic acid was predicted as a potential therapeutic compound. Herein, we revealed potential networks involving AS-MI etiologies.
CONCLUSIONS Our study demonstrates new insights into the mechanism AS-MI. SYK, S100A12 and TLR4 may be used as potential biomarkers or therapeutic targets for AS-MI patients.
GW35-e0486
Chunying Liu, Haixu Song, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, No. 83 Wenhua Road, Shenyang 110016, China
OBJECTIVES The overall mortality rate of acute myocardial infarction (AMI) is increasing rapidly, which is a serious threat to public health. Cardiomyocyte apoptosis is the main cause of myocardial injury induced by AMI and it plays a key role in the occurrence and development of ventricular remodeling and heart failure. G protein, as a 7 transmembrane coupled receptor, has a conductive effect and plays an important role in the occurrence and development of myocardial infarction. However, the exact role of G proteinγsubunit 2 (GNG2) in myocardial infarction has been unclear.
METHODS Recombinant adeno-associated virus 9 (rAAV9)-cTnT-mediated GNG2 was used to determine to evaluate the function of GNG2 in myocardial infarction. Cardiac function, tissue injury, myocardial apoptosis, and signaling changes in the left ventricular tissues were analyzed after MI. Furthermore, we combined RNA-sequencing and interactome analysis that was followed by multiple molecular biological methodologies to identify the direct target and corresponding molecular events contributing to GNG2 function.
RESULTS We found a high correlation of GNG2 expression with MI-induced heart failure. The results showed that GNG2 expression was up-regulated in cardiomyocytes located in the infarct border at the early phase of MI and in hypoxia-treated neonatal rat cardiac myocytes (NRCMs). Cardiomyocyte-specific GNG2 overexpression inhibited cardiomyocyte apoptosis, decreased infarct size and ameliorated cardiac function. In contrast, inhibition of GNG2 in cardiomyocytes aggravates MI-induced cardiac ischemic injury. Mechanically, GNG2 regulates mitochondrial damage and endoplasmic reticulum stress induced by myocardial infarction by targeting DNAJB6, thereby inhibiting excessive apoptosis of cardiomyocytes after myocardial infarction. Thus, GNG2 overexpression protected against cardiac dysfunction and remodeling after MI.
CONCLUSIONS Our study provides new insights into the underlying role of GNG2 in cardiomyocyte apoptosis and progression of ischemic injury induced by MI, which represents a promising therapeutic strategy for MI-induced heart failure. Our findings provide new therapeutic options for patients with myocardial infarction.
GW35-e0487
Jinping Jiang, Xiaolin Zhang, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, No. 83 Wenhua Road, Shenyang 110016, China
OBJECTIVES Abdominal aortic aneurysm (AAA) is a chronic vascular inflammatory disorder for which there is currently no effective drug therapy. S100A12 plays a significant role in regulating inflammatory processes and immune responses. However, the role of S100A12 in the pathogenesis of AAA remains unclear. In this study, we identified how S100A12 affects AAA and the underlying mechanisms.
METHODS For in vivo experiments, lysozyme M promoter S100A12 transgenic mice (S100A12Tg) were generated and infused with angiotensin II (Ang II) for four weeks. Reverse Transcription-Polymerase Chain Reaction (RT-PCR), western blotting, immunohistochemistry, and gelatin zymography were performed to examine the aortas of each group. RAW264.7 cells were stimulated in vitro by human recombinant S100A12 protein, plasmid, and relative RNA interference. STAT3 inhibitor S31-201 was intraperitoneally injected in S100A12Tg mice and infused with angiotensin II for four weeks to induce AAA formation. Finally, an enzyme-linked immunosorbent assay was used to assess S100A12 levels in patients with AAA and normal controls.
RESULTS S100A12 greatly increased the incidence of Ang II-induced AAA in vivo, leading to AAA characterized by inflammation, oxidative stress, elastin fragmentation, degradation of the extracellular matrix, and increased expression of matrix metalloproteinase 9 (MMP9). Expression of the inflammatory factor MCP-1, oxidative stress marker COX2, and MMP9 in RAW264. Seven cells increased with S100A12 stimulation. We demonstrated that S100A12 stimulated macrophages to promote inflammation, oxidative stress, and extracellular matrix degradation by activating the TLR4/JAK2/STAT3 signaling pathway. The incidence of Ang II – induced AAA was significantly lower in the S3I-201 group than that in the control group. Plasma S100A12 levels were significantly higher in patients with AAA than those in healthy subjects.
CONCLUSIONS S100A12 aggravated AAA by promoting inflammation, oxidative stress, and extracellular matrix degradation in macrophages via activation of the TLR4/JAK2/STAT3 signaling pathway.
GW35-e0492
Ziqi Liu, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES S100A12 is a calcium-binding protein of the S100 subfamily of myeloid-related proteins that acts as an alarmin to induce a pro-inflammatory innate immune response. The aim is to determine the mechanism by which S100A12 can decrease cardiac function and induce myocardial interstitial fibrosis with cardiomyocyte hypertrophy.
METHODS Angiotensin II (1000 ng kg−1 min−1, AngII) was administrated to wild-type (WT) mice and transgenic (Tg) mice expressing human S100A12 in myeloid cells for 28 days. Before and after administering Ang II, cardiac function was measured by means of echocardiography with the use of a Vevo2100 Imaging System (Toronto, Canada) fitted with a 30-MHz high-frequency scan head. H&E, masson, WGA and immunohistochemical staining were conducted for histopathology study. Cultured primary Mouse Embryonic Fibroblasts (MEFs) were incubated with different concentrations (100, 200, 400 pg/mL respectively) of S100A12 protein. The expression of fibrotic biomarkers was determined by RT-PCR and western blotting. Co-immunoprecipitation was performed to determine how the RAGE increased the expression of phosphorated GSK-3β.
RESULTS Humanized S100A12 markedly aggravated Ang II-induced myocardial fibrosis and hypertrophy compared with that in WT mice. Mechanically, S100A12 (200 pg/mL) significantly promoted the proliferation, migration, collagen production, and phenotypic transdifferentiation of primary MEFs. Silence of RAGE (RAGE-siRNA, 20 μmol/L) ameliorated the potent fibrotic role of S100A12 by phosphorylation of GSK-3β. Furthermore, RAGE blocker (Tranilast, 5 mg kg−1 d−1) administration significantly attenuated the Ang II-induced myocardial fibrosis and dysfunction in Tg mice. Notably, circulating and heart S100A12 level were higher in patients with heart failure compared with normotensive individuals.
CONCLUSIONS Ang II-induced myocardial dysfunction and remodeling is largely mediated by S100A12-RAGE-GSK-3β axis. Inhibition of S100A12 may represent a new therapeutic target for treating myocardial fibrosis and hypertrophy.
GW35-e0493
Ting Zhou, Chenghui Yan, Haixu Song, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province 110016, China
OBJECTIVES Pathological cardiac hypertrophy is a major risk factor for heart failure (HF) and a leading cause of morbidity and mortality worldwide. However, the molecular mechanisms underlying pathological cardiac hypertrophy remain largely unclear. In the present study, we investigated the possible underlying effects of UBC9 on cardiac hypertrophy and heart failure, and whether the effects depend on SUMOylation.
METHODS UBC9 expression was analyzed in samples of 30 human hypertrophic hearts compared to 166 normal controls using RNA sequencing analysis of GSE141910 from the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo). Real-time polymerase chain reaction (RT-PCR), western blotting, and immunohistochemistry (IHC) were utilized to analyze the expression of UBC9 in samples of 4 recruited human hypertrophic hearts and 4 normal controls. Mice with cardiac-specific over-expression and low-expression of UBC9 by intravenous injection of adeno-associated virus 9 (AAV9) – encoding UBC9 or shUBC9 under the control of cardiac troponin T (cTnT) promoter were subjected to sham or transverse aortic construction (TAC) surgery for 8 weeks to induce heart failure in vivo. Isolated Neonatal Mouse Cardiomyocytes (NMCMs), rat cardiomyocyte line (H9C2) and human cardiomyocyte line (AC16), transfected with UBC9 adenovirus or UBC9 siRNA followed by phenylephrine (PE 500 μM) treatment for 48 h, were utilized to identify the effects of UBC9 on cardiac hypertrophy in vitro. Unbiased screening was performed on myocardial samples from UBC9flox/floxαMyHCcre and UBC9flox/flox embryonic mice, or Myh7-cre UBC9flox/flox and UBC9flox/flox adult mice, using protein mass spectrometry (MS) analysis and further analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify the potential downstream targets of UBC9. A dual-luciferase reporter gene experiment was conducted to confirm the transcription factor of LIM and cysteine-rich domain 1 (LMCD1). Co-immunoprecipitation assays were performed to determine the mechanism by which UBC9 regulates the expression of forkhead box O3 (FOXO3) and downstream cardiac hypertrophic related signaling cascade. We constructed a plasmid harboring FOXO3 with six major functional phosphorylation site mutations: Thr32, Ser253, Ser315, Ser 294, Ser 344, Ser 425, to determine whether UBC9 regulate LMCD1 expression, dependent of FOXO3 dephosphorylation and nuclear translocation.
RESULTS UBC9 mRNA and protein expression increased in the hearts of patients with hypertrophic cardiomyopathy (HCM) and pressure overload-induced mice, as well as in the NMCMs, H9C2, and AC16 treated with PE. Besides, UBC9 translocated from cytoplasm to nuclear in the cardiomyocytes treated with PE. Cardiac cell-specific UBC9 over-expression alleviates cardiac hypertrophy, cardiac fibrosis, and dysfunction in vivo and in vitro. Cardiac cell-specific UBC9 knockout aggravates cardiac hypertrophy and heart failure in vivo and in vitro. Mechanistically, UBC9 inhibits the expression of downstream target-LMCD1, and the activation of calcineurin-Nuclear Factor of the Activated T Cell (NFAT)-Myocyte-enriched calcineurin interacting protein 1.4 (MCIP1.4) signaling cascade by directly binding to forkhead box O3 (FOXO3), a transcription factor of LMCD1, and promoting FOXO3 dephosphorylation and nuclear translocation, independent of SUMOylation.
CONCLUSIONS This study provides a new insight that UBC9, as a novel negative regulator of pathological cardiac hypertrophy and a potential intervention target in cardiac hypertrophy and HF, may contribute to exploring effective therapeutic strategies for pathological cardiac hypertrophy treatment.
GW35-e0494
Ning Zhao, Xiaolin Zhang, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Cardiovascular diseases are the main cause of death worldwide, and atherosclerosis is the dominant cause of cardiovascular diseases. Previous studies have found that cellular repressor of E1A stimulated genes 1 (CREG1) expression is decreased during the process of atherosclerosis, and exogenously added recombinant CREG1 has an anti-atherosclerosis effect. Therefore, this study conducted an in-depth study on the anti-atherosclerosis effect of CREG1.
METHODS ApoE−/− CREG1fl/flLyz2cre mice and ApoE−/− AAV-F4/80-CREG1 mice were were generated to study the effect of CREG1 on atherosclerosis. The role of CREG1 was determined by transplanting bone marrow and performing assays for foam cell formation, Dil-Ac-LDL (acetylated low-density lipoprotein) uptake, lysosome labeling dye.
RESULTS In vivo results showed that the degree of atherosclerosis was significantly increased in ApoE−/− CREG1fl/flLyz2cre mice, and the level of SRA was increased in atherosclerotic plaques. The degree of atherosclerosis in ApoE−/− AAV-F4/80-CREG1 mice was significantly reduced, and the level of SRA in atherosclerotic plaques was reduced. In vitro studies have shown that CREG1 overexpression in macrophages leads to decreased SRA levels, decreased foam cell formation, and decreased SRA mediated phagocytosis in the atherosclerotic microenvironment. Macrophage CREG1 deficiency leads to increased SRA levels, increased foam cell formation, and increased SRA mediated phagocytosis in the atherosclerotic microenvironment. SRA knockdown inhibited the increase in foam cell formation caused by CREG1 deficiency in macrophages, and SRA overexpression inhibited the decrease in foam cell formation caused by CREG1 overexpression in macrophages. CREG1 did not affect the mRNA level and protein synthesis process of SRA, but could increase the degradation of SRA, mainly through lysosome degradation pathway, and could promote lysosome function.
CONCLUSIONS The level of CREG1 in macrophages is closely related to the occurrence and development of atherosclerosis. In the atherosclerotic microenvironment, macrophage CREG1 can increase the degradation of SRA through lysosomes, reduce the phagocytosis of OX-LDL by macrophages, inhibit the formation of foam cells, and alleviate atherosclerosis.
GW35-e0495
Ning Zhao, Xiaolin Zhang, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Atherosclerosis (AS) is the principal pathological cause of atherosclerotic cardiovascular diseases (ASCVD). Although chronic endoplasmic reticulum stress (ERS) has been implicated in AS aetiopathogenesis, the underlying molecular interactions involved remain unclear. This study aims to identify the molecular mechanisms of ERS in AS pathogenesis to inform innovative diagnostic approaches and therapeutic targets for managing AS.
METHODS GSE28229 and GSE43292 – human early and advanced carotid atherosclerotic tissue samples – were obtained from the Gene Expression Omnibus (GEO) database. A set of endoplasmic reticulum stress-related genes (ERSRGs) were procured from GeneCards. Differential gene expression and weighted gene co-expression network analyses (WGCNA) were conducted to identify genes associated with atherosclerosis, and intersection with ER-related genes led to identification of endoplasmic reticulum stress-related genes associated with advanced atherosclerotic plaque (AAERSRGs). Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted. Protein – protein interaction (PPI) networks, least absolute shrinkage and selection operator (LASSO) regression, and random forest algorithms were employed to identify the critical AAERSRGs. Their diagnostic effectiveness was validated against consolidated and external datasets. The CIBERSORT algorithm assessed immune cell infiltration and applied the consensus clustering algorithm to create patient subgroups. Based on subtype heterogeneity and each critical AAERSRGs gene, small molecule compounds were predicted by the Connectivity Map (CMap) database. Finally, the expression levels of critical AAERSRGs were validated in the human carotid artery, mouse aortic tissues, and cellular models.
RESULTS Three critical AAERSRGs (i.e., CTSB, LYN, and CYBB) distinguishing early from advanced atherosclerotic plaque specimens and demonstrating diagnostic accuracy were identified. Advanced atherosclerotic plaques and these three AAERSRGs exhibited associations with various immune cells. Significant transcriptomic differences and variations in the degree of immune cell infiltration were evident among the ERS-related subtypes. Potential small-molecule drugs were identified based on subtype heterogeneity and each critical AAERSRG gene. Additionally, the critical AAERSRGs were upregulated in human atherosclerotic tissues, mouse models of progressive atherosclerotic lesions, and in vitro macrophage models.
CONCLUSIONS This study identified CTSB, LYN, and CYBB as potentially critical AAERSRGs, demonstrating their robust diagnostic utility and offering novel insights into the potential pathobiology of AS progression, paving the way for exploring innovative therapeutic targets.
GW35-e0496
Xiaolin Zhang, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Atherosclerosis is one of the most common forms of cardiovascular disease. Recent studies have shown that the inflammatory process in the vessel wall accounts for a key role in the development of atherosclerotic plaques. S100A12 has been shown to activate inflammation in different experimental autoimmune disease models. Due partly to its cellular origins, the exact role of S100A12 in the atherosclerotic plaque remains elusive. The aim of the present study was to evaluate the impact of S100A12 on atherosclerosis and to elucidate the underlying molecular mechanisms.
METHODS S100A12 gene expression and plasma levels and their correlation with disease severity were evaluated in coronary artery disease (CAD) patients. Cellular sources of S100A12 and its biological effects were evaluated in vitro and in vivo in Lyz-S100A12/ApoE−/− and littermate mice fed western diet for 16 weeks. RNA interference technology was used to knockdown RAGE, PDCD4 and NF-κB in vivo.
RESULTS S100A12 in coronary artery and plasma levels was increased in CAD patient which associated with the degree of atherosclerosis, disease severity scores and adverse outcomes of cardiovascular event. Moreover, macrophages were identified as the main S100A12 producing cell in the human coronary atherosclerotic plaque. Macrophage specific S100A12 expression aggravated the atherosclerotic lesion size in the aorta, modulated local and systemic inflammatory responses and significantly upregulated the PDCD4-NF-κB expression in the atherosclerotic plaques compared to those found in littermate mice in vivo. In vitro PDCD4-specific siRNA abolished NF-κB-induced macrophage modulated local and systemic inflammatory responses. Finally, we found S100A12 markedly promoted the binding of CEBP-β to PDCD4 promoter and modulated signaling pathway. Tranilast, blocking S100A12 interaction RAGE, ameliorated vascular inflammation and alleviated plaque regression or prevented progression of established atherosclerosis compared with the ApoE−/− mice.
CONCLUSIONS Taken together, S100A12 released by macrophages promoted the inflammation responses and increased atherosclerosis through activating the PDCD4-NF-κB signal pathway. This suggested that macrophage specific S100A12 expression within the atherosclerotic plaque may be promising early clinical diagnosis or therapy target for the occurrence and development of CAD.
GW35-e0497
Yuxin Bu, Dan Liu, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Trim55 (tripartite motif-containing 55) is mainly expressed in the myocardium and skeletal muscle. Trim55 plays an important role in promoting mouse heart embryo development and promoting cardiomyocytes apoptosis after ischemia-reperfusion. However, the effect and mechanism of Trim55 on cardiomyocytes apoptosis after myocardial infarction (MI) needs to be further explored.
METHODS The MI model was established in C57BL/6J mice, Trim55 gene knockout and Trim55 gene overexpression mice using by permanently ligating the left anterior descending coronary artery. At 3 and 28 days after MI, cardiac function, fibrosis and cardiomyocyte apoptosis were evaluated through echocardiography, HE staining, Masson staining, TUNEL staining and Western blot. In vitro, primary rat cardiomyocytes (NRCMs) were isolated and cultured. NRCMs were treated with Trim55 overexpressed or knockdown adenovirus, and then cells were stimulated with hypoxia. The effects of Trim55 on cardiomyocyte apoptosis were determined by quantitative PCR, Western blot, flow cytometry and TUNEL staining.
RESULTS We found that the mRNA and protein expression of Trim55 was increased in the border zone of myocardium post-MI and increased in hypoxic cardiomyocytes. In vivo, Trim55 knockout improved cardiac systolic function, reduced cardiomyocytes apoptosis and the infarct size after MI. Overexpression of Trim55 could exert the opposite effects. In vitro, overexpression of Trim55 increased oxidative stress, followed by inducing cardiomyocytes apoptosis, while Trim55 knockdown showed the opposite results. The mechanism of Trim55 was achieved by binding to Nrf2 to accelerate the degradation of Nrf2 proteasome pathway, thereby inhibiting the expression of HO-1. Moreover, Trim55 was a direct target of forkhead box transcription factor 3 in cardiomyocytes.
CONCLUSIONS Trim55 overexpression promoted the cardiomyocytes apoptosis by inhibiting Nrf2/HO-1 pathway, thereby aggravated myocardial injury after MI.
GW35-e0498
Dan Liu, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Cardiovascular diseases and cancers are two important causes of human death. Doxorubicin (DOX) is currently one of the most used broad-spectrum anthracycline anticancer drugs. However, some cancer patients may experience significant myocardial damage after the use of doxorubicin, which limits its application in cancer patients. At present, there is no effective prevention and treatment for DOX-induced cardiotoxicity. Therefore, clarifying the mechanism of DOX-induced cardiotoxicity and finding intervention targets will provide the basis for clinical prevention and treatment of DOX-induced cardiotoxicity. Cellular repressor of E1A-stimulated genes (CREG1) is an important cardioprotective factor, which plays an important role in maintaining cardiomyocyte differentiation and homeostasis regulation. However, the roles and mechanisms of CREG1 in DOX-induced cardiotoxicity have not been reported.
METHODS In vivo, the intraperitoneal injection of DOX was used to establish a mouse DOX-induced cardiotoxicity model, the mRNA and protein expression of CREG1 in the myocardium was examined using real-time PCR and western blot. To clarify the role of CREG1 in the development of DOX-induced cardiotoxicity, CREG1 transgenic mice, cardiac-specific CREG1 knockout mice and its littermate controls were used to establish DOX-induced cardiotoxicity model. HE staining, Masson staining, WGA staining and western blot were applied to examine fibrosis, myocardial hypertrophy and ferroptosis of myocardium. In vitro, neonatal mouse cardiomyocytes (NMCMs) were cultured and stimulated with DOX, CREG1 overexpression adenovirus and small interfering RNA was used to examine the role of CREG1 on the ferroptosis of NMCMs.
RESULTS In vivo, the mRNA and protein expression of CREG1 were significantly reduced in DOX-treated myocardium. CREG1 transgenic mice significantly alleviated the myocardial damage induced by DOX, and CREG1 deficiency in heart aggravated the DOX-induced cardiotoxicity. The abnormal increase in ferroptosis and impaired mitochondrial function were shown in the DOX-treated heart tissues. CREG1 transgenic mice inhibited the ferroptosis and improved mitochondrial function, and CREG1 deficiency aggravated the ferroptosis and mitochondrial dysfunction induced by DOX. In vitro, the mRNA and protein of CREG1 was reduced in DOX-treated NMCMs. CREG1 overexpression reduced the ferroptosis of cardiomyocytes induced by DOX, CREG1 knockdown aggravated the ferroptosis of cardiomyocytes induced by DOX. Mechanically, CREG1 inhibited the mRNA and protein expression of pyruvate dehydrogenase kinase 4 (PDK4), by regulating FBXW7-FOXO1 pathway. The effect of CREG1 overexpression on cardiomyocytes ferroptosis was reversed by PDK4 overexpression.
CONCLUSIONS CREG1 alleviated DOX-induced cardiotoxicity by inhibiting ferroptosis of cardiomyocytes. Our findings might help clarify new roles of CREG1 in the development of DOX-induced cardiotoxicity.
GW35-e0499
Hanling Wu, Dan Liu, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Cardiology and Cardiovascular Research Institute, General Hospital of Northern Theater Command, Shenyang, Liaoning Province 110016, China
OBJECTIVES Diabetic cardiomyopathy (DCM) is one of the most significant cardiovascular complications in patients with diabetes. Ubiquitin-conjugating enzyme E2 I (UBC9) is the only SUMO-E2 enzyme that plays a key role in cardiomyocytes homeostasis. The present study aimed to elucidate the roles and mechanisms of UBC9 in the development of DCM.
METHODS In vivo, we established cardiomyocyte-specific UBC9 knockout (UBC9-CKO) mice for the first time and UBC9-overexpressing mice. A model of DCM was established using high-fat diet feeding and low-dose streptozotocin injection. Proteomics, H&E staining, sirius red staining, WGA staining, real-time PCR, and western blotting were performed to examine fibrosis, hypertrophy and mitophagy in the myocardium. In vitro, neonatal mouse cardiomyocytes (NMCMs) were cultured and stimulated with palmitic acid (PA), UBC9 overexpression adenovirus, and small interfering RNA was used to establish UBC9 overexpression or knockdown NMCMs. Real-time PCR, western blotting, and immunoprecipitation were used to examine the roles and mechanisms of UBC9 in the mitophagy of cardiomyocytes.
RESULTS The transcription and protein levels of UBC9 were significantly decreased in the myocardium of DCM patients and mice. Cardiac-specific UBC9 knockout aggravated cardiac dysfunction, myocardial fibrosis and hypertrophy, and accelerated mitophagy dysfunction. Meanwhile, UBC9 overexpression exhibited the opposite effects. UBC9 exerted the protective effects in mitophagy of cardiomyocytes independent of SUMOylation. By directly binding to NEDD4, UBC9 increased RUNX2 ubiquitination degradation thus increased PSEN2 expression to exert protective effects against excessive mitophagy. Moreover, the effect of UBC9 on mitophagy of cardiomyocytes was reversed upon PSEN2 knockdown.
CONCLUSIONS UBC9 alleviates DCM development through the NEDD4/RUNX2/PSEN2 pathway. These findings provide novel perspectives on the application of UBC9 as a therapeutic target for DCM.
GW35-e0500
Jing Wang, Dan Liu, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Abdominal aortic aneurysm (AAA) is a chronic vessel wall degenerative disease characterized by the irreversible progressive dilatation of the abdominal aorta over 3.0 cm (1.5-fold of normal abdominal aorta). The LIM-only protein FHL2 (four-and-a-half LIM-domain protein 2) belongs to the FHL protein family of transcriptional cofactors present in various cell lines. Many studies have shown that FHL2 plays different roles in cardiovascular disease. However, it is not yet clear whether FHL2 plays a role in AAA.
METHODS In this study, ApoE−/− mice were injected with AAV-sm22-NC, AAV-sm22-FHL2, AAV-sm22-shRNA, AAV-sm22-shFHL2 for 21 days, and mice were further administered with angiotensin II (Ang II) by using osmotic pumps to induce the AAA model or saline for 28 days. Blood pressure, weight and other basic physiological indexes of AAA were measured. In addition, primary mouse vascular smooth muscle cells (VSMCs) were treated with TNFα to simulat cytological pathological model. Real-time PCR or western blot was used to measure mRNA or protein levels of matrix metalloproteinases (MMP2 and MMP9), apoptosis-related proteins (Bax, Bcl-2, and active caspase-3). Transwell assay and cell scratch assay were used to evaluate the migration ability of VSMC as well as explore the associated mechanisms. HE and Masson staining were used to detect the basic conditions of abdominal aorta in different groups. Verhoeff staining was used to evaluate the damage of different groups of elastic plate. The expression of MMP2 and MMP9 was assessed by immunohistochemical staining. Tunel staining was used to evaluate the apoptosis of vascular smooth muscle cells in vitro and in vivo.
RESULTS We first discovered FHL2 was significantly decreased in both human and mouse abdominal aortic aneurysms and TNFα induced VSMCs. In vivo, compared with the control group, FHL2 overexpression alleviated the formation of AAAs induced by Ang II, as evidenced by a smaller maximal aortic diameter and less medial elastin degradation. Moreover, the expression of α-SMA and SM-22α was increased, and MMP2 was decreased in the abdominal aortas. FHL2 knockdown accelerated the formation of AAAs induced by Ang II. In vitro, FHL2 knockdown aggravated the phenotypic switching and migration of VSMCs, whereas the opposite effect was observed when FHL2 was overexpression. Using quantitative proteomic analysis data from AngII-infused ApoE−/− aneurysm tissue, we identified 144 differentially expressed proteins in FHL2 overexpression tissues compared to those of control tissues: 56 upregulated and 68 downregulated transcripts. Functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that pyroptosis may play crucial roles related to FHL2 and AAA.
CONCLUSIONS We found that FHL2 as a VSMC fate-shaping regulator in AAA and reveal the underlying mechanism associated with pyroptosis, which may lead to the development of strategies based on FHL2 to restoreVSMC homeostasis in AAA.
GW35-e0501
Jing Wang, Dan Liu, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Vascular calcification (VC) is highly correlated with the mortality of cardiovascular diseases, especially in high-risk patients with diabetes and chronic kidney diseases. The cellular repressor of E1A-stimulated genes (CREG) is a lysosomal glycoprotein, which is related to maintaining vascular homeostasis. The aim of this study is to clarify the role and mechanism of CREG in the development of vascular calcification.
METHODS We generated smooth muscle-specific CREG-knockout (CREG-SMKO) mice and CREG transgenic (CREG-TG) mice and three different mouse models of vascular calcification by means of 5/6 nephrectomy, adenine diet to induce chronic kidney failure, or 1,25(OH)2 VitD3 injection were used to establish vascular calcification models. RNA-seq was performed to determine the transcriptional profile of CREG-SMKO and littermate control treated with 1, 25(OH)2 VitD3. MicroCT, Alizarin red staining, Von Kossa staining and calcium deposition detection were used to assess the severity of VC. In vitro, mouse primary vascular smooth muscle cells (VSMCs) were isolated and cultured. VSMCs were infected with CREG overexpressing adenovirus or CREG small interfering RNA, followed by phosphate (Pi) stimulation, Alizarin red staining, calcium deposition detection, western blotting and real-time PCR, were used to assess the severity of calcification of VSMCs.
RESULTS CREG expression was downregulated in calcified aortic tissues from chronic kidney disease mice, 1, 25(OH)2 VitD3 overload induced mice, and human calcified aortas. The CREG-SMKO mice were more susceptible to the development of vascular calcification relative to control mice, as verified by an increased calcification extent showed in MicroCT and more calcium deposition. Likewise, aortic rings from CREG-SMKO mice showed more significant vascular calcification than those from control mice ex vivo. In vitro, CREG deficiency aggravated high phosphate-induced vascular smooth muscle cell osteogenic differentiation, whereas CREG overexpression had a protective effect. Mechanistic studies further showed that CREG negatively regulating RUNX2 transcription by directly binding with FHL2. Consistently, overexpression of FHL2 attenuated calcium deposition in CREG deficiency in vascular smooth muscle cells, whereas inhibition of FHL2 reversed the anticalcific effect of CREG overexpressed in vascular smooth muscle cells. The same conclusion was drawn from the in vivo rescue experiment.
CONCLUSIONS Thus, our study reveals that CREG is a novel negative regulator of vascular calcification, which inhibits osteogenic differentiation of vascular smooth muscle cell and vascular calcification via negatively regulating RUNX2 transcription. Hence, CREG may provide a promising target for the prevention and treatment of vascular calcification.
GW35-e0505
Jiayu Ren1, Jing Li1, Peng Qu1,2
1The Department of Cardiology, Institute of Heart and Vascular Diseases, Second Affiliated Hospital of Dalian Medical University
2Faculty of Medicine, Dalian University of Technology
OBJECTIVES The infiltration of monocyte-derived macrophages plays a crucial role in cardiac remodeling and dysfunction. The serum and glucocorticoid-inducible protein kinase 3 (SGK3) is a downstream factor of PI3K signaling, regulating various biological processes via an AKT-independent signaling pathway. A recent study has demonstrated that SGK3 was involved in cardiac remodeling. However, the importance of SGK3 in hypertensive cardiac remodeling is unclear.
METHODS Angiotensin II (Ang II) infusion was used to induce cardiac remodeling in SGK3-Lyz2-CRE (f/f, +), AAV9-sh-Ndufa13 and wild-type mice. Additionally, a co-culture system of neonatal rat cardiomyocytes or neonatal rat fibroblasts and BM-derived macrophages was treated with Ad-sh-Ndufa13 and NLRP3 agonist to evaluate the effects of SGK3 on the Ang II-induced cardiac remodeling and explore the underlying mechanisms.
RESULTS Our data showed that SGK3 levels were significantly elevated in both peripheral blood mononuclear cells and serum from patients with heart failure. SGK3 deletion attenuated Ang II-induced macrophage infiltration, IL-1β release, and Ndufa13-mediated mitochondrial oxidative stress (mtROS) in heart, consequently reducing myocardial hypertrophy via the ERK1/2/CaNA pathways and fibrosis via the TGF-β/Smad2/3 pathways. The absence of SGK3 led to a reduction in IL-1β secretion by inhibiting the NLRP3/Caspase-1/IL-1β pathway in macrophages. Furthermore, it was observed that IL-1β can promote mtROS in CMs and CFs via the regulation of Ndufa13.
CONCLUSIONS This study provides new evidence that SGK3 is a potent contributor to the pathogenesis of hypertensive cardiac remodeling, and SGK3 may serve as a potential therapeutic target for cardiac remodeling.
GW35-e0506
Mintao Gai1, Xiaoming Gao1,2
1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Clinical Medical Research Institute, Xinjiang Medical University
2Xinjiang Key Laboratory of Medical Animal Model Research
OBJECTIVES This study was set to explore the effects and mechanisms of a recombined MIF on ischemia/reperfusion (I/R) injury.
METHODS A recombined double-stranded adeno-associated virus serotype 9 (dsAAV9) with MIF or GFP genes (dsAAV9-MIF/GFP) was transduced to mice and neonatal rat ventricular myocytes (NRVMs). Its transduction efficiency and safety were evaluated. The models of I/R and hypoxia/reoxygenation (H/R) were constructed in mice and NRVMs, respectively.
RESULTS The recombinant dsAAV9 vector was highly efficiently and relatively specifically overexpressed in heart of C57BL/6J mice. In vivo, endogenous overexpressing of MIF by dsAAV9-MIF in C57BL/6J mice resulted in a significant decrease of 40.53% in infarct size and an improvement in cardiac function compared to the dsAAV9-GFP group after I/R injury. Furthermore, in the dsAAV9-MIF group, the AMPK signal pathway was activated and autophagy was augmented only during the myocardial ischemia period, and the ERK1/2 signal pathway was upregulated and apoptosis was reduced during the reperfusion period. In vitro, transfection of dsAAV9-MIF in NRVMs also upregulated AMPK and ERK1/2 signal pathways during the hypoxia and reoxygenation periods, respectively. Furthermore, we demonstrated that overexpressing of MIF endogenously was an effective method to enhance autophagy and mitochondrial function via AMPK pathway during the hypoxia period and mitigate cardiomyocyte apoptosis following H/R partially through ERK1/2 signal pathway.
CONCLUSIONS The endogenous overexpressing of MIF by dsAAV9-MIF represents a potential strategy for the alleviation of I/R injury by enhancing autophagy via AMPK pathway during the ischemia period and reducing apoptosis through ERK1/2 signal pathways during the reperfusion period.
GW35-e0512
Lan Chen, Longfu Jiang
Department of Cardiovascular Medicine, Ningbo No. 2 Hospital
OBJECTIVES The CACNA1D gene encodes the core part of α1-subunit of voltage-gated Cav1.3 L-type Ca2+ channels. Somatic or germline missense mutations of the CACNA1D gene are associated with central nervous system disorders, endocrine imbalance, cardiac arrhythmia, and primary aldosteronism. CACNA1D D307G mutation is a novel germline mutation that contributes to early-onset hypertension and preeclampsia. In this study, we aim to investigate the effects of Cacna1d D307G mutation in rats fed with high salt diet.
METHODS we used CRISPR/Cas9 technique to generate the Cacna1d D307G mutation rat model and investigated the effects of Cacna1d D307G mutation on blood pressure (BP) and renal function. Rats fed normal-salt diet (NSD) had normal plasma aldosterone levels but higher plasma ET-1 and mildly elevated systolic blood pressure (SBP) in D307G and G307G rats compared with the wild type (WT) until 24 weeks. Renal function and renal histopathology did not significantly differ among the three groups.
RESULTS When fed high-salt diet (HSD), D307G and G307G rats showed more sensitivity to HSD. The results showed a further increase in SBP than in WT rats. Plasma and vascular ET-1 level and cortex and renal artery endothelin type A receptor (ETA) protein expression were significantly increased. Enhanced renal injury was also noted as indicated by an increased ratio of kidney weight/body weight, elevated urinary protein and albumin/creatinine ratio, higher kidney injury molecule-1 (KIM-1) levels, advanced fibrosis and apoptosis, and inflammation. Further experiments revealed a reduction in urinary sodium excretion and creatinine clearance. Higher protein expression of renal cortex epithelial sodium channel α subunit (αENaC) was confirmed in D307G and G307G rats fed HSD. However, a selective ETA receptor blockade (ABT-627) could partially reverse the increased SBP, increased serum KIM-1 level, upregulated renal cortex protein expression of αENaC, and reduced urinary sodium excretion with reduced creatinine clearance in D307G rats fed HSD.
CONCLUSIONS Activation of ET-1/ETA system in D307G mutation rats might contributed to increased sensitivity to salt loading, augmented hypertension, and exacerbated the renal injury.
GW35-e0524
Xueqing Yang, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China.
OBJECTIVES Once pathological injury or myocardial cell death, the loss of regenerative ability of adult cardiomyocytes drives the progression of heart failure. Therefore, understanding how heart regeneration occurs in these contexts can help illuminate cellular and molecular events that can be targets for heart failure prevention or treatment. Hence, this study obtained protein molecules with significant differential expression and their main cellular localization functions in the heart of mice at 1 and 7 days after birth, attempting to elucidate the molecular basis of cellular heterogeneity in myocardial regeneration.
METHODS To characterize the molecular mechanisms underlying heart regeneration in neonatal hearts, we harvested heart tissues of postnatal day 1 (P1) mice and postnatal day 7 (P7) mice (n = 3 per group) for RNA sequencing (RNA-Seq) and mass spectrometry. Single cell RNA sequencing with mice tissues from the GSE153480 dataset for P1 and P8 samples of sham group identified molecular signaling pathways related to the effects of microfibril associated protein 2 (MFAP2) were assessed through western blot, immunofluorescence, and quantitative reverse transcription polymerase chain reaction. The ability of cardiomyocyte proliferation was assessed in neonatal rat cardiomyocytes (NRCM) by transfecting fibroblasts with a siRNA against MFAP2 and an overexpression plasmid increasing its expression.
RESULTS Through the combined detection and analysis of RNA seq and mass spectrometry, we obtained 93 differentially expressed genes (DEGs) with co directional changes at the mRNA and protein levels, including 90 downregulated genes and 3 upregulated genes. Gene Ontology pathway (GO) enrichment analysis revealed significant enrichment in the DNA replication, extracellular matrix structural constituent and actin binding pathways. Further, Cellratio analysis from the GSE153480 dataset for P1 and P8 samples of sham group identified that the most significant change in cell identity from P1 to P8 is a decrease in FB subclusters with a increase in EC subclusters. Integration of 93 DEGs into the GSE153480 dataset for joint analysis confirms that significant differences in expression of microfibril associated protein 2 (MFAP2), fibrillar protein 2 (FBN2), collagen XIV type alpha 1 chain (Col14a1), insulin-like growth factor 2 (IGF2), and insulin-like growth factor 2 receptor (IGF2R) were observed in the fibroblast subpopulations. Among them, MFAP2, a cardiac fibroblast – derived extracellular matrix component, was confirmed to upregulate in P1 mice and downregulate in P7 mice. We found that the overexpression of MFAP2 in fibroblasts and co-culturing them with cardiomyocytes could promote cardiomyocyte proliferation.
CONCLUSIONS Together, this study identifies MFAP2 as a cardiac fibroblast – derived glycoprotein, demonstrates a novel role for MFAP2 signaling directly on cardiomyocytes during heart regeneration and suggests the potential for it as one potential therapeutic target for promoting myocardial repairment.
GW35-e0529
Daoyang Zhang1,2
1General Hospital of Northern Theatre Command
2Graduate School of Dalian Medical University
OBJECTIVES To investigate the effects of mechanical stretch injury on the electrophysiological properties of Purkinje fibers in false tendons and its potential role in ventricular arrhythmias.
METHODS Mechanical traction was applied to false tendons in the left ventricle of 9 isolated canine hearts, followed by direct visualization electrophysiological mapping of the left ventricular false tendons and left anterior fascicle before and after traction.
RESULTS Among the 9 isolated canine hearts, 2 exhibited intractable ventricular arrhythmias at the onset of the experiment, leading to premature termination. In the remaining 7 hearts, the conduction velocity of the left ventricular false tendons significantly decreased after mechanical traction. The conduction velocities before and after traction were 1.79 ± 0.11 mm/ms and 1.09 ± 0.51 mm/ms, respectively, representing a reduction of approximately 40% (P < 0.05). Moreover, the reduction in conduction velocity was more pronounced at the junction of the false tendons with the endocardium, where the conduction velocity after traction was 0.13 ± 0.05 mm/ms, only 10% of the average conduction velocity of the entire length of the tendon after traction (1.09 ± 0.51 mm/ms) (P < 0.05). In 6 hearts, the S1S1 stimulation cycle for ventricular arrhythmia induction in the left ventricle prolonged from 217 ± 14 ms before traction to 275 ± 17 ms after traction (P < 0.05), indicating increased susceptibility to ventricular arrhythmias.
CONCLUSIONS Mechanical traction injury to false tendons leads to a significant reduction in conduction velocity, especially at the junction with the endocardium, potentially serving as a slow conduction zone for ventricular arrhythmias. This may be one of the mechanisms for the occurrence and maintenance of false tendon-related ventricular arrhythmias.
GW35-e0531
Xiaoping Li1,2
1Daping Hospital
2The 921st Hospital of the Joint Logistics Support Force of the People’s Liberation Army of China
OBJECTIVES Doxorubicin is a powerful chemotherapeutic agent for cancer, whose use is limited due to its potential cardiotoxicity. Semaglutide (SEMA), a novel analog of glucagon-like peptide-1 (GLP-1), has received widespread attention for the treatment of diabetes. However, increasing evidence has highlighted its potential therapeutic benefits on cardiac function. Therefore, the objective of this study was to examine the efficacy of semaglutide in ameliorating doxorubicin-induced cardiotoxicity.
METHODS Doxorubicin-induced cardiotoxicity is an established model to study cardiac function. Cardiac function was studied by transthoracic echocardiography and invasive hemodynamic monitoring. RNA sequencing suggested that Bnip3 is the candidate gene that impaired the protective effect of semaglutide in doxorubicin-induced cardiotoxicity. To determine the role of BNIP3 on the effect of semaglutide in doxorubicin-induced cardiotoxicity, BNIP3 with adeno-associated virus serotype 9 (AAV9) expressing cardiac troponin T (cTnT) promoter was injected into tail vein of C57/BL6J mice to overexpress BNIP3, specifically in the heart.
RESULTS The results showed that semaglutide significantly ameliorated doxorubicin-induced cardiac dysfunction. Over-expression of BNIP3 prevented the improvement in cardiac function caused by semaglutide. In vitro experiments showed that semaglutide, via PI3K/AKT pathway, reduced BNIP3 expression in the mitochondria, improving mitochondrial function.
CONCLUSIONS Semaglutide ameliorates doxorubicin-induced mitochondrial and cardiac dysfunction via PI3K/AKT pathway, by reducing BNIP3 expression in mitochondria. The improvement in mitochondrial function reduces doxorubicin-mediated cardiac injury and improves cardiac function. Therefore, semaglutide is a potential therapy to reduce doxorubicin-induced acute cardiotoxicity.
GW35-e0541
Jin Gong1,2,3,4,5, Liangdi Xie1,2,3,4,5
1Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350000, People’s Republic of China
2Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350000, People’s Republic of China
3Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350000, People’s Republic of China
4Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fujian Province, Fuzhou, Fujian 350000, People’s Republic of China
5Department of Geriatrics, National Regional Medical Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, People’s Republic of China
OBJECTIVES Our previous RNA-seq analyses showed an increased expression of cAMP response elements (CRE) in lungs tissues from monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rats. Furthermore, cAMP response element binding protein (CREB), a transcription factors which bind to CRE response elements in the gene promoter regions, could promote the proliferation of cells. But the therapeutic effect of CREB inhibitor in PAH is still unclear. Our current study is aimed to demonstrate the therapeutic effect of CREB inhibitor in PAH.
METHODS Rats were divided into three groups, control group (Ctrl), MCT-induced PAH group (PAH), and 666-15 therapy group (666-15). Rats in the PAH group received twice injections of 20 mg/kg MCT on days 0 and 7. Rats in control group received and identical volume of normal saline on the same days. Rats in 666-15 group received 6 mg/kg 666-15 every two days and twice injections of 20 mg/kg MCT on days 0 and 7. Characteristic changes of pulmonary arterial variables and right ventricle features were evaluated 4 weeks after the first-time injection. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the mRNA levels of CREB, mitochondrial fission 1 protein (Fis1), mitofusin-2 (Mfn2), dynamin-related protein 1(Drp1). The expression of CREB, Fis1, Mfn2, Drp1 and PCNA proteins were detected by Western Blot.
RESULTS Compared to control groups, the mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI), percentage of total wall thickness to external diameters of pulmonary arterioles diameter (WT%) and the percentage of wall area to the total area of vessels (WA%), right ventricular end diastolic diameter (RVEED) and right ventricular end systolic diameter (RVESD) were higher in those with PAH, which could be rescued after 666-15 therapy[ctrl vs. PAH vs. 666-15, mPAP 18.35 ± 2.69 mmHg vs. 31.88 ± 1.79 mmHg vs. 20.61 ± 1.96 mmHg, RVHI 24.05 ± 3.06% vs. 59.61 ± 6.67% vs. 30.28 ± 5.56%, WT% 27.39 ± 4.44 vs. 64.81 ± 7.71 vs. 30.10 ± 4.12, WA% 53.50 ± 2.59 vs. 87.95 ± 5.92 vs. 58.32 ± 3.02, RVEED 2.87 ± 0.33 mm vs. 5.84 ± 0.36 mm vs. 3.14 ± 0.36, RVESD 1.94 ± 0.28 mm vs. 4.93 ± 0.44 mm vs. 2.20 ± 0.23 mm, all P < 0.05]. The tricuspid annular plane systolic excursion (TAPSE), adjusted pulmonary artery acceleration time (PAAT/HR), left ventricular fraction shortening rate (LVFS%), right ventricular fraction shortening rate (RVFS%) were lower in PAH-rats when compared to control groups, which also could be reversed after 666-15 therapy [ctrl vs. PAH vs. 666-15, TAPSE 2.30 ± 0.23 mm vs. 1.25 ± 0.22 mm vs. 2.24 ± 0.22 mm, PAAT/HR 0.16 ± 0.04 vs. 0.10 ± 0.02 vs. 0.15 ± 0.02, LVFS% 35.62 ± 4.04 vs. 27.78 ± 4.81 vs. 39.22 ± 4.71, RVFS% 32.16 ± 7.44 vs. 15.72 ± 4.31 vs. 29.88 ± 3.91, all P < 0.05]. In addition, compared to control groups, the expression of Drp1, Fis1 mRNA as well as Drp1, Fis1, PCNA proteins were increase in PAH-rats, while the expression of Mfn2 protein was decrease. After 666-15 injection, the expression of Fis1 mRNA and protein was reduce compare to PAH-rats, but the expression of Drp1 and Mfn2 mRNA as well as proteins have no changed.
CONCLUSIONS 666-15, a CREB inhibitor, could against MCT-induced PAH, which may be via preventing mitochondrial fission.
GW35-e0567
Li Liu1,2
1Affiliated Hospital of Guizhou Medical University
2Liupanshui City People’s Hospital
OBJECTIVES Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). Dysbiosis of gut microbiota has been implicated in agerelated diseases, but its role in AF development remains unclear. This study aimed to investigate the correlations between changes in the autonomic nervous system, short-chain fatty acids (SCFAs), and alterations in gut microbiota in aged rats with AF.
METHODS Electrophysiological experiments were conducted to assess AF induction rates and heart rate variability in rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography – mass spectroscopy was used to identify SCFAs in fecal samples.
RESULTS Studies have shown that the incidence of atrial fibrillation (AF) significantly increases in aged rats (5 out of 6), accompanied by a decrease in heart rate variability (HRV) (SDRR value decreased, P < 0.01) and a slowdown in cardiac conduction velocity. Dysbiosis of the gut microbiota was observed, with an increase in Bacteroidetes and a decrease in Firmicutes, leading to a significantly reduced F/B ratio. Principal Coordinate Analysis (PCoA) displayed significant separation along PC1 and PC2 axes. The total levels of short-chain fatty acids (SCFAs) were markedly reduced, with acetate (P = 0.006) and butyrate (P = 0.001) levels decreasing and isovalerate levels increasing (P = 0.028). Correlation analysis indicated a negative association between acetate and the Prevotellaceae family (r = −0.705, P = 0.0104), and a significant positive correlation between butyrate and HRV indicators (SDRR, r = 0.8649, P = 0.0003).
CONCLUSIONS These findings suggest that SCFAs, as metabolites of gut microbiota, may play a regulatory role in autonomic nervous function and potentially influence the onset and progression of AF in aged rats. These results provide novel insights into the involvement of SCFAs and autonomic nervous system function in the pathogenesis of AF. These results provide novel insights into the involvement of SCFAs and autonomic nervous system function in the pathogenesis of AF.
GW35-e0575
Long Chen, Zhaohua Cai, Danrui Xiao, Yiping Shi, Qin Shao, Ben He
Shanghai Chest Hospital
OBJECTIVES SUMO/deSUMOylation, a crucial post-translational modification that regulates inflammatory response activation, is implicated in cardiovascular disease. Abdominal aortic aneurysm (AAA) is a high-risk inflammatory disorder without an effective cure. This study aims to determine the role of SENP3, a redox-sensitive SUMO2/3-specific protease, in macrophages in AAA.
METHODS Angiotensin II – induced AAA model and CaPO4-induced AAA model were used to determine the role of SENP3 in AAA development. Whole transcriptome RNA sequencing was utilized to recapitulate possible changes in the transcriptome profile and verify the downstream pathway. Immunoprecipitation-coupled mass spectrometry (IP-MS) was used to further identify the interacting proteins and substrates of SENP3 in macrophages in AAA.
RESULTS SENP3 protein was upregulated in both human and mouse AAA specimens. Knocking out SENP3 in myeloid cells inhibited AAA formation in both AngII- and CaPO4-induced models. By RNA-sequencing, SENP3 in macrophages was demonstrated to exacerbate vascular inflammation in AAA through the PI3K-AKT signaling pathway. Mechanistic studies identified Cystathionine Gamma-Lyase (CTH), a critical enzyme involved in H2S production within the vessels, as a target protein of SENP3 that mediated the regulatory effects of SENP3 on metabolic and inflammatory programs in macrophages. CTH was SUMOylated at Lysine 361 and could be de-SUMOylated by SENP3. SUMO-3 promoted CTH stability, whereas SENP3 facilitated its proteasome-dependent degradation. Moreover, we discovered an upstream regulator of SENP3, STUB1, which regulated SENP3 protein stability by ubiquitin-mediated degradation. Additionally, supplementation with ATB346, an H2S-donating derivative of the non-steroidal anti-inflammatory compound naproxen, was beneficial in preventing and treating AAA in mice.
CONCLUSIONS Our studies identified a previously unrecognized role of SENP3 in AAA pathogenesis and an undescribed SENP3-CTH axis involved in regulating inflammatory programs in macrophages. Importantly, we found that ATB346 supplementation may represent a potential treatment against AAA.
GW35-e0579
Yiping Shi, Long Chen, Qin Shao, Ben He
Shanghai Chest Hospital
OBJECTIVES Rupture of vulnerable carotid plaque is one of the leading causes of stroke. But the underlying mechanisms responsible for the transition from stable to vulnerable plaque remain largely unknown. Nur77 is an orphan nuclear receptor that participates in the occurrence and development of a variety of cardiovascular diseases. However, the effect of Nur77 on vulnerable plaque rupture and its underlying mechanisms are still unclear.
METHODS The rupture-prone vulnerable carotid plaques were induced by partly ligating the left renal artery and the left internal and the external carotid arteries by using perivascular collars. Whole transcriptome RNA sequencing was utilized to recapitulate possible changes in the transcriptome profile and verify the downstream pathway. ChIP-seq was employed to further elucidate the substrates in macrophages that may be subject to regulation by Nur77.
RESULTS Our research revealed that Nur77 deletion significantly worsened the development of vulnerable plaques, leading to a notable increase in intracavicular hemorrhage by 46% and a higher occurrence of spontaneous plaque rupture accompanied by intracavicular thrombosis by 57%. Nur77 deficiency exacerbated macrophage infiltration, inflammation, and oxidative stress. Additionally, the deletion of Nur77 was associated with a markedly increased expression of genes related to pyroptosis. Mechanistic studies identified FOXO3a, a master regulator that contributes to antioxidant defenses and the autophagy process, as a target protein of Nur77 that mediated the regulatory effects of Nur77 on pyroptosis and inflammatory programs in macrophages. Besides, treatment of celastrol (an agonist of Nur77) attenuated inflammation, thereby retarded the development of vulnerable plaques.
CONCLUSIONS Our studies identified a previously unrecognized role of Nur77 in vulnerable plaques pathogenesis and an undescribed Nur77-FOXO3a axis involved in regulating pyroptosis and inflammatory in macrophages. Importantly, we found that Celastrol supplementation may represent a potential treatment against vulnerable plaques.
GW35-e0609
Yang Yang1, Yu Li1, Zhiqiang Yang2
1Xiang’an Hospital of Xiamen University
2School of Medicine, Xiamen University
OBJECTIVES Emerging evidence indicates that exosomes play a critical role in the development of atherosclerosis (AS). This study investigates the role of non-lethal sonodynamic therapy (NL-SDT)-mediated exosome secretion in atherosclerotic lesion stability and explores the potential underlying mechanisms.
METHODS Murine bone marrow-derived foam cells (FC) were incubated with 1 mM 5-aminolevulinic acid (ALA). Following ALA-mediated SDT, exosomes were isolated via ultracentrifugation, purified by sucrose density gradient centrifugation, and characterized based on specific morphology and surface markers. Exosomes were then labeled with membrane-labeling dye PKH67 and incubated with macrophages, smooth muscle cells, and human umbilical vein endothelial cells (HUVECs) to assess cellular uptake. RNA sequencing (RNA-seq) was performed to determine the miRNA profiles of SDT-mediated exosomes. Quantitative real-time PCR (qRT-PCR) analysis was used to detect miRNA expression levels. The roles of the candidate miRNA and its target gene were assessed using specific miRNA mimics. Western blotting was employed to detect candidate protein expression levels. A dual-luciferase reporter system was utilized to confirm the binding of the specific miRNA to its target gene. Cholesterol efflux and anti-inflammatory reactions were measured in HUVECs in vitro.
RESULTS HUVECs cocultured with SDT-derived exosomes in vitro demonstrated increased cholesterol efflux and anti-inflammatory capacity. MiRNA profiling revealed a decrease in miR-17-5p levels in SDT-derived exosomes. This miRNA was shown to play a key role in regulating the effects of SDT-derived exosomes by directly targeting ATP-binding cassette transporter A1 (ABCA1) and tissue inhibitor of metalloproteinases 2 (TIMP2).
CONCLUSIONS These findings indicate that exosomal miR-17-5p from SDT-induced FCs may alleviate AS by enhancing endothelial cell cholesterol efflux and anti-inflammatory responses through its targets ABCA1 and TIMP2. This discovery could elucidate the mechanism underlying NL-SDT as a potential treatment to prevent atherothrombotic events.
GW35-e0611
Jinsheng Shen, Yafeng Zhou
The Fourth Affiliated Hospital of Soochow University
OBJECTIVES Angiotensin-converting enzyme (ACE) gene polymorphisms have recently been shown to be associated with risk of developing left ventricular hypertrophy (LVH). However, the results were controversial. We aimed to conduct this meta-analysis to further confirm the association between ACE rs4646994 polymorphism and hypertrophic cardiomyopathy (HCM)/dilated cardiomyopathy (DCM).
METHODS PubMed, Embase, the Chinese National Knowledge Information, and Wanfang databases were searched for eligible studies. The Newcastle – Ottawa Scale (NOS) was used to evaluate the quality of included studies. Then we evaluated the association between ACE gene mutation and HCM/DCM by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs). Subgroup analysis was further performed to explore situations in specialized subjects. Sensitivity analysis and publication bias was assessed to confirm the study reliability.
RESULTS There were 13 studies on DCM (2004 cases and 1376 controls) and 16 studies on HCM (2161 controls and 1192 patients). ACE rs4646994 polymorphism was significantly associated with DCM in all genetic models. However, in HCM, four genetic models (allele model, homozygous model, heterozygous model, and dominant model) showed significant association between ACE rs4646994 polymorphism and DCM. In subgroup analysis, we found that ACE rs4646994 polymorphism was significantly associated with DCM/HCM in Asian population. Finally, we also conducted a cumulative meta-analysis, which indicates that the results of our meta-analysis are highly reliable.
CONCLUSIONS ACE rs4646994 polymorphism increases the risk of DCM/HCM in Asians, but not in Caucasians. More case – control studies are needed to strengthen our conclusions and to assess the gene – gene and gene – environment interactions between ACE rs4646994 polymorphism and DCM/HCM.
GW35-e0618
Yiyao Zeng, Yafeng Zhou
The Fourth Affiliated Hospital of Soochow University
OBJECTIVES High blood pressure is the main cause of cardiovascular diseases. Kidney damage is one of the most common organ secondary damage to hypertension. The study of hypertension gene polymorphisms is an important means of precision treatment of primary hypertension. Objectives: The objective of this study was to explore the relationship between AGTR1 (c.1166 A>C) gene polymorphisms and hypertension combined with kidney damage, while exploring the relationship between codominant, dominant and recessive gene model and hypertension with kidney injury and the susceptibility of different genotypes to hypertension with kidney injury.
METHODS The distribution of AGTR1 polymorphism in the AGTR1 in hypertensive patients (hypertension group, 292 patients) and hypertension with kidney injury patients (44 patients) were detected and compared by PCR-melting curve method.
RESULTS The genotype distribution of hypertension and combined groups met Hardy-Weinberg equilibrium (P > 0.05); the distribution difference between the three genotypes was statistically significant (P < 0.05), the codominant, dominant and recessive distribution frequency of genotypes (P < 0.05), and no difference between A allele and C allele (P > 0.05).
CONCLUSIONS Our study identified the relationship of AGTRA (c.1166 A>C) with hypertension combined with renal injury, and compared the susceptibility of different genetic models, which may provide novel targets for precision gene therapy of hypertension.
GW35-e0622
Yufeng Jiang, Yafeng Zhou
The Fourth Affiliated Hospital of Soochow University
OBJECTIVES Ferroptosis is a new form of cell death recently discovered that is distinct from apoptosis, necrosis and autophagy. This article is expected to provide a new direction for the treatment of cardiomyopathy in the future by screening potential drug targets associated with ferroptosis.
METHODS Differential expression analysis of GSE5406 from the Gene Expression Omnibus (GEO) database was performed using the GEO2R tool. Functional annotation of ferroptosis related genes was also performed. Then we constructed protein-protein interaction networks and identified hub genes using Cytoscape. The candidates for pharmacological compounds targeting the hub genes were screened by cMap.
RESULTS Totally 15 ferroptosis related genes (4 upregulated and 11 downregulated) for ischemic cardiomyopathy and 17 ferroptosis related genes (13 upregulated and 4 downregulated) for idiopathic cardiomyopathy were found. The biological processes involved in these genes mainly include negative regulation of apoptotic process, flavonoid metabolic process, response to drug for ischemic cardiomyopathy and cellular response to fibroblast growth factor stimulus, negative regulation of apoptotic process, and response to drug for idiopathic cardiomyopathy. KEGG results showed that these genes were mainly involved in MAPK signaling pathway for ischemic cardiomyopathy and PI3K-Akt signaling pathway for idiopathic cardiomyopathy. We generated a co-expression network for hub genes and obtained top 10 medications suggested respectively for ischemic/idiopathic cardiomyopathy.
CONCLUSIONS Our study reveals the potential role of ferroptosis related genes in ischemic and idiopathic cardiomyopathy through bioinformatics analysis. The hub genes and potential drugs may become novel biomarkers for prognosis and precision treatment in the future.
GW35-e0623
Wenyuan Cai, Yafeng Zhou
The Fourth Affiliated Hospital of Soochow University
OBJECTIVES The use of doxorubicin (DOX) may contribute to cardiotoxicity, limiting its clinical application. Thiolutin (THL) has been found to exert protective roles in various biological activities, while its effects on DOX-induced cardiotoxicity are still uncovered.
METHODS Cell counting kit 8 assay was utilized to detect cell viability and half maximal inhibitory concentration of THL in H9c2 cardiomyocytes. The level of lactate dehydrogenase (LDH), adenosine triphosphate (ATP), interleukin (IL)-18 and IL-1 beta (IL-1β) were measured using the corresponding detection kits, and flow cytometry determined cell apoptosis rate. The reactive oxygen species (ROS) accumulation was evaluated by utilizing immunofluorescence or flow cytometry assay. The protein levels of NLR family Pyrin domain 3 (NLRP3), pro-Caspase1, cleaved-Caspase1, gasdermin D (GSDMD) and cleaved-GSDMD (GSDMD-N) in H9c2 cells were detected by immunoblotting assay. The treatment of THL reduced H9c2 cell viability in a gradient-dependent manner.
RESULTS THL treatment reversed the DOX-induced inhibition of proliferation, decrease of AT P, up-regulation of LDH, IL-18, IL-1β and production of ROS, activation of NLRP3 and inflammasome-mediated pyroptosis in H9c2 cells. Additionally, NLRP3 knockdown abolished the effects of THL in DOX-treated H9c2 cells remarkably. This investigation proved that THL notably ameliorated DOX-induced apoptosis, oxidative stress, and pyroptosis in H9c2 cardiomyocytes. Besides, THL effectively inactivated DOX-induced NLRP3 inflammasome in H9c2 cells.
CONCLUSIONS These findings revealed a promising drug to assist DOX in its anti-cancer effects and protect the heart of patients.
GW35-e0628
Liang Hou1, Yanchun Ding2
1General Hospital of The Yangtze River Shipping
2Second Affiliated Hospital of Dalian Medical University
OBJECTIVES Atherosclerosis is a chronic inflammatory reactive lesion. It is widely recognized that innate immunity participates in atherosclerosis. Receptor Interacting Protein 2 (RIP2) is a key member of the innate immune response pattern recognition receptor. Researchers have divided macrophages into two major types: M1, which promotes inflammatory responses, and M2, which has anti-inflammatory properties. The study aims to investigate the impact of RIP2 on macrophages inflammatory activation and polarization switch in THP-1 derived macrophages induced by OX-LDL.
METHODS THP-1 derived macrophages were stimulated with varying concentrations (10, 25, 50 mg/L) of OX-LDL for different durations (8, 16, 24 hours). Quantitative real-time PCR was utilized to measure the mRNA expression of RIP2, Western blotting was used to detect the protein levels of RIP2. TNF-α, MCP-1 secretion in cell culture supernatants was measured by ELISA. Three pairs of RIP2-siRNA were designed, delivering them into cells using hiperfict transfection reagent. Subsequent evaluation of RIP2 mRNA expression and protein levels post-transfection was achieved with quantitative real-time PCR and Western blot. The most effective RIP2 siRNA transfection was followed with 50 mg/L OX-LDL for 24 hours. ELISA was employed to assess TNF-α and MCP-1 secretion, whereas quantitative real-time PCR analyzed the expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1). Additionally, flow cytometry was used to evaluate the expression of cell surface antigens CD86, CD80, and CD163. iNOS, CD86 and CD80 serve as markers of M1 macrophages, while Arg-1 and CD163 act as markers of M2 macrophages.
RESULTS Exposure to OX-LDL, the expression of RIP2 mRNA and proteins in THP-1 derived macrophages increased in a dose and time-dependent manner. RIP2 protein were 7.6 times higher in the 50 mg/L group and 17.9 times higher in the 24 hour group compared to the control (P < 0.001). Elevated TNF-α and MCP-1 expression were observed with escalating OX-LDL concentrations and durations (P < 0.05). Following the most effective RIP2 siRNA transfection and 24 hours OX-LDL exposure, ELISA revealed that TNF-α and MCP-1 expressions were 2.4 and 2.9 times higher, respectively, in the 50 mg/L OX-LDL group compared to the control (P < 0.01). Moreover, after RIP2 siRNA transfection, TNF-α and MCP-1 expressions decreased by 37.4%, 45.3% (P < 0.05). Flow cytometry and real-time quantitative PCR showed that compared with the blank control group, the expression of surface antigen CD86 in the OX-LDL stimulated group was 14.2 times higher than that in the control group, CD80 expression was 33.8 times higher, iNOS mRNA expression was 4.5 times higher, CD163 expression decreased by 33.4%, and Arg-1 mRNA expression decreased by 41.2% (P < 0.05). Compared with the OX-LDL stimulated group, after transfection with RIP2 siRNA, the expression of surface antigen CD86 in the OX-LDL stimulated group decreased by 27.6%, CD80 expression decreased by 29.3%, iNOS mRNA expression decreased by 30.3%, CD163 expression increased by 30.3%, and Arg-1 mRNA expression increased by 38.6% (P < 0.05).
CONCLUSIONS RIP2 activation in macrophages by OX-LDL is influenced by the dosage and exposure duration of OX-LDL. Silencing the RIP2 gene effectively inhibits the M1 transformation of macrophages induced by OX-LDL.
GW35-e0630
Jiayin Li, Xiaozeng Wang
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Endothelial cell dysfunction is a crucial factor in the development of age-related vascular diseases. Previous studies have suggested that Mitofusin 2 (MFN2) expression decreases in senescent endothelial cells and angiotensin II-treated mouse aortas. However, the functional significance of MFN2 in endothelial cell senescence and the underlying molecular mechanisms remain unclear.
METHODS To investigate the role of MFN2 in endothelial cell senescence, we conducted an extensive analysis of public databases and mouse tissues. Additionally, human endothelial cells were treated with Angiotensin II to induce senescence, and siMFN2 and ovMFN2 treatments were used to inhibit or overexpress MFN2, respectively. Various assays were performed to assess senescence markers, mitochondrial function, and morphological changes within the cells.
RESULTS Our analysis revealed a significant decrease in MFN2 expression in senescent endothelial cells and angiotensin II-treated mouse aortas. Angiotensin II treatment resulted in reduced MFN2 expression and increased levels of senescence markers P21 and P53 in human endothelial cells. Surprisingly, inhibition of MFN2 worsened Angiotensin II-induced senescence, while overexpression of MFN2 alleviated this process. Moreover, both siMFN2 treatment and Angiotensin II exposure induced mitochondrial dysfunction, including increased production of reactive oxygen species and reduced respiration. However, these effects were mitigated when treated with ovMFN2.
CONCLUSIONS Our findings highlight the critical regulatory role of MFN2 in endothelial cell senescence, emphasizing its importance in maintaining endothelial homeostasis and preventing age-related vascular diseases. We identified BCL6 as a key mediator linking Angiotensin II signaling to MFN2 downregulation. This provides valuable insights into potential therapeutic targets for age-related vascular diseases. Future studies should focus on elucidating the precise mechanisms through which MFN2 modulates endothelial cell senescence and exploring pharmacological interventions to restore MFN2 expression and function in aging vasculature.
GW35-e0631
Jiayin Li1,2, Xiaozeng Wang2
1College of Medicine and Biological Information Engineering, Northeastern University
2State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Aortic dissection (AD) is a severe cardiovascular disease with limited treatment options. To develop effective therapeutic strategies, it is crucial to understand the molecular mechanisms underlying AD pathogenesis. Cuproptosis, a form of cell death caused by copper overload, has been implicated in various diseases. However, its role in AD and the associated molecular mechanisms remain poorly understood.
METHODS In this study, we analyzed serum copper levels in AD patients and controls to assess the involvement of copper dysregulation in AD. Pyruvic acid levels were also examined as copper dysregulation can influence cellular metabolism. Bioinformatics analysis was performed to identify crucial hub genes potentially involved in AD development. Expression validation of these hub genes, SLC31A1 and GLS, was conducted in clinical specimens. Immune cell analysis was performed to investigate the potential involvement of specific immune cell subtypes in AD pathogenesis. Additionally, ROC curve analysis was conducted to evaluate the diagnostic value of the hub genes.
RESULTS Our findings revealed a significant increase in copper concentrations in serum and aortic tissue of AD patients compared to controls. Alterations in pyruvic acid levels further supported the role of copper in AD pathogenesis. Expression validation confirmed the dysregulation of SLC31A1 and GLS in AD patients. Immune cell analysis suggested the involvement of specific immune cell subtypes in AD pathogenesis. ROC curve analysis demonstrated the potential of SLC31A1 and GLS as valuable diagnostic markers for AD.
CONCLUSIONS This study establishes a close relationship between AD and cuproptosis, shedding light on the molecular mechanisms underlying AD pathogenesis. The identification of SLC31A1 and GLS as key players in AD provides potential therapeutic targets for future treatments. The involvement of copper dysregulation and immune cell dysregulation in AD offers avenues for developing novel treatment strategies. These findings contribute to early detection and diagnosis of AD, enabling timely intervention and improved patient outcomes. This study advances our understanding of AD pathophysiology and paves the way for promising therapeutic interventions.
GW35-e0633
Jiayin Li, Xiaofeng He, Xiaozeng Wang
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Abdominal aortic aneurysm (AAA) is a life-threatening vascular pathology and is usually asymptomatic until rupture resulting a high mortality. No non-invasive therapeutics have been approved for preventing AAA growth and/or rupture. Rivaroxaban, an oral direct factor Xa (FXa) inhibitor, has recently been reported to have benefits other than antithrombotic effects such as anti-inflammatory and anti-atherosclerotic effects in cardiovascular diseases and peripheral artery diseases. However, the potential effects of rivaroxaban on AAA progression or rupture and its underlying mechanism have not been clarified. Here we investigated the effects of rivaroxaban on AAA formation, progression and rupture and its underlying mechanisms.
METHODS Apolipoprotein E knockout (ApoE−/−) male mice aged for 8 weeks (n = 72) had been fed with western diet (WD) for 4 weeks, then treated by angiotensin (Ang)II subcutaneously infusion for 28 days to induce AAA. Some of mice (n = 42) received a WD supplemented with rivaroxaban (5 mg/kg body weight/day) as soon as they were treated with AngII. AAA formation and characteristics were investigated after 28-days AngII infusion by histological analyses, quantitative RT-PCR, western blotting and gelatin zymography. The plasma MMP-9 and interleukin (IL)-6 level were examined by ELISA. In vitro experiments aortic vascular smooth muscle cells (VSMCs) cell line was used to perform to investigate anti-inflammation effect of rivaroxaban.
RESULTS Although ApoE−/− mice fed with the rivaroxaban-supplemented WD showed slightly reduced maximal aortic diameter with differences not reaching statistical significance compared to controls, they showed significantly reduced AAA formation rate (P < 0.05) and mortality due to AAA rupture (P < 0.01). Rivaroxaban treatment significantly decreased the plasma MMP-9 level and activity (P < 0.01), and it alleviated elastin degradation, collagen loss, macrophage infiltration, reduced MMP-9 and IL-6 expression, increased alpha-smooth muscle actin (α-SMA) expression in the aortic wall. In mouse VSMCs, tumor necrosis factor-alpha (TNF-α) stimulation increased the expression of IL-6 was dose-dependently suppressed by rivaroxaban treatment. In addition, TNF-α stimulation increases HIF1-α expression and increases PAR-2 expression at the transcriptional level to activate downstream inflammation. In Raw264.7 cell line, rivaroxaban showed similar anti-inflammatory and anti-MMP-9 effects upon TNF-α stimulation.
CONCLUSIONS Rivaroxaban attenuates formation and rupture of AngII-induced AAA via inhibition of inflammation and MMP-9 expression and alleviation of elastin degradation and collagen loss. HIF1-α/PAR-2 signaling pathway may participate in these processes.
GW35-e0634
Jingyuan Li, Jiayin Li, Xiaozeng Wang
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Abdominal aortic aneurysm (AAA) is a vascular condition characterized by the weakening and dilation of the abdominal aorta, often leading to life-threatening complications. In this study, we aimed to investigate the potential therapeutic effects of vinpocetine (VINP) on AAA by regulating vascular smooth muscle cell (VSMC) apoptosis and senescence. Additionally, we aimed to elucidate the underlying molecular mechanism involved.
METHODS To establish an AAA model, apolipoprotein E-deficient (ApoE−/−) mice were treated with angiotensin II (AngII). In vitro, VSMCs were subjected to hydrogen peroxide (H2O2) to induce oxidative stress. Apoptosis and senescence were assessed using Western blot, TUNEL assay, immunofluorescence staining, and SA β-Gal staining.
RESULTS Our findings demonstrated that VINP attenuated AAA formation and reduced apoptosis and senescence in aortic VSMCs, both in vivo and in vitro. Specifically, VINP reversed the increased levels of apoptotic markers such as cleaved caspase 3 (C-cas 3) and Bax, as well as senescence markers including P53, P21, and P16, induced by H2O2 treatment. Mechanistically, VINP inhibited the expression of miR-155, a key regulator of apoptosis and senescence in VSMCs, in a time- and concentration-dependent manner following H2O2 stimulation. Furthermore, VINP alleviated the H2O2-induced upregulation of Yin Yang 1 (YY1), a transcription factor that controls miR-155 expression. To confirm the role of YY1, we utilized adeno-associated virus-YY1, which exacerbated AAA occurrence and progression in vivo.
CONCLUSIONS In conclusion, our study demonstrates that VINP ameliorates AAA formation by modulating VSMC apoptosis and senescence through the YY1-miR-155 pathway. These findings provide new insights into the potential therapeutic application of VINP for AAA treatment. Targeting the YY1-miR-155 axis may represent a promising strategy for developing novel therapeutic interventions against AAA. Further investigations are warranted to explore the full therapeutic potential of VINP and its underlying mechanisms in AAA pathology.
GW35-e0635
Wang Xuejun, Cheng Leilei
Zhongshan Hospital of Fudan University
OBJECTIVES Nutritional and pharmaceutical interventions act as preventive and therapeutic approaches against ICIs-associated myocarditis (ICIAM). This study aims to explore potential molecular mechanisms for preventing myocarditis based on arginination modification while treating cancer in the future.
METHODS Non-targeted metabolomics examined changes in differential metabolites in the serum of myocarditis patients and myocarditis mice cardiac tissues. Amino acid with significant differences in metabolomic results were detected in the serum of the patients. Mice were orally administered with arginine to observe its effects on ICIAM. Mass spectrometry identified substrates and modification sites of the enzyme acting on aminoacyl-tRNA synthetases. The levels of endogenous and exogenous arginine acylation-modified RALBP1 were validated in cell lines. Immunofluorescence staining verified the correlation between the degree of acylation modification in cardiac tissues from patients with hypertrophic cardiomyopathy and ICIAM. RALBP1 knockout mice were generated to investigate cardiac function and related signaling pathways. Specific site modification antibodies validated arginylation modification of RALBP1. SIRT3 was used to verify RALBP1 deacylation modification in vivo and in vitro. Selective inhibitor RBC8 were applied to validate the therapeutic effects of arginylation modification. Finally, the effect of acylation modification on RALBP1399th lysine spot mutation (K399R) and demodification (K399A) in vivo and in vitro.
RESULTS Non-targeted metabolomics indicated that arginine-related metabolic pathway was enriched in ICIAM patients, and arginine was the most significantly different amino acid in mice model. Biochemical results verified arginine significantly upregulated in the serum of myocarditis patients. Meanwhile, aminoacyl-tRNA synthetases (ARSs) for arginine, RARS, could catalyze arginylation of RALBP1 on site of K399, which was significantly increased in cardiac tissues of patients with ICIAM. We found ICIs could induce necroptosis in cardiomyocytes through receptor-interacting serine/threonine-protein kinase 3 (RIP3)-calmodulin-dependent protein kinase II delta (CaMKIIδ) and mixed lineage kinase domain-like protein (MLKL) pathways. RALBP1 knockout mice induced ICIAM showed significantly improved cardiac function, reduced arginylation reaction, downregulation of p-DRP1 expression, and inhibition of MAM-CAMKIIδ pathway. SIRT3 could inhibit acylation reaction by binding to RALBP1. Increased arginylation reaction and necroptosis could be observed in SIRT3 knockout mouse cardiac tissue. Moreover, RALBP1 selective inhibitor RBC8 could significantly inhibit arginylation reaction, improve mouse cardiac function, and suppress necroptosis occurrence compared to myocarditis group in ICIAM mouse model. K399A-RALBP1 point mutation myocardium-specific adenovirus in ICIAM mouse model exhibited an increased cardiac function after deacetylation modification, reduced arginylation reaction, and inhibited MAMs-CaMKIIδ pathway. Conversely, K399A-RALBP1 point mutation myocardium-specific adenovirus in mouse model exhibited a decreased cardiac function after modification, increased arginylation reaction, and activated MAMs-CaMKIIδ pathway.
CONCLUSIONS Increased serum arginine level increases the risk of developing myocarditis in cancer patients receiving immune checkpoint inhibitors therapy by promoting RALBP1 signaling. Inhibiting RALBP1 acylation reaction or RARS activity, suppressing MAMs-CaMKIIδ pathway activation, prevents the occurrence of ICIAM, highlighting the potential role of nutritional and drug interventions as a novel strategy for prevention and treatment of ICIAM.
GW35-e0636
Liang Hou1, Yanchun Ding2
1General Hospital of The Yangtze River Shipping
2Second Affiliated Hospital of Dalian Medical University
OBJECTIVES To investigate the influence of sodium butyrate (NaB) on plaque formation and inflammatory response in AS rats based on the nucleotide binding oligodomain-like receptor 1 (NOD1)/receptor interacting protein 2 (RIP2)/NF-κB signaling pathway.
METHODS Forty-one rats were fed with balloon damage combined with high-fat diet to establish AS model, and a total of 36 rats were successfully modeled. Thirty-six model rats were divided into model group, NaB group, and NaB+NOD1 agonist diaminopimelic acid (iE-DAP) group, with 12 rats in each group. In the 12 rats in the sham operation group, only the left common carotid artery was isolated and then sutured. The model group, NaB group, and NaB + iE-DAP group were fed with high-fat diet, the sham operation group was fed with basal diet, the NaB group and NaB + iE-DAP group were gavaged with 10 g/kg/d NaB, the NaB + iE-DAP group was gavaged with 10 g/kg/d NaB and intraperitoneally injected with 1 mL/piece/week of iE-DAP, and the model group and the sham operation group were given the same amount of normal saline for 12 weeks. The contents of serum TG, TC, LDL-C, HDL-C, hs-CRP, ox-LDL, MCP-1, IL-1, TNF-α were determined by ELISA; HE was performed to measure the morphology of the aorta; immunohistochemistry was performed to measure cell adhesion molecule (ICAM-1) protein in the aorta; Western blot was performed to measure NF-κB, NOD1 and RIP2 proteins in aorta.
RESULTS In the model group, the intimal endothelial cells were damaged, some nuclei were outside the cells, the medial smooth muscle cells proliferated severely, the cells were irregularly arranged, and localized into a plaque-like structure, calcification appeared in part of the media, and a large number of foam cells appeared; in the NaB group, the damage of intimal endothelial cells was alleviated, the smooth muscle cells of the intima were arranged regularly, the structure of each layer was complete, and no plaques and calcifications were found; the symptoms of NaB + iE-DAP group were severe. Compared with the sham operation group, the levels of TC, TG, LDL-C, hs-CRP, ox-LDL, MCP-1, IL-1 and TNF-α in serum, the positive rate of aortic ICAM-1, the levels of NOD1, RIP2 and nuclear NF-κB protein increased in the model group (P < 0.05), the content of HDL-C and cytoplasmic NF-κB protein decreased (P < 0.05); the levels of TC, TG, LDL-C, hs-CRP, ox-LDL, MCP-1, IL-1 and TNF-α in serum, the positive rate of aortic ICAM-1 (4.98 ± 0.53 vs. 16.79 ± 1.78), the levels of NOD1 (1.29 ± 0.11 vs. 1.73 ± 0.16), RIP2 (0.73 ± 0.06 vs. 1.39 ± 0.12) and nuclear NF-κB protein in the NaB group decreased compared with those in the sham group (P < 0.05), and the content of HDL-C and the cytoplasmic NF-κB protein level increased compared with those in the sham group (P < 0.05); compared with NaB group, the levels of TC, TG, LDL-C, hs-CRP, ox-LDL, MCP-1, IL-1 and TNF-α in serum, the positive rate of aortic ICAM-1(9.36 ± 0.97 vs. 4.98 ± 0.53), the levels of NOD1(1.53 ± 0.16 vs. 1.29 ± 0.11), RIP2(1.01 ± 0.13 vs. 0.73 ± 0.06) and nuclear NF-κB protein increased in the NaB + iE-DAP group (P < 0.05), and the content of HDL-C and cytoplasmic NF-κB protein level decreased (P < 0.05).
CONCLUSIONS This study suggests that NaB can inhibit NOD1/RIP2/NF-κB signaling pathway to relieve plaque formation and inflammatory response in AS rats.
GW35-e0643
Shuli Zhang1,2, Jiayin Li1,2, Xiaozeng Wang2
1College of Medical and Bioinformatics Engineering, Northeastern University
2State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Abdominal aortic aneurysm (AAA) is the most prevalent dilated arterial aneurysm that poses a significant threat to the older adults. Aging is an independent risk factor for AAA occurrence. However, whether cell senescence related genes can be used as early biomarkers to identify the occurrence and rupture of AAA remains to be investigated.
METHODS We carried out a combination of bioinformatics, machine learning techniques, and molecular biology experiments to elucidate the association between senescence-related genes (SRGs) and the occurrence and progression of AAA, further identify potential SRGs that could serve as reliable biomarkers for AAA diagnosis.
RESULTS 429 DEGs were identified from the GSE57691 training set, and 867 SRGs were obtained. By combining DEGs with SRGs, 19 overlapping DESRGs were identified. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest revealed seven common hub genes: BTG2, ETS1, FOS, ID1, ITPR3, MAP3K6, and MTHFD2. In the initial validation set, significant differences in the expression levels of BTG2, ETS1, ID1, and ITPR3 were observed between the AAA and control groups. ROC analysis demonstrated a robust diagnostic performance. Further validation across small, large, and ruptured AAA subsets identified ETS1 and ITPR3 as potential diagnostic genes. In addition, scRNA-seq highlights senescent cells play an important role in AAA. Bioinformatics prediction combined experimental validation identified ETS1 and ITPR3 as possible cellular senescence-related biomarkers of AAAs, with ETS1 being more likely.
CONCLUSIONS Our study highlights the potential role of cellular SRGs in different degrees of AAA. ETS1 and ITPR3 are promising biomarkers for AAA diagnosis.
GW35-e0644
Shuli Zhang1,2, Xiaozeng Wang2
1College of Medical and Bioinformatics Engineering, Northeastern University
2State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by local lesions of the aortic wall, which can lead to fatal ruptures. Immune cells infiltrate lesions are important for AAA progression and immunotherapies. This study was aimed at gaining important new insights into the heterogeneity of immune cells in AAA.
METHODS Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by local lesions of the aortic wall, which can lead to fatal ruptures. Immune cells infiltrate lesions are important for AAA progression and immunotherapies. This study was aimed at gaining important new insights into the heterogeneity of immune cells in AAA.
RESULTS Integrative analyses identified 23 distinct subpopulations based on gene expression profiles. Further analysis demonstrated that these cells manifested high heterogeneity at the levels of tissue preferences, genetic perturbations, functional variations, immune dynamics, metabolic changes, and communication patterns. Our findings reveal distinct T cell subpopulations with specialized roles in mitochondrial biogenesis, apoptosis, immune activation and metabolic regulation. Additionally, T3 serves as main signal receiver. B cells exhibit diverse functionalities and maintain close relationships with T cells in both pathway and cellular communication. Macrophages and monocytes play unique roles in AAA, contributing to both pro-inflammatory and reparative processes. Notably, the cellular communication landscape highlights critical signaling pathways and ligand-receptor interactions that regulate the immune dynamics in AAA.
CONCLUSIONS This study uncovers distinct immune cell subpopulations, elucidates functional pathways, analyzes differentiation trajectories, and reveals ligand-receptor interactions in the pathophysiology of AAA. By mapping the immuno-topology of AAA, we identify potential therapeutic targets for modulating the immune response and mitigating disease progression. Our findings underscore the importance of a detailed understanding of the immune microenvironment in developing targeted interventions for AAA.
GW35-e0645
Xiaoliang Zhang, Jing Geng, Lang Hu, Yan Li
Department of Cardiology, Tangdu Hospital, Airforce Medical University
OBJECTIVES Reduced fatty acid oxidation (FAO) capacity is generally accepted as the hallmark of metabolic reprogramming in heart failure (HF) and pathological myocardial remodeling. However, the underlying mechanisms are poorly understood. Here, we postulated that coupling may occur between mCa2+ and mitochondrial FAO in the myocardium. The present study aimed to clarify the roles of mCa2+ in cardiac lipid oxidation and energy production and explore the mechanism linking mCa2+ to lipid metabolism disorder in the failing heart.
METHODS Clinical data and heart tissue samples were collected from patients with or without HF. Cardiac hypertrophy and HF models were induced in mice by using transverse aortic constriction (TAC) surgery to create a sustained pressure overload. Cardiac FAO capacity and mCa2+ concentration were evaluated in isolated mitochondria and adult mouse cardiomyocytes. Heart tissue samples and isolated adult cardiomyocytes were examined by transmission electron and confocal microscopy. Purified protein was isolated, extracted and further subjected to biochemical analysis.
RESULTS The mCa2+ concentration and the mitochondrial FAO capacity simultaneously declined in the failing heart whereas mitochondrial Ca2+ recovery restored its mitochondrial FAO capacity and myocardial contractility. Combination analysis of metabolic flow and biochemical analysis showed that Ca2+ acutely increased FAO by direct activation of MTP in the mitochondrial matrix. We established that dissociation of the mitochondria-associated endoplasmic reticulum [ER] membrane (MAM) is the major cause of insufficient Ca2+ uptake and mCa2+ starvation in the mitochondria. We constructed a synthetic mitochondria-ER (mito-ER) linker to rescue the MAM and mCa2+ concentration and found that it improved lipid metabolism and cardiac function in the failing heart. Furthermore, decreased mCa2+, disassociated MAM and dysregulated lipid metabolism was also observed in the heart tissue sample of patients with HF.
CONCLUSIONS In this study, for the first time we established a direct link between mCa2+ and mitochondrial FAO. Inadequate mCa2+ uptake results in reduced FAO and contractility in the failing heart. Modulating the mCa2+ concentration through an in vivo mito-ER linker is potentially a novel approach to the reversal of metabolic rewiring and pathological remodeling in HF progression.
GW35-e0659
Lina Lyu1,2,3, Xuewei Xia1,2,3, Chunyu Zeng1,2,3
1Department of Cardiology, Daping Hospital, Army Medical University, Chongqing 400042, China
2Key Laboratory of Cardiovascular and Cerebrovascular Diseases in the Elderly, Ministry of Education, Chongqing 400042
3Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing 400042, China
OBJECTIVES Zinc-α2-glycoprotein (ZAG/AZGP1), a significant plasma protein, plays a crucial regulatory role in the development of various diseases. However, its role in myocardial injury after myocardial infarction (MI) is poorly understood. This study aims to investigate the role of AZGP1 in myocardial infarction and its potential mechanisms.
METHODS We analyzed the correlation between cardiac function and plasma AZGP1 levels in 200 patients with acute myocardial infarction using multiple regression analysis. Furthermore, we examined the expression and distribution of AZGP1 in myocardial cells before and after infarction in C57BL/6 mice. Overexpression and silencing of AZGP1 in mouse hearts were achieved through myocardial injection of adenoviruses and gene knockout to evaluate various parameters including cardiac function, infarct size, and myocardial cell apoptosis. We isolated and cultured neonatal mouse myocardial cells, induced myocardial cell apoptosis with H2O2, investigated the influence of AZGP1 on myocardial cell apoptosis, its mechanism of action, the interaction between AZGP1 and USP10, and the regulation of GADD45G expression. Further exploration was conducted to address issues such as the short half-life of AZGP1 and the rationality of its use in clinical applications. We also developed a cardiac-targeted nanocarrier system based on liposome structure (CTP-LIPs-cy7) to deliver AZGP1 protein via tail vein injection in infarcted mice, observing its effects on cardiac function, infarct size, and myocardial cell apoptosis to explore the therapeutic efficacy in infarcted mice.
RESULTS Multiple regression analysis of 200 acute myocardial infarction patients revealed a decrease in plasma AZGP1 expression post-MI, positively correlated with cardiac function and independently predictive of decreased post-infarction cardiac function. After 48 hours of infarction in C57BL/6 mice, cardiac AZGP1 mRNA and protein levels significantly decreased, possibly due to hypoxia and ROS. AAV9-AZGP1 overexpressing mice showed improved cardiac function, reduced infarct size, and myocardial cell apoptosis post-infarction compared to the control group. Conversely, AZGP1 global knockout mice exhibited decreased cardiac function, increased infarct size, and myocardial cell apoptosis post-infarction. In the H2O2-induced myocardial cell apoptosis model, myocardial cell apoptosis significantly reduced with rhAZGP1 overexpression compared to the empty vector group. RNAseq sequencing, significant gene changes between the two groups, combined with mass spectrometry analysis and co-immunoprecipitation, identified the AZGP1-interacting protein USP10. The immunofluorescence and WB analysis revealed that the binding of AZGP1 and USP10 inhibits nuclear translocation of USP10, induces P53 degradation via the ubiquitin-proteasome pathway, further inhibits GADD45G expression, reduces myocardial cell apoptosis, and protects against myocardial injury post-infarction. Cardiac-targeted nanocarriers effectively enhance targeting to the heart for treatment, improving AZGP1 expression localization in the heart, cardiac function post-infarction, reducing infarct size and myocardial cell apoptosis, effectively ameliorating cardiac damage post-myocardial infarction, and enhancing clinical application value.
CONCLUSIONS AZGP1 suppresses myocardial cell apoptosis, improves cardiac function, and reduces myocardial injury post-myocardial infarction by binding and inhibiting nuclear translocation of USP10 and decreasing GADD45G expression. Cardiac-targeted AZGP1-loaded lipid nanoparticles can also reduce myocardial injury post-myocardial infarction.
GW35-e0670
Panting Wei, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Macrophages are one of the most active cell types during all stages after myocardial infarction (MI). Different subsets of macrophages originating from tissue-settled and bone marrow monocytes coexist in the infarcted heart. However, the impact of the macrophage subsets on MI remains incompletely understood. This study aimed to investigate the dynamic changes and biological functions of macrophage subsets in the initiation and progression of MI.
METHODS The single-cell transcriptomic data from the control and MI (at 1, 2, 3, and 8 weeks) were integrated from the GEO database (GSE163956). Using computational methods implemented in R package Seurat, we applied unsupervised graph-based clustering on the pool of all samples. The Harmony method is utilized for integrating data and correcting batch effects. Cell types were annotated based on the expression of marker genes reported in previous literatures. GO analysis was conducted to investigate the biological functions of these distinct subsets. Monocle2 was employed to conduct pseudo-temporal analysis on the macrophage subsets.
RESULTS A total of seven cell types were identified in integrated cardiac tissue from control and MI mice excepted to cardiomyocytes, in which macrophages increased significantly after 1-week. Then, subsequent analysis of macrophages revealed six subsets, including a monocyte subset Ly6c+ Mono, tissue-resident macrophages RM_Lyve1+ and three types of bone marrow-derived macrophage Ccr2+, H2-Eb1+Ccr2−, and Trem2+Spp1+, and others that cells with a small number of cells and a far deviation in the UMAP. The proportion of RM_Lyve1+ remarkedly decreased at 1-week (30.8%–10.2%) but restored at the 2-week (15.3%) and continuously increased at the 8-week (57%) post-MI. Ly6c+ Mono showed rapidly decline (37.1%–3.3%), while Trem2+Spp1+ displayed significantly increase at 1-week (5%–37.1%) post-MI. The Ccr2+ peaked at 2-week post-MI (32.4%), while H2-Eb1+Ccr2− reached their peak at 3-week after MI. GO analysis showed that the RM_Lyve1+and Ccr2+ subsets were associated with immune inflammation, with key genes including Pf4, Gas6, Il1b, Thbs1, and Clec4e. The H2-Eb1+Ccr2− was linked to type II interferon response and antigen processing and presentation, with related genes Cd74, Cd83, Ighm, and Axl. Within the Trem2+Spp1+, genes involved in the regulation of chromosome segregation (Mki67, Spdl1, Igf1) exhibited significant up-regulation, potentially due to substantially increased in cell numbers 1-week post-MI. The Ly6c1+ Mono demonstrated functions related to migration and regulation of angiogenesis, with associated genes Cdh5, Kdr and Pecam1. Trajectory analysis revealed that Trem2+Spp1+and Ly6c1+ Mono shared the common branch, suggesting a potential differentiation from Ly6c1+ Mono, whereas RM_Lyve1+, Ccr2+and H2-Eb1+Ccr2− straddled all branches.
CONCLUSIONS This study provides a comprehensive map of the transformation of different macrophage subsets in the middle and late stages of MI. These findings provide valuable insights for further research on how to use and modulate these macrophage subsets to promote cardiac repair after MI.
GW35-e0675
Jingjin Hou, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Hypertension is a common metabolism-related disease, and prolonged uncontrolled hypertension can lead to serious diseases such as heart failure or heart attack. The dysfunction of vascular smooth muscle cells (VSMCs) is an important cause of hypertension. Although AMPK may be a therapeutic target to reduce hypertension, the role of the γ2 subunit in AMPK heterotrimers in the development of hypertension has not been explored so far, and more direct and effective targets are still needed to treat hypertension. Neural progenitor cells express the developmentally down-Regulated 4-like (NEDD4L) gene, an E3 ligase that ubiquitinates its substrates for degradation and plays an important role in the regulation of blood pressure, but the specific mechanisms need to be elucidated. Also, it remains unclear whether AMPKγ2 subunits regulate phenotypic switching in VSMCs via NEDD4L. Therefore, we investigated the role of AMPKγ2 in blood pressure regulation in blood vessels.
METHODS AMPKγ2 expression in hypertensive patients was determined by bioinformatics analysis. Hypertension animal models were established in whole-body AMPKγ2 or VSMCs-specific AMPKγ2 knockout mice to evaluate the role of AMPKγ2. RNA sequencing and pull-down experiments were performed to investigate the downstream mechanisms. QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PAMPK/NEDD4L pathway, respectively. HE, Masson staining were performed on vascular tissues from mice of different genotypes to illustrate the effect of AMPKγ2 on vascular remodeling. After confirming the binding between NEDD4L and AMPKγ2 and their positive correlation by bioinformatics analysis, the relationship between the two was further verified.
RESULTS The expression of AMPKγ2 was decreased in the vascular tissues of patients with hypertension. AMPKγ2 was downregulated in hypertensive models and TNF-α-induced smooth muscle cells. AMPKγ2 KO mice had higher systolic and diastolic blood pressure than their littermate controls; systemic overexpression of AMPKγ2 ameliorated the increase in systolic and diastolic blood pressure in AngII-pump-stimulated mice. AMPKγ2 KO mice had aggravated vascular fibrosis, and systemic overexpression of AMPKγ2 attenuated the degree of AngII-induced vascular fibrosis. Adenoviral overexpression of AMPKγ2 suppressed increases in α-SMA and SM22 phenotypic switch marker molecules in VSMCs exposed to TNF-α (25 ng/mL). Smooth muscle cell-ospecific overexpression of AMPKγ2 through PAMPK and NEDD4L pathways can reduce AngII-induced increases in blood pressure and reduce adverse remodelling of vessels, thereby improving vascular function. Interference with AMPKγ2 increased VSMC migration, invasion, and phenotypic switching. Mechanistically, we found that deletion of AMPKγ2 specifically reduced NEDD4L expression, thereby promoting smooth muscle cell migration and triggering phenotypic switching of smooth muscle cells. TNF-α treatment decreased AMPKγ2 in smooth muscle cells and promoted the decreased expression of NEDD4L. In conclusion, AMPKγ2 positively impacts NEDD4L expression changes via the PAMPK pathway, thereby regulating phenotypic switching in smooth muscle.
CONCLUSIONS The reduction of AMPKγ2 expression in vascular smooth muscle cells can reduce the level of NEDD4L through the PAMPK pathway, thereby regulating the phenotypic switch of smooth muscle and leading to the development of hypertension.
GW35-e0684
Yuto Kawase1, Toshihide Hamabehoriike1,2, Ryosuke Tsukabe1, Hanhao Wu1, Yoichi Sunagawa1,2, Yasufumi Katanasaka1,2, Ryuya Naruta1, Koji Hasegawa1,2, Tatsuya Morimoto1,2
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
2Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan
OBJECTIVES Heart failure is a leading cause of death worldwide. Resolving this problem is extremely important. Cardiac hypertrophy is involved in the development of heart failure. Chinese herbal medicines are expected to be used in the treatment of heart failure in terms of drug repositioning. In this study, we screened Chinese herbal medicines that suppress cardiomyocytes hypertrophy and found Goshajinkigan and Ninjinyoeito. The purpose of this study is to investigate the effect of Goshajinkigan and Ninjinyoeito on cardiomyocytes hypertrophy and the development of heart failure.
METHODS First, primary cultured cardiomyocytes prepared from neonatal rat hears were treated with 100 μg/mL Goshajinkigan and Ninjinyoeito, and then stimulated with phenylephrine for 48 hours. Immunofluorestaining and qPCR were performed on these cardiomyocytes. SD rats were subjected to myocardial infarction (MI) surgery and then given a mixed feed with 2.65% Goshajinkigan and 3.3% Ninjinyoeito for 7 weeks. Moreover, C57BL/6J mice were subjected to transverse aortic constriction (TAC) surgery and then given a daily oral administration of 1 g/kg Goshajinkigan and 1.25 g/kg Ninjinyoeito for 14 weeks. Echocardiographic analysis, histological staining, and qPCR analysis were performed.
RESULTS In the primary cultured cardiomyocytes, Goshajinkigan and Ninjinyoeito significantly suppressed PE-induced increases in cell surface area and mRNA levels of hypertrophic related genes, such as ANF and BNP. Since these Goshajinkigan and Ninjinyoeito inhibited the cardiomycyte hypertrophy, we then examined the effects of these Chinese herbal medicines on systolic function. Echocardiography showed that Goshajinkigan and Ninjinyoeito didn’t prevent MI- and TAC-induced decreases in systolic function. Moreover, Goshajinkigan and Ninjinyoeito did not inhibited the MI- and TAC-induced increases in cardiomyocyte cross-sectional area, interstitial fibrosis area, mRNA levels of cardiac hypertrophic related genes.
CONCLUSIONS Both Goshajinkigan and Ninjinyoeito failed to inhibit the progression of heart failure in vivo. One of the possible reasons is that the active ingredients do not reach the heart sufficiently. In the future, identification of active ingredients from Goshajinkigan and Ninjinyoeito, analysis of these pharmacokinetics, and formulation studies are expected to lead to the development of heart failure treatments using Chinese herbal medicines.
GW35-e0686
Xiaohui Liu1, Qin Fang1, Lu Fang2, Lemin Zheng2,3, Xiaoquan Rao1, Yan Wang1
1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
2The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, Beijing 100191, China
3Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, Capital Medical University, 6 Tiantan Xili, Chongwen District, Beijing 100050, China
OBJECTIVES Lentinan (LNT), a natural β-(1,3)-glucan polysaccharide extract from shiitake mushroom, has demonstrated a role in several diseases such as cancer. However, the effect of LNT on atherosclerosis and its underlying mechanisms remain unclear.
METHODS ApoE−/− mice were fed with a high-fat diet (HFD) with or without simultaneous oral administration of LNT for 12 weeks. Area, lipid deposition, and collagen content of the aortic plaque were then determined. Foam cell formation, cholesterol uptake and efflux were measured in bone marrow-derived macrophages (BMDMs) incubated with 50 mg/mL ox-LDL for 24 hrs with or without LNT pretreatment. RNA sequencing (RNA-seq) was used to identify downstream genes regulated by LNT in macrophages. Immunofluorescence staining and immunoprecipitation-mass spectrometry (IP-MS) were employed to track the cellular localization of Cy5 labeled LNT and identify the target proteins binding with LNT. Molecular docking, co-IP, and the cellular thermal shift assay (CETSA) were utilized to validate the binding of LNT and targeted proteins.
RESULTS LNT administration significantly attenuated atherosclerotic plaque progress, evidenced by decreased plaque area, less lipid deposition, and increased collagen in the plaque. Oil red O staining and in vitro cell culture experiment revealed that LNT decreased lipid accumulation in macrophages. There was an increase in cholesterol efflux to HDL, without impact on the uptake of Dil-LDL, upon LNT treatment. The total protein level of SR-B1 did not show significant differences, nevertheless, the LNT group exhibited elevated levels of plasma membrane-localized SR-B1 compared to the control group. RNA-seq revealed a significant impact of LNT on the ferroptosis pathway, especially the increase of Slc7a11. Compared with control group, the deposition of iron was decreased while the expression of Slc7a11 in atherosclerotic root macrophages was increased in LNT treated mice. In vitro experiment with BMDMs confirmed that LNT suppressed ox-LDL-induced ferroptosis through improving mitochondrial function, attenuating oxidative stress, and reducing lipid peroxidation in a Slc7a11 dependent way. Inhibition of Slc7a11 abolished the protective effects of LNT on ferroptosis and SR-B1 expression. Mechanistically, LNT directly binds to Fubp1, which may compete for its binding with p53, ultimately relieving the transcriptional repression of p53 on Slc7a11.
CONCLUSIONS We identified a previously unrecognized role of LNT in atherosclerosis, which attenuates macrophage ferroptosis via activating Fubp1/p53/Slc7a11 pathway and improves cholesterol efflux via subsequent SR-B1 translocation. Our study underscores that LNT, a nature fungal component, could serve as a novel therapeutic agent for atherosclerosis.
GW35-e0699
Ziyu Wang1, Wenyi Zhang1, Panpan Yu1, Xue Jiang1, Xiangjun Zeng2, Caixia Guo1
1Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University
2Department of Physiology and Pathophysiology, Capital Medical University
OBJECTIVES In recent years, regulatory T cells (Treg cells) have been found to play an important role in myocardial ischemia-reperfusion (I/R) injury. Previous studies have demonstrated that soluble receptor for advanced glycation end-products (sRAGE) inhibits cardial ischemia-reperfusion injury through Treg cells. MHCII mediated antigen presentation is required for the activation of Treg cells. This study aimed to investigate whether sRAGE activates Treg cells during myocardial ischemia-reperfusion by affecting the expression of MHCII in cardiac microvascular endothelial cells and its possible mechanisms.
METHODS The myocardial ischemia-reperfusion process at the whole animal level was stimulated by constructing myocardial-specific sRAGE transgenic mice and ligating and releasing the left anterior descending branch of the mice. In vitro, the mouse cardiac microvascular endothelial cells were cultured, and the oxygen glucose deprivation/reoxygenation (OGD/R) model was replicated. The expression of MHCII in cardiac microvascular endothelial cells was measured by immunohistochemistry, immunofluorescence and Western Blotting.
RESULTS In vivo, compared with sham operation group, the level of MHCII in cardiac microvascular endothelial cells was significantly increased at 72 hours after I/R in sRAGE-overexpressing group, and similar results was found in vitro at 24 hours after OGD/R. At 30 min after OGD/R, the levels of phosphorylated signal transducer and activator of transcription 1 (STAT1) in cytoplasm and nucleus of cardiac endothelial cells in sRAGE-overexpressing group were significantly higher than those in control group.
CONCLUSIONS Our data suggest that sRAGE may activate Treg cells by promoting MHCII expression in cardiac microvascular endothelial cells, thereby achieving an inhibitory effect on myocardial ischemia-reperfusion injury. The mechanism may be that sRAGE promotes the phosphorylation and nuclear-importing of STAT1.
GW35-e0700
Jia Zhang1,2,3
1Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
2State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
3Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES Angiogenesis is a dynamic process fine-tuned by transcription factors in endothelial cells. Krüpple-like factors 15 (KLF15)-mediated transcriptional regulation mechanism is critical for cardiovascular diseases. Therefore, we explore the role of endothelial KLF15 in governing angiogenesis.
METHODS KLF15 and vasorin (VASN) were deleted from endothelial cells with tamoxifen-inducible Cdh5-promoter-driven Cre recombinase in EC-KLF15 KO and EC-VASN KO mice, respectively. EC-KLF15 KO, EC-VASN KO and control mice were subjected to retinal angiogenesis or xenograft tumor assay. RNA-seq, ATAC-seq, and ChIP-seq were carried out to identify the downstream effector of KLF15. Cell proliferation, wound healing, and tube formation assays were performed to delineate endothelial cell function.
RESULTS In EC-KLF15 KO mice and adenovirus-mediated KLF15 overexpression mice, we showed that KLF15 negatively regulated retinal angiogenesis, as confirmed in cultured endothelial cells. KLF15 opened chromatin, bound with the promoters of GC-rich sequences, and transactivated the expression of VASN. VASN suppressed endothelial angiogenic function which was essential for Dll4-induced Notch1 signaling activation. Moreover, increased expression of VASN in EC-KLF15 KO mice suppressed retinal angiogenesis, which was attenuated by γ-secretase inhibitor. EC-VASN KO mice recapitulated the promotion of retinal angiogenesis in EC-KLF15 KO mice. Finally, EGF-like domain of VASN was essential for its interaction with Notch1, and VASN EGF-like domain-derived peptides activated Notch1 signaling and suppressed angiogenesis.
CONCLUSIONS KLF15/VASN axis negatively regulates angiogenesis by activating Notch1 signaling. KLF15 and VASN in endothelial cells might represent novel therapeutic targets for the treatment of impaired angiogenesis-related diseases and tumors.
GW35-e0706
Elizaveta Marasaeva1, Dmitry Kashirskikh1, Raisa Surkova1, Tatiana Kovyanova1, Igor Sobenin1,2, Alexander Orekhov1,3
1Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
2V.N. Smirnov Institute of Experimental Cardiology, E.I. Chazov National Medical Research Center of Cardiology, Moscow, Russian Federation
3Institute for Atherosclerosis Research, Moscow, Russian Federation
OBJECTIVES Neuraminidases are enzymes that catalyze the hydrolysis of the terminal sialic acid. The involvement of this enzyme has been noted in several diseases, including atherosclerosis. By desialylation, neuraminidases can modify the functionality of the target compound such as low-density lipoprotein (LDL), which acquires atherogenic properties and triggers the mechanism of LDL aggregation. Modulating neuraminidase activity with selective inhibitors is a promising approach for understanding sialidase function and preventing the development of atherosclerotic manifestations at the initial stages of the disease. This study was aimed to find out whether the natural bioactive compounds may inhibit neuraminidase activity and further to choose the most active ones to investigate the earliest mechanism of LDL modifications, specifically desialylation.
METHODS Eight bioactive flavonoids were selected using molecular docking with the Schrödinger program and isolated from native sources by pressurized liquid extraction. Purification and identification of the compounds were carried out using thin-layer chromatography, NMR and HPLC. To assess neuraminidase activity, a fluorometric assay was performed using the Sialidase Activity Assay Kit. Cell viability was analyzed with MTT Assay on THP-1 cells, and IC50 values were calculated.
RESULTS As a result of fluorescent analysis, the percentage inhibition of sialidase and concentration of half-maximal inhibition (IC50) were determined. Five active inhibitors were chosen with IC50 values ranging from 11.5 to 73.9 μM (Epigallocatechin, Avicularin, Kaempferol-7-O-neohesperidoside, Vescalagin, and Afrormosin-7-glucoside). These compounds were extracted from such native sources as Camellia sinensis, Cichorium intybus, Castanea sativa and Vaccinium vitis-idaea. The lowest IC50 were identified for Epigallocatechin (11.5 ± 0.3 μM) and Kaempferol-7-O-neohesperidoside (27.1 ± 0.3 μM). MTT test showed that Epigallocatechin had the lowest cytotoxicity, as the reduction in cell survival did not reach 50%, while the most toxic inhibitor was Kaempferol-7-O-neohesperidoside (IC50 1.2 ± 0.1 μM).
CONCLUSIONS This study demonstrates that natural bioactive compounds, especially Epigallocatechin, exhibit excellent activity against the neuraminidase enzyme; they can be used for further investigations of the prevention the initial stages of atherosclerotic plaque formation. This study was supported by Russian Science Foundation, Grant # 23-65-10014.
GW35-e0707
Elizaveta Marasaeva1, Dmitry Kashirskikh1, Raisa Surkova1, Tatiana Kovyanova1, Igor Sobenin1,2, Alexander Orekhov1,3
1Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
2V.N. Smirnov Institute of Experimental Cardiology, E.I. Chazov National Medical Research Center of Cardiology, Moscow, Russian Federation
3Institute for Atherosclerosis Research, Moscow, Russian Federation
OBJECTIVES Atherosclerosis, the chronic vascular disease, starts with endothelial dysfunction. This condition leads to penetration of circulating low-density lipoprotein (LDL) under the damaged endothelium and its accumulation within the subendothelial layer, where LDL is prone to various alterations, including oxidation and deglycosylation. Such atherogenic modifications are related to intermediate or progressing atherosclerotic lesions. The studying of the initial stages of atherogenesis allow to identify the triggering mechanisms of the pathological. Deglycosylation, namely, desialylation, is the primary step of LDL modification by neuraminidase in the blood plasma of atherosclerotic patients. Desialylated LDL more easily penetrates the blood vessel due to the loss of the screening function for sialic acid and acquires the ability to aggregate. Modulation of the activity of the neuraminidase through its selective inhibition can prevent the initial processes of the development of atherosclerosis.
METHODS The tested compounds (47 potential neuraminidase inhibitors in total) were selected from such classes as oxazolinones, benzylidene-succinimides, and benzylidene-imidazoles using the Schrödinger program and further synthesized according to the approach of dehydration/cyclization of hippuric acid. Purification and identification of the compounds were performed using thin-layer chromatography, NMR and HPLC. Inhibitory activity was determined using the Sialidase Activity Assay Kit. To study the cytotoxic effect of neuraminidase inhibitors on THP-1 cells, MTT test was used with target compounds at various concentrations (0.3–20 μM), and IC50 values were determined.
RESULTS Fluorimetric analysis identified five most active neuraminidase inhibitors: (1) cyclohexyl-4-furan-2-ylmethien-1-4-trifluorophenyl-pyrrolidine-2,5-dione (IC50 = 2, 5 ± 0, 1 μM), (2) (Z)-4-(4-methoxybenzylidene)-2-methyloxazol-5(4H)-one (oxazolinone) (IC50 = 4, 6 ± 0, 1 μM), (3) (Z)-2-(2,4-dichlorophenyl)-4-(pyridin-3-ylmethylene)oxazol-5(4H)-one (oxazolinone) (IC50 = 4, 8 ± 0, 1 μM), (4) (E)-3-(4-diethylamino)-2-hydroxybenzylidene-pyrrolidine-2,5-dione) (IC50 = 8, 6 ± 0, 1 μM), (5) N-TEMPO-5-((Z)-4-nitrobenzylidene)-2-((E)-styryl)-3,5-dihydro-4H-imidazol-4-one) (IC50 = 29, 6 ± 0, 1 μM). According to the results of MTT analysis performed in THP-1 cells, the safest inhibitor was (E)-3-(4-diethylamino)-2-hydroxybenzylidene-pyrrolidine-2,5-dione), which did not access half-maximal reduction in cell survival. Otherwise, the most toxic one was N-TEMPO-5-((Z)-4-nitrobenzylidene)-2-((E)-styryl)-3,5-dihydro-4H-imidazol-4-one) (IC50 1.4 ± 0.2 μM). The remaining three selected inhibitors have survival values of IC50 ranged 2.3–32.5 μM.
CONCLUSIONS This study revealed effective neuraminidase inhibitors, oxazolinone and benzylidene-imidazole derivatives, that may provide an insightful help in preventing the early atherogenic LDL modification, namely, desialylation. This study was supported by Russian Science Foundation, Grant # 23-65-10014.
GW35-e0717
Qingyuan Yang, Zhihui Zhang
Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University
OBJECTIVES Coronary microvascular disease is an important cause of myocardial ischemia, with high morbidity and poor prognosis, clinical diagnosis and treatment is a bottleneck problem, and it is crucial to find effective interventions and explore their mechanisms. Time-restricted feeding plays an important role in cardiovascular disease mainly by changing the eating time window. We aimed to investigate whether time-restricted feeding can improve the process of coronary microvascular disease.
METHODS Leptin-deficient ob/ob mice were applied to construct a coronary microvascular disease model, and were randomly divided into an ad libitum diet group and a time-restricted feeding group. The feeding regimen in the time-restricted feeding group was such that the daily feeding window was limited to 9 hours, with the remaining 15 hours in a fasting state. After 8 weeks of intervention, laser Speckle Contrast Imaging was performed to detect coronary perfusion, cardiac ultrasound was performed to detect ejection fraction, fractional shortening, and coronary flow reserve, and immunofluorescence to detect cardiac microvessel density and expression of endothelial cell apoptosis-related proteins.
RESULTS Laser Speckle Contrast Imaging and cardiac ultrasound results showed that coronary perfusion was significantly increased and coronary flow reserve was significantly improved in the time-restricted feeding group compared with the ad libitum diet group, but there were no significant differences in the ejection fraction and fractional shortening. Immunofluorescence results in mouse hearts showed that cardiac microvessel density was significantly increased in the time-restricted feeding group, and further by co-localization staining with endothelial cells, it was found that the expression of Bcl2 was elevated in the endothelial cells of mice in the time-restricted feeding group, and the expression of Bax was down-regulated.
CONCLUSIONS Our results reveal that time-restricted feeding improves microvascular endothelial cell function and delays the progression of coronary microvascular disease by inhibiting endothelial cell apoptosis.
GW35-e0746
Xiaoqing Jiang, Mindian Li, Zhihui Zhang
Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Army Medical University
OBJECTIVES Atherosclerosis is a chronic inflammatory disease of the arterial wall, mainly caused by the accumulation of low-density lipoprotein cholesterol in the arterial wall. Abnormal cholesterol metabolism in humans not only leads to NAFLD, but also causes the development of atherosclerotic dyslipidemia. Mutations in the essential activator gene of lipolysis, the gene for CGI-58, cause progressive hepatic steatosis and ultimately causes liver fibrosis in mice and humans. Emerging evidence suggests that targeting peripheral droplet proteins such as Perilipin-3 can prevent fatty liver and inflammation in CGI-58-deficient mice. However, it is unclear whether this effect is limited to Perilipin-3 or related to lipid droplet biogenesis, and Perilipin-2 has sequence homology with Perilipin-3. The purpose of this study is to determine whether hepatocellular Perilipin-2 is involved in the development of fatty liver associated with CGI-58 deficiency in mice and affecting the progression of atherosclerosis.
METHODS In this study, we sought to explore the role of hepatocyte Perilipin-2 in the development of mouse hepatic steatosis induced by CGI-58 deficiency and compare the effects of Perilipin-2 and Perilipin-3 in regulating the lipid metabolism in hepatocytes. We used the hepatocyte-restricted co-expression adeno-associated viral system to induce the loss of CGI-58 by Cre and the expression of Plin 2-miRNA (Plin 2-KD) or control miRNA (NC) by the miR-155 promoter. Plin2 KD and NC mice were fed a high-fat diet for 5 weeks and examined for metabolic phenotype and liver pathology. Meanwhile, we evaluated the effect of Plin 2-KD on hepatocytes of fatty acid-loaded AML-12 mice, and compared the effects of Plin 2 and Plin 3 on lipid droplet biogenesis in AML-12 cells and CGI-58-specific knockout-induced mouse liver fatty liver.
RESULTS Plin 2 knockdown reduced Plin 2 protein levels in mouse liver by >99%, which was associated with increased glucose tolerance and insulin resistance. Plin 2-KD reduced hepatomegaly and liver damage in CGI-58 deficient mice, while reducing the histological NAS score and hepatic lipid content by 3.2 points (P = 0.0121) and 46% (P = 0.0166). Notably, Plin 2-KD prevented microbubble hepatic steatosis in CGI-58-deficient female mice, which was associated with reduced lipid droplet formation in AML-12 Plin 2-deficient hepatocytes.
CONCLUSIONS In conclusion, our results indicate that hepatocyte Plin 2 is crucial in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency, and clarify the therapeutic potential of hepatic steatosis and hepatic fibrosis by intervening with the development of microvesicular hepatic steatosis, while still requiring further investigation.
GW35-e0749
Xiaoqin Wan, Zhihui Zhang
Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Army Medical University
OBJECTIVES The area above 2500 m is defined as plateau area. Elevated pulmonary artery pressure due to low partial oxygen pressure in high altitude areas can cause serious harm to the heart. Pulmonary hypertension is a common clinical disease characterized by right heart dysfunction caused by chronic hypoxic pulmonary vascular remodeling. It is the third largest cardiovascular disease after coronary heart disease and hypertension. One of the main characteristics of right ventricular energy metabolism in pulmonary hypertension is reduced utilization of fatty acids. As a lipid factor, 12, 13-DIHOME has been confirmed to increase fatty acid uptake and oxidation in skeletal muscle of mice, but whether it can improve right heart function impairment caused by long-term hypoxia at high altitude remains to be explored.
METHODS C57BL/6J mice were divided into 4 groups: plateau group, plateau+ administration group, plain group and plain+ administration group. The plateau group was fed in a low-pressure hypoxic simulated chamber (10% O2 concentration) at a simulated altitude of 5800 meters, and the plain group was fed in an atmospheric normoxic SPF animal house (21% O2 concentration). The administration group was intraperitoneally injected 12, 13-Dihome 10 μg/kg daily, and the control group was injected with PBS. After 4 weeks of feeding, the relevant indexes were detected by ultrasound.
RESULTS Compared with the plain group, after 4 weeks of chronic hypoxia, the pulmonary artery pressure in the plateau group was significantly increased (0.31 ± 0.007 vs. 0.40 ± 0.016, P = 0.002), and the inner diameter of the pulmonary artery was significantly widened (1.10 ± 0.011 mm vs. 1.0 ± 0.017 mm, P = 0.003). Right heart function was significantly decreased (1.31 ± 0.051 mm vs. 1.57 ± 0.040 mm). After treatment with 12, 13-DIHOME, pulmonary artery pressure (0.35 ± 0.017 vs. 0.31 ± 0.007, P = 0.04), pulmonary artery diameter (1.04 ± 0.033 mm vs. 1.10 ± 0.011 mm), right heart function (1.44 ± 0.072 mm, n = 6 vs. 1.31 ± 0.051 mm) were significantly improved compared with the plateau group.
CONCLUSIONS Long-term hypoxia at high altitude often causes pulmonary vasoconstriction, resulting in the increase of pulmonary artery blood pressure and the increase of the right heart load, which ultimately leads to the decline of right heart function. 12, 13-DIHOME, as a lipid factor, significantly improves the increase of pulmonary artery pressure, the widening of pulmonary artery inner diameter and the decline of right heart function caused by hypoxia. In the future, it is planned to further analyze whether 12, 13-DIHOME can improve the right heart function impairment caused by chronic hypoxia by enhancing the molecular pathway of right heart fatty acid uptake and oxidation.
GW35-e0752
Ziyang Wang1,2, Chun Liu1,2, Wei Zhang1,2, Zhihui Zhang1,2
1Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Army Medical University
2Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Diseases (Army Medical University), Ministry of Education
OBJECTIVES Diabetic patients frequently experience microvascular complications. Ginkgo Leaf Tablets, a traditional Chinese medicine, have been shown to promote vasodilation, angiogenesis, and overall microvascular function. This study aims to investigate the efficacy of Ginkgo Leaf Tablets in the treatment of coronary microvascular disease (CMD) and to elucidate its specific mechanisms of action.
METHODS We utilized 8-week-old ob/ob−/− mice as a model for CMD and intervened with Ginkgo Leaf Tablets for 12 weeks. Coronary flow reserve (CFR) was assessed using echocardiography, while myocardial blood flow (MBF) was measured via laser speckle imaging. Immunohistochemistry analysis was conducted to examine microvascular density, inflammation, and fibrosis in cardiac tissues, evaluating the therapeutic effects of Ginkgo Leaf Tablets on CMD. Additionally, we analyzed the differential expression of Wnt, β-catenin, and activated β-catenin in heart tissues using qPCR. A CMD cell model was established by treating coronary microvascular endothelial cells with high glucose concentrations. In vitro verification of gene expression differences was performed using Western blot. The proliferation, migration, and invasion of HCMECs were evaluated by CCK8, transwell and tube formation assays.
RESULTS After 12 weeks of treatment with Ginkgo Leaf Tablets, CFR and MBF in ob/ob−/− mice showed significant improvement. Additionally, there was a notable amelioration in coronary microvascular density, as well as in inflammation and fibrosis indicators in cardiac tissues. However, in HCMECs with overexpressed β-catenin, the beneficial effects of Ginkgo Leaf Tablets on cell proliferation, migration, and tube formation were diminished.
CONCLUSIONS Ginkgo Leaf Tablets can ameliorate diabetes-induced CMD by inhibiting the activation of the Wnt/β-catenin signaling pathway. This pathway may potentially serve as a therapeutic target for CMD in the future.
GW35-e0758
Shiliang Chen, Yong Sun, Jian Wu
Department of Cardiology, Second Affiliated Hospital of Harbin Medical University
OBJECTIVES Heart failure with preserved ejection fraction (HFpEF) is a devastating health issue associated with poor quality of life and premature mortality although limited knowledge is available for its pathogenesis and therapeutics. Given that monocyte/macrophage aggregation and inflammation are considered key factors in HFpEF, and that the long non-coding RNA (lncRNA) NEAT1 regulates macrophage polarization, the aim of this study was to investigate the role of lncRNA NEAT1-mediated macrophage polarization in HFpEF.
METHODS Adult wild type mice and NEAT1−/− knockout mice were fed a high-fat diet for 15 consecutive weeks and N[w]-nitro-l-arginine methyl ester hydrochloride (L-NAME) was added to the drinking water to construct a model of HFpEF. The above animal model was used to assess the role of NEAT1-regulated macrophage polarization on cardiac function.
RESULTS We found that macrophages, the main infiltrating immune cells of the heart in the HFpEF mouse model, highly expressed the lncRNA NEAT1. Lack of NEAT1 impeded macrophage infiltration and the inflammatory response in the hearts of HFpEF mice, which ameliorated pathological manifestations such as cardiac fibrosis and cardiac diastolic function. In addition, knockdown of NEAT1 inhibited M1 macrophage polarization and infiltration and reduced the expression of TNFα, IL-β, and other inflammatory cytokines.
CONCLUSIONS Collectively, these findings suggest that NEAT1 expression regulates macrophage infiltration and polarization in the heart and promotes disease progression in HFpEF.
GW35-e0761
Vasily Sukhorukov1,2, Victoria Khotina2, Vladislav Kalmykov2, Tatiana Kovyanova2, Alexander Orekhov1,2
1Institute for Atherosclerosis Research, Moscow, Russia
2Institute of General Pathology and Pathophysiology, Moscow, Russia
OBJECTIVES Mutant mitochondrial DNA (mtDNA) copies can accumulate in intima cells during atherogenesis, leading to mitochondrial dysfunctions. Mitochondrial dysfunction can be a mechanistic factor in various pathologies, including atherosclerosis. In our previous studies, we identified several mitochondrial mutations: m.15059G>A, m.13513G>A, and m.652delG, which correlate with cardiovascular diseases. We created cytoplasmic hybrids based on THP-1 cells bearing these mutations. Mitochondria are promising organelles for the search for molecular targets for gene therapy, and mitochondrial editing is a desirable approach for treating mitochondrial-related diseases. The aim of our study is to evaluate the role of mtDNA mutations in the inflammatory response in macrophages.
METHODS The human monocytic cell line THP-1 and the cybrid cell line TC-HSMAM1 were used. An original approach based on the CRISPR/Cas9 system was developed and utilized to eliminate mtDNA copies with m.15059G>A, m.13513G>A, and m.652delG mutations. The NLRP3 gene expression level was analyzed by qPCR. TNF secretion was evaluated using ELISA. A tolerant immune response was defined as a decrease in TNF secretion by the cells after secondary LPS stimulation compared to the secretion of this cytokine after the first LPS stimulation. A non-tolerant response was defined as no difference in cytokine secretion after the first and secondary LPS stimulation of the cells.
RESULTS We obtained Cas9-TC-HSMAM1 cells, where the levels of m.15059G>A, m.13513G>A, and m.652delG mutations were dramatically decreased: from 55.8% to 2.3% for m.13513G>A, from 43.3% to 4.9% for m.15059G>A, and from 27.4% to 9.5% for m.652delG. It was shown that THP-1 cells and Cas9-TC-HSMAM1 cells demonstrated a tolerant immune response, whereas TC-HSMAM1 cells demonstrated an intolerant immune response. Compared to Cas9-TC-HSMAM1 cybrids, TC-HSMAM1 cybrids exhibited increased basal expression of the NLRP3 gene. After LPS stimulation, NLRP3 gene expression increased in Cas9-TC-HSMAM1 cybrids, whereas it remained unchanged in TC-HSMAM1 cybrids.
CONCLUSIONS As a result, it was established that mitochondrial mutations (m.15059G>A, m.13513G>A, and m.652delG) can influence the pro-inflammatory status of macrophages and may potentially be a cause of chronic inflammation in diseases such as atherosclerosis. This work was supported by Russian Science Foundation Grant #22-15-00064.
GW35-e0772
Zhengfeng Wu1,2, Honghong Zhang1,2, Haijng Zhao1,2, Li Zheng2,3, Yue Zhu1,2, Yuhan Ma2,3, Yuqi Liu2
1PLA Medical College, Beijing 100853, China
2Department of Cardiology, the Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
3School of Medicine, Nankai University, Tianjin 300071, China
OBJECTIVES Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. Accumulating evidence highlights the pivotal roles of immune-related processes in the pathogenesis and progression of AMI. A comprehensive understanding of the molecular mechanisms governing immune regulation during AMI may provide valuable insights for developing innovative diagnostic and therapeutic strategies. In this study, we aimed to discover key immune-related regulatory genes in AMI by applying machine learning algorithms and in-depth bioinformatics analyses, laying a solid foundation for further exploration of molecular mechanisms and identification of potential therapeutic targets in AMI.
METHODS We retrieved AMI RNA sequencing dataset (GSE183272) and single-cell sequencing dataset (GSE163465) from the GEO database. Differential expression genes (DEGs) in the GSE183272 dataset were screened using R language’s “Limma” package, and further selected via machine learning approaches, such as support vector machines (SVM) and random forests (RF). Concurrently, weighted gene co-expression network analysis (WGCNA) was employed to identify gene modules significantly associated with AMI. Protein–protein interaction (PPI) networks were established for DEGs and module-enriching genes utilizing STRING, followed by enrichment analysis via the Metascape database. Key candidate genes for AMI were determined by integrating machine learning and WGCNA results. In the GSE163465 dataset, we validated the expression of key genes and analyzed their expression across different cell subpopulations and immune infiltration. Finally, we established 3-day, 7-day, and 21-day AMI mouse models and quantitatively assessed the differential expression of key genes at various time points using techniques such as RT-qPCR, IHC, and Western blot. The cellular localization of target genes in myocardial tissue was determined using immunofluorescence double staining.
RESULTS The differential analysis revealed 59 DEGs, which were primarily enriched in pathways connected to cell chemotaxis, leukocyte migration, and IL-17 signaling. Machine learning algorithms yielded 13 significantly differentially expressed genes. WGCNA analysis identified 39 gene modules, with the Lightcyan module demonstrating the highest correlation with AMI. Genes within this module were mainly enriched in leukocyte chemotaxis pathways. Comparatively, Chil3, Cxcr6, Ccl7, and Clec4d were ultimately chosen as key candidate genes. Single-cell dataset analysis showed significant differences in key gene expression among various cell subpopulations, closely correlated with immune cell infiltration. Experimental results demonstrated that the expression of the four key genes increased significantly in AMI models compared to the control group, with gene expression levels progressively rising with a prolonged duration of infarction. Immunofluorescence double staining results indicated that Clec4d is predominantly expressed in Vimentin-positive fibroblasts.
CONCLUSIONS This study identified and validated four immune-related key genes demonstrating significantly differential expression during AMI development. The discovery of these key genes offers novel potential biomarkers or molecular therapeutic targets for AMI treatment.
GW35-e0791
Wenhua Jiang1, Zihui Zhang1, Heng Ma2
1Northwestern Polytechnical University
2Fourth Military Medical University
OBJECTIVES Doxorubicin (DOX), an anthracycline drug commonly used in the treatment of various solid and hematological malignancies, is known to cause cardiotoxicity, which limits its clinical utility. Ferroptosis plays a significant role in the development of DOX-induced cardiotoxicity (DIC). MG53 has been identified as a potential protective factor for myocardial cells, aiding in the repair of cell membranes and showing promise in mitigating myocardial ischemic injury. However, the potential of MG53 to inhibit ferroptosis induced by DOX remains largely unexplored. This study aims to investigate the pathophysiological role of MG53 in DOX-induced ferroptosis.
METHODS DIC models were established both in vivo and in vitro to investigate cardiac injury in mice. Echocardiography and histological analysis were utilized to assess the extent of cardiac damage. The expression of MG53 in the DIC model was analyzed through western blot and immunohistochemistry. Ferroptosis was evaluated by measuring various indicators including cell viability, ROS levels, Fe2+ levels, malondialdehyde, 4-hydroxynonenal and glutathione peroxidase 4 (GPX4) levels. Mice with myocardium-specific overexpression of MG53 protein were generated through intracardiac injection of MG53 carried by adeno-associated virus serotype 9 containing the promoter of cardiac troponin T. These mice were then used to investigate the impact of MG53 overexpression on cardiac function in mice with DIC.
RESULTS The study revealed that MG53 expression was reduced in mouse hearts and cardiomyocytes treated with DOX, while overexpression of MG53 improved cardiac function in a model of DIC. In vitro experiments demonstrated that MG53 overexpression effectively reduced ferroptosis by increasing SLC7A11 and GPX4 levels that were decreased by DOX. Mechanistically, it was found that MG53 binds to P53 to regulate its ubiquitination and degradation. Additionally, either MG53 overexpression or p53 knockdown in cardiomyocytes could prevent DIC-induced ferroptosis. Overall, the study presents direct evidence that MG53 overexpression can alleviate DOX-induced ferroptosis through the p53/SLC7A11/GPX4 pathway. These results highlight the significance of MG53 in inhibiting ferroptosis to prevent DIC-induced ferroptosis.
CONCLUSIONS Our study indicates that overexpression of MG53 protects against DOX-induced cardiotoxicity by decreasing p53 ubiquitination. These results highlight a previously unidentified role of MG53 in ferroptosis and suggest that targeting MG53 could be a potential therapeutic strategy to mitigate DIC, offering new perspectives on MG53 as a promising candidate for cardiac protection.
GW35-e0798
Yuto Suzuki1, Yoichi Sunagawa1,2,3, Ayaka Ishima1, Ryuji Minegishi1, Yuto Kawase1, Ryuya Naruta1, Toshihide Hamabehoriike1,2,3, Yasuhumi Katanasaka1,2,3, Koji Hasegawa1,2, Morimoto Tatsuya1,2,3
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
2Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan
3Shizuoka General Hospital, Shizuoka, Japan
OBJECTIVES Cardiac hypertrophy is involved in the development of heart failure. Nuclear acetylation is one of critical events that activate this response genes expression, and mediated, in part, by an intrinsic histone acetyltransferase (HAT), p300. To determine the mechanism of p300-HAT activation during the development of heart failure, we identified 193 p300 binding proteins from mouse hearts by a proteomic approach. In this study, we investigated the role of p300 binding protein 1 (p300BP1) which belongs to a lysine methyltransferase, on hypertrophic responses in vitro and in vivo.
METHODS To confirm the binding between p300BP1 and p300, we used the recombinant proteins. In vitro p300-mediated histone acetylation assay was investigated. Primary cultured cardiomyocytes prepared from neonatal rat hears were knock down with si-p300BP1 or si-control and then stimulated with phenylephrine (PE) or infected with lentivirus encoding p300BP1 or LacZ. These cells were subjected to the fluorescent immunostaining and cell surface area is measured. Real-time PCR and western blotting were performed. Finally, cardiac-specific p300BP1 knockout (p300BP1-KO) mice and control mice were subjected to TAC or sham surgery. At 6 weeks after surgery, echocardiographic, histological, and real-time PCR analyses were performed.
RESULTS p300BP1 physically interacted with p300 and enhanced p300-mediated histone acetylation in vitro. In cultured cardiomyocytes, the knockdown of p300BP1 prevented phenylephrine-induced increases in cell size, mRNA levels of ANF and BNP, and histone H3K9 acetylation. Conversely, overexpression of p300BP1 induced hypertrophic responses in cardiomyocytes. At 6 weeks after surgery, p300BP1-KO significantly suppressed TAC-induced cardiac hypertrophy and cardiac dysfunction in mice. Histological analysis showed that p300BP1-KO significantly prevented TAC-induced myocardial cell hypertrophy, perivascular fibrosis, and interstitial fibrosis. TAC-induced increases in mRNA levels of ANF, BNP, β-MHC, Col1a1, Col3a1, and CTGF were significantly attenuated in p300BP1-KO mice compared to control mice.
CONCLUSIONS These results found that p300BP1, which we identified as a novel p300 binding protein, was required for cardiac hypertrophy and the development of heart failure in vivo. Further examinations are needed to establish the noble heart failure therapy targeting p300BP1.
GW35-e0806
Jingjin Hou, Chenghui Yan
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES The aim of this study is to evaluate the relationship between [18]F-FDG tracers and plaque properties using positron emission tomography with computed tomography (PET/CT) imaging.
METHODS A PET/CT scan was performed 30 min after tail vein injection of 0.2 MCI/25G [18]F-FDG tracers for Male ApoE knockout (ApoE−/−) mice fed on a Western diet at 0 week, 8 weeks, and 20 weeks (n = 40). Changes in atherosclerotic formation were assessed at four aortic segments (abdominal aorta, aortic arch, ascending aorta, and thoracic aorta) by calculation of the standardized uptake value (SUV) of [18]F-FDG. The properties of arteries were identified in vitro by the detection oil-red O, CD68, MMP13, CD163, SSTR2 and GLP1R in the blood wall. Mice was fed with different doses of metformin to evaluate the preventive or therapeutic effects of metformin on atherosclerosis by PET/CT imaging.
RESULTS The degree of plaque was determined according to the oil-red O staining of the isolated blood vessel divided into mild, moderate and severe plaques. The mean uptake of [18]F-FDG in SUV (SUVmean) (1.65 ± 0.36 vs. 0.66 ± 0.18, P < 0.05) and the maximum value of SUV (3.52 ± 0.65 vs. 1.75 ± 0.68) in the severe plaque group were significantly higher than those in the mild plaque group, which positively correlated with the area and size of the plaque (P < 0.05). Compared with the baseline value of the abdominal aorta, the [18]F-FDG (SUV: 2.01 ± 0.32 vs. 0.99 ± 0.21, P < 0.05) uptake in the abdominal aorta of ApoE−/− mice at week 20 was significantly increased. Similarly, [18]F-FDG uptake in other aorta tissues also exhibited a gradual increase trend consistent with the disease progressed. The thickness of the fibrous cap was negatively correlated with the SUVmean (r = −0.6, P < 0.05). Spearman correlation analysis showed that there was a significant positive correlation between SUVmean and the expression of MMP13, CD163, SSTR2, GLP1R and CD68 (P < 0.05). The correlation between MMP13 and CD68 and SUVmean was the most significant (r = 0.79, P < 0.05). Finally, PET/CT living image shown that metformin (250 mg/kg/day) pretreatment remarkedly reduced the uptake of SUV value (1.56 ± 0.22 vs. 1.18 ± 0.26, P < 0.05; 1.81 ± 0.24 vs. 1.54 ± 0.35, P < 0.05) in the aortic arch and ascending aorta but not in thoracic aorta and abdominal aorta in western diet-ApoE−/− mice. However, continuous metformin treatment for 20 weeks did not reduce the uptake of [18]F-FDG in formed severe atherosclerotic plaque and calcified plaque in ApoE−/− mice.
CONCLUSIONS The study identified that [18]F-FDG uptake in arteriosclerosis plaques correlates with severity of atherosclerotic plaque with macrophage activity and inflammatory changes, which is a useful live imaging tool in mice atherosclerosis model.
GW35-e0812
Tomohiro Manae1, Sho Uehara1, Masafumi Funamoto1,2,4, Mizuho Yamamoto1,4, Yoichi Sunagawa1,2,3, Yasufumi Katanasaka1,2,3, Toshihede Hamabe1,2,3, Yuto Kawase1, Ryuya Naruta1, Yasumasa Ikeda4, Koji Hasegawa1,2, Tatsuya Morimoto1,2,3
1Department of Molecular Pathophysiology, Faculty of Pharmaceutical Sciences, University of Shizuoka
2Department of Deployment Medicine and Research, National Hospital Organization Kyoto Medical Center
3Shizuoka General Hospital
4Department of Physiological Pharmacology, Division of Medical Sciences, Graduate School of Biomedical Sciences, The University of Tokushima
OBJECTIVES Heart failure is a disease with a poor prognosis, and no effective treatment strategy has not been established. Therefore, the development of noble therapeutic drugs is awaited. During the development of heart failure, the interaction between BRG1, a major component of the SWI/SNF complex, and p300, a histone acetylase, was enhanced, and the acetylation of H3K122 in the globular domain of histones was increased. However, the precise mechanisms of how BRG1 regulated the development of heart failure and histone acetylation are unclear. This study investigated the effects of PFI-3, a BRG1 inhibitor, on cardiomyocyte hypertrophy and pressure-overload heart failure model.
METHODS Primary cultured cardiomyocytes prepared from rat neonatal hearts were treated with 1, 3, or 10 μM of PFI-3 and then stimulated with phenylephrine (PE) for 48 hrs. These cells were subjected to fluorescent immunostaining with an anti-α-actinin antibody, and cardiomyocyte surface area was measured. To investigate the expression levels of cardiac hypertrophy response genes, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), we performed the real-time PCR. We investigated H3K9 acetylation using Western Blotting (WB). Next, to examine the effect of PFI-3 on a heart failure mouse model, eight-week-old male C57BL/6J mice underwent transverse aortic constriction (TAC) surgery were randomly divided into three groups: PFI-3 groups (3 mg/kg or 10 mg/kg) or a solvent group (2% DMSO, 30% PEG300, 2% Tween80). Echocardiography, real-time PCR, immunohistochemistry, and western blotting were performed eight weeks after the surgery.
RESULTS PFI-3 treatment significantly inhibited PE-induced cardiomyocyte hypertrophy. Real-time-qPCR analysis showed that PFI-3 suppressed the expression of ANF and BNP, which increased with PE stimulation. Furthermore, PE-induced acetylation of H3K122 was inhibited by PFI-3. An echocardiographic study revealed that PFI-3 significantly improved the TAC-induced increase in the left ventricular posterior wall thickness and decrease in systolic function. PFI-3 also significantly suppressed the increase in heart weight ratio induced by TAC. Hematoxylin and eosin staining showed that PFI-3 significantly suppressed TAC-induced cardiomyocyte hypertrophy. TAC-induced mRNA levels of ANF and BNP were inhibited by PFI-3. Finally, WB results showed that TAC-induced increase in histone acetylation was significantly inhibited by PFI-3.
CONCLUSIONS These results suggest that BRG1 inhibitors ameliorated the onset and progression of heart failure by inhibiting the histone acetylation. These findings indicate that PFI-3 may be used for heart failure therapy in humans.
GW35-e0813
Natsumi Hagawa1, Yasuhumi Katanasaka1,2,3, Hyuma Mogi1, Ryuya Naruta1, Yoichi Sunagawa1,2,3, Toshihide Hamabe1,2,3, Yuto Kawase1, Koji Hasegawa1,2, Tatsuya Morimoto1,2,3
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
2Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto 612-8555, Japan
3Shizuoka General Hospital, Shizuoka 420-8527, Japan
OBJECTIVES The estimated prevalence of chronic kidney disease (CKD) worldwide is 9.1%, and managing this disease is a major clinical challenge, as it leads to end-stage renal disease (ESRD) and dialysis therapy. Kidney fibrosis is caused by ESRD, and there is still no effective treatment. Our previous studies have shown that protein arginine methyltransferase 5 (PRMT5) is important for transforming growth factor-β (TGF-β)-activated transcription of fibrosis-related genes in primary cultured cardiac fibroblasts and for the myofibroblast differentiation in vivo. TGF-β signaling is important in many tissue fibrosis processes. In this study, we aimed to investigate the function of PRMT5 in renal fibrosis and the effects of PRMT5 inhibitors on renal fibrosis.
METHODS The renal fibroblast cell line NRK-49f was cultured and stimulated with TGF-β, and changes in PRMT5 expression were examined by qPCR and Western blotting (WB). The expression levels of myofibroblast marker α-smooth muscle actin (α-SMA) and fibrosis-related genes after TGF-β stimulation by PRMT5 knockdown were examined. Similarly, the expression of α-SMA was examined using the WB method. Finally, to examine the effect of EPZ015666, a selective inhibitor of PRMT5, on the renal fibrotic response, NRK-49f cells were pretreated with EPZ015666 (30, 100, and 300 μM), and the expression levels of α-SMA were examined by qPCR and WB.
RESULTS The expression of PRMT5 was increased by TGF-β stimulation. TGF-β stimulation significantly upregulated the expression of α-SMA and fibrosis-related genes, but PRMT5 knockdown suppressed the upregulation of these genes. Moreover, PRMT5 knockdown suppressed the increase in α-SMA protein expression upon TGF-β stimulation. EPZ015666 treatment significantly suppressed the TGF-β-induced increase in gene and protein expression of α-SMA.
CONCLUSIONS These results suggest that PRMT5 inhibitors are effective against renal fibrosis. Further studies on the role of PRMT5 in animal models may lead to the development of PRMT5-targeted drugs for treating CKD.
GW35-e0824
Daria Borodko1, Kharis Mustafin2, Tatiana Kovyanova1, Orekhov Alexander1, Omelchenko Andrey1
1Institute of General Pathology and Pathophysiology
2Moscow Institute of Physics and Technology
OBJECTIVES Recent studies have revealed numerous genomic and epigenomic evolutionary changes potentially associated with inflammatory diseases such as atherosclerosis, obesity and type 2 diabetes. This study focuses on identifying variants in ancient nuclear DNA that may be linked to atherosclerosis. By analyzing genetic material from ancient human remains, we aim to determine if genetic markers associated with atherosclerosis were present during the lifetimes of these individuals. Our goal is to provide insights into the evolutionary background of atherosclerosis and to lay the foundation for developing an accurate prognostic model using a set of SNPs, which could facilitate early diagnosis of this complex disease.
METHODS The synthesis of genomic libraries was carried out using the KAPA HyperPrep kit (Roche, Switzerland). Using a specially designed probe panel, target regions of the genome were enriched. This custom marker panel includes target regions such as SNPs of the non-recombining region of the Y chromosome (NRY), complete mitochondrial DNA, and SNPs associated with the prediction of phenotypic traits. The quality control of the obtained libraries was performed on an Agilent Bioanalyzer 2100 using the High Sensitivity Kit (Agilent Technologies, USA) according to the manufacturer’s protocol. NGS was conducted on the MiSeq sequencing platform (Illumina, USA). Resulting data was analysed with nf-core/eager pipeline (v2.5.1). Mapping step was performed with bwa aln (v0.7.17-r1188) and variant caller was Freebayes (v1.3.5).
RESULTS We sequenced 38 genomes of ancient Russians of the East European Plain and 15 genomes of ancient scythians. The data quality assessed with fastQC and DamageProfiler was sufficient for the following analysis. As a result, we obtained a set of 15 most probable variants that were consistent among the samples and were similar to those discovered in genomes of atherosclerotic patients. These variants are mostly located in mitochondrial DNA and chromosomes 2, 4, and 7.
CONCLUSIONS In this study, we sequenced 53 ancient genome panels, evaluated their quality, and identified a set of 15 variants likely to serve as strong predictors for the atherosclerosis prognostic model. However, to achieve more robust results, higher coverage samples are necessary. This will improve the accuracy and reliability of our findings, ultimately enhancing the precision of the model, which holds significant potential for providing early diagnosis and personalized therapeutic approaches. This study was supported by Russian Science Foundation, Grant # 24-15-00217.
GW35-e0835
Andrey Omelchenko1, Daria Borodko1, Elizaveta Pleshko1,2, Evgeny Borisov3, Tatiana Kovyanova1, Alexander Orekhov1
1Institute of General Pathology and Pathophysiology
2Lomonosov Moscow State University
3Petrovsky National Research Centre of Surgery
OBJECTIVES The basis of atherosclerotic diseases is the process of chronic inflammation. One of the reasons for chronic inflammation is defective mitophagy. Defective mitophagy leads to the accumulation of damaged mitochondria, increasing reactive oxygen species (ROS) production and triggering inflammation. This inflammation and oxidative stress cause endothelial dysfunction, reducing nitric oxide availability and promoting monocyte recruitment. Monocytes transform into macrophages and foam cells, contributing to atherosclerotic plaque formation. Chronic inflammation weakens the fibrous cap of plaques, increasing the risk of rupture and thrombus formation, which can cause acute cardiovascular events. Enhancing mitophagy, targeting inflammatory pathways, using antioxidants, and improving endothelial function are potential therapeutic strategies to combat atherosclerosis. Understanding the molecular mechanisms by which mitochondrial mutations influence atherosclerosis is crucial for developing targeted therapies, early detection methods, and personalized treatments. It enhances pathophysiological insights, predicts disease progression, and identifies new biomarkers. This knowledge leads to better management, prevention strategies, and comprehensive disease management, ultimately improving patient outcomes and advancing cardiovascular research.
METHODS Previously, we created a collection of cytoplasmic hybrids, i.e. cells having the same nuclear DNA, but differing in the mitochondrial genome due to atherosclerosis-associated mutations. Data on heteroplasmy and mitophagy were obtained using qPCR and confocal microscopy. Modeling and data analysis were carried out using original software written in the Python programming language. The development of artificial neural networks was carried out using the “pybrain”, “scikit-learn” and “TensorFlow” modules; reading, saving and preprocessing of data sets was carried out using the “pandas” module, mathematical analysis was carried out using the “numpy” and “math” modules, and data visualization using the “matplotlib” module.
RESULTS The developed models make it possible to predict an increase in the level of mitophagy in a cell above the baseline level with the accumulation of these mutations and, more importantly, to associate an increase or decrease in mitophagy with the presence of mutations in the mitochondrial genome. It is worth noting that in many cases the effect sharply manifests itself upon reaching a certain heteroplasmy threshold, specific for each mutation (m.652delG, m.3336T>C, m.3256C>T, m.15059G>A, m.1555A->G, m.13513G>A, m.14459G>A, m.14846G>A), which is consistent with observations about the nature of the manifestation of symptoms of mitochondrial diseases. For two mutations (m.5178C>A, m.12315G>A), on the contrary, the absence of a significant effect on mitophagy was shown.
CONCLUSIONS The results obtained during the modeling process suggest that heteroplasmy of mitochondrial atherosclerosis-associated mutations significantly affects the level of mitophagy, and the effect often manifests itself when the heteroplasmy level of mutation content exceeds a certain threshold, and predicts it using the proposed methods of statistical and neural network modeling. Such models make it possible to assess the level of mitophagy, to show whether it is defective or normal, even with a lack of empirical data on the heteroplasmy of a particular mutation, which is important when studying chronic inflammation, atherogenesis and the resulting atherosclerotic diseases. This study was supported by Russian Science Foundation, Grant # 24-65-00027.
GW35-e0837
Long Chen, Zhaohua Cai, Yiping Shi, Qin Shao, Ben He
Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES Vascular calcification (VC) is highly prevalent in chronic kidney disease (CKD) and is associated with further cardiovascular morbidity and mortality. NR4A1 is an orphan nuclear receptor that participates in the pathology progression of a variety of cardiovascular diseases. However, the effect of NR4A1 on VC and its underlying mechanisms are still unclear.
METHODS To gain insight of the role of NR4A1 in VC, we induced VC through 2 CKD models (adenine and phosphorus diet– induced [AP-induced] mode and 5/6 nephrectomy mode) in mice. Whole transcriptome RNA sequencing was utilized to recapitulate possible changes in the transcriptome profile and verify the downstream pathway. ChIP-seq was employed to further elucidate the substrates in vascular smooth muscle cells (VSMCs) that may be subject to regulation by NR4A1.
RESULTS We demonstrated that NR4A1 was markedly downregulated in the radial artery tissue of patients with CKD with VC or in the mouse models of VC. NR4A1 knockout (NR4A1−/−) accelerated the development of VC in mice, as evidenced by the changes in calcium deposition and osteogenic markers. Consistent with this, deletion of NR4A1 accelerated VSMCs osteogenic transdifferentiation. Mechanistically, transcriptome analysis and ChIP-seq identified CDC42, a small GTPase of the Rho-subfamily that contributes to VC, as a target protein of NR4A1 that mediated the regulatory effects of NR4A1 on osteogenic reprogramming in VSMCs. Additionally, supplementation with celastrol, a natural friedelane pentacyclic triterpenoid isolated from the root extracts of Tripterygium wilfordii, was beneficial in preventing and treating VC in mice.
CONCLUSIONS Our studies identified a previously unrecognized role of NR4A1 in VC pathogenesis and an undescribed NR4A1-CDC42-PI3K axis involved in regulating osteogenic reprogramming in VSMCs. Importantly, we found that celastrol supplementation may represent a potential treatment against VC.
GW35-e0840
Shuai Yuan
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
OBJECTIVES ltered glycolytic activity is an important aspect of metabolic remodelling in heart failure. Glycolytic metabolic enzymes were reported to locate in cytosol and nuclear fractions and participate in multifarious biological processes through classical or moonlighting functions. However, the role and underlying mechanism of glycolytic metabolic enzymes in heart failure are unclear. We aimed to elucidate the function and mechanism of dysregulated glycolytic enzymes identified from pressure-overload induced heart failure, which might provide novel therapeutic targets for clinical practice.
METHODS Cell fraction separation followed by western blotting was used to detect the expression level of glycolytic enzymes. The enzyme activity detection kit was used to detect the enzyme activity of ENO1. The nuclear localization sequence (NLS) and nuclear export sequence (NES) were used to achieve over-expression of ENO1 in the nucleus or cytoplasm specifically in vivo or in vitro.
RESULTS Cell fraction separation followed by western blotting revealed that nuclear ENO1 was robustly increased among glycolysis metabolic enzymes in transverse aortic constriction (TAC)-induced mouse failing heart. Meanwhile, the enzymatic activity of ENO1 was significantly decreased during heart failure. Cytoplasmic or nuclear specific overexpression of ENO1 uncovered that nuclear ENO1 exacerbated heart failure while cytoplasmic ENO1 exerted the opposite effect. Mechanistically, cytoplasmic ENO1 enhanced the contractility of cardiomyocytes by promoted the phosphorylation of AKT in dependent of improved enzyme activity. Furthermore, immunoprecipitation coupled with mass-spectrometry detection and cut-tag sequencing indicated that nuclear ENO1 bound to NOC2L to up-regulate the transcription of GPNMB through altering H3K27Ac modification level on GPNMB promoter. Furthermore, co-culture assays showed that GPNMB secreted by cardiomyocytes activated the differentiation of cardiac fibroblasts in a paracrine model, augmenting pathological cardiac remodeling.
CONCLUSIONS These findings uncovered the classic enzyme role of cytoplasmic ENO1 in alleviating heart failure and the moonlighting function of nuclear ENO1 in exacerbating heart failure. Targeting the nuclear ENO1-GPNMB pathway by siRNA based GPNMB knockdown or GPNMB antibody provide new strategies for treating heart failure.
GW35-e0841
Jingci Xing1, Zhiyong Du1, Fan Li1,2, Huahui Yu1, Yanwen Qin1
1Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease
2School of Basic Medical Sciences, Binzhou Medical University
OBJECTIVES Atherosclerosis is the leading cause of death worldwide, caused by the rupture and erosion of advanced atherosclerotic lesions combined with myocardial infarctions or strokes. Hypercholesterolemia accelerates the development of atherosclerosis as an independent modifiable risk factor. Reduction of cholesterol levels has been shown to be advantageous in the prevention of atherosclerotic cardiovascular disease. Acetyl-l-carnitine (ALC) is an endogenous molecule that plays a primary role in energy metabolism. However, its effects on cholesterol metabolism remain unclear.
METHODS We collected plasma and clinical characteristics from 868 individuals with hyperlipidemia, conducted high-throughput metabolomics to permit accurate qualitative and quantitative assessment of a variety of metabolites, and examined the correlation between multiple metabolites and routinely measured lipid parameters based on regression analyses. To investigate the effect of ALC on cholesterol levels, mice were provided with a high-cholesterol diet enriched with ALC, and the total cholesterol levels in both liver tissue and plasma were assessed. Additionally, the hepatic gene expression related to cholesterol metabolism was evaluated. Furthermore, Ldlr −/− mice were established to induce a hypercholesterolemic atherosclerosis model, with ALC supplementation aimed at investigating its potential involvement in atherosclerosis development.
RESULTS Analysis of the serum metabolic and lipid panel datasets identified a substantial negative correlation between plasma ALC concentrations and plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels (R = −0.55, P value <2.2e−16). Dietary incorporation of ALC resulted in a significant reduction in plasma TC and LDL-C, accompanied by the downregulation of genes associated with cholesterol synthesis, including SREBP2 and HMGCR, and the upregulation of LDLR expression. ALC supplementation notably decreased plasma TC levels and demonstrated beneficial effects on atherosclerosis in Ldlr −/− mice.
CONCLUSIONS ALC exerts a preventive effect on the formation of atherosclerotic plaques by reducing plasma cholesterol levels via the downregulation of SREBP2-mediated cholesterol synthesis. These findings highlight the potential of ALC as a promising therapeutic target for atherosclerotic cardiovascular disease (ASCVD).
GW35-e0853
Zehao Yao1, Lina Bai1, Houzao Chen2, Chengran Xu3,4,5, Yu Nie1
1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
3Department of Human Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Peking University, Beijing, China
4Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
5State Key Laboratory of Female Fertility Promotion, Peking University, Beijing, China
OBJECTIVES The heart is one of the earliest developing organs in the embryo. Investigating the spatiotemporal dynamics of heart development is crucial for understanding the maturation of the heart and the pathogenesis of heart diseases. However, current research lacks an exploration of the maturation characteristics of heart development at the microenvironment level. We performed 10× Visium spatial transcriptomics sequencing on multiple layers of embryonic hearts at various time points (8, 9, 10, and 15 weeks) to investigate the spatial characteristics of the heart niche at different developmental stages and their changes over time.
METHODS We consider a sequencing spot as a niche, where multiple cells within the niche collectively perform biological functions. In this study, we integrated multi-timepoint and multi-plane data for analysis. Initially, we did quality control and data cleaning, followed by dimensionality reduction and clustering after removing batch effects. We identified markers and spatial location for each niche population. We then extracted and re-clustered cardiac subpopulations and performed trajectory inference on these subpopulations to analyze the key regulatory networks influencing heart development.
RESULTS We identified a total of 21 subclusters, which can be consolidated into 7 major categories. We discovered a TBX3+/BMP2+ endocardial cushion region with atrial characteristics. Additionally, we identified a previously unreported cardiac subpopulation with high ACTA1 expression, predominantly located in the left ventricular outflow tract and adjacent to the valves. Data from different developmental stages exhibited significant trends in PCA, and trajectory inference indicated that the trajectory differences stem from two sources: changes from the endocardium to the compact layer and variations in developmental timing. Functional annotation of cardiac lineage revealed that early stages are characterized by extracellular matrix organization and conduction system development, mid-stages by the activation of energy metabolism, and late stages by the maturation of cardiac contractile function.
CONCLUSIONS Our data comprehensively depict the temporal and spatial characteristics of cardiac embryonic development and identify new spatial markers during the developmental process. These findings provide new insights into the occurrence of congenital heart disease and the spatial characteristics of structural heart disease.
GW35-e0854
Shiran Yu1,2, Junxian Song1, Ziqi Song1, Hong Chen1
1Peking University People’s Hospital
2Beijing Friendship Hospital, Capital Medical University
OBJECTIVES Atherosclerosis (AS) is generally considered to be a chronic vasculitis disease. Lymphatic system is an important regulatory system for inflammation. On the one hand, its particularly unidirectional transportation could promote inflammatory factors remove from tissue. On the other hand specific receptor D6 in the lymphatic system is involved in inflammation resolution. Our previous research found that there were lymphatic system remodeling and dysfunction in atherosclerosis. However, how the lymphatic system regulates inflammatory response, and the mechanism are not clear.
METHODS In this article we respectively carry out animal and cell level research. Firstly, we use ApoE−/− mice to investigate whether the function of lymphatic system regulating inflammation resolution is changed. Secondly, we overexpress or knockdown D6 in ApoE−/− mice to vivificate whether improving the function of lymphatic system regulating inflammation resolution could inhibit the progression of AS. The mechanism research is finished on cell level.
RESULTS In the progression of AS, the ability of lymphatic system to clear inflammation was increased first (2 W) and then decreased (4 W, 8 W), including the drainage function of lymphatic vessels, the ability of lymphatic vessels to transport macromolecules and the ability of lymphatic vessels to clear inflammatory T cells (Th1 cell and Th17 cell). At the same time the expression of inflammation clearance related receptor D6 was first increased and then at 8 W decreased. To explore the effects of D6 receptor mediated the function of lymphatic system regulating inflammation resolution on AS, we found D6 overexpression could improve the function of lymphatic system regulating inflammation resolution, further downregulate the degree of general and arterial local inflammatory response. Finally, the degree of stenosis in the lumen is significantly decreased. However, knockdown the D6 receptor had opposite ends. In vitro experiment we find destroyed the lymphatic endothelial cell’s cytoskeleton, D6 receptors originally gathered on the cell membrane transfer to cytoplasm and then its function to clear CCL2 is limited. All of them is through Rac-1 protein.
CONCLUSIONS Upregulation of D6 receptor improves the function of lymphatic system regulating inflammation resolution, thus reducing the systemic and arterial local inflammatory reactions, and ultimately inhibiting the development of AS. This progression may rely on D6 receptor-Rac-1-lymphatic endothelial cytoskeletal homeostasis.
GW35-e0879
Ying Sun1,2, Jiabao Xu3, Jie Li1, Xiaochao Yang3, Fang Deng2, Zhihui Zhang1
1Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University
2Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University
3School of Biomedical Engineering and Medical Imaging, Army Medical University
OBJECTIVES Ischemic heart disease (IHD) is one of the biggest killers in the world. Early reperfusion therapy is now standard treatment for patients with acute myocardial infarction. However, myocardial ischemia-reperfusion injury (MIRI) frequently leads to the generation of excessive reactive oxygen species (ROS), causing prominent and irreversible damage to the cardiomyocytes. ROS are mainly produced in mitochondria and are by-products of ATP synthesis in mitochondria. Mitochondrial dysfunction is primarily regulated by molecules that modulate inter-mitochondrial fission and fusion events. The dynamic processes of mitochondrial fusion and division are known as mitochondrial dynamics. Both fission and fusion are regulated by a family of dynamin-related proteins (DRPs). One of the major mediators of fission is dynamin-related protein 1 (Drp1). Studies on cardiac tissues under hypoxic glucose deprivation (OGD) and ischemia-reperfusion have shown that calmodulin phosphatase-mediated phosphorylation of Ser616 and subsequent activation of Drp1, mitochondrial fragmentation, and apoptotic cell death. Therefore, how to target mitochondria from the perspective of mitochondrial dynamics to treat MIRI has become a hot issue.
METHODS Due to the lack of sufficient active agent protection on the surface of Ceria nanoparticles (CNPs), their stability, enzyme activity, and biocompatibility are affected to some extent. In our previous experiments, we synthesized small-sized (4 nm) spherical CNPs and modified them with ligands of Succinic acid (SA) and Polyethylene glycol (PEG 600/2000) to make them well dispersed and stable. The nanoparticle SOD activity test confirmed that all three CNPs could achieve more than 90% ROS inhibition at a concentration of 50 μg/mL. We established mature in vitro cardiomyocyte models (hypoxia-reperfusion (H/R)-induced H9c2 cardiomyocyte injury model) and in vivo rat models (MIRI-induced rat cardiac injury model), respectively, with the hope of probing deeper into the mitochondria. The rat MIRI model was established by ligating the left anterior descending coronary artery for 30 minutes, followed by unligation and blood reperfusion.
RESULTS Researchers explored CNPs in vitro and in vivo to protect mitochondrial dynamics and reduce apoptosis by inhibiting ROS and mitochondrial accumulation for the treatment of MIRI. Mechanically we also demonstrated that CNPs effectively prevented mitochondrial fission by decreasing Drp1 phosphorylation at Ser616 to maintain the integrity of mitochondrial structure and function. The in vitro results demonstrated that CNPs could protect the OGD-treated H9c2 from apoptosis. The short-term (24 h after CNPs treatment) in vivo results showed that CNPs could effectively reduce the myocardial infarction area, enhance the left ventricular pumping function and decrease the serum myocardial enzyme expression. The long-term (28 days after CNPs treatment) in vivo results revealed that CNPs could decrease the myocardial fibrosis level. Within the three CNPs, the PEG2000 demonstrated the best anti-MIRI performance in most of the tested parameters.
CONCLUSIONS In rat MIRI models, CNPs pretreatment results in effectively improved cardiac functionality, decreased cardiac infarct size and much-relieved apoptosis severity of the hearts. Our study demonstrates that the synthesized CNPs are efficient nanomedicines featuring effective cardiac antioxidation and protection with satisfactory biocompatibility, revealing promising clinical translation prospects shortly.
GW35-e0892
Panpan Yu1, Xue Jiang1, Wenyi Zhang1, Ziyu Wang1, Haosheng Wu1, Xiangjun Zeng2, Caixia Guo1
1Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University
2Department of Physiology and Pathophysiology, Capital Medical University
OBJECTIVES It has been proven that extracellular MG53 can attenuate myocardial ischemia-reperfusion (I/R) injury. This study aims to explore whether sRAGE affects the levels of MG53 during myocardial I/R and whether sRAGE reduces myocardial I/R injury through MG53.
METHODS The cardiac I/R model was constructed in cardiomyocyte-specific sRAGE knock-in mice and littermate control mice. Neonatal rat ventricular myocytes were used to construct the myocardial oxygen-glucose deprivation/reoxygenation (OGD/R) model. The echocardiographic was used to evaluated the cardiac function of mice. The levels of MG53 in cell culture medium was detected by western blot. An enzyme-linked immunosorbent assay was used to detect the serum MG53 levels of mice.
RESULTS The left ventricular ejection fraction (LVEF) and the left ventricular anterior wall motion amplitude decreased in the I/R group compared to the sham group; however, the LVEF increased and the left ventricular anterior wall motion amplitude improved in the I/R + sRAGE group compared to the I/R group. The MG53 levels in the cell medium was significantly higher in the OGD/R + sRGAE group than the OGD/R group. Compared with the sham group, the serum MG53 levels in the I/R group was decreased; the serum MG53 levels in the I/R + sRAGE group was higher than the I/R group.
CONCLUSIONS sRAGE increased MG53 levels during myocardial I/R both in vivo and vitho. sRAGE may alleviate myocardial I/R injury by promoting the secretion of MG53 in cardiomyocytes. The present study contributes to the understanding of myocardial I/R pathogenesis and provided a novel MG53-dependent therapy strategy for sRAGE ameliorating I/R injuries.
GW35-e0913
Liyan Niu1,2, Yangjuan Jiang2, Yuhui Yang1, Xiaoyang Lai2, Peng Yu2
1Nanchang University
2The Second Affiliated Hospital of Nanchang University
OBJECTIVES Diabetic cardiomyopathy (DCM) is the main cause of heart failure in diabetic patients, which is extremely dangerous. Due to the complexity of the pathogenesis of DCM, the current treatments for DCM mainly focus on controlling blood glucose level or improving cardiac functiond, failing to fundamentally block the development of DCM. Ferroptosis plays a key role in the development of DCM, which involved many genes, but its mechanism and its relationship with metabolism have not been clarified. Therefore, we aim to identify the key genes regulating ferroptosis in DCM and the mechanism affecting metabolism, so as to provide a theoretical basis for finding therapeutic targets, maintaining cardiomyocyte homeostasis and function, and delaying the progression of DCM.
METHODS In the type I DCM model of C57BL/6 mice induced by streptozotocin (STZ) combined with angiotensin II (ATII), and the type II DCM model of Db/db mice induced by ATII, we used transcriptomics and metabolomics to screen key genes and differential metabolites and to search for potential pathogenesis. Then the phenotype was verified by CCK-8, echocardiography and immunohistochemistry in vivo and in vitro. ELISA, immunofluorescence, RT-qPCR, Western Blot and other experiments were carried out to explore the mechanism.
RESULTS Transcriptomic correlation analysis and PPI interaction network showed the expression of arachidonate 5-lipoxygenase (Alox5), an important regulatory gene of ferroptosis, was significantly higher in the myocardia of DCM mice than in normal myocardia. Moreover, Alox5 is involved in fatty acid biosynthesis and metabolism of fatty acid derivatives, suggesting Alox5 is highly correlated with DCM. After knock-down of Alox5 gene in vitro, the viability of cardiomyocytes was decreased, and the degree of ferroptosis and myocardial injury was increased, which suggested that Alox5 directly promoted ferroptosis in cardiomyocytes. The results of PCA analysis and pathway enrichment showed the contents of differential metabolites, such as Lobelanine and Manzamine_A, were related to total cholesterol, mostly involving in the biosynthesis of branched-chain amino acids. The combined transcriptome-metabolome analysis showed the metabolism of branched-chain amino acids in the myocardial tissue of DCM mice was abnormal and regulated by Alox5, which was negatively correlated with Lobelanine and positively correlated with Manzamine_A. After the addition of BT2 in hyperglycemic primary cardiomyocytes promoted the break-down of branched-chain amino acids, the effect on the cells was similar to that of Alox5 knock-down However, when BAY-069 was used to inhibit the decomposition of branched-chain amino acids under the knock-down of Alox5, cardiomyocytes still showed decreased vitality and activation of ferroptosis, indicating the decomposition process of branched-chain amino acids was regulated by Alox5. This in turn affects ferroptosis and cardiomyocyte function. In DCM mice model, we confirmed the above mechanism and tested the therapeutic effect of Zileuton, an Alox5 inhibitor, suggesting the possibility of targeting Alox5 with Zileuton to treat DCM.
CONCLUSIONS Through regulating metabolism of branched-chain amino acids, Alox5 is involved in cardiac dysfunction caused by ferroptosis induced by DCM. Further animal validation showed that targeting intervention of Alox5 or branched-chain amino acid metabolism disorders has the prospect of improving the treatment of DCM.
GW35-e0924
Ziheng Jia, Daiqi Liu, Lu Zhou, Xinyi Gao, Bingxin Xie, Nan Zhang, Qiankun Bao, Tong Liu
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
OBJECTIVES Atrial fibrillation (AF) is the most common persistent arrhythmia in clinical practice, and advanced age is an important independent risk factor for it. However, the mechanism of age-related AF remains unclear. Inflammation is one of the common mechanisms of aging and AF, because it exists along with the aging process and also participates in the occurrence and progression of AF. But the specific role of inflammation in aging-related atrial fibrillation still needs further research. This study aims to explore the mechanisms of atrial REG3G (regenerating family member 3 gamma) promoting aging-related AF by regulating macrophages.
METHODS In animals, natural aging rat models (≥20 months) and d-galactose-induced aging mouse models were constructed (n = 6–8). Echocardiography, transjugular electrophysiological study, epicardial mapping electrograms, and Masson’s trichrome staining were performed to observe atrial remodeling. Western blotting (WB) and immunofluorescence (IF) were used to measure REG3G levels in atrial tissues, and immunohistochemistry (IHC) and flow cytometry were employed to assess macrophage distribution and polarization in the atria. Cardiac-specific Reg3g gene knockout mouse model was utilized to evaluate influence on the susceptibility of atrial fibrillation. In cell experiments, transwell assays were conducted to observe the chemotactic effect of recombinant REG3G protein on mouse bone marrow-derived macrophages. Then, we test the levels of inflammatory factors and activation of the JAK1-STAT3 signaling of macrophages culturing with REG3G protein. Further, we also evaluate the alternations of aforementioned indicators of macrophages after Stat3 or Gp130 knockdown by siRNA following culturing with REG3G protein. IF was employed to investigate the localization of REG3G and GP130.
RESULTS In both natural and induced aging animals, atrial remodeling was evident with increased left atrial diameter, atrial fibrosis, prolonged sinus node recovery time, disrupted atrial electrical conduction, and decreased conduction velocity, particularly increasing susceptibility to atrial fibrillation. Macrophage infiltration could be seen in in aging atria, predominantly of the pro-inflammatory type, and REG3G levels increased significantly in aging groups. Cardiac-specific knockout of Reg3g gene in mice resulted in significantly reduced susceptibility to atrial fibrillation compared to aging group, indicating REG3G has an important effect in regulating aging-related atrial fibrillation. Transwell assays demonstrated a significant chemotactic effect of human recombinant REG3G protein on mouse bone marrow-derived macrophages, suggesting the role of REG3G in macrophage recruitment. We found the activation of JAK1-STAT3 pathway and increased levels of inflammatory cytokines of macrophages culturing with REG3G protein, which were alleviated upon knockdown of Stat3 or Gp130 in macrophages. Importantly, we revealed co-localization of REG3G with GP130 using IF, suggesting that REG3G may exert its pro-inflammatory effects by activating the intracellular JAK1-STAT3 signaling pathway via the macrophage membrane receptor GP130.
CONCLUSIONS In the context of aging, atrial REG3G interacts with the macrophage membrane receptor GP130 to activate downstream JAK1-STAT3 signaling, thereby promoting inflammation and ultimately contributing to the development of atrial fibrillation.
GW35-e0938
Luyao Huang1, Bohan Xing1, Bingyu Wang2, Yuxi Xu2, Ziyang Xue2, Jinkun Xi1,2
1Basic School of Medicine, Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan, China
2School of Public Health, North China University of Science and Technology, Tangshan, China
OBJECTIVES By constructing a rat H9c2 myocardial ischemia/reperfusion injury (MI/RI) model, To investigate whether Astragaloside IV (AS-IV) regulates mitochondrial calcium uniporter (MCU) through Zn2+. Furthermore, inhibition of the opening of mitochondrial permeability transition pore (mPTP) protected cardiomyocytes, and the possible intracellular signal transduction mechanism were investigated.
METHODS Rat H9c2 cardiomyocytes were cultured conventionally, and I/R models were prepared using simulated blood deficiency and a complete medium. The experiment was divided into the control group, I/R group, I/R + AS-IV group, I/R + AS-IV + zinc ion chelating agent (TPEN) group, and AS-IV group. Cell activity was detected by CCK8 method; LDH kit was used to detect cytotoxicity; Western blot and immunofluorescence assay of inositol 1,4,5-triphosphate receptor 1 (IP3R1), glucose regulatory protein 75 (GRP75), voltage-dependent anion channel 1 (VDAC1), inositol 1,4,5-triphosphate receptor 2 (IP3R2), and FUN14 domain containing 1 (FUNDC1) and MCU protein expression; cell zinc probe newport green DCF, mitochondrial zinc probe Rhodzin-3 AM, cellular calcium probe Fluo-4 AM, mitochondrial calcium probe Rhod-2 AM, cellular ROS probe DCFH-DA, and mitochondrial ROS probe Mito SOX were prestained cells. The changes of Zn2+, Ca2+, and ROS in cells and mitochondria and the level of mitochondrial membrane potential (mPTP opening) were detected by laser scanning confocal microscopy or multifunctional enzyme marker.
RESULTS Compared with the control group, the cell viability and cytotoxicity of the I/R group were significantly decreased (55.70 ± 13.38) and significantly increased (225.65 ± 37.35). The protein expressions of IP3R1, GRP75, VDAC1, IP3R2, FUNDC1 and MCU were up-regulated (1.44 ± 0.23, 1.45 ± 0.93, 1.54 ± 0.13, 1.61 ± 0.09, 1.94 ± 0.47, 1.33 ± 0.13). The green fluorescence intensity of the cell zinc probe Newport green DCF decreased significantly, and the zinc content in the cell was reduced (42.25 ± 7.07) by the zinc ion detection kit. The green fluorescence intensity of cellular calcium probe Fluo-4 AM and cellular ROS probe DCFH-DA increased significantly, and the red fluorescence intensity of mitochondrial calcium probe Rhod-2 AM and mitochondrial ROS probe Mito SOX increased significantly. Mitochondrial membrane potential decreased. AS-IV significantly inhibited the above processes, and TPEN significantly reversed the effects of AS-IV. This process was further verified by siRNA silencing VDAC1/FUNDC1/MCU (P < 0.05).
CONCLUSIONS By increasing Zn2+, AS-IV regulates IP3R1/GRP75/VDAC1 and IP3R2/FUNDC1 signaling pathways to inhibit MCU, reduce calcium overload in cells and mitochondria and increase ROS, thereby preventing mPTP opening and alleviating I/R injury of H9c2 cardiomyocytes.
GW35-e0942
Dan Yang, ZhiYu Ling
the Second Affiliated Hospital of Chongqing Medical University
OBJECTIVES Doxorubicin (DOX), an effective and commonly used chemotherapeutic agent, often triggers dosage-dependent and potentially lethal cardiotoxicity, which heavily limits its clinical application in cancer survivors. However, no actual pharmacological therapeutics for this adverse effect are available. Tirzepatide (TZP), a novel GIP/GLP-1 receptor agonist, exhibits efficacy in controlling glycemia and very recently has been approved for the treatment of type 2 diabetes. Several clinical trials provided evidence that TZP treatment contributed to a substantial reduction in HbA1c levels, body weight, and cardiovascular risk factors through the involvement of biochemical and molecular mechanisms that needed to be deeply explored. Here, we aimed to investigate the role of TZP in DOX-induced cardiotoxicity and to clarify the underlying mechanisms.
METHODS Male C57BL/6 mice were exposed to subcutaneous injections of TZP or an equal volume of vehicle once a day for 14 consecutive days. To generate DOX-induced cardiotoxicity, the mice received a single intraperitoneal injection of DOX (15 mg/kg). In vitro studies were performed on the H9c2 cell line in exposure to DOX alone or combined with TZP incubation. Echocardiographic measurement, histological assessment, and molecular analysis were obtained to determine the impact of TZP treatment on cardiotoxicity induced by DOX insult. To explore the underlying mechanisms, we performed RNA-sequencing of murine heart tissue to screen for the potential targets.
RESULTS Mice with TZP administration were protected from myocardial injury, cardiac dysfunction, and fatality in response to DOX. A significant reduction in both oxidative stress and cardiomyocyte apoptosis induced by DOX injection was also observed in the presence of TZP. Consistently, results obtained from in vitro studies revealed that DOX challenge impaired cell viability and led to elevated oxidative damage and cellular apoptosis, which were significantly alleviated in TZP-treated H9c2 cells. Mechanistically, we provided direct evidence that the cardioprotective effect of TZP was mediated by the transcription factor Nrf2 in an HRD1-dependent manner. TZP incubation could prevent the expression level of HRD1 in cardiomyocytes and subsequently decrease the ubiquitylation and degradation of Nrf2, thus enhancing its protein expression level, nuclear translocation, and transcription activity, and contributing to TZP’s defense against oxidative stress and cardiomyocyte apoptosis induced by DOX insult.
CONCLUSIONS Our study suggested that TZP attenuated oxidative stress and cardiomyocyte apoptosis by modulating HRD1-mediated Nrf2 expression and activity, thereby protecting against the cardiotoxic effects exerted by DOX. These results supported that TZP might be a promising therapeutic option for reducing chemotherapy-related cardiotoxicity.
GW35-e0967
Xiaolu Jiao1,2, Wenbin Zhang1,2
1Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
2Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Hangzhou, China
OBJECTIVES Angiopoietin-like protein8 (ANGPTL8), a novel hormone produced in liver and adipose tissue, is a hormone involved in regulating lipid metabolism and inflammation. Recently, it is reported that ANGPTL8 plays important roles in various vascular disease, including hypertension and thoracic aortic dissection. Our previous studies have identified a prominent role of ANGPTL8 in atherosclerosis and its clinical complications including coronary artery disease (CAD). However, the role of ANGPTL8 in atherosclerotic plaque vulnerability has not been explored.
METHODS In the present study, 691 subjects with acute coronary syndrome (ACS) and 105 stable-CAD were enrolled. Circulating ANGPTL8 levels were determined by ELISA. We induced experimental atherosclerosis in ApoE−/−mice, and ANGPTL8−/−ApoE−/− (DKO) mice. Raw 267.4 macrophages were used to explore the mechanism of ANGPTL8 in plaque vulnerability.
RESULTS The levels of circulating ANGPTL8 were significantly increased in ACS patients compared with stable-CAD. In the human and mouse vulnerable atherosclerotic lesions, ANGPTL8 expression was increased and expressed predominantly in macrophages. Deletion of ANGPTL8 reduces lesional macrophage content whilst increasing fibrous cap thickness thus conferring plaque stability. Moreover, deletion of ANGPTL8 inhibited the expression of NLRP3, interleukin-18 and interleukin-1β in vulnerable atherosclerotic lesions. In macrophages, ANGPTL8 knockdown macrophages resisted the induction of pyroptosis by cytosolic lipopolysaccharide. Accordingly, both recombinant human ANGPTL8 (rANGPTL8) protein and ANGPTL8 overexpression significantly aggravates the pyroptosis of macrophages. The expression of Caspase-1, NLRP3, GasderminD and interleukin-18 and interleukin-1β were induced by rANGPTL8 and inhibited by ANGPTL8 knockdown.
CONCLUSIONS This study provides the first evidence that deletion of ANGPTL8 prevents atherosclerotic plaque vulnerability by regulating pyroptosis of macrophages. It is suggesting that ANGPTL8 may be a novel therapeutic target to stable vulnerable plaque.
GW35-e0993
Zhijun Lei, Wenhui Peng
Shanghai Tenth People’s Hospital
OBJECTIVES Survivors of myocardial infarction (MI) are at a higher risk of recurrent cardiovascular events, particularly strokes and subsequent MIs. It remains unclear whether neutrophils, as the first responders to inflammation in MI, play a role in MI-accelerated atherosclerotic plaque progression. The present study aims to investigate the role and mechanism of neutrophils in atherosclerotic plaque progression after MI.
METHODS A retrospective cohort study was conducted to explore the relationship between neutrophils and plaque progression. MI was induced in atherosclerotic Ldlr −/− mice. Neutrophils depletion and adoptive transfer experiments were carried out to elucidate the role of neutrophils in MI-accelerated atherosclerotic plaque progression. Additionally, bioinformatic analyses and in-vitro experiments were utilized to explore the underlying mechanisms. Finally, rescue experiments were performed in-vivo using appropriate small-molecule inhibitor.
RESULTS The association between neutrophils and MI-accelerated plaque progression was observed both in patients and mice. In mice model, we identified a causal role for neutrophils in accelerating atherosclerotic plaque progression after MI. Next, we demonstrated that MI induced the activation of neutrophils and subsequent formation of neutrophil extracellular traps (NETs) within plaques, thereby accelerating atherosclerotic plaque progression. Mechanistically, S100A8/A9 released from infarcted myocardium was responsible for the activation of neutrophils via pyruvate kinase M2 (PKM2)-dependent glycolysis. Briefly, MI-derived S100A8/A9 promotes PKM2 translocate into nucleus, where it interacts with STAT3 to upregulate glycolytic genes. Furthermore, pharmacological inhibition of S100A8/A9 effectively prevented neutrophil activation and subsequent NETs formation, attenuating atherosclerotic plaque progression after MI.
CONCLUSIONS Our findings identify the pivotal role of neutrophils in MI-accelerated atherosclerotic plaque progression and indicate that pharmacological inhibition of S100A8/A9 may serve as a potential target for preventing recurrent cardiovascular events in MI patients.
GW35-e0994
Yuying Wang1, Xuena Xie2, Pengqi Li1, Mei Liu3, Lantian Hu3, Han Zhao3, Rong Yuan1, Yu Miao1, Qiqi Xin1, Weihong Cong1
1Xiyuan Hospital, China Academy of Chinese Medical Sciences
2Macau University of Science and Technology
3Tianjin University of Traditional Chinese Medicine
OBJECTIVES In recent years, m6A RNA methylation has gained attention as an essential epigenetic regulatory mechanism, with the m6A demethylase FTO playing a crucial role in cardiac pathophysiology. However, the specific role of FTO in myocardial infarction (MI) and its regulatory mechanisms remain unclear. Studies indicate that the Ligusticum chuanxiong Hort. (Chuanxiong, CX) and Paeonia lactiflora Pall. (Chishao, CS) herbal pair (CX-CS) offers significant cardioprotective effects, but its molecular mechanisms need further exploration. This study aims to investigate the role of FTO in myocardial infarction and to elucidate the mechanisms and targets by which CX-CS promotes endothelial cell angiogenesis through FTO-mediated m6A modification.
METHODS Male wild-type (Wt) C57BL/6 mice (25 ± 5 g) and FTO knockout (FTO-KO) mice were used to induce a MI model by ligating the left anterior descending coronary artery. The experimental groups included the sham group (Wt), the model group (Wt, FTO-KO), the CX-CS group (Wt, FTO-KO), and the positive group (Wt). The CX-CS group received CX-CS (3.9 g/kg/d) via gavage, while the positive group received perindopril tert-butylamine (3 mg/kg/d) and metoprolol tartrate (30 mg/kg/d) via gavage. The model and sham groups received an equivalent volume of saline. After four weeks of treatment, left ventricular ejection fraction (LVEF), myocardial fibrosis, and histopathological changes were evaluated using animal ultrasound, Masson’s trichrome staining, and hematoxylin-eosin staining. Network pharmacology and RNA sequencing (RNA-seq) were utilized to identify key targets and possible mechanisms of CX-CS in MI. CD31 immunofluorescence was performed to assess microvascular density in the infarct border zone. Human vascular endothelial cells (EA.hy926) were cultured to evaluate the effects of CX-CS on angiogenesis through proliferation and migration assays. EA.hy926 cells were infected with lentivirus to achieve FTO knockdown and overexpression. Gene expression and protein levels were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA).
RESULTS The results showed that CX-CS significantly improved cardiac function, increased LVEF, reduced myocardial fibrosis, and promoted angiogenesis in the infarct border zone of MI mice. Compared to the model group, the CX-CS group had significantly higher expression levels of FTO, VEGFA, and bFGF. FTO-KO mice exhibited significantly lower cardiac function, larger myocardial fibrosis areas, and more severe pathological damage than Wt C57BL/6 mice. FTO knockdown eliminated the cardioprotective effect on CX-CS and reduced its promotion of angiogenesis. Additionally, CX-CS enhanced the proliferation and migration of hypoxic EA.hy926 cells; VEGFA levels increased after FTO knockdown.
CONCLUSIONS This study provide evidence that CX-CS improves cardiac function and reduces myocardial fibrosis in an acute myocardial infarction model. The underlying mechanism may involve the regulation of FTO expression, which promotes angiogenesis in endothelial cells.
GW35-e0996
Bingjie Li, Fei Sun, Xi Zhang, Huirong Liu, Suli Zhang
Capital Medical University
OBJECTIVES This study aims to elucidate the role of angiotensin II-1 type receptor (AT1R) on cardiomyocytes in the pathogenesis of dilated cardiomyopathy (DCM) and the underlying mechanisms.
METHODS Data sets relating to AT1R and dilated cardiomyopathy were extracted from the GEO database to assess changes in AT1R expression. DCM mice models were established via intraperitoneal injection of Adriamycin. Cardiomyocytes were extracted by Langendorff perfusion method, and the expression of AT1R was detected by western blot. Cardiomyocyte-conditional AT1R knockout mice (AT1R-CKO) were generated utilizing Cre-loxP gene recombination technology, and the cardiac function of AT1R-CKO mice was evaluated using dynamic ultrasound. The hearts of AT1R-CKO mice were subjected to proteomic analysis, and differential genes were identified and validated to elucidate the relationship between cardiomyocyte AT1R expression and dilated cardiomyopathy.
RESULTS Analysis of the GEO database revealed down-regulation of AT1R expression in human and mouse hearts with DCM. Adriamycin-induced DCM mouse models demonstrated unchanged AT1R expression in the whole heart tissue, but decreased AT1R expression in cardiomyocytes. Dynamic M-mode echocardiography and HE staining showed that AT1R-CKO mice had a typical phenotype of DCM after 12 weeks. The proteomic analysis of the AT1R-CKO mouse heart revealed a significantly reduced protein expression profile in the enriched DCM pathway, characterized by the down-regulation of the dystrophin-associated glycoprotein complex (DGC), including dystrophin and sarcoglycans (α, β, γ, and δ) subunits. In vitro, AT1R agonists or inhibitors were administered, or AT1R was either overexpressed or knocked out in neonatal rat cardiomyocytes, leading to the increased or decreased DGC subunits expressions.
CONCLUSIONS Our findings suggest that down-regulation of AT1R expression in cardiomyocytes leads to reduced expression of skeletal protein DGC subunits, resulting in cytoskeletal rearrangement in dilated cardiomyopathy.
GW35-e0999
Jinhua Huang
OBJECTIVES Obesity causes various cardiovascular system changes that result in metabolic cardiomyopathy, which is the cause of heart failure in obese persons. Therefore, the underlying processes of the cardiomyopathy brought on by obesity are complicated and still unwell understood. The purpose of the current investigation was to investigate potential causes of high-fat diet-induced cardiomyopathy.
METHODS We examined changes in the cardiac global proteome and proteomics of lysine beta-hydroxybutyrylation (Kbhb) in male mice that had either had 24 weeks of chow or high fat diet (HFD) nutrition using high-performance liquid chromatography-tandem mass spectrometry. The next step was bioinformatic evaluation.
RESULTS In the high fat diet-feeding mice, a total of 97 proteins and 133 Kbhb sites on 92 proteins were differently expressed. While the most substantially changed activities for Kbhb proteins were energy generation and conversion, the significantly proteomic were mostly related to lipid transport and metabolism. Interestingly, almost all of the overlapping processes involved in fatty acid metabolism, carbon metabolism, propanoate metabolism, and branched chain amino acid breakdown were partially or totally localized to the mitochondria.
CONCLUSIONS Our global proteomics and Kbhb data, along with functional information, revealed how obesity-induced cardiomyopathy results from fatty acid oxidation, branched chain amino acid degradation, and ketone body metabolism in a HDF feeding environment. These findings offer new avenues for exploring the pathogenesis of HDF-induced cardiomyopathy and highlight potential treatments for heart failure.
GW35-e1010
Rujie Zheng1,2, Wenjuan Song1,2, Chengzhi Lu1,2
1Tianjin First Central Hospital
2Tianjin Medical University
OBJECTIVES Cardiac hypertrophy is a prevalent cardiovascular disorder typically induced by pressure overload, leading to pathological cardiac remodeling and subsequent heart failure. Despite various therapeutic strategies, the underlying mechanisms of cardiac hypertrophy remain inadequately understood. This study investigates the role of OTUD7B-mediated deubiquitination of hepatocyte nuclear factor 4α (HNF4α) in ameliorating pressure overload-induced cardiac hypertrophy and explores the potential mechanisms, focusing on fatty acid oxidation (FAO) modulation and ferroptosis inhibition.
METHODS Blood samples were collected from the patients with hypertrophic cardiomyopathy (n = 11) and non-hypertrophic cardiomyopathy controls (n = 26). Then, serum OTUD7B levels were then detected. Eight-week-old wild type male C57BL/6 mice were subjected to transverse aortic constriction (TAC), a classical pressure overload-induced cardiac hypertrophy mouse model, and the expression changes of OTUD7B were validated by western blotting and quantitative real-time PCR. To elucidate the specific role of OTUD7B in cardiac hypertrophy, we administered the recombinant adeno-associated virus 9 (rAAV9)-shOTUD7B vectors via tail vein injection into mice subjected to TAC. Cardiac function and the degree of cardiac hypertrophy was assessed through echocardiography and histopathological analysis. Transmission electron microscopy (TEM) was used to investigate the mitochondrial morphology. Total RNA was extracted from left ventricular myocardial tissues of mice for RNA sequencing. The expression levels of genes associated with fatty acid oxidation were evaluated by qPCR. Neonatal rat ventricular myocytes (NRCMs) were isolated from 1 to 3-day old neonatal Sprague–Dawley rats. NRCMs were infected with lv-shOTUD7B and lv-HNF4α and then treated with phenylephrine at a concentration of 50 μM for 24 h. ROS, lipid peroxidation assessment and measurement of malondialdehyde (MDA) and glutathione (GSH) were also performed. To investigate the interaction between OTUD7B and HNF4α, Co-immunoprecipitation (Co-IP) assay was conducted.
RESULTS The expression level of OTUD7B was significantly upregulated, both in patients with hypertrophic cardiomyopathy, and in mice subjected to TAC. OTUD7B knockdown mice display worsened myocardial hypertrophy and cardiac function following TAC. TEM analysis showed a disorganized arrangement of mitochondria, with mitochondria exhibiting wider and less packaged cristae with bulge tips in OTUD7B-knockdown hearts, confirming mitochondrial dysfunction. In addition, ferroptosis, as verified by higher levels of 4-hydroxynonenal, MDA, ROS and lower levels of GSH, was accelerated when OTUD7B was knocked down. RNA-seq analysis revealed that gene expression related to lipid metabolism were decreased due to TAC, indicating impaired FAO. Importantly, HNF4α is closely associated with FAO in both cellular processes and disease conditions and showed a significant decrease in OTUD7B knockdown mice. In vitro experiments demonstrated that HNF4α overexpression enhances FAO and mitigates ferroptosis in cardiomyocytes stimulated with phenylephrine, while OTUD7B knockdown suppresses the effect of HNF4α. Mechanistically, immunoprecipitation analysis confirmed that OTUD7B binds to HNF4α via its OTU domain and promotes HNF4α deubiquitination, thus stabilizing HNF4α.
CONCLUSIONS This study provides compelling evidence that the regulatory effect of OTUD7B on HNF4α plays a crucial role in the modulation of FAO and ferroptosis during pathological myocardial hypertrophy caused by pressure overload. These results provide valuable insights and establish a theoretical foundation for developing intervention strategies and clinical treatments targeting pathological cardiac hypertrophy. Moreover, these findings pave the way for potential therapeutic approaches to address pathological cardiac hypertrophy, offering promising prospects for improving patient outcomes in the future.
GW35-e1011
Fei Sun, Bingjie Li, Ruiqi Hou, Xiaotong Zhang, Suli Zhang, Huirong Liu
Capital Medical University
OBJECTIVES Investigating the effect of β1-AA (β1-adrenergic receptor autoantibody) on the level and distribution of CD28 molecule in CD4+T cells and the underlying mechanism, to provide a new therapeutic idea for heart failure from the perspective of immune blockade.
METHODS Fresh peripheral blood of heart failure patients was collected and β1-AA-positive mouse models were constructed. The loss of CD28 molecules on CD4+T cells membrane and the function of CD4+T cells were detected by flow cytometry, cytokine chip, multiple fluorescence immunohistochemical staining, and cell co-culture. The mechanism of CD28 loss after β1-AA stimulation was detected by proteomics, confocal microscopy, plasma membrane separation, and scanning electron microscopy. The interaction between β1-AR and CD28 on CD4+T cell membrane was investigated by employing immunoprecipitation, molecular docking, and bioluminescence resonance energy transfer (BRET). The downstream signals of β1-AR involved in CD28 macropinocytosis were investigated using mass spectrometry, protein knockdown, and overexpression.
RESULTS The CD28 molecule on CD4+T cell membrane downregulated in β1-AA-positive patients with heart failure, to increase the proportion of CD4+CD28−T cells and enhanced inflammation in peripheral blood. β1-AA-positive mouse models has the similar phenomenon, in which the migration of CD4+CD28−T cells to the heart increased and caused myocardial injury. Proteomics and scanning electron microscopy found that CD28 molecule macropinocytosis on CD4+T cells was enhanced after β1-AA stimulation. BRET and mass spectrum tests found that the C-terminal of β1-AR and the C-terminal of CD28 molecule directly interacted, that is, the two proteins existed in a complex state under physiological conditions. After β1-AA stimulation, the downstream Gi signal of β1-AR was significantly activated in CD4+T cells; subsequently, CD28 macropinocytosis is mediated by the recruitment of 14-3-3-ε and GRP75 to the CD28-β1-AR complex.
CONCLUSIONS There is a direct interaction between β1-AR and CD28 on CD4+T cells, and β1-AA-activated β1-AR leads to CD28 downregulation through macrocytosis, via selective activation of Gi pathway. Increased CD4+CD28−T cells infiltrate into the heart and participate in the development of heart failure.
GW35-e1016
Bingjie Li, Fei Sun, Xi Zhang, Huirong Liu, Suli Zhang
Capital Medical University
OBJECTIVES This study aims to elucidate the role of angiotensin II-1 type receptor (AT1R) on cardiomyocytes in the pathogenesis of dilated cardiomyopathy (DCM) and the underlying mechanisms.
METHODS Data sets relating to AT1R and dilated cardiomyopathy were extracted from the GEO database to assess changes in AT1R expression. DCM mice models were established via intraperitoneal injection of Adriamycin. Cardiomyocytes were extracted by Langendorff perfusion method, and the expression of AT1R was detected by western blot. Cardiomyocyte-conditional AT1R knockout mice (AT1R-CKO) were generated utilizing Cre-loxP gene recombination technology, and the cardiac function of AT1R-CKO mice was evaluated using dynamic ultrasound. The hearts of AT1R-CKO mice were subjected to proteomic analysis, and differential genes were identified and validated to elucidate the relationship between cardiomyocyte AT1R expression and dilated cardiomyopathy.
RESULTS Analysis of the GEO database revealed down-regulation of AT1R expression in human and mouse hearts with DCM. Adriamycin-induced DCM mouse models demonstrated unchanged AT1R expression in the whole heart tissue, but decreased AT1R expression in cardiomyocytes. Dynamic M-mode echocardiography and HE staining showed that AT1R-CKO mice had a typical phenotype of DCM after 12 weeks. The proteomic analysis of the AT1R-CKO mouse heart revealed a significantly reduced protein expression profile in the enriched DCM pathway, characterized by the down-regulation of the dystrophin-associated glycoprotein complex (DGC), including dystrophin and sarcoglycans (α, β, γ, and δ) subunits. In vitro, AT1R agonists or inhibitors were administered, or AT1R was either overexpressed or knocked out in neonatal rat cardiomyocytes, leading to the increased or decreased DGC subunits expressions.
CONCLUSIONS Our findings suggest that down-regulation of AT1R expression in cardiomyocytes leads to reduced expression of skeletal protein DGC subunits, resulting in cytoskeletal rearrangement in dilated cardiomyopathy.
GW35-e1018
Zhixiang Wang, Kaifan Niu, Xinyun Wang, Xian Jin
Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
OBJECTIVES Progressive cardiac fibrosis leads to ventricular wall stiffness, cardiac dysfunction, and eventually heart failure, but the underlying mechanism remains to be elucidated. AMFR (Autocrine Motility Factor Receptor) is an E3 ubiquitin ligase which was found to regulate endoplasmic reticulum-selective (ER-phagy); however, the role of AMFR in cardiac fibrosis is largely unknown. ER-phagy plays a protective role against ER stress in eukaryotic cells by mediating damaged ER degradation. However, despite the potentially beneficial function of ER-phagy in heart, only a few reports show the presence or the function of ER-phagy in cariac fibroblasts post myocardial infarction. Therefore, this study aims at exploring the possible role and underlying mechanisms of AMFR in the pathogenesis of cardiac fibrosis.
METHODS Animal model of myocardial infarction was established in wild type and AMFR−/− mice. We characterized single-cell RNA-sequencing and in vitro studies to investigate the role of AMFR in fibrosis post-myocardial infarction. Transfection of Adv-mcherry-GFP-FAM134B and transmission electron microscope were used to observe ER-phagy. CO-IP assay and AMFR mutant plasmid were used to investigate the binding mechanism of AMFR and FAM134B. Chloroquine and MG132 were used to determine the degradation way of FAM134B. siFAM134B was employed to investigate the antifibrotic effect of AMFR.
RESULTS AMFR levels were found to be elevated in fibrotic mice heart tissues after myocardial infarction, and in cardiac fibroblasts stimulated by TGF-β1 (transforming growth factor-β1). Overexpression of AMFR in cardiac fibroblasts reduced the expression of profibrogenic proteins in response to TGF-β1 stimulation, while knock-out of AMFR in mice aggravated cardiac fibrosis after myocardial infarction and worsen cardiac function. Single-cell RNA sequencing revealed AMFR null fibroblasts express higher levels of genes encoding important ECM proteins while simultaneously exhibiting a phenotype that inhibits autophagy. Transfection of Adv-mcherry-GFP-FAM134B and transmission electron microscope revealed that ablation of AMFR in cardiac fibroblasts resulted in the reduced ER-phagy activity. CO-IP assay demonstrated that AMFR interacts with ubiquitin and FAM134B, a protein that is also known as receptor of endoplasmic reticulum selective autophagy. Subsequently, overexpression of AMFR leads to the degradation of FAM134B which can be reversed by the autophagy inhibitor chloroquine, suggesting that AMFR ubiquitinates FAM134B and targets it for degradation via the autophagy pathway. Importantly, knockdown of FAM134B reversed the antifibrotic effect of AMFR, indicating that the antifibrotic effect of AMFR is at least partially mediated through ER-phagy. Furthermore, AMFR inhibits the phosphorylation of mTORC1 downstream targets such as S6K1 and 4E-BP.
CONCLUSIONS The findings of this study demonstrated that AMFR is upregulated and activats ER-phagy after myocardial infarction, which subsequently ameliorated progressive fibrosis and cardiac dysfunction. Thus, our findings highlight a compensatory role of AMFR-driven ER-phagy in suppressing the progression of fibrotic responses.
GW35-e1026
Zhengbin Zhang, Ziqian Wang, Shunying Hu, Yundai Chen
Chinese PLA general hospital
OBJECTIVES The diminishing reparative activity of aging mesenchymal stem cells (MSCs) constrains their potential in regenerative medicine. Asprosin is a newly reported protein hormone that regulates glucose metabolism. Omics screening has revealed widespread downregulation of the fbn1 gene (encoding asprosin through its last two exons) in multiple organs of aging mice and in MSCs derived from induced pluripotent stem cells of aged and progeria patients. However, it is currently unclear whether asprosin affects the repair activity of aging MSCs and their therapeutic efficacy in myocardial infarction (MI).
METHODS Acute and replicative MSC senescence were established by H2O2 and continuous passage respectively. Naturally senescent MSCs (OMSC) and young MSCs (YMSCs) were isolated from 20-month-old and 5-month-old mice. PCR and western blotting were used to detect asprosin expression in senescent MSCs. Asprosin is stably overexpressed in OMSC and silenced in YMSC with lentiviral vectors and CRISPR-Cas9 technology. SA-β-Gal and γH2AX staining, CCK-8, clone formation assay, and flow cytometry were used to detect the cellular senescence, self-renewal, and apoptosis. Recombinant human asprosin proteins prepared by HEK293 cells (ASPH) was used to directly treat OMSCs, and celluar self-renewal, migration and pro-angiogenesis were evaluated. Additionally, the impact of glycosylation modifications on asprosin function was analyzed with LC-MS/MS and enzymatic deglycosylation. Metabolomics, glycolytic stress test, and lactate detection were used to elucidate the glycolysis of OMSCs. Transcriptomics and CUT&Tag were combined to jointly analyze the molecular mechanisms. Finally, the efficacy of asprosin gene-modified OMSCs on MI will be evaluated through cardiac ultrasound, immunofluorescence and Masson staining.
RESULTS Asprosin expression in MSCs from three senescent models was lower than that in the control group respectively. Asprosin knock-out aggravated cellular senescence induced by H2O2 in YMSCs, and impaired cell proliferation and anti-apoptosis ability; conversely, overexpression of asprosin delayed OMSC senescence, enhanced self-renewal. ASPH, but not ASPE (expressed by E. coli), directly promoted MSC proliferation from human white adipose tissue (AT), rat brown AT, and mouse bone marrow. Furthermore, ASPH directly promoted the self-renewal, migration, and paracrine-mediated pro-angiogenesis of OMSCs. ASPH have multiple N-glycosylation sites compared to ASPE, and the aforementioned effects vanished after the removal of N-glycosylation modifications. Metabolomics and transcriptomics suggested that glycolysis and the AKT-HIF1α pathway were involved in molecular mechanisms of ASPH regulating OMSCs. ASPH directly increases OMSC glucose uptake, pyruvate and lactate production, and enhances glycolysis capacity. ASPH upregulated the key glycolysis proteins (GLUT1/HK/PFKL/PFKP) and pro-angiogenic factors VEGF/TIMP1 both through the AKT-HIF1α axis. After inhibiting glycolysis and lactate production with 2-DG or LDH inhibitors, the effects of ASPH on MSC self-renewal and migration disappeared, but VEGF/TIMP1 production and pro-angiogenesis were not affected. Furthermore, ASPH increased the levels of pan-lactylation and H3K18 lactylation (H3K18 la) in OMSCs owing to glycolysis and lactate production. H3K18 la CUT&Tag, transcriptomics and Chip-PCR found the expression of Ccna2/Ccnb1 and Mmp3/Mmp9 increased, and the H3K18 la marks in promoter regions of these genes were also enhanced. A486, a histone lactyltransferase p300 inhibitor, or siP300 suppressed OMSC self-renewal and migration induce by ASPH. Finally, overexpression of asprosin could increase the survival of OMSCs in vivo, improve heart function, cardiac fibrosis, and angiogenesis in the border zone of MI in mice.
CONCLUSIONS Asprosin activates the AKT-HIF1α axis in MSC cells, upregulating VEGF/TIMP1 and promoting glycolysis-lactate-H3K18 lactylation modification respectively, ultimately enhancing MSC paracrine secretion and self-renewal, and improving the efficacy of aged MSCs in repairing myocardial infarction.
GW35-e1028
Xuhong Wang1,2,3, Tingting Tang1,2,3, Zihua Zhou1,2,3, Xiang Cheng1,2,3
1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, Wuhan, China
3Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
OBJECTIVES Inflammatory response has been linked to cardiac repair and ventricular remodeling after myocardial infarction (MI). Thymic stromal lymphopoietin (TSLP), as a pivotal orchestrator of homeostasis and inflammation belonging to the interleukin-1 cytokine family, has been implicated in various pathological conditions related to immunity. However, its significance and function in cardiac repair after MI remain uncertain. In the present study, we hypothesized that TSLP may play a role in cardiac ventricular remodeling following MI.
METHODS Wild-type (WT) and TSLP receptor (TSLPR)-knockout (Crlf2−/−) mice were subjected to MI by ligation of the left descending artery. To mimic the in vivo absence of TSLP/TSLPR signaling, we used TSLPR knockout mice (Crlf2 −/−). We employed western blotting, real-time quantitative PCR, and flow cytometry to analyze TSLP expression, identify its cellular sources, and assess TSLPR levels on immune cells in infarcted hearts and spleens. Additionally, we used Masson’s trichrome staining, immunofluorescence, and echocardiography to assess TSLP’s role in adverse left ventricle remodeling and heart failure progression. Flow cytometry further explored the MI-induced inflammatory response in TSLP/TSLPR deficiency. Finally, RNA sequencing provided transcriptional insights.
RESULTS TSLP expression was upregulated in the infarcted heart, with a peak observed on day 7 post MI. The expression of TSLP was mainly observed in cardiomyocytes located within the border area of the infarction, while dendritic cells showed the highest level of TSLPR expression in cardiac tissue and spleen. Compared to WT mice, Crlf2−/− mice exhibited significantly reduced survival and worsened cardiac function after MI. Concomitantly, Crlf2−/− mice exhibited augmented interstitial fibrosis and increased cross-sectional area of cardiomyocytes, accompanied by a reduced proportion of CD31+ staining. However, there was no apparent change in the proportion of TUNEL+ cardiomyocytes within the border zone compared to WT mice. Mechanistically, a reduction in regulatory T cells (Treg) and a decrease in the ratio of Treg to conventional CD4+T cells, and an increased abundance of innate immune cells and their subsets, were observed in the infarcted hearts of Crlf2−/− mice. Moreover, TSLP regulated CD4+T cell activation and proliferation at baseline and after MI, with a greater impact on Treg cells than on conventional T cells, as indicated by the reduced expression of CD69 and Ki67 on these cells. Furthermore, RNA-seq analysis revealed significant downregulation of genes involved in T cell activation and TCR signaling in the infarcted cardiac tissue of Crlf2−/− mice compared to their WT counterparts.
CONCLUSIONS Collectively, our data indicate a critical role for TSLP in facilitating cardiac repair and conferring protection against MI, primarily through regulating T cell responses, which may provide a potential novel therapeutic approach for managing heart failure after MI.
GW35-e1029
Jiao Wenhui, Qi Xiangyang, Chen Xiongwen
Tianjin Medical University
OBJECTIVES Fatty acids (FAs) must traverse the endothelial barrier, composed of endothelial cells (ECs), to reach cardiomyocytes (CMs). The multiligand receptor cluster of differentiation 36 (CD36), a crucial receptor for FA uptake in the heart, is expressed in both cell types. The dependence of EC-CM crosstalk on CD36 within ECs or CMs, or both, particularly during acute stress or pathological states, remains unclear. In this study, we investigated the modulation of EC FA uptake by CMs under energy stress, with a focus on the source and localization of CD36, to elucidate its role in physiological equilibrium and the progression of heart failure (HF).
METHODS Wild-type (WT), EC- or CM-conditional CD36 knockout (KO), and CM CD36 heterozygous KO (HET KO) male mice were utilized to determine the roles of CD36 in HF induced by myocardial infarction (MI) or energy stress induced by running. Cardiac function was assessed using echocardiography and hemodynamics. Protein abundance and phosphorylation were measured via Western blotting and immunostaining. Cardiac morphology was examined using hematoxylin-eosin (HE) and wheat germ agglutinin (WGA) staining. Lipid accumulation was assessed by measuring tissue triglycerides (TGs), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. The role of protein kinase A (PKA) in HF and regulated FA uptake was examined using PKA inhibitor peptide transgenic mice.
RESULTS (1) Isoproterenol (ISO) stimulation enhanced sympathetic nerve activation, promoting active FA uptake by ECs in CMs; (2) CMs activated the AKT-AS160 signaling pathway in ECs via CAMKII, facilitating CD36 targeting to the EC membrane; (3) CD36 in CMs was more critical than CD36 in ECs for maintaining metabolic balance under running-induced energy stress; (4) Under sympathetic nervous system activation, CD36 was secreted by CMs and transported to ECs, mediating FA uptake regulation by ECs; (5) PKA was the key molecule regulating the transport of CD36 from CMs to the EC membrane; (6) During the compensatory stage of HF, excessive sympathetic nervous system activation triggered regulatory pathways in CMs that control FA uptake by ECs, leading to lipid accumulation, mitochondrial dysfunction, and accelerated HF progression; (7) Specific overexpression of CD36 in CMs exacerbated myocardial function impairment post-HF by increasing mitochondrial damage; (8) Heterozygous knockout of CD36 or inhibition of PKA activity in CMs mitigated cardiac function impairment post-HF and improved animal survival.
CONCLUSIONS The sympathetic nervous system triggers CMs to ECs fatty acid uptake. PKA in CMs directs CD36 to the ECs membrane, boosting cardiac fatty acid uptake essential for exercise metabolism. Overactivation of the sympathetic nervous system during HF compensation promotes CD36 targeting, leading to cardiac lipotoxicity and hastening HF progression. CD36 HET KO in CMs could be a new treatment for heart failure.
GW35-e1035
Huiyuan Qin, Jiuzhou Chen
The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES Epicardial adipose tissue (EAT) is implicated in atrial fibrillation (AF) progression, with increased white adipocytes correlating with atrial fibrosis. However, the precise mechanisms remain unknown.
METHODS EAT samples from 26 AF patients and 24 sinus rhythm individuals underwent metabolomics and proteomics analysis. A lentiviral vector overexpressing NogoB was used to generate 3T3-L1-NogoB-OE cells for in vitro studies. Western blotting, qRT-PCR, and ELISA assessed lipid differentiation and inflammation. RNA-seq and western blot examined NogoB’s role in differentiation pathways. Optical mapping described electrical changes in cardiomyocytes. In vivo, AAV8-mediated NogoB overexpression in CS-CREM mice was used to observe AF and fibrosis. SKL2001’s efficacy in mitigating atrial arrhythmia was evaluated.
RESULTS In a cohort of 26 individuals with atrial fibrillation (AF) and 24 with sinus rhythm, demographic characteristics like age, gender, hypertension, and diabetes were balanced. AF patients had significantly larger epicardial adipose tissue and adipocytes (P = 0.004, 0.001). Metabolomic profiling showed distinct metabolic features in AF patients, including reduced anti-inflammatory lipids (LPC 16:0, LPC 18:1) and increased lipid storage molecule Phosphatidylglycerol 16. Proteomics linked NogoB with these changes, influencing cell differentiation via the AKT2/GSKβ/catenin pathway. Co-culture experiments involving 3T3-L1-NogoB overexpressing (OE) cells with cardiomyocytes and cardiac fibroblasts demonstrated elongated action potentials and enhanced fibroblast activity, evidenced by increased expression of αSMA, collagen I, and TGF-β. In animal models, NogoB overexpression via AAV8 increased AF incidence and fibrosis, but β-catenin agonist SKL2001 reduced these effects, suggesting a potential therapeutic approach.
CONCLUSIONS NogoB exacerbates EAT inflammation and promotes AF by inducing preadipocyte differentiation into white-like adipocytes via the AKT2-GSK3β-Catenin pathway.
GW35-e1049
Yudai Irokawa1, Yoichi Sunagawa1,2,3, Miho Yamada1, Takahiro Katagiri1, Kenya Maekawa1, Satoshi Shimizu1, Yasufumi Katanasaka1,2,3, Toshihide Hamabehoriike1,2,3, Yuto Kawase1, Ryuya Naruta1, Masafumi Funamoto1, Kana Shimizu1, Tomohiro Asakawa4, Koji Hasegawa1,2, Tatsuya Morimoto1,2,3
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka
2Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto
3Shizuoka General Hospital, Shizuoka
4Institute of Innovative Sciences and Technology, Tokai University
OBJECTIVES When the heart is exposed to stresses such as myocardial infarction or hypertension, it responds to them and undergoes compensatory hypertrophy. However, a continuation of the stresses causes the failure of this compensatory mechanism and eventually leads to systolic dysfunction or decompensated heart failure. Since the hypertrophy of individual cardiomyocytes has been observed in this process, controlling cardiomyocyte hypertrophy is a potential target for preventing and treating heart failure. Anserine, an imidazole dipeptide, is observed in birds and fish and has various bioactivities, such as anti-inflammatory and anti-fatigue effects. However, the effect of anserine on the development of heart failure remains unknown. This study aimed to investigate the role of anserine on cardiac hypertrophy and the development of heart failure in vivo.
METHODS Cultured primary cardiomyocytes prepared from rat neonatal hearts were treated with 10 mM anserine and then stimulated with phenylephrine (PE) for 48 h. These cells were subjected to fluorescent immunostaining with α-actinin, and cardiomyocyte surface area was measured using an ArrayScan™ system. Then, we investigated H3K9 acetylation using Western Blotting and the inhibition of the mRNA levels of the cardiac hypertrophy response genes ANF and BNP using real-time PCR. Next, to examine whether anserin can directly inhibit the p300 histone acetyltransferase (HAT) activity, an in vitro HAT assay was performed. Finally, eight-week-old male C57BL/6J mice were subjected to transverse aortic constriction (TAC) and randomly assigned to daily oral treatment with anserine-containing material, Marine Active® (60 or 200 mg/kg anserine) or vehicle for eight weeks. To assess the effect of anserin on systolic function, we conducted cardioecography, qPCR, immunohistochemistry, and western blotting.
RESULTS Anserine significantly suppressed the PE-induced increases in cardiomyocyte size, ANF and BNP mRNA levels, and histone H3K9 acetylation. An in vitro histone acetyltransferase (HAT) assay showed that anserine directly suppressed p300-HAT activity with an IC50 of 1.87 mM. An echocardiographic study revealed that anserine 200 mg/kg significantly suppressed the TAC-induced increase in left ventricular posterior wall thickness and decrease in left ventricular fractional shortening. Moreover, anserine significantly inhibited the TAC-induced ANF and BNP mRNA levels, cardiomyocyte hypertrophy, cardiac fibrosis, and acetylation of histone H3K9.
CONCLUSIONS Anserine suppressed TAC-induced development of heart failure, at least in part, by inhibiting p300-HAT activity. These findings suggest that anserine may be an effective agent for heart failure therapy in humans.
GW35-e1073
Ya Zhao, Xiaoli Tian
Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, and Jiangxi Province Key Laboratory of Aging and Disease, Nanchang, Jiangxi 330031, China
OBJECTIVES Vascular aging is an independent risk factor for age-related complex diseases, such as hypertension and atherosclerotic diseases, the leading causes for global disability and mortality. Early reports showed that citrate extended lifespan in fruit flies and improved memory in high-fat diet mice. Whether sodium citrate is able to alleviate vascular aging and age-related vascular dysfunction, however, remains unknown.
METHODS In aged (>20 months) and high fat diet (HFD)-fed ApoE knockout (ApoE −/−) mice, we evaluated the effects of sodium citrate on vascular aging and age-related vascular dysfunction and searched for the possible mechanisms.
RESULTS Supplementation of sodium citrate extended healthspan and decreased frailty index, increased bone density, and improved maximal grip strength and maximal balance speed in both aged and HFD-fed ApoE −/− mice. Importantly, administration of sodium citrate lowered blood pressure and improved sensitivity to endothelial-dependent vasodilators. Moreover, in HFD-fed ApoE −/− mice, sodium citrate treatment reduced the size of atherosclerotic plaque in aortic tree, decreased necrotic core area and vulnerability index in aortic root plaque. Further, sodium citrate delayed vascular aging, such as maintaining integrity of elastic fibers and prohibiting the expression of CDKN1A (p21), the senescent marker. To illustrate the mechanism, we found sodium citrate treatment delayed human umbilical vein endothelial cell senescence, evident by decreased number of cells stained with senescence associated-β-galactosidase and downregulation of p21 as well as the recovered population-doubling level. Sodium citrate reversed senescence-related mitochondrial dysfunction, including basal respiration, maximal respiration and ATP production. Finally, sodium citrate specifically reduced the production of reactive oxygen species (ROS) in mitochondria.
CONCLUSIONS For the first time, we demonstrate sodium citrate reverses age-related mitochondrial dysfunction and reduces ROS production to delay vascular aging and alleviate age-related vascular dysfunction. These novel findings have potential clinical implications for interventions against vascular aging and age-related vascular diseases.
GW35-e1075
Wang Xiaoqi, Zhang Maomao
Department of Cardiology, Experimental Animal Centre, and Department of Ultrasound (P.S.), the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
OBJECTIVES Lactylation, a glycolysis-derived post-translational modification, is involved in cardiovascular disease. However, there is a lack of studies investigating the distribution and role of overall protein lactylation in neutrophils post-MI/R. This study aimed to investigate the role of lactylation in remote neutrophil priming after myocardial ischemia reperfusion (MI/R) injury.
METHODS Bone marrow and circulating neutrophils at various times of MI/R were subjected to single-cell transcriptome. The lactylated proteins were identified by proteomics and lactyl proteomics analysis. Genetically modified mice and multiple molecular biological methodologies were used to demonstrate the role of S100a9 lactylation and explore its molecular mechanisms in MI/R. Serum S100a9K26la levels were measured in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).
RESULTS Neutrophils initiated a distinct transcriptional pattern involving migratory and glycolytic signals before cardiac infiltration post-MI/R. S100a9 lactylation was identified as the target of neutrophil lactylation, which elevated remotely and contributed to cardiac dysfunction post-MI/R. Mechanistically, S100a9 lactylation boosts migratory transcription by binding to promoter region of genes, thereby promoting neutrophil migration. NLRP3/IL-1β from homing neutrophils facilitated remote lactylation. Moreover, we identified dihydrolipoyllysine-residue acetyltransferase (DLAT), which is a component of pyruvate dehydrogenase complex and catalyses the conversion of pyruvate to acetyl-CoA, to be a novelty lactyltransferase that can directly catalyze lactylation of S100a9 at K26 site. Consistently, Gevokizumab, α-lipoic acid and S100a9K26la neutralizing antibody treatments protected against reperfusion injury by inhibiting the IL-1β/DLAT-lactylation axis. Furthermore, we demonstrated the association of S100a9K26 lactylation with cardiac death in patients with acute myocardial infarction (AMI) receiving percutaneous coronary intervention (PCI).
CONCLUSIONS This study demonstrate a previously unknown role of neutrophil S100a9 lactylation in driving remote activation of the intrinsic migratory transcriptional response in neutrophils, unveiling a paradigm that lactylation genetically governs neutrophil behavior to MI/R through a non-histone protein. S100a9 lactylation is a promising prognostic biomarker or potential therapeutic target for MI/R.
GW35-e1100
Lulu Zhu, Wenting Wang, Jianshu Chen, Qiongying Wang, Jing Yu
Center of Hypertension, Lanzhou University Second Hospital
OBJECTIVES Elevated testosterone concentrations induce left ventricular hypertrophy of the postmenopausal hypertension women, but the molecular mechanisms are poorly understood. MuRF1, a muscle-specific E3 ubiquitin ligase in the proteasome ubiquitination process, was newly identified as a negative regulatory factor of the heart and muscle tissue. There have been little study to certify whether MuRF1 take part in testosterone-induced the left ventricular hypertrophy of the postmenopausal hypertensive women.
METHODS Femal spontaneously hypertensive rats (SHR) (N = 28, 12 week) were divided into three groups: (1) Sham group (n = 6), (2) ovariectomized (OVX, n = 6), (3) ovariectomized + testosterone intervention (OVX + T, 4 mg/kg, QOD, n = 6), in addition, the age-matched Wistar-Kyota (WKY) as the control. Testosterone was intramuscularly injected after ovariectomy 1 week and repeat every three days at 4 mg/kg concentration for 4 weeks. we compared the weight/tibial length and the levels of IVST, LVPWT, LVM among four groups, and measured the expression of the β-myosin heavy chain (β-MHC), AMPK, FOXO1, MuRF1 and ubiquitinated proteins, as well as the phosphorylation expression of AMPK (p-AMPK) and Forkhead box O 1 (p-FOXO1) proteins by using western blot method. ANOVA analysis was used for comparison among the different groups. There was statistically significant difference when the P value was less than 0.05. The data were processed by SPSS 26.0 software.
RESULTS After 4 weeks of testosterone intervention, compared to other three groups, the rats from OVX + T group showed the greatest elevation both systolic blood pressure and diastolic blood pressure, and presented the most significant left ventricular hypertrophy (P < 0.05), which was evaluated by the elevation of weight/tibial length ratio, some echocardiography parameters and the protein expression of the β-MHC protein (P < 0.05). Moreover, the expression of the p-AMPK, p-FOXO1, MuRF1 and ubiquitinated proteins was lowest in OVX + T group (P < 0.05).
CONCLUSIONS Collectively, Atrophy-related MuRF1 molecular might as an essential molecular mechanism modulated testosterone-induced the left ventricular hypertrophy of female ovariectomized SHR in AMPK-FOXO1-dependent signalling pathway manner.
GW35-e1101
Zhen Ma1, Ming Li2, Rui Guo1, Bingxin Huang1, Yunpeng Ling1
1Department of Cardiac Surgery, Peking University Third Hospital
2Ultrasound Medical Center, Lanzhou University Second Hospital
OBJECTIVES Following myocardial infarction (MI), the early accumulation of M1-like macrophages in the ischemic injury zone exacerbates the effects of immune modulation, leading to secondary myocardial damage, adverse ventricular remodeling, and eventual heart failure. Precise pharmacological intervention targeting this process remains a formidable challenge. The aim of this study was to engineer a nanotherapeutic delivery system with M1-like macrophage-specific targeting and ultrasound-triggered release capabilities by leveraging nanoultrasound contrast agents and exploiting the unique acoustic cavitation effect of ultrasound.
METHODS In this study, a folic acid (FA)-modified gene delivery system based on the self-assembly of DOTAP, DSPE-PEG2000-FA, and perfluorohexane, namely FA-PNBs, to achieve small interfering RNA of STAT1 (siSTAT1) and a small molecule compound, nitro-oleic acid (OA-NO2) co-delivery into M1 macrophages. FA-PNBs was exposed to low-intensity focused ultrasound (LIFU) irradiation to induce PFH phase transition and NPs collapse, which promoted the release of siSTAT1 and OA-NO2.
RESULTS Through comprehensive in vitro and in vivo investigations, we demonstrated the system’s exceptional targeting specificity and highly controllable cargo release. Furthermore, the combined effect of OA-NO2 and siSTAT1 administration induced M1-like macrophage polarization into Cx3cr1-positive macrophages, increased macrophage proliferation, substantially down-regulated pro-inflammatory molecules (including TNF-α, IL-1β) and recruited regulatory T cells to the ischemic injury zone. Implementation of this nanotherapeutic strategy effectively alleviated adverse post-MI ventricular remodeling, thereby preserving cardiac function. This approach holds promise for clinical intervention strategies after MI.
CONCLUSIONS Precision Nanomedicine Delivery System Targeting Post-Myocardial Infarction M1-like Macrophages: We present a highly efficient nanotherapeutic delivery system specifically designed for precise targeting of M1-like macrophages in the aftermath of myocardial infarction. This sophisticated platform demonstrates versatility in delivering both compound drugs and nucleic acid drugs. Conjoint Effect of OA-NO2 and Stat1-siRNA: The combined influence of OA-NO2 and Stat1-siRNA orchestrates a cascade of effects, promoting the polarization of M1-like macrophages towards Cx3cr1-positive macrophages. Moreover, this cooperative interaction stimulates robust macrophage proliferation and orchestrates the in vivo recruitment of regulatory T cells to the injury site, imparting potent therapeutic effects. Clinical Translation Potential: The nanotherapeutic showcased herein exhibits substantial promise by ameliorating adverse ventricular remodeling in post-myocardial infarction mice, thereby preserving a greater extent of cardiac function. These findings underscore its significant clinical relevance and translational potential.
GW35-e1110
Liming Chen
Zhongshan Hospital, Fudan University
OBJECTIVES Mitochondria-associated apoptosis exacerbates cardiac dysfunction in ischemic heart failure. The translocator protein (TSPO), anchoring on the outer membrane of mitochondria, plays important roles in mitophagy and apoptosis. However, its modulation of the interplay between mitophagy and apoptosis in ischemic heart failure remains unexplored. The present study aimed to uncover the critical role of TSPO following myocardial infarction and its underlying mechanisms.
METHODS Bulk RNA-seq data from left ventricles of healthy controls and patients with ischemic heart disease were reanalyzed. Three machine learning algorithms, including random forest, SVM-RF, and LASSO, were used to identify key genes. ROC curve and nomogram were utilized to assess the diagnostic value of TSPO. Permanent ligation of the left anterior descending (LAD) artery was performed to establish a murine model of myocardial infarction. Cardiac function was assessed using echocardiography. Histology was evaluated using H&E and Masson staining techniques. The mRNA and protein levels of TSPO were determined using RT-qPCR and Western blotting, respectively. Mitophagy was assessed using transmission electron microscopy and Mitotracker-Lysotracker tracing, while apoptosis was examined using TUNEL staining and Western blotting. The mitochondrial localization of Parkin, Cytochrome C, and LC3B was determined using immunofluorescence staining. The binding of P53 to its motif in the promoter region was examined using ChIP-qPCR.
RESULTS We reanalyzed bulk RNA-seq data from human left ventricles following myocardial infarction. TSPO was identified as a key gene involved in the pathogenesis of ischemic heart failure following integrated analysis of three machine learning algorithms. TSPO was upregulated in the border zone of ischemic hearts and localized to the mitochondria. Overexpression of TSPO exacerbated mitochondrial fragmentation, loss of mitochondrial potential, and cardiomyocyte death. Furthermore, we found that Pink1/Parkin-mediated mitophagy post-MI was dampened by TSPO overexpression, thus leading to mitochondria-dependent apoptosis. Molecular docking and Co-IP assays revealed that TSPO suppressed mitophagy by binding with p62 and inhibiting its assembly. TSPO silencing by specific siRNA normalized mitophagy and promoted cardiomyocyte survival. Rapamycin was used to improve mitophagy and thus reverse TSPO-induced apoptosis. p53 was positively correlated with TSPO in the heart tissue post-MI. We identified a conserved P53-binding motif on the promoter region of TSPO. We used ChIP-qPCR with anti-P53 antibody and specific primers and determined that the transcription of TSPO was p53-dependent. A mitochondrial targeting sequence (MTS) of TSPO was predicted, and a mutant plasmid with TSPO lacking MTS was constructed. TSPO failed to translocate to mitochondria and bind with p62 after deletion of MTS. TSPO without correct mitochondrial localization could not interfere with mitophagy and thus had no impact on cardiomyocyte survival.
CONCLUSIONS TSPO was able to inhibit Pink1-Parkin mediated mitophagy and thus accerated mitochondria-dependent apoptosis post-MI. The transcription of TSPO was p53-dependent, and its function was mitochondria-anchored.
GW35-e1129
Yan Tang1, Suxin Deng1,2, Yongnan Fu1, Yuan Wen1, Liang Wang1, Xiaoping Peng1
1Department of Cardiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, P.R. China
2Department of Cardiology, Gaoxin Branch of The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China
OBJECTIVES Cardiac dysfunction, a common and early complication of sepsis and endotoxemia, is the major cause of death in intensive care units. No specific therapy is available at present for this cardiac dysfunction; thus, elucidating the key mechanisms that initiate endotoxin-induced myocardial dysfunction (EIMD) to develop novel therapeutic approaches is a public health priority.
METHODS Male C57BL/6J, Tlr4 −/−, Casp11 −/−, Nlrp3 −/−, Casp1 −/−, Gsdmd −/−, Gsdmdfl/fl , and cardiomyocyte-specific knockout (Gsdmdfl/fl ; Myh6-Cre [Gsdmd-CKO]) mice were subjected to endotoxemia challenges. Neonatal rat cardiomyocytes and AC16 cardiac cells were treated with poly (I:C) followed by lipopolysaccharide. Cardiac function was measured by echocardiography, terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling, and immunostaining. Mitochondrial function in cardiomyocytes was assessed by fluorescence staining, flow cytometry, and transmission electron microscopy. The specific mechanisms mediating cardiac dysfunction were determined by bulk RNA sequencing and Western blot assays. Cardiolipin and its oxidized forms were quantified by ultra-high performance liquid chromatography-high-resolution tandem mass spectrometry.
RESULTS We discovered that gasdermin D (GSDMD) initiates mitochondrial pore formation and cardiac cell apoptosis via a cardiolipin-dependent mechanism during endotoxin challenge. Short-term exposure to endotoxin promotes GSDMD cleavage and activation via both canonical and noncanonical inflammasome signaling. The pyrolytic executive form of GSDMD (GSDMD-N) targets oxidized and externalized cardiolipin in mitochondria to form the GSDMD oligomer, which occurs prior to the formation of plasma membrane pores and conventional apoptotic pores, such as BAX/BAK and VDAC1 pores. Moreover, we found that mitochondrial reactive oxygen species generated from mitochondrial complex II are the major contributors to cardiolipin oxidation in cardiomyocytes exposed to endotoxin.
CONCLUSIONS Our data reveal a novel pathogenic mechanism mediated by the oxidized cardiolipin-GSDMD interaction in endotoxin-induced heart dysfunction and highlight modulation of cardiolipin oxidation status as an early therapeutic target for EIMD.
GW35-e1142
Bo Li1, Yefei Shi1, Qinfang Miao2, Haikun Qi2, Wenhui Peng1
1Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai, China
2School of Biomedical Engineering, ShanghaiTech University, Shanghai, China
OBJECTIVES Cardiac magnetic resonance (CMR) and transthoracic doppler echocardiography (TTDE) are commonly used for diagnosing coronary microvascular dysfunction (CMD) by myocardial perfusion reserve (MPR) and coronary flow velocity reserve (CFVR). In this study, we aimed to compare their effectiveness in evaluating CMD, and investigate the difference of CMD between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).
METHODS Two diabetes mouse models were established to represent T1DM and T2DM. Specially, a convenient arterial spin labeling CMR (ASL CMR) sequence adapted for mouse heart was performed in this study. ASL CMR and TTDE were performed for myocardial blood flow (MBF, mL/g/min) and coronary flow velocity (CFV, mm/s). Both of detection methods were repeated twice per mouse at rest stage and stress stage of coronary microvascular. 2.5% isoflurane was used to induce coronary microvascular stress. MPR and CFVR were analyzed as the ratios of MBF and CFV during stress and at rest, respectively. Isolectin B4 immunofluorescence staining was used to determine cardiac capillary density, which was regarded as the reference for comparing CMR and TTDE.
RESULTS Both T1DM and T2DM mice had reduced coronary microvascular dilation as determined by MPR (diastole: Ctrl MPR 2.2 ± 0.5 vs. T1DM MPR 1.7 ± 0.1, P < 0.05, vs. T2DM MPR 1.4 ± 0.1, P < 0.05; systole: Ctrl MPR 2.2 ± 0.3 vs. T1DM MPR 1.7 ± 0.1, P < 0.05, vs. T2DM MPR 1.5 ± 0.1, P < 0.05) and CFVR (Ctrl CFVR 2.7 ± 0.2 vs. T1DM CFVR 2.4 ± 0.2, P > 0.05, vs. T2DM CFVR 1.6 ± 0.2, P < 0.05). Thus, CMD occurred in T1DM and T2DM mouse models, and the latter was more severe at functional and histological levels. Correlation analysis showed both CFVR (R 2 = 0.6743, P < 0.0005) and MPR (R 2 = 0.8097, P < 0.0001) had positive correlation with the percentage of IB4 area while the latter had stronger correlation. Moreover, ASL CMR could detect reduced myocardial perfusion in mice with 4-week high fat diet (diastole: chow MPR 2.2 ± 0.1 vs. 4 w HFD MPR 2.0 ± 0.1, P < 0.05; systole: chow MPR 2.1 ± 0.0 vs. 4 w HFD MPR 2.0 ± 0.1, P > 0.05), even though there was no change in cardiac capillary density.
CONCLUSIONS ASL CMR was more precise in assessing coronary microvascular function than TTDE with the pathology as reference. T2DM mice had more severe CMD than T1DM at functional and histological levels.
GW35-e1152
Teng Ma, Dachun Xu
Shanghai Tenth People’s Hospital
OBJECTIVES Adverse remodeling after myocardial infarction (MI) result in heart failure and sudden cardiac death. Growth arrest-specific 6 (GAS6) is a member of the vitamin K-dependent protein family that is involved in the regulation of the cardiovascular system. However, whether and how GAS6 affects post-MI cardiac remodeling remains to be elucidated.
METHODS To examine the correlation of plasma GAS6 with heart failure, we analyzed plasma GAS6 level in patients with acute heart failure (AHF). MI was mimicked by permanent left anterior descending artery ligation in global GAS6 knockout and cardiac fibroblast-specific GAS6 overexpression via AAV9 (adeno-associated virus serotype 9) mice to study the function of GAS6 during post-MI cardiac remodeling. Primary cardiac fibroblasts from wild type mice or GAS6 knockout mice were used to explore the effect of GAS6 on cardiac fibroblasts activation and proliferation. Coimmunoprecipitation assays were conducted to identify the interaction between GAS6 and p53.
RESULTS The expression level of GAS6 significantly increases in plasma of the patients with AHF and infarcted area at day 7 and day 28 after myocardial infarction in mice, while there is no significant change in expression level at day 3 after MI and in the non-infarcted area. It indicates that GAS6 may play a critical role in cardiac repair after MI. The results of echocardiography and histology demonstrated that GAS6 knockout in mice protected the hearts against MI-induced cardiac dysfunction. Also, GAS6 knockout aggravates cardiac fibroblasts senescence in vivo and in vitro, which resulted in a notable decline in the population of myofibroblasts. Mechanistically, GAS6 knockout significantly reduces the activation of ERK1/2 and further decreases the activation tripartite motif containing 72 (TRIM72), which reduces degradation of p53 and farther promote cellular senescence. Coimmunoprecipitation assays were conducted and found that there was a direct interaction between TRIM72 and p53. The role of GAS6 in MI-induced cardiac remodeling was mediated by the ERK1/2/TRIM72/p53/p16 signaling pathway. Conversely, overexpression of GAS6 can significantly aggravate fibroblasts activation and reduce cellular senescence in vitro. In addition, overexpression of GAS6 specifically in cardiac fibroblasts exacerbates post-myocardial infarction fibrosis and impair cardiac function in vivo. Furthermore, we demonstrated that addition of ERK1/2 inhibitor can abolish ability of GAS6 overexpression to activate ERK1/2/TRIM72/p53/p16 pathway and exacerbate fibrosis and reduce cellular senescence.
CONCLUSIONS We identified GAS6 as a key therapeutic target for MI induced cardiac remodeling. We also found a novel mechanism regulated by GAS6. GAS6 promotes activation of ERK1/2 and exacerbates cardiac fibrosis and reduces cellular senescence by the ERK1/2/TRIM72/p53/p16 pathway.
GW35-e1182
Li Yuetong
Department of Physiology and Pathophysiology, School of Basic Medicine, Air Force Medical University, Xi’an, Shaanxi 710032, P.R. China
OBJECTIVES Ketone bodies, the main component is β-hydroxybutyrate (βOHB), which is produced in the liver and metabolized by extra-hepatic tissues. The heart has a high energy demand and ketone oxidation is an important source of myocardial ATP production. Ketone oxidation rates are important regulated by ketone oxidative enzymes, such as key enzymes of ketone oxidation d-β-hydroxybutyrate dehydrogenase I (BDH1). Reviewing the literature also confirms that cardiac-specific BDH1 overexpression ameliorates oxidative stress and cardiac remodeling in pressure overload-induced heart failure and evidence suggests that ketones also act as significant signaling molecules influencing cardiovascular function, such as modulating the NLRP3, FGF21 and so on. Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in aging. Telomeres attrition lead to increased cellular senescence and apoptosis, resulting in reduced cell number and function, leading to overall tissue and organ dysfunction. Although others have demonstrated presence of short telomeres in genetic cardiomyopathic and heart failure cardiomyocytes, little is known about how short-telomere cardiomyocytes (sTL-CMs) cause or exacerbate cardiovascular disease.
METHODS Search articles and databases, and analyze the RNA-sequencing data of sTL-CMs and isolated cardiomyocytes from miceof pressure overload (by transverse aortic constriction, TAC). Establish an in vitro (use AC16 or H9C2 cell line) model of cardiomyocyte senescence induced by hydrogen peroxide (H2O2) to mimic oxidative stress, representing an aging state akin to that observed in cardiomyocytes with shortened telomeres. Cell senescence will be evaluated by senescence-associated β-g alactosidase (SA-β-Gal) activity. The expression of BDH1 in the cellular senescence model was analyzed through western blot and RT-qPCR. TAC model was established in vivo and use telomere Q-FISH to detect telomere length shortening. Echocardiography and histological analysis were utilized to assess the extent of cardiac damage as well as assessing the success of the modeling procedure. Using adeno-associated virus (AAV) to deliver the BDH1 gene, perform intramyocardial injections to achieve BDH1 overexpression in mouse cardiac cells. These mice were then used to investigate the impact of BDH1 overexpression on cardiac function in mice with TAC.
RESULTS We performed RNA-seq analyses on cardiomyocytes with short telomeres (sTL-CMs) and normal telomeres (nTL-CMs), and the results revealed that among the significantly downregulated genes, BDH1 expression was notably prominent. Similarly, in the analysis of RNA-seq results from TAC model mice, a statistically significant decrease in BDH1 expression was also observed. Utilizing the CCK-8 assay to screen for an appropriate concentration of hydrogen peroxide to induce senescence in AC16 cells. The senescent AC16 cells was achieved, with a significant increase in p21 (CDKN1A) confirmed by Western Blot.
CONCLUSIONS Our study indicates that sTL-CMs contribute to or exacerbate cardiovascular disease, with a critical link to BDH1-regulated ketone metabolism. This study innovatively presents ketone body metabolism as a pivot connecting the cellular aging of cardiomyocytes to cardiovascular diseases, elucidating a broader relationship from a molecular perspective. It explains the dual role of ketones as an energy source and their potential protective effect against pathological remodeling induced by pressure overload in the heart. In the future, ketone body metabolism may be potentially a novel therapeutic target in heart failure.
GW35-e1202
Du Tang1, Junpeng Fan2, Junbo Li3, Peixiang Lan3, Chaoyang Sun2, Xiaoquan Rao1
1Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
OBJECTIVES Cardiac transplantation is a crucial treatment for end-stage heart disease, but acute rejection remains a major barrier to transplant success and long-term survival. Increasing evidence suggests that neutrophils in the innate immune system play a significant role in transplant immune responses. However, the specific mechanisms by which neutrophils contribute to acute rejection in cardiac transplantation are not well understood. This study aims to systematically investigate the dynamic changes in neutrophils during acute rejection in cardiac transplantation, elucidating their specific roles in this process. The goal is to optimize transplant management and identify new immunoregulatory targets.
METHODS This study employed single-cell sequencing to perform high-resolution gene expression analysis of the grafts, combined with TCR sequencing to analyze T cell clonal expansion post-transplantation. Spatial transcriptomics was used to determine the precise locations and microenvironments of neutrophils within the tissue, thereby understanding their spatial dynamics during rejection. Full-spectrum flow cytometry was utilized for precise phenotypic analysis, detecting activation markers and functional states of neutrophils.
RESULTS Single-cell sequencing identified a total of 41 clusters. We accurately identified four functionally distinct neutrophil subsets at single-cell resolution, exhibiting significant dynamic features during transplant rejection. Intercellular communication analysis revealed that some donor immune cells “betrayed” and exhibited strong chemotactic effects on neutrophils and other immune cells. Neutrophils underwent a unique differentiation trajectory within the graft, transitioning from classical to interferon-related neutrophils, and ultimately to antigen-presenting neutrophils. These antigen-presenting neutrophils, compared to other subsets, exhibited higher degranulation activity and high expression of MHC I and MHC II, significantly activating T cells. Spatial transcriptomics identified 13 cellular niches, with neutrophils consistently located in specific niches closely related to the rejection process. Spatial communication analysis showed that in the early stages of rejection, neutrophils interacted closely with parenchymal cells via surface molecules.
CONCLUSIONS This study systematically reveals the critical role of neutrophils in acute rejection of cardiac transplantation using multiple advanced techniques. These findings provide new insights into the role of neutrophils in acute rejection of cardiac transplantation and suggest potential targets for developing new immunoregulatory strategies.
GW35-e1206
Jiangyou Wang1,3, Chunyan Zhang2, Shuya Li1,2, Ruisong Huang2, Xiaolu Cao2
1Department of Cardiology, Wuhan Asia General Hospital
2Department of Medicine, Wuhan University of Science and Technology
3Department of Cardiology, Wuhan Asia Heart Hospital
OBJECTIVES This study aims to elucidate the pathological mechanism underlying myocardial ischemia/reperfusion (MI/R) for developing safe, effective and specific drugs based on pathological targets, and to intervene timely to repair the myocardial injury of ischemic area in early stage.
METHODS Differentially expressed genes and KEGG pathway enrichment of myocardial ischemia and early reperfusion transcriptional profiles were analyzed using the transcriptional data of GSE6381 from the Gene Expression Omnibus database. Key pathological target genes were identified by analyzing MI/R-related pathways. A machine learning method, natural language processing-based embedding and traditional 2D fingerprints, was employed to encode chemical structures from the CHEMBL. Following batch molecular docking with the pathology target genes, respectively, the set of drug candidates for the treatment of MI/R injury was obtained by predictive assessment of the binding affinity of drugs to the target genes. Secondary screening criteria, including pharmacological effects, clinical trials, and patent status, were applied to finalize potential therapeutic drugs, which were pharmacologically validated in MI/R rat models. The efficacy of potential therapeutic drugs Roxadustat in alleviating MI/R whether through the ferroptosis pathway was assessed by measuring myocardial infarction volume, cardiomyocyte ultrastructure, iron deposition and expression of ferroptosis-related proteins.
RESULTS A total of 447 differentially expressed genes were identified during myocardial ischemia and early reperfusion, including MAP3K12, LTBR, P53, CREBBP, SLC7A4, IL-1β, etc. The mainly affected signaling pathways included MAPK, ferroptosis, Wnt, HIF-1, and NF-κB. Three key pathological molecules for machine learning, MAPK, PHD, and P53, were identified from the transcriptional profiling. 1500 candidate drugs were obtained from the CHEMBL through machine learning, ultimately identifying Roxadustat by secondary screening criteria as a potential therapeutic drug for MI/R. In vivo, MI/R-induced abnormal myocardial and cellular changes, including iron deposition and ferroptosis activation, were significantly reversed by 20 mg/kg Roxadustat that was evidenced by reduced myocardial infarct size, lower apoptosis rates, intact mitochondrial structure, and decreased iron deposition. Additionally, myocardial iron deposition decreased, and the expression of ferroptosis pathway proteins SLC7A11 and GPX4 increased, enhancing glutathione (GSH) activity after Roxadustat treatment. However, Erastin-induced the activation of the ferroptosis pathway in Roxadustat-treated MI/R rats, resulted in severely damaged to cardiomyocyte and mitochondrial ultrastructure, increased iron deposition, reduced expression of SLC7A11 and GPX4, decreased GSH activity, and inhibited the cardioprotective effects of Roxadustat.
CONCLUSIONS Transcriptome analysis combined with machine learning facilitates efficient and precise identification of potential therapeutic drugs for treating MI/R injury. Roxadustat effectively alleviates MI/R injury by inhibiting the ferroptosis pathway through activation of the SLC7A11-GSH-GPX4 signaling axis. This study reveals a potential new strategy for treating of acute myocardial infarction and offers new insights into developing clinical indications for Roxadustat.
GW35-e1207
Sheng Xu1, Y Xu1, Feng Liu2, Wenhui Yue1
1Shanghai Tenth People’s Hospital
2Shanghai Sixth People’s Hospital
OBJECTIVES Kruppel-like factor 9 (Klf9) is a ubiquitously expressed member of the Sp1 C2H2-type zinc finger family of transcription factors. Previous studies have shown that KLF9 is downstream of the glucocorticoid receptor and is involved in regulating the metabolism and development of many types of cells. However, Whether KLF9 is involved in regulating the pathological process of myocardial infarction (MI) remains unclear. Our study will reveal that KLF9 has an important role in the early inflammatory response after acute myocardial infarction.
METHODS A model of MI through surgical ligation of the left anterior descending artery was utilized to detect differences between WT and Klf9−/− mice in survival rate and cardiac function etc. Immunohistochemical staining was performed to detect the fibrosis markers and angiogenesis. Heart non-cardiomyocytes from WT and Klf9−/− mice 3 days after MI were selected for single-cell RNA sequencing to discover cell populations and genes with significant differences. Subsequently, immunofluorescence staining and flow cytometry were used to verify the differences in macrophage polarization and number between WT and Klf9−/− groups after MI. Western and qPCR were used to detect related protein and genes expression in tissues and cells. WT and Klf9−/− BMDMs were isolated for in vitro stimulation and verification. CHIP and luciferase reporter gene experiments were used to detect the binding of KLF9 and target gene promoters.
RESULTS Klf9 deficiency did not affect infarct size and myocardial enzymes after MI, but the Klf9−/− mice had thinner ventricular walls, worse cardiac function, higher mortality and cardiac rupture rates. Collagen deposition, fibroblast activation, and angiogenesis of Klf9−/− mice were significantly reduced too. 3 days after MI, the number of infiltrating macrophages and the proportion of M2 macrophages in Klf9−/− mice were reduced compared with those in the WT group, while the expression of inflammatory pathway genes were higher. Compared with the WT group, Stat1 expression in Klf9−/− cardiac macrophages was decreased 1 day after MI, but increased 3 days late. After LPS and IFN-γ stimulation, Klf9 inhibited the expression of Stat1 and its downstream genes in BMDMs. Mechanistically, Klf9 can regulate the expression of Stat1 by directly binding to the two promoters of Stat1.
CONCLUSIONS Our study found that Klf9 regulates the response of macrophages to IFN-γ signals by regulating the expression and phosphorylation of Stat1 after MI, that is, it enhances the chemotaxis of macrophages in the early stage of MI, and inhibits excessive inflammatory response and promotes macrophage M2 polarization in the middle stage of MI, finally promotes moderate repair after MI. Klf9 can regulate the balance between pro-inflammatory and anti-inflammatory effects in macrophages after MI, and its agonists may be potential targets for future treatment of post-MI repair.
GW35-e1214
Yuwu Chen1,2, Biyi Xu1,2, Haibo Jia1,2, Bo Yu1,2
1The 2nd Affiliated Hospital of Harbin Medical University
2The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin
OBJECTIVES Emerging evidence indicates that oxidative stress and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome mediated pyroptosis have a considerable influence on the pathogenesis of atherosclerosis. Quercetin is known to possess atherosclerosis protective effects. However, the effects and underlying mechanisms of quercetin on pyroptosis and oxidative stress are largely unclear. Here, we evaluate the effect and the underlying mechanism of quercetin on macrophage pyroptosis in vivo and vitro.
METHODS The carotid plaques and monocytes from atherosclerotic patients were used to evaluate the macrophage/monocytes pyroptosis level. ApoE−/− mice were divided into ND group (feed with normal diet), HD group (feed with high fat diet for 16 weeks) and Quer + HD group (feed with high fat diet supplemental with 1% quercetin for 16 weeks). Oil red, Masson and HE staining were used to evaluated the plaque area and collagen content in the plaque. The serum of MDA, GSH, SOD and IL-1β were also analyzed. To explore the molecular mechanisms, we treated the THP-1 original macrophages with oxldl (100 ng/mL) and examined the effects of quercetin on pyroptosis and the activation of NLRP3 inflammasome. Furthermore, molecular binding and amino residues mutation of KEAP1 were used to assess the significance of NRF2 signaling in quercetin functions in macrophages.
RESULTS We found that pyroptotic macrophages and monocytes were more frequently observed in coronary heart disease (CHD) and acute myocardial infarction (AMI) patients. Nevertheless, quercetin oral administration significantly attenuates the progression of atherosclerosis, characterized by reduced plaque area, increased collagen content, decreased oxidative stress and suppressed macrophage pyroptosis in ApoE−/− mice. In THP-1 original macrophages, quercetin suppresses macrophage pyroptosis induced by ox-LDL, demonstrated by inhibiting the activation of NLRP3 inflammasome, lowering the level of oxidative stress and activating NRF2 pathway. Mechanistically, quercetin promotes NRF2 to dissociate from Kelch-like ECH-associated protein 1 (KEAP1), enhances NRF2 nuclear translocation, increases the expression of antioxidant proteins, attenuates ROS generation and suppresses macrophages pyroptosis. Moreover, molecular docking is performed to observe the interaction between quercetin and KEAP1, the results suggests that quercetin could bind with KEAP1 competitively at Arg415 and Arg483. In order to verify the binding sites, KEAP1 mutated at Arg415 and Arg483 to Ser (R415S or R483S) or wild type was transfected into macrophages. The anti-pyroptotic and anti-oxidant effects of quercetin were abrogated by KEAP1 Arg483 mutation obviously, but not Arg415 mutation.
CONCLUSIONS In conclusion, these findings illustrate that quercetin protects against atherosclerosis in vivo and in vitro, partially by suppressing macrophage pyroptosis and ROS overproduction via binding with KEAP1 at Arg483 competitively.
GW35-e1220
Xino Qun Wang
Rui Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, P.R. China
OBJECTIVES Atherosclerosis is predisposed at bifurcations, branch points and arterial curvatures where the blood flow is disturbed. Deposition and oxidative modification of low-density lipoprotein (LDL) in the subendothelial intima is an early event in the pathogenesis of atherosclerosis. However, the effect of disturbed flow (d-flow) on LDL oxidation and the underlying mechanisms remain unclear. In this study, we investigated the role of 12/15-lipoxygenase (LOX) in LDL oxidation in endothelial cells (EC) and the development of atherosclerosis at d-flow sites.
METHODS En face immunofluorescence was performed to analyze the expression of 12/15-LOX in EC under exposure to different flow patterns. Protein expression and LDL oxidation was studied in vitro by using 2 different flow apparatuses. Animal model of d-flow was established by partial ligation of the carotid artery.
RESULTS En face staining exhibited a significant increase in 12/15-LOX protein expression in EC in areas exposed to d-flow than those exposed to steady flow (s-flow). Carotid partial ligation in ApoE knockout mice led to substantially increased deposition of oxidized LDL in the subendothelial intima and formation of atherosclerotic plaques in the carotid artery, whereas these detrimental effects by d-flow were markedly attenuated in ApoE/12/15-LOX double knockout mice. In cultured EC, d-flow generated by a reversal flow pump markedly promoted the expression of 12/15-LOX and translocation of the protein onto the cell membrane. Inhibition of 12/15-LOX in EC, either by knockdown with its specific siRNA or a pharmacological inhibitor, suppressed production of 15s-HETE and LDL oxidation in response to d-flow. Mechanically, we found d-flow induced the expression of 12/15-LOX by activating a specific responsive element in the 12/15-LOX promoter through recruiting a shear stress-sensitive transcriptional factor SREBP2. Chromatin immunoprecipitation further confirmed the interaction of SREBP2 with the promoter of 12/15-LOX upon d-flow exposure.
CONCLUSIONS These data define an essential role of 12/15-LOX in promoting the pathogenesis of atherosclerosis under d-flow by increasing LDL oxidation in EC through SREBP2 signaling.
GW35-e1221
Minglu Ma1,2, Jian Liu1,2
1Department of Cardiology, Peking University People’s Hospital, Beijing, China
2Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People’s Hospital, Beijing, China
OBJECTIVES As limited knowledge is available for the pathogenesis and therapeutics of heart failure with preserved ejection fraction (HFpEF), we aimed to find a functional metabolite for the diagnosis and treatment of HFpEF. Considering the important role of metabolic and immune dysfunction in the development and progression of HFpEF, we were interested to explore whether this newly discovered functional molecule affects HFpEF by mediating an immune-metabolic cross-talk.
METHODS GEO database were used to analyze the differential expressed genes (DEG) in heart tissues between HFpEF and normal rats. Using website Metascape, we performed enrichment analysis for all DEG and paid close attention to the top 10 pathways associated with HFpEF. After checking gene list involved in key signaling pathways and finding Cyp1a1, which has the largest |logFC| value, gene set enrichment analysis (GSEA) were performed using R software package. Though Mendelian Randomization analysis, we explored the relationship between Cyp1a1 and HFpEF and IL-6. Adult male mice were placed on a high fat diet plus L-NAME in drinking water for 15 consecutive weeks to induce HFpEF. Echocardiography were used to evaluate cardiac function. ELISA were used to detect plasma Cyp1a1 and IL-6 levels in HFpEF mice and HFpEF patients. qPCR, WB and co-IP were used to detect Cyp1a1 and downstream signaling pathway AhR/STAT3/IL-6 in HFpEF mice heart.
RESULTS By analyzing data from GEO database, a total of 170 genes were found to have significant expression changes in heart tissues of HFpEF rats compared with normal rats, of which 148 genes were down-regulated and 22 genes were up-regulated. Using website metascape, we found Cyp1a1 with largest difference in the top pathway associated with HFpEF. Using Mendelian randomization, Cyp1a1 is associated with HFpEF and IL-6. In vivo, compared with normal wild-type mice, Cyp1a1 was significantly down-regulated in heart tissues and peripheral blood samples of HFpEF mice. Using Western bloot and co-IP, up-regulated triglycerides may be the direct factor leading to the down-regulation of Cyp1a1. These results were confirmed in peripheral blood samples obtained from HFpEF patients and normal human. Through Western bloot and qPCR, we found that down-regulated Cyp1a1 promotes the progression of HFpEF by activating the AhR/STAT3/IL-6 signaling pathway in mice heart.
CONCLUSIONS When HFpEF occurs, down-regulated Cyp1a1 promotes the progression of heart failure with preserved ejection fraction by activating the AhR/STAT3/IL-6 signaling pathway.
GW35-e1238
Tianlun Li, Zhaoliang Shan
Medical School of Chinese PLA/Chinese PLA General Hospital
OBJECTIVES This study aims to investigate the effects and underlying mechanisms of omentin-1 on atrial fibrosis and atrial fibrillation (AF).
METHODS A mouse model of atrial fibrosis was established by subcutaneously implanting osmotic pumps to administer angiotensin II (Ang II) or saline for four weeks. Plasma levels of omentin-1 were measured using ELISA. An adipose tissue-specific adeno-associated virus (AAV) system was used to construct omentin-1 overexpression mice. LA reservoir, conduit, and contractile strain were measured using speckle-tracking echocardiography from a modified parasternal long-axis window. The extent of atrial fibrosis was assessed using Masson staining. Programmed transesophageal electrical stimulation were used to induce atrial fibrillation. The expression of fibrosis-related proteins was evaluated by Western blot, and α-SMA was detected by immunohistochemistry to assess fibroblast activation. Atrial tissue was harvested and dissociated into single-cell suspensions using enzymatic digestion. Atrial fibroblasts were sorted by two-color flow cytometry as Thy1-positive (Thy1+), lineage-negative (Lin: Ter119−CD45−CD11b−CD31−) populations. These sorted atrial fibroblasts from the Sham, Ang II, and AAV-OMT + Ang II groups were then subjected to proteomic analysis. Bioinformatics analysis was performed to explore the effects of omentin-1 on atrial fibroblasts. Finally, the in vitro effects of omentin-1 on Ang II-induced fibroblast-related protein expression were validated.
RESULTS In vivo experiments showed that Masson staining indicated disrupted atrial structure and significant collagen fiber increase in Ang II-treated mice. Plasma levels of omentin-1 were significantly lower in the model group compared to the control group. Immunofluorescence and ELISA confirmed successful omentin-1 overexpression. Omentin-1 overexpression mice exhibited a significantly reduced incidence and duration of AF. LA reservoir, conduit, and contractile strain were significantly improved in AAV-OMT + Ang II mice compared with Ang II. Western blot and immunohistochemistry results showed decreased expression of COL-I, COL-III, TGF-β, MMP2, and TIMP1, and reduced fibroblast activation in the omentin-1 overexpression group. Proteomic analysis identified 1691 differentially expressed proteins (DEPs) between the Sham and Ang II groups’ atrial fibroblasts and 536 DEPs between the AAV-OMT + Ang II and Ang II groups. A Venn diagram revealed 216 common DEPs, with trend analysis showing 200 proteins exhibiting opposite trends. Protein interaction network and MCODE module analysis indicated that these trend proteins were mainly involved in cell adhesion and collagen catabolic processes, with the extracellular matrix as the primary cellular component. KEGG analysis identified the PI3K-Akt signaling pathway and focal adhesion as the top two pathways by gene ratio. Using six algorithms in cytoHubba, IRS1 and COL1A2 were identified as hub proteins. In vitro experiments, pretreatment with exogenous human omentin-1 protein resulted in decreased expression of collagen proteins compared to the Ang II group, while IRS1 protein levels and activity increased. This was accompanied by elevated phosphorylation levels of PI3K and Akt. The protective effects of omentin-1 were inhibited by the IRS1 inhibitor (NT157).
CONCLUSIONS Omentin-1 mitigates atrial fibrosis and reduces the incidence of AF by inhibiting the expression of fibrosis-related proteins and fibroblast activation, primarily through the regulation of IRS1. Its mechanism likely involves the regulation of the PI3K-Akt signaling pathway and focal adhesion pathway.
GW35-e1242
XIngxu Zhang
Shanghai Tenth People’s Hospital
OBJECTIVES Macrophages are multifunctional cells of the innate immune system, playing a crucial role in homeostasis. However, the regulation mechanism of the polarization phenotype and metabolic characteristics of macrophages by the tissue physical properties of the extracellular matrix (ECM) in the microenvironment after myocardial infarction (MI) is still poorly understood.
METHODS Using transcriptome data from the infarcted border area of human MI (EGAS00001006330), differentially expressed genes of macrophages in ECM with different stiffness were screened, and MCPIP1 was identified as an important differentially expressed gene. In subsequent experiments, we used MCPIP1 Δ LysM mice as the experimental group and MCPIPfl/fl as the control group to explore the polarization phenotype and metabolic characteristics of macrophages in MI modeling.
RESULTS MCPIP1 is highly expressed in macrophages in the microenvironment of myocardial infarction. It can inhibit IFN γ/LPS induced M1 macrophages and significantly increase IL4/IL10 induced M2 macrophages by inhibiting NFκB and promoting STAT6 activation. However, macrophages lacking MCPIP1 have difficulty sensing changes in ECM microenvironment stiffness and still maintain their M1 pro-inflammatory phenotype, making it difficult to transition to the M2 repair phenotype and continuously release various inflammatory factors such as IL-1b and IL-6. In addition, flow cytometry sorting of MCPIP1 Δ LysM macrophages in the infarcted border area showed reduced MTT ability, making it difficult to replenish the large number of myofibroblasts required for cardiac repair. Compared with the control group mice, MCPIP1 Δ LysM mice showed significantly increased mortality and decreased cardiac function after MI surgery. When MCPIP1 deficient macrophages (BMDM and THP-1) constructed in vitro were cultured in a hard matrix (high concentration gelatin), seahorse results showed that MCPIP1 deficiency resulted in sustained enhanced glycolysis metabolism of macrophages, which relied on glycolysis metabolism to produce a large number of inflammatory factors such as IL-1b and TNF-a. Compared with the control group, the CD86 (M1 marker)/RG1 (M2 marker) ratio was significantly increased. In addition, the cytoskeleton is a key structure for macrophages to sense ECM stiffness, pressure, and shear force. Ghost pen peptide staining showed that macrophages lacking MCPIP1 exhibited reduced F-actin, significantly weakened migration, deformation, and ability to perceive external mechanical stress. On the 7th day after MI surgery, flow cytometry was used to identify macrophages in the infarct border area for RNA seq detection. The comparison of MCPIP1 Δ LysM and MCPIPfl/fl results suggests that the ATF3/AP1S2 axis is a key signaling pathway for MCPIP1 to exert stress sensing and transcriptional regulation in macrophages.
CONCLUSIONS MCPIP1 is a key protein for macrophages to perceive the mechanical and physical strength of the ECM microenvironment after myocardial infarction. Macrophages in the infarcted border area sense changes in the mechanical stress of surrounding tissues through MCPIP1, regulate and inhibit glycolysis through the ATF3/AP1S2 axis, and promote the transition of macrophages from M1 to M2, thereby achieving functions such as inhibiting inflammation, promoting collagen secretion, and maintaining mechanical strength in the infarcted area to protect the heart.
GW35-e1247
Zupei Miao
Chinese People’s Liberation Army General Hospital
OBJECTIVES Although sleep quality and sleep duration have been related to cardiovascular endpoints, the mechanism of how sleep deprivation causes atrial fibrillation remains unclear. Besides, Brain and muscle arnt-like protein 1 (Bmal1), a crucial transcription factor, is in charge of regulating circadian rhythm and is involved in the occurrence of multiple heart diseases. Hence, we aimed to investigate the effect of acute sleep deprivation on the level of Bmal1 in atrium and to find out whether it is related to the key factors of atrial fibrillation occurrence including calcium ion and its regulating proteins.
METHODS A total of 80 healthy C57BL/6J male mice aged 6–8 weeks were randomly divided into the sleep deprivation group and the control group. The acute sleep deprivation mouse model was established using a modified multi-platform water environment method for 7 consecutive days. The mice were placed on the platforms for 20 h daily, taken out, dried, and then placed back in clean and dry cages for 4 h of rest (17:00–21:00). This cycle was repeated seven times. For the control group, mice were placed in normal cages. After 7 days of modeling, in both groups, the level of Bmal1 mRNA in the atrium was assessed using RT-qPCR, while the level of Bmal1 protein was assessed by Western blotting. The levels of Ca2+ handling proteins including Cav1.2, NCX1, and RyR2, and electrical conduction gap junction channel Cx40, and PI3K-AKT signal pathway proteins in the atrium were also detected by using Western Blotting. Masson’s trichrome staining and hematoxylin and eosin staining were performed in heart tissue to evaluate the structural changes and the degree of fibrosis after sleep deprivation.
RESULTS (1) Clock gene Bmal1 expression: compared with the control group, both the mRNA and protein levels of Bmal1 decreased in the sleep deprivation group (reduced by 17.9% and 83.3% vs. control group respectively). (2) Ca2+ handling proteins: compared with control group, sleep deprivation downregulated the expression of Na+/Ca2+ exchanger1 (NCX1) (reduced by 25.0%) and increased ryanodine-receptor channel type-2 (RyR2) level (increased by 89%). However, it had little effect on Cav1.2 and Cx40. (3) PI3K-AKT signal pathway: the difference of the level of PI3K and AKT protein in the two groups were not significant. (4) Structure and fibrosis: the degree of fibrosis was higher in the sleep deprivation group than in the control group, at 17.61% and 9.49%, respectively.
CONCLUSIONS These findings show that sleep deprivation may increase the incidence of atrial fibrillation by raising the atrial degree of fibrosis and increasing the level of intracytoplasmic Ca2+ through decreasing the Ca2+ efflux protein NCX1 and increasing the endoplasmic reticulum calcium-pumping protein RyR2. Further study on the relationship between the clock gene Bmal1 and Ca2+ handling proteins is needed and the levels of p-PI3K and p-AKT were to be assessed in the subsequent experiments.
GW35-e1260
Xuhong Wang1,2,3, Tingting Tang1,2,3, Zihua Zhou1,2,3, Xiang Cheng1,2,3
1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, Wuhan, China
3Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
OBJECTIVES Inflammatory response has been linked to cardiac repair and ventricular remodeling after myocardial infarction (MI). Thymic stromal lymphopoietin (TSLP), as a pivotal orchestrator of homeostasis and inflammation belonging to the interleukin-2 cytokine family, has been implicated in various pathological conditions related to immunity. However, its significance and function in cardiac repair after MI remain uncertain. In the present study, we hypothesized that TSLP may play a role in cardiac ventricular remodeling following MI.
METHODS Wild-type (WT) and TSLP receptor (TSLPR)-knockout (Crlf2 −/−) mice underwent MI by ligation of the left descending artery. To mimic the in vivo absence of TSLP/TSLPR signaling, we utilized TSLPR knockout mice (Crlf2 −/−). We employed western blotting, real-time quantitative PCR, and flow cytometry to analyze TSLP expression, determine its cellular sources, and assess TSLPR levels on immune cells in infarcted hearts and spleens. Furthermore, we used Masson’s trichrome staining, immunofluorescence, and echocardiography to evaluate the role of TSLP in adverse left ventricle remodeling and heart failure progression. Flow cytometry was also applied to delve deeper into the inflammatory response induced by MI in the context of TSLP/TSLPR deficiency. Lastly, RNA sequencing provided transcriptional insights.
RESULTS TSLP expression was upregulated in the infarcted heart, with a peak observed on day 7 post MI. The expression of TSLP was mainly observed in cardiomyocytes located within the border area of the infarction, while dendritic cells showed the highest level of TSLPR expression in cardiac tissue and spleen. Compared to WT mice, Crlf2 −/− mice exhibited significantly reduced survival and worsened cardiac function after MI. Concomitantly, Crlf2 −/− mice exhibited augmented interstitial fibrosis and increased cross-sectional area of cardiomyocytes, accompanied by a reduced proportion of CD31+ staining. However, there was no apparent change in the proportion of TUNEL+ cardiomyocytes within the border zone compared to WT mice. Mechanistically, a reduction in regulatory T cells (Treg) and a decrease in the ratio of Treg to conventional CD4+T cells, and an increased abundance of innate immune cells and their subsets, were observed in the infarcted hearts of Crlf2 −/− mice. Moreover, TSLP regulated CD4+T cell activation and proliferation at baseline and after MI, with a greater impact on Treg cells than on conventional T cells, as indicated by the reduced expression of CD69 and Ki67 on these cells. Furthermore, RNA-seq analysis revealed significant downregulation of genes involved in T cell activation and TCR signaling in the infarcted cardiac tissue of Crlf2 −/− mice compared to their WT counterparts.
CONCLUSIONS Collectively, our data indicate a critical role for TSLP in facilitating cardiac repair and conferring protection against MI, primarily through regulating T cell responses, which may provide a potential novel therapeutic approach for managing heart failure after MI.
GW35-e1267
Xihan Fan, Juxiang Hou, Wei Chen
The First Affiliated Hospital of Kunming Medical University
OBJECTIVES To evaluate whether can iron chelation therapy improves cardiac function in iron overload cardiomyopathy (IOC) rats via cardiac magnetic resonance feature-tracking (CMR-FT).
METHODS IOC rats model was induced by intraperitoneal injection of iron dextran for 2 months. Subsequently, 7 IOC rats received saline injections for another 2 months as the IOC group, while 5 IOC rats were treated with deferoxamine (DFO) for the same period, forming the IOC + DFO group. Additionally, 7 healthy rats received saline injections for 4 months as the control group. All rats underwent a 7.0 T CMR scan to assess myocardial iron overload, left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and myocardial fibrosis via using cine, T2 mapping, and late gadolinium enhancement (LGE) imaging, respectively. Post-CMR, all rats underwent open-chest blood collection for serum iron level assessment, and heart tissues were examined histologically for cellular morphology (HE staining), iron deposition (Prussian blue staining), and fibrosis (Masson staining). Finally, the ultrastructure of the cardiomyocytes was observed under the transmission electron microscopy (TEM) and the severity of mitochondrial injury was quantified by Image J.
RESULTS Compared with the control group (37.5 ± 12.5 μmol/L), serum iron levels were significantly elevated in the IOC group (368.6 ± 181.0 μmol/L) and IOC + DFO group (106.1 ± 32.2 μmol/L). The T2 value, measured in the mid-layer of the LV septum wall, was significantly decreased in the IOC group compared with the control group but showed no significant difference when compared with the IOC + DFO group. Similarly, the LVEF and GLS were decreased in the IOC group compared with the control group, yet not significantly different from the IOC + DFO group. HE staining showed normal myocardial cell arrangement across all groups, with no degeneration or necrosis in both the three groups. Prussian blue staining identified extensive iron deposits in the interstitial tissue of myocardium in both the IOC and IOC + DFO groups. Masson staining showed no evidence of blue-stained areas, indicating a negative result for myocardial fibrosis. TEM revealed injured myocardial mitochondria characterized by ruptured outer membranes, reduced cristae, and vacuolization. Quantization the ratio of mitochondrial vacuolization in 15000× magnification images showed significant differences between the IOC group and the IOC + DFO group (9.86 ± 0.44% vs. 15.99 ± 0.41%).
CONCLUSIONS After iron chelation therapy, the iron overload in the blood was relieved, but myocardial iron overload persisted with no significant improvement in cardiac function in IOC rats, which may be related to mitochondrial injury.
GW35-e1269
Yu Huahui, Jiao Xiaolu, Lv Qianwen, Wang Yu, Gao Xiaoqian, Han Lijie, Sun Xuechun, Qin Yanwen
Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease
OBJECTIVES Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular disease, but there is a lack of approved medical therapies to prevent AAA progression and rupture. Activating Transcription Factor 4 (ATF4) has been established to be involved in cardiovascular diseases, such as heart failure and calcific aortic valve disease. However, the role of ATF4 in the pathogenesis of AAA remains unclear.
METHODS We profiled ATF4 expression in the human AAA tissues and mouse model of AAA by Western blotting and immunofluorescence staining. We induced experimental AAA in ATF4-knockdown ApoE−/− mice and ATF4-overexpression ApoE−/− mice to investigate the effect of ATF4 on AAA. We conditionally deleted ATF4 in macrophages in vivo to investigate the role of ATF4 in the macrophage in AAA. RNA sequencing, ChIP sequencing and standard ChIP analyses were performed to identify key target genes regulated by ATF4 in macrophages.
RESULTS We found that ATF4 expression were significantly increased in patients with AAA and an AAA mouse model, and was mainly confined to macrophages in arteries. ATF4 knockdown significantly attenuated aneurysm formation in experimental mouse model of AAA, while ATF4 overexpression promoted the development of AAA. RNA sequencing suggested that ATF4 was strongly related to the biological functions of acute inflammatory response. Macrophages-specific ATF4 knockout significantly reduced the incidence and development of AAA, and reduced M1 polarization of macrophages in mice. Sphingomyelin phosphodiesterase 3 (SMPD3), which regulates the inflammatory responses in monocytes/macrophages, has been identified as a target gene of ATF4. Consequently, ATF4 induces M1 polarization of macrophages through the activation of SMPD3, thereby promoting inflammatory responses.
CONCLUSIONS Together, these results suggest that ATF4 mediated macrophage M1 polarization by regulating the expression of target genes SMPD3, leading to an increased inflammatory response, which further promotes the formation and development of AAA. These findings suggest ATF4 may be a new therapeutic target for AAA.
GW35-e1273
Lijie Han, Yanwen Qin
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES High-fat diet (HFD)-induced hyperlipidemia, which is associated with gut microbiota disturbances, remains a major public health challenge. Glycerolipid metabolism is responsible for lipid synthesis and is thus involved in the development of hyperlipidemia. However, possible associations between the HFD-modulated gut microbiome and the glycerolipid metabolism pathway remain unclear.
METHODS Hamsters were fed a HFD for 4 weeks to establish a hyperlipidemia model. Fecal and plasma samples collected from hamsters fed a HFD or a normal chow diet (NCD) were used for integrative metagenomic and untargeted metabolomic analyses to explore changes in the composition and functions of the gut microbiota, and circulating metabolites. Spearman rank correlation analysis was used to explore correlations between gut microbes and circulating glycerolipid metabolites, gut microbes and lipids, and circulating glycerolipid metabolites and lipids.
RESULTS Circulating lipids in hamsters fed 4-week HFD were increased compared with those in NCD hamsters (total cholesterol, 2.92 ± 0.16 vs. 28.22 ± 3.12 mmol/L, P < 0.001; triglyceride, 1.67 ± 0.15 vs. 16.55 ± 4.04 mmol/L, P = 0.003; LDL-C, 1.42 ± 0.11 vs. 38.67 ± 3.68 mmol/L, P < 0.001; HDL-C, 3.23 ± 0.29 vs. 24.61 ± 1.86 mmol/L, P < 0.001). The gut microbial composition of HFD hamsters showed significant alterations at the phylum, genus, and species levels that were skewed toward metabolic disorders compared with that of NCD hamsters, evidenced by an increased Firmicutes/Bacteroidetes ratio (1.42 ± 0.29 vs. 4.32 ± 0.37, P < 0.001). Functional characterization by KEGG analysis identified enrichment of the glycerolipid metabolism pathway in the gut microbiome of HFD hamsters (log10[linear discriminant analysis score] = 3.80, P = 0.004). Plasma metabolomics further confirmed the upregulation and enrichment of glycerolipid metabolites in HFD hamsters, including MAG (18:2), MAG (18:1), phosphatidylethanolamine (PE) (18:1(9Z/0:0)) and glycerol 1-hexadecanoate. The Faecalibaculum, Allobaculum, and Eubacterium genera were positively correlated with glycerolipid metabolites and plasma lipids.
CONCLUSIONS The findings of this study suggest an association between glycerolipid metabolism and the HFD-modulated gut microbiome that is involved in the development of hyperlipidemia.
GW35-e1275
Qingyuan Gao1,2, Haifeng Zhang1,2, Yangxin Chen1,2, Jingfeng Wang1,2
1Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China
2Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangdong 5101120, P.R. China
OBJECTIVES Although mitochondrial fission has been reported to increase proliferative capacity and collagen production, it can also contribute to mitochondrial impairment, which is detrimental to cell survival. The aim of the present study was to investigate the role of mitochondrial fission in cardiac fibroblasts (CF) activation and explore the mechanisms involved in the maintenance of mitochondrial health under this condition.
METHODS Changes of mitochondrial fission/fusion-related proteins and mitochondrial morphology were assessed in transforming growth factor-β1 (TGF-β1) activating CF. The roles of mitochondrial fission and its underlying mechanisms, glycolysis, during this process were elucidated. The interaction between mitochondrial fission and mitophagy, the main safeguard mechanism against mitochondria impairment, were explored.
RESULTS The results showed that the mitochondria in TGF-β1-treated CF were noticeably more fragmented than those of controls. The expression of several mitochondrial fission-related proteins was markedly upregulated, and the levels of fusion-related proteins were also altered, but to a lesser extent. Inhibiting mitochondrial fission resulted in a marked attenuation of TGF-β1-induced CF activation. The TGF-β1-induced increase in glycolysis was greatly suppressed in the presence of a mitochondrial inhibitor, whereas a glycolysis-specific antagonist exerted little additional antifibrotic effects. TGF-β1 treatment increased cellular levels of reactive oxygen species and triggered mitophagy, but this effect was reversed following the application of reactive oxygen species scavengers. For the signals mediating mitophagy, the expression of Pink1, but not Bnip3l/Nix or Fundc1, exhibited the most significant changes, which could be counteracted by treatment with a mitochondrial fission inhibitor. Pink1 knockdown suppressed CF activation and mitochondrial fission, which was accompanied by increased CF apoptosis.
CONCLUSIONS Mitochondrial fission resulted in increased glycolysis and played a crucial role in CF activation. Moreover, mitochondrial fission promoted reactive oxygen species production, leading to mitophagy and the consequent degradation of the impaired mitochondria, thus promoting CF survival and maintaining their activation.
GW35-e1277
Chaoqun Ma
National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110000, P.R. China
OBJECTIVES CircRNAs have recently emerged as critical modulators in vascular remodeling-related diseases. However, the interaction between circRNAs and protein post-translational modifications during vascular remodeling remains poorly understood. This study aims to identify novel circRNA regulators implicated in the phenotypic switch of human vascular smooth muscle cells (VSMCs) and the development of neointima formation.
METHODS RNA sequencing profiled circRNA expression in human VSMCs during both their synthetic and contractile phenotypes. QRT-PCRs, RNA fluorescence in situ hybridization (FISH) and nucleocytoplasmic RNA separation were performed to verify the expression of the candidate circRNAs. The circular structure of the target circRNA was verified by cDNA/gDNA assay, Sanger sequencing, actinomycin D assay and RNase R digestion assay. Furthermore, gain-of-function and loss-of-function experiments were conducted to explore the biological roles of circSATB2_015 in VSMCs through EdU assays, scratch healing assay, transwell migration assay, qRT-PCR and western blots. In addition, a mouse carotid artery guidewire injury model was established to evaluate the effect of circSATB2_015 expression on intimal hyperplasia after injury. Mechanistically, RNA pull-down, mass spectrometry, and RNA-binding protein immunoprecipitation were performed and identified the potential circSATB2_015-interacting protein. Finally, smooth muscle-specific YBX1 knockout mice was constructed to the verify role of circSATB2_015 in vascular remodeling via the regulation of YBX1.
RESULTS CircSATB2_015 was significantly downregulated in PDGF-stimulated proliferative VSMCs and upregulated during VSMC differentiation. This downregulation was also observed in the coronary arteries of patients with severe CAD. We further demonstrated that overexpression of circSATB_015 accelerated VSMC differentiation and inhibited PDGF-induced proliferation and migration. Moreover, circSATB2_015 overexpression ameliorated neointima formation in guidewire-injured carotid arteries, while its silencing enhanced neointimal hyperplasia, confirming its role in vascular remodeling. Mechanistically, RNA pull-down, mass spectrometry, and RNA-binding protein immunoprecipitation were performed and identified that YBX1 was the potential circSATB2_015-interacting protein. Next, circSATB2_015 facilitates the interaction between the E3 ubiquitin ligase RNF8 and YBX1, promoting RNF8-dependent ubiquitination and degradation of YBX1. Additionally, circSATB2_015 overexpression inhibited SRF mRNA stability via YBX1–SRF interaction, altering VSMC differentiation marker genes and reducing VSMC proliferation. Finally, smooth muscle-specific YBX1 knockout mice showed reduced intimal hyperplasia following carotid artery ligation-induced vascular injury, which could not be reversed by silencing circSATB2_015.
CONCLUSIONS We identified a novel circRNA, circSATB2_015, that regulates the VSMC phenotypic switch and vascular remodeling by regulating RNF8-dependent ubiquitylation of YBX1. These findings suggest that targeting circSATB2_015 or its specific downstream targets in human VSMCs may represent a promising approach for treating proliferative vascular diseases.
GW35-e1293
Yueyang Li, Zhenyu Xiong, Yundai Chen
Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
OBJECTIVES Revascularization therapy is critical to myocardial salvage in the event of myocardial infarction, yet it paradoxically leads to ischemia/reperfusion (I/R) injury. A shift in metabolic fuel has been demonstrated to sensitize the heart to I/R insult and subsequent cardiac dysfunction. However, therapeutic options to maintain metabolic homeostasis are scarce. Metaxin-2 (MTX2), initially identified as a fundamental element of protein import complexes, has recently been characterized in mitochondrial dynamics. Despite its expanding range of functions, its involvement in myocardial I/R injury remains unclear.
METHODS The protein and mRNA levels of MTX2 were determined both in vivo and in vitro in the context of I/R injury. A tamoxifen-inducible cardiomyocyte-specific Mtx2 knockout mice model and adenovirus carrying Mtx2 gene were used to investigate the role of MTX2 in myocardial I/R injury. Seahorse metabolic analysis was conducted to determine myocardial glucose and fatty acid oxidation. RNA sequencing and mass spectrometry were performed to elucidate the molecular mechanisms.
RESULTS Herein, we establish for the first time a causative relationship between MTX2 and I/R injury. Both protein and mRNA expression of MTX2 was decreased in mice I/R hearts. Cardiac-specific knockdown of Mtx2 exacerbated I/R injury with impaired cardiac function and enlarged infarct size. Notably, RNA sequencing highlighted the TCA cycle and respiratory electron transport as among the most significantly downregulated terms in Mtx2 cKO + I/R heart. Mechanistically, by using co-immunoprecipitation-mass spectrometry analysis, MTX2 was found to interact with pyruvate kinase M2 (PKM2) to facilitate its tetramer formation via its Tom37 domain and rectify the metabolic flux in hearts. Mtx2 deficiency led to a dramatic accumulation of dimeric PKM2, which is less active compared with its tetrameric form. Moreover, the reconstitution of MTX2 restored the metabolic defect and cardiac dysfunction, which was induced by I/R attack.
CONCLUSIONS Our findings outline a novel role for MTX2 in the regulation of myocardial glucose metabolism and tetrameric PKM2 formation. Targeting MTX2 to correct metabolic abnormalities might emerge as a promising approach for alleviating I/R injury.
GW35-e1298
Lu Peng, Yongzhen Guo, Xue Han, Shiyue Wang, Zhaoyi Luo, Yunlong Xia, Xiaoming Xu, Quanchi Liu, Fengyue Ding, Huishou Zhao, Congye Li, Ling Tao, Wenjun Yan
Department of Cardiology, Xijing Hospital, Fourth Military Medical University
OBJECTIVES Phagocytic clearance of dying cells by efferocytosis is pivotal for the inflammation resolution and cardiac repair after myocardial infarction (MI). Macrophages are considered to be key phagocytes involved in efferocytosis. However, it is unclear whether and how MI alters the efferocytotic activity of monocyte-derived macrophages.
METHODS GFP labeled Piezo1 transgenic mice (Piezo1GFP), myeloid cell-specific Piezo1 deficient mice (Piezo1Lyz2) and their littermate controls (Piezo1fl/fl) underwent MI or sham operation. AAV2 viral vectors containing macrophage-specific SLC7A11 short hairpin RNAs (AAV2-F4/80-SLC7A11-shRNA) were locally injected into the intramedullary space 2 weeks before MI. Bone marrow-derived macrophages (BMDMs) and peritoneal macrophages (PMs) were utilized to perform in vitro experiments. RNA sequencing (RNA-seq) analysis was used to explore the possible molecular mechanism.
RESULTS Compared to BMDMs isolated from sham mice, BMDMs from MI mice showed significant and consistent increase of Piezo1 expression among 12 mechanosensory ion channels. Piezo1 positive macrophage was also increased in the infarcted area from 3 days to 4 weeks after MI. The increased Piezo1 positive macrophage was further confirmed in bone marrow, blood, and heart tissues in post-MI Piezo1GFP mice. Piezo1Lyz2 mice exhibited a significant amelioration in left ventricular function and remodeling after MI, accompanied with less accumulation of apoptotic cardiomyocytes, decreased inflammation and an increased index of in vivo efferocytosis in the border area. We found significantly enhanced uptake of apoptotic cells by Piezo1Lyz2 macrophages compared with Piezo1fl/fl macrophages in vitro. Furthermore, Piezo1 activation by Yoda1 induced defective efferocytosis in both BMDMs and PMs. Yoda1 significantly increased the phagocytosis related genes, in which SLC7A11 showed the most significant difference. Yoda1 significantly increased SLC7A11 expression, while Piezo1Lyz2 macrophages showed significantly reduced SLC7A11 expression. SLC7A11 knockdown or erastin-mediated SLC7A11 inhibition effectively reversed Piezo1 induced defective efferocytosis in BMDMs. From four transcription factors, we found ATF4 is the upstream regulator of SLC7A11 expression in BMDMs after Piezo1 activation. The calcium chelator BAPTA also significantly blocked the upregulated ATF4 and SLC7A11 in Yoda1-treated BMDMs. Finally, macrophage specific knockdown of SLC7A11 by intramedullary injection of AAV2-F4/80-SLC7A11-shRNA significantly increased efferocytosis, reduced apoptotic cardiomyocytes and inflammation, and ameliorated left ventricular remodeling and function after MI.
CONCLUSIONS We revealed an early Piezo1 activation in bone marrow and its novel role in the insufficient macrophage efferocytosis during MI. Inhibiting myeloid Piezo1 is a potential therapeutic strategy to enhance efferocytosis and post-MI heart repair.
GW35-e1319
Juxiang Hou, Lihong Zi, Xihan Fan, Wei Chen
The First Affiliated Hospital of Kunming Medical University
OBJECTIVES Ferroptosis is a novel form of cell death, and its role in iron overload cardiomyopathy (IOC) has not been elucidated. This study aims to explore whether ferroptosis of cardiomyocytes contributes to cardiac dysfunction in IOC by cardiac MR (CMR) and molecular biology techniques in vivo.
METHODS A total of 14 Spraque-Dawley (SD) rats were randomly divided into two groups: the control group (n = 6) and the IOC group (n = 8). The latter was induced by intraperitoneal injection of iron dextran on alternate days for weeks and underwent a 7T CMR for assessment of cardiac function, including left ventricular ejection fraction (LVEF) and global longitude strain (GLS), along with the assessment of iron overload severity and fibrosis using Cine, T2 mapping, and late gadolinium enhancement (LGE), respectively. Circulating iron overload was determined via blood biochemistry analysis, measuring serum iron, ferritin, and transferrin levels. Furthermore, Prussian blue and Masson staining were employed to identify iron and fibrosis deposition within the myocardium. Cardiac ultrastructure, especially mitochondria, was examined via transmission electron microscopy (TEM). A sensitive fluorescent probe, dihydroethidium (DHE), was employed for the detection of reactive oxygen species (ROS) levels. Malondialdehyde (MDA), prostaglandin-endoperoxide synthase 2 (PTGS2), and glutathione peroxidase 4 (GPX4) were utilized to identify and quantify levels of lipid peroxidation, thereby providing comprehensive insights into cardiac cellular ferroptosis.
RESULTS Six rats survived in the control group and 5 in the IOC group. Compared with the control group, the IOC rats had reduced T2 values of the cardiac septum (P < 0.001), with normal LVEF (P > 0.05) but decreased GLS (P < 0.01). Based on blood biochemistry and Prussian blue staining, they were evident that IOC rats exhibited both circulating and cardiac iron overload. Masson staining showed no obvious myocardial fibrosis, which was consistent with negative CMR LGE results. TEM further elucidated cardiac mitochondrial injuries in IOC rats, including focal vacuolization, swelling, crest disruption, and even disappearance. The fluorescent probe results revealed a striking increase in red fluorescence within the myocardium of IOC rats. Additionally, IOC rats exhibited significantly elevated levels of MDA and PTGS2 mRNA (P < 0.001), accompanied by notable downregulation of GPX4 mRNA expression (P < 0.001). These findings suggested the occurrence of ferroptosis in the myocardium of lOC rats.
CONCLUSIONS In IOC, ferroptosis rather than necrosis is the primary driver of cardiac dysfunction, which is characterized by maintaining normal LVEF but experiencing a reduction in GLS without accompanying myocardial fibrosis, Our study sheds light on the potential involvement of ferroptosis in the pathogenesis of IOC.
GW35-e1333
Ge Mang, Suhui Zhang, Jiahui Wu
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
OBJECTIVES Heart failure (HF) is one of the leading causes of mortality worldwide, with associated co-morbidities and dismal prognosis. Neutrophil extracellular traps (NETs) can aggravate inflammation in various cardiovascular diseases; however, the function of NETs in HF pathogenesis and their mechanism of action remain underexplored. This study aimed to investigate whether a new VWF-SLC44A2-NET axis was involved in the progression of HF.
METHODS The level of NETs was examined in patients with HF and mouse models of transverse aortic constricted (TAC) HF. Pad4 knockout or NET inhibitors (GSK-484, DNase I, NEi) were used in TAC mice to evaluate the role of NETs in HF. RNA sequencing was used to investigate the downstream mechanisms. Adamts13 knockout, recombinant human ADAMTS13 (rhADAMTS13), and Slc44a2 knockout were used to identify novel factors acting upstream of NETs.
RESULTS Increased levels of NETs were observed in patients with HF and TAC mouse models of HF. Use of Pad4 knockout or NET inhibitors improved cardiac function. Functional studies revealed that NETs caused mitochondrial dysfunction in cardiomyocytes. Mechanistically, NETs inhibited mitochondrial biogenesis via NE-TLR4-mediated suppression of PGC-1α. Furthermore, VWF/ADAMTS13 regulated the formation of NETs via SLC44A2. Finally, evidence showed that sacubitril/valsartan may amplify the cardioprotective effects of VWF-Slc44a2-NETs axis blockade.
CONCLUSIONS The role of a novel VWF-Slc44a2-NETs axis in regulating mitochondrial homeostasis and function, which leads to cardiac apoptosis and contributes to HF pathogenesis, was established. In the present study, the contribution of the VWF-SLC44A2-NET axis to the progression of HF was clarified, providing key insights regarding the potential therapeutic targets for HF prevention. Sacubitril/valsartan amplify the cardioprotective effects of VWF-Slc44a2-NETs axis blockade in an additive manner were indicated.
GW35-e1345
Maolin Zhao1, Weijie Fu1, Siyi He2
1Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China
2Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, Chengdu, China
OBJECTIVES Non-coding RNAs (ncRNAs) play pivotal roles in both physiological and pathological processes due to their diverse regulatory functions implicated in various diseases, notably cardiovascular disease. Circular RNAs (circRNAs), a recently identified RNA class, represent a significant component of the mammalian transcriptome and exhibit abundant expression within the cardiovascular system. Nonetheless, the precise regulatory mechanisms of circRNAs in ischemic cardiac disease remain largely unexplored. The aim of this study was to identify and characterize novel circRNAs for the development of innovative therapeutics aimed at diagnosing and treating ischemic heart diseases.
METHODS Dysregulated circRNAs were identified through microarray screening of myocardial tissues from patients with cyanotic and non-cyanotic heart diseases. The circular structure was validated using Sanger sequencing and RNase R digestion. Subcellular localization of circRNA was determined using fluorescence in situ hybridization (FISH). Comprehensive analysis of the ceRNA network revealed potential interactions involving circRNA, miRNA, and mRNA. Mechanistic investigations included luciferase reporter assays, RNA Immunoprecipitation (RIP), and RNA pull-down assays to examine the interaction of ceRNA network. Animal studies involved a myocardial ischemia-reperfusion (I/R) mouse model to evaluate the impact of circRNA on cardiac function and cardiomyocyte apoptosis.
RESULTS Expression of hsa_circ_0005255 was significantly increased in cyanotic heart disease. Interaction studies demonstrated that hsa_circ_0005255 acts as a sponge for hsa-miR-3916, thereby positively regulating fat mass and obesity-associated (FTO) protein expression. Furthermore, inhibition of hsa-miR-3916 enhanced FTO expression, subsequently decreasing N6-methyladenosine (m6A) levels and mitigating cardiomyocyte apoptosis. Conversely, elevated hsa-miR-3916 levels induced FTO expression, increased m6A levels, and promoted apoptosis in AC16 cells. Knockdown of hsa_circ_0005255 elevated hsa-miR-3916 levels in AC16 cells. Elevated hsa-miR-3916 levels suppressed FTO expression, leading to increased m6A levels and myocardial apoptosis. Overexpression of hsa_circ_0005255 reduced hsa-miR-3916 levels in AC16 cells. Reduced hsa-miR-3916 levels promoted FTO expression, thereby decreasing m6A levels and myocardial apoptosis. Moreover, induction of hsa_circ_0005255 expression counteracted the elevation of m6A levels induced by low FTO expression in AC16 cells. Knockdown of hsa_circ_0005255 in mouse heart tissues reduced FTO levels, increased m6A levels, and exacerbated apoptosis and ischemia/reperfusion injury.
CONCLUSIONS Our findings suggest that hsa_circ_0005255 could serve as a potential drug target for treating I/R injury. By sponging has-miR-3916 and enhancing FTO expression to alleviate m6A levels and cardiomyocyte apoptosis, hsa_circ_0005255 may offer a novel therapeutic strategy for ischemic heart diseases.
GW35-e1348
Miaomiao Qi, Qiongying Wang, Jing Yu
Lanzhou University Second Hospital
OBJECTIVES Postmenopausal estrogen deficiency is associated with an increased cardiovascular risk, hypertension, and heart failure. Mitochondrial dysfunction plays a key role in pathology of heart failure with preserved ejection fraction (HFpEF). We aimed to investigate the effect and mechanism of estrogen deficiency on left ventricular diastolic dysfunction and mitochondrial dysfunction in HFpEF mice.
METHODS Eighteen 6-week-old female C57BL/6J mice were randomly divided into normal control group, sham HFpEF group and ovariectomized (OVX) HFpEF group. Mice were fed high-fat diet (HFD) and L-NAME (0.5 g/L in drinking water) for 10 weeks to establish a “two-hit” mouse model of HFpEF, showing risk factors such as hypertension, obesity, metabolic dysfunction, and so on. Body weight and blood pressure were measured weekly. Left ventricular (LV) structure and function was monitored by echocardiography. At the end of experiment, animals were starved and histological measures of chamber morphometry and collagen density evaluated. Oxidative stress, mitochondrial function and mitophagy activity were evaluated by western blotting. All experimental procedures were approved by Lanzhou University Second Hospital Committee on Animal Care and conformed to the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health. Statistical analysis was conducted by software SPSS 22.
RESULTS Eighteen 6-week-old female C57BL/6J mice were randomly divided into normal control group, sham HFpEF group and ovariectomized (OVX) HFpEF group. Mice were fed high-fat diet (HFD) and L-NAME (0.5 g/L in drinking water) for 10 weeks to establish a “two-hit” mouse model of HFpEF, showing risk factors such as hypertension, obesity, metabolic dysfunction, and so on. Body weight and blood pressure were measured weekly. Left ventricular (LV) structure and function was monitored by echocardiography. At the end of experiment, animals were starved and histological measures of chamber morphometry and collagen density evaluated. Oxidative stress, mitochondrial function and mitophagy activity were evaluated by western blotting. All experimental procedures were approved by Lanzhou University Second Hospital Committee on Animal Care and conformed to the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health. Statistical analysis was conducted by software SPSS 22.
CONCLUSIONS Our findings indicated that estrogen deficiency may aggravate left ventricular diastolic dysfunction and mitochondrial dysfunction in HFpEF mice by activating mitophagy.
GW35-e1353
Yuyu Li, Jiaqi Yu, Weiyao Chen, Jie Du, Yuan Wang
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Thoracic aortic dissection (TAD) is a life-threatening vascular disease that requires effective drug treatment to prevent progression and rupture. Because arachidonic acid metabolism is involved in inflammation and vascular homeostasis, we investigated the roles of arachidonic acid metabolites in TAD pathogenesis and their utility as therapeutic targets.
METHODS Serum metabolomics analysis was performed to characterize arachidonic acid metabolites in TAD patients and a TAD mouse model. 12/15-LOX expression was profiled in the aortic tissues of TAD patients and the TAD mouse model. Four-week-old male Alox15 knockout mice (Alox15−/−), 12-HETE-treated mice, ML351 (12/15-LOX inhibitor)-treated mice, and LY255283 (leukotriene B 4 receptor 2 [BLT2] antagonist)-treated mice received β-aminopropionitrile monofumarate (BAPN, 1 g/kg/day) for 4 weeks to model TAD, then underwent assessment of TAD progression. Interaction of 12-HETE produced by macrophages with BLT2 receptor-expressing cells was detected by molecular docking and immunoblotting.
RESULTS Serum levels of 12-HETE and the expression of 12/15-LOX in aortic tissue were significantly increased in TAD patients and BAPN-treated TAD mice. BAPN-induced TAD progression was significantly ameliorated in Alox15-deficient or -suppressed mice. 12-HETE directly interacted with BLT2 receptors on macrophages, activating the downstream NOX-1/ROS/NF-κB signaling pathway to induce inflammatory cytokine release. This initiated inflammatory cell recruitment and exacerbated extracellular matrix degradation, leading to phenotype switching in vascular smooth muscle cells (VSMCs). Additionally, treatment with ML351 and LY255283 significantly reduced the rates of dissection rupture and combined treatment could maximize the curative effect.
CONCLUSIONS 12-HETE may amplify the inflammatory cascade and trigger aberrant phenotype switching in VSMCs during TAD development. The reduction of circulating 12-HETE or antagonism of its receptor may be new targets for TAD prevention and treatment.
GW35-e1365
Sailun Wang1, Nils Kremer1, Christina Pilz1, Jochen Wilhelm1, Werner Seeger1,2, Ralph Schermuly1, Khodr Tello1, Baktybek Kojonazarov1,2
1Department of Internal Medicine, Member of the German Center for Lung Research (DZL), Member of the Excellence Cluster Cardio-Pulmonary Institute (CPI), – Germany, Justus Liebig University, Giessen, Germany
2Institute for Lung Health (ILH), Justus Liebig University, Giessen, Germany
OBJECTIVES Right ventricular (RV) function is the critical determinant for the survival of patients with pulmonary hypertension (PH). Although multiple factors have been linked to the adaptation of the RV to pressure overload, the contribution of microvascular density to RV hypertrophy and failure remains unclear. This study’s aim is to implement microscopic computed tomography (μCT) imaging combined with an artificial intelligence (AI) convolutional neural network (CNN)-based cardiac segmentation for the accurate phenotyping of the RV and to evaluate the contribution of myocardial blood volume (MBV) in monocrotaline-induced (MCT) PH.
METHODS The experiments were approved by the University Animal Care Committee and the federal authorities for animal research of the Regierungspraesidium Giessen (Germany). Sprague-Dawley rats were injected with monocrotaline (MCT) and kept for 14 days, 21 days, or 35 days. Echocardiography, in vivo contrast-μCT and invasive hemodynamic measurements, were performed under isoflurane anesthesia in rats on each time point. Instantaneous RV pressures and volumes were measured by micromanometer-tipped catheters and μCT.
RESULTS The cardiac μCT images were reconstructed, segmented, and analysed using an artificial intelligence convolutional neural network. The MCT injection caused a significant gradual rise in RV systolic pressure and RV hypertrophy compared to controls. In the MCT rats, compensatory RV function was observed at days 14 and 21, followed by RV systolic dysfunction and pronounced RV-pulmonary arterial uncoupling, as evidenced by the ratio of end-systolic (Ees) to arterial (Ea) elastances at day 35. Analyses of the RVMBV revealed that the RVMBV at end-diastolic (ED) and end-systolic (ES) cardiac phases significantly increased in MCT rats at days 21 and 35. However, when MBV was normalized to RV myocardial volume, a significant decrease was seen in MCT rats at day 35 compared to controls at ED, but not at ES phases. No significant changes in MBV were observed in rats on days 14 and 21. We have demonstrated non-invasive analysis of cardiac blood volume in animal models of PH for the first time. Also, the comparison between the AI CNN and semi-automatic segmentation revealed excellent correlations.
CONCLUSIONS This study showed an increase in RVMBV alongside an increase in RV mass in response to pressure overload, but a decrease in relative RVMBV in maladaptive RV hypertrophy.
GW35-e1368
Fan Yang, Youfu He, Jing Huang, Zhi Jiang
Guizhou provincial people’s hospital
OBJECTIVES Metabolic reprogramming, the shifting from fatty acid oxidation to glucose utilization, improves cardiac function as heart failure (HF) progresses. Leptin plays an essential role in regulating glucose metabolism. However, the crosstalk between leptin and metabolic reprogramming is poorly understood.
METHODS In the present study, we tested the hypothesis that leptin improves cardiac function after myocardial infarction via enhancing glucose metabolism. In isoproterenol (ISO)-induced heart failure model in vitro, H9c2 cells apoptosis was assessed by the TUNEL and Annexin V/PI staining assay. Leptin-mediated mitochondrial fussion was performed via TEM, and glucose oxidation was explored ECAR, OCR and protein expression of some metabolic key enzymes. With transfected with lentiviruses containing shOPA1 and/or the HDAC5 selective inhibitor (LMK-235) administration, the mitochondrial dynamic and glucose metabolic were detected to evaluate the role of OPA1 and HDAC5 in leptin-stimulated glucose metabolism. In the mouse model of HF in vivo, intraperitoneal leptin administration appreciably increased glucose oxidation and preserved cardiac function at 56 days after coronary artery ligation.
RESULTS In vitro assay, we identified the OPA1-dependent HDAC5 nucleus export as a crucial process in leptin-boosting glucose utilization by activating MEF2 to upregulate Glut4 expression through using the RNA interference technique in the H9c2 cells. In vivo assay, leptin promotes glucose utilization and confers heart functional and survival benefits in chronic ischemic HF.
CONCLUSIONS We elucidated that leptin played a crucial role to intermediate mitochondrial fusion and metabolism remodeling to enhance H9c2 cells survival in vitro and improve cardiac function in vivo. Furthermore, we explored for the first time that the leptin-mediated glucose oxidation by means of HDAC5 nucleus export to activate MEF2 to increase Glut4 transcription level dependent on the appropriated OPA1 level, which providing a novel insight into the protective effect of leptin on intermediate mitochondrial and glucose metabolism during HF development.
GW35-e1369
Yue Ding1, Yuan Ji Wang1, Shu Han1, Xiaoting Liang2,3
1Department of Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai, China
2Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
3Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
OBJECTIVES Achieving long-term graft survival while minimizing the adverse effects of immunosuppression is a critical challenge in transplantation medicine. This study investigated the immunomodulatory potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), with a particular focus on vesicles conditioned by mixed lymphocyte reaction (MLR) medium (MSC-EVMLR), compared to those conditioned by IFN-γ alone (MSC-EVIFN).
METHODS We performed in vitro experiments to assess the ability of MSC-EVMLR and MSC-EVIFN to suppress lymphocyte proliferation and modulate cytokine expression, respectively. The identification of miR-638 as a key effector was accomplished using molecular analysis. Further in vivo validation was conducted using allogeneic heart transplant model to evaluate the graft survival.
RESULTS MSC-EVMLR outperformed MSC-EVIFN in suppressing lymphocyte proliferation and steering cytokine expression towards an anti-inflammatory profile in vitro. The discovery of miR-638 as a pivotal effector within MSC-EVMLR highlights its role in enhancing the immunoregulatory function of vesicles. In vivo validation showed that MSC-EVMLR significantly prolonged graft survival, an effect that was attenuated upon miR-638 knockdown. Additionally, the miR-638/Fosb axis was identified as a key pathway that promoted regulatory T cell (Treg) differentiation and induced immune tolerance.
CONCLUSIONS Preconditioning MSCs with MLR-conditioned medium, a blend of inflammatory stimuli, potentiates the immunoregulatory capacity of MSC-EV beyond the effects of IFN-γ stimulation alone. This study advances the understanding of MSC-EV-based therapies in transplantation, highlighting the therapeutic potential of MSC-EVMLR and the pivotal role of miR-638, thereby offering a potential alternative to conventional immunosuppressive therapies.
GW35-e1370
Wenjun XIONG, Yuan Sui, Mengxuan XIAO
The First Affiliated Hospital of Nanchang University
OBJECTIVES Mitochondrial dynamics are crucial for the functionality of mitochondria. The MFN2 gene is responsible for the production of a mitochondrial membrane protein that contributes to the fusion of mitochondria, which is necessary for preserving and functioning the mitochondrial network. Additionally, MFN2 is vital for mitophagy. In the context of Angiotensin II-induced cardiac remodeling, it is yet to be fully understood how the combined effects of MFN2-regulated mitochondrial fusion and mitophagy impact the process. This study aims to investigate a novel approach to preventing cardiomyocyte injury by manipulating mitochondrial dynamics.
METHODS We investigated the role of MFN2 in promoting mitochondrial fusion and mitophagy during Ang II-induced cardiomyocyte injury. Experimental assays were conducted to assess cardiomyocyte injury, including the generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential (MMP), and the rate of apoptosis in cardiomyocytes. The morphology of mitochondria in cardiomyocytes was analyzed using transmission electron microscopy (TEM) and confocal microscopy. Levels of autophagy in response to Ang II were evaluated by examining the expression of autophagy-related proteins through immunoblotting. Additionally, we examined proteins related to the PINK1/MFN2/Parkin pathway.
RESULTS Receiving stimulation from Ang II led to a gradual decrease in MFN2 expression. Deficiency of MFN2 had a negative impact on the quality of mitochondria, which resulted in worsened mitochondrial damage caused by Ang II. The increase in ROS production and apoptosis rate induced by Ang II was relieved by overexpression of MFN2. Additionally, MFN2 mitigated the reduction in MMP caused by Ang II. Furthermore, MFN2 promoted mitochondrial fusion and facilitated Parkin translocation and phosphorylation, ultimately leading to mitochondrial autophagy. The effects of overexpressing MFN2 were counteracted by autophagy inhibitors.
CONCLUSIONS The promotion of Parkin translocation and phosphorylation by Mitofusin 2 results in the initiation of mitophagy for the clearance of damaged mitochondria. Nevertheless, the positive impacts of MFN2 were negated when autophagy inhibitors were used. Furthermore, MFN2 is involved in maintaining mitochondrial quality through its participation in mitochondrial fusion. Therefore, MFN2 played a role in both mitophagy and mitochondrial fusion as a response to Ang II-induced cardiomyocyte injury.
TRANSLATIONAL MEDICINE RESEARCH IN CARDIOVASCULAR DISEASE
GW35-e0047
Yufei Zhao, Lixin Wang, Weiguo Fu
Zhongshan Hospital Fudan University
OBJECTIVES Adverse aortic remodeling increases the risk of aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) and affects the overall prognosis of aortic dissection (AD). It is imperative to delve into the exploration of prognostic indicators to streamline the identification of individuals at elevated risk for postoperative AAEs, and therapeutic targets to optimize the efficacy of TEVAR for patients with AD.
METHODS We performed proteomic and single-cell transcriptomic analyses of peripheral blood samples and aortic lesions, respectively, from patients with AD and healthy subjects. We performed in vivo experiments to further confirm the effect of inhibiting NETs. Kaplan–Meier and Cox regression analysis were used to identify independent risk factors for AAEs.
RESULTS Integrated multi-omics profiling identified highly phenotype-associated macrophages, which frequently interacted with neutrophils via CXCL3/CXCR2 axis, and promoted neutrophil extracellular traps (NETs) in driving and fueling the development of AD. Increased NETs formation is a defining feature of systemic immunity and aortic microenvironment of AD. Furthermore, we demonstrated that the level of citrullinated histone H3 (CitH3), a NETs associated marker, could serve as a risk factor for AAEs following endovascular therapy. Inhibiting NETs formation through the blockade of CitH3 alleviated the progression and rupture of AD in mice.
CONCLUSIONS The multi-omics profiling reveals NETs formation features in the development of AD. NETs associated markers could facilitate the risk stratification and prognostic evaluation, and might serve as potential therapeutic targets of patients with AD.
GW35-e0050
Chang Cui1, Feng Zhang1, Yike Zhang1, Sichong Qian2, Haiyang Li2, Minglong Chen1
1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
2Department of Cardiac Surgery, Beijing Anzhen Hospital, Beijing 100029, China
OBJECTIVES Substantial advancements have been achieved in the realm of cardiac tissue repair utilizing functional hydrogel materials. Additionally, drug-loaded hydrogels have emerged as a research hotspot for modulating adverse microenvironments and preventing left ventricular remodeling after myocardial infarction (MI), thereby fostering improved reparative outcomes.
METHODS Diacrylated Pluronic F127 micelles were used as macro-crosslinkers for the hydrogel, and the hydrophobic drug α-tocopherol (α-TOH) was loaded. Through the in-situ synthesis of polydopamine (PDA) and the incorporation of conductive components, an injectable and highly compliant antioxidant/conductive composite FPDA hydrogel was constructed. In a rabbit model, the material was surgically implanted onto the myocardial tissue subsequent to the ligation of the left anterior descending coronary artery. Four weeks post-implantation, echocardiography and histological analysis were performed to evaluate the cardiac function.
RESULTS The present study developed an injectable, multi-component self-assembling FPDA conductive hydrogel with simplicity in execution and controlled biocompatibility. Our in vitro experiments demonstrated that under FPDA conditions, PDA and α-TOH effectively synergized to eliminate ROS from cells and attenuate cellular apoptosis. Evidence based on intracellular rhythmic calcium transients and gap junction formation also indicated that the FPDA hydrogel enhanced the electrical and contractile performance of myocardial cells. Following the loading of FPDA in rabbits with myocardial infarction, significant restoration of cardiac function was observed due to the modulation of the infarct microenvironment, manifested by increased left ventricular ejection fraction, reduced infarct area, and decreased fibrosis area.
CONCLUSIONS The findings of this investigation underscore the substantial utility of FPDA hydrogels, given their proactive capacity to modulate the post-MI infarct microenvironment and thereby enhance the therapeutic outcomes of myocardial infarction.
GW35-e0122
Ling Sun1,2, Yuan Ji1,2, Boyu Chi1,3, Tingting Xiao1, Chenkai Li1, Xuejiao Yan1,2, Xu Xiong4, Lipeng Mao1,3, Dabei Cai1,3, Ailin Zou1, Yu Wang1, Le Zhang5, Liming Tang6, Qingjie Wang1,2
1Institute of Cardiovascular Disease, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University
2Department of Cardiology, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University
3Dalian Medical University, Dalian
4Institute of Chemical and Pharmaceutical Engineering, Changzhou Vocational Institute of Engineering
5Department of Neonatology, The Affiliated Wuxi Children’s Hospital of Nanjing Medical University
6Center of Gastrointestinal Disease, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University
OBJECTIVES Extracellular Vehicles (EVs) derived from mesenchymal stem cells (MSCs) have shown great value in the treatment after myocardial injury. However, the clinical application of EVs was limited by their low yields. In the current study, MSCs were cultured within a hollow-fiber-bioreactor. The yields and the therapeutic efficacy were evaluated in a rat acute myocardial infarction (AMI) model.
METHODS MSCs were cultured using the FiberCell system. This in-vivo-like cell culture system consists of a two-way pump, a medium cartridge, connecting tubes and a reservoir bottle. The cell culture medium flows through the inner hollow fibers. A semi-permeable membrane barrier is formed between the cultured cells and the flowing medium. Small molecules, such as lactic acid and glucose, are allowed to penetrate the fibers freely. When the cells are cultured in the system, the exosomes, which are secreted from MSCs and have penetrated the fibers, cannot enter the space where MSCs grow. EVs were extracted from the culture supernatants. Characteristics and yields of EVs from two culture systems, namely 2D-EVs and 3D-EVs, were compared. A rat model of AMI was built up to assess their therapeutic efficacy on AMI.
RESULTS The yield of 3D-EVs was higher, with biofunctions similar to those of 2D-EVs. 3D-EVs repressed the apoptosis of cardiomyocytes, facilitated angiogenesis, and regulated the transition of macrophage subpopulations after myocardial infarction, and eventually improved cardiac function in the AMI rats.
CONCLUSIONS A high yield of MSCs-derived EVs can be produced by a 3D cell culture system based on hollow fiber bioreactors. The 3D-EVs exhibit a stronger cardioprotective effect than the 2D-EVs. The 3D culture system shows a great potential to be replicated in clinical practice.
GW35-e0177
Liming Chen, Yunzeng Zou
Zhongshan Hospital, Fudan University
OBJECTIVES Mitochondria are a significant source of reactive oxygen species (ROS) in cardiovascular diseases, and mitochondrial oxidative stress (MitOS) plays a crucial role in the development of heart failure (HF). However, comprehensive investigation into MitOS-related genes in dilated cardiomyopathy (DCM) is lacking. This study aimed to assess the significance of MitOS-related genes in the prognosis and identification of therapeutic targets for DCM.
METHODS We retrieved mitochondria and oxidative stress-related genes from various public databases, identifying three potential diagnostic candidate genes for DCM using bioinformatics and machine learning algorithms. The ROC curve was used to evaluate their performance. The ROC curve was used to evaluate their performance. Additionally, the JC-1 assay and ATP levels were used to assess the mitochondrial function of adult cardiomyocytes isolated from DCM mice, while intracellular ROS levels were measured using MitoSOX. Lastly, we silenced one of the candidate genes and assessed mitochondrial function and MitOS levels.
RESULTS Differential expression analysis and machine learning algorithms screened three MitOS-related genes (TARS2, SNCA, NOL3), resulting in strong prediction accuracy (AUC value = 0.902). External datasets were used to validate the potential diagnostic value of these candidate genes for DCM. We found that these genes were particularly enriched in cardiomyocytes using single-cell RNA sequencing data. Finally, we selected TARS2 for further validation in vitro and in vivo. The results demonstrated elevated TARS2 levels in hearts of DCM mice. Knockdown of TARS2 disrupted mitochondrial homeostasis and increased MitOS levels in cardiomyocytes. These findings suggest that upregulated TARS2 levels are an adaptive response to DCM and may be cardioprotective.
CONCLUSIONS Our study is the first to propose a prognostic model involving mitochondria and oxidative stress-related genes in DCM pathogenesis, offering potential therapeutic strategies for DCM patients.
GW35-e0209
Chaofu Li, Chuanwei Li
Chongqing University Central Hospital
OBJECTIVES Extracellular vesicles (EVs) has emerged as one of the best tools for cardiac therapeutic interventions due to its biological properties similar to parent cells, long-term expression and safety. However, a significant challenge to its successful clinical use is targeting, which are prone to phagocytosis by the mononuclear phagocytic system, leading to reduced accumulation at target sites and limiting therapeutic efficacy. Here, we described endothelial progenitor cell membrane-fused biomimetic-modified extracellular vesicles, which, by leveraging the natural homing ability of endothelial progenitor cells, improve their targeting specificity, increase accumulation at target sites, and exert superior therapeutic effects.
METHODS In this study, we engineered a nanovesicle system named Endo@EVs by biomimetically modifying EVs with endothelial progenitor cell membrane (Endo), integrating therapeutic and targeting capabilities. We compared the targeting and therapeutic efficacy of Endo@EVs through immunofluorescence imaging, flow cytometry, live animal imaging, and immunohistochemistry both in vitro and in vivo. Additionally, the biosafety of Endo@EVs was investigated through ELISA, coagulation factor assays, and HE staining.
RESULTS Firstly, we demonstrated that Endo@EVs successfully fused Endo with EVs, while simultaneously possessing a proteomic profile from both EVs and endothelial progenitor cells (EPCs). Comparative analysis of the targeting efficiency between Endo@EVs and EVs, revealed that Endo@EVs exhibited superior tissue/cellular targeting ability by evading immune surveillance compared to EVs, both in vitro and in vivo. Moreover, intravenous injection of Endo@EVs into myocardial infarction mice significantly improved ejection fraction and fractional shortening, along with promoting angiogenesis. In vitro, Endo@EVs notably enhanced the viability and proliferative capacity of damaged endothelial cells. These data validate the enhanced therapeutic efficacy of Endo@EVs compared to EVs. Lastly, safety analysis demonstrated that both Endo@EVs and EVs exhibited favorable biosafety profiles.
CONCLUSIONS By employing the extrusion method to construct the membrane biomimetic-modified nanovesicle system Endo@EVs, we have demonstrated its significantly higher targeting efficiency and therapeutic efficacy. These results establish the potential of Endo@EVs as a targeted therapeutic tool in myocardial infarction.
GW35-e0223
Li Feng
The Second Affiliated Hospital of Soochow University
OBJECTIVES The molecular mechanisms underlying diabetic vasculopathy remain elusive.
METHODS Diabetic vasculopathy-related differentially expressed genes (DEGs) were identified using GSE13760, including arterial samples from type 2 diabetes milieus (T2DM) and control (Con) groups. We performed enrichment analysis to explore the possible mechanisms. We screened the potential small-molecular drugs for diabetic vasculopathy therapy via cMAP online database with up-regulated DEGs. We identified the possible hub genes via protein–protein interaction (PPI), and performed the expression analysis and correlation analysis. We determined the key genes of diabetic vasculopathy via overlapping three algorithms. We constructed mRNA–miRNA and mRNA–transcription factor (TF) network and conducted immune infiltration analysis for the key genes. Finally, we performed the animal study to validate our bioinformatics analysis.
RESULTS A total of 139 DEGs were identified between T2DM and Con arterial samples. Enrichment analysis showed that DEGs may be involved in multiple pathological processes, such as cytokine-cytokine receptor interaction, regulation of phosphatidylinositol 3-kinase activity, and TGF-beta signaling pathway. The top ten small-molecular compounds for diabetic vasculopathy therapy were screened. The two up-regulated genes (BMP4 and LEP) were predicted as key genes. The mRNA–miRNA and mRNA–TF network and immune infiltration analysis revealed that multiple miRNAs or TFs, as well as immune cells, might modulate the BMP4 and LEP expression. Finally, experimental study with T2DM mice model showed consistent results on key genes expression and enrichment analysis.
CONCLUSIONS Our study suggests that two up-regulated key genes (BMP4 and LEP) might be involved in the pathophysiological process in diabetic vasculopathy.
GW35-e0327
Zhaohua Cai, Liang Fang, Min Liang, Yangjing Jiang, Ben He
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES Although the pathogenesis of abdominal aortic aneurysm (AAA) remains largely unclear, evidence is accumulating to suggest the systemic nature of this disease. Here, we comprehensively assessed the whole aortic tree with its major branches based on computed tomography angiography (CTA) in AAA patients compared to ascending thoracic aortic aneurysm (ATAA) patients and nonaneurysmal controls, and in an original mouse model of AAA.
METHODS The morphology and dimensions of the whole aorta (at different levels) and its major branches were compared among 47 AAA patients, 47 ATAA patients, and 46 nonaneurysmal controls based on CTA images. To further characterize AAA growth, tamoxifen-inducible Lkb1flox/flox ; Myh11-Cre/ERT2 mice which induced Lkb1 deficiency in adult VSMC were generated by intercrossing Lkb1flox/flox mice with Myh11-Cre/ERT2 mice. CTA and magnetic resonance imaging (MRI) were performed to evaluate the morphology and dimensions of the whole aortic tree in Lkb1flox/flox ; Myh11-Cre/ERT2 mice which spontaneously developed AAA.
RESULTS The whole aorta extending from the sinotubular junction of the aortic root to the terminal aortic bifurcation, along with its major branches, was diffusely enlarged in AAA patients, whereas the dilatation was localized and restricted to the ascending aorta in ATAA patients. Lkb1flox/flox ; Myh11-Cre/ERT2 mice spontaneously and progressively developed AAA, accompanied by aneurysms in renal artery, iliac artery, caudal artery, or femoral artery. Moreover, the mean cross-sectional diameters of the whole aortic tree with its major branches were diffusely larger in Lkb1flox/flox ; Myh11-Cre/ERT2 mice compared with wild-type mice.
CONCLUSIONS This original morphologic study demonstrated that abdominal but not thoracic aortic aneurysm is a systemic and generalized arteriomegaly both in mice and humans.
GW35-e0367
Yi Li1,2, Xiuxian Wei1,2, Mulin Xu2,3, Cuntai Zhang1,2, Yu Liu1,2
1Department of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
3Department of General Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
OBJECTIVES The purpose of this study was to assess the effect of Nicotinamide Mononucleotide (NMN) on vascular smooth muscle cell (VSMC) phenotype switching and investigate the underlying mechanism by which NMN ameliorates VSMC phenotypic switching.
METHODS VSMC-specific Nrf2 knockout mice were employed to evaluate whether NMN protected against neointima hyperplasia via Nrf2 signal, which was mainly caused by VSMC phenotype switching. Wire injury model was performed to induce neointima hyperplasia in vivo. Platelet-derived growth factor-BB (PDGF-BB) was employed to induce VSMC phenotype switching in vitro. Molecular docking in silico was used to predict the molecular mechanisms of NMN regulating Nrf2 signal and Co-immunoprecipitation (Co-IP) was performed to testify it. RNA-seq and qRT-PCR was employed together to find Lamc1, the novel downstream target of Nrf2. Chromatin immunoprecipitation (ChIP) assays and luciferase reporter assays were carried out to identify Nrf2 bound to the promoter of Lamc1.
RESULTS NMN treatment effectively reduced wire-induced neointima hyperplasia, accompanied by Nrf2 nuclear translocation. To further investigate the role of Nrf2 in this process, we utilized VSMC-specific Nrf2 knockout mice and observed that the absence of Nrf2 in VSMCs not only exacerbated neointima formation but also abolished the beneficial effects of NMN on neointima hyperplasia. Gain-and-loss function experiments targeting Nrf2 provided additional evidence supporting its critical role in VSMC phenotypic switching in vitro. Moreover, we confirmed that NMN exerted a protective effect against VSMC phenotypic switching by promoting Nrf2 nuclear translocation in vitro. Mechanistically, we elucidated that NMN competitively binds to the Kelch domain of KEAP1, which serves as the binding site for NRF2 and KEAP1. This interaction led to the de-ubiquitination of NRF2 and facilitated its nuclear translocation. Subsequently, Nrf2 bound to the promoter region of Lamc1, promoting Lamc1 transcription and effectively protecting against VSMC phenotypic switching.
CONCLUSIONS Our findings demonstrate that NMN alleviates VSMC phenotypic switching through the Nrf2/Lamc1 signal. These results provide novel insights into the potential therapeutic use of NMN for the treatment of in-stent restenosis.
GW35-e0387
Tingting Lyu
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of clinical medicine, Tsinghua University
OBJECTIVES Ryanodine receptor 2 (RyR2) protein, a calcium ion release channel located in the sarcoplasmic reticulum of myocardial cells, is essential for regulating the cardiac systolic and diastolic function. Despite the importance of this topic, a systematic and comprehensive review of mutant RyR2 associated various types of inherited heart diseases and the electrophysiological mechanisms has not yet been conducted.
METHODS To address this, researchers have created various mutant RyR2 models, which have shown evidence of mutant RyR2′ ability to cause dysfunction in calcium (Ca2+) release, such as functional gain or loss, involving electrophysiological mechanisms of calcium induced calcium release (CICR) and storage overload induced storage overload induced calcium release (SOICR).
RESULTS Previous studies have shown that mutations in the RYR2 gene, responsible for encoding the RyR2 protein, can leader to severe cardiac arrhythmia, such as catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), and idiopathic ventricular fibrillation (IVF), as well as potentially contributing to atrial fibrillation (AF). Furthermore, Mutations in RyR2 have been linked to various genetic cardiomyopathies, including left ventricular non-compaction cardiomyopathy (LVNC), arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), often in conjunction with CPVT.
CONCLUSIONS Understanding the potential correlation between genotype and phenotype of mutant RyR2 is crucial for enhancing diagnostic and therapeutic approaches. This review will address this gap in the literature by providing a thorough understanding of RyR2 related inherited heart diseases and their potential impact on cardiac electrophysiology.
GW35-e0389
Tingting Lyu, Ping Zhang
Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University
OBJECTIVES Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal arrhythmia mainly caused by calcium disorder induced by mutant ryanodine receptor 2 (RyR2). We previously firstly found in clinical practice that a patient with CPVT carrying a heterozygous RyR2 R1760W experienced sudden cardiac death during exercise. However, the effect of electrical activity of this mutant RyR2 on the heart is unclear.
METHODS Crispr/Cas 9 gene editing was used to create a heterogeneous RyR2 R1761W+/− mutation mouse model. The structure and function were evaluated by echocardiology. Ex vivo optical mapping was used to evaluate the changed electrophysiology parameters and calcium handling properties.
RESULTS Echocardiography found that there was no significant difference in structure and function between WT and RyR2 R1761W+/− mice, including left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), left ventricular inner dimension (LVID) and left ventricular posterior wall end-diastolic thickness (LVPWD). Ex vivo optical-mapping showed that compared with WT mice, parameters of action potential duration was reduced in heterogeneous RyR2 R1761W+/−, which indicated the increased arrhythmia sensitivity. Isoproterenol treatment induced the ventricular arrhythmia in RyR2 R1761W+/− mice.
CONCLUSIONS The RyR2 R1760W mutation from CPVT patient increased the calcium leak in HEK 293 cell model expressing mutant RyR2. Furthermore, RyR2 R1760W mutation may affect the cardiac electrophysiological characterization of the mice under the stimulation of catecholamine but not at baseline. The underlying mechanisms need further research.
GW35-e0449
Lingbing Meng
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University
OBJECTIVES Long QT syndrome (LQTS) and Beckwith–Wiedemann syndrome (BWS) are complex disorders with unclear origins, underscoring the need for in-depth molecular investigations into their mechanisms. The main aim of this study is to identify the shared key genes between LQTS and BWS, shedding light on potential common molecular pathways underlying these syndromes.
METHODS The LQTS and BWS datasets are available for download from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) was used to detect significant modules and central genes. Gene set enrichment analysis (GSEA) was performed. CIBERSORT was used for immune cell infiltration analysis. The predictive protein interaction (PPI) network of core genes was constructed using search tool for the retrieval of interacting genes (STRING), and miRNAs regulating central genes were screened using TargetScan.
RESULTS A total of 500 DEGs associated with long QT syndrome and Beckwith–Wiedemann syndrome were identified. GSEA revealed enrichment in pathways such as T cell receptor signaling, MAPK signaling, and adrenergic signaling in cardiac myocytes. Immune cell infiltration indicated higher levels of memory B cells and naive CD4 T cells. Four core genes (CD8A, ICOS, CTLA4, LCK) were identified, with CD8A and ICOS showing low expression in the syndromes and high expression in normal samples, suggesting potential inverse regulatory roles.
CONCLUSIONS The expression of CD8A and ICOS is low in long QT syndrome and Beckwith–Wiedemann syndrome, indicating their potential as key genes in the pathogenesis of these syndromes. The identification of shared key genes between LQTS and BWS provides insights into common molecular mechanisms underlying these disorders, potentially facilitating the development of targeted therapeutic strategies.
GW35-e0483
Haixu Song, Chunying Liu, Chenghui Yan, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Yangxinshi tablet (YXST), a traditional Chinese medicine, can significantly improve cardiac function in patients with heart failure; however, whether YXST has the potential effect in heart failure induced skeletal muscle injury is still unclear. In this study, we investigated the efficacy and explored the molecular mechanisms.
METHODS Mice were divided randomly into five groups (n = 10/group) and treated for 6 weeks: control group (sham group), myocardial ischemia-reperfusion group (I/R group), YXST group (I/R treated with YXST, 250 or 500 mg/kg/day) and trimetazidine (TMZ) group (I/R treated with TMZ, 20 mg/kg/day). Cardiac function, exercise tolerance, muscle gripstrength and mitochondria were analyzed, and RNA-sequence assays and mass spectrometry analysis of C2C12 myotubes were performed. The key ingredients and target genes of YXST were assessed by network pharmacology and molecular docking methods. YXST improved cardiac function, exercise tolerance and grip strength, enhanced the expression of slow type I fibers, ameliorated mitochondrial biogenesis, and attenuated the level of inflammation.
RESULTS The key ingredients and target genes of YXST were assessed by network pharmacology and molecular docking methods. YXST improved cardiac function, exercise tolerance and grip strength, enhanced the expression of slow type I fibers, ameliorated mitochondrial biogenesis, and attenuated the level of inflammation in vivo. YXST also promoted the differentiation of C2C12 myoblasts and formation of myotubes by regulating mitochondrial biogenesis, mitophagy, and oxidative phosphorylation in vitro. Molecular docking analysis revealed that the top five active ingredients of YXST may bind with BTB and CNC homology 1 protein. Moreover, YXST stimulated the secretion of cardioprotective myokines.
CONCLUSIONS This study demonstrated that YXST improved cardiac function, exercise endurance, grip strength and upregulated the expression of slow type I fibers in I/R mice. Moreover, YXST significantly promoted mitochondrial biogenesis, oxidative phosphorylation and myokine production in myotubes. Our findings may provide a potential therapeutic target for YXST against heart failure and induced skeletal muscle injury.
GW35-e0515
Xianwu Cheng
Department of Cardiology and Hypertension, Jilin Provincial Key Laboratory of Stress and Cardiovascular Disease, Yanbian University
OBJECTIVES Exposure to chronic psychosocial stress is a risk factor for metabolic disorders. Because dipeptidyl peptidase-4 (DPP4) and cysteinyl cathepsin K (CTSK) play important roles in human pathobiology, we investigated the role(s) of DPP4 in stress-related adipocyte differentiation, with a focus on the glucagon-like peptide-1 (GLP-1)/adiponectin-CTSK axis in vivo and in vitro.
METHODS Plasma and inguinal adipose tissue from non-stress wild-type (DPP4+/+), DPP4-knockout (DPP4−/−) and CTSK-knockout (CTSK−/−) mice, and stressed DPP4+/+, DPP4−/−, CTSK−/−, and DPP4+/+ mice underwent stress exposure plus GLP-1 receptor agonist exenatide loading for 2 weeks and then were analyzed for stress-related biological and/or morphological alterations.
RESULTS On day 14 under chronic stress, stress decreased the weights of adipose tissue and resulted in harmful changes in the plasma levels of DPP4, GLP-1, CTSK, adiponectin, and tumor necrosis factor-α proteins and the adipose tissue levels of CTSK, preadipocyte factor-1, fatty acid binding protein-4, CCAAT/enhancer binding protein-α, GLP-1 receptor, peroxisome proliferator-activated receptor-γ, perilipin2, secreted frizzled-related protein-4, Wnt5α, Wnt11 and β-catenin proteins and/or mRNAs as well as macrophage infiltration in adipose tissue; these changes were rectified by DPP4 deletion. GLP-1 receptor activation and CTSK deletion mimic the adipose benefits of DPP4 deficiency. In vitro, CTSK silencing and overexpression respectively prevented and facilitated stress serum and oxidative stress-induced adipocyte differentiation accompanied with changes in the levels of pref-1, C/EBP-α, and PPAR-γ in 3T3-L1 cells.
CONCLUSIONS These findings indicated that increased DPP4 plays an essential role in stress-related adipocyte differentiation, possibly through a negative regulation of GLP-1/adiponectin-CTSK axis activation in mice under chronic stress conditions.
GW35-e0638
Kun Li
Beijing Tsinghua Changgung Hospital
OBJECTIVES Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies. Over 95% of FSHD cases are caused by deletion of the subtelomeric macrosatellite repeats (D4Z4) on human chromosome 4q35. Directly sequencing these repetitive regions is difficult owing to the high similarity among repeat units and high GC content. The existing FSHD1 diagnostic approaches, including Southern blot and Molecular combing, are not widely used for the reason of time-consuming, labor-intensive, and high equipment requirements. We aim to develop an efficient and accurate procedure for the diagnosis of FSHD.
METHODS Whole genome sequencing was performed for ten individuals from a large FSHD family. Parametric linkage analysis was performed via Merlin (v1.1.2) with the following parameters: dominant model, an estimated population allele frequency of 1E−5, and penetrance of 90%. 4q and 10q haplotypes were characterized by alignment to the chm13 reference genome. A BLAT of the pLAM sequence were performed to identify the A/B haplotypes. We realigned the 250-bp paired end whole genome sequencing reads to the chm13 reference genome using BWA-MEM and then measured the read count for reads containing either the 4q-specific D4Z4 sequence of 4q-specific pLAM sequence and normalized counts to the read depth of the p-arm of chromosome 4. Ultra-long read Nanopore long read genome sequencing were applied to genotype the pathogenic allele.
RESULTS Rare variants-based linkage analysis identified one single 1.7 MB haplotype on chromosome 4q35.2, presenting in affected individuals and absent from unaffected family members. Parametric linkage analysis resulted in a LOD score of 3.228 for the region. All pedigree samples contained 4q-pLAM sequence suggesting at least one copy of an 4qA permissive haplotype. Normalized counts of reads containing 4q-specific pLAM sequence were comparable between the FSHD patients, while 4q-specific D4Z4 repeat sequence demonstrated fewer reads in pedigree samples. Ultra-long read Nanopore sequencing of one affected individual detected a pathogenic FSHD allele containing a 4qA permissive haplotype and 5 D4Z4 repeats.
CONCLUSIONS Genome-wide rare variants-based linkage analyses is a powerful tool for the detection of pathogenic regions in family study. Ultra-long read Nanopore sequencing is capable of genotyping pathogenic FSHD1 alleles.
GW35-e0658
Shaoheng Zhang, Chen Li, Zhichuan Huang, Jianshuo Wang, Zhanyu Deng, Pengzhen Wang
GuangZhou Red Cross Hospital Medical College of Ji-Nan University
OBJECTIVES Myocardial infarction (MI) is characterized by cardiomyocyte (CM) loss and intensive sympathetic nervous system (SNS) activation. Renal denervation (RD) presents a safe and minimally invasive treatment option for MI. The aim of the current study was to assess cooperative effects of peripheral blood mesenchymal stem cell-derived exosomes (PBMSC-Exos) on RD-induced cardiac repair.
METHODS Adult domestic pigs underwent ligation of left anterior descending coronary artery to induce MI and randomly received sham-RD (CON) or RD. PBMSC-Exos were collected from these pigs at 14 days post-MI, After 30 days post-MI, Both sets were randomly allocated to receive either 2 × 1013 particles or the same volume of PBS, and underwent follow-up for a period of 90 days.
RESULTS After 30 days, RD-treated pigs exhibited better left ventricular EF and less LV dilatation compared with CON. Moreover, RD resulted in upregulated expression of connexin 43 (CX43), which promoted the exosomal uptake by CMs. In an in vitro coculture model, RD-elicited PBMSC-derived exosomes (Exos) overexpressed with CX43 promoted myocardial exosomal uptake, proliferation, and redifferentiation. Then, infarcted hearts underwent a “two-hit” treatment via an injection of empty AAV6-transfected Exos or AAV6-CX43-transfected Exos by peripheral vein, and continuously followed up to 90 d post-MI. By comparison, RD provides a novel cardioprotection by remote activation of CX43 which enhances myocardial uptake of PBMSCs-derived Exos, reduces renal sympathetic activity, stimulates cardiomyocyte proliferation and regeneration, attenuates LV fibrosis, and improves cardiac function.
CONCLUSIONS Delivery of PBMSC-derived exosomes may synergize to promote cardiac repair of renal denervation in ischemic cardiomyopathy.
GW35-e0708
Elizaveta Pleshko, Daria Borodko, Andrey Omelchenko, Nikolay Orekhov, Tatiana Kovyanova, Alexandra Melnichenko
Institute of General Pathology and Pathophysiology
OBJECTIVES Mitophagy, the selective degradation of defective mitochondria, plays a crucial role in maintaining cellular homeostasis. Disruptions in this process can result in chronic inflammation, contributing to the development of various diseases such as atherosclerosis and cardiometabolic syndrome. Our study aims to identify potential activators of mitophagy, with the goal of developing novel anti-inflammatory therapeutics. By targeting mitophagy pathways, we seek to mitigate the inflammatory responses associated with non-infectious diseases.
METHODS An original python program was written to search for compounds in chemical databases. Molecular dynamics methods in the Schrödinger Biologics Suite and Schrödinger Maestro software packages were for evaluating mitophagy stimulating activity. The selection of discovered organic molecules was synthesized by a third-party laboratory using the Wittig reaction.
RESULTS We developed a custom Python program to search for compounds with a known ability to stimulate mitophagy. 100 compounds with four types of biological activity were selected as a result of this script launch, i.e. PINK1 protein kinase activators (artificial cytokinin-like plant hormone kinetin and its analogues), sirtuin-3 activators (compound ADTL-SA1215), deubiquitation inhibitors (compounds MF-094 and MF-095), as well as compounds that alter the membrane potential of mitochondrial membranes (Jatrophone and Jatrogossone A). Then we obtained conformational characteristics of the most active stimulators of mitophagy by conducting simulations of molecular dynamics. Based on these data, 30 molecules with the best predicted mitophagy-stimulating activity were selected for in vitro tests. The organic synthesis of these compounds was carried out by conducting the Wittig reaction between maleinimide and aromatic aldehydes of various structures. The obtained benzylidene succinimides were used to produce diazo compounds for their subsequent modification with various heterocycles functionalized with hydroxyl groups.
CONCLUSIONS Our study identified and synthesized potential mitophagy activators for developing anti-inflammatory therapeutics for non-infectious diseases. Molecular dynamics simulations refined the selection to 30 candidates with predicted efficacy. However, in vitro experiments are still required to test these potential mitophagy stimulators, which could lead to the preclinical phase of drug development.
GW35-e0762
Yujie Zhang
The General Hospital of Northern Theatre Command
OBJECTIVES Qiliqiangxin capsule (QLQX), has been used in the treatment of chronic heart failure (CHF) in China, providing an effective treatment for CHF. QLQX has the characteristics of “multi-component, multi-target, multi-channel” treatment of traditional Chinese medicine, so it is difficult to study all the drug targets of QLQX one by one. In order to deeply understand the pharmacological mechanism of QLQX on chronic heart failure, we designed this study by combining network pharmacology with experiment.
METHODS Network pharmacology analysis was performed to identify the potential active constituents, candidate targets, target cell types and major pathways. Additionally, we evaluated the cardiovascular protective effects of QLQX using the CHF mouse models induced by Ang II, and further verified the results predicted by network pharmacology via real-time quantitative polymerase chain reaction (qPCR), western blot and so on.
RESULTS The target and mechanism of QLQX in the treatment of CHF were analyzed based on network pharmacology: the results of the study showed that pharmacological studies yielded 700 targets for CHF and 239 targets for QLQX. The target of QLQX was combined with the target of Chronic heart failure to obtain 99 overlapping targets. The top six targets of correlation strength were interleukin-6, albumin, threonine kinase 1, vascular endothelial growth factor, tumor necrosis factor, and nitric oxide synthase 3. It is suggested that they play an important role in QLQX anti CHF. By analyzing KEGG signaling pathway of nodes in the network, we found that the top 15 signaling pathways related to CHF. It is suggested that QLQX may play a role in the treatment of CHF. In order to verify the results of network pharmacology, we established a mouse model of chronic heart failure by Angiotensin II (Ang II) intervene for 4 weeks. Forty-five C57 mice were randomly divided into Control group, Ang II group and Ang II + QLQX group, 15 mice in each group. The cardiac function of mice in Ang II group was significantly lower than that in Control group, which could be reflected by the decrease of EF and FS. After drug treatment, the EF and FS value of Ang II + QLQX group was significantly higher than that of Ang II group. Immunofluorescence staining showed that after Ang IIintervention, IL-6 in heart from the Ang II group was significantly higher than that in the Control group, and QLQX could alleviate the heart inflammation induced by Ang II. The inflammatory markers in heart (IL-6, IL-1β, TNF-a) detected by RT-PCR and serum (IL-6, IL-1β, TNF-a) detected by ELISA also supported the above results. Western blot showed that QLQX alleviated Ang II induced cardiac inflammation by regulating RAGE/NF-κB pathway.
CONCLUSIONS This study revealed the pharmacodynamic material basis of QLQX and its potential multicomponent–multitarget–multipath pharmacological effects, confirmed the anti-CHF effects of QLQX, and showed that its mechanism may be related to inhibiting RAGE signaling pathway, partially verifying the results from network pharmacology. The results from this study could provide a theoretical basis for the development and clinical application of QLQX.
GW35-e0804
Bifang Mai1, Xinru You2, Liying Wang3, Yuyang Chen1, Yuan Li1, Wei Tang1, Jingfeng Wang1, Jun Wu4,5, Shuanglun Xie1
1Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China
2Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
3Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
4Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Nansha, Guangzhou 511400, China
5Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR 999077, China
OBJECTIVES Excessive and prolonged inflammatory responses lead to adverse cardiac remodeling and impaired cardiac function post myocardial infarction (MI). Polysalicylic acid (PSA), a major byproduct during aspirin synthesis, can be formulated into nanoparticles (PSA NPs). Given its aspirin-like inflammatory suppression properties, we investigated whether PSA NPs, a novel treatment for MI, provide cardiac protection and elucidate the underlying mechanism.
METHODS Permanent left anterior descending (LAD) artery ligation was used to induced MI in C57BL/6 mice. The mice were treated with daily intravenous injections of 6 mg/kg PSA NPs for either 7 or 28 days. For blockade of CSF1r, 40 mg/kg GW2580 was administrated orally in post-MI mice. Echocardiographic and histology were used to detected cardiac function, fibrosis levels post-MI. Through flow cytometry, RNA-sequencing, western blotting, and RT-qPCR, we investigated macrophage dynamics, CSF1r expression, and inflammation with PSA NPs treatment.
RESULTS PSA NPs improved cardiac function, suppressed cardiac fibrosis, and promoted angiogenesis post MI in mice on day 28, whereas the aspirin group showed minimal effects. We further investigated that PSA NPs increased the number of reparative Ly6Clo monocyte/macrophages and enhanced CSF1r expression in heart and spleen on day 7 post MI, in contrast to the minimal changes observed in MI mice treated with aspirin. Additionally, we explored the potential role of CSF1r in post MI mice treated with PSA NPs. Blockade of CSF1r using GW2580 led to progressive deterioration of cardiac function and a reversal of reparative Ly6Clo macrophages. Meanwhile, we demonstrated that PSA NPs mediated CSF1r evaluation and thus facilitated the anti-inflammatory response in activated bone marrow derived macrophages (BMDMs).
CONCLUSIONS PSA NPs ameliorate post-MI cardiac remodeling and promote macrophage transition towards a reparative phenotype. This mechanism may involve CSF1r modulation.
GW35-e0916
Qiaofei Chen1,2, Guotao Yuan1,2, Zhengyu Cao1, Zhiwen Liu1, Yue Pan1,2, Yuling Zhang1,2
1Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
2Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Foshan 528200, China
OBJECTIVES As a promising modality for treating atherosclerosis (AS), sonocatalytic therapy (SCT) offers advantages such as being non-invasive, having high tissue penetrability and no systemic side effects. The underlying mechanism of SCT involves the generation of reactive oxygen species (ROS) when minor ultrasound (US) activates sonosensitizers by consuming O2. However, the ROS yield from existing organic sonosensitizers is inefficient, and the metallic toxicity of inorganic sonosensitizers poses safety concerns. Additionally, the hypoxic environment within plaques severely restricts the efficacy of SCT. Therefore, it is necessary to explore new sonosensitizers that have low toxicity, high ROS generation, and O2 generation capabilities for optimized SCT. Herein, we fabricated a carbon nanoframe-confined N-coordinated manganese single sonocatalysis with five-coordinated structure (MnN5 SA/CNF). Hyaluronic acid (HA) modification was used to specifically target M1 macrophage.
METHODS The generation of ROS (•OH and 1O2) in vitro was evaluated by ESR spectra. The produced O2 was detected using a ST400D portable dissolved oxygen meter. RAW264.7 cells differentiated into M1 macrophages after incubation with lipopolysaccharide (LPS) for 12 hours. Flow cytometry and fluorescence microscopy were used to assess M1 macrophage apoptosis and intracellular ROS generation. Western blot analysis was performed to investigate apoptosis-related proteins and HIF-1α expression. In vivo, ApoE−/− mice were fed with western diets, and the left carotid arterial branches were ligated on day 14 to accelerate atherosclerotic lesion formation. After injection with nanoparticles, the aorta, heart, liver, spleen, lung, and kidney were harvested and imaged using the IVIS system. The colocalization of MnN5 SA/CNF-HA and M1 macrophages was further investigated by confocal microscopy. For morphometric analysis, cross-sections were stained with Oil Red O to evaluate plaque areas. Necrotic core size and cap thickness were assessed by collagen staining with Masson’s trichrome.
RESULTS We successfully synthesized a new sonosensitizer, MnN5 SA/CNF-HA, which not only facilitates US-triggered ROS generation but also exhibits excellent catalase-like (CAT-like) activity to produce additional O2. HA can specifically bind to CD44, which is highly expressed on M1 macrophages. After LPS stimulation, CD44 expression significantly increased, leading to greater phagocytosis of MnN5 SA/CNF-HA by M1 macrophages compared with MnN5 SA/CNF. Additionally, fluorescence images of arterial transverse sections showed evident colocalization, indicating that MnN5 SA/CNF-HA accumulated in intraplaque macrophages. In vitro, US irradiation alone had no effect on M1 macrophages. However, the combination of MnN5 SA/CNF-HA and US significantly increased intracellular ROS and induced apoptosis in M1 macrophages. Our results demonstrated that the MnN5SA/CNF-HA+ US group had a significant increase in Bax/Bcl-2 expression compared with those treated with US or MnN5 SA/CNF-HA. Interestingly, co-stimulation with LPS and CoCl2 significantly increased HIF-1α expression, but this expression was significantly decreased after adding MnN5SA/CNF-HA. In ApoE−/− mice, SCT also efficiently increased macrophage apoptosis and reduced HIF-1α expression. These effects ultimately led to the inhibition and stabilization of atherosclerotic plaques. In the treatment groups, no tissue damage of major organs was observed.
CONCLUSIONS MnN5 SA/CNF-HA can effectively target macrophage-enriched plaques and modulate the hypoxic microenvironment, thereby enhancing SCT efficacy and inducing greater apoptosis of M1 macrophages. This enzyme-responsive SCT was safe and effectively inhibited the progression of plaque and enhanced plaque stability, further preventing the development and exacerbation of AS.
GW35-e0991
Mengqi Su
The University of Hong Kong-Shenzhen Hospital
OBJECTIVES Stable coronary artery disease (SCAD), though labeled ‘stable,’ often progresses to severe events like myocardial infarction (MI) or major adverse cardiovascular events (MACE), despite adherence to guideline-recommended therapies. Consequently, there is a critical need for more sensitive, specific, and non-invasive biomarkers to identify patients with significant coronary artery disease at high risk of imminent cardiovascular events, enabling timely intervention. Furthermore, post-PCI SCAD patients still face the risk of recurrent events and rehospitalization due to ongoing disease progression. While cardiopulmonary exercise testing (CPET), especially the VO2max metric, correlates with clinical outcomes, its use is limited by operational demands and contraindications. Therefore, exploring biomarkers identified through CPET to predict cardiac function and readmission risk post-PCI offers a more accessible and less invasive strategy for patient management and care. Our study aims to identify biomarkers for diagnosing high-risk SCAD, predicting post-PCI cardiac function, and hospital readmission risks, thus providing a comprehensive approach to enhancing patient outcomes.
METHODS We conducted a comprehensive analysis involving SCAD patients and healthy controls. Protein expression was assessed using the OLINK proteomics method. Machine learning techniques were applied to integrate clinical risk factors and biomarkers, aiming to enhance diagnostic precision. CPET was utilized to evaluate the cardiac function of SCAD patients post-PCI, and the Weber classification was employed to stratify patients by cardiac function severity. Combining CPET metrics and the Weber classification, we identified biomarkers associated with cardiac function and hospital readmission. Additionally, we investigated potential drugs and regulatory factors targeting these key proteins.
RESULTS Significant differences in protein expression were identified between SCAD patients and controls. The integration of biomarkers (BOC, LGALS9, ADM, ACE2, NPPB) with the clinical risk factor (gender) using machine learning significantly improved diagnostic accuracy, achieving an AUC greater than 0.9 in both the training and test sets. CPET analysis revealed persistent deficits in cardiac function in SCAD patients compared to healthy individuals, especially during exercise, despite undergoing PCI. Stratification using the Weber classification showed distinct biomarker variations across different severity levels of cardiac dysfunction. Notably, ADAMTS13, HAVCR1, PGF, TNFRSF11A, and VSIG2 were closely associated with cardiac function classification and hospital readmission. Additionally, potential therapeutic targets, including regulatory proteins and drugs such as resveratrol, were analyzed for modulating these key proteins to improve cardiac function and reduce hospital readmissions.
CONCLUSIONS Utilizing biomarkers for the timely diagnosis of SCAD patients requiring PCI offers non-invasive and convenient advantages, enabling earlier and more accurate detection, and potentially reducing cardiovascular events. Additionally, employing specific biomarkers to predict post-PCI cardiac function and readmission risk can optimize treatment plans and enhance the monitoring of high-risk patients. Furthermore, analyzing potential therapeutic targets, such as regulatory proteins and drugs like resveratrol, can contribute to improved patient management and outcomes.
GW35-e1117
Linyi Li, Yu Wang, Zhiyong Du, Yanwen Qin
Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, People’s Republic of China
OBJECTIVES Hyperlipidemia is a major and modifiable risk factor for atherosclerotic cardiovascular diseases. Although various therapeutic drugs are available, a significant portion of patients do not achieve target lipid levels, and some lipid-lowering drugs carry the risk of hyperglycemia. Thus, new intervention targets are needed.
METHODS We investigated the therapeutic effects of liver-specific overexpression of aconitase 1 (ACO1), a key enzyme in citrate metabolism, on hyperlipidemia and related diseases using multiple hyperlipidemic mouse models, including high-cholesterol diet-fed C57BL/6J mice, LDLR knockout mice, and ApoE knockout mice. Additionally, we analyzed the impact of ACO1 overexpression on hepatic metabolic homeostasis through metabolomics and metabolic flux analysis.
RESULTS Our study confirmed that ACO1 expression and activity are reduced in hyperlipidemic mouse models. Liver-specific ACO1 overexpression significantly reduced atherogenic lipoproteins, improved fatty liver, alleviated experimental atherosclerosis, and improved hyperglycemia in multiple hyperlipidemic models. Through metabolomics and metabolic flux analysis, we elucidated that the overexpression of ACO1 in the liver promotes the metabolism of citrate to α-ketoglutarate, thereby reducing the metabolic flux of citrate to acetyl-CoA and inhibiting de novo lipogenesis. Furthermore, ACO1 overexpression in the liver enhances glycolysis to replenish citrate diverted by ACO1 and to maintain citrate homeostasis and energy production.
CONCLUSIONS Our findings suggest that promoting ACO1-mediated hepatic citrate metabolism remodeling improves lipid metabolic disorders by inhibiting de novo lipogenesis and alleviates hyperglycemia by activating glycolysis in hyperlipidemic mouse models. This highlights the potential of ACO1 as a therapeutic target for glucolipid-lowering treatments.
GW35-e1141
Dong Guo, Xue Yang, Jing Geng, Lang Hu, Yan Li
Department of Cardiology, Tangdu Hospital, Airforce Medical University, China
OBJECTIVES Iron overload is an important detrimental factor contributing to the poor prognosis of myocardial infarction (MI). Establishing effective iron chelation strategy to reduce iron content is of great significance for improving cardiac function post MI. Macrophages play a crucial role in iron homeostasis. However, there are few reports on the function and mechanism of macrophages in myocardial iron overload post MI.
METHODS Macrophages depleted mice (Macdepleted mice) were developed by expressing the diphtheria toxin receptor under Siglec1 (marker of macrophages). MI model was constructed by left anterior descending coronary artery ligation. Cardiomyocytes and macrophages were isolated, co-cultured, and subjected to hypoxia treatment in vitro. Macrophages derived extracellular vesicles (MΦ-EVs) were collected from the culture medium of macrophage by ultracentrifugation.
RESULTS Firstly, we discovered MI mice showed significantly elevated iron content and expression of transferrin (Tf) and ferritin heavy chain 1 (FTH1), and obviously increased cardiac ferroptosis, as evidenced by increased malondialdehyde (MDA) and 4-hydroxynonenal (4HNE) level and decreased glutathione (GSH) and glutathione peroxidase 4 (GPX4) content, demonstrating the existence of myocardial iron overload post MI. Then, Macdepleted mice were subjected to MI. Compared to control MI mice, the cardiac iron level and ferroptosis was further increased in Macdepleted mice post MI. Besides, macrophage depletion led to infarcted myocardium expansion and cardiac dysfunction aggravation post MI. Macrophages were then isolated and cocultured with cardiomyocytes in vitro. Compared to those cultured alone, cardiomyocytes cocultured with macrophages showed decreased iron level and LDH releases post hypoxia treatment. These results suggested that macrophages exerted protective effect on alleviating iron overload and cardiac dysfunction post MI. Next, we collected MΦ-EVs and discovered that intramyocardial injection of MΦ-EVs significantly relieved cardiac iron overload and ferroptosis in MI hearts. MI mice treated with MΦ-EVs exhibited significant cardiac function improvement.We then intended to explore the mechanism by which MΦ-EVs exerted cardiac protective effect. Immunoelectron microscopy and mass spectrometry results revealed that transferrin receptor (TfR), a critical receptor for Tf-mediated iron uptake, was enriched on surface of MΦ-EVs. Nano-flow cytometry results demonstrated that TfR on EVs surface could bind to Tf. Besides, MΦ-EVs incubation could significantly reduce Tf and iron level in myocardium and cardiomyocyte lysate, demonstrating MΦ-EV could bind with Tf through TfR on its surface and thus exert iron chelation effect. To validate that, we generated MΦ-EVs with TfR deficiency (MΦ-EVTfR-low). The effect on alleviating iron overload and cardiomyocytes ferroptosis was barely lost in MΦ-EVTfR-low, as evidenced by comparable cardiac iron, MDA, GPX4 and 4-HNE levels between MI mice injected with PBS and MΦ-EVTfR-low. MΦ-EVTfR-low treatment also could not mitigate the cardiac dysfunction in post-MI mice.
CONCLUSIONS Collectively, we demonstrated a new endogenous iron chelation mechanism mediated by MΦ-EVs: MΦ-EV bound with Tf through TfR on its surface and removed excess Tf-bound iron from infarcted myocardium, thus mitigating myocardial iron overload and cardiac dysfunction post MI. These results highlight the potential of MΦ-EV as a candidate for iron chelation therapy, offering a novel and promising therapeutic approach against iron overload in MI and other cardiovascular diseases.
GW35-e1201
Yanghui Chen, Daowen Wang
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
OBJECTIVES The genetic basis of aortic dissection (AD) has expanded from a germline to somatic genome, including clonal hematopoiesis of indeterminate potential (CHIP). How CHIP confers AD risk in East Asian individuals was completely unknown.
METHODS Using stepwise calling on next-generation sequencing data from 1694 patients with AD referred to 3 centers between October 2005 and February 2024, CHIP mutations were identified. We associated CHIP with short-term complications in hospital and long-term all-cause mortality in patients with AD. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined.
RESULTS In total, 272 (16.1%) patients with AD carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, P53, and ASXL1. Patients with CHIP mutations were older than noncarriers (52±7.9 versus 60±8.8; P<0.001). Notably, individuals with clones demonstrated a higher complications risk after surgery, including postoperative pneumonia (OR: 1.59, 95% CI: 1.16–2.14), postoperative renal insufficiency (OR: 1.65, 95% CI: 1.18–2.28), gastrointestinal bleeding (OR: 2.34, 95% CI: 1.36–3.92) and stroke (OR: 2.3, 95% CI: 1.36–3.76). Additionally, CHIP was associated with death risk compared with non-CHIP carriers. Moreover, patients with CHIP mutations showed higher circulating hypersensitive C-reactive protein, procalcitonin, interleukin-6 and N-terminal pro-B-type natriuretic peptide.
CONCLUSIONS This is the first study to show that CHIP mutations occurred in 16.1% of patients with AD are associated with a severe inflammatory state and confer a poorer prognosis.
GW35-e1253
Pengqi Lin, Lina Zou, Lu Xia, Dechun Yin
The First Affiliated Hospital of Harbin Medical University
OBJECTIVES Atrial fibrillation (AF) is the most common arrhythmia in patients with stress cardiomyopathy (SCM), and SCM patients with AF have a poorer long-term prognosis and higher mortality compared to those without AF. Both the pathogenesis of SCM and the occurrence of AF are closely related to the excitement of sympathetic nerves. In the central nervous system, microglia participate in the regulation of neurons in various diseases by regulating the secretion of neuroinflammatory factors. Therefore, this article will mainly verify the central nervous mechanism of the activation of hypothalamic microglia in regulating AF in SCM rats.
METHODS Male Sprague-Dawley (SD) rats were divided into three groups: SCM, SCM + Mino, and control. An SCM model was created using male SD rats, restraint for 6 h every day for a week. In the SCM + Mino group, minocycline was administered via intraperitoneal injection 2 hours before the start of the restraint stress (RS) experiment to inhibit microglial activation. Determined structural and functional changes in the ventricles and atria through echocardiography, and detected myocardial injury markers and stress hormone levels through plasma ELISA. The possibility of AF was assessed by detecting IL-6 levels using ELISA. RNA sequencing, immunohistochemistry, Western blotting, and ELISA were employed to explore and validate the involvement of hypothalamic microglia, neuroinflammation, and central sympathetic nervous activity in SCM.
RESULTS (1) RS successfully induced SCM in SD rats, SCM rats showed atrial enlargement and an increased incidence of AF. (2) Microglia in the hypothalamus were activated, showing an activated state, increased numbers, and specific enrichment in the paraventricular nucleus (PVN). (3) In the SCM rats, the expression of neuroinflammatory factors increased in the PVN, and central sympathetic nervous activity increased. (4) Minocycline inhibited the activation of microglia, reduced sympathetic nervous activity, improved cardiac structure and function in SCM rats, and enhanced atrial electrical stability.
CONCLUSIONS RS induced a model of SCM in SD rats, activating microglia in the hypothalamus. The activated microglia accumulated in the PVN, increasing central neuroinflammation, mediating increased central and peripheral sympathetic nervous activity, altering atrial structure, and ultimately increasing susceptibility to AF.
GW35-e1352
Jiaqi Yu, Yuyu Li, Weiyao Chen, Jie Du, Yuan Wang
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Cardiac fibrosis is a prevalent pathological process observed in the progression of numerous cardiovascular diseases and is associated with an increased risk of sudden cardiac death. The BRD4 inhibitor JQ1 has powerful anti-fibrosis properties, its clinical application is extremely limited due to its side effects. There is still an unmet need for effective, safe and low-cost treatment. To develop safe, effective and low-cost targeted therapies that reduce the burden of heart disease on both patients and health care systems.
METHODS A novel JQ1-encapsulated antifibrotic drug-loading system was developed by encapsulating fused platelet and erythrocyte membranes with PLGA nanoparticles (JQ1 NPs) loaded with the antifibrotic drug JQ1. Membrane fusion was validated by fluorescence resonance energy transfer method and immunoblotting. Proteins were identified and classified using proteomics. Pressure overload-induced and MI-induced mouse models of myocardial fibrosis were used to assay targeting ability and antifibrotic effects. Pathologic staining and public databases were used to demonstrate the toxic effects of drug-carrying systems in other organs.
RESULTS A multifunctional biomimetic nanoparticle drug delivery system (PM&EM nanoparticles) is presented, which is assembled by platelet membranes and red blood cell membranes to deliver JQ1 for treating cardiac fibrosis. The platelet membrane endows PM&EM nanoparticles with the ability to target cardiac myofibroblasts and collagen, while the participation of erythrocyte membrane can increase the long-term circulation ability of the nano drug-loaded system and can be further engineered to increase fluidity. In addition, PM&EM nanoparticles can deliver sufficient JQ1 with controllable release to achieve excellent anti-fibrosis effects. Based on these advantages, it is demonstrated in both pressures overloaded induced mouse cardiac fibrosis model and MI-induced mouse cardiac fibrosis that injection of novel fusion membrane biomimetic nanodrug carrier system can effectively reduce fibroblast activation, reduce collagen secretion, and improve cardiac fibrosis. In addition, it can greatly reduce the toxic and side effects of long-term JQ1 treatment on the liver, kidney and intestinal tract.
CONCLUSIONS Ours results suggest that the integration of native platelet and erythrocyte membranes as a multifunctional biomimetic drug delivery system has great potential value in the treatment of cardiac fibrosis and the prevention of drug side effects.
CARDIOVASCULAR DISCIPLINARY RESEARCH
PULMONARY VASCULAR RELATED DISEASES
GW35-e0039
Guangwei Hunag
Yan’an Affiliated Hospital of Kunming Medical University
OBJECTIVES Evidence from observational studies and clinical trials suggests that the gut microbiota is associated with pulmonary embolism. However, a causal relationship between the gut microbiota and pulmonary embolism remains to be determined. Pulmonary embolism poses a significant health risk, and understanding its potential links to the gut microbiota could inform preventive and therapeutic strategies.
METHODS In this study, we employed two-sample Mendelian randomization (mR) to assess the causal effects of gut microbes on pulmonary embolism. We genetically predicted the composition of the gut microbiota using data from three databases and correlated them with pulmonary embolism. Five Mendelian randomization methods, including inverse variance weighted (IVW), MR-Egger, weighted median, simple model, and weighted mode, were utilized to investigate the causal relationship between intestinal flora and pulmonary embolism.
RESULTS At the genus level, our analysis, particularly the Inverse Variance Weighted (IVW) method, indicated that Anaerotruncus (OR = 0.997, 95% CI = 0.995–0.999, P = 0.007) and the Eubacteriumhallii group (OR = 0.997, 95% CI = 0.995–0.999, P = 0.004) were associated with a decreased risk of pulmonary embolism. Notably, we observed no evidence of heterogeneity or pleiotropy in our analyses, strengthening the validity of our findings.
CONCLUSIONS Our study provides compelling evidence suggesting that the presence of Anaerotruncus and the Eubacteriumhallii group in the gut microbiota is associated with a reduced risk of pulmonary embolism. These findings underscore the potential importance of specific bacterial groups in modulating the risk of pulmonary embolism. Future research should delve into the mechanistic roles of these bacterial taxa in the pathophysiology of pulmonary embolism, offering insights into novel therapeutic avenues and preventive strategies. Further exploration of the intricate interplay between the gut microbiota and pulmonary health could pave the way for personalized interventions targeting microbial dysbiosis in individuals at risk of pulmonary embolism.
GW35-e0173
Xin Li, Tao Yang, Qin Luo, Qing Zhao, Qixian Zeng, Yi Zhang, Anqi Duan, Zhihua Huang, Sicheng Zhang, Luyang Gao, Yijia Wang, Sicong Li, Zhihui Zhao, Zhihong Liu
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Pulmonary artery lesions in Takayasu arteritis can be successfully addressed by percutaneous transluminal pulmonary angioplasty (PTPA). However, the complexity of technical procedures and treatment response to PTPA significantly differ across various types of pulmonary artery lesions. Currently, there is an absence of definitive guidelines on the performance of PTPA in managing pulmonary artery lesions associated with Takayasu arteritis. Therefore, we aim to propose a novel classification for pulmonary artery lesions in Takayasu arteritis to guide the performance of PTPA. Additionally, we seek to evaluate the success rate of PTPA and assess the technical challenges associated with different lesion types.
METHODS We screened all patients diagnosed with Takayasu arteritis who had pulmonary artery involvement and underwent pulmonary angiography from July 2014 to April 2022 in Fuwai Hospital.
RESULTS A total of 365 pulmonary vascular lesions were observed in 63 patients based on pulmonary angiography. According to morphology, the pulmonary arterial lesions were classified into four groups: stenosis, dilation, subtotal occlusion, total occlusion. Total occlusion was further subclassified as cone-shape occlusion, pocket-like occlusion, ostium occlusion. PTPA succeeded in 96.81% of all treated lesions. The success rate of PTPA was associated with the type of lesion. All the PTPA succeed in stenosis, subtotal occlusion, whereas none of the attempt in ostium occlusion succeed. Dissection was the most commonly observed complication (2.94%). The 2-year survival rate was 97.3% in patients who underwent PTPA.
CONCLUSIONS The morphology of pulmonary lesions in Takayasu arteritis had a significant impact on the PTPA success rate. The failure rate and technical difficulty of PTPA increased in the following order: stenosis, dilation, subtotal occlusion, and total occlusion. Our classification scheme could guide the performance of PTPA for pulmonary artery lesions in Takayasu arteritis.
GW35-e0194
Yin Wang, Chunyan Rong, Ming Lu
The First Hospital of Jilin University
OBJECTIVES Pulmonary artery in situ thrombosis (PAIST) is a thrombus that forms within the pulmonary arterial system, as opposed to an embolus from another part of the body (e.g., the deep veins of the lower extremities) that dislodges into the lungs and forms.
METHODS A 59-year-old man was admitted to the hospital with “sudden onset dyspnea for more than half a day”, and a dual-source Computed Tomography Angiography (CTA) for Chest Pain suggesting a nodular low-density filling defect in the lumen of the left pulmonary artery trunk in close relation to the ductus arteriosus.
RESULTS The patient was initially considered to have Pulmonary Embolism (PE), and this diagnosis was ruled out on re-reading of the radiographs, and was then treated surgically in cardiac surgery, where the postoperative pulmonary artery growths were suggestive of coagulated tissue. Combined with the patient’s history of congenital heart disease and the imaging of chest pain dichotomy CTA, the final diagnosis was “PAIST”. The patient was admitted to the hospital and treated with anti-infection, anticoagulation, and correction of cardiac machine remodeling, and was later discharged from the cardiac surgery department after an operation of vein catheter ligation and resection of pulmonary artery lesion and extracorporeal circulation-assisted open cardiac surgery, which alleviated the patient’s discomfort, such as dyspnea.
CONCLUSIONS Both PAIST and PE present as low-density filling defects of the pulmonary arteries, but because we know less about PAIST, low-density filling defects of the pulmonary arteries are often considered as PE.
GW35-e0263
Jing Zhang, Xiaoxiao Guo, Xiaohan Qin, Yuhan Qin, Yule Wang
Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Right ventricular (RV) remodeling, which currently has no targeted and effective treatment, has been demonstrated to be more severe in males than in females under similar pressure overload. Testosterone was thought to be potentially involved in the sex differences in RV remodeling. However, the exact mechanism underlying this effect remains unknown.
METHODS We performed RV myocardial proteomics and metabolomics in male and castrated male RV remodeling SD rats induced by pulmonary artery banding (PAB), and further validated the expression of key proteins in testosterone-replacement castrated male rats and monocrotaline (MCT)-induced RV remodeling rats.
RESULTS With the same extent of increases in RV afterload, male PAB rats showed more pronounced RV hypertrophy and fibrosis than castrated male PAB rats (all P < 0.05). The omics analysis indicated that the platelet-derived growth factor receptors beta (PDGFRB) was uniquely upregulated in the RV remodeling process of male rats, with significant upregulation of signal transducer and activator of transcription 3 (STAT3), which were not presented in castrated male rats. Impaired microtubule dynamics, downregulated organization of cytoskeleton, increased production of reactive oxygen species, and cytokine storm were also specifically demonstrated in the male group, which acted downstream of STAT3. More metabolites associated with fatty acids (FA) metabolism were downregulated in males, indicating a greater extent of impairment of FA oxidation. Correlation analysis showed that PDGFRB and STAT3 were negatively correlated with carnitine metabolites only in male rats, suggesting that testosterone might influence FA metabolism by modulating the PDGF pathway. Western blotting and immunohistochemistry verified the activation of the PDGF pathway in the process of RV remodeling in male and other testosterone-replacement castrated male PAB rats. The total protein of PDGFRB was also increased in MCT-induced RV remodeling rats. Cmap analysis showed that Olaparib, a poly (ADP-ribose) polymerases inhibitor, could reverse the differential protein profile in male rats, but not in castrated rats.
CONCLUSIONS Testosterone might exaggerate RV hypertrophy and fibrosis by regulating the PDGFRB-STAT3 signaling pathway, contributing to insufficient energy supply and increased synthesis of ROS. Olaparib might be a potential therapy for RV remodeling, especially in males.
GW35-e0297
Wenqing Xu1,2, Lingfeng Xi3, Anqi Liu4, Wanmu Xie2, Min Liu4, Shihua Zhao1,
1Department of Magnetic Resonance Imaging, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
3National Center for Respiratory Medicine; Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
4Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China
OBJECTIVES The morphological difference between chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) is unclear. We aim to identify morphological markers using computed tomography pulmonary angiography (CTPA) through automated segmentation technology and analyze changes in peripheral lung blood volume in CTEPD.
METHODS The morphological difference between chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) is unclear. We aim to identify morphological markers using computed tomography pulmonary angiography (CTPA) through automated segmentation technology and analyze changes in peripheral lung blood volume in CTEPD.
RESULTS A total of 190 patients (20 control individuals, 54 CTEPD, 116 CTEPH) were ultimately included. The results of quantitative analysis showed that the pulmonary artery tortuosity of the three groups in the control group, CTEPD group, and CTEPH group showed a gradually increasing trend (1.07 [1.06–1.10] vs. 1.10 [1.07–1.14] vs. 1.14 [1.10–1.18], P < 0.01). Pulmonary artery tortuosity was moderately positively correlated with mean pulmonary artery pressure and pulmonary vascular resistance at rest (P < 0.01). In addition, pulmonary artery BV5 and BV10 standardized indicators in CTEPD patients were significantly higher than those in CTEPH patients (P < 0.01).
CONCLUSIONS The pulmonary arterial tortuosity may serve as an imaging marker for distinguishing between CTEPH, CTEPD and control people. The performance of CTEPD in the volume of middle to small arteries remains normal, indicating that it may serve as a pivotal factor contributing to the absence of pulmonary hypertension during CTEPD at rest.
GW35-e0301
Zexiang Deng1,2, Dan Luo1,2, Xiaomei Zhang3, Lianggeng Gong1,2
1Department of Radiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China
2Intelligent Medical Imaging of Jiangxi key Laboratory, Nanchang 330006, China
3Department of Radiology, The First Affiliated Hospital of Gannan Medical University
OBJECTIVES Elderly populations as a high-incidence group for acute pulmonary embolism (APE) face an increased risk of acute respiratory failure. If pulmonary perfusion is not improved, mechanical ventilation or even endotracheal intubation may be required to sustain life, particularly in those with common geriatric conditions such as chronic obstructive pulmonary disease (COPD). Moreover, age-related degeneration of chest muscles further impairs respiratory function, potentially increasing the risk of respiratory distress events. This study will employ CT histogram analysis to quantify chest muscle degeneration and integrate this data with prevalent geriatric comorbidities (e.g., COPD, hypertension, diabetes) to develop machine learning (ML) models for predicting the requirement for mechanical ventilation in elderly APE patients during hospitalization.
METHODS We retrospectively collected data on 261 elderly patients (age ≥65) from the Second Affiliated Hospital of Nanchang University between January 2020 and April 2024. Chest muscle CT histogram features were obtained from non-contrast CT scans conducted within 14 days. At the T4 vertebral level, the pectoralis major and minor muscles were delineated and measured areas. Based on the standard workflow in Python, we extracted 10 CT histogram features for these muscles, including the 10th, 25th, 50th, 75th, and 90th percentiles of CT values for both muscles. To quantify muscle fat infiltration, we proposed the Chest Muscle Fat Ratio (definition: intermuscular fat area/chest muscle area). Lasso regression was used to select features from these 15 chest muscle characteristics and 15 clinical features, and a correlation matrix was employed to remove highly correlated features. The dataset was split into training and test sets in a 7:3 ratio, and five ML models including, support vector classifier (SVC), XGBoost, RandomForest, K-Nearest Neighbors (KNN), logistic regression (LR) were developed. The optimal model was externally validated using data from 60 elderly APE patients whom were consecutively collected from Gannan Medical University.
RESULTS Among the 261 patients used for model development, a total of 50 patients exhibited indications for mechanical ventilation during hospitalization. In the external validation set of 60 patients, 10 patients presented indications for mechanical ventilation. Three chest muscle features and 9 clinical features were used to construct the machine learning models. The LR and SVC models performed comparably on the test set. However, in the external validation set, the SVC model outperformed the others (AUC: 0.855, Accuracy: 0.867, Recall: 0.6364, Specificity: 0.9184).
CONCLUSIONS This study developed a generalizable ML model capable of predicting the need for mechanical ventilation in elderly APE patients, which performed excellently on the external validation set. This model is valuable for optimizing patient risk stratification and facilitating the development of personalized treatment plans.
GW35-e0875
Xin Li, Tao Yang, Luo Qin, Zhao Qing, Huang Zhihua, Zhao Zhihui, Liu Zhihong
Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Although Japanese researchers have modified balloon pulmonary angioplasty (BPA), its success rate in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) has been significantly improved, and the incidence of complications has been significantly reduced, total occlusion remains a challenge for BPA. Owing to their low success and high complication rates, most interventional cardiologists are reluctant to address total occlusion. There is a paucity of guidance on BPA performance in total occlusion. We aimed to classify total occlusion according to morphology and present an illustrative approach for devising a tailored treatment strategy for each distinct type of total occlusion.
METHODS All patients diagnosed with CTEPH who underwent BPA between May 2018 and May 2022 at Fuwai Hospital were included retrospectively.
RESULTS A total of 204 patients with CTEPH who underwent BPA were included in this study. Despite comparable baseline demographics, patients with total occlusion had significantly worse hemodynamics than those without total occlusion, as evidenced by higher mean pulmonary arterial pressure (50.51 ± 11.89 mmHg vs. 47.16 ± 12.23 mmHg, P = 0.049) and pulmonary vascular resistance (10.07 ± 4.72 wood units vs. 8.71 ± 4.33 wood units, P = 0.029). Based on the morphology, we categorized the lesions into three groups: pointed-head, round-head, and orifice occlusions. Pointed-head occlusion could be successfully addressed using soft-tip wire, round-head occlusion warranted hard-tip wire and stronger backup, and orifice occlusion warranted the strongest backup force. The success rates for each group were as follows: pointed-head (95.45%), round-head (46.15%), and orifice occlusion (33.33%), with orifice occlusion having the highest complication rate (50%). The classification of occlusion was associated with BPA success (round-head occlusion vs. pointed-head occlusion, odds ratio 24.500, 95% confidence interval 2.498–240.318, P = 0.006; orifice occlusion vs. pointed-head occlusion, odds ratio 42.000, 95% confidence interval 3.034–581.434, P = 0.005).
CONCLUSIONS Occlusion morphology has a significant impact on BPA success and complication rates. A treatment strategy tailored to each specific occlusive lesion, as outlined in the present study, has the potential to serve as a valuable guide for clinical practitioners.
GW35-e0998
Zhijun Lei, Wenhui Peng
Shanghai Tenth People’s Hospital
OBJECTIVES The prognostic value of atrial fibrillation (AF) burden in pulmonary embolism (PE) is unclear. We aimed to investigate the prognostic impact of AF burden in patients with PE.
METHODS This retrospective study was conducted among patients diagnosed as PE in the Medical Information Mart for Intensive Care IV (MIMIC-IV 2.0) database. AF was defined using the non-invasive continuous electronic monitoring (CEM) record charted by nurse. AF burden was calculated as percentage of AF duration to total CEM duration during ICU stay. AF patients were stratified into low-burden or high-burden groups according to optimal cut-off value (12.0%). Baseline characteristics were compared among patients with sinus rhythm (SR), low-burden AF and high-burden AF. Univariate and multivariate analyses were used to evaluate the outcome.
RESULTS Of 1307 patients included, 246 (20.9%) patients coexisted with AF (84 with low-burden AF and 162 with high-burden AF). During 1-year follow-up, 205 (22.1%), 22 (26.2%) and 66 (40.7%) patients suffered from all-cause death, respectively. Compared with SR, it was high-burden AF (HR: 1.67, 95% CI: 1.22–2.29, P = 0.001) rather than low-burden AF (HR: 0.97, 95% CI: 0.62–1.53, P = 0.906) that was significantly associated with 1-year mortality after full adjustment. Our subgroup and sensitivity analyses further verified the robustness of these findings. Furthermore, our restricted cubic spline (RCS) analysis illustrated an inverted U-shaped relationship between AF burden and 1-year mortality.
CONCLUSIONS In patients with PE, AF burden was significantly associated with 1-year mortality and it might be beneficial to risk stratification.
GW35-e1146
Yi Ye1,2, Song Yu3, Wang Yanjun1,2, Liu Juanli1,2, Ge Rili1,2, Tana Wuren1,2
1Research Center for High Altitude Medicine, Qinghai University, Xining, China
2Qinghai Provincial Key Laboratory for Application of High-Altitude Medicine, Xining, China
3Affiliated Hospital of Southwest Jiao Tong University, The General Hospital of Western Theater Command, Chengdu, Sichuan, China
OBJECTIVES Chronic exposure to hypoxia, whether due to residence at high altitudes or underlying diseases, has emerged as a significant cause and promoter of pulmonary hypertension. During prolonged exposure to hypoxia, the infiltration of circulating immune cells and the expression of pro-inflammatory factors contribute to immune inflammatory dysregulation in the pulmonary arteries. Inflammation and endothelial-to-mesenchymal transition (EndMT) are notable features of endothelial dysfunction in hypoxic pulmonary hypertension (HPH). Neutrophil extracellular traps (NETs), which are produced during neutrophil death have been implicated in the pathogenesis of multiple vascular disorders, yet their role in HPH remains understudied. To address this gap, we aimed to uncover evidence of NETs formation, also called NETosis, in pulmonary hypertension and explore the potential protective effects of cl-amidine, a potent inhibitor of NETs, against EndMT in HPH mice.
METHODS Plasma and serum samples were collected from patients with HPH to measure circulating neutrophils and markers of NETs. To further investigate the underlying mechanisms, two animal models were utilized, the chronic hypoxia mouse model and the Sugen/hypoxia mouse model. Followed by assessing the efficacy of CI-amidine, an inhibitor of NETs, in reversing pulmonary vascular remodeling. Lung tissues were harvested and subjected to flow cytometry and ELISA testing to determine NETosis. We further examined the protein levels of endothelial and mesenchymal markers using western blot analysis to confirm the induction of EndMT in HPH by NETosis.
RESULTS Patients with HPH showed elevated levels of circulating neutrophils and NETs markers, which were similarly observed in HPH mice with increased neutrophils and NETosis. HPH mice exhibited significant hemodynamic changes and extensive pulmonary vascular remodeling. Furthermore, western blot analysis and IHC staining confirmed increased endothelial cells transition to a mesenchymal phenotype. Notably, administering a specific NETs inhibitor via intraperitoneal injection successfully reduces neutrophil infiltration and effectively prevents and reverses the pulmonary hypertensive phenotype as well as attenuated expression of EndMT markers.
CONCLUSIONS NETs may play a contributory role in the vascular pathology of HPH, characterized by the activation of local proinflammatory processes and endothelial dysfunction through EndMT. Inhibiting NETosis may provide novel therapeutic target for HPH management.
GW35-e1210
Jie Yang, Peiran Yang
Chinese Academy of Medical Sciences & Peking Union Medical College
OBJECTIVES Pulmonary hypertension due to left heart disease (PH-LHD) is a common subtype of pulmonary hypertension, characterized by elevated pulmonary vascular pressure and pulmonary vascular lesions caused by LHD. The increased pulmonary circulation pressure is usually due to blood flow obstruction caused by left ventricular (LV) dysfunction (such as heart failure), left atrial disease, or cardiac valve abnormalities. However, small animal models capable of simulating LHD-PH require further exploration. This study reports a novel mouse model and compares the effects of different ages on the model phenotype, which aids in the research of PH-LHD.
METHODS We established a model of LHD-PH in C57BL/6J mice of different ages induced by pressure overload. We utilized the Transverse Aortic Constriction (TAC) method to construct a mouse model of heart failure by creating a localized narrowing in the transverse section of the thoracic aorta, thereby applying a pressure load on the heart, especially the left ventricle, to simulate the pathophysiological conditions of heart disease. By extending the model duration, pulmonary arterial pressure was induced to rise. Mice aged 8 weeks and 20 weeks underwent sham operations and the same aortic constriction scheme, respectively. Sixteen weeks later, left heart function and pulmonary arterial hemodynamics were evaluated by ultrasound, followed by invasive hemodynamic testing and pathological examination.
RESULTS Twelve weeks after TAC, echocardiography revealed that different group of mice all exhibited LV concentric hypertrophy and systolic dysfunction, which subsequently led to increased end-systolic and end-diastolic pressures in the LV and pulmonary hypertension (22.60 ± 2.039 mmHg vs. 28.32 ± 1.312 mmHg). Additionally, pathological examinations showed characteristics of LHD, such as LV fibrosis and cardiomyocyte hypertrophy. Invasive hemodynamic testing found that both groups of mice had elevated pulmonary artery pressure, but the degree of increase varied; compared to 8-week-old mice, the 20-week-old mice exhibited a more severe phenotype of pulmonary hypertension (28.32 ± 1.312 mmHg vs. 32.52 ± 3.839 mmHg), as represented by hemodynamics.
CONCLUSIONS The long-term TAC mouse model can serve as an animal model for PH-LHD, and be used to investigate the pathogenesis and potential intervention methods. Older mice exhibit a more severe disease phenotype, suggesting the potential significance of aging-related mechanisms in the development and progression of PH-LHD.
GW35-e1271
Chanjuan Zheng, Jingping Sun, Xueli Cai
Lishui Municipal Central Hospital
OBJECTIVES Acute tandem occlusion of anterior circulation (TOs) accounts for 15–20% of all vascular occlusions. The therapeutic options of extracranial lesions differ. At present, extracranial ICA stenting (eCAS) is often used while others prefer balloon dilation alone. Otherwise the extracranial ICA lesion is thought to be unnecessary for treatment by some doctors. The main objective of this study is to determine the efficacy and safety for TOs by comparing the results of various endovascular approaches in a large multi-center dataset of 130 individual cases.
METHODS We retrospectively analyzed the data from 6 main comprehensive stroke centers in China from June 2020 to July 2022.
Inclusion criteria: (1) 18≥ years onset within 24 hours; (2) mRS of 0–1 before this stroke; (3) CT or CTA is used to select patients admitted within 6 hours of onset of symptoms, and DEFUSE-3 and DAWN criteria are used to select patients with wakeup or unknown onset. Exclusion criteria: (1) Isolated extracranial ICA lesions; (2) Expected survival time less than 1 year; (3) Unable to complete follow-up visits. The criteria also include routine embolization criteria for AIS. Patients were divided into two groups based on eCAS treatment depending on screening criteria. No treatment randomization was performed. The following variables were collected: Baseline demographic data, laboratory and imaging studies, clinical and surgical data, etc, need to be collected. Endovascular procedures could be performed under general anesthesia or conscious sedation. Mechanical endovascular therapy consisted of two stages: treatment of ICA and treatment of intracranial occluded vessels. Treatment of ICA lesions in the neck is left to the discretion of the treating physician, and can be managed by stenting, angioplasty, or other therapy. If a stent is placed in an ICA, the type of anti-platelet treatment should be administered in accordance with the local protocols of the respective centers. The study outcomes with a predictive mean matching method for continuous variables and logistic regression models for categorical variables.
RESULTS The final cohort comprised 130 patients treated in 6 centers throughout China between June 2020 and July 2022. The gender distribution follows 18 females and 112 males whose mean age was 68.92 ± 10.02 years. The ASPECTS is calculated from CT or magnetic resonance imaging scans in 128 cases (98.5%). Thrombolysis was administered in 47 patients (36.1%). Protect expand-aspiration-revascularization-stent (PEARS) technique was performed in 32 patients (24.6%). The treatment orders had an antegrade (stenting first) and retrograde (MT first) in 34 (26.1%), 64 (49.2%) cases, respectively. As a first-line approach, an eCAS was used in 103 (79.2%) patients and a non-CAS in 27 patients (20.7%). 90d mRS 0–2 was compared in the eCAS and the non-CAS (58.3% [n = 60] vs. 51.8% [n = 14]; P = 0.079).
CONCLUSIONS Our results suggest the independent prognosis rate of neurological function (mRS 0–2) of the non-stent group was not inferior to that of the stent group in tandem occlusion. It is of guiding significance for the selection of operation. Subsequent data from the study sample are still being refined.
GW35-e1286
Wang Zhongchao
General Hospital of Northern Theater Command
OBJECTIVES The pathological changes in arterial pulmonary arterial hypertension (PAH) are manifested as pulmonary vascular remodeling characterised by pulmonary arterial endothelial cell (PAECs) dysfunction and abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs). Oxidative stress plays significant roles in vascular remodeling. Based on the targeted antioxidant capacity of MitoQ on mitochondria, the present study was aimed to investigate the effects of MitoQ on PAH-induced pulmonary vascular remodeling and potential mechanism.
METHODS MCT (40 mg/kg) was used to construct PAH rat model, and Mito Q (2.5 kmg/kg) was applied to construct treatment group; echocardiographic parameters were obtained to assess pulmonary arterial pressure, and the degree of right ventricular hypertrophy was assessed by right ventricular mass/(left ventricular mass + interventricular septal mass). Changes in morphology of the pulmonary vasculature were observed with HE staining, and the morphology of the mitochondria of the pulmonary vasculature was observed with transmission electron microscopy. The changes in the morphology of pulmonary vessels were observed by HE staining, the morphology of pulmonary vascular mitochondria was observed by transmission electron microscopy, and the content of reactive oxygen species (ROS) was measured by DHE staining. In addition, the expression of Mitochondrial Calcium Uniporter (MCU), NADPH oxidase 4 (NOX4), Keap-1, Nrf2, HO-1 and [NAD(P)H: quinone oxidoreductase-1, NQO-1] proteins in the pulmonary vasculature was examined by Western blotting. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced and oxidised glutathione (GSH), cytosolic mitochondrial respiratory chain complex I (NADH–coenzyme Q reductase), and ATP levels in the pulmonary vasculature were examined by using barbiturates sulphate, WST-8, and colorimetric methods.
RESULTS Compared with PAH group, pulmonary artery pressure and right ventricular mass/(left ventricular mass + interventricular septal mass) in MitoQ group were significantly decreased, and the degree of pulmonary vascular wall thickening and fibrosis in PAH group was significantly higher than that in MitoQ group. Mitochondria in PAH group were swollen, mitochondrial matrix electron density decreased, mitochondrial ridge was reduced, broken or disappeared, mitochondrial inner and outer membranes were blurred and broken, visible deposits in mitochondrial inner membrane accumulated and formed vacuoles, mitochondrial outer membranes were broken, mitochondrial residues and dispersed mitochondria were formed, isolation membranes were formed around mitochondria, and autophagosomes and lysosomes were fused. The damaged mitochondrial structure was significantly improved in MitoQ group. Compared with PAH group, mitochondrial functional markers mitochondrial respiratory chain complex I decreased, ATP content increased and MCU protein expression decreased in MitoQ group. Compared with PAH group, the expression of ROS, MDA and NOX4 proteins in MitoQ group decreased. The activity of SOD and CAT, GSH/GSSG and the expression of Nrf2, HO-1 and NQO-1 protein were significantly increased.
CONCLUSIONS MitoQ not only enhances the antioxidant stress level by improving mitochondrial structural damage and reducing mitochondrial dysfunction, but also activates the Keap-1/Nrf2/HO-1 signaling pathway to further improve the antioxidant stress level of the body. Together, they can effectively protect PAECs and PASMCs from oxidative damage, thus alleviating pulmonary vascular remodeling and delaying the pathologic progression of PAH, providing ideas for the treatment of PAH.
Keywords: Mito Q, mitochondria, oxidative stress, pulmonary hypertension, pulmonary vasculature
DIABETES, CEREBROVASCULAR DISEASE, KIDNEY DISEASE, ONCOLOGY AND CARDIOLOGY
GW35-e0006
Meiqi Miao1, Xinxin Liu1, Hailong Dai2, Han Zhang2
1Heilongjiang University of Traditional Chinese Medicine
2Yan’an Hospital, Kunming Medical University
OBJECTIVES Cardio-oncology is an emerging interdisciplinary field concerned with cancer treatment-related cardiovascular toxicities (CTR-CVT) and concomitant cardiovascular diseases (CVD) in patients with cancer. In addition to the mutual exacerbating effects of tumor and CVD through immune inflammation, tumor treatments, including immunotherapy, chemotherapy, radiation therapy, and targeted therapy, may induce immune inflammatory reactions leading to cardiovascular damage. Therefore, immune inflammation serves as a shared mechanism between CVD and cancer. Understanding the relevant inflammatory factors and pathological mechanisms of immune inflammation in CTR-CVT and tumor-associated CVD is crucial for protecting patients against secondary complications and improving patient safety and treatment efficacy.
METHODS We conducted a comprehensive review and retrieved relevant literature from PubMed, Google Scholar, WOS, and Scopus, focusing on the relationship between inflammation and cardio-oncology. This article systematically explores the involvement of immune inflammation in CTR-CVT, cancer-associated cardiovascular diseases, and discusses the application of targeted immunotherapy in cardio-oncology. It thoroughly analyzes the role of inflammation in cardio-oncology, highlighting the potential diagnostic biomarkers of inflammation in cancer and cardiac diseases.
RESULTS Immunotherapy including immune checkpoint inhibitors (ICIs) markedly improve cancer treatment and prolong survival but lead to immune-related adverse events (IRAEs), especially CTR-CVT. Targeting inflammation is a promising approach for treating CTR-CVT, but challenges remain to be solved.
CONCLUSIONS Understanding the potential mechanisms of immune inflammation in cardio-oncology and establishing specific evaluation, diagnostic, and monitoring criteria (e.g., immune-inflammatory markers) for immunotherapy-related cardiovascular toxicity is vital to guide clinical practice.
GW35-e0098
Jiayin You, Xianfeng Wu, Niansong Wang
Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
OBJECTIVES End-stage renal disease (ESRD) is often complicated by left ventricular dysfunction, which is associated with a poor prognosis. This study aims to investigate the association between baseline left ventricular ejection fraction (LVEF) plus left ventricular end-diastolic diameter (LVEDD) with outcomes in peritoneal dialysis (PD) patients.
METHODS In this multicenter retrospective study, 1511 incident Chinese patients on PD between January 1, 2005 and December 31, 2021 were enrolled. Restricted cubic splines (RCS) were used to explore the non-linear associations between LVEF + LVEDD and the risk of mortality. Parametric models for interval-censored survival-time data (stintreg) were used to examine the association between LVEF + LVEDD quartiles and the outcomes.
RESULTS During 6451.11 person-years of follow-up [median 4.81 (IQR 3.61–6.81) years], 247 (17.8%) patients died, including 88 cardiovascular deaths. RCS showed a U-shaped association between LVEF + LVEDD and the risks of all-cause and CV mortality. According to the quartiles, the optimal range of LVEF + LVEDD associated with the lowest risk of all-cause and CV mortality was 103–107, which was set as the reference range. Both higher (≥115) and lower (<103) levels of LVEF + LVEDD were associated with increased risks of all-cause mortality (hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.58–3.07; HR 1.68, 95% CI 1.19–2.36) and cardiovascular mortality (HR 2.51, 95% CI 1.33–4.75; HR 1.86, 95% CI 0.96–3.61).
CONCLUSIONS Low and high levels of baseline LVEF + LVEDD were associated with increased risks of all-cause and cardiovascular mortality in PD patients.
GW35-e0100
Guoliang Hu, Shujuan Li
Department of Neurology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
OBJECTIVES Heart failure (HF) constitutes the source of various damaging pathophysiologic mechanisms in ischemic stroke. However, the effect of a previous HF on the in-hospital outcomes for patients with acute ischemic stroke (AIS) still lacks effective research. We aimed to determine the effect of HF on AIS outcomes: in-hospital mortality, and major adverse cardiovascular events (MACEs).
METHODS This study was conducted at 1476 participating hospitals in the Chinese Stroke Center Alliance (CSCA) among patients with AIS enrolled in the CSCA between August 1, 2015, and July 31, 2019. Multivariable logistic regression and propensity score-matched analyses were used to assess the association between a medical history of HF and in-hospital mortality and MACEs.
RESULTS Of 836,885 patients with AIS, we identified 8950 (1.1%) patients with a medical history of HF (HF group). Compared with patients with AIS without HF, HF group patients had higher rates of all-cause mortality (2.8% versus 0.4%, ASD = 19.2%) and MACEs (15.9% versus 6.6%, ASD = 29.8%). In the multivariable logistic regression analysis, the HF group patients had higher risks of in-hospital all-cause mortality (odds ratio (OR) = 1.87; 95% confidence interval (CI): 1.58–2.21; P < 0.001) and MACEs (OR = 1.27; 95% CI: 1.18–1.36; P < 0.001). After propensity score-matching analysis, the higher risks of in-hospital all-cause mortality (OR = 1.62, 95% CI: 1.30–2.02; P < 0.001) and MACEs (OR = 1.39, 95% CI: 1.26–1.53; P < 0.001) remained in the HF group patients.
CONCLUSIONS Considerable excess risks for in-hospital mortality and MACEs were found in AIS patients with a history of HF. Our findings reinforce the need for systematic cardiovascular evaluation and integrated multidisciplinary care in patients with AIS.
GW35-e0146
Siqi Luo
First Affiliated Hospital of Fujian Medical University
OBJECTIVES Renal denervation, as a minimally invasive interventional therapy for the treatment of refractory hypertension effectively, has been verified to inhibit the excessive activation of sympathetic nerve and reduce blood pressure. However, the target organ protection and cardiovascular events benefits of RDN are still unclear, renal injury plays an important role in the target organ damage of hypertension. Podocyte injury is an important factor leading to the progression of hypertensive kidney injury, but how RDN reduces podocyte injury and regulates autophagy is still unknown. Therefore, we hypothesized that RDN is involved in the regulation of glomerular podocyte autophagy by regulating autophagy and beclin1 regulator 1 (AMBRA1). It can delay the renal injury of hypertension.
METHODS Ten weeks old male SHR rats were randomly divided into renal denervation group, sham operation group and Benazepril treatment group. Male WKY rats of the same age were used as the blank control group. In RDN group, phenol solution was applied to the renal artery to destroy sympathetic nerve. The rats in Bena group were treated with benazepril suspension by gavage at a dose of 0.9 mg · kg/d until 22 weeks of age. In Sham group, the renal artery was exposed, and the abdominal cavity was closed after normal saline application for the same time. The WKY group was fed routinely without any intervention. Blood pressure and urine biochemistry were measured every two weeks, and samples were taken at 12 weeks after intervention. The expression levels of norepinephrine, Ang II, nephrin, AMBRA1, Beclin1, LC3B, and P62 were detected by Elisa, Western blot, and PCR. Renal function and pathological changes were evaluated by blood and urine tests and histology. The impaired autophagy and injury of glomerular podocytes were observed.
RESULTS After 12 weeks of intervention, the mean SBP of RDN group was significantly decreased (P < 0.01). In histological examination, HE staining and transmission electron microscopy results of renal cortex showed that the injury degree of RDN group was lighter than that of Sham group, the fusion of foot processes and the number of autophagosomes were significantly reduced. The results of immunofluorescence and immunohistochemistry confirmed the significant regulatory effect of RDN on AMBRA1. In addition, the values of blood biochemical indexes (urea nitrogen, creatinine and uric acid) and urinary biochemical indexes (urinary protein, urinary microalbumin and urinary β2-microglobulin) related to renal injury were effectively reduced in RDN group (P < 0.05). At the molecular level, NE content in serum and kidney of RDN group decreased (P < 0.01). The expression level of Ang II gene showed the same trend. In addition, the expression of related autophagy factors such as AMBRA1, Beclin1 and LC3B was down-regulated and the expression of P62 factor was up-regulated in RDN group. At the same time, the expression of podocyte specific protein nephrin was decreased.
CONCLUSIONS Renal denervation can inhibit abnormally active sympathetic nerves and over-activation of renin-angiotensin-aldosterone system, and reduce systolic blood pressure in SHR rats. At the same time, it can regulate AMBRA1 factor by inhibiting abnormal autophagy of glomerular podocytes to delay the process of hypertensive kidney injury caused by glomerular podocyte injury.
GW35-e0193
Yu Ma, Hui Fan, Ximing Li
Chest Hospital, Tianjin University
OBJECTIVES Contrast-associated acute kidney injury (CA-AKI) may occur in patients undergoing medical procedures involving X-rays and radiocontrast media, potentially resulting in prolonged renal impairment. However, no effective treatments are available. Therefore, this study aimed to investigate the efficacy of evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in reducing CA-AKI incidence among patients with atherosclerotic cardiovascular disease (ASCVD) undergoing percutaneous coronary intervention.
METHODS This retrospective cohort study included patients who underwent percutaneous coronary intervention between January 2020 and December 2021 at Tianjin Chest Hospital. The study endpoint was CA-AKI incidence, and the impact of selection bias and other potential confounding factors was mitigated using bias matching. Overall, 1642 patients were included in this study: 821 patients received evolocumab treatment before contrast agent application, and 821 did not receive such treatment.
RESULTS CA-AKI incidence was 6.21% and 8.04% in the evolocumab and control groups, respectively. After propensity-score matching, the incidence rate was 5.09% and 14.16% in the evolocumab and control groups, respectively. Evolocumab treatment significantly reduced CA-AKI incidence (P < 0.001). Consistent findings were obtained in the subgroups of individuals with type II diabetes mellitus, chronic heart failure, and hypertension. Evolocumab exhibited a significantly greater protective effect in the high- and extremely high-risk populations than in the low- and middle-risk populations (P < 0.001).
CONCLUSIONS Evolocumab administration significantly reduced CA-AKI incidence among patients with ASCVD. Notably, this effect was more prominent within the subset of high- and extremely high-risk individuals who were already experiencing CA-AKI.
GW35-e0199
Xinning Guo, Meng Jiang
Division of Cardiology, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai, China
OBJECTIVES The clinical utility of doxorubicin (DOX) is constrained by its cardiotoxicity, known as DOX-induced cardiomyopathy (DIC). 5-oxoproline (5-OXO), a degradation product of glutathione, can be converted into glutathione by OPLAH (5-oxoprolinase). However, the role of 5-oxoproline/OPLAH in DIC remains largely unknown.
METHODS By analyzing murine DIC metabolomics, we identified 5-oxoproline as an important metabolite involved in DIC. To investigate the role of 5-oxoproline/OPLAH axis in DIC, we adopted 5-OXO (5 μmol/L; 28 days) and used global OPLAH-knockout mice in DIC mouse models induced with DOX.
RESULTS 5-oxoproline exhibited the highest fold change among all metabolites in murine DIC tissues and 5-oxoproline was downregulated in both serum and myocardial tissues of DIC mice. In DIC mouse model, administration of 5-oxoproline significantly alleviated heart dysfunction, oxidative stress and ferroptosis, while OPLAH knockout exacerbated DOX-induced heart dysfunction, oxidative stress and ferroptosis in mice. Moreover, OPLAH knockout abolished the cardioprotective effect of 5-OXO in DIC model. Mechanistically, doxorubicin induced the translocation of FOXO1 from the cytoplasm to the nucleus, facilitating FOXO1’s transcriptional inhibitory effect on OPLAH (5-oxoprolinase) and downregulated the expression of OPLAH. Reduced OPLAH expression in cardiomyocytes decreases the conversion of 5-oxoproline to glutathione, thus aggravated oxidative stress and ferroptosis. Interestingly, 5-OXO supplement inhibited tumor growth while protecting DOX-induced cardiotoxicity in nude mice with implanted breast cancer. Regarding clinical significance, we found that downregulated expression of 5-OXO correlated with high risk in breast cancer patients with DOX treatment.
CONCLUSIONS Our findings indicate a previously unrecognized role of 5-oxoproline in DIC treatment and an undescribed 5-oxoproline/OPLAH axis involved in regulating therapeutic metabolism in cardiomyocytes. It is important that our findings suggest 5-oxoproline can be used as a potential therapeutic agent for DIC and simultaneously antagonizing cancer growth.
GW35-e0208
Yingzhen Gu, Aimin Dang, Naqiang Lv
Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College
OBJECTIVES There is growing evidence that arterial stiffness is recognized as a new risk factor for stroke. However, previous studies often utilized complex measures of arterial stiffness or primarily focused on specific populations, thereby restricting their generalizability. In the present study, we aimed to investigate the associations of estimated pulse wave velocity (ePWV), a well-established indirect measure of arterial stiffness, with incident stroke risk among middle-aged and older population.
METHODS This study used data from three prospective and nationally representative cohorts: the Health and Retirement Study (HRS) in the United States, the English Longitudinal Study of Ageing (ELSA) in the United Kingdom, and the China Health and Retirement Longitudinal Study (CHARLS) in China. The estimated pulse wave velocity (ePWV) was calculated using an algorithm based on age and mean blood pressure. Stroke incidence was determined via self-reported physician-diagnosed stroke. Cox proportional hazard models adjusted for potential confounders were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Restricted cubic spline (RCS) analysis was conducted to investigate potential nonlinear associations.
RESULTS The final analysis included 6458 participants from the HRS (mean age: 66.99 years; 40.4% men), 6458 from the ELSA (mean age: 66.32; 44.4% men), and 12,415 from the CHARLS (mean age: 58.60; 46.2% men). Over follow-up periods of 10.28 years in the HRS, 9.95 years in the ELSA, and 6.30 years in the CHARLS, 624 (9.7%), 374 (5.8%), and 656 (5.3%) participants developed stroke, respectively. Fully adjusted Cox regression analysis revealed a significant association between ePWV and incident stroke across all cohorts (HRS: HR 1.29, 95% CI: 1.24–1.34; ELSA: HR 1.36, 95% CI: 1.27–1.45; CHARLS: HR 1.18, 95% CI: 1.13–1.24). RCS analysis demonstrated a positive linear association between ePWV and stroke incidence in the HRS (P for nonlinear = 0.238) and the ELSA (P for overall < 0.001, P for nonlinear = 0.747) and a nonlinear association in the CHARLS (P for overall < 0.001, P for nonlinear = 0.004).
CONCLUSIONS This study revealed a significant correlation between ePWV and incident stroke among middle-aged and older population. Arterial stiffness has emerged as a valuable tool that may improve primary prevention and treatment strategies for stroke.
GW35-e0252
Xing Yu, Liangdi Xie
Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
OBJECTIVES Type 2 diabetes mellitus (T2DM) has been established as an independent risk factor for osteoporosis, leading to poor prognosis. Thus, it is crucial for clinicians to timely diagnose osteoporosis in diabetic patients. This study aimed to establish a machine-learning screening model for osteoporosis in Chinese T2DM patients.
METHODS A clinical analysis was retrospectively carried out using our hospital database for patients with definite T2DM diagnosed between January 1, 2012, and December 31, 2020. All patients were randomly divided into either the training group or the validation group. Then, multivariate logistic regression analysis was used to screen independent risk factors for osteoporosis. Machine learning (ML) models were developed to predict osteoporosis risk using different methods such as logistic regression (LR), naive Bayes (NB), neural network (NNET), support vector machine (SVM), gradient boosting machine (GBM), and k-nearest neighbor (KNN). Furthermore, in order to enhance the applicability of our model in the clinical setting, a web-based online calculator was developed. In addition, Shapley additivity explanations (SHAP) were employed to determine the significance of selected features and interpret the ML models.
RESULTS A total of 2029 patients were enrolled in the study, of which 457 suffered from osteoporosis. Based on the analysis, five characteristic variables were selected to construct the predictive model for osteoporosis in T2DM patients, comprising gender, age, BMI, heart rate, and alkaline phosphatase. Internal validation of the GBM model revealed an AUC of 0.791 in the test set and 0.886 in the external validation set. Furthermore, the calibration curves, decision curve analysis, and precision-recall curves highlighted the satisfactory clinical applicability of the GBM model. According to this model, an online calculator was built for clinicians to diagnose and treat diabetes related osteoporosis patients.
CONCLUSIONS ML models can indeed be a reliable tool to predict the risk of osteoporosis. In addition, the SHAP method improved the transparency of the model, enabling physicians to understand the reliability of the model. Overall, this screening model provides an accurate, easy-to-implement, and cost-effective tool for the early diagnosis of osteoporosis in T2DM patients in China.
GW35-e0272
Fenghua Wang, Maoti Wei
TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
OBJECTIVES To understand the effects of family history of diabetes (FHD) and different types of obesity (general obesity, central obesity) on the risk of diabetes and the interaction between them on the risk of diabetes, so as to provide evidence for the early prevention and control of diabetes.
METHODS From June 2019 to November 2023, a multi-stage random sampling method was used to select 177,160 permanent residents aged 35–75 years in Tianjin as the survey subjects. Questionnaire survey, physical examination and laboratory test were conducted. Body mass index was used to measure general obesity, and waist circumference was used to measure central obesity. The sixth national census data was used for age-standardized prevalence. Multivariate logistic regression was used to analyze the independent and interactive effects of FHD and different types of obesity on the prevalence of diabetes. The relative excess risk of interaction (RERI), attributable proportion of interaction (AP) and the synergy index (SI) were calculated using the parameter estimates and covariance matrix of the regression model and the Excel sheet prepared by Andersson et al.
RESULTS A total of 177,160 participants were included, with an average age of 56.44 ± 8.62 years. The crude prevalence of diabetes was 16.65% (95% CI: 16.47%–16.82%), and the standardized prevalence was 12.80%. There were 25,456 (14.36%) people with FHD, 29,535 (16.67%) people with general obesity and 67,338 (38.01%) people with central obesity. Multivariate logistic regression analysis showed that after adjusting for confounding factors such as gender, age, education level, smoking, and drinking, FHD (OR = 4.19, 95% CI: 4.06–4.32), general obesity (OR = 1.85, 95% CI: 1.80–1.91), and central obesity (OR = 1.87, 95% CI: 1.83–1.92) were all associated with a higher risk of diabetes (all P < 0.001). The combination of FHD and general obesity was associated with a 6.39 times higher risk of developing diabetes than the absence of either (OR = 6.39, 95% CI: 6.03–6.78, P < 0.001). The risk of diabetes in patients with FHD and central obesity was 7.07 times higher than that in patients without either (OR = 7.07, 95% CI: 6.76–7.38, P < 0.001). The interaction analysis showed that after adjusting for confounding factors, the RERI, AP, and SI of FHD and general obesity were 1.06 (95% CI: 0.68–1.44), 16.6 (95% CI: 11.4%–21.8%) and 1.25 (95% CI: 1.16–1.34), respectively, and the RERI, AP, and SI of FHD and central obesity were 1.77 (95% CI: 1.45–2.08), 0.25 (95% CI: 0.21–0.29), and 1.41 (95% CI: 1.33–1.50), respectively, indicating the significant additive interaction between general obesity and FHD as well as between central obesity and FHD on the risk of diabetes (all P < 0.05).
CONCLUSIONS Here were positive interactions between general obesity and FHD, central obesity and FHD on the risk of diabetes. For people with FHD, controlling body mass index and waist circumference may effectively reduce the risk of diabetes.
GW35-e0287
Junwen Wang, Yuyang Ye, Xinru Hu, Xuefeng Chen, Peng Yong
Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China
OBJECTIVES The objective of this study is to investigate the correlation between glycated hemoglobin (HbA1C) levels and the risk of cardiovascular mortality and all-cause mortality.
METHODS The study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2014, which included diabetic patients. Logistic regression was utilized to evaluate the statistical significance of linear or nonlinear trends. The study employed the Cox proportional hazards model and Kaplan-Meier survival curves to conduct multivariate analyses investigating the associations between HbA1C.
RESULTS The study included 6516 participants and found that the control rate of HbA1C in diabetic patients increased significantly from 41.61% in 1999 to 58.72% in 2014 (P < 0.001). However, there was no statistically significant trend in the overall all-cause mortality (from 10.79% in 1999 to 12.08% in 2014, P = 0.608) and cardiovascular mortality (from 4.47% in 1999 to 4.24% in 2014, P = 0.371) among diabetic patients. There were no statistically significant differences in the risks of all-cause (HR: 0.64, 95% CI: 0.36–1.13; P = 0.13) death and cardiovascular death (HR: 1.11, 95% CI: 0.41–3.02; P = 0.84) between the HbA1C control and uncontrolled groups, as indicated by a Cox proportional hazard model. The utilization of sulfonylureas decreased from 30.25% in 1999 to 12.42% in 2014 (Linear P value < 0.001).
CONCLUSIONS Although there was an improvement in HbA1C control rates, it did not result in a significant reduction in 5-year mortality among diabetic patients. Lowering HbA1C levels to less than 7% was associated with a no decrease in cardiovascular mortality and all-cause mortality. The utilization of hypoglycemic agents may contribute to the lack of reduction in mortality rates.
GW35-e0302
Dan Luo1,2, Xin Lan Xiao1,2
1Department of Radiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University
2Intelligent Medical Imaging of Jiangxi Key Laboratory
OBJECTIVES Some patients with basilar atherosclerosis undergo endovascular therapy, during which displacement or a “snow shoveling effect” at the perforator artery site can occur, leading to stroke recurrence and even death. Therefore, accurate identification of stroke subtypes before surgery can assist clinicians in selecting the appropriate treatment. To explore the rapid identification of perforation groups in basilar artery ischemic stroke using high-resolution vascular wall imaging (HR-VWI).
METHODS A retrospective analysis was conducted on 147 patients with posterior circulation ischemic stroke (PCI), who were treated at the Second Affiliated Hospital of Nanchang University between October 2019 and October 2023. Patients were categorized into the perforation group and multiple mechanism groups based on imaging findings and the China ischemic stroke subclassification (CISS). Clinical and plaque characteristics were compared between the two groups, and a simple model was constructed to identify patients in the perforation group.
RESULTS Patients in the perforation group exhibited higher rates of limb weakness and diabetes mellitus compared to the multiple mechanism group. Plaques in the perforation group were predominantly located dorsally (38/57, 66.7%), while plaques in the multiple mechanism group were more frequently located ventrally (53/90, 58.9%). A model incorporating diabetes, ventral, and dorsal plaque location parameters was constructed using stepwise logistic regression to predict branch atheromatous disease stroke, achieving an AUC of 0.863, with a sensitivity of 73.68% and a specificity of 86.67%.
CONCLUSIONS A model that incorporates diabetes, the location of dorsal plaque, and the absence of ventral plaque can quickly predict the perforation group in basilar artery stroke.
GW35-e0303
Dan Luo1,2, Xin Lan Xiao1,2
1Department of Radiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University
2Intelligent Medical Imaging of Jiangxi Key Laboratory
OBJECTIVES Vascular morphological variation is one of the risk factors for posterior circulation infarction (PCI). We utilized Vessel Wall Magnetic Resonance Imaging and 3D-TOF MRA to measure the morphology and diameter of posterior circulation arteries, explore the correlation between posterior circulation vascular variations and posterior circulation stroke, and help identify high-risk patients for posterior circulation stroke and prevent PCI in advance.
METHODS We compared the presence or absence of dominant vertebral arteries, the displacement of the basilar artery and dominant vertebral arteries, the fetal-type posterior cerebral artery (FPCA), and the development of the basilar artery and cerebellar arteries between the PCI group and the no cerebral infarction (NCI) group.
RESULTS There was no statistically significant difference in the presence or absence of vertebral artery and basilar artery displacement, as well as in the displacement distance of the basilar artery, between the two groups (P > 0.05). Among the poorly developed cerebellar arteries, only the incidence of poorly developed posterior inferior cerebellar arteries (PICA) differed between the two groups (P = 0.042). There was no statistically significant difference in the development of the basilar artery, superior cerebellar artery (SCA), or anterior inferior cerebellar artery (AICA) between the two groups (P > 0.05). There was a significant difference in the presence of FPCA between the two groups (P = 0.007).
CONCLUSIONS Patients with developmental abnormalities of the basilar artery and PICA have a higher incidence of stroke. FPCA serves as an effective compensatory mechanism, leading to a lower incidence of infarction.
GW35-e0383
Yukun Li, Ribo Tang
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100012, China
OBJECTIVES The prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, Metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce. The objective of our research is to investigate the potential of metformin in modulating cardiac metabolic risks in cancer population, and to explore whether this protective potential is associated with mitigating factors such as oxidative stress.
METHODS A prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003–2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants’ levels of oxidative stress. Logistic regression and Cox proportional hazards regression models were employed to evaluate the association between metformin use and the risk of cardiometabolic diseases and related mortality. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin.
RESULTS Among 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47–0.81) and cardiometabolic (HR, 0.65; 95% CI: 0.44–0.97) mortality compared with metformin nonusers. Metformin use was also associated with a lower risk of total cardiovascular disease (OR, 0.41; 95% CI: 0.28–0.59), stroke (OR, 0.44; 95% CI: 0.26–0.74), hypertension (OR, 0.27; 95% CI: 0.14–0.52), and coronary heart disease (OR, 0.41; 95% CI: 0.21–0.78). The observed cardiometabolic protective effects remained consistently robust across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analysis indicated that metformin, through its antagonistic effect on oxidative stress, offered protection against all-cause mortality (relative excess risk due to interaction [RERI], −0.37; 95% CI: −0.61 to −0.13), cardiometabolic mortality (RERI, −0.35; 95% CI: −0.68 to −0.02), and specific cardiometabolic diseases.
CONCLUSIONS In this cohort study involving a nationally representative population of cancer survivors, metformin use is significantly associated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality. The observed cardiometabolic protective effects of metformin in cancer survivors are likely attributable to its antagonistic effect on oxidative stress, suggesting a potential therapeutic approach for improving cardiometabolic health in this population.
GW35-e0560
Yi Zheng1, Ziliang Chen1, Wenhua Song1, Yu Xu2, Zhiqiang Zhao1, Yihong Sun3, Yuanyuan Wang1, Jun Zhao1, Xiaowei Zhang1, Yanmin Xu1, Jeffrey Shi Kai Chan4, Gary Tse1, Guangping Li1, Lili Hong2, Tong Liu1
1Second Hospital of Tianjin Medical University
2Tianjin Huanghe Hospital
3China-Japan Friendship Hospital
4Cardiovascular Analytics Group
OBJECTIVES Immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs can cause immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its potentially high fatality rate. This multicenter study aimed to characterize ICI-related myocarditis and prognostic factors.
METHODS The study included patients with ICIs-associated myocarditis at four medical centers in China from January 28, 2019 to June 15, 2023. Logistic regression was used to identify significant risk factors of severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of biomarkers to distinguish severe myocarditis, and the performance and calibration were evaluated using the Hosmer-Lemeshow test. Cox regression analysis was employed to investigate the influential risk factors affecting the prognosis of ICI-related myocarditis. Kaplan-Meier survival curve analyses were conducted to assess the differences in survival times among different myocarditis groups.
RESULTS A total of 35 patients with ICIs-associated myocarditis were identified. Of these, 21 patients (60%) were classified as having severe myocarditis, and had higher cardiac troponin I (cTnI) (P = 0.013), higher N-terminal pro-B-type natriuretic peptide (P = 0.031), higher creatine kinase (P = 0.018), higher creatine kinase-MB (P = 0.026), and higher neutrophil-to-lymphocyte ratio (NLR) (P = 0.016) compared to those with non-severe myocarditis. Multivariate logistic regression showed that cTnI (adjusted odds ratio: 1.021, 95% confidence interval (CI): 1.002–1.039, P = 0.03) and NLR (adjusted odds ratio: 1.890, 95% CI: 1.026–3.483, P = 0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.765 (95% CI: 0.601–0.929, P = 0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597–0.948, P = 0.016). Multivariable Cox regression showed that NLR (adjusted hazard ratio: 1.189, 95% CI: 1.028–1.376, P = 0.020) and pneumonitis (adjusted hazard ratio: 8.142, 95% CI: 1.191–55.651, P = 0.032) were independent prognostic factors.
CONCLUSIONS As independent risk factors for the development of ICI-associated severe myocarditis, cTnI and NLR demonstrated a promising predictive utility for the identification of ICI-associated severe myocarditis. NLR and the presence of pneumonitis were identified as independent prognostic factors in ICI-related myocarditis.
GW35-e0590
Beizheng Xu1, Xu Yao Han1, Nan Zhang1, Gary Tse1,2, Guangping Li1, Tong Liu1
1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
2School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China
OBJECTIVES The ratio of red blood cell distribution width (RDW) to albumin concentration (RAR) serves as a biomarker for the risk assessment of various diseases. However, limited research exploring the correlation between RAR and cardiovascular disease (CVD) in cancer patients.
METHODS This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) in 1999–2018. The LE8 score comprises eight metrics: diet, physical activity, tobacco/nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. Weighted logistic regression and restricted cubic splines (RCS) assessed the association between RAR and CVD.
RESULTS A total of 3600 individuals were selected, representing 14.5 million noninstitutionalized civilians of the United States, with a mean RAR of 3.17 ± 0.01. After the adjustment of potential confounders, a statistically significant inversely nonlinear dose – response relationship (nonlinear P-value < 0.001) was observed between RAR and CVD (odds ratio, 1.49; 95% CI: 1.18–1.89). Compared to participants with low RAR values (Quartile 1), those with high RAR values (Quartile 4) had multivariable adjusted OR for CVD of 2.28 (95% CI: 1.61–3.22, P < 0.0001, P for trend < 0.001). Furthermore, the effect size of the RAR on CVD remained stable in all subgroups, with all p-values for interaction exceeding 0.05.
CONCLUSIONS The results indicate a significant inversely nonlinear relationship between RAR score and CVD in cancer patients. The elevated RAR increases the incidence of CVD in cancer patients.
GW35-e0592
Beizheng Xu1, Xu Yao Han1, Nan Zhang1, Gary Tse1,2, Guangping Li1, Tong Liu1
1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
2School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China
OBJECTIVES The American Heart Association recently developed Life’s Essential 8 (LE8) for assessing cardiovascular health (CVH). However, few studies have explored the possible association between LE8 and type 2 diabetes mellitus (T2DM).
METHODS This was a population-based, cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) in 2005–2018. The LE8 score comprises eight metrics: diet, physical activity, tobacco/nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. Weighted logistic regression and restricted cubic splines (RCS) assessed the association between LE8 score and T2DM.
RESULTS A total cohort of 24,890 individuals was included, representing 100.2 million non-institutionalized civilians of the United States. After the adjustment of potential confounders, a statistically significant inversely nonlinear dose–response relationship was observed between LE8 score and T2DM (odds ratio [OR] for per 10 score increase, 0.49; 95% CI 0.47–0.51). Compared to participants with high CVH scores, those with moderate CVH scores had higher odds of T2DM (OR: 6.78, 95% CI: 4.97–9.24), which were even higher for those with low CVH scores (OR: 27.62, 95% CI: 19.70–38.73) on multivariable regression. Furthermore, significant interactions between CVH level and age strata, education levels with T2DM status were found (P < 0.05 for interaction).
CONCLUSIONS The results indicate a significant inversely nonlinear relationship between LE8 score and T2DM. These findings suggest that improving cardiovascular health could potentially reduce the burden of T2DM.
GW35-e0671
Xin Hu, Yuquan He
Department of Cardiology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, Jilin, China
OBJECTIVES Epidemiologic studies have revealed that patients with cardiovascular diseases are at high risk of developing cancer. Recent studies on animals have demonstrated that cardiac remodeling in the absence of heart failure promotes cancer progression. However, despite their prominent association with cardiac remodeling, whether hypertrophic cardiomyocytes play an important role in cancer progression is unknown.
METHODS To investigate the effect of exosomes from hypertrophic cardiomyocytes on cancer progression, we treated AC16 cardiomyocytes with Ang II to induce hypertrophic growth, and subsequently injected exosomes from these cells into nude mice previously implanted with breast cancer cells.
RESULTS Compared with controls, TAC-operated mice displayed higher proliferation rates of implanted cancer cells along with increased tumor volumes; however, these cancer-promoting effects induced by TAC were suppressed following treatment with GW4869, an inhibitor of exosome release. Exosomes from Ang II-treated AC16 cardiomyocytes enhanced the growth, invasion, and migration of cancer cells both in vitro and in vivo. RNA sequencing revealed that the miRNA expression profile was altered in Ang II-treated AC16 cells. In particular, miR-10040-3p levels were decreased in exosomes derived from Ang II-treated AC16 cells, which was accompanied by changes in the expression of cancer-associated genes, such as TRAF2. Moreover, the expression of the RNA-binding protein hnRNPQ was decreased in Ang II-treated AC16 cells, which likely led to decreased exosomal sorting of miR-10400-3p. In line with these findings, the expression of miR-10400-3p was also found to be downregulated in the plasma of patients with cardiac hypertrophy.
CONCLUSIONS Our study highlighted the essential role of hypertrophic cardiomyocytes in promoting breast cancer progression during cardiac remodeling.
GW35-e0693
Cong Liu
Cardiovascular Medicine Department, General Hospital of Northern Theater Command, Shenyang
OBJECTIVES Vascular stiffness increased and vascular compliance decreased on vasculature is a progressive process in diabetics. The pathogenesis underlying diabetic-induced vasculature damages is complex and multifactorial. This paper aim to clarify putative link between aorta abdominal and central retinal artery and the therapeutic implication of antioxidant N-acetylcysteine.
METHODS Forty-two male C57BL/6 mice (20–25 g) were included. Thirty mice were injected intraperitoneally with 150 mg/kg of STZ (STZ, Sigma-Aldrich, St. Louis, MO) in 0.05 M citrate buffer (pH 4.2). As a control group and an only treated with NAC group, 12 mice were injected with equal volume of citrate buffer. Mice with blood glucose levels exceeding 13.5 mmol/L were considered diabetic after five days. The 30 diabetic mice were divided into 5 groups with 6 animals in each group: including DM group (diabetes without NAC treatment), and 4 different NAC treatment groups, namely NAC1, NAC3, NAC5 and NAC7, with the number defining the initiation time of NAC treatment (NAC treatment was done via drinking water starting from 1 week, 3 weeks, 5 weeks and 7 weeks after STZ injection till the end of the 12 weeks, respectively). The 12 non-DM mice were either untreated (Ctrl) or treated with NAC from 5 weeks (only NAC treated). Vascular function and structure were analyzed by both ultrasound and histology. Body weight and blood glucose level were measured regularly, and the mice were sacrificed at the experimental end points. Aorta abdominal and central retinal artery were collected for Hematoxylin Eosin (HE) and Trichrome staining and ROS staining of all mice after ultrasound.
RESULTS We found that abdominal aorta, retina structure and function were impaired, coupled with endothelial cells, smooth muscle cell and cellular matrix impaired 12 weeks after STZ induction. NAC treatment significantly reduced ROS generation, and suppressed abdominal aorta remodeling and retina damage. Strikingly, the earlier and longer treatment, produced significant improvement of vascular function and structure.
CONCLUSIONS Our study demonstrated that earlier NAC treatment in diabetic effectively defends from diabetic vasculature disease through inhibiting the ROS dependent artery stiffness and restruction, which warrants further clinical trial.
GW35-e0803
Wen Zhang1, Yixuan Ma2, Masahiro Kohzuki3, Qi Guo4
1Department of Rehabilitation Medicine, School of Medical Technology, Tianjin Medical University, Tianjin, China
2Division of Sports Science and Physical Education, Tsinghua University, Beijing, China
3Yamagata Prefectural University of Health Sciences, Yamagata, Japan
4Department of Rehabilitation, Shanghai University of Medical and Health Sciences, Shanghai, China
OBJECTIVES Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength which is linked to multiple chronic diseases, such as type 2 diabetes and kidney disease. On the other hand, an age-related decline in muscle strength before the reduction of muscle mass is proposed to be “dynapenia”. Some studies have proved that muscle strength does not depend solely on muscle mass, and muscle power rather than muscle mass is the most linked to frailty. It may be an indication that, to only focus on muscle mass is too narrow to evaluate health conditions; muscle strength and physical performance are all important indexes. The aim of the present study is to determine whether there is relationship between sarcopenia or dynapenia and abnormal renal function in impaired fasting glucose (IFG) and type 2 diabetes among community-dwelling elderly.
METHODS Our study population comprised of six hundred and forty community elderly without sarcopenia (mean ± SD age: 68.0 ± 6.1 years; 57.0% women) from Tianjin, China. IFG is defined by having fasting plasma glucose (FPG) levels ≥100 mg/dL (5.6 mmol/L) but <126 mg/dL (7.0 mmol/L); Type 2 diabetes is defined by self-reported or FPG ≥126 mg/dL (7.0 mmol/L). According to the Asian Working Group for Sarcopenia criteria (2019 Consensus Update), sarcopenia was defined by ASM/Ht2 <7.0 kg/m2 in men and <5.7 kg/m2 in women, with grip strength <28 kg for men and <18 kg for women or walking speed <1.0 m/s or repeated chair stand ≥12 s or SPPB ≤9. Dynapenia is defined by grip strength <28 kg for men, <18 kg for women or low knee extension strength <1.13 Nm/kg for men, 1.01 Nm/kg for women. Estimated glomerular filtration rate (eGFR) is defined by using the JSN equation as eGFRcrear (mL/min/1.73 m2) = 194 × Cre−1.094 × age−0.287 (×0.739 if female).
RESULTS Firstly, we found that more men suffered from sarcopenia than women (normoglycemia P = 0.044; IFG P = 0.030; diabetes P = 0.003). Moreover, we found that men was associated with sarcopenia with IFG (OR: 3.98) and diabetes (OR: 6.49) after adjusted age. After multivariate adjustments for all the concomitants, including sex, age, body composition variables, lifestyle-variables, health status variables, we found that the lowest quarter of eGFR was associated with dynapenia in subjects with IFG (OR 4.70, P = 0.039) and diabetes (OR 9.19, P = 0.036). However, we did not find the relationship between sarcopenia and renal function in IFG and diabetes.
CONCLUSIONS The present study indicates that a positive relationship among dynapenia and renal dysfunction in IFG and diabetes. Moreover, it seems that men were more prone to loss of muscle mass compared with women who were more prone to loss of physical capacity. This result may indicate that assessment of muscle functionality may provide additional diagnostic and prognostic information about renal function to muscle-mass evaluation among community elderly with IFG and diabetes and there may be some gender differences for the underlying mechanisms driving muscle mass loss in IFG and diabetes.
GW35-e0820
Mei Zhao1, Chuanfen Liu2,3,4, Dongyang Zhou5, Xiaohong Zhang1, Hong Chen2,3,4, Junxian Song2,3,4
1Department of Pharmacy, Peking University People’s Hospital, Beijing, People’s Republic of China
2Department of Cardiology, Peking University People’s Hospital, Beijing, People’s Republic of China
3Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People’s Hospital, Beijing, People’s Republic of China
4Center for Cardiovascular Translational Research, Peking University People’s Hospital, Beijing, People’s Republic of China
5Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
OBJECTIVES Anthracyclines are highly effective chemotherapeutic agents widely used in the treatment of various malignancies. However, their use is often limited by the development of cardiotoxicity, which can lead to serious cardiovascular complications and a decreased quality of life for cancer survivors. This study aimed to provide a comprehensive overview of interventional clinical trials focusing on anthracycline-induced cardiotoxicity (AIC) by analyzing data from the International Clinical Trial Registration Platform (ICTRP).
METHODS The ICTRP was used as the data source. Information of each trial was collected. Linked publications were searched through PubMed and Google Scholar.
RESULTS Overall, 100 interventional trials were identified. A substantial increase in the number of registered AIC trials, with a majority conducted in North America, Europe, and Asia. Most trials were prospective and focused on prevention and treatment. The trials’ interventions were categorized into five main classes: cardioprotective agents, monitoring strategies, exercise and lifestyle interventions, and novel strategies like device and stem cell therapy. Cardioprotective agents, particularly neurohormonal antagonists, were extensively studied, as were monitoring strategies for early detection. Exercise and lifestyle interventions, although promising, were underrepresented. Novel strategies such as stem cell therapy and devices were still in their early stages. Additionally, a limited number of trials had been published by 2023. The results from clinical trials were heterogeneous.
CONCLUSIONS Interventional clinical trials targeting AIC offered hopes for improving the safety and efficacy of anthracycline-based chemotherapy. Despite challenges, the diverse range of strategies explored, coupled with promising findings, underscores the importance of continued research, long-term follow-up and interdisciplinary collaboration.
GW35-e0838
Alexey Churov1,2, Tatiana Kovyanova1, Viktoria Khotina1, Alexander Orekhov1,3
1Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow 125315, Russia
2Pirogov Russian National Research Medical University, Russian Gerontology Clinical Research Centre, Moscow, Institute on Aging Research, Russian Federation, 16, 1st Leonova Street, Moscow 129226, Russia
3Insitute of Human Morphology, Petrovsky Russian National Center of Surgery, 2 Abrikosovsky Lane, Moscow 119991, Russia
OBJECTIVES Regulatory T cells (Tregs) with suppressive properties effectively inhibit various immune responses (CD4+ and CD8+ T cells, NKT cells etc.) and play an important role in immune tolerance. The aim of this study was to investigate the numbers and suppressive activity of CD4+ regulatory T (Treg) cell subsets in acute and chronic phase of cerebrovascular disease.
METHODS Peripheral blood samples were collected from 19 patients with acute (stroke) and chronic (cerebral ischemia) forms of cerebrovascular diseases (age of 72.3 ± 8.9 years) before any therapeutic interventions. Exclusion criteria: history of neoplasms, presence of cardiovascular disorders (apart from the mentioned above), as well as immunoinflammatory diseases. Peripheral blood samples from 25 healthy individuals (age of 64.9 ± 10.5 years) were used as control. The expression of membrane and intracellular markers of peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry with the addition of monoclonal antibodies to membrane antigens CD4, CD25, CD127, CD3 (BD, USA) and to the intracellular transcription factor FOXP3 (eBioscience, USA). The Mann-Whitney U test was used to compare differences between two independent groups. Differences were considered significant at P < 0.05. The results are presented as the M ± SD.
RESULTS We studied the Treg (CD4+CD25+CD127low) cell numbers in patients with stroke and cerebral ischemia. In our study, patients with cerebrovascular diseases demonstrated a significant rise in Treg cell count. The number of CD4+CD25+CD127low Treg cells in peripheral blood of patients was 7.35 ± 1.69 against 4.21 ± 1.35 in the control (P < 0.05). Additionally, we divided all patients with cerebrovascular diseases into two groups: patients with acute condition (recent stroke) and with chronic cerebral ischemia. Patients with stroke (n = 9) showed no significant difference from the control in the number of Tregs, whereas patients with cerebral ischemia (n = 10) showed almost twice more Treg cells compared to the control (8.79 ± 1.91 and 4.21 ± 1.35, respectively; P < 0.05). The suppressive activity of Tregs in both groups (acute and chronic phase of cerebrovascular diseases) was similar.
CONCLUSIONS An essential feature of human Treg cells is the ability to suppress the functional activity of other immunocytes, including T- and B lymphocytes, as well as antigen-presenting cells. In our study, patients with cerebrovascular diseases had an increased number of CD4+CD25+CD127low Treg cells. Treg cell numbers were higher in patients with a chronic form of cerebrovascular disease as compared to stroke. We hypothesize that the increase in peripheral Treg cell numbers in patients with brain ischaemia may be considered as a compensatory mechanism, leading to activation of immune suppression and ensure prevention of excessive inflammatory processes. The study was funded by the Russian Science Foundation.
GW35-e0915
Ran Guo1,2, Kaihang Yiu1,2
1Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
2Division of Cardiology, Department of Medicine, The University of Hong Kong Shen Zhen Hospital, Shen Zhen, China
OBJECTIVES To evaluate the effectiveness and mode of action of Sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with Type 2 diabetes mellitus (T2DM) exhibiting varying levels of long-term glycemic variability (GV).
METHODS This territory-wide cohort study enrolled patients with T2DM initiating SGLT2 inhibitors or dipeptidyl-peptidase 4 (DPP-4) inhibitors in Hong Kong between 2015 and 2022. Long-term GV was measured by hemoglobin A1C variability score (HVS). After propensity score matching, Cox regression analysis was used to compare the risk of outcomes between SGLT2 inhibitors users and DPP-4 inhibitors users. Primary outcomes included major adverse cardiovascular events (MACE) and serious renal events (SRE). Mediation effect of HVS variation was evaluated using traditional mediation analysis.
RESULTS Overall, 26,272 patients initiating SGLT2 inhibitors or DPP-4 inhibitors (13,136 pairs) were 1:1 propensity score–matched. SGLT2 inhibitors vs. DPP-4 inhibitors were associated with a lower risk of MACE (HR 0.72; 95% CI 0.65–0.78) and SRE (HR 0.39; 95% CI 0.36–0.43), with no heterogeneity across baseline HVS. SGLT2 inhibitors yielded a modestly lower probability of HVS ≥ 50 compared with DPP-4 inhibitors, irrespective of the baseline HVS (high-HVS group: OR 0.64, 95% CI 0.60–0.69; low-HVS group: OR 0.63, 95% CI 0.59–0.68). HVS variation mediated 5.1% of the total effect on MACE and 3.0% on SRE.
CONCLUSIONS SGLT2 inhibitors protected patients against MACE and SRE regardless of baseline GV status and independent of GV control. SGLT2 inhibitors represented a compelling therapeutic option for patients with both stable and labile T2DM, measured by long-term GV.
GW35-e0923
Ting Wu1,2,3, Qing Zhu1,2,3, Nanfang Li1,2,3
1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region
2Xinjiang Hypertension Institute
3NHC Key Laboratory of Hypertension Clinical Research
OBJECTIVES Objective: Chronic kidney disease commonly occurs in the general adult population, especially in people with diabetes and hypertension. Higher serum aldosterone levels among individuals with CKD are independently associated with an increased risk for kidney disease progression. Through metabolic profiling, this study aimed to investigate the associations between metabolites and aldosterone in diabetes and hypertension patients with CKD to provide insights into the complex interactions between metabolism, aldosterone and CKD.
METHODS An untargeted and metabolomic approach was used to identify possible metabolic signatures that have altered levels with CKD and aldosterone >15 (n = 30), non-CKD and aldosterone >15 (n = 30) and non-CKD and aldosterone <15 (n = 15) in plasma of diabetes and hypertension patients, and explained the correlation between aldosterone and differential metabolite. Univariate and multivariate analysis approaches were used to identify differential metabolites.
RESULTS Forty-one differences metabolites were signifificantly upregulated and 8 metabolites were signifificantly downregulated in non-CKD and aldosterone >15. Ten differences metabolites were signifificantly upregulated and 4 metabolites were signifificantly downregulated non-CKD and aldosterone >15 vs. non-CKD and aldosterone <15. One compound duplicated in 2 groups was removed in non-CKD and aldosterone >15 and the KEGG of 61 compound shows Histidine metabolism and Pentose and glucuronate interconversions Disturbed when CKD exists in the hypertension and diabetes mellitus. Seventy-seven metabolites of them were related to aldosterone for simple correlation, gamma-Tocopheryl quinone was associated with aldosterone after adjusting for sex, age, and BMI. The receiver operating characteristic curves of 8 metabolites showed high sensitivity and specificity.
CONCLUSIONS These findings suggest gamma-Tocopheryl quinone as novel biomarkers for CKD of diabetes and hypertension patients, and aldosterone plays a important role in this process. Thus, this study provides new insights for further investigations into the prevention and management of CKD.
GW35-e0928
Xiaoqing Zhu1,2, Tao Chen1, Jun Guo1
1Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital
2Medical School of Chinese PLA
OBJECTIVES Insulin resistance (IR) is a noteworthy risk factor in the development of cardiovascular disease (CVD), with the estimated glucose disposal rate (eGDR) serving as a reliable indicator of IR. However, the association between the long-term effect of eGDR on the risk of CVD remains unclear. Consequently, we aimed to determine the relationship between the cumulative eGDR correlated and incident CVD.
METHODS The data for this prospective nationwide cohort were obtained from the China Health and Retirement Longitudinal Study. The cumulative eGDR was calculated as follows: (eGDR2012 + eGDR2015)/2 × time (2015–2012). Participants were categorized into four groups based on quartiles of cumulative eGDR. Multivariate logistic regressions were used to assess the associations between cumulative eGDR and the incidence of CVD, heart disease (HD), and stroke. Restricted cubic spline (RCS) analysis was employed to characterize the dose-response relationship between cumulative eGDR and incident CVD, HD, and stroke. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the predictive ability of cumulative eGDR versus baseline eGDR for CVD, HD, and stroke.
RESULTS A total of 4237 participants were included in the analysis, of whom 2303 (54.4%) were female, with a mean age of 57.4 years at baseline. Over a 5-year follow-up, 768 (18.1%) participants developed CVD, 536 developed HD (12.7%), and 308 developed stroke (7.3%). Fully adjusted logistic regression analyses revealed significant inverse associations between cumulative eGDR and incident CVD. Compared to participants in Quartile 1 of cumulative eGDR, the odds ratios (95% CI) for CVD were 0.74 (0.56–0.97), 0.49 (0.34–0.72), and 0.37 (0.25–0.55) for participants in Quartile 2, Quartile 3, and Quartile 4, respectively. The AUROC for predicting CVD was significantly higher for cumulative eGDR compared to baseline eGDR (0.611 vs. 0.600, P = 0.006). The RCS analysis showed a linear inverse association between cumulative eGDR and CVD risk (P for non-linearity >0.05). Similar findings were observed for incident HD and stroke.
CONCLUSIONS Lower cumulative eGDR level was associated with heightened risk of CVD, HD, and stroke. Cumulative eGDR demonstrated improved predictive ability for CVD, HD, and stroke compared to baseline eGDR.
GW35-e0930
Xiaoqing Zhu1,2, Tao Chen1, Jun Guo1
1Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital
2Medical School of Chinese PLA
OBJECTIVES Stroke is closely associated with the triglyceride glucose (TyG) index and its related indicators, particularly its combination with obesity indices. However, there is limited research on the relationship between changes in TyG-related indices and stroke, as most studies have focused on baseline TyG-related indices.
METHODS The data for this prospective cohort study were obtained from the China Health and Retirement Longitudinal Study. The exposures were changes in TyG-related indices and cumulative TyG-related indices from 2012 to 2015. The K-means algorithm was used to classify changes in each TyG-related index into three classes (Class 1 to Class 3). Multivariate logistic regressions were used to evaluate the associations between the changes in TyG-related indices and the incidence of stroke.
RESULTS In total, 4064 participants were included in this study, of whom 2266 (55.83%) were female, with a mean age of 58.18 years at baseline. Over a 5-year follow-up, 368 (9.1%) participants developed stroke. Fully adjusted logistic regression analyses revealed significant positive associations between changes in TyG-related indices, cumulative TyG-related indices and the incidence of stroke. Among these changes in TyG-related indices, changes in TyG-waist circumference (WC) showed the strongest association with incident stroke. Compared to the participants in Class 1 of changes in TyG-WC, the odds ratio (OR) for participants in Class 2 was 1.52 (95% confidence interval (CI): 1.13–2.05), and the OR for participants in Class 3 was 1.96 (95% CI: 1.35–2.84). Moreover, cumulative TyG-WC exhibited the strongest association with incident stroke among these cumulative TyG-related indices. Compared to the participants in Tertile 1 of cumulative TyG-WC, the OR for participants in Tertile 2 was 1.45 (95% CI: 1.06–1.98), and the OR for participants in Tertile 3 was 1.67 (95% CI: 1.17–2.37). Changes in TyG-WC significantly outperformed changes in TyG alone (ΔC-statistic = 0.031, 95% CI: 0.003–0.063). Cumulative TyG-WC (ΔC-statistic = 0.037, 95% CI: 0.013–0.063) and cumulative TyG-WHtR (ΔC-statistic = 0.030, 95% CI: 0.006–0.058) displayed significantly increase in the ΔC-statistic compared to cumulative TyG.
CONCLUSIONS Changes in TyG-related indices are independently associated with the risk of stroke. Changes in TyG-WC are expected to become more effective indicators for identifying individuals at a heightened risk of stroke.
GW35-e1046
Zheng Mengyi1, Guo Caixia2, Wu Shouling3
1Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
2Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
3Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, China
OBJECTIVES This study aims to elucidate the impact of short, medium, and long-term trajectories of low-density lipoprotein cholesterol (LDL-C) on the incidence risk of cardiometabolic diseases (CMD) and to predict the lifetime risk.
METHODS The study included individuals aged 18–40 from the Kailuan study who had no prior history of cardiovascular disease, atrial fibrillation, or diabetes. Among them, 18,844, 17,208, 14,044, and 8075 participants were assigned to the LDL-C 4-year, 6-year, 8-year, and 10-year trajectories, respectively. Group-based trajectory models segmented participants with similar LDL-C change patterns into five groups (referred to as G1–G5 groups). Cox proportional hazards regression models were employed to investigate the association between LDL-C trajectories and CMD. The study used the practical incidence estimation method to calculate lifetime risks of CMD. Subgroup analyses were performed based on gender, blood pressure, body mass index (BMI), and health behaviors. New occurrences of myocardial infarction, stroke, or type 2 diabetes during the follow-up period defined the development of CMD.
RESULTS The average follow-up durations for CMD with 4-year, 6-year, 8-year, and 10-year trajectories were 11.6 years, 9.58 years, 7.89 years, and 6.62 years, respectively. After adjusting for confounders, the analysis of 4-year LDL-C trajectory showed no significant difference in the risk of CMD incidence in other groups as compared to the G1 group. In the 6-year LDL-C trajectory, the G3 and G5 groups showed an increased risk of CMD by 27% and 49% respectively. Progressing to the 8-year LDL-C trajectory, CMD risk rose by 38%, 42%, 72%, and 80% in the G2 to G5 groups, correspondingly. Similarly, over the 10-year LDL-C trajectory, CMD risk surged by 43%, 51%, 74%, and 98% in the G2 to G5 groups. Among men or individuals with a BMI >24 kg/m2, those with high LDL-C trajectories within the normal range show an increased risk of adverse events. In contrast, non-hypertensive individuals and those with ≥5 healthy behavioral factors demonstrate a clearer difference in risk across various LDL-C trajectories. In individuals aged over 40, over 35, over 30, and over 25 years, the lifetime risk of CMD within LDL-C 4-year trajectory groups G1 to G5 increased as follows: from 10.9% to 16.4%, from 11.3% to 17.3%, from 12.2% to 20.5%, and from 12.7% to 20.7% respectively. The lifetime risk for LDL-C 6-year trajectories rose from 9.56% to 16.4%, 10.4% to 18.6%, 11.5% to 21.1%, and 12.0% to 24.3%. Additionally, the 8-year LDL-C trajectories led to the increase in lifetime risk from 6.58% to 13.3%, 8.16% to 16.7%, 9.21% to 19.5%, and 9.63% to 21.6%. The lifetime risk for LDL-C 10-year trajectories in the G1 to G5 groups, increased from 6.99% to 17.1%, 9.06% to 19.1%, 9.71% to 23.4%, and 9.27% to 22.9%.
CONCLUSIONS The LDL-C levels in young adults aged 18–40 years exhibit a progressive rise with advancing age. High-to-moderate long-term trajectories within the normal LDL-C range for ≥6 years independently elevate the risk of developing CMD, offering a more consistent classification and risk forecast during early adulthood.
GW35-e1080
Xiaofang C
Fujian Provincial Hospital
OBJECTIVES Obesity is recognized as a risk factor for diabetes mellitus (DM). Several new abdominal obesity indices (AOI), including WHtR, WWI, BRI, ABSI, ConI, were considered an effective and convenient tool for assessing abdominal adiposity recently. However, the association between the new AOI and newly diagnosed DM in population at high cardiovascular diseases (CVD) risk remains uncertain. Our study assessed the relationship between the new AOI and the incidence of newly diagnosed DM in these population.
METHODS A total of 19,549 non-diabetic individuals (aged 35–75 years old) at high CVD risk were enrolled during 2017–2021 from Fujian Province, China. Participants were divided into 4 groups according to the quartile of the indices. The correlation between the new AOI and newly diagnosed DM were asscessed by receiver operating characteristic (ROC), restricted cubic spline (RCS) and multivariable logistic regression analysis.
RESULTS The incidence of newly diagnosed DM was 8.3% (n = 1629) in participants without diabetes at high CVD risk within 3 years of follow-up. In the overall study population, the mean age of all participants was 57.1 ± 9.5 years, 40.9% were male. After adjusting for potential confounding factors, the multivariate model showed that the higher the level of the new AOI are significantly related to the risk of new onset diabetes [Q4WHtR vs. Q1WHtR: OR 2.212, P < 0.0001; Q4BRI vs. Q1BRI: OR 2.194, P < 0.0001; Q4ConI vs. Q1ConI: OR 1.552, P < 0.0001; Q4WWI vs. Q1WWI: OR 1.527, P < 0.0001], except for ABSI (Q4 vs. Q1: OR 1.090, P = 0.259). Further analysis and comparison of ROC curves showed that WHTR and BRI had the best predictive ability for new onset diabetes (AUCWHTR = 0.611; AUCBRI = 0.611; AUCConI = 0.575; AUCWWI = 0.576; AUCABSI = 0.544; P < 0.05).
CONCLUSIONS The new abdominal obesity indices, especially WHTR and BRI, were significantly associated with the occurrence of newly diagnosed DM and may be helpful in preventing DM in population at high CVD risk.
GW35-e1092
Chen Du, Hao Yang
Guangdong Provincial People’s Hospital
OBJECTIVES The purpose of this study is to investigate whether there is a difference in inflammatory state between patients with atrial fibrillation (AF) and those without AF in acute stroke events, and whether the difference in inflammatory state has predictive value for thrombosis formation and endovascular treatment. This study is based on clinical basic examinations such as blood routine, and the inflammatory state is transformed into a composite inflammation index.
METHODS Patients who received endovascular treatment for acute ischemic stroke in Guangdong General Hospital from 2018 to 2024 were retrospectively and prospectively collected. The baseline data of the patients, the occurrence of atrial fibrillation and the test results before and after treatment were recorded. The outcome after 90 days was defined as good outcome and poor outcome based on the modified Rankin scale (mRS) score. R language and P were used to perform data distribution display, single factor analysis, multi-factor regression and machine learning, and SII, SIRI, NLR, PLR, etc., were used as indicators for the evaluation of systemic inflammation.
RESULTS A total of 245 atrial fibrillation (AF) patients and 198 non-AF patients were included. After adjusting for confounding factors, machine learning methods such as Naive Bayes and Logistic Regression were applied, followed by internal validation and data analysis. Among the parameters, postoperative NLR demonstrated the strongest predictive ability, while SIRI had the highest overall predictive value with an AUC of 0.768 (P < 0.001). Further subgroup analyses concluded: (1) AF patients had higher pre-treatment systemic inflammation indices compared to non-AF patients; (2) AF was significantly associated with an increased risk of cardioembolic stroke; (3) AF patients with cardioembolic events had higher pre-treatment systemic inflammation indices compared to non-cardioembolic patients. This suggests a clear relationship between AF and inflammation, though it remains unclear whether AF directly causes or indirectly induces cardioembolic stroke through inflammatory states, warranting further pathological analysis of stroke thrombi by our research group.
CONCLUSIONS Composite inflammatory biomarkers, including SII, SIRI, and NLR, hold clinical significance in studying the systemic inflammatory state and cerebrovascular adverse events such as acute stroke in patients with atrial fibrillation (AF). Exploring the relationship between AF, thrombosis, and inflammation involves understanding changes in coagulation function, the role of neutrophil extracellular traps, and other mechanisms. Enhancing our understanding of the pathophysiological links between thrombosis, AF, and stroke, combined with clinical outcome analysis, is crucial for investigating the pathological mechanisms by which AF leads to stroke and for identifying new therapeutic targets. This is vital for improving the comprehensive treatment of AF and stroke.
GW35-e1120
Caie Li, Yuchen Jin, Jie Ma, Qiongying Wang, Jing Yu
The Second Hospital of Lanzhou University
OBJECTIVES The early identification and timely intervention of immune checkpoint inhibitor (ICI)-associated myocarditis are crucial for improving patient prognosis. However, specific diagnostic markers for this condition are currently lacking. This study aims to explore the levels of ROCK2 protein in patients with ICI-associated myocarditis and evaluate its diagnostic value. The findings aim to provide a basis for the diagnosis and potential treatment strategies for ICI-associated myocarditis.
METHODS Patients diagnosed with ICI-associated myocarditis at the Second Hospital of Lanzhou University from January 1, 2023, to June 1, 2024, were included in this study. An equal number of tumor patients who had not used ICIs were included as the control group. Levels of RhoA, ROCK2, and inflammation-related markers (IL-1β, IL-17A, IL-6, IL-21, TNFα), as well as myocardial injury markers (cTnI, CK-MB, NT-proBNP, sST2), were measured and compared between the two groups. In this study, blood samples were collected from both groups to measure the specified biomarkers. The levels of RhoA and ROCK2 were determined using enzyme-linked immunosorbent assay (ELISA), while inflammation-related cytokines (IL-1β, IL-17A, IL-6, IL-21, TNFα) were quantified using multiplex bead-based assays. Myocardial injury markers (cTnI, CK-MB, NT-proBNP, sST2) were measured using standard laboratory techniques. Statistical analyses were performed to compare the levels of these markers between the ICI-associated myocarditis group and the control group, using appropriate tests to determine significance.
RESULTS A total of 10 patients were included in the ICI-associated myocarditis group and 10 in the control group. In the myocarditis group, 3 patients showed elevated cTnI levels, and all 10 patients had elevated NT-proBNP levels. There were no significant differences in cTnI levels between the myocarditis and control groups, but NT-proBNP levels were significantly higher in the myocarditis group. No significant differences were found in IL-6 and TNFα levels between the two groups. However, levels of RhoA, ROCK2, IL-1β, IL-17A, and IL-21 were significantly higher in the myocarditis group compared to the control group. The elevated levels of RhoA and ROCK2 suggest that the ROCK2 signaling pathway might play a crucial role in the pathogenesis of ICI-associated myocarditis. The significant increase in inflammatory cytokines (IL-1β, IL-17A, IL-21) in the myocarditis group indicates an enhanced autoimmune response, which is likely mediated by the ROCK2 pathway. These findings suggest that ROCK2 not only serves as a potential diagnostic marker but might also be involved in the progression of myocarditis through the activation of inflammatory pathways.
CONCLUSIONS The occurrence of ICI-associated myocarditis is accompanied by ROCK2 activation and an enhanced autoimmune response mediated by ROCK2. The level of ROCK2 protein may serve as a diagnostic marker for ICI-associated myocarditis and holds potential as a therapeutic target. The significant elevation of ROCK2 and associated inflammatory markers in patients with ICI-associated myocarditis underscores the importance of this pathway in the disease’s pathogenesis. Further studies are warranted to explore the therapeutic potential of targeting ROCK2 in the treatment of ICI-associated myocarditis. This study provides a promising direction for improving the diagnosis and management of this severe adverse effect associated with immune checkpoint inhibitors.
GW35-e1143
Ziliang Chen1, Yukun Zhang1, Ying Liu1, Gary Tse1,2,3, Guangping Li1, Kangyin Chen1, Tong Liu1
1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University, Tianjin, China
2Kent and Medway Medical School, Canterbury, Kent, UK
3School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China
OBJECTIVES To analyze the cardiovascular prognosis of acute myocardial infarction (AMI) patients combined with prostate cancer (PCa).
METHODS The data for this study were derived from the Tianjin Health and Medical Big Data Platform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals in Tianjin City from 2010 to 2023. AMI patients were grouped based on the presence of concomitant PCa. The major adverse cardiovascular events (all-cause death, recurrent MI, or ischemic stroke) were defined as the primary outcome events. Propensity score matching (PSM) (1:3) and Cox regression analysis were used to assess the long-term (5 years) and short-term (30 days) cardiovascular prognosis of patients.
RESULTS A total of 100,708 male patients with initial diagnosis of AMI were included, of whom 375 complicated with PCa. Patients in the PCa group were older, had higher proportions of Killip classification III-IV and co-morbidities, and lower proportions of optimal medical therapy (OMT) and percutaneous coronary intervention (PCI) during hospitalization (all P < 0.001). After PSM analysis, it was found that PCa group had a higher 5-year MACE rate than non-PCa group (48.3% vs. 42.2%, P = 0.043). Kaplan-Meier survival curves showed a significant difference in 5-year cumulative MACE events (P = 0.012) between the two groups, mainly attributed to all-cause mortality events (P = 0.005). Multivariable Cox regression analysis showed that PCa was a risk factor for 5-year MACE events, whereas PCI, antiplatelet agents, and angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists (ACEI/ARB) during hospitalization were protective factors.
CONCLUSIONS AMI patients complicated with PCa have a higher burden of cardiovascular disease, lower rates of OMT and PCI, and a higher risk of long-term adverse cardiovascular events and mortality.
GW35-e1147
Yizhou Zhuang1,2,3,4,5, Meixia Ren1,2,3,4,5, Fan Lin1,2,3,4,5, Zhilong Jia6
1Fujian Provincial Key Laboratory of Geriatric Diseases
2Fujian Medical University
3Fujian Provincial Hospital
4Fuzhou University Affiliated Provincial Hospital
5Fujian Provincial Center for Geriatrics
6Medical Innovation Research Division of Chinese PLA General Hospital
OBJECTIVES In recent years, diabetes has become a serious global health problem, with cardiovascular complications remaining the leading cause of death among diabetic patients. Diabetes significantly increases the development, incidence, and mortality of heart failure with preserved ejection fraction (HFpEF). HFpEF is a complex and heterogeneous syndrome with significant knowledge gaps and treatment challenges. This study aims to explore the potential physiological and pathological mechanisms linking diabetes and HFpEF, to identify potential comorbid genes and related mechanisms in the disease process; at the cellular level, to investigate the damage caused by high glucose to human cardiomyocytes (AC16), and the role of the key gene MTHFD2 in this process.
METHODS Using WCGNA, RRA, LASSO, and other algorithms to analyze public RNA-seq data for diabetes and HFpEF, key genes linking the two diseases were identified. A high-glucose-induced damage model was established in AC16 cells, where the key gene was knocked down, and intervention experiments were conducted using a specific inhibitor. CCK-8, LDH assays, flow cytometry apoptosis detection, ELISA, and RT-PCR were used to evaluate cell viability, toxic effects, apoptotic damage, inflammatory factor secretion, and mRNA expression of inflammation-related genes, respectively. Finally, RNA-seq was utilized to explore the possible mechanism involved.
RESULTS Using three machine learning methods, the RRA algorithm, WGCNA results, and differential gene expression analysis of eight datasets, we narrowed the study target genes to MTHFD2, BTNL9, HMGCS2, CHRNA2, ACOT1, and ANGPTL4. After a literature review and preliminary gene expression detection in cell model, we ultimately chose MTHFD2 as the target gene for following study. After knock-down or inhibition of the MTHFD2 gene in AC16, cells function studies revealed the MTHFD2 interventions improved the high-glucose-induced decrease cell viability (P < 0.05), they reduced the cytotoxic effects of high glucose on AC16 cells (P < 0.05), alleviated high-glucose-induced apoptosis in AC16 cells (P < 0.05), and reduced the inflammatory effects induced by high glucose (P < 0.05). Moreover, RT-PCR results demonstrated that knocking down or inhibiting MTHFD2 also reduced the mRNA expression levels of inflammation-related genes such as IL-18, IL-6, and IL-1β in AC16 cells exposed to high glucose (P < 0.05). Finally, RNA-seq results showed that knocking out MTHFD2 inhibited inflammation-related pathways in AC16 cells, such as the AGE-RAGE signaling pathway in diabetes, the TNF signaling pathway, and the IL-17 signaling pathway, and also inhibited cell death, apoptosis, and programmed cell death, which are consistent with our cell function detection.
CONCLUSIONS High glucose could induce damage to myocardial cells, and MTHFD2 may potentially mediate myocardial damage under high glucose conditions by regulating the AC16 inflammation and apoptosis, thereby participating in the occurrence and development of HFpEF in diabetic patients.
GW35-e1193
Li Yin1, Xiaoge Zhang2, Huanji Zhang1, Changming Xie1, Zhengzhipeng Zhang1, Dong Wang1, Mingxing Mo1, Jie Liu2, Hui Huang1
1Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, P.R. China
2School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong 518107, P.R. China
OBJECTIVES Vascular calcification (VC) is highly associated with cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD). While the effective prevention and treatment of VC remain unavailable in the clinic. Sirtuin 6 (SIRT6) has been recently reported to prevent VC by suppressing the osteogenic trans differentiation of vascular smooth muscle cells (VSMCs) and could be a potential therapeutic target. Natural products, such as cyanidin, exhibit robust agonistic activity on SIRT6. However, poor bioavailability and lack of an effective delivery strategy hinder its clinical application.
METHODS We developed a dual-targeting Ti3C2 nanosheets for cyanidin delivery, which were co-assembled with osteocalcin antibody (OCN Ab) and receptor activator of the nuclear factor kappa B ligand antibody (RANKL Ab) (Ti3C2/RANKL/OCN/Cyanidin, TROC).
RESULTS In this study, we first identified dietary cyanidin as an independent protective factor of aortic calcification by the Framingham Heart Study offspring cohort. In vitro and in vivo assays indicated that TROC possessed excellent stability, and alleviated VC capacity. Moreover, the in vitro cellular studies suggested that cyanidin dose-responsiveness and TROC reduced calcium deposition in VSMCs under phosphate treatment. At mean time, we also observed that cyanidin dose-responsively increased the expression of SIRT6 by western blot analysis. Fluorescence (FL) and Computed tomography (CT) multimodal imaging in vivo confirmed that TROC could selectively accumulate on vascular calcification sites and alleviate calcification.
CONCLUSIONS In conclusion, this study developed a targeting drug delivery system to treat VC, which provides an emerging therapeutic approach for VC clinic treatment.
GW35-e1281
Qiang Xu, Yuqin Mao, Li Shen, Junbo Ge
Zhongshan Hospital, Fudan University
OBJECTIVES To study the short-term effects of the GLP-1 receptor agonists (GLP-1RA) liraglutide and semaglutide on left ventricular function in mice with myocardial infarction, and to analyze the short-term effects of liraglutide and semaglutide on the body weight of normally fed mice.
METHODS Forty 7-week-old C57BL/6J mice were randomly divided into the sham surgery group (SHAM group), myocardial infarction group (MI group), myocardial infarction + liraglutide group (LIRA group), and myocardial infarction + semaglutide group (SEMAG group). The SHAM and MI groups were fed normally until 8 weeks of age. The LIRA and SEMAG groups were subcutaneously injected with liraglutide and semaglutide at a dose of 60 μg/kg/day, respectively, for 1 week until 8 weeks of age. At 8 weeks, the SHAM group underwent a sham operation, while the MI, LIRA, and SEMAG groups underwent myocardial infarction modeling surgery. Cardiac function was assessed using echocardiography one week before and one week after surgery. Body weight changes were measured and analyzed during the 1-week drug administration period and the 1-week post-administration period.
RESULTS Echocardiography results indicated no statistically significant differences in preoperative ejection fraction (EF), left ventricular fractional shortening (FS), or baseline body weight among the groups (P > 0.05). One week postoperatively, echocardiography showed a significant decline in left ventricular function in the MI, LIRA, and SEMAG groups compared to the SHAM group. However, there were no significant differences in EF and FS values among the MI, LIRA, and SEMAG groups (P > 0.05). No significant differences in 2-week body weight gain were observed among the groups (P > 0.05). During the 1-week administration period, the SEMAG group showed slightly better inhibition of body weight gain than the LIRA group (P > 0.05). However, one week after the end of administration, the SEMAG group had a significantly higher increase in body weight compared to the LIRA group (P < 0.05).
CONCLUSIONS Short-term use of GLP-1RAs liraglutide and semaglutide did not significantly improve cardiac function in mice after myocardial infarction. Liraglutide and semaglutide did not show a significant effect on inhibiting body weight gain over the administration and post-administration periods. Moreover, semaglutide resulted in a more pronounced weight gain post-administration compared to liraglutide.
GW35-e1287
Xixiang Tang1, Xiaolan Ouyang2, Hongxing Wu2, Yina Wang1, Suhua Li2
1VIP Medical Service Center, The Third Affiliated Hospital, Sun Yat-sen University
2Department of Cardiovascular Medicine, The Third Affiliated Hospital, Sun Yat-sen University
OBJECTIVES Metabolic-dysfunction-associated fatty liver disease (MAFLD) is associated with cardiac dysfunction. This study was aim to explore the relationship between distinct novel phenotypes of MAFLD and cardiac remodeling.
METHODS This cross-sectional study included 3233 participants who underwent hepatic ultrasonography and echocardiography at the Third Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2023. All participants were diagnosed with MAFLD based on standard clinical criteria. Cluster analysis was performed using gender, body mass index (BMI), total cholesterol (TC), triglyceride (TG), HbA1C, triglyceride-glucose (TyG) index, uric acid, and fibrosis index based on the 4 factor (FIB-4) as variables to identify subgroups with similar metabolic profiles. The clinical characteristics of each subgroup were analyzed, and the impact of MAFLD phenotypes on cardiac structure and function was evaluated. Multivariable linear regression analyses were conducted to determine the influence of different MAFLD phenotypes on cardiac parameters.
RESULTS Four distinct clusters were identified. Cluster 1 (n = 1381) comprised males with a relatively normal metabolic state and low FIB-4 levels. Cluster 2 (n = 453) included males with the highest BMI and uric acid levels. Cluster 3 (n = 474) consisted of males with the most severe glucose and lipid metabolic disturbances. Cluster 4 (n = 925) comprised females with the highest FIB-4 levels. Compared to Cluster 1, participants in Clusters 2 and 3 exhibited worse cardiac structure and function, including enlargement of the left atrium, right atrium, left ventricular internal end-diastolic dimension (LVDd), interventricular septum (IVS), left ventricular posterior wall thickness (LVPW), right ventricle, and reduced left ventricular ejection fraction (LVEF). Conversely, participants in Cluster 4 had better cardiac structure and function compared to those in Cluster 1. In multivariable regression analyses, after adjusting for confounding factors, Cluster 2 participants were independently positively associated with the left atrium (β = 2.07; P < 0.001), IVS (β = 0.48; P < 0.001), LVPW (β = 0.42; P < 0.001), right atrium (β = 2.05; P < 0.001), and right ventricle (β = 1.07; P < 0.001). Conversely, Cluster 4 participants were independently negatively associated with these cardiac parameters.
CONCLUSIONS Among patients with MAFLD, males with the highest BMI and uric acid levels were associated with adverse cardiac remodeling, while females with the highest FIB-4 levels exhibited better cardiac structure and function.
GW35-e1332
Jiayin You, Niansong Wang
Shanghai Sixth People’s Hospital
OBJECTIVES Protein convertase subtilisin/kexin type9 (PCSK9) is known to play a key role in dyslipidemia. An increase in serum PCSK9 has been reported in patients with nephrotic syndrome (NS). However, the specific mechanisms and the therapeutic potential of targeting PCSK9 in kidney disease remain elusive.
METHODS We thus investigated the effects and mechanisms of PCSK9 in patients with focal segmental glomerulosclerosis (FSGS) and in mice with adriamycin (ADR)-induced nephropathy. Male C57/BL6 mice were divided into the following 4 groups: Control; evolocumab (EVO); ADR; ADR+EVO. In vitro studies were used to validate the direct effects of PCSK9 on podocytes.
RESULTS We found that serum PCSK9 was significantly increased in FSGS patients and in ADR mice and was associated with increased creatine levels and urinary protein excretion compared with that of the control group. EVO could significantly decrease the levels of PCSK9 and improve the renal function in ADR mice. Mechanistic study found that PCSK9 could promote the pyroptosis of podocyte. High throughput sequencing study found that LncRNA MEG3, a non-coding RNA that has been reported to be associated with pyroptosis, was significantly increased in PCSK9 pretreated podocyte.
CONCLUSIONS This study revealed that serum PCSK9 was increased in FSGS and ADR induced nephropathy, thus promoting the pyroptosis of podocytes through elevating Lnc RNA MEG3. Targeting PCSK9 via EVO represents a potential therapeutic strategy for FSGS and ADR-nephropathy.
GW35-e1344
Weiwei Zhu1, Lin Zhao2
1Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
2Beijing Chaoyang Hospital, Capital Medical University
OBJECTIVES The microvasculature of small arterioles and venules, interconnected by a vast capillary network, is essential for the functionality of all organs, particularly the brain, which has high energy demands. Alterations in microvasculature are linked to various brain disorders and aging. Microvascular obstruction by small emboli is common in both healthy and diseased brains. While the capacity of vessels to recanalize themselves after blockage by microemboli has been studied, the immune responses triggered by such obstructions remain largely unknown.
METHODS In this study, 5 μm microspheres were used to simulate microemboli and investigate the immune responses following microvascular blockade in the brain. The recruitment of immune cells was assessed at different time points post-blockade. Splenectomy was performed to determine the source of recruited monocytes, and the roles of VCAM-1 and TNF-α signaling in monocyte recruitment and activation were analyzed.
RESULTS The 5 μm microspheres predominantly localized to the capillaries without causing immediate adverse effects. A significant increase in Ly6Cint monocyte recruitment was observed 12 hours post-blockade, with negligible recruitment of neutrophils and lymphocytes. Splenectomy indicated that the spleen serves as the primary reservoir for these recruited monocytes. VCAM-1, which is constitutively expressed on cerebral endothelial cells, was found to be crucial for mediating monocyte recruitment. Monocyte activation via TNF-α signaling occurred mainly in the spleen rather than in the brain parenchyma. Additionally, although infrequent, the recruited monocytes were capable of removing microspheres from the capillaries and transporting them to other locations.
CONCLUSIONS This study reveals a unique monocyte recruitment strategy that has the potential to recanalize blocked microvasculature in the brain. The findings highlight the critical roles of the spleen as a monocyte reservoir and VCAM-1 and TNF-α signaling in the recruitment and activation of monocytes.
GW35-e1363
Yilin Pan, Kexin Peng, Weiwei Chen, Ping Yang, Beibei Du
China-Japan Union Hospital of Jilin University
OBJECTIVES Osimertinib, a third-generation EGFR-TKI, is approved for the first-line treatment of EGFR-mutated advanced NSCLC and for T790M-positive NSCLC after progression on previous EGFR-TKI therapy. Despite its general tolerability, osimertinib is associated with cardiotoxicity, including QT interval prolongation, which necessitates detailed evaluation due to its increasing use.
METHODS This retrospective, single-center study conducted at Jilin University China-Japan Union Hospital evaluated electrocardiographic changes in Chinese patients with EGFR-mutated NSCLC treated with osimertinib. The study included 41 patients who received osimertinib (80 mg daily) and had both pre- and post-treatment ECG records. ECG parameters such as heart rate, PR interval, QRS duration, QRS axis, and QT intervals were manually calculated and analyzed.
RESULTS The study population had a mean age of 68.56 ± 8.73 years, comprising 46.34% males. Significant changes were observed in the QRS axis (P = 0.0387), QTc Bazett interval (P < 0.0001), and QTc Fridericia interval (P = 0.0002) post-treatment. QT interval prolongation was significant (McNemar test P = 0.0039), with both QTc Bazett and QTc Fridericia intervals showing notable prolongation. However, the changes in heart rate, PR interval, and QRS duration were not statistically significant.
CONCLUSIONS This study is the first to investigate osimertinib-induced cardiac adverse events in Chinese patients with EGFR-mutated NSCLC. The significant prolongation of QTc intervals and changes in the QRS axis underscore the need for rigorous ECG monitoring to mitigate potential cardiotoxicity.
PERIPHERAL VASCULAR DISEASE
GW35-e0081
Hong Zhe Zhang
The Seventh Affiliated Hospital of Southern Medical University
OBJECTIVES Previously, we reported the angio-vasculogenic properties of human stromal vascular fraction (SVF) and adipose tissue-derived mesenchymal stem cells (ASCs). In this study, we investigated whether the combination of mesenchymal stem cells (ASCs) and stromal vascular fraction (SVF) cells exhibited synergistic angiogenic properties.
METHODS We conducted quantitative qRT-PCR, Matrigel plug, tube formation assays, and in vivo therapeutic assays using an ischemic hind limb mouse model. Immunohistochemical analysis was also conducted.
RESULTS qRT-PCR results revealed that FGF-2 was highly upregulated in adipose tissue-derived mesenchymal stem cells (ASCs) compared with stromal vascular fraction (SVF), while PDGF-b and VEGF-A were highly upregulated in SVF. Conditioned medium from mixed cultures of ASCs and SVF (A+S) cells showed higher Matrigel tube formation and endothelial cell proliferation in vitro. The stromal vascular fraction (SVF) and adipose tissue-derived mesenchymal stem cells (ASCs) transplantation into ischemic mouse hind limbs strongly prevented limb loss and augmented blood perfusion compared with SVF cell transplantation. Transplanted A+S cells also showed high capillary density, cell proliferation, angiogenic cytokines, and anti-apoptotic potential in vivo compared with transplanted SVF.
CONCLUSIONS Our data indicate that stromal vascular fraction (SVF) and adipose tissue-derived mesenchymal stem cells (ASCs) transplantation results in synergistic angiogenic therapeutic effects. Accordingly, stromal vascular fraction (SVF) and adipose tissue-derived mesenchymal stem cells (ASCs) injection could be an alternative therapeutic strategy for treating ischemic diseases.
GW35-e0082
Hong Zhe Zhang
The Seventh Affiliated Hospital of Southern Medical University
OBJECTIVES Although stem cells have extensively been studied as a novel vehicle for tissue repair, their sustained efficacy remains controversial. In this study, we aimed to investigate the angiogenic potency over time of stromal cell-derived factor-1 (SDF-1) gene-edited amniotic mesenchymal stem cells (AMM/S) in a hindlimb ischaemia model.
METHODS An stromal cell-derived factor-1 (SDF-1) transgene was inserted into the amniotic mesenchymal stem cells (AMM) genome via transcription activator-like effector nuclease (TALEN) mediated knock-in, and cell migration, Matrigel tube formation, and in vivo Matrigel plug assays were performed. The stromal cell-derived factor-1 (SDF-1) gene-edited amniotic mesenchymal stem cells (AMM/S) were also transplanted into hindlimb ischaemia model mice. Blood perfusion, therapeutic potential, histology, capillary density and in vivo angiogenic assays were performed.
RESULTS The stromal cell-derived factor-1 (SDF-1) gene-edited amniotic mesenchymal stem cells (AMM/S) exhibited high expression of the SDF-1 gene, and robustly promoted migration, proliferation and microvascular formation. The stromal cell-derived factor-1 (SDF-1) gene-edited amniotic mesenchymal stem cells (AMM/S) transplantation significantly increased blood perfusion and limb loss prevention compared with the amniotic mesenchymal stem cells (AMM). The stromal cell-derived factor-1 (SDF-1) gene-edited amniotic mesenchymal stem cells (AMM/S) also significantly inhibited increased capillary density and expression of angiogenic factors in the ischaemic hindlimb.
CONCLUSIONS Our study demonstrated that stromal cell-derived factor-1 (SDF-1) gene-edited amniotic mesenchymal stem cells (AMM/S) provides a significant therapeutic effect in ischaemic hindlimbs by enhancing angiogenesis.
GW35-e0695
Honggang Sui, Zhiqiang Zhang, Xiaozeng Wang, Yasong Wang
General Hospital of Northern Theater Command
OBJECTIVES This study aimed to investigate the risk factors and prognosis associated with Stanford type B aortic dissection on the lesser curvature side.
METHODS A total of 1251 patients diagnosed with aortic disease underwent computed tomography angiography (CTA) examinations post admission. The analysis focused on endpoint events of aortic dissection occurring on the lesser curvature side versus the larger curvature side of the aorta.
RESULTS The study found that the descending aortic lumen diameter (1.466 (1.062, 2.022), P = 0.020), aortic bending index (2.415 (1.061, 5.496), P = 0.036), and aortic bending angle (1.018 (1.005, 1.031), P = 0.007) were independently identified as risk factors for aortic dissection on the lesser curvature side. The optimal cutoff values for the circumference and diameter of the lesser curvature side were determined to be 157.05 mm and 78.03 mm, respectively, with corresponding areas under the curve of 0.614 and 0.597. The main composite endpoint events were lower in aortic dissections on the lesser curvature side compared to the larger curvature side, with a statistically significant difference (0.98% vs. 6.35%, P = 0.028). Additionally, secondary composite endpoint events were also less frequent in aortic dissections on the lesser curvature side compared to the larger curvature side, with a statistically significant difference (4.95% vs. 14.81%, P = 0.007).
CONCLUSIONS This research highlights the importance of the diameter of the descending aorta lumen, aortic curvature index, and aortic curvature angle as independent risk factors for aortic dissection on the lesser curvature side in cases of TBAD. Specifically, if the diameter of the lesser curvature exceeds 78.03 mm or the circumference is greater than 157.05 mm, the likelihood of TBAD occurring on that side is higher. Moreover, both short-term and long-term aortic dissection events are less common on the lesser curvature side compared to the larger curvature side.
GW35-e0696
Honggang Sui, Shuhuai Hou, Xiaozeng Wang, Zhiqiang Zhang, Yasong Wang, Xiaofan Cao
General Hospital of Northern Theater Command
OBJECTIVES Explore the risk factors of bird-beak configuration occurrence and its outcomes after thoracic aortic endovascular repair (TEVAR) for Stanford B-type aortic dissection (TBAD).
METHODS 701 patients are enrolled, they are divided into two groups according to the occurrence of bird-beak configuration in the proximal end of the stent graft, i.e., bird-beak group (n = 291) and no-bird-beak group (n = 410). And then we analyze the risk factors and prognosis of the bird-beak configuration. The subgroup sub-analysis based on immediate intraoperative endoleak in bird-beak group was performed.
RESULTS Multivariate logistic analysis shows that the aortic proximal landing in Zone 2 (OR = 1.839, 95% CI: 1.133–2.985; P = 0.014) and the length of stents (OR = 1.013, 95% CI: 1.002–1.025; P = 0.021) are independent risk factors for the bird-beak configuration. The proximal bare stents (OR = 0.019, 95% CI: 0.010–0.039; P < 0.001) are a independent protective factor for the bird-beak configuration. The subgroup’s Kaplan Meier analysis reveals a significant increase in the incidence of aortic-related adverse events (Logrank P = 0.005) and clinical adverse events (Logrank P = 0.031) between the immediate intraoperative endoleak group and the no immediate intraoperative endoleak group.
CONCLUSIONS The aortic proximal landing in Zone 2 and the length of stent are independent risk factors, and proximal bare stents are a protective factor for the bird-beak configuration. Bird-beak configuration combined with intraoperative immediate endoleak is associated with worse outcomes.
GW35-e0847
Huimin Ma, Delian Zhang
People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES The aim of our study was to determine the expression concentrations of 10 pre-selected microRNAs (miRNAs/miRs) in the plasma of patients with Takayasu’s arteritis (TA) and essential hypertension (EH) were detected in order to verify whether these miRNAs could be used as biomarkers for the differential diagnosis of TA and EH.
METHODS Plasma samples was collected from 20 patients with TA and 20 age/gender-matched patients with EH, who served as the control group. The plasma concentrations of the above miRNAs was detected through quantitative PCR.
RESULTS The results showed that compared with patients with EH, Levels of the expression of miR-125a-5p, miR-155-5p, miR-181a-5p, miR-203a-3p, miR-326 and miR-346 were lower in patients with TA (P < 0.05). After adjusting for potential confounding variables, including age, gender, systolic blood pressure, erythrocyte sedimentation rate and renin, the difference in the expression of miR-155-5p, miR-181a-5p and miR-203a-3p between patients with TA and EH was still statistically significant (P < 0.05). Receiver operating characteristic curve analysis revealed that when the above three microRNAs were combined, the sensitivity increased to 0.95 and the specificity was 0.80, with an area under the curve value of 0.805 (95% confidence interval, 0.634–0.977).
CONCLUSIONS The results of the present study suggested that the combined expression of miR-155-5p, miR-181a-5p and miR-203a-3p could be used as a biomarker to distinguish hypertension caused by TA and EH.
GW35-e0943
Shuo Zheng1, Yi Yang2, Fangqin Wu3, Danyang Ling1, Ziwei Chen1, Zhizhi Hu4, Lisha Ai5, Guanhua Su6, Qi Wang1, Wenzhu Li7
1Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
2Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
3Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University
4Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
5Division of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
6Division of Cardiovascular Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
7Shanghai Aging and Degeneration Association, Vascular Aging and Cardio-Cerebrovascular Disease Council
OBJECTIVES Thromboangiitis obliterans (TAO) is a rare, nonatherosclerotic, segmental inflammatory disease that typically onsets in male at young age with heavy smoking. TAO commonly affects small and medium-sized arteries, veins, and nerves of extremities, with symptoms ranging from intermittent claudication, digital gangrene, and limb amputation. Up to 1/3 of patients with TAO will experience limb amputation within 15 years from diagnosis. In this study, we aim to address sex-based differences of cumulative limb amputation for patients with TAO in a real-world dataset.
METHODS A cross-sectional study was performed in Nationwide Inpatient Sample (NIS) of United States, from calendar year 2016–2021. The diagnosis of diseases was identified by ICD-10-CM codes. Comparisons of risk factors for cumulative limb amputation (CLA) between female and male patients were assessed by univariable regression analysis. Multivariate logistic regression model was further employed to analyze association between risk factors and CLA grouped by sex, adjusted with demographics, cardiovascular risk factors and comorbidities.
RESULTS In this study, 27.8% (N = 363) patients with TAO (N = 1297) had cumulative limb amputation. The CLA rate was up to 32.7% in male (N = 267) and 19.5% in female (N = 94) patients. Female patients showed significant lower CLA risk than male patients (P < 0.001). Among male patients, elderly showed lower CLA risk compared young patients in NIS (adjusted OR = 0.41; 95% CI: 0.21–0.80; P = 0.009), and no significant difference was observed between different races/ethnicities. Among female patients, middle-aged patients showed higher CLA risk compared to young patients (adjusted OR = 3.06; 95% CI: 1.38–6.80; P = 0.006), and Black patients showed higher CLA risk compared to White patients (adjusted OR = 2.41; 95% CI: 1.19–4.86; P = 0.014).
CONCLUSIONS Male patients showed significant higher CLA risk than female patients, and the CLA rate was up to 32.7% in male and 19.5% in female. Compared to young patients, elderly male patients showed lower CLA risk while middle-aged female patients showed higher CLA risk. Black female patients showed higher CLA risk compared to White female patients. The sex-based disparities on age and race spur further studies on mechanism, health equity and multidisciplinary care to decrease CLA for patients with TAO.
GW35-e1139
Xiaofan Cao, Xiaozeng Wang
General Hospital of Northern Theater Command
OBJECTIVES Aortic dissection poses a serious threat to the lives of patients, and type Ia endoleak is a common complication following thoracic aortic endovascular repair (TEVAR). The risk factors for type Ia endoleak in patients with uncomplicated Stanford type B aortic dissection (TBAD) after TEVAR remain unclear.
METHODS A total of 410 patients with uncomplicated TBAD were included in this retrospective study and were randomized to a training (70%) or validation (30%) cohort. In the training cohort, least absolute shrinkage and selection operator regression (LASSO) and multivariate Cox regression analyses were used to identify independent risk factors for the occurrence of type Ia endoleak after TEVAR. Based on these factors, a nomogram prediction model was constructed. The area under the receiver operating characteristic curve (AUC), concordance indexes (C-index) and calibration curve were used to assess the efficiency of the nomogram, and clinical utility was evaluated using decision curve analysis (DCA) in both training and validation cohorts.
RESULTS The shorter proximal landing zone length, type III aortic arch, immediate endoleak and bird-beak configuration were independent risk factors for type Ia endoleak. These factors were integrated into the development of the nomogram model. In the training cohort, the AUC of the model was 0.72 (0.63–0.81), 0.75 (0.66–0.83) and 0.77 (0.69–0.85) for 1-year, 3-year and 5-year occurrence of type Ia endoleak, while in the validation cohort, it was 0.78 (0.63–0.93), 0.79 (0.67–0.91) and 0.72 (0.57–0.86), respectively. The C-indexes of the nomogram in the training and validation cohorts were 0.728 and 0.712, respectively. Moreover, the calibration curve demonstrated a good consistency between the predicted and actual 1-year, 3-year and 5-year probabilities for occurrence of type Ia endoleak. DCA indicated that the nomogram prediction model could achieve greater clinical net benefits compared to “treat all” or “treat none” options within a certain threshold range.
CONCLUSIONS The development of a nomogram for type Ia endoleak after TEVAR in patients with uncomplicated TBAD will help aid clinical decision-making. By facilitating the early identification of type Ia endoleak, it is possible to optimize patient management and improve the prognosis of these high-risk patients.
GW35-e1194
Kaiwen Jiang, Hui Dong, Hongwu Li, Yujie Zuo, Wentao Ma, Yubao Zou, Xiongjing Jiang
Department of Cardiology, National Center for Cardiovascular Diseases and Fuwai Hospital
OBJECTIVES The management of supra-aortic arteries stenosis caused by Takayasu arteritis (SAASTA) through endovascular therapy remains an unresolved issue in clinical practice. This study aims to investigate the perioperative and long-term outcomes of endovascular therapy in patients with SAASTA.
METHODS From January 2002 to December 2021, patients with SAASTA who underwent endovascular therapy were enrolled in Fuwai Hospital, National Center for Cardiovascular Diseases. All lesions received percutaneous transluminal angioplasty (PTA) by the conventional balloon or the drug-coated balloon. The presence of significant dissection and/or residual stenosis of more than 50% was defined as failure of PTA and then stent implantation was carried out. Perioperative and long-term clinical outcomes were followed up and recorded.
RESULTS A total of 375 lesions were successfully treated in 266 interventional procedures in 219 patients (1.74 lesions per patient), involving subclavian artery, 198; vertebral artery, 55; carotid artery, 109; brachiocephalic artery, 13. Supra-aortic artery-related symptoms were relieved in 93.2% (204/219) of patients after the first procedure. Cerebral hyperperfusion syndrome occurred in 5 patients during the perioperative period, one of whom died of cerebral hemorrhage. During a median follow-up of 66 (24, 120) months, restenosis occurred in 155 of 375 lesions (41.3%). According to the Kaplan–Meier analysis, at the last follow-up, lesions receiving selective stent placement had a lower primary patency rate than lesions undergone conventional balloon angioplasty (26.6% vs. 42.7%, P = 0.024) and lesions undergone drug-coated balloon angioplasty (26.6% vs. 64.0%, P = 0.032), but there was no significant difference between the latter two (42.7% vs. 64.0%, P = 0.347). Stenting placement [HR = 1.57 (1.027–2.412), P = 0.037], and the state of active inflammation before procedure [HR = 1.50 (1.008–2.251), P = 0.046] were independent predictors of the restenosis. The 1, 5, and 10-year SAASTA-related symptom recurrence rates were 15.2%, 26.7%, and 34.1%, respectively. The 1, 5, and 10-year cumulative composite clinical events-free survival rates were 98.9%, 90.2%, and 82.6%, respectively.
CONCLUSIONS Endovascular therapy was safe and effective for patients with SAASTA, with a high rate of symptom relief and a low incidence of long-term composite clinical adverse events. Postoperative restenosis posed a significant clinical challenge, particularly in patients who received stent placement and those with active inflammation.
GW35-e1329
Weijie Fu1, Maolin Zhao1, Siyi He2
1Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China
2Associated Professor, The General Hospital of Western Theater Command, Rongdu Avenue No. 270, Jinniu District, Chengdu City 610083, Sichuan Province, China
OBJECTIVES Anticoagulants are the primary means for the treatment and prevention of venous thromboembolism (VTE), but their clinical standardized application still remains controversial.
METHODS Objective: To comprehensively evaluate the efficacy and safety of different anticoagulants in the management of venous thromboembolism (VTE). Data sources: Medline, Embase, and Cochrane Library from their inception up to August 2023. Study selection: Randomized controlled trials were searched to compare efficacy and safety of various anticoagulants in VTE. Data extraction and synthesis: Data extraction and quality assessment were completed by 2 independent reviewers. Network meta-analyses were performed based on Bayesian generalized linear models, and a frequentist framework with multivariate random effects was used to fit the model. Main outcomes and measures: Primary outcome was the recurrence or incidence of VTE as well as major bleeding events.
RESULTS In terms of treatment, 58 trials with 119,417 patients proved eligible, while 125 trials with 225,414 patients were included in terms of prevention. All anticoagulants were found to reduce the recurrence or incidence of VTE compared with Placebo, of which high-level evidence indicated that direct thrombin inhibitors (TIs) and novel oral anticoagulants (NOACs) were the two most effective drugs. For treatment, low molecular weight heparin (LMWH), unfractionated heparin (UFH), and vitamin K antagonists (VKAs) significantly increased the risk of major bleeding in comparison to Placebo. Subgroup analyses showed that NOACs had better efficacy in reducing the recurrence of VTE compared to VKA, Placebo, and AP, indicating. For prevention, only UFH and NOACs showed significant increased risks in major bleeding. Subgroup analyses showed that NOACs reduced the incidence of VTE compared to placebo, but increased the incidence of clinically relevant non-major bleeding. Additionally, after an exhaustive analysis of NOACs, the analysis showed that apixaban had a superior performance in major bleeding compared to rivaroxaban. There were also significant differences in effectiveness of preventing VTE, and results indicated that TTP889 was less effective than the other NOACs.
CONCLUSIONS TIs and NOACs were superior in efficacy with minimal side effects, making them pivotal choices for both prevention and treatment of VTE. Clinical practitioners must carefully weigh drug characteristics, indications, and contraindications to optimize treatment outcomes.
GW35-e1364
Jang Hyuk Cho
Department of Rehabilitation Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea
OBJECTIVES Leriche Syndrome is a rare and critical vascular condition that causes the progressive atherosclerotic obliteration of the terminal part of the abdominal aorta, iliac arteries and femoropopliteal vessels. This disease is frequently unrecognized or misdiagnosed, the exact prevalence and incidence are also unknown. Sjogren syndrome is a systemic autoimmune disease commonly presenting with dryness involving the eyes and mouth due to inflammation. Atherosclerosis risk increases in patients with systemic autoimmune diseases, there were few data on Sjogren syndrome.
METHODS A 69-year-old female patient was referred to our clinic from the Department of Rheumatology due to progressive and constant cramping pain and intermittent claudication in bilateral extremities for 6 months. She reported Sjogren syndrome, taking celecoxib and hydroxychloroquine for 4 years. The patient denied other medical conditions as hypertension, hyperlipidemia, hyperglycemia and smoking. Motor and sensory examination revealed normal. Nerve conduction studies of her lower extremities performed were normal and symmetrical. Magnetic resonance imaging revealed a protruded intervertebral disc at the L4 and L5 vertebral levels, but no obvious stenotic findings was seen in spinal canal. She underwent conservative managements including physical therapy, caudal approach epidural steroid injection, and pregabalin medication. However, the pain was refractory to those managements.
RESULTS The ankle-brachial index was 0.44 on the right side and 0.51 on the left side, indicating bilateral vascular disease. Abdominal contrast-enhanced computed tomography angiography showed occlusion from the infrarenal abdominal aorta to bilateral common iliac arteries, with collateral pathways. Based on the clinical and radiographic findings, a diagnosis of aortoiliac occlusive disease, also called Leriche syndrome was made. She underwent an aorto-biiliac bypass surgery and showed no other complication in Department of Vascular Surgery.
CONCLUSIONS Atherosclerosis could be caused and accelerated by inflammation of arteries’ wall, however, the exact immune mechanisms are still unknown. The association between Sjogren syndrome and atherosclerosis haven’t been explained for now, and the pathophysiology of atherosclerosis in Sjogren syndrome are also yet be discovered. More studies need to be conducted to find the pathophysiology of atherosclerosis in Sjogren syndrome with Leriche syndrome or vascular event.
BIPSYCHIC MEDICINE
GW35-e0010
Fengyao Liu1,3, Bingqing Bai1,3, Han Yin2, Yuting Liu2, Haochen Wang1, Huan Ma1, Qingshan Geng2
1Guangdong Provincial People’s Hospital
2Shenzhen People’s Hospital
3South China University of Technology
OBJECTIVES Angina with no obstructive coronary artery disease (ANOCA) and mental stress-induced myocardial ischemia (MSIMI) are currently distinct and poorly understood conditions. This study aimed to characterize the myocardial blood flow (MBF) changes associated with mental stress.
METHODS This single-blind, parallel-group clinical trial enrolled 84 women with ANOCA aged 18–75 years old and 42 age-matched healthy women between June 2019 and April 2021 in Guangdong Provincial People’s Hospital, China. Participants completed standardized mental stress, adenosine vasodilator stress tests. Myocardial perfusion defects and MBF changes were assessed by 13NH3 Positron Emission Tomography. MSIMI was defined as a summed difference score (SDS) ≥3.
RESULTS A significantly higher prevalence of MSIMI was observed in women with ANOCA than in controls (42.9% vs. 2.4%, P < 0.001). Hemodynamic response to mental stress was also greater but MBF change was statistically similar between groups. A reduction in MBF early post mental stress was found to correlate with higher SDS and angina grading and was a significant independent indicator of MSIMI. Additionally, an overall MBF post to during mental stress difference ratio of ≤−10% was associated with a 4-times higher risk of MSIMI; a difference ratio of ≤−10% in the right coronary artery was associated with a 28-times higher risk of MSIMI.
CONCLUSIONS MSIMI is a common and neglected phenomenon in women with ANOCA. We found a lower-than-expected correlation with CMD but characterized an early decline in MBF post mental stress that may have a critical role in the pathophysiology of MSIMI.
GW35-e0795
Zhuofei Shi1, Kun Xia2, Jianchao Li3, Jianqi Lu4, Hongping Lu5, Yanli Li6, Jifeng Zhang7, Qilan Chen8, Jing Liu9, Rongjing Ding1
1Department of Cardiology, Peking Union Medical College Hospital, Beijing, China
2Department of Cardiology, Beijing Chaoyang Hospital Affiliated to Capital University of Medical Science, Beijing, China
3Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, China
4Department of Cardiology, Guangxi University of Chinese Medicine Affiliated Hospital, Nanning, Guangxi, China
5Department of Cardiology, Nanning Red Cross Hospital, Nanning, Guangxi, China
6Department of Cardiology, Jiamusi Central Hospital, Jiamusi, Heilongjiang, China
7Department of Cardiology, Zhejiang Provincial Tongde Hospital, Hangzhou, Zhejiang, China
8Department of Cardiology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, China
9Department of Cardiology, The Fourth Hospital of China Medical University, Shenyang, Liaoning, China
OBJECTIVES Growing evidence shows that there is a complex interplay between cardiovascular diseases (CVD) and mental health issues, such as depression and anxiety. Most research investigating the characteristics of psycho-cardiovascular disease (PCD) has come from physicians’ perspective. We knew little about how PCD patients understand the effect of depression and anxiety on CVD and how those affect their preferred treatment choice. This study aims to investigate the characteristics and illness comprehension bias in patients with PCD, and how the illness comprehension affects their choice of psycho-cardiology therapy from the patients’ perspective in China.
METHODS This is a multi-center cross-sectional survey study conducted in Chinese tertiary and secondary hospitals. Eight hundred and sixty-four PCD patients’ questionnaires were collected in the cardiovascular outpatient department in 11 provinces. The questionnaire included the seven-item General Anxiety Disorder (GAD-7) scale, the nine-item Patient Health Questionnaire (PHQ-9), and a self-designed survey on the illness comprehensibility of PCD. The PCD patients’ characteristics and illness comprehension bias were analyzed by chi-square test, univariate and multivariate logistic regression analysis.
RESULTS Of 864 enrolled PCD patients, over 90% of PCD patients experienced mild to moderate anxiety and depression, yet less than 10% received treatment. Patients with disease duration >1 year, psychological consultation, and from the south had lower anxiety. Patients aged over 40, with a high family income and from the south showed lower depression level. The percentage of patients with high illness comprehension stood at 52.9%. The high comprehension group showed fewer laborers (19.3% vs. 26.4%, P < 0.05), fewer older individuals (39.2% vs. 46.9%, P < 0.05), less lower household income (15.6% vs. 30.5%, P < 0.05), a greater proportion lacked insurance (17.5% vs. 10.0%, P < 0.05), more highly educated individuals (42.9% vs. 32.1% with college education), more patients who received psychological consultation (24.0% vs. 5.1%, P < 0.05) and therapy (7.7% vs. 2.3%, P < 0.05). More patients in high comprehension group were very satisfied (20.2% vs. 15.6%, P < 0.05) and fewer patients were dissatisfied with current efficacy evaluation (2.5% vs. 5.9%, P < 0.05). Patients in high comprehension group tended to prioritize hospital level (68.03% vs. 58.72%, P < 0.05), especially tertiary hospitals (71.66% vs. 63.33%, P < 0.05), and psycho-cardiology clinics (40.14% vs. 25.9%, P < 0.05). Patients in low comprehension group were more likely to prioritize treatment cost (32.65% vs. 46.41%, P < 0.05) and favored a transition from tertiary to community hospitals (16.55% vs. 25.38%, P < 0.05).
CONCLUSIONS More than 90% of PCD patients in Chinese CVD departments experience mild to moderate anxiety and depression with low treatment rates. Different illness comprehension levels lead to variations in treatment willingness, considerations, healthcare preferences, medication choices, and illness knowledge acquisition methods.
CARDIOVASCULAR IMAGING
GW35-e0064
Zhang He1, Wang Shijing2
1The Affiliated Hospital of Nantong University
2First Affiliated Hospital of China Medical University
OBJECTIVES Evaluation of left atrial dysfunction is of great value to assess reperfused chronic myocardial infarction. LA volumetric and strain parameters can be of great help to estimate left atrial function. However, limited data are accessed on its prognostic value in reperfused chronic myocardial infarction. In order to evaluate the relationship between LA volumetric and strain parameters in patients with chronic myocardial infarction.
METHODS In this retrospective study, recruited people (included from April in 2017 to the June in 2021) experience cardiovascular MRI. The relationship between LA volumetric and strain parameters and chronic myocardial infarction was evaluated by linear regression.
RESULTS Eighty-three patients with chronic myocardial infarction (mean age ± standard deviation, 58.16 years ± 9.58; 69 men) were included. LATEF was weakly correlated with LAVmin (Pearson correlation coefficient r = −0.674, P < 0.001), Booster longitudinal strain (r = 0.577, P < 0.001), GLSRa (r = −0.567, P < 0.001), Total longitudinal strain (r = 0.574, P < 0.001). Better passive radial strain is correlated to a lower rate of chronic myocardial infarction (hazard ratio, 0.789 [0.699, 0.892]; P < 0.001) after adjusting for multiple clinical and CMR-based variables.
CONCLUSIONS Left atrial volumetric parameters, strain and strain rate can be of great value in reperfused chronic myocardial infarction.
GW35-e0087
Yao Lu, Xiaoli Zhang
Department of Nuclear Medicine, Laboratory for Molecular Imaging, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
OBJECTIVES This study assessed the predictive value of hibernating myocardium (HM) proportion in total perfusion deficit (TPD) for reverse left ventricular (LV) remodeling and its prognostic significance in heart failure with reduced ejection fraction (HFrEF) patients after revascularization.
METHODS A retrospective analysis of 201 HFrEF patients (178 males, 60.6 ± 9.3 years) who underwent gated myocardial perfusion imaging, 18F-FDG cardiac PET/CT, and echocardiography was performed. Patients were followed for a median of 13.0 (7.0) months and received follow-up echocardiography 6 months post-revascularization. Reverse remodeling (RR) was defined as ≥10% reduction in LV end-systolic diameter (LVESD). Logistic regression identified predictors of RR, with the predictive value of HM/TPD validated in a prospective cohort (n = 30). Changes were expressed as Δ(post-pre).
RESULTS HM/TPD independently predicted RR (OR = 1.042, 95% CI: 1.019–1.065, P < 0.001) in the retrospective cohort. A HM/TPD cutoff of 38.5% demonstrated significant associations with reversed LV remodeling and improved cardiac function post-revascularization, along with a favorable prognosis. The prospective cohort validated these findings. Correspondingly, there was a significant association between HM/TPD and cardiac function (ΔLVEF, ΔLVEDD, and ΔLVESD, all P < 0.05) in the retrospective and prospective cohort. Additionally, ΔTPD exhibited a positive correlation with ΔHM (r = 0.825, P < 0.001), which indicated that the decrease in impaired myocardial perfusion exhibited a positive correlation with the recovery in HM.
CONCLUSIONS Higher HM/TPD proportion in HFrEF patients was associated with an increased likelihood of RR, improved cardiac function, and favorable outcomes post-revascularization.
GW35-e0136
Leyi Zhu1, Jing Xu1, Chen Cui1, Peng Sun2, Zhigang Wu2, Shihua Zhao1, Minjie Lu1
1Department of Magnetic Resonance Imaging, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
2Clinical & Technical Support, Philips Healthcare
OBJECTIVES Diffusion tensor cardiac magnetic resonance (DT-CMR) is a novel tool that shows potential for non-invasive assessment of myocardial microstructures, specifically the cardiac fiber orientation. However, limited data are available on the comprehensive validation of biventricular myocardial fiber orientation assessed with DT-CMR against histology. The purpose of this study is to validate the accuracy of high-resolution DT-CMR in evaluating the arrangement of biventricular myocardial fibers in a miniature-swine model, using histological findings as the reference standard.
METHODS High-resolution ex-vivo DT-CMR data of one healthy miniature swine were acquired by a 3.0 T MRI system using a second-order motion-compensated single-shot spin echo planar imaging sequence at the systolic state. Each data set constituted 32 non-collinear diffusion-weighted acquisitions with b-values of 600 s/mm2. Fiber tracking was performed in three myocardial layers (subepicardial, intramyocardial, and subendocardial wall) according to the American Heart Association (AHA) 16-segment model for the left ventricle (LV) wall, and two layers (subepicardial and subendocardial wall) according to an 8-segment model for the right ventricle (RV) wall. Histology with hematoxylin and eosin (HE) staining was compared in each myocardial segment. The correlations between helix angles (HAs) assessed with DT-CMR and histology were analyzed by linear regression.
RESULTS A total of 64 segments including 48 LV segments and 16 RV segments were head-to-head analyzed. In this normal heart, LV myocardial fibers followed a symmetric arrangement around the midmyocardium, with negative and positive HAs in the subepicardial and subendocardial walls, respectively. The subepicardial HAs in basal segments were −63.9 ± 5.5 degrees in DT-CMR and −51.9 ± 6.7 degrees in histology, while the subepicardial HAs in mid-cavity segments were −48.3 ± 8.7 degrees in DT-CMR and −40.4 ± 7.3 degrees in histology, which suggested that the subepicardial fibers may become more circumferential with higher HAs when approaching apex segments (all P < 0.05). The main fiber orientation of the RV wall from subepicardial to subendocardial layers was asymmetric and presented HAs of close-to-zero to positive degrees in both DT-CMR and histology. HAs evaluated by DT-CMR were closely correlated with those assessed with histology (r = 0.958, P < 0.001) in 64 myocardial segments.
CONCLUSIONS Using histological validation in a miniature-swine model, high-resolution DT-CMR demonstrated good performance in non-invasively evaluating the arrangement of biventricular myocardial fibers.
GW35-e0138
Leyi Zhu, Jian He, Shihua Zhao, Minjie Lu
Department of Magnetic Resonance Imaging, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Left ventricular (LV) strain derived from cardiac magnetic resonance feature tracking (CMR-FT) has emerged as a powerful predictor of poor prognosis in patients with heart failure with preserved ejection fraction (HFpEF). Right ventricular (RV) function is an independent determinant of clinical status and prognosis in multiple cardiovascular diseases; however, limited data are available on the prognostic value of RV function assessed by strain analysis in patients with HFpEF. The purpose of this study is to evaluate the association between RV strain parameters derived from CMR-FT and adverse outcomes in patients with HFpEF.
METHODS Patients with HFpEF who underwent CMR examination from January 2010 to December 2018 were retrospectively enrolled. FT strain analysis was performed to measure LV, left atrial (LA), and RV strain parameters. The primary endpoint was all-cause death, and the secondary endpoint was cardiovascular death. The association between variables and clinical outcomes was assessed by Cox proportional regression and receiver operating characteristic (ROC) analysis.
RESULTS A total of 1170 consecutive patients with HFpEF (age 56.7 ± 12.2 years; 70% male) were enrolled in this study. During a median follow-up of 7.3 years (interquartile range, 5.2–10.1 years), 128 (10.9%) patients reached the primary endpoint, and 111 (9.5%) patients reached the secondary endpoint. In multivariable Cox regression analysis, RV global longitudinal strain (RV-GLS) and RV global circumferential strain (RV-GCS) were independent predictors for the primary endpoint (hazard ratio [HR] per 1% increase, 1.08 [95% CI: 1.02, 1.14; P = .007] and 1.11 [95% CI: 1.02, 1.21; P = 0.017], respectively) and for the secondary endpoint (HR per 1% increase, 1.09 [95% CI: 1.03, 1.17; P = .006] and 1.12 [95% CI: 1.02, 1.23; P = 0.016], respectively). The full model (Model 3) based on clinical, conventional imaging, and RV strain (RV-GLS and RV-GCS) variables for the primary endpoint improved the discrimination ability (C-index = 0.785) compared with Model 1 based solely on clinical variables (C-index = 0.708, P < 0.001) and Model 2 incorporating clinical variables and left atrial volume index (C-index = 0.746, P < 0.001). In ROC analysis for the primary endpoint, the addition of left atrial volume index and RV strain (RV-GLS and RV-GCS) yielded an improved area under the curve (AUC) of 0.793 for Model 1 (AUC = 0.729, P < 0.05).
CONCLUSIONS RV-GLS and RV-GCS derived from CMR-FT were independent predictors of adverse clinical outcomes in patients with HFpEF, providing incremental prognostic value over traditional clinical and CMR-derived risk markers.
GW35-e0176
Di Zhou, Minjie Lu
Department of Magnetic Resonance Imaging, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES As the cornerstone of decision-making and prognosis, there is currently a lack of data focusing on the association between phenotype and underlying mechanisms among various conduction delay patients. We aimed to elucidate the phenotyping characteristics among different QRS duration and morphology in patients with non-ischemic heart failure and reduced ejection fraction (HFrEF) and explore predictive metrics for survival outcomes following cardiac resynchronization therapy (CRT).
METHODS A retrospective analysis was conducted on 887 consecutive patients with non-ischemic HFrEF and prolonged QRS duration who underwent cardiac magnetic resonance (CMR) imaging, as well as 200 subjects with HFrEF and normal QRS duration as the control group. Survival estimates for patients who underwent CRT were determined using Kaplan-Meier curves with the log-rank test.
RESULTS Patients with left bundle branch block (LBBB) had a higher right ventricular ejection fraction (RVEF) and worse LV torsion and strains compared to controls and patients with right bundle branch block (RBBB). Late gadolinium enhancement (LGE) percentage was significantly larger in patients with RBBB and non-specific intra-ventricular conduction delay (IVCD) than in controls and LBBB patients (LBBB vs. RBBB vs. IVCD vs. controls: 4.5% ± 6.7 vs. 8.9% ± 9.1 vs. 8.3% ± 8.0 vs. 4.9% ± 7.0). Multivariable logistic regression revealed that LGE presence and torsion were independent determinants of IVCD. Over a median follow-up of 4.7 years, RVEF ≤48.1% (HR [95% CI]: 6.247 [1.923–20.294]), torsion ≥ 0.1°/cm (HR [95% CI]: 2.692 [1.310–5.532]), and LGE ≥2.3% (HR [95% CI]: 7.948 [3.108–20.328]) were associated with reduced survival after CRT.
CONCLUSIONS RBBB is associated with reduced RVEF and larger LGE burden, indicating a worse prognosis after undergoing CRT. LV torsion was notably impaired in patients with LBBB and IVCD, suggesting decreased LV synchrony, which may benefit from CRT.
GW35-e0189
Danni Wu1, Xiao Li2, Tianchen Guo1, Xiaojin Feng1, Xinhao Li1, Yining Wang2, Wei Chen1
1Deptartment of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
2Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
OBJECTIVES Late gadolinium enhancement (LGE) has been found in patients with autoimmune rheumatic disease (ARD). However, the prevalence and clinical significance of some LGE subtypes have not been well demonstrated. The study aims to explore and compare the clinical characteristics, imaging features and adverse outcomes of ARD patients with and without left ventricular (LV) subendocardial involvement on MRI.
METHODS This retrospective study evaluated 176 patients diagnosed with ARD with clinically suspected cardiac involvement between 2018 and 2023. LV subendocardium-involved LGE (LGEse) was defined as LGE involving the LV subendocardium that did not correspond to a coronary vascular distribution. The endpoints included a composite of cardiac death, heart failure-related admission, cardiogenic shock, and appropriate pacemaker or implantable cardioverter-defibrillator therapy.
RESULTS Of the 176 consecutive patients, LV LGEse was observed in 22 patients (12.5%). During a median follow-up of 776.50 days (interquartile range, 394.75–1405.00 days), 20 patients (11.4%) experienced a composite endpoint. Compared with those without LV LGEse, the LV LGEse group had the higher proportion of men (63.6% vs. 14.3%; P < 0.001), lower LV ejection fraction (49.85 vs. 60.00; P = 0.001), larger LV end-diastolic volume index (78.05 vs. 74.50; P = 0.043), and more adverse outcomes (31.8% vs. 8.4%; P = 0.005). In the univariable and multivariable Cox regression analyses, the LV LGEse showed independent prognosis value. In the sensitivity analyses, the prognostic difference in terms of LV subendocardial involvement remained.
CONCLUSIONS In patients with autoimmune disease, LV subendocardial involvement, an underrecognized LGE pattern, indicates a worse prognosis.
GW35-e0232
Yankai Mao
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, China
OBJECTIVES Left atrial (LA) and left atrial appendage (LAA) mechanical dysfunction account for an increase in cardioembolic stroke risk in atrial fibrillation (AF), and more recently in individuals in sinus rhythm (SR). However, the exact contribution of LA and LAA to the pathogenesis of thromboembolic events is not fully understood. Here, we aimed to assess the alterations of LA and LAA mechanics in different stroke subtypes.
METHODS We recruited three groups of participants: patients with paroxysmal or persistent AF with a history of stroke (AF-stroke, n = 69, respectively), individuals in SR with no history of AF but with acute ischaemic stroke (non-AF stroke, n = 46); individuals with no history of AF or stroke (control group, n = 17). Patients with AF were further categorized into sinus rhythm group (AF-stroke-SR, n = 24) and AF rhythm group (AF-stroke-AF, n = 45) according to the rhythm at the time of echocardiography. Using speckle-tracking echocardiography, global longitudinal strain (GLS) and mechanical dispersion (MD) of LA and LAA were measured in all patients. Mechanical dispersion was defined as the standard deviation of the time to peak of the regional strain corrected by R-R interval.
RESULTS Patients with AF-stroke demonstrated prominently impaired LA and LAA mechanics (LA GLS: 20 ± 6% (AF-stroke-SR), 11 ± 4% (AF-stroke-AF); LA MD: 9 ± 3%, 11 ± 3%; LAA GLS: 15 ± 3%, 11 ± 4%; LAA MD: 11 ± 4%, 12 ± 3%, respectively) compare with those with non-AF stroke and controls (LA GLS: 35 ± 8%, 41 ± 11%; LA MD, 6 ± 2%, 4 ± 2%; LAA GLS: 21 ± 5%, 23 ± 7%; LAA MD: 8 ± 4%, 7 ± 3%, respectively) (all P < 0.01). Patients with non-AF strokes displayed similar LA and LAA mechanical function as the control group. In multivariable analysis, only AF-strokes were independently associated with LA and LAA GLS after adjusting for age and comobidities (both P < 0.01).
CONCLUSIONS Mechanical dysfunction of LA and LAA might play a greater role in pathogenesis of strokes related to AF rather than non-AF strokes.
GW35-e0348
Jiaqi Ma1, Cuiying Zhang1, Zhihao Guo1, Jie Geng1,2,3,4
1Department of Cardiology, Clinical School of Thoracic, Tianjin Medical University
2Department of Cardiology, Chest Hospital, Tianjin University
3Tianjin Key Laboratory of Cardiovascular Emergency and Critical Care
4Tianjin Municipal Science and Technology Bureau, Tianjin, China
OBJECTIVES The study sought to explore the association of left atrial phasic function with demographic, clinical, laboratory, and echocardiographic characteristics.
METHODS Three hundred and three participants (56.4% man, mean age 66 ± 9 years) with unexplained chest tightness were surveyed. The LA reservoir strain (LASr), LA conduit strain (LAScd), LA contractile function (LASct) were obtained by the Two-dimensional Speckle Tracking Echocardiography (2DSTE). And we used simple linear regression and stepwise multivariable linear regression to evaluate the demographic, clinical, laboratory, and echocardiographic correlates of LASr, LAScd, and LASct, respectively.
RESULTS In multivariable models, Age (β = −0.19, P < 0.001), hypertension (β = −3.52, P = 0.016), AF (β = −4.25, P = 0.002), Log (BNP) (β = −3.22, P = 0.002), LVEF (β = 0.25, P = 0.024), LVMI (β = −0.08, P < 0.001) and LA (β = −0.45, P < 0.001) were significantly associated with LASr. Age (β = −0.16, P < 0.001), LVMI (β = −0.05, P < 0.001), LVEF (β = 0.16, P = 0.035), E/A (β = 6.78, P < 0.001), E/e (β = −0.21, P = 0.033), LA (β = −0.19, P = 0.009) were significantly associated with LAScd. Heart rate (β = 0.06, P = 0.023), DM (β = −2.40, P = 0.002), AF (β = −2.68, P = 0.006), Log (BNP) (β = −1.91, P = 0.005), E/A (β = −4.64, P < 0.001) and LA (β = −0.25, P < 0.001) were significantly associated with LASct.
CONCLUSIONS Phases of LA function were related to demographic and clinical characteristics and were associated with established echocardiographic traits of cardiac structure. Besides, our results would advance the future clinical applications of the LA function derived from 2DSTE.
GW35-e0425
Guangjie Lv, Ai li Li
China-Japan Friendship Hospital
OBJECTIVES As a well-adopted surrogate of right ventricular-arterial coupling (RVAC), the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio (TAPSE/sPAP) has limitations, especially when pulmonary artery pressure cannot be accurately estimated by tricuspid regurgitation or when the TAPSE is reduced after cardiac surgery, such as pulmonary endarterectomy (PEA). Therefore, this study aimed to explore the value of three-dimensional echocardiography (3DE) coupling parameters in evaluating RVAC in patients with precapillary pulmonary hypertension (PH), to compare the changes of echocardiographic coupling parameters before and after PEA and to analyze the relationship between echocardiographic coupling parameters and risk stratification of PH prognosis.
METHODS Fifty-nine patients with precapillary PH were retrospectively recruited. The “gold standard” of RVAC was derived from right heart catheterization (RHC) and cardiac magnetic resonance imaging (CMR). 3DE coupling parameters included right ventricular end-systolic maximum elasticity (3DE Ees), pulmonary artery effective elasticity (3DE Ea) and storke volume/end-systolic volume (3DE SV/ESV) for RVAC. The relationships between echocardiographic RVAC parameters and RHC-CMR coupling standard were analyzed by Pearson’s test and Bland–Altman test. Multivariate ordinal regression analysis was used to identify echocardiographic parameters associated with prognostic risk stratification. Twenty-four patients with chronic thromboembolic pulmonary hypertension (CTEPH) were enrolled to explore the changes of echocardiographic RVAC parameters before and after PEA.
RESULTS The 3DE coupling parameters showed a strong correlation and good agreement with the RHC-CMR coupling standard. The TAPSE/sPAP were moderately related to the RHC-CMR coupling standard, but their consistency was poor, with a significant bias of 0.44 (95% CI: 0.374, 0.511). TAPSE/sPAP was only associated with pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (mPAP) in CTEPH patients before PEA (r = −0.605, −0.758, P < 0.001), but 3DE SV/ESV remained moderately correlated with PVR and mPA P before and after PEA (r = −0.614, −0.655, P < 0.001). The TAPSE/sPAP was the strongest predictor of prognostic risk after multivariate regression analysis.
CONCLUSIONS 3DE-derived coupling parameters can noninvasively evaluate the RVAC of precapillary PH. 3DE SV/ESV is superior to TAPSE/sPAP in evaluating postoperative condition of CTEPH patients. While TAPSE/sPAP has advantages in predicting the prognosis of patients with precapillary PH.
GW35-e0548
Yipu Ding1,2, Zinuan Liu1,3, Ziqiang Guo1,3, Yundai Chen1, Junjie Yang1
1Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, China
2School of Medicine, Nankai University, Tianjin, China
3Medical School of Chinese PLA, Beijing, China
OBJECTIVES Coronary computed tomography angiography (CCTA) is a first-line imaging modality that enables comprehensive evaluation of coronary atherosclerotic lesions, including anatomical information (e.g., plaque characteristics), functional information related to hemodynamics, and inflammatory information assessed by the perivascular fat attenuation index (PFAI). It also allows for precise assessment of coronary plaque progression at both per-patient and per-plaque levels. However, the predictive ability of hemodynamic or inflammatory parameters for plaque progression, especially in patients with non-obstructive coronary artery disease (CAD), remains poorly understood.
Our study aims to search for predictive or effective alternative indicators derived from CCTA, such as PFAI or computed tomography-derived fractional flow reserve across the lesion (ΔCT-FFR), that can potentially indicate rapid plaque progression (RPP), providing a reliable and simple risk assessment method for vulnerable plaques in non-obstructive CAD patients.
METHODS This study involved a single-center cohort of non-obstructive CAD patients who underwent serial CCTA examinations, totaling 91 cases and including 283 plaques. Plaque progression was defined in terms of plaque volume progression and plaque burden progression. Plaque Volume Progression was measured as the annual rate of change in plaque volume (PV), denoted as ΔPV/y. Plaque Burden Progression was measured as the annual rate of change in the percentage of atheroma volume (PAV), denoted as ΔPAV/y. Rapid plaque progression was defined using the 90th (P90) and 75th (P75) percentiles of ΔPAV/y. Generalized estimating equations were used to analyze the correlation between baseline PFAI, the annual change rate of PFAI, baseline ΔCT-FFR, the annual change rate of ΔCT-FFR, and ΔPAV/y, ΔPV/y for total plaques and individual plaque components. Additionally, the ability of changes in PFAI to identify RPP was assessed.
RESULTS Baseline ΔCT-FFR significantly correlated with the volume of individual plaque components (all P ≤ 0.003), but neither baseline ΔCT-FFR nor its changes were associated with overall plaque progression (P > 0.05). The annual change rate of PFAI showed a significant positive correlation with total plaque ΔPAV/y (β: 0.022; 95% CI: 0.006–0.037, P = 0.008), especially with non-calcified plaque ΔPAV/y (β: 0.019; 95% CI: 0.007–0.031, P = 0.003) and fibrous plaque ΔPAV/y (β: 0.025; 95% CI: 0.013–0.037, P < 0.001). PFAI change was also associated with RPP, showing significant positive correlations whether the RPP was defined by the P90 of total plaque ΔPAV/y (β: 0.007; 95% CI: 0.001–0.013, P = 0.014) or by the P75 of total plaque ΔPAV/y (β: 0.010; 95% CI: 0.001–0.202, P = 0.040).
CONCLUSIONS While there is no clear correlation between plaque-level ΔCT-FFR and plaque progression, making it unsuitable as a marker for plaque progression assessment, our findings highlight the significant potential of PFAI as a positive predictor. An increase in PFAI is significantly and positively correlated with the progression of the atherosclerotic burden, particularly in non-calcified plaques. This suggests that PFAI could be a valuable marker for identifying and monitoring the progression of vulnerable plaques in non-obstructive CAD patients.
GW35-e0641
Jie Wang1, Jinquan Zhang1, Yuanwei Xu1, Jiayu Sun2, Qing Zhang1, Yucheng Chen1
1Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
2Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
OBJECTIVES In patients with hypertrophic cardiomyopathy (HCM), the prognostic value of native T1 and extracellular volume fraction (ECV) for adverse cardiovascular events has not been well defined.
METHODS Consecutive 663 participants with HCM who underwent 3 Tesla cardiovascular magnetic resonance (CMR) were recruited. The follow-up endpoints included heart failure (HF)-related death, HF rehospitalization, and sudden cardiac death (SCD) or aborted SCD.
RESULTS On Cox proportional hazards regression multivariable analyses, global native T1 excluding LGE (late gadolinium enhancement) areas (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 0.99–1.08; P = 0.1) and global ECV (HR: 1.03; 95% CI: 0.96–1.11; P = 0.42) were not associated with SCD. Conversely, global native T1 (HR, 1.09–1.11 per 10 ms increase; 95% CI: 1.03–1.17; all P < 0.05) and global ECV (HR, 1.18–1.23 per 1% increase, 95% CI, 1.09–1.36, all P < 0.001) were both independently associated with HF-related death after the adjustment for left ventricular (LV) LGE extent. In addition, global native T1 and ECV were both independently associated with the composite endpoint of HF-related death or HF rehospitalization.
CONCLUSIONS In this study of patients with HCM, T1 mapping was not independently associated with SCD, whereas global native T1 and global ECV were both independently associated with HF-related death or the composite endpoints for HF death and HF rehospitalization.
GW35-e0647
Yao Lu, Xiaoli Zhang
Beijing Anzhen Hospital Affiliated Capital Medical University
OBJECTIVES This study aims to dynamically evaluate the spatial and temporal changes in myocardial perfusion, viability, inflammation, and fibrosis in a porcine myocardial ischemic reperfusion (MIR) model through multi-target molecular imaging (myocardial perfusion, metabolism, inflammation, and fibroblast activation). Additionally, to assess the effects and mechanisms of remote ischemic conditioning (RIC) on the MIR model, in combination with histologic examination in vitro.
METHODS MIR was established in 14 Chinese mini pigs (7 males; age: 6–8 months) and they were randomly divided into RIC group and non-RIC group. RIC was performed in pigs by blood pressure inflation on the upper and lower limbs for 5 min period and 4 cycles immediately after surgery. A series of myocardial perfusion imaging, 18F-FDG myocardial metabolism and fasting 18F-FDG myocardial inflammatory imaging, and 18F-FAPI imaging were performed longitudinally at the 3rd, 14th, 28th, 56th day after MIR. Independent-samples t-test or MannWhitney U test was used to compare the changed values (Δ value, each time point subtracted the 3rd day) of multiple parameters. Differences were considered significant at the level of P < 0.05. The correlation between imaging parameters and cardiac outcomes was analyzed.
RESULTS (1) At the acute phase, significant uptake of FAPI and FDG was observed in LV myocardium of MIR pigs, with partial overlap between FAPI+ and FDG+ areas, primarily located in the infarct and peri-infarct regions [3d: (53.9 ± 16.8)% vs. (39.2 ± 13.3)%, P = 0.026]. With time prolonged, both FAPI+ and FDG+ uptake extent and intensity showed a decreased trend (all P < 0.05). (2) Compared with the non-RIC group, RIC group exhibited significantly reduced infarct size (ΔMI2w−3d, and ΔMI8w−3d, both P < 0.05). The RIC group also showed a significant increase in ΔLVEF [2w−3d; 4w−3d; 8w−3d, all P < 0.05] and a significant decrease in ΔESV [2w−3d; 4w−3d, both P < 0.05]. At the acute phase, RIC group had significantly lower FAPI uptake intensity in the peri-infarct region [SUVmax: (5.39 ± 1.55) vs. (8.26 ± 2.26), P = 0.014]; at the subacute phase, RIC group had significantly lower FDG uptake extent and intensity in the FDG+ area, infarct region, and peri-infarct compared with the non-RIC group (all P < 0.05). At both the acute and subacute phases, bone marrow uptake in the RIC group was lower than that in the non-RIC group (both P < 0.05). (3) The extent and intensity of FAPI and FDG uptake at the acute phase were negatively correlated with cardiac function at the chronic phase and positively correlated with ventricular remodeling (all P < 0.05). Furthermore, we found that the changes of FAPI uptake intensity from 3 day to 2 week was positively correlated with ΔLVEF and negatively correlated with ΔESV at the subacute and chronic phases (all P < 0.05), whereas the changes of FDG uptake intensity from 3 day to 2 week was negatively correlated with ΔLVEF and positively correlated with ΔESV at subacute and chronic phases (all P < 0.05).
CONCLUSIONS The dynamic cardiac inflammatory-fibrotic process after MIR was analyzed by in vivo molecular imaging, and we found that early inflammation and fibroblast activation could predict cardiac function and LV remodeling. RIC could reduce systemic inflammation at acute and subacute phases, attenuate fibrosis in the peri-infarct region at the acute phase, and cardiac inflammation in both infarct and peri-infarct region, ultimately resulting in a reduction in infarct size, improvement in cardiac function and reverse LV remodeling, which may provide a new therapeutic approach for MIRI.
GW35-e0726
Yuming Mu1,2, Jiaxin Zhao1,2, Lina Guan1,2, Shangke Chen2
1Department of Echocardiography, The First Affiliated Hospital of Xinjiang Medical University
2Xinjiang Key Laboratory of Ultrasound Medicine
OBJECTIVES To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection.
METHODS New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 hours after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared.
RESULTS The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (β, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability.
CONCLUSIONS This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.
GW35-e1041
Meng Wang1,2, Ruining Liu1,2, Shangke Chen2, Baihetiya Tayier1,2, Lina Guan1,2, Yuming Mu1,2
1Department of Echocardiography, The First Affiliated Hospital of Xinjiang Medical University
2Xinjiang Key Laboratory of Ultrasound Medicine
OBJECTIVES To prepare dual-targeted lipid ultrasound microbubbles loaded with ANM33 (HA-PANBs) and evaluate their feasibility in targeting foam cells by stages and achieving precise intracellular drug release in vitro.
METHODS The dual-targeteded lipid ultrasound microbubbles were designed with nanobubbles (NBs) as the microbubble core, hyaluronic acid (HA) as the first-stage targeting ligand for damaged endothelial cells, aptamer PM1 as the second-stage targeting moiety for foam cells, and ANM33 as the therapeutic factor. Simultaneously with the characterization of the lipid bubbles, their stability and in vitro contrast-enhanced ultrasound imaging capability were detected. Then a co-culture model of damaged human umbilical vein endothelial cells (HUVEC) and macrophages (RAW264.7, MΦ was established, combined with flow cytometry, oil red O staining and small animal in vivo imaging to evaluate the abilities of HA-PANBs to target foam cells precisely and release ANM33.
RESULTS The HA-PANBs exhibited regular morphology and good structural stability, with a particle size of (1357.53 ± 140.20) nm and a surface potential of (−5.61 ± 0.73) mV. HA, PM1 and ANM33 were effectively connected. In the damaged HUVEC/MΦ co-culture system, the HA-PANBs group demonstrated the best targeting effect on foam cells, with an effective uptake of (80.65 ± 2.12)%, which was 56.74% higher than that of the NBs group. Oil red O staining revealed that the cholesterol efflux capacity of foam cells in the HA-PANBs group was significantly better than that in the NBs group, the results were statistically different [(629.80 ± 21.99) a.u. vs. (1071.00 ± 55.49) a.u., P < 0.05].
CONCLUSIONS The dual-targeted lipid ultrasound microbubbles (HA-PANBs) can precisely target foam cells and significantly enhance their cholesterol efflux, providing a new strategy for the early non-invasive diagnosis and treatment of atherosclerosis.
GW35-e1085
Qin Duan, Ping Ge, Kangla Liao, Yunjing Yang, Qian Dong
The First Affiliated Hospital of Chongqing Medical University
OBJECTIVES Left ventricular (LV) global longitudinal strain (GLS) derived from two-dimensional speckle tracking echocardiography (STE) has been confirmed to accurately detect LV systolic dysfunction in various cardiovascular diseases. Ventricular-arterial coupling (VAC) reflects the global cardiovascular efficiency. However, the association between GLS and VAC remains unclear. This study aims to investigate the correlation between global longitudinal strain (GLS) and ventricular-arterial coupling index (VVI) in hypertensive patients with preserved left ventricular ejection fraction.
METHODS A total of 104 cases of essential hypertension patients and 40 cases of normotensive control were retrospectively included in the study. All subjects underwent conventional echocardiography, as well as 2D speckle-tracking echocardiography to assess for global longitudinal strain (GLS). Arterial elastance (Ea), end-systolic ventricular elastance (Ees), and VVI (Ea/Ees) were calculated. One hundred and four cases of hypertension patients were divided into tertiles based on VVI.
RESULTS Hypertensive and normotensive participants had similar Ea/Ees, whereas GLS differed significantly between the two groups. The mean of GLS in hypertensives was 18.99 ± 2.09%. The median VVI for low, medium, and high tertile groups were 0.48 (0.46–0.50), 0.56 (0.55–0.58) and 0.67 (0.63–0.70), respectively. Simple regression analysis revealed a significant positive correlation between GLS and VVI tertile (β = −0.276, 95% CI: −1.190 to −0.224, P = 0.005). This association remained statistically significant even after controlling for major confounding factors in multiple regression analysis (β = −0.237, 95% CI: −1.041–0.173, P = 0.007).
CONCLUSIONS VVI is independently related to GLS in hypertensives with preserved left ventricular ejection fraction, which suggest that VVI might predict subclinical LV systolic dysfunction as assessed by global longitudinal strain.
GW35-e1265
Xihan Fan, Peihong Guo, Wei Chen
The First Affiliated Hospital of Kunming Medical University
OBJECTIVES To identify the specific cardiac magnetic resonance (CMR) imaging features associated with immune checkpoint inhibitor (ICIs)-related myocarditis, and to assess myocardial tissue abnormalities and cardiac dysfunction in patients undergoing ICIs treatment using CMR-T1 mapping and feature tracking techniques. Additionally, this study aims to monitor the severity of these abnormalities over time.
METHODS A prospective study was conducted involving 31 patients with malignant tumors undergoing immune checkpoint inhibitor (ICIs) treatment, including 12 patients who underwent CMR follow-up. Additionally, 30 age- and sex-matched patients were recruited as a control group. All subjects underwent 3.0 T CMR scans, which included cine imaging, cardiac morphology imaging, T2-STIR or T2 mapping, modified Look-Locker inversion recovery (T1 mapping), first-pass perfusion, and delayed enhancement imaging. Cardiac function and myocardial strain parameters were analyzed using CVI 42 cardiac post-processing software, and native T1, post-contrast T1, and extracellular volume (ECV) values of the left ventricular myocardium at the basal, mid, and apical segments were measured according to the American Heart Association (AHA) 17-segment model. Relevant clinical and biochemical parameters were collected prior to the CMR examination.
RESULTS Compared with the control group, patients in the ICIss treatment group showed no significant decrease in left ventricular ejection fraction (LVEF) (60.27% ± 6.21% vs. 57.43 ± 4.25%; P > 0.05), but a significant reduction in global longitudinal strain (GLS) (−18.76 ± 2.42% vs. −16.93% ± 2.39%; P < 0.05). There were no significant differences in global circumferential strain (GCS) and global radial strain (GRS) (P > 0.05). Additionally, in the 12 patients who underwent CMR follow-up, there was no significant difference in LVEF between the two CMR examinations (59.30% ± 3.64% vs. 56.67 ± 4.44%; P > 0.05), but GLS was significantly reduced (−18.86 ± 2.16% vs. −16.51% ± 2.26%; P < 0.05). CMR-T1 mapping results showed that the ICIss treatment group had significantly higher native T1 and ECV values of the left ventricular myocardium overall and in the three segments compared with the control group (P < 0.05). Among the follow-up patients, the native T1 and ECV values of the mid-segment of the left ventricle significantly increased in the second examination compared with the first (native T1: 1263.10 ± 52.50 ms vs. 1207.80 ± 58.24 ms; ECV: 35.43% ± 4.65% vs. 33.94% ± 7.11%; P < 0.05).
CONCLUSIONS CMR-T1 mapping and feature tracking techniques demonstrate that ICIss treatment can cause diffuse myocardial fibrosis and cardiac dysfunction, with myocardial damage progressively worsening over the treatment period.
GW35-e1294
Wei Tong1, Ying Han1, Hui Hui2, Jie Tian2, Yundai Chen1
1Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital
2CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences
OBJECTIVES Atherosclerosis imaging has traditionally focused on detection of obstructive luminal stenoses or measurements of plaque burden. However, it remains a great challenge to noninvasively interrogate plaque composition and vulnerability, thereby measuring the severity of atherosclerotic disease and potentially evaluating the therapeutic response. Magnetic particle imaging (MPI) is a highly sensitive, radiation-free, and no-tissue-background tomographic technique that uses superparamagnetic iron oxide (SPIO) as contrast agents. We recently found that MPI enables the detection and monitoring of intraplaque hemorrhage in atherosclerosis via imaging of hemoglobin degradation products. Recent studies reported that SPIO can be taken up by accumulated macrophages via surface scavenger at inflammation sites of atherosclerosis. This study aimed to determine whether SPIO-enhanced MPI could be applied to detect response to therapeutic intervention and changes in plaque stability via SPIO-mediated inflammation imaging in atherosclerosis.
METHODS RAW264.7 macrophage and foam cells were incubtated with the Nanoeast (novel synthesized PEG-coated SPIO), Vivotrax (commercially available carboxydextran-coated SPIO), and Ferumoxytol (FDA-approved clinically used carboxymethyl dextran-coated SPIO) to demonstrated the uptake of SPIO by macrophage and foam cell in vitro. To establish atherosclerotic unstable plaques, we fed six-week-old male ApoE−/− mice a high-fat diet and induced unstable plaque by cast placement over the left carotid artery. After twenty weeks, mice were divided in three groups (N = 3–4 per group) and intravenously administered with different types of SPIO (Fe concentration, 8 mg/kg), including Nanoeast, Vivotrax, and Ferumoxytol. The maximum MPI signal-to-noise ratio (SNR) value and the optimal imaging time point were compared among the three groups to choose the appropriate contrast agent. Another four groups of ApoE−/− mice on a high-fat diet (N = 6–7 per group) were treated with novel clinically therapeutic agents (including SGLT2i and PBS, and PCSK9i and saline) for nine weeks, and then we assessed vascular inflammation and several features of plaque vulnerability by Nanoeast-enhanced MPI and histopathology, respectively. Prussian blue Fe staining was used for analyzing SPIO.
RESULTS Prussian blue staining demonstrated the concentration-dependent SPIO uptake by macrophages and foam cells after 1 hour incubation. For the ApoE−/− mice injected with Nanoeast, the MPI SNR values of unstable plaques reached the peak at 24 h post-injection, and were significantly higher than the peak SNR values of the Vivotrax, and Ferumoxytol group (P < 0.05). Prussian blue staining confirmed that more SPIO accumulated in the unstable plaques of Nanoeast group than in those of the other groups. Nanoeast-enhanced MPI SNR values were significantly reduced in SGLT2i-treated (6.84 ± 2.28 vs. 10.69 ± 2.09, P = 0.016, respectively) and PCSK9i-treated (3.41 ± 0.96 vs. 7.07 ± 2.22, P = 0.012, respectively) group compared with the controls. Histopathologically-proven changes in plaque stability were confirmed using HE staining, picrosirius red staining, and CD68 and ɑ-SMA immunohistochemical staining. Moreover, MPI SNR values positively correlated with multiple characteristics of lesion instability, including the macrophages, necrotic core and plaque size (P < 0.05).
CONCLUSIONS Nanoeast-enhanced MPI can allow for the detection of vulnerable atherosclerotic plaques and their response to therapeutic intervention. This noninvasive imaging approach may prove useful as a anti-atherosclerosis drug discovery and prioritization method.
CARDIOVASCULAR DISEASE CARE
GW35-e0867
Xueli Shen1, Xiaolei Wei1, Linyan Zhang2, Tao Liang1
1School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College
2Department of Nephrology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College
OBJECTIVES In recent years, heart failure has a high prevalence in the world, which brings a heavy medical and economic burden. Inadequate self-care ability and poor compliance in patients with chronic heart failure lead to reduced quality of life and increased readmission rates. However, the results of current studies on remote health monitoring are controversial, and the impact on patients’ self-care ability and quality of life is not clear. This article discusses the impact of mobile device-based remote health monitoring on self-care ability and quality of life in patients with chronic heart failure.
METHODS Computer searches were conducted in PubMed, The Cochrane Library and Web of Related literature on the effects of mobile device based remote health telemonitoring on self-care ability and quality of life of patients with chronic heart failure in Chinese and English databases and clinical trial registration platforms, such as web of Science, CINAHL, Embase, CNKI, WanFang Database, VIP database, China Biomedical Literature Database, etc. The search period is up to November 23, 2023. According to the inclusion and exclusion criteria, two researchers independently screened, extracted, and evaluated the literature quality.
RESULTS A total of 10 articles were included, including 2578 patients. The results of meta-analysis showed that in terms of self-care ability, patients with chronic heart failure with remote health monitoring intervention duration ≥6 months had a higher improvement in self-care ability score compared with routine follow-up [SMD = 0.27, 95% CI (0.17, 0.38), P < 0.001]. Moreover, the improvement of self-care ability was better than that of receiving remote health monitoring intervention time <6 months [SMD = 0.03, 95% CI (−0.24, 0.29), P = 0.04]. The improvement of self-care management scores in the remote health monitoring group was better than that in the routine follow-up group [MD = 5.39, 95% CI (0.31, 10.47), P = 0.038], and there was no statistical difference in self-care maintenance [MD = −0.82, 95% CI (−1.65, −0.02), P = 0.055]. There was no advantage in self-care confidence [MD = −1.81, 95% CI (−2.76, −0.86), P < 0.001]. For quality of life, Remote health monitoring has a positive effect on the improvement of emotional state [MD = −0.76, 95% CI (−1.22, −0.30), P = 0.001] and physical function [MD = −1.63, 95% CI (−2.32, −0.95), P < 0.001] in patients with chronic heart failure.
CONCLUSIONS Long-term remote health monitoring can help patients with chronic heart failure improve their self-care ability, mainly in the improvement of self-care management level, but self-care maintenance and self-care confidence is not clear or has not yet shown improvement, and it also has a positive effect on the improvement of health-related quality of life such as emotional state and physical function.
TRADITIONAL CHINESE MEDICINE
GW35-e0262
Tianzhen Liang1, Tianzhen Liang1, Xiaofeng Xia2, Yin Jiang3, Wuwen Feng4, Herong Cui5
OBJECTIVES Atherosclerosis is a widespread illness that gravely endangers human health and is the fundamental pathological foundation of various cardiovascular and cerebrovascular diseases. The absorption and storage of oxidatively modified LDL by certain specific cells in immune cells, such as macrophages, causes varieties of immune-oxidative processes. These processes of stress lead to plaque rupture through inflammatory processes, and then drives the development of atherosclerotic lesions. Now, the medications for the treatment of atherosclerosis are mostly lipid-lowering, anticoagulant, and thrombolytic agents, but the therapeutic outcomes are insufficient. It is determined that traditional Chinese medicine (TCM) has achieved good clinical efficacy in treating atherosclerotic illnesses. However, the mechanism of TCM therapy for atherosclerosis needs to be elucidated.
METHODS This paper highlights the target mechanism and structural features of TCM components and compounds in controlling the connections mentioned above and then regulating atherosclerosis, hoping to propose novel strategies for treating and preventing the disease.
RESULTS This manuscript explains how lipids and oxidative stress-induced immune cell metabolism is reorganized and changed in atherosclerosis, as well as traditional Chinese medicines, compounds, and active ingredients that interfere with this process in the long-term medical practice of traditional Chinese medicine, to discover and identify immunometabolic markers/targets for the prevention and treatment of atherosclerosis.
CONCLUSIONS In terms of lipids, the retention of lipoproteins in the vascular wall of arteries is an important factor in triggering atherosclerosis. In the pathology of atherosclerosis caused by oxidative stress, glycolysis is a vital part of the response of macrophages and T cells. Changes in the metabolism of these immune cells affect the growth and stability of plaques. Even though these results look good, there is insufficient research on how immune cell metabolism responds to pathological changes in vivo. Putting any therapies mentioned above into practice in the real world is still hard. More early research funding and large-scale randomized clinical trials will help find new ways to prevent and treat this disease.
GW35-e0401
Wei Liu1, Xingjiang Xiong2, Fuyong Chu1, Jinyuan Zhang1,3, Jie Wang2, Juju Shang1, Hongxu Liu1
1Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical University
2Guang’anmen Hospital, China Academy of Chinese Medical Sciences
3Beijing University of Chinese Medicine
OBJECTIVES The study’s purpose was to determine the curative effect of Bu-Shen-Jiang-Ya decoction (BSJYD) on hypertensive left ventricular hypertrophy and whether BSJYD alleviates myocardial fibrosis in Dahl salt-sensitive (SS) rats through modulating RAS-mediated expression of the TGF-β/Smads signaling pathway.
METHODS Dahl SS rats on a high sodium diet were given either BSJYD (n = 12) or valsartan (n = 12) prospectively for eight (8) weeks, and were compared to rats on a high sodium diet only (n = 12). The rats’ blood pressure and cardiac functions were measured before the rats’ hearts were dissected and measured to calculate the left ventricular mass index (LVMI). In addition, hematoxylin-eosin (H&E) staining, Masson trichrome staining, real-time polymerase chain reaction (PCR), and Western blot analysis were performed on the heart tissue.
RESULTS The primary results showed that BSJYD lowered blood pressure (P < 0.01), reduced LVMI (P < 0.01), improved cardiac function (P < 0.01), and decreased cardiac pathological changes. As a potential therapeutic mechanism, BSJYD reduced the expression of ACE/AT1R and TGF-β/Smads signaling pathways (P < 0.01) and led to a decrease in connective tissue growth factor (CTGF) expression (P < 0.01) thereby inhibiting myocardial fibrosis.
CONCLUSIONS BSJYD significantly reduced the blood pressure and improved left ventricular hypertrophy and cardiac function of the Dahl SS rats on a high-sodium diet. This effect may have been facilitated by the downregulation of the ACE/AT1R and TGF-β/Smads pathways, which would inhibit myocardial fibrosis and ventricular remodeling.
GW35-e0748
Liying Sun1,2, Hongbo Huang1,2, Zirui Wang1,3, Guanqi Fan1,3, Peili Wang1
1Xiyuan Hospital of Chinese Academy of Traditional Chinese Medicine
2Chinese Research Academy of Traditional Chinese Medicine College
3Beijing Graduate School of Traditional Chinese Medicine
OBJECTIVES To evaluate the effect of fecal bacteria transplantation on angiogenesis of acute ischemic myocardium through cardiac function, cardiac pathology, serology, protein expression, and intestinal flora, and to study the effect of fecal bacteria transplantation on angiogenesis of ischemic myocardium in mice.
METHODS Forty B6 inbred mice with aseptic myocardial ischemia were randomly divided into four groups, with 10 mice in each group, which were divided into control group, model group, common FMT group and heart-spleen FMT group. Acute myocardial ischemia model was established by intraperitoneal injection of pituitrin, and then the specific flora of patients before and after intervention was transplanted into myocardial ischemia model mice by “fecal transplantation”, and the heart structure and function of mice were evaluated by echocardiography. Serum myocardial infarction markers, inflammatory factors and VEGF were analyzed by Elisa. Masson staining and PAS staining were used to observe cardiac pathology. The expressions of Ang-1, Tie-2 and angiogenic protein were detected by western blot. The intestinal flora of mice was detected by 16 s sequencing.
RESULTS 1. In the aspect of cardiac function, there are significant differences in ejection fraction and left ventricular short axis contraction rate in each group. 2. Compared with the blank control group, the cTnT of the other three groups increased significantly. 3. Compared with the model group, the levels of TNF-α and IL-6 in the normal FMT group and the heart and spleen FMT group decreased. In terms of hs-CRP, the FMT group of heart and spleen is equivalent to the blank group, but lower than the model group and the ordinary FMT group. 4. In terms of angiogenesis metabolites, the level of VEGF in the blank group was higher than that in the other three groups, but there was no significant difference among the other three groups. 5. The results of PAS staining and Masson staining showed that the contents of collagen fibers and PAS positive substances in normal FMT group and heart and spleen FMT group increased significantly, which was significantly different from that in the blank control group. 6. In terms of protein expression, compared with the model group, the heart and spleen FMT group and the common FMT group can significantly increase the expression of Tie-2, and the expression level of ICAM1 in the blank control group is significantly higher than that in the other three groups. 7. Through the 16 s sequencing analysis of the above intestinal flora, we found 4 main phyla and 31 different species.
CONCLUSIONS The fecal bacteria transplantation has a certain protective effect on myocardial function, cardiac structure and inflammatory factors in mice with acute ischemia. In terms of angiogenesis, fecal bacteria transplantation can not increase the content of VEGF in myocardial serum of mice with acute ischemia, but in terms of protein expression, fecal bacteria transplantation can significantly increase the expression of Tie-2. In terms of intestinal flora, there are significant differences among different groups, and fecal bacteria transplantation effectively improves the diversity of individual intestinal flora.
GW35-e0898
Yan Wei, Weili Li, Guanjing Ling, Yong Wang
Beijing University of Chinese Medicine
OBJECTIVES Doxorubicin (DOX) is a first-line chemotherapy drug that effectively inhibits the growth of a variety of solid and hematologic malignant tumors. However, DOX is seen as a double-edged sword due to its severe dose-dependent and life-threatening cardiotoxicity manifested as left ventricular dysfunction and even heart failure. At present, the main pathological mechanisms of doxorubicin-induced cardiotoxicity (DIC) is autophagy-lysosome and fatty acid metabolism disorders. TFEB is a major regulatory factor extensively involved in the occurrence and development of cardiovascular diseases. This study aimed to investigate whether Qishen Granule (QSG), a traditional Chinese medicine, could alleviate DIC and its mechanism of action via TFEB-LAMP2/PGC-1α, so as to provide a combination drug for the continuous application of DOX in clinical practice.
METHODS Eight-week-old C57BL/6 mice (22 g ± 2 g) were injected with DOX (5 mg · kg−1) into the tail vein once a week for 4 weeks to establish the DIC model. Fifty mice were randomly divided into 5 groups: DOX (model group), DOX+QSG-L (low dose QSG-treated group), DOX+QSG-H (high dose QSG-treated group), DOX+ENA (positive drug group) and saline group (control group). The protective effect of QSG on the heart was evaluated by echocardiographic assessment, histological examination, energy metabolism gene (qPCR) and pathway protein (WB) analysis. Mechanistically, H9c2 cells were induced with 1 μmol/L DOX and QSG for 24 h, combined with Tfeb siRNA model. Autophagy-lysosome and fatty acid metabolism levels were detected by mRFP-GFP-LC3, BODIPY493/503 and Mito-SOX immunofluorescence, respectively, to further explore the mechanism of QSG.
RESULTS In vivo, echocardiography and histology results showed that QSG effectively improved the cardiac structure and function of DIC mice. Remarkably, we discovered that QSG prevented DIC in mice by promoting autophagy-lysosome pathway and improving fatty acid metabolism. Moreover, TFEB, LAMP2 and PGC-1α protein levels were upregulated in the hearts in QSG-treated DIC mice. Mechanistically, the protective effects of QSG against autophagy-lysosome, lipid accumulation and mitochondrial oxidative stress in cardiac myocytes were reversed by Tfeb gene silencing in vitro. Meanwhile, the expression of LAMP2 and PGC-1α were decreased. Of note, the protective effect of QSG was also attenuated after interfering with LAMP2 and PGC-1α, but TFEB expression was unaffected.
CONCLUSIONS Herein, we demonstrated that QSG administration protected against DOX-induced cardiotoxicity by activating TFEB-LAMP2/PGC-1α based autophagy-lysosome pathway and fatty acid metabolism. Mechanistically, DOX strongly destroyed the TFEB-LAMP2/PGC-1α network both in vivo and in vitro, while QSG eliminated this damage. Thus, QSG is a robust candidate for DOX-induced cardiotoxicity therapy.
GW35-e1232
Zirui Wang1,2, Hongbo Huang1, Guanqi Fan1,2, Liying Sun1, Peili Wang1
1Xiyuan Hospital, China Academy of Chinese Medical Sciences
2Graduate School, Beijing University of Chinese Medicine
OBJECTIVES To explore the effect of Xinpi Tongzhi Formula on the improvement of myocardial ischemia and mitochondria during MIRI using the rat MIRI model.
METHODS Wistar rats were randomly divided into sham operation group, model group, aspirin group, high-dose Xinpi Tongzhi Formula group, Xinpi Tongzhi Formula medium-dose group, and Xinpi Tongzhi Formula low-dose group, respectively, and were given equal volume distilled water/drug gavage intervention, and after 14 days of continuous gavage, MIRI model was made, blood and heart were taken. The contents of cTnT, CK-MB, LDH, K+-Na+-ATPase, Ca2+-Mg2+-ATPase and ROS in the serum of rats in each group were measured, and cardiac sections were prepared for HE staining and Masson staining.
RESULTS (1) cTnT: Compared with the sham operation group, the levels of the middle-dose group and the low-dose group were significantly decreased (P < 0.01), and compared with the model group, the levels of aspirin group, high-dose group, medium-dose group and low-dose group were significantly decreased (P < 0.01). (2) CK-MB: Compared with the sham group, the levels of aspirin group and low-dose group of traditional Chinese medicine were significantly decreased (P < 0.01), and compared with the model group, the levels of aspirin group, high-dose group and medium-dose group of traditional Chinese medicine were significantly decreased (P < 0.01). (3) LDH: Compared with the sham operation group, the level of LDH in the low-dose group was significantly decreased (P < 0.01), and compared with the model group, the level of LDH in the high-dose group and the middle-dose group was significantly decreased (P < 0.01). (4) K+-Na+-ATPase: Compared with the sham operation group, the level of the middle-dose group and the low-dose group of traditional Chinese medicine decreased significantly (P < 0.01), and compared with the model group, the level of the middle-dose group decreased significantly (P < 0.01). (5) Ca2+-Mg2+-ATPase: Compared with the sham group, the levels of aspirin group, high-dose group, medium-dose group and low-dose group were significantly decreased (P < 0.01), and compared with the model group, the levels of high-dose group and medium-dose group were significantly decreased (P < 0.01). (6) ROS: compared with the sham operation group, the level of ROS in the model group and the low-dose group of traditional Chinese medicine decreased significantly (P < 0.01), and compared with the model group, the level of high-dose traditional Chinese medicine group and the middle-dose group of traditional Chinese medicine decreased significantly (P < 0.01). (7) Pathological tissue: The myocardial fibers in the sham operation group were regularly arranged, the horizontal lines were clear, a small number of inflammatory cells were infiltrated, and a small number of myocardial cells were broken; compared with the sham operation group, the myocardial fibers in the model group, the aspirin group and the three groups were disordered, the cardiomyocyte hyperplasia and arrangement were disordered, and the extracellular fibrous tissue was significantly increased, but the myocardial fibers in the aspirin and three groups were neater than those in the model group.
CONCLUSIONS Xinpi Tongzhi Formula can effectively improve myocardial reperfusion injury and have a positive effect on mitochondria.
GW35-e1359
Zihao Fu, Xiaoyun Xu, Yiqiang Wu, Aidi Pan, Lilei Chen, Weimin Zhang
Department of Cardiology and Endocrinology, No. 907 Hospital of PLA Joint Logistics Support Force, Nanping, China
OBJECTIVES To date, studies have reported that panax ginseng and other medicinal plants were beneficial to health including reducing risk of all-cause mortality and cognitive impairment. However, research on the association of medicinal plants and metabolic heart disease was currently limited. This study aimed to evaluate effects of medicinal plant consumption on the risk of heart disease, diabetes and dyslipidemia in older Chinese adults.
METHODS The raw data were accessed from the latest wave (2017–2018) of Chinese Longitudinal Healthy Longevity Survey (CLHLS). Participants were divided to 3 groups according to the frequency of consuming medicinal plants, including Panax ginseng, Astragalus membranaceus, Lycium barbarum, Angelica sinensis, etc. Multiple imputations were performed to complete missing values. Logistic regression models were established to calculate odds ratios (OR) and confidence intervals (CI) for the associations between the consumption of medicinal plants and the above 3 diseases. Interaction effects and sensitivity tests were examined to further check the associations.
RESULTS A total of 15,534 participants were included in the cross-sectional analysis. Compared to rarely or never consumption group, occasional consumption group was associated with a higher risk of diabetes (adjusted OR = 1.07, 95% CI = 1.01–1.14, P < 0.05), dyslipidemia (adjusted OR = 1.07, 95% CI = 1.05–1.09, P < 0.01) and heart diseases (adjusted OR = 1.12, 95% CI = 1.08–1.16, P < 0.01). Similarly, frequent consumption group raised the risk of diabetes (adjusted OR = 1.10, 95% CI = 1.05–1.14, P < 0.01), dyslipidemia (adjusted OR = 1.06, 95% CI = 1.04–1.07, P < 0.01) and heart diseases (adjusted OR = 1.11, 95% CI = 1.09–1.14, P < 0.01). In addition, there were no significant interaction effects between medicinal plants consumption and participant characteristics on the above 3 diseases. Sensitivity analyzes found the associations remained unchanged.
CONCLUSIONS Occasional and frequent consuming medicinal plants including panax ginseng, astragalus membranaceus, lycium barbarum, angelica sinensis, etc were associated with a higher risk of diabetes, dyslipidemia and heart diseases among older Chinese adults. Further cohort studies are needed to validate these associations.
CARDIOVASCULAR PREVENTION AND REHABILITATION
EPIDEMIOLOGY AND EVIDENCE-BASED MEDICINE
GW35-e0008
Weiya Li, Hongde Li, Shiqin Peng, Junli Li, Mao Chen
Department of Cardiology, West China Hospital, Sichuan University
OBJECTIVES Due to differences in valve structure between Chinese and Western populations, such as a 20 times higher prevalence of bicuspid aortic valves, a greater calcium burden, and a higher number of patients with aortic regurgitation. While the trends in postoperative TAVR outcomes of China in recent years have not been described. We want to fill in the gaps in this area. Our study revealed a significantly decrease trend of 1-year outcome in China recent years and existed some gender differences. Our study provides some insights from sex difference for further improve outcomes for TAVR patients in China.
METHODS We included patients at a high-volume Chinese TAVR center, West China Hospital, from 2015 to 2022, and described the multivariable adjusted time trends of their 1-year follow-up outcomes including 30-day mortality, 1-year all-cause mortality, 1-year cardiac mortality, 1-year Major Adverse Cardiovascular Event (MACE), 1-year stroke, and 1-year permanent pacemaker implantation (PPI). The gender differences of time trends were also explored.
RESULTS The overall crude poor prognosis all showed a decrease trend in recent years. After multivariate adjustment, 30-day mortality, 1-year all-cause mortality, 1-year cardiac mortality, and 1-year PPI incident rate showed a significantly decrease trend (Adjusted P for trend <0.05). 1-year MACE, 1-year stroke incident rate also had a decrease trend but did not reach statistically significant. In the subgroup analysis of sex differences, we found that men had a more pronounced time trend of decreasing all-cause and cardiac mortality than women, while women had a more pronounced trend of decreasing PPI rate than men.
CONCLUSIONS In summary, our study demonstrates, for the first time, a declining trend in adverse prognosis among postoperative TAVR patients in China in recent years, with some notable gender differences.
GW35-e0062
Xiaofei Liu1, Xun Tang1,2, Pei Gao1,2,3
1Department of Epidemiology and Biostatistics, Peking University Health Science Center
2Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education
3Center for Real-world Evidence evaluation, Peking University Clinical Research Institute
OBJECTIVES Hematological biomarkers have shown potential for predicting incident cardiovascular disease (CVD) due to their underlying physiological mechanisms. However, the prognostic value of these biomarkers in CVD primary prevention is unclear. This study aims to investigate their association with incident CVD and quantify their predictive value in a large general population.
METHODS We analyzed individuals aged 40–74 years without CVD at baseline from the UK Biobank study. Incident CVD was defined as the first occurrence of non-fatal or fatal coronary heart disease and stroke during follow-up. Baseline hematological biomarkers, including white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), hemoglobin, mean corpuscular volume (MCV), red blood cell distribution width (RDW), platelet count, mean platelet volume (MPV), platelet-to-lymphocyte ratio (PLR), were assessed. Hazard ratios (HRs) per quartile of each marker for incident CVD were estimated using Cox regression models, adjusting for traditional CVD risk factors such as sex, age, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol and history of diabetes. The predictive value of these markers was assessed by the change in the C-statistic when added to the above-established risk factors.
RESULTS 337,659 individuals (median age, 58 years [50–63 years] and 54% were women) were included. There were 16,643 incident CVD cases during a median of 12.3 years follow-up. After adjusting for major traditional cardiovascular risk factors, the HR for incident CVD gradually and significantly increased with the RDW quartiles [1.05 (1.00–1.10) in Q2, 1.12 (1.07–1.17) in Q3, and 1.33 (1.28–1.39) in Q4]. Compared to the lowest quartile, the HR for the highest quartile for WBC was 1.32 (95% CI: 1.26–1.38), 1.17 (95% CI: 1.13–1.23) for NLR, 1.11 (95% CI: 1.06–1.16) for platelet count, 0.87 (95% CI: 0.83–0.92) for hemoglobin, and 0.94 (95% CI: 0.90–0.98) for mean platelet volume. We observed a U-shaped relationship between PLR and incident CVD after smoothing spline fitting. The same pattern was observed for MCV. Only the addition of RDW, WBC and NLR to the established risk factors improved the C-statistic by 0.0027, 0.0019 and 0.0011 for 10-year and 0.0041, 0.0023 and 0.0020 for 5-year CVD risk prediction, respectively.
CONCLUSIONS Hematological biomarkers were associated with incident CVD. Notably, both high and low MCV and PLR are associated with increased risk. Adding some of these biomarkers to established risk factors could slightly improve cardiovascular risk prediction performance.
GW35-e0114
Ruoyun Fan1, Jitao Ling1, Bing Yuan2, Yuting Wu1, Yifan Wu1, Xinrui Qi1, Peng Yu1, Zhiqiang Chen3,4, Xiao Liu3,4
1The second Affiliated Hospital of Nanchang University
2The First Affiliated Hospital of Nanchang University
3Sun Yat-sen Memorial Hospital of Sun Yat-sen University
4Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine
OBJECTIVES This study aims to investigate the association between the e-cigarettes and ischemic heart disease (IHD).
METHODS Data were acquired from the National Health and Nutrition Examination Survey (NHANES) 2015–2018. Weighted logistic regression and propensity score matching (PSM) analysis (1:1) were employed to assess the relationship between various smoking statuses and self-reported IHD.
RESULTS A total of 11,257 adults met the inclusion criteria for this study, with 878 (7.79%) cases identified as IHD. The cohort comprised Mexican Americans (8.60%), other Hispanics (6.59%), non-Hispanic Whites (63.57%), non-Hispanic Blacks (11.22%), and individuals of other races (10.01%). Nearly half (47.90%) were male, the weighted mean age was 49.0 years. Among them, the non-smokers comprised 6115 individuals (56.5%), the exclusive traditional smokers included 3132 individuals (28.9%), and the dual smokers comprised 1588 individuals (14.6%). In comparison to non-smokers, the odds ratio (OR) for participants exclusively engaged in traditional smoking and those who were dual smokers were 1.63 (95% CI: 1.03–2.58) and 4.32 (95% CI: 2.56–7.31), respectively. After adjustments, dual smokers exhibited a higher association with IHD than exclusive traditional smokers (OR: 2.59, 95% CI: 1.58–4.25). No significant interactions were observed in all predefined subgroups (all P interaction >0.05), including sex (male vs. female), age (<60 vs. ≥60 years). Baseline characteristics after PSM analysis of the traditional smoker group and dual smoker group showed no significant differences. The results indicated a higher prevalence of IHD in the dual smoker group (OR: 1.83, 95% CI: 1.24–2.72) compared to exclusive traditional smokers. Sensitivity analysis involving multiple imputations demonstrated minimal impact on the results. Propensity score matching confirmed the association of exclusive traditional smokers with IHD (OR: 1.83, 95% CI: 1.24–2.72).
CONCLUSIONS Our findings indicate elevated odds of IHD among individuals using both e-cigarettes and combustible cigarettes. Longitudinal studies are imperative to further evaluate the adverse cardiovascular effects induced by e-cigarettes and dual usage.
GW35-e0124
Jingyi Huang1, Peng Yu1, Xiao Liu2
1The Second Affiliated Hospital of Nanchang University
2Sun Yat-sen Memorial Hospital, Sun Yat-sen University
OBJECTIVES The efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) for improving cardiovascular outcomes has been extensively studied in patients with chronic cardiovascular diseases. However, their benefits for patients with acute myocardial infarction (AMI) remain uncertain. We aim to investigate the effectiveness of SGLT2i and GLP-1RA in patients with AMI.
METHODS We conducted a comprehensive search of PubMed, the Cochrane Library, Embase, and ClinicalTrials.gov to identify relevant randomized controlled trials (RCTs) up to April 7, 2024. The primary outcomes of interest included all-cause mortality and left ventricular ejection fraction (LVEF). We utilized Trail Sequential Analysis (TSA) to analyze outcomes. We assessed the quality of evidence for included outcomes according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS Four RCTs investigated the use of SGLT2i (5566 patients on SGLT2i, 5549 patients on placebo), and five RCTs focused on GLP-1RA (300 patients on GLP-1RA, 333 patients on placebo). The results revealed that SGLT2i improved LVEF (mean difference = 1.72, P = 0.01, high certainty) and reduced heart failure hospitalization (HHF) (hazard ratios = 0.78, P = 0.027, high certainty) in AMI patients compared to placebo. No significant difference was observed in all-cause mortality with SGLT2i, and no significant benefits of GLP-1RA were observed in all-cause mortality, cardiac death, myocardial infarction relapse, infarct size, LVEF, left ventricular end-diastolic volume, and left ventricular end-systolic volume. TSA revealed a possibility of false positive result for LVEF and HHF in the SGLT2i group. Other outcomes in both the SGLT2i and GLP-1RA groups remained negative. The quality of evidence of outcomes was assessed as high certainty for LVEF in the GLP-1RA and SGLT2i groups and infarct size in the GLP-1RA groups, and as moderate certainty for other outcomes according to GRADE.
CONCLUSIONS Use of SGLT2i improved LVEF and reduced HHF in AMI patients, but did not show significant benefits in all-cause mortality. GLP-1RA did not demonstrate significant benefits in LVEF and hard outcomes. Further large-scale RCTs are needed to confirm these findings and provide more robust evidence.
GW35-e0129
Qian Zhao1,2, Yining Yang1
1People’s Hospital of Xinjiang Uyghur Autonomous Region
2First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES Metabolic syndrome (MetS) is the most important risk factor for cardiovascular disease attributable burden and a major risk factor for mortality. To investigate the prevalence of MetS and components and explore the association of local dietary patterns with disease risk among Uyghur populations in rural areas of Xinjiang.
METHODS Based on the population-based cohort study of chronic diseases in Xinjiang, the study recruited Uyghur residents over 30 years old from July to September 2022 in LuoPu County, Hotan prefecture, where Uyghur people were concentrated. Participants completed questionnaires, physical examinations, and cardiovascular and metabolic biochemical examinations. The questionnaire included general demographic information, sleep status, and exercise status, and a modified semi-quantitative food frequency questionnaire was used to investigate dietary status. Principal component factor analysis was used to extract dietary patterns with local characteristics, and multivariable Logistic regression model was used to analyze the correlation between MetS and dietary patterns.
RESULTS Finally, 3208 Uyghur subjects (53.11 ± 10.8 years old, 54.9% male) were included. The overall prevalence of MetS was 54.9%, which was higher in males than in females (58.2% vs. 51.81%, P < 0.001). Two local dietary patterns were extracted, namely, animal staple food pattern and confection, aquatic, nut and poultry pattern. After adjusting for general demographic and lifestyle factors, it was found that the increase of animal staple food pattern score (quartile group) was associated with an increased risk of MetS. The second, third and fourth OR of dietary score were 1.08 (95% CI: 0.874~1.343), 1.27 (95% CI: 1.020~1.570), 1.35 (95% CI: 1.077~1.683), P for trend = 0.037. The risk of abdominal obesity, high triglycerides and low high-density lipoprotein cholesterol increased with the increase of dietary scores (P for trend <0.05).
CONCLUSIONS The burden of abnormal cardiovascular and metabolic diseases is heavy in Uyghur population in rural areas of Xinjiang, and the dietary pattern of staple food of animal meat is closely related to the increased risk of MetS.
GW35-e0316
Qiang Qu1,2, Qixin Guo1,2, Jinjing Shi1,2, Shengen Liao1,2, Wenming Yao1,2, Xinli Li1,2
1State Key Laboratory for Innovation and Transformation of Luobing Theory, Department of Cardiology
2The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China
OBJECTIVES Early-life cardiovascular risk factors (CVRFs) are known to be associated with target organ damage during adolescence and premature cardiovascular morbidity and mortality during adulthood. However, contemporary data describing whether the prevalence of CVRFs and treatment and control rates have changed are limited. This study aimed to examine the temporal trends in the prevalence, treatment, and control of CVRFs among US adolescents over the past 2 decades.
METHODS This is a serial cross-sectional study using data from nine National Health and Nutrition Examination Survey cycles (January 2001–March 2020). US adolescents (aged 12–19 years) with information regarding CVRFs (including hypertension, elevated blood pressure [BP], diabetes, prediabetes, hyperlipidemia, obesity, overweight, cigarette use, inactive physical activity, and poor diet quality) were included. Age-adjusted trends in CVRF prevalence, treatment, and control were examined. Joinpoint regression analysis was performed to estimate changes in the prevalence, treatment, and control over time. The variation by sociodemographic characteristics were also described.
RESULTS A total of 15,155 US adolescents aged 12–19 years (representing ≈ 32.4 million people) were included. From 2001 to March 2020, there was an increase in the prevalence of prediabetes (from 12.5% [95% confidence interval (CI), 10.2%–14.9%] to 37.6% [95% CI, 29.1%–46.2%]) and overweight/obesity (from 21.1% [95% CI, 19.3%–22.8%] to 24.8% [95% CI, 21.4%–28.2%]; from 16.0% [95% CI, 14.1%–17.9%] to 20.3% [95% CI, 17.9%–22.7%]; respectively), no improvement in the prevalence of elevated BP (from 10.4% [95% CI, 8.9%–11.8%] to 11.0% [95% CI, 8.7%–13.4%]), diabetes (from 0.7% [95% CI, 0.2%–1.2%] to 1.2% [95% CI, 0.3%–2.2%]), and poor diet quality (from 76.1% [95% CI, 74.0%–78.2%] to 71.7% [95% CI, 68.5%–74.9%]), and a decrease in the prevalence of hypertension (from 8.1% [95% CI, 6.9%–9.4%] to 5.5% [95% CI, 3.7%–7.3%]), hyperlipidemia (from 34.2% [95% CI, 30.9%–37.5%] to 22.8% [95% CI, 18.7%–26.8%]), cigarette use (from 18.0% [95% CI, 15.7%–20.3%] to 3.5% [95% CI, 2.0%–5.0%]), and inactive physical activity (from 83.0% [95% CI, 80.7%–85.3%] to 9.5% [95% CI, 4.2%–14.8%]). Sex and race/ethnicity affected the evolution of CVRF prevalence differently. Whilst treatment rates for hypertension and diabetes did not improve significantly (from 9.6% [95% CI, 3.5%–15.8%] to 6.0% [95% CI, 1.4%–10.6%]; from 51.0% [95% CI, 23.3%–78.7%] to 26.5% [95% CI, 0.0%–54.7%]; respectively), BP control was relatively stable (from 75.7% [95% CI, 56.8%–94.7%] to 73.5% [95% CI, 40.3%–100.0%]), while glycemic control improved to a certain extent, although it remained suboptimal (from 11.8% [95% CI, 0.0%–31.5%] to 62.7% [95% CI, 62.7%–62.7%]).
CONCLUSIONS From 2001 to March 2020, although prediabetes and overweight/obesity increased, hypertension, hyperlipidemia, cigarette use, and inactive physical activity decreased among US adolescents aged 12–19 years, whereas elevated BP, diabetes, and poor diet quality remained unchanged. There were disparities in CVRF prevalence and trends across sociodemographic subpopulations. While treatment and control rates for hypertension and diabetes plateaued, BP control were stable, and improved glycemic control was observed.
GW35-e0324
Tao Wang, Huihui Bao, Xiaoshu Cheng
The Second Affiliated Hospital of Nanchang University
OBJECTIVES Despite the extensive research conducted on sex differences in peripheral artery disease (PAD) through preclinical, epidemiologic, and clinical trial investigations, there remain significant gaps in our knowledge, particularly regarding lipoprotein (a) [Lp(a)]. Few studies have evaluated the association between Lp(a) and PAD in a gender-specific manner. Therefore, our objective was to investigate the gender disparities in the association between Lp(a) and PAD among hypertensive patients.
METHODS This cross-sectional study was conducted from June 2022 to August 2022 to collect basic information from hypertensive residents in rural areas of Wuyuan, China. PAD was defined as an ankle-brachial index of less than 0.9. Multivariable linear regression was performed to analyze associations between Lp(a) and PAD among all participants, as well as within each gender subgroup.
RESULTS The average age (mean ± standard deviation) of the participants was 65.7 ± 9.3 years, 45.6% were males. The prevalence of PAD was 4.9%. In the males but not in the females, Lp(a) were positive associated with PAD (male: OR = 1.25, 95% CI: 1.13–1.39, P < 0.001; female: OR = 1.08, 95% CI: 0.97–1.21, P = 0.174). Moreover, a significant interaction between gender and Lp(a) levels was observed by subgroup analysis (P-interaction = 0.004).
CONCLUSIONS The study demonstrates a positive association between Lp(a) and PAD prevalence in hypertensive adults. Notably, this association was observed exclusively in males, while not in females. When screening for peripheral artery disease, it is important to pay attention to Lp(a) levels in addition to traditional risk factors such as smoking and obesity, especially among men. Furthermore, in clinical practice, clinicians treating patients with hypertension can pay close attention to Lp(a) that act as risk enhancers, which may contribute to the prevention of the occurrence and development of PAD. Therefore, further large-scale prospective cohort studies are needed to explore the process of Lp(a) and PAD in patients with hypertension and encourage researchers to dissect the molecular mechanisms involved.
GW35-e0438
Qianhui Wang
The first Affiliated Hospital of Xinjiang Medical University
OBJECTIVES Sedentary behavior and Phenotypic Age Acceleration (PhenoAgeAccel) have been identified as significant factors in cardiovascular disease (CVD) and mortality. However, the combined impact of sitting time and accelerated aging (PhenoAgeAccel >0) on the risk of CVD and mortality among middle-aged and older adults has not been investigated.
METHODS This cross-sectional study enrolled middle-aged and older American adults who partcipanted in the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Cox proportional hazards model and logistic regression analyses were used to assess the joint association of sitting time and accelerated aging with the risk of CVD and mortality.
RESULTS A total of 6277 participants were included, with a CVD prevalence of 17.06%. Participants exhibiting accelerated aging and prolong daily sitting (more than 6 hours) had a 69% increased risk of CVD compared to those without accelerated aging and daily sitting time <6 hours. Among participants with CVD at baseline, all-cause and CVD related deaths occurred in 523 (48.83%) and 198 (18.49%) individuals during a median follow-up of 114 months. Joint analysis revealed that participants with accelerated aging and prolong sitting time had significantly increased risk of all-cause [hazard ratio (HR): 2.29, 95% confidence interval (CI): 1.69–3.12, P < 0.001] and CVD mortality (HR: 2.77, 95% CI: 1.66–4.62, P < 0.001) compared to those with delayed aging and daily sitting time <6 hours.
CONCLUSIONS Accelerated aging and sedentary behavior jointly contribute to the risk of CVD and the long-term risk of all-cause and CVD mortality among middle-aged and older adults in the US.
GW35-e0511
Minmin Wu1,2, Chen Junhan2,3, Lin Zhijie1,3, Lin Kaiyang1,2,3, Guo Yansong1,2,3
1Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, China
2Center for Cardiovascular Epidemiology Research and Prevention of Fuzhou University Affiliated Provincial Hospital, Fuzhou 350000, China
3Shengli Clinical Medical College of Fujian Medical University, Department of Cardiology, Fuzhou 350000, China
OBJECTIVES Metals are recognized as contributors to cardiovascular diseases. However, studies focusing on cardiovascular events in myocardial infarction patients have not been conducted.
METHODS This prospective study enrolled 1146 volunteers diagnosed with myocardial infarction and undergoing percutaneous coronary intervention (PCI) at the Cardiology Department, Fujian Provincial Hospital, China. Plasma levels of 25 metal(loid)s were measured using inductively coupled plasma mass spectrometry (ICP-MS). The association between plasma metal levels and the risk of major adverse cardiovascular events (MACE) was estimated using multivariate logistic regression. We also explored the combined effects of metal pairs on the risk of MACE. Weighted quantile sum (WQS) regression was conducted to assess the joint effects of metal mixtures. Stratification analysis by age was also examined.
RESULTS A total of 146 cases of MACE occurred. After adjusting for potential confounders, the single-metal models showed that each unit increase in ln-transformed plasma barium (OR: 0.70; 95% CI: 0.58, 0.84) and lithium (OR: 0.66; 95% CI: 0.53, 0.84) were significantly associated with a decreased risk of MACE, while each unit increase in ln-transformed plasma nickel (OR: 1.52; 95% CI: 1.13, 2.04) and lead (OR: 1.29; 95% CI: 1.08, 1.55) were significantly associated with an increased risk of MACE. Participants with high exposure to protective metals and low exposure to harmful metals showed the most significant protective effect against MACE. WQS regression exhibited a significant association between multi-metal exposures and MACE. The modifying effect of age phenotype was observed across all exposure combinations.
CONCLUSIONS The study revealed that plasma levels of barium, lithium, nickel, and lead are significantly associated with the risk of MACE in patients with myocardial infarction, exhibiting age-related heterogeneity. Our findings underscore the importance of monitoring harmful metal exposures to guide targeted interventions.
GW35-e0556
Weiya Li, Hongde Li, Shiqin Peng, Mao Chen
Department of Cardiology, West China Hospital, Sichuan University
OBJECTIVES Due to differences in valve structure between Chinese and Western populations, such as a 20 times higher prevalence of bicuspid aortic valves, a greater calcium burden, and a higher number of patients with aortic regurgitation. While the trends in postoperative TAVR outcomes of China in recent years have not been described. We want to fill in the gaps in this area.
METHODS We included patients at a high-volume Chinese TAVR center, West China Hospital, from 2015 to 2022, and described the multivariable adjusted time trends of their 1-year follow-up outcomes including 30-day mortality, 1-year all-cause mortality, 1-year cardiac mortality, 1-year Major Adverse Cardiovascular Event (MACE), 1-year stroke, and 1-year permanent pacemaker implantation (PPI). The gender differences of time trends were also explored.
RESULTS The overall crude poor prognosis all showed a decrease trend in recent years. After multivariate adjustment, 30-day mortality, 1-year all-cause mortality, 1-year cardiac mortality, and 1-year PPI incident rate showed a significantly decrease trend (Adjusted P for trend <0.05). 1-year MACE, 1-year stroke incident rate also had a decrease trend but did not reach statistically significant. In the subgroup analysis of sex differences, we found that men had a more pronounced time trend of decreasing all-cause and cardiac mortality than women, while women had a more pronounced trend of decreasing PPI rate than men.
CONCLUSIONS In summary, our study demonstrates, for the first time, a declining trend in adverse prognosis among postoperative TAVR patients in China in recent years, with some notable gender differences.
GW35-e0673
Jingjin Hou, Chenghui Yan
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Rheumatoid arthritis (RA) not only impacts the musculoskeletal system but also increases the risk of developing cardiovascular disease (CVD). Over the past few decades, the introduction of biologic agents has revolutionized the treatment of RA. However, their impact on cardiovascular risk remains a topic of debate. The purpose of the study is to evaluate the effects of biologic therapy on cardiovascular risk factors in rheumatoid arthritis patients to determine its clinical efficacy.
METHODS Relevant literature was systematically searched in PubMed, Embase, and Cochrane Library databases. Dual-independent study selection, data extraction and quality assessment were conducted. The statistical analysis was conducted using STATA 14.0 software (Stata Corporation). Meta-analysis was conducted using standardized mean differences (SMDs) and 95% confidence intervals (CIs) to evaluate cardiovascular risk factors and atherosclerosis. Furthermore, we will explore potential sources of heterogeneity, perform subgroup analyses, and conduct sensitivity analyses to assess the robustness of our findings. Statistical significance was set at P < 0.05.
RESULTS The meta-analysis revealed that biologic treatment in RA patients was associated with decreased high-density lipoprotein cholesterol (HDL-C) levels compared to controls (MD: −0.10, 95% CI: [−0.14, −0.05], P < 0.0001). Subgroup analysis based on treatment duration showed heterogeneity and a potential decrease in total cholesterol levels after 12 months of treatment (MD = −0.03, 95% CI [−0.21, −0.15], P = 0.76). Biologic therapy significantly reduced triglyceride levels compared to controls (MD = −0.23, 95% CI [−0.37, −0.09], P = 0.001), as observed in subgroup analysis. Moreover, biologics effectively decreased low-density lipoprotein cholesterol (LDL-C) levels (MD: −0.10, 95% CI: [−0.14, −0.05], P < 0.0001). However, biologic treatment was associated with increased inner carotid artery thickness (MD: 0.05, 95% CI: [0.03, 0.07], P < 0.0001), indicating potential adverse effects on cardiovascular health. No significant effect on pulse wave velocity (PWV) was observed (MD: −0.23, 95% CI: [−0.80, 0.34], P = 0.43, I2 = 0%, P = 0.55).
CONCLUSIONS Biologic agents may improve lipid profiles in RA patients but could also have adverse effects on cardiovascular health. Further research is needed to comprehensively understand the impact of biologic therapy on lipid metabolism and cardiovascular outcomes in RA patients.
GW35-e0674
Jingjin Hou, Chenghui Yan
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China.
OBJECTIVES A novel class of hypoglycemic medications known as sodium-glucose cotransporter 2 (SGLT2) inhibitors has not yet been completely established for the effectiveness and safety of SGLT2 inhibitors in acute heart failure (AHF) or acute decompensated heart failure (ADHF). And their association with improving quality of life has been variably studied. Consequently, we sought to compare the prognostic and safety outcomes of patients given SGLT2 inhibitors for AHF and ADHF.
METHODS An extensive search of the Web of Science, PubMed, EMBASE and Cochrane CENTRAL database was conducted for randomized controlled trials (RCTs) and observational studies that have evaluated SGLT2 inhibitors in AHF and ADHF from inception to the present. Dual-independent study selection, data extraction and quality assessment were conducted. We used the Cochrane risk of bias (RoB 2) tool to assess the randomization process for parallel and crossover randomized trials. We used the Newcastle-Ottawa Scale (NOS) to assess the risk of bias for observational studies. We compiled data relating to all-cause mortality, readmission events and cardiovascular-related incidents from studies that met the inclusion criteria. We also examined safety outcomes of interest, including urinary tract infection, diabetic ketoacidosis (DKA), hypotension, hypoglycemia and acute kidney injury (AKI). We generated and aggregated risk ratios (RR) and 95% confidence intervals (CIs) for outcomes like all-cause mortality and rehospitalization using either fixed or random-effects models in order to evaluate the predictive significance of SGLT2 usage in patients with acute or decompensated heart failure.
RESULTS At last, we identified a total of 4047 patients from 13 studies. Patients experienced a substantial reduction in all-cause mortality (RR = 0.82; 95% CI: 0.70–0.96; P = 0.02), readmission rates (RR = 0.77; 95% CI: 0.64–0.93; P = 0.008), and the number of HFE events (RR = 0.69; 95% CI: 0.50–0.95; P = 0.02) in the SGLT2 group. SGLT2 inhibitors improved patients’ quality of life (Cohen’s d = −0.24, 95% CI: −0.40 to −0.09, P = 0.002) and cumulative urine output during hospitalization (MD = 2.83, 95% CI: 1.36–4.29, P < 0.001, I2 = 97%) relative to controls. Combining the patients’ NT-proBNP levels at the final post-treatment follow-up revealed that the SGLT2-treated group had significantly lower NT-proBNP levels than the control group (MD = −601.11, 95% CI: −935.15 to −267.06, P < 0.001, I2 = 0%). In the end, the intervention group showed a significant 11% reduction in the risk of severe adverse events (RR = 0.89, 95% CI: 0.80–1.00, P = 0.05). Lastly, SGLT2 inhibitor users with AHF/ADHF did not have a higher risk of acute kidney injury (AkI) (RR = 0.97, 95% CI: 0.66–1.43, P = 0.88, I2 = 0%).
CONCLUSIONS SGLT2 addition to conventional diuretic therapy reduced all-cause death, readmissions for HF, and the composite of cardiovascular death or readmissions for HF. This meta-analysis suggests that the use of SGLT2 has a better prognosis for patients with AHF or ADHF compared to controls. It is safe and effective for patients with AHF or ADHF to start SGLT2 inhibitors during or shortly after hospitalization.
GW35-e0891
Qinghui Zeng1,2,3,4,5, Qiuju Deng1,2,3,4,5, Piaopiao Hu1,2,3,4,5, Jiayi Sun1,2,3,4,5, Jing Liu1,2,3,4,5
1Center for Clinical and Epidemiologic Research, Beijing An Zhen Hospital, Capital Medical University, Beijing, China
2Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
3National Clinical Research Center of Cardiovascular Diseases, Beijing, China
4The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
5The Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
OBJECTIVES Acute myocardial infarction (AMI), a severe outcome of ischemic heart disease (IHD), contributes to more than 30% of IHD-related fatalities. It has been noted that environmental factors like temperature and PM2.5 can trigger AMI and have garnered significant attention. Yet, the relationship between air pressure and AMI remains unclear. Moreover, the joint effect of air pressure with other meteorological factors or pollutants on AMI is also uncertain.
METHODS We obtained AMI morbidity data for permanent Beijing residents between 2007 and 2021 from the Beijing Cardiovascular Disease Surveillance System. Daily air pressure, temperature, and PM2.5 exposure data were linked to patients’ addresses. The associations of daily air pressure with AMI onset were estimated through conditional logistic regression and distributed lag nonlinear models, with adjustments for potential confounders. We calculated cumulative odds ratios (ORs) over the lag period and explored how PM2.5 and temperature modify these effects using a Z test to compare effect estimates across subgroups.
RESULTS A total of 473,599 AMI events were identified in Beijing, China. The air pressure varies from 949.93 hPa to 1027.53 hPa with a daily mean of 1004.57 hPa. The dose-response relationship between low air pressure and AMI morbidity was non-linear. Both low and high air pressure were associated with an increased cumulative risk of AMI onset. The odds ratio (OR) of AMI onset associated with extremely low and high air pressure were 1.06 (95% confidence interval [CI] 1.01–1.12) and 1.16 (95% CI, 1.11–1.20), respectively. Notably, the effect of extreme low air pressure appeared to be modified by PM2.5, showing a higher risk of AMI onset under more polluted days (OR = 1.13, 95% CI 1.02–1.25). Similarly, the impact of extreme high air pressure appeared to be modified by temperature, indicating an elevated risk during higher temperature days (OR = 1.76, 95% CI 1.55–1.99).
CONCLUSIONS Our findings highlight a significant association between extreme air pressure and AMI morbidity. Moreover, the effects of extremely low and high air pressure were modified by PM2.5 and temperature. These results underscore the importance of considering multiple meteorological and pollution factors and their joint effects in preventing cardiovascular disease.
GW35-e0902
Piaopiao Hu, Qiuju Deng, Qinghui Zeng, Jiayi Sun, Jing Liu
Center for Clinical and Epidemiologic Research, Beijing An Zhen Hospital, Capital Medical University, Beijing, China; Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
OBJECTIVES In the context of escalating global warming, the association between high temperatures and health outcomes has garnered attention. However, whether the adverse health effect of extreme temperature changed over years remains largely unknown. We aim to estimate the temporal changes of the association between heat waves and myocardial infarction (MI) mortality in Beijing, China, from 2007 to 2021.
METHODS MI deaths occurring between 2007 and 2021 were identified from the Beijing Cardiovascular Disease Surveillance System. High-resolution gridded exposure data were geographically matched to the patients’ addresses. Restricting to the warm season (May to October), heat waves were defined as consecutive days with a daily maximum temperature exceeding the 90th (32.1 °C), 92.5th (32.9 °C), and 95th (33.9 °C) percentiles for durations of over 2, 3, and 4 days respectively. Employing an individual-level time-stratified case-crossover design, the associations between heat waves and MI mortality were analysed using conditional logistic regression models. The temporal changes were assessed by including a linear interaction between time (a sequence from the first day to the last day during the study period) and heat wave in the model, and the odds ratio (OR) and 95% confidence interval (CI) for the midpoints in both 2007 and 2021 was calculated.
RESULTS During a 15-year period from 2007 to 2021, a total of 276,157 MI deaths and their corresponding 938,656 controls were included, of which 52.2% were males and 69.4% were aged over 75 years. The median daily maximum temperature was 17.6 °C with a range from −21.0 °C to 41.6 °C. The effect of heat waves generally increased significantly during the study period. The risk of MI mortality associated with heat waves, defined as exceeding the 90th percentile (32.1 °C) for more than 2 consecutive days, increased from 1.038 (95% CI, 1.001–1.077) in 2007 to 1.109 (95% CI, 1.073–1.147) in 2021. Similarly, under a more extreme definition, the effect of heat waves defined as exceeding the 95th percentile (33.9 °C) for more than 4 days increased from 1.069 (95% CI, 1.007–1.136) in 2007 to 1.123 (95% CI, 1.063–1.187) in 2021. The results remained robust across different definitions of heat waves with multiple temperatures and days of duration. The increasing effect of heat waves associated with MI mortality was greater for males than females and for individuals over 75 years old than those under 75.
CONCLUSIONS The magnitude of associations between heat waves and MI mortality has exhibited a progressive increase from 2007 to 2021. Our study suggests that the adverse impacts of heat waves are progressively intensifying, and in conjunction with the projected escalation in extreme events due to global warming, there is an urgent need to address this worsening health threat in public health policy making.
GW35-e0910
Xueting Sun, Youling Duan, Jiangtao Li, Yongchen Hao, Qiuju Deng, Yunqi Zhang, Yue Qi, Jing Liu
Center for Clinical and Epidemiologic Research, Beijing An Zhen Hospital, Capital Medical University
OBJECTIVES Lipoprotein (a) [Lp(a)] has been established as a risk factor for atherosclerotic cardiovascular disease independent of low-density lipoprotein cholesterol (LDL-C) in multi-dimensional studies. The association of vascular disease with Lp(a) levels has been reported, yet whether there is a correlation between Lp(a) level and multivascular diseases remains unclear. This study aims to evaluate the association between elevated Lp(a) levels and multivascular diseases.
METHODS Study participants were recruited from the Chinese Multi-provincial Cohort Study-Beijing project, a prospective population-based cohort study. Serum Lp(a) concentration was measured among 1210 participants with the cardiovascular disease risk factor survey in 2012. The presence of carotid plaque, arteriosclerosis and fundus microvascular lesions were determined by ultrasound, ankle/arm blood pressure index (ABI) and fundus examination, respectively. Participants were divided according to Lp(a) levels (<50.0 and ≥50.0 mg/dL).
RESULTS The average age of participants was 68.9 (±7.9) years old, and 44.9% (543) were male. Serum Lp(a) levels have a skewed distribution, Lp(a) ≥50.0 mg/dL accounted for 12.0% (145 individuals). Participants with an elevated Lp(a) levels were more likely to have higher total cholesterol and LDL-C level, and had higher prevalent rate of carotid atherosclerotic plaque and arteriosclerosis, but non-significant differences were found for fundus microvascular lesions (P > 0.05). In addition, the proportion of participants with one vascular disease (55.9%, 81 individuals) and two or more vascular diseases (31.7%, 46 individuals) in participants with Lp(a) ≥50 mg/dL was higher than participants with Lp(a) <50 mg/dL (P < 0.05), respectively. After adjustment for cardiovascular risk factors, the multiple regression analysis showed that participants with Lp(a) levels ≥50 mg/dL had a 94.3% increased risk of carotid plaque (95% CI: 1.217–3.104), a 63.6% increased risk of arteriosclerosis (95% CI: 1.014–2.638), compared with the participants with Lp(a) level <50 mg/dL. Moreover, Lp(a) ≥50.0 mg/dL was associated with an 81.5% increased risk of suffering from one vascular disease (95% CI: 1.038–3.175), and 2.259 times higher risk of developing two or more types of vascular disease (95% CI: 1.219–4.184).
CONCLUSIONS The present study found that elevated Lp(a) levels (≥50.0 mg/dL) were associated with an increased risk of multivascular diseases in the community-based population, suggesting the importance of targeting Lp(a) levels in the prevention of multivascular diseases.
GW35-e0953
Wenbo Yang, Xintian Cai, Nanfang Li
Hypertension Center, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES We aimed to evaluate the METS-IR (metabolic score for insulin resistance) index for the prediction of incident cardiovascular disease (CVD) and its subtypes (coronary artery disease and stroke) in patients with hypertension and obstructive sleep apnea (OSA).
METHODS A retrospective cohort study was conducted with 2031 adults with hypertension and OSA, participants from the Urumqi Research on Sleep Apnea and Hypertension study (UROSAH). The hazard ratios and 95% CIs (credibility interval) for CVD and its subtypes were estimated using multivariate Cox proportional hazards regression models.
RESULTS After a median follow-up of 6.80 years (interquartile range: 5.90–8.00 years), a total of 317 (15.61%) participants developed new-onset CVD, including 198 (9.75%) incident coronary heart disease (CHD) and 119 (5.86%) incident stroke. After adjusting for as many relevant confounding factors as possible, each SD increase in METS-IR was associated with a 30% increased risk of new onset overall CVD events, a 32% increased risk of new onset CHD, and a 27% increased risk of new onset stroke. When METS-IR was assessed as tertiles, after adjustment for fully confounding factors, the highest tertiles versus the lowest tertiles were associated with a greater hazard of CVD (HR 2.05; 95% CI 1.52−2.77), CHD (HR 1.96; 95% CI 1.35–2.84), and stroke (HR 2.24; 95% CI 1.35–3.72). The results of various subgroups and sensitivity analyses were similar. When METS-IR was added, CVD predictions were reclassified and identified more accurately than baseline models for the C-index, continuous net reclassification improvement, and integrated discrimination index. CHD and stroke showed similar results.
CONCLUSIONS METS-IR is a powerful predictor of CVD and its subtypes in patients with hypertension and OSA, which can facilitate the identification of high-risk individuals and provide individualized CVD prevention.
GW35-e0992
Junhan Yang1,2,3, Yao He3,4, Shengshu Wang3, Miao Liu2
1Medical School of Chinese PLA
2Department of Anti-NBC Medicine, Graduate School, Chinese PLA General Hospital
3Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatric Diseases, Second Medical Center, Chinese PLA General Hospital
4State Key Laboratory of Kidney Diseases
OBJECTIVES CKD is a major risk factor for the development of cardiovascular disease. The prevalence of CKD is usually higher in the elderly population than in adults due to the presence of underlying diseases such as diabetes and hypertension. The urine albumin-creatinine ratio (UACR) plays an important role in the early diagnosis of CKD, with UACR ≥30 mg/g defined as kidney damage. Studies have shown that the risk of cardiovascular and all-cause mortality increases with elevated UACR, and higher CVH scores may be associated with lower mortality. Therefore, to reduce the disease burden of CKD, investigating the impact of CVH status and UACR on population health risk has important public health implications for CKD prevention and management strategies. In this study, we investigated the association of UACR and CVH scores within the normal range with cardiovascular and all-cause mortality in the elderly population to provide a scientific basis for the effective prevention and management of CKD in the elderly and the achievement of healthy aging.
METHODS Based on Beijing Healthy Aging Cohort Study (BHACS), data were analyzed from 1817 elderly participants with UACR in the normal range (<30 mg/g). UACR was categorized into tertiles delineated as low (<5.80 mg/g), medium (5.80–9.55 mg/g), and high (9.56–29.9 mg/g). The study used Life’s Essential 8 to develop a cardiovascular health score (CVH) and categorised it into the low CVH score (≤72.5 points) and the high CVH score (>72.5 points). The restricted cubic spline was plotted to explore the non-linear relationship between UACR and risk of cardiovascular and all-cause mortality. Multivariable Cox proportional risk regression models were used to analyse the association of UACR with the risk of cardiovascular and all-cause mortality.
RESULTS As of 31 March 2021, the median follow-up of the study was 11.28 years (P 25~P 75: 10.84–11.36 years), with a total of 308 deaths during follow-up, giving a mortality density of 163.87/10,000 person-years. The study included 1817 participants (mean age 71.4 ± 6.6 years; 1070 females). The results showed that continuous UACR was almost linearly associated with cardiovascular and all-cause mortality. In the low CVH score group, there was a decreasing trend in the risk of both cardiovascular and all-cause mortality with decreasing levels of UACR (HR = 0.500, 95% CI: 0.341–0.734; HR = 0.793, 95% CI: 0.647–0.971). Compared with participants with low CVH score and high UACR, the risk of cardiovascular and all-cause mortality was reduced by 68.9% and 45.6%, respectively, in participants with high CVH score and low UACR (HR = 0. 311, 95% CI: 0.131–0.739; HR = 0.544, 95% CI: 0.360–0.822), and the risk of all-cause mortality was reduced by 26.7% with high CVH score and high UACR (HR = 0.733, 95% CI: 0.542–0.993).
CONCLUSIONS In the elderly population, elevated levels of normal-range UACR were associated with a significantly increased risk of cardiovascular and all-cause mortality, and the combined effect of CVH status and UACR in the normal range had a greater protective effect on the risk of cardiovascular and all-cause mortality. It is proposed that the management and intervention of cardiovascular health indicators for early renal dysfunction can offset some of the adverse effects of UACR and reduce the risk of cardiovascular and all-cause mortality in the elderly population.
GW35-e1019
Qingan Fu, Renqiang Yang
The Second Affiliated Hospital of Nanchang University
OBJECTIVES Cardiovascular disease (CVD) is a leading cause of mortality worldwide, with environmental pollutants such as volatile organic compounds (VOCs) recognized as significant contributors to CVD risk. This study aims to develop a predictive model using machine learning (ML) to assess CVD risk based on VOC exposure and demographic data. The model incorporates SHapley Additive exPlanations (SHAP) to enhance interpretability and provide insights into the interaction effects between various factors and CVD risk.
METHODS Data were sourced from the National Health and Nutrition Examination Survey (NHANES) spanning 2011–2018, encompassing 5098 participants. VOC exposure was quantified through 15 urinary metabolite measurements. The dataset was divided into a training set (70%) and a test set (30%). Six ML models were constructed: Random Forest (RF), Light Gradient Boosting Machine (LightGBM), Decision Tree (DT), Extreme Gradient Boosting (XGBoost), Multi-Layer Perceptron (MLP), and Support Vector Machines (SVM). The models’ performance was evaluated using the Area Under the Receiver Operating Characteristic Curve (AUROC). SHAP was employed to interpret the best-performing model, elucidating the contribution of each variable to the prediction.
RESULTS Among the six models, the RF model demonstrated superior predictive performance, achieving an AUROC of 0.8143. SHAP analysis revealed that age and ATCA were the most significant predictors of CVD risk. ATCA exhibited a protective effect against CVD, which was particularly pronounced in older adults and individuals with hypertension. The interaction effect analysis highlighted that older individuals benefited more from higher ATCA levels due to increased oxidative stress and inflammatory responses associated with aging. Furthermore, the protective effect of ATCA was more significant in hypertensive individuals, underscoring its potential role in mitigating CVD risk in this population.
CONCLUSIONS This study represents a pioneering effort in using VOC exposure data to develop an ML model for predicting CVD risk. The findings underscore the potential of integrating environmental exposure metrics with demographic data to improve CVD risk prediction. The use of SHAP for model interpretation provides valuable insights into the interaction effects of various factors, such as age and ATCA levels, on CVD risk. These results support the development of personalized prevention and intervention strategies, emphasizing the importance of considering both environmental and demographic factors in CVD risk assessment.
GW35-e1024
Kuangyi Wu1, Shouling Wu2, Youren Chen1
1Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, China
2Department of Cardiology, Kailuan General Hospital, Tangshan, China
OBJECTIVES The predictive value of a single visceral adiposity index (VAI) assessment for incident heart failure (HF) is well-established. However, there is limited understanding of the long-term changes in the Chinese (C) VAI and its relationship with the incidence of HF. Here, we aimed to assess the longitudinal relationship between the trajectory of CVAI and new-onset HF.
METHODS We performed a prospective study of 76,822 participants in the Kailuan Study who were free of HF or cancer up to 2012. The CVAI was calculated using the age, body mass index, waist circumference, and metabolic parameters of the participants, and latent mixed modelling was used to identify the trajectory of CVAI during the exposure period (2006–2012). Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for incident HF of the trajectory groups.
RESULTS Five trajectory groups based on the changes in CVAI were identified. During a median follow-up period of 7.78 years, 1480 participants developed HF. Compared with the Low-stable group, the HRs of HF in High-stable and High-increasing groups were 2.01 (1.11, 3.63) and 2.43 (1.28, 4.62), respectively. The correlations were strongest in participants <60 years of age and those that did not have hypertension. Sensitivity analyses generated similar findings.
CONCLUSIONS Long-term high CVAI is associated with higher risk of HF, irrespective of conventional risk factors. The regular monitoring of CVAI may help identify individuals at high risk of HF in the general population.
GW35-e1053
Jinxing Liu, Xiaorong Han, Jiangshui Wang, Yingzhen Gu, Yifan Li, Wei Zhang, Naqiang Lv, Aimin Dang
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES To investigate the associations between triglyceride (TG) and C-reactive protein (CRP) levels and adverse cardiovascular outcomes in the general population.
METHODS The participants of this study were selected from the National Health and Nutrition Examination Survey (NHANES). The baseline characteristics of the included participants mainly included smoking history, alcohol consumption, physical activity, self-reported medical history, systolic blood pressure, body mass index (BMI), TG, CRP, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), glycosylated hemoglobin (HbA1c), and estimated glomerular filtration rate (eGFR). The endpoints of the study were cardiovascular death and all-cause death. In this study, CRP >0.3 mg/dL was defined as high CRP, and TG >2.3 mmol/L was defined as high TG. According to TG and CRP levels, the study participants were divided into four groups: Group I (low CRP and low TG), Group II (low CRP and high TG), Group III (high CRP and low TG), and Group IV (high CRP and high TG).
RESULTS A total of 11,293 NHANES participants (2001–2010) were included in this study, and the median follow-up time was 159.0 (29.0–193.0) months. TG and CRP were included as continuous variables in Cox univariate and multifactorial regression analyses using restricted cubic spline (RCS). Univariate analysis revealed that both TG and CRP levels were nonlinearly correlated with the risk of all-cause death and cardiovascular death. According to the multivariate analysis, TG was not independently associated with the risk of all-cause death or cardiovascular death, and CRP was independently associated with all-cause death and cardiovascular death, and the relationship with all-cause death remained nonlinear. Univariate Cox regression analysis after grouping suggested that the risk of all-cause death and cardiovascular death gradually increased from group I to group IV. And comparing to Group I, the hazard ratios (HRs) of the three groups were 1.456 (95% CI: 1.181–1.795), 1.580 (95% CI: 1.434–1.741) and 2.063 (95% CI: 1.690–2.518), respectively. However, after adjusting for basic demographic characteristics (age, sex, race, poverty income ratio, education level; Model 1) and other factors (cardiovascular disease, heart failure status, stroke status, BMI, smoking status, physical activity status, LDL-C level, HbA1c level; Model 2), there was no statistically significant increase in the risk of all-cause death or cardiovascular death in Group II compared with Group I. The HRs after adjusting the two models were 1.105 (95% CI: 0.898–1.360) and 1.020 (95% CI: 0.744–1.398), respectively. Compared with those in group I, the risks of all-cause death and cardiovascular death in groups III and IV gradually increased. The HRs after adjusting the two models in group III were 1.306 (95% CI: 1.177–1.448) and 1.277 (95% CI: 1.110–1.469), respectively, and the HR in group IV was 1.652 (95% CI: 1.67–1.469). 1.362–2.003), 1.532 (95% CI: 1.178–1.991). The addition of TG-CRP group significantly improved the predictive performance of the traditional model for all-cause death (NRI: 8.6%, P = 0.030; IDI: 0.2%, P < 0.001) and cardiovascular death (NRI: 12.2%, P < 0.001; IDI: 0.5%, P < 0.001).
CONCLUSIONS In the general population, TG-CRP group was significantly associated with adverse outcomes, including cardiovascular death and all-cause death, and elevated TG levels were independently associated with the risk of adverse outcomes only when combined with elevated CRP levels. The inclusion of TG-CRP group in the traditional model can significantly improve its predictive power.
GW35-e1064
Yixin Tian, Xue Cao, Zengwu Wang
Fuwai Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences
OBJECTIVES Previous studies have quantified the burden attributable to high LDL-C globally or in high-income countries, providing crucial information in informing dyslipidemia control planning. However, the disease burden of high low-density lipoprotein cholesterol (LDL-C) in China have not been fully elucidated.
METHODS In this population-based study, we obtained 813,349 adults from three large-scale, nationally representative and provincially studies, including the China Chronic Disease and Risk Factor Surveillance, the China National Nutrition Survey, and the China Hypertension Survey. Average LDL-C levels were estimated using a temporal-spatial hierarchical Bayesian model. Mortality data was derived from the National Mortality Surveillance System. A comparative risk assessment method was used to quantify deaths, years of life lost (YLLs), and life expectancy lost attributable to high LDL-C by age, sex, and for 31 provinces in China from 2010 to 2020. A Bayesian Age-Period-Cohort analysis was used with integrated nested Laplace approximations to project the future trends through 2030. Decomposition analysis was used to assess the drivers of changes in attributable deaths.
RESULTS Nationally, the mean LDL-C was 2.92 mmol/L (95% UI, 2.58–3.26) for males and 2.89 mmol/L (95% UI, 2.56–3.22) for females in 2020. The age-standardized LDL-C increased by 23.72% for males and 26.20% for females from 2010 to 2020. Approximately 937.47 thousand (95% UI, 866.69–1003.09) deaths and 18.93 million (95% UI, 18.02–19.76) YLLs were attributable to high LDL-C in China in 2020, with 483.79 thousand (95% UI, 447.76–517.31) deaths and 11.33 million (95% UI, 10.86–11.75) YLLs from males, and 454.19 thousand (95% UI, 392.64–504.82) deaths and 7.62 million (95% UI, 6.85–8.26) YLLs from females. There were 785.54 thousand (95% UI, 722.62–841.18) deaths and 15.97 million (95% UI, 15.19–16.69) YLLs from ischaemic heart disease, and 150.75 thousand (95% UI, 123.38–179.91) deaths and 2.95 million (95% UI, 2.61–3.34) YLLs from ischaemic stroke. Between 2010 and 2020, there was 24.29% increase in age-standardised mortality rate attributable to high LDL-C, while death number increased by 78.88%. This dramatical increasing trend of deaths was closely associated with the rapid increase in LDL-C level, population growth, and population aging during the last 11 years. By 2030, the projected age-standardised mortality rates attributable to high LDL-C will be 76.56 per 100,000 people (95% UI, 51.94–107.92) for males and 47.17 (33.77–61.31) for females. The mortality burden attributable to high LDL-C increased with ageing. The high LDL-C related mortality rates increased from 6.53 per 100,000 people (95% UI 6.11–6.73) aged 25–29 years to 1534.88 (1267.49–1800.35) aged ≥80 years for males, and increased from 2.00 (1.93–2.06) aged 25–29 years to 1767.87 (1429.05–2045.71) aged ≥80 years for females. There were considerable variations in the mortality burden attributable to high LDL-C among regions in China. The highest age-standardised mortality rate for high LDL-C in Northeast, Northwest, and Circum-Bohai Sea Regions of China. We also estimated that if the high LDL-C was removed, the average life expectancy would have been 0.78 years longer in China, ranging from 0.33 years longer in Tibet to 1.35 years longer in Liaoning in 2020.
CONCLUSIONS The substantial disparities in age, sex, and regions highlighted the need for equitable implement in resource mobilization and education for LDL-C control in China.
GW35-e1285
Yixin Tian, Zengwu Wang
Division of Prevention and Community Health, National Center for Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 102308, China
OBJECTIVES Hypertension is a major cause of end-stage renal disease. Assessing the prevalence of chronic kidney disease (CKD) in hypertension could provide information for public health policies and plans.
METHODS From a national and provincial representative study from 2020–2022, a total of 244,541 adults aged ≥18 was collected. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI equation. CKD defined as presence of impaired kidney function (eGFR of <60 mL/min/1.73 m2). High blood pressure was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, self-reported history of high blood pressure, or use of antihypertensive medication. The primary outcome was prevalence of CKD in the overall population and different strata. Secondary outcomes were usage of antihypertensive medication and control of hypertension among adults with hypertension and CKD.
RESULTS A total of 83,001 adults with hypertension were included in this study in 2020–2022, the mean age was 56.57 years, and the proportion of women was 45.47%. The estimated prevalence of CKD were 4.86% in hypertension in China, with 4.14% from males and 5.72% from females. The estimated prevalence of CKD in hypertension increased with age, ranging from 0.26% in 18–24 years to 17.05% in 74 + years. Blood pressure levels also affect the status of kidney function in hypertension. According to the classification of blood pressure level, the estimated prevalence of CKD in hypertension were 3.73%, 5.01%, and 7.47% at stage 1, 2, and 3 hypertension, respectively. Among the adults with hypertension, 52,784 (63.59%), 26,187 (31.55%), 2969 (3.58%), 830 (1.00%), and 231 (0.28%) were at stage 1, 2, 3a, 3b, and 4–5 CKD, respectively. In patients with hypertension and CKD, 66.21% take one or more antihypertensive drugs, while 13.39% take two or more antihypertensive drugs. With the decline in kidney function, the proportion of antihypertensive medication use significantly increases. The proportions of combined use of 2 or more antihypertensive drugs were 5.74%, 9.79%, 13.07%, 14.1%, and 15.15% at stage 1, 2, 3a, 3b, and 4 to 5 CKD, respectively. The proportion of patients at stage 3a (45 mL/min/1.73 m2 ≤eGFR <60 mL/min/1.73 m2) taking three or more medications is the highest (4.21%). In patients with hypertension and CKD, the control rate of hypertension is 22.48%. Among hypertensive patients, as renal function declines, the number of patients with controlled hypertension were 6538, 4716, 661, 199, 46 at stage 1, 2, 3a, 3b, and 4 to 5 CKD, respectively, and the hypertension control rate were 12.39%, 18.01%, 22.26%, 23.98%, 19.9% at stage 1, 2, 3a, 3b, and 4 to 5 CKD, respectively. Currently, CKD guidelines have inconsistent standards for blood pressure control in patients with CKD. When using a standard of 130/80 mmHg, the blood pressure control rate in the hypertensive population with CKD is 8.71%. When using a control standard of SBP <120 mmHg, the control rate is 4.94%.
CONCLUSIONS Among Chinese adults with hypertension, the proportion of CKD increased with higher blood pressure. Patients with hypertension and CKD had limited control rates of hypertension, which need more attention.
GW35-e1323
Xuyan Pei
Peking Union Medical College and Chinese Academy of Medical Sciences
OBJECTIVES To investigate the effects of cold and heat on cardiovascular disease incidence in four Chinese municipalities (Beijing, Tianjin, Shanghai, and Chongqing); and to examine the temporal relationship between cold and heat cardiovascular disease incidence in each city.
METHODS The study monitored 27,550 cardiovascular disease cases recorded by sentinel surveillance systems in four municipalities during 2023. A negative binomial regression model combined with a distributed lag nonlinear model was used to examine the effects of specific temperatures on cardiovascular disease incidence in each city, with a lag period of up to 21 days. A meta-analysis was used to pool the cold effects and hot effects across the four cities.
RESULTS The relationship between temperature and CVD incidence was nonlinear in all four municipalities, with increased morbidity rates on days with hot and cold temperatures. The effects of cold were delayed in northern cities (Beijing, Tianjin), while immediate in southern cities (Shanghai and Chongqing). The effects of heat appeared immediately in all cities except Tianjin. Meta-analysis showed that the incidence of cardiovascular disease increased by 145% (95% CI: 1.33–4.49) under high temperature conditions, and by 152% (95% CI: 1.65–3.84) under low temperature conditions, relative to the minimum morbidity temperature.
CONCLUSIONS Results indicate that both cold and hot temperatures increased the incidence of cardiovascular disease in China. The effects of heat and cold on cardiovascular morbidity was characteristic in each city. Policies to address climate change should take into account the relationship between local climate and cardiovascular morbidity.
GW35-e1337
Xue Cao, Yixin Tian, Tuerdi Nuerguli, Yujie Zhang, Zengwu Wang
National Center for Cardiovascular Disease, National Clinical Research Center of Cardiovascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences
OBJECTIVES Hypertension has consistently maintained a high prevalence rate in China, however, comprehensive evidence for recent hypertension trends across specific population subgroups was limited. Our study aimed to examine trends in prevalence, awareness, treatment, and control of hypertension in China.
METHODS Data was derived from two cross-sectional nationally representative surveys, which enrolled 455,770 participants aged 18 years or older in the 2012–2015 and 297,065 participants in the 2020–2022. Hypertension was defined as a systolic blood pressure ≥140 mmHg, and/or a diastolic blood pressure ≥90 mmHg, and/or taking antihypertensive medication. The main outcome were prevalence of hypertension and awareness, treatment, and control rates for hypertension. We classified regions by socioeconomic status using the human development index (HDI). We also decomposed changes in hypertension prevalence into population growth, shift in population age structure, and changes in age-specific rate.
RESULTS The mean age [SD] were 45.5 (17.6) years in 2012–2015, and 47.9 (18.1) in 2020–2022 in China. The weighted prevalence of hypertension increased from 23.2% (95% confidential interval [95% CI] 22.2%–24.3%) in 2012–2015 to 31.9% (95% CI 30.3%–33.4%) in 2020–2022, with the prevalence among 25–34 years old more than doubling. The gap in hypertension prevalence between urban and rural areas has widened, and the prevalence in rural areas exceeded that in urban areas in 2020–2022. In both surveys, the highest age-standardised prevalence was observed in very-high HDI region, north and northeast China, with the largest increase areas with upper-middle HDI level. In 2020–2022, the awareness, treatment, and control of hypertension were 43.8% (95% CI 41.4%–46.1%), 38.3% (95% CI 36.0%–40.6%), and 13.6% (95% CI 11.9%–15.5%), respectively. Higher age-standardised awareness, treatment, and control rates was observed in high and very-high HDI region in 2020–2022, and improvements were noted in very-low HDI and high HDI region. Nationally, changes in age-specific hypertension prevalence were the primary driver of increased prevalence of hypertension from 2012 to 2022.
CONCLUSIONS Hypertension prevalence was still high in China, with an upward trend from 2012 to 2022. Awareness, treatment, and control of hypertension remained low. Findings in this study highlight the necessity for a more targeted strategy in addressing hypertension management.
GW35-e1371
Shiqiang Xiong, Yan Luo, Zhen Zhang, Hanxiong Liu
The Third People’s Hospital of Chengdu
OBJECTIVES Insulin resistance (IR) is associated with both the enlargement of the left atrium and the pathogenesis of atrial fibrillation (AF). However, the exact extent of this correlation and its influence on AF recurrence in individuals undergoing radiofrequency catheter ablation (RFCA) is currently unclear.
METHODS A total of 910 patients with AF who underwent RFCA were included in this analysis. IR was evaluated using the triglyceride glucose-body mass index (TyG-BMI), while the left atrium’s enlargement was assessed using the left atrium anteroposterior dimension (LAD). The association between TyG-BMI and LAD with AF recurrence was examined through the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Receiver operating characteristic curve (ROC) analysis was conducted to evaluate the predictive capabilities of TyG-BMI and LAD for outcomes. Additionally, mediation analysis was utilized to explore the indirect impact of TyG-BMI on AF recurrence mediated through LAD.
RESULTS Over a median 12-month follow-up period, 189 (20.77%) cases of AF experienced recurrence. All patients were further stratified into three groups in accordance with tertiles of the TyG-BMI index. The levels of LAD and recurrence rate were significantly higher in patients with a higher level of TyG-BMI, compared to those in the tertile 1 group. Over a median 12-month follow-up period, 189 (20.77%) cases of AF recurrence were observed. The likelihood of AF recurrence rose with elevated TyG-BMI and LAD levels. The areas under the ROC curves for TyG-BMI and LAD in predicting AF recurrence were 0.634 and 0.639, respectively. After adjusting for multiple factors, both TyG-BMI and LAD were significant predictors of AF recurrence. The risk of AF recurrence for patients in tertile 3 of TyG-BMI was 3.026 times greater (95% CI 1.903–4.811, P < 0.001) than in patients with tertile 1 group after adjusting for sex, AF type, duration of AF (≥12 months), congestive heart failure, BNP, HDL-C, HGB, and CHA2DS2-VASc score. The TyG-BMI was a significantly independent risk factor for AF recurrence whether as a continuous variable or categorical variable by tertiles (P < 0.001). Furthermore, after adjusting for potential confounding factors, the risk of AF recurrence in patients with LAD ≥40 mm was 1.713 times higher (95% CI 1.150–2.553, P < 0.008) compared to those with LAD <40 mm. Subgroup and interaction analyses reaffirmed the consistency of the main findings. Both TyG-BMI (non-linear, P = 0.302) and LAD (non-linear, P = 0.001) demonstrated a positive dose-response relationship with AF recurrence, as depicted by the RCS curves. The results of Kaplan-Meier analysis showed a significantly increased risk of AF recurrence in patients belonging to the third tertile of TyG-BMI when compared to the remaining groups. The cumulative incidence of AF recurrence was markedly higher in patients with LAD ≥40 mm than in those with LAD <40 mm. Notably, LAD partly mediated the association between TyG-BMI and AF recurrence, accounting for an 19.23% proportion.
CONCLUSIONS Elevated baseline TyG-BMI and LAD were associated with a higher risk of AF recurrence in patients undergoing RFCA. Furthermore, the enlargement of the left atrium partially mediated the relationship between IR and AF recurrence. Ameliorating IR may serve as a potential upstream therapy for the comprehensive management of AF in clinical practice.
PREVENTION RESEARCH
GW35-e0174
Antian Chen, Jian Zhang, Yuhui Zhang
Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College/National Center for Cardiovascular Diseases
OBJECTIVES Cardiovascular diseases (CVD) remain a major global health challenge, particularly in older populations. The Triglyceride-Glucose (TyG) index, known for indicating insulin resistance, has emerged as a significant predictor of cardiometabolic risk.
METHODS This study enrolled participants from the China Health and Retirement Longitudinal Study (CHARLS) who had no baseline cardiovascular diseases with a 9-year follow-up. We performed adjusted Cox proportional hazards regression analyses and restricted cubic spline regression.
RESULTS From 11,847 participants in Wave 1 of the study, 4800 were included, with 55.23% females and 44.77% males. The median age was 57 years. Significant elevations were noted in BMI (23.16 in Wave 1–23.51 in Wave 3), TyG index (8.59–8.63), and TyG-BMI index (199.13–204.24) over 4 years. The study assessed the impact of 10-unit increments in these indices on CVD risk over 4 and 9 years. The TyG index showed a 10% non-significant risk increase at 4 years (HR = 1.100, 95% CI 0.965–1.254, P = 0.153) and a significant 19.2% at 9 years (HR = 1.192, 95% CI 1.081–1.315, P < 0.001). The TyG-BMI index increments correlated with a 0.5% risk increase at both time points (HR = 1.005, 95% CI 1.003–1.007, P < 0.001; HR = 1.006, 95% CI 1.004–1.007, P < 0.001). The cumulative TyG index showed an increasing trend (HR = 1.050, 95% CI 0.998–1.105, P = 0.062) and a significant 8.3% increase at 9 years (HR = 1.083, 95% CI 1.042–1.125, P < 0.001). The cumulative TyG-BMI index consistently elevated CVD risk by 0.2% (HR = 1.002, 95% CI 1.001–1.003, P < 0.001). Individuals categorized in the higher quartiles for the TyG index, TyG-BMI index, and cumulative TyG index, demonstrate a progressively higher risk of developing cardiovascular diseases. Specifically, those in Q4, representing the highest range of index values, face a greater risk when compared to their counterparts in Q1, Q2, and Q3, who have lower index values.
CONCLUSIONS TyG index, TyG-BMI index, cumulative TyG index, and cumulative TyG-BMI index were all positively related to increased risk of CVD. Individuals in the higher quartiles exhibit a significantly elevated risk compared to those in the lower quartiles.
GW35-e0285
Yajing Zhao, Peizhen Zhang
Beijing Sport University
OBJECTIVES Intermittent fasting is an eating behavior characterized by a lack of food consumption and eating periods, alternating eating windows with fasting for a specified period of time (greater than 12 hours–48 hours or more). Time-restricted eating (TRE) is a specific type of intermittent fasting regimen that alternates between eating and fasting within a 24-hour period without limiting total calorie intake. Researches have shown that TRE can impact circadian rhythms, body composition and dietary habits and neuroregulation to improve and reduce the risk of chronic metabolic disease and cardiovascular disease. This review focus on the effects of TRE on several prevalent chronic metabolic disease and provides a scientific eating recommendations for improving the dietary patterns of chronic metabolic disease populations.
METHODS Using the method of literature review, the related articles were searched in PubMed, Web of Science, GoogleScholar, CNKI and other databases. The search was conducted using the following key words: “time-restricted eating”, “metabolic diseases”, “cardiometabolic health”, “obesity.” The studies analyzed articles with outcome indicators related to chronic metabolic disease. Repeated studies and studies with low relevance were excluded. Thirty relevant articles were selected for further analysis.
RESULTS (1) TRE regimens with calorie limitation are effective in reducing body weight, body fat, and metabolic risk factors for the obese population. However, it does not offer significant advantages over other dietary regimens. (2) TRE effectively improve metabolic syndrome by reducing body weight, blood pressure, blood glucose, and low-density lipoprotein cholesterol levels in patients with metabolic syndrome. (3) TRE have multiple benefits to cardiometabolic health. Energy deficit due to shortened eating window results in weight loss, lower fasting insulin levels, decreased insulin resistance, lower blood pressure, lower triglyceride levels and markers of oxidative stress, which in turn reduces the risk of cardiovascular disease.
CONCLUSIONS TRE have shown significant potential in prompting reductions in overall calorie consumption, weight loss, and enhancements in glucose and lipid metabolism. These effects could serve as a complementary approach in the prevention of chronic metabolic disease and cardiovascular disease. Further investigation is imperative to better understand the potential benefits and broader utilization of these dietary strategies in the future.
GW35-e0594
Jamol Uzokov1,2, Alyavi Bakhromkhon1,2, Payziev Djamshid 1,2, Abdullaev Akbar1
1Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation
2Tashkent Pediatric Medical Institute
OBJECTIVES The objective of this study was to evaluate the impact of a low glycemic diet on inflammatory biomarkers in patients with coronary artery disease (CAD). The investigation aimed to determine whether dietary modifications could lead to significant changes in biomarkers associated with inflammation, thereby potentially improving clinical outcomes for CAD patients.
METHODS A randomized controlled trial was conducted with 100 patients diagnosed with CAD, aged 45–70 years, recruited from interventional cardiology department of the tertiary center. Participants were randomly assigned to either the intervention group (n = 50), which received a low glycemic diet, or the control group (n = 50), which followed a standard diet. The intervention lasted for 12 weeks. Inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were measured at baseline and at the end of the study period. Dietary adherence was monitored through weekly food diaries and periodic dietary recalls. Statistical analysis was performed using SPSS version 27.0. The primary outcome measures were the changes in CRP, IL-6, and TNF-α levels. Paired t-tests were used to compare pre- and post-intervention values within each group, and independent t-tests were employed to compare changes between the groups. A significance level of P < 0.05 was considered statistically significant.
RESULTS The intervention group demonstrated significant reductions in inflammatory biomarkers compared to the control group. Specifically, the mean CRP level decreased from 3.5 ± 0.8 mg/L to 2.1 ± 0.6 mg/L (P < 0.001), IL-6 decreased from 4.8 ± 1.2 pg/mL to 3.0 ± 1.0 pg/mL (P < 0.001), and TNF-α decreased from 5.6 ± 1.4 pg/mL to 3.7 ± 1.1 pg/mL (P < 0.001). In contrast, the control group showed no significant changes in these biomarkers: CRP (3.4 ± 0.7 mg/L–3.2 ± 0.8 mg/L, P = 0.21), IL-6 (4.7 ± 1.1 pg/mL–4.6 ± 1.2 pg/mL, P = 0.42), and TNF-α (5.5 ± 1.3 pg/mL–5.4 ± 1.4 pg/mL, P = 0.38). The between-group comparisons revealed statistically significant differences in the changes in CRP (P < 0.001), IL-6 (P < 0.001), and TNF-α (P < 0.001), favoring the intervention group.
CONCLUSIONS The findings suggest that a low glycemic diet significantly reduces inflammatory biomarkers in patients with CAD. This dietary approach may be an effective adjunctive strategy for managing inflammation in CAD patients, potentially improving their clinical outcomes. Further long-term studies are warranted to confirm these results and explore the underlying mechanisms.
GW35-e0646
Tao Liu, Weihong Jiang
Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University
OBJECTIVES The association between dietary lutein and zeaxanthin (L+Z) intake and the likelihood of developing cardiometabolic syndrome (CMS) in United States adults is not well understood. Our study aims to elucidate whether L+Z intake is associated with CMS likelihood.
METHODS Data for this cross-sectional study were sourced from the 2007–2018 National Health and Nutrition Examination Survey (NHANES). Weighted multivariable regression and subgroup analyses were conducted to estimate the independent relationship between L+Z intake and the likelihood of developing CMS. Non-linear associations were explored using restricted cubic splines.
RESULTS A total of 13,968 participants were included, with 10,285 without CMS and 3683 with CMS. The median intake of L+Z was 0.87. A significant association between L+Z intake and the likelihood of CMS was observed (Adjusted model: OR = 0.95, 95% CI: 0.93–0.98, P < 0.001). This inverse association remained stable across the quartiles, with the highest quartile demonstrating the most pronounced effect (OR = 0.79, 95% CI: 0.65–0.96, P = 0.002). An approximately linear association was found between L+Z intake and the likelihood of developing CMS (P for overall = 0.002, P for nonlinear = 0.59). Interaction tests indicated that this inverse association was modified by gender and race (P for interaction = 0.02/0.04).
CONCLUSIONS A higher L+Z intake is associated with a decreased likelihood of CMS in United States adults. Improving L+Z intake through diet is anticipated to lower the risk of CMS, particularly when considering gender and racial differences.
GW35-e0912
Yitian Chen, Zeya Li, Weihua Chen, Yu Zhao, Rongchong Huang
Beijing Friendship Hospital
OBJECTIVES Abdominal obesity is a risk factor for cardiovascular disease (CVD). The Chinese visceral adiposity index (CVAI) is a new measurement for abdominal obesity, but limited data is available on the relationship between CVAI and CVD incidence. This study aims to evaluate the association between CVAI and the occurrence of CVD among middle-aged and elderly individuals.
METHODS A total of 7697 middle-aged and elderly residents from the China Health and Retirement Longitudinal Study (CHARLS) in 2011 were recruited. The participants were divided into groups based on the quartiles of CVAI. Logistic regression analysis was used to validate the association between CVAI and CVD. Subsequently, in the follow-up cohort study from 2011 to 2018, the Kaplan-Meier curve was used to estimate the cumulative incidence of CVD. Cox regression analysis and restricted cubic spline (RCS) curves were further used to assess the relationship between CVAI and CVD events.
RESULTS There was a significant association between CVAI and CVD in the cross-sectional study in 2011. The risk increased by 1.14 (95% confidence interval [CI]: 1.08–1.26) with every 1.0 standard deviation (SD) increase in CVAI in the fully adjusted model (Model 3). Furtherly, during a follow-up period of 84 months from 2011, 946 participants (16.54%) experienced CVD events, and the CVD incidence rates for the 1st–4th quartiles of CVAI were 10.64%, 16.08%, 18.23%, and 22.64%, respectively. Model 3 showed a significant increase in CVD risk with each 1.0-SD increase in CVAI, with a hazard ratio (HR) of 1.17 (95% CI: 1.09–1.25). Compared to the 1st quartile, the HRs (95% CI) for CVD incidence in the 2nd–4th quartiles of CVAI were 1.46 (1.18–1.80), 1.48 (1.20–1.83), and 1.54 (1.25–1.91), respectively. The subgroup analysis consistently showed an association between CVAI and CVD incidence across different subgroups. Additionally, RCS curves demonstrated a dose-response relationship between CVAI and CVD risk (non-linear trend P = 0.309).
CONCLUSIONS Increased CVAI is significantly associated with CVD incidence among middle-aged and elderly individuals. The CVAI is a reliable indicator for identifying individuals at high risk of CVD and can be used for primary prevention among middle-aged and older people.
GW35-e1261
Qunyuan Wang, Zongbin Li
The Sixth Medical Center of the General Hospital of the Chinese People’s Liberation Army
OBJECTIVES Previous studies have shown a close relationship between m.149333T>C and AMS (Acute mountain sickness. Hypoxia activates the sympathetic nervous system, leading to increased blood pressure, heart rate, and peripheral vasoconstriction, all of which could exacerbate cardiovascular strain. The sympathetic nervous system is activated by this hypoxia, and sympathetic activation raises blood pressure, heart rate, and peripheral vasoconstriction, all of which might worsen cardiovascular strain. This paper aims to explore the relationship between m.14933T>C and cardiac function in both plateau and plain states.
METHODS We conducted PCR amplification and subsequent sequence analysis on 84 young Han Chinese males recruited for this study. Subsequently, we monitored ambulatory blood pressure and conducted cardiac ultrasound examinations on these volunteers, both on the plains and at altitudes exceeding 4000 m (the plateau). Clinical data were analyzed using SPSS software, and results are presented as mean ± SD, with statistical significance set at P < 0.05.
RESULTS Among the 84 volunteers, 15 were found to have m14933T>C. In the plains, ambulatory blood pressure monitoring revealed statistically significant differences in n-DBP (64.9 ± 8.7 vs. 61.1 ± 6.9, P = 0.028), nDBPL (10.7 ± 10.4 vs. 3.9 ± 8.5, P = 0.003), nSBPL (17.9 ± 16.3 vs. 10.1 ± 15.5, P = 0.038), 24h-DBP (72.7 ± 5.2 vs. 68.6 ± 5.9, P = 0.014), and d-sBP (119.1 ± 5.9 vs. 115.2 ± 7.6, P = 0.015). Ultrasound examination of the heart indicated statistically significant differences in TAPSE (19.8 ± 5.0 vs. 22.4 ± 4.7, P = 0.037) and PASP (16.1 ± 8.3 vs. 22.9 ± 11.1, P = 0.022). Ambulatory blood pressure monitoring in the plateau showed statistically significant differences in dDBPL (23.4 ± 18.9 vs. 14.2 ± 12.6, P = 0.004), dSBPL (29.3 ± 19.6 vs. 16.1 ± 14.8, P = 0.049), and d-DBP (83.8 ± 7.9 vs. 78.6 ± 8.9, P = 0.038). Ultrasound examination of the heart showed statistically significant differences in TAPSE (20.0 ± 5.0 vs. 22.3 ± 4.7, P = 0.038) and PASP (16.5 ± 8.3 vs. 22.8 ± 11.1, P = 0.041). In addition to the aforementioned findings, blood pressure indices such as dDBPL and dSBPL were lower in the plains compared to the plateau, suggesting compensatory mechanisms of the cardiovascular system in response to hypoxia, as previously observed.
CONCLUSIONS We observed that participants with the m.14933T>C mutation exhibited higher blood pressure levels compared to non-mutants, both in low-altitude plains and under hypoxic conditions. Changes in blood pressure play a critical role in cardiovascular compensatory mechanisms, and sustained hypertension is often linked to impaired left ventricular function. Additionally, individuals with the m.14933T>C mutation showed poorer right ventricular function as assessed by TAPSE and PASP, in contrast to non-mutant controls. This study suggests that m.14933T>C may represent a cardiovascular risk factor. Located within the gene sequence encoding the synthetic mitochondrial complex subunit, this mutation could potentially disrupt respiratory chain integrity. Further investigation is warranted to elucidate the underlying mechanisms.
GW35-e1349
Shifeng Qiu, Jiancheng Xiu
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
OBJECTIVES The stress–hyperglycemia ratio (SHR) was conspicuously correlated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped. The aim was to explore which indicators exerted a mediating effect in this association.
METHODS This cross-sectional study analyzed representative samples of the United States (n = 18,480; NHANES 1994–2004) populations. The associations among SHR (exposure), all cause mortality and cardiovascular mortality (outcome), and blood pressure (BP) as well as metabolic indicators (mediators) were evaluated by means of multivariate linear and logistic regression models and mediation analysis.
RESULTS Mediation analyses affirmed that SBP and serum uric acid (SUA) functioned as mediators in the association between SHR and all cause mortality [mediated effect: SBP: 0.035 (0.007, 0.017), P < 0.001; SUA: 0.016 (0.004, 0.007), P < 0.001]. In the unadjusted model, adjusted model 1, adjusted model 2, and adjusted model 3, the proportions of mediation for SBP and SUA were 26.37%, 6.25%, 4.90%, 100.00%, and 12.09%, 1.12%, 0.00%, 100.00%, respectively. The mediating effect of SBP was more prominent than that of SUA. Further mediation analysis of SBP alone disclosed the mediated effect and the mediation proportion in the unadjusted model [0.034 (0.007, 0.017), P < 0.001; 26.662%], adjusted model 1 [0.008 (0.002, 0.004), P < 0.001; 6.22%], adjusted model 2 [0.007 (0.001, 0.004), P < 0.001; 6.25%], and adjusted model 3 [0.010 (0.000, 0.007), P < 0.001; 100.00%]. Similar mediating results were observed for cardiovascular disease regarding waist and SUA. Waist and SUA served as mediators in the association between SHR and cardiovascular mortality [mediated effect: waist: 0.017 (0.005, 0.010), P < 0.001; UA: 0.018 (0.006, 0.011), P < 0.001]. Chain mediation analysis indicated that SHR influenced SUA via waist circumference and subsequently affected cardiovascular mortality.
CONCLUSIONS These findings imply that SBP and SUA mediate the correlation between SHR and all-cause mortality. SHR influenced SUA via waist circumference and subsequently affected cardiovascular mortality.
GW35-e1356
Liu Yuanyuan1, Zhang Ye2, Han Xiaofei4, Wang shuai3, Huang yuanxun1
1Wuhan University of Engineering Science
2Hubei University of Science Technology
3Hubei University
4Hubei Vocational College of Physical Education
OBJECTIVES Flavanone is a chemical substance, which has not been found in nature, The flavanones studied in this thesis are mainly a kind of black tea extract, the main component of black tea extract is tea polyphenols, most of which are flavanones. The anti-oxidation and anti-fatigue substances in black tea extract are helpful for people to further understand the composition and efficacy of black tea, the research of flavanones is of great significance to the development of a sports drink, sports tonic and health product with Chinese characteristics.
METHODS The research methods of this paper are experimental methods, 40 male SD rats, adaptive feeding for a week, before the experiment, all rats for a week of adaptive swimming exercise, once a day. Swim 15 minutes a day on days 1–2; 20 minutes a day on days 3–4; 25 minutes a day on days 5–7. After one week of adaptive feeding, the rats were randomly divided into four groups: control group (n = 10), gastric perfusion group (n = 10), exercise group (n = 10), gastric perfusion plus exercise group (n = 10). After 12 weeks, four groups of rats were subjected to an exhaustive exercise, the exhaustive time was recorded, and the criterion of exhaustion judgment was as follows: The Rats were continuously moving under the water surface, they could not float freely after 10 seconds in the water, the movement of limbs was not coordinated, and they choked water, pull out after no turn over reflex, shortness of breath, can be judged as exhaustion. After exhausting, he was put to death under anaesthesia. Take out the blood to measure each index.
RESULTS (1) The activity of Superoxide dismutase SOD: the activity of serum SOD in the exercise group was higher than that in the exercise group, and the activity of SOD in the exercise group was higher than that in the gastric perfusion group. (2) GSH-PX activity: the activity of GSH-PX in the serum of rats in the exercise group was higher than that in the exercise group. The activity of GSH-PX in the Glutathione peroxidase group was higher than that in the exercise group. (3) The level of malondialdehyde (MDA): the level of serum MDA in the exercise group was higher than that in the exercise group, and the level of MDA in the exercise group was higher than that in the exercise group. (4) Exhaustion time: the exhaustion time of rats in the exercise group was longer than that in the exercise group, and the exhaustion time of rats in the exercise group was longer than that in the exercise group.
CONCLUSIONS (1) Flavanones can increase the activity of SOD, increase the activity of GSH-PX, decrease the level of MDA, and eliminate the oxygen anion free radical produced by exercise, free machine to reduce the damage of tissue cells, in addition, flavonoids can eliminate lactic acid, thereby increasing the body’s anti-fatigue capacity. (2) Flavanones could increase the time of exhaustion and exercise ability.
CARDIAC REHABILITATION
GW35-e0019
Caiyi Jin, Kexin Wang, Zhe Wang, Weizhu Ju, Minglong Chen
Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
OBJECTIVES Exercise-based cardiac rehabilitation (CR) after atrial fibrillation (AF) ablation has been shown to be beneficial for AF patients, however, the kinesiophobia has been proved as a significant barrier to CR. The aim of the study was to investigate the perioperative risk factors of kinesiophobia, as well as its impact on postprocedural syndrome after AF ablation.
METHODS Consecutive patients with paroxysmal AF receiving ablation between January 2023 and April 2023 were included. Kinesiophobia and exercise self-efficacy was assessed by scales 48–72 hours after the ablation. Scheduled follow-up was conducted 1, 2, 3, 6 months after the procedure.
RESULTS Among 87 patients enrolled, 54 (62.1%) patients suffered from a high level of postoperative kinesiophobia. Patients with kinesiophobia were more likely to suffer from postoperative non-specific symptoms (P < 0.001) and decreased exercise tolerance (P < 0.001) during early recovery period. Anesthesia method (OR = 0.05, 95% CI 0.01–0.17) and preoperative EHRA scores (OR = 6.60, 95% CI 1.85–26.95) were important risk factors for postoperative kinesiophobia. Patients receiving their redo procedure, receiving ablation under general anesthesia and patients with lower preoperative EHRA scores had higher exercise self-efficacy (P < 0.001). After causal mediation analyses, kinesiophobia fully mediated the effects of anesthesia method on certain postoperative adverse events.
CONCLUSIONS Kinesiophobia was significantly correlated with adverse experiences during early recovery period after AF ablation. The choice of anesthesia, management of AF-related symptoms, and patient education are crucial in reducing kinesiophobia.
GW35-e0076
Ziqian Huang1, Youjia Kong2, Xueru Yang1, Xi Cao1
1School of Nursing, Sun Yat-sen University
2Department of Hematology, The First People’s Hospital of Yunnan Province
OBJECTIVES The research related to eHealth cardiac rehabilitation has developed rapidly in recent years, however, the research trends and hotspots in this field remain unclear. Our objective is to systematically review the global advances in eHealth cardiac rehabilitation and provide reference for domestic eHealth cardiac rehabilitation practice.
METHODS Searching relevant research literature of Web of Science Core Collection, PubMed and Embase from January 2004 to September 2023. Using VOSviewer software for cooperation network analysis among countries (regions), inter-author collaborations and co-cited authors. CiteSpace software was used for the visual analysis of the keywords co-occurrence, clustering, timeline distribution and burst terms were performed.
RESULTS A total of 815 papers were included, and the publication volume of eHealth cardiac rehabilitation showed an overall increasing trend. The top 3 countries in the publication volume were the United States, Australia and China, the top 5 high-frequency keywords were “cardiac rehabilitation” “cardiovascular diseases” “middle aged” “quality of life” and “heart failure”, and the top 5 high centrality keywords were “coronary artery diseases” “heart rate” “pilot projects” “follow-up studies” and “motor activity”. The top 3 clusters by scale were “medication adherence” “surveys and questionnaires” and “mobile application”. The timeline distribution suggested that clusters such as “medication adherence” “digital health” “exercise test” and “single-blinded method” were classic research directions in this field. With respect to bursting terms, the top 5 keywords were “patient compliance” “cell phone” “digital health” “motor activity” and “health behavior”.
CONCLUSIONS Research in eHealth cardiac rehabilitation focuses on coronary heart disease and heart failure, different digital health medium, exercise therapy, and patient compliance such as physical activity and medication, the population of young adults and digital health media of wearable electronic device may be research trends in the future. It is suggested that our country should enhance relevant support such as policies and network hardware, draw lessons from foreign experience, and carry out high-quality research based on China’s reality, to improve our research quality and mode transformation of domestic remote care for cardiovascular diseases.
GW35-e0158
Yongzhen Zhang1, Yaorui Ding2
1Taishan University
2Nanchang University
OBJECTIVES This study aims to investigate the mechanisms of protective effects of exercise-derived exosomes in cardiovascular disease and to evaluate their potential application in the prevention and treatment of Cardiovascular disease (CVD).
METHODS Studies published prior to April 30, 2024, were retrieved from five academic databases including PubMed, Science Direct, Web of Science, Ovid, and Wiley. keyword searches were conducted for ‘exercise, “extracellular vesicles”, “exosomes”, “cardiovascular disease”, “myocardial ischemia/reperfusion” atherosclerosis’, ‘acute myocardial infarction’, ‘heart failure’, ‘atherosclerosis’, and ‘angiogenesis’ etc. and a total of 43 papers were included for summarisation and generalisation.
RESULTS Exercise has been shown to enhance the release of exosomes, which are integral to cardiovascular protection through a variety of molecular mechanisms. These include the inhibition of cardiomyocyte apoptosis, the promotion of angiogenesis, the improvement of endothelial function, and the inhibition of myocardial fibrosis. Those Specific roles are as follows: ① miR-125b-5p targets the pro-apoptotic MAPK pathway and Caspase-3, leading to a reduction in myocardial ischemia/reperfusion (MI/R) injury and providing protection to cardiomyocytes. ② miR-122-5p upregulates fatty acid utilization in endothelial cells and promotes angiogenesis by targeting 1-acyl-glycerol-3-phosphate acyltransferase (AGPAT1), leading to increased VEGF expression and ultimately contributing to the enhancement of the heart’s blood supply and repair mechanisms. ③ miR-342-5p exerts its inhibitory effects on caspase-9 and stress-activated protein kinase (JNK2), while also downregulating the Mg2+/Mn2+ dependent phosphatase PPM1F. This leads to enhanced phosphorylation of the survival signal p-Akt in cardiomyocytes, ultimately resulting in the suppression of myocardial apoptosis, reduction of the infarct area, and improvement in ventricular ejection fraction. ④ miR-126 has been shown to regulate the PI3K/Akt signaling pathway and VEGF expression, thereby protecting endothelial cell function and promoting vascular repair and angiogenesis. It shows potential for treating cardiovascular diseases linked to endothelial dysfunction. ⑤ miR-130a has been shown to augment endothelial cell function, promote angiogenesis and repair in skeletal muscle through activation of the NF-kB signaling pathway, and hinder the advancement of myocardial fibrosis. ⑥ miR-455 demonstrates potential therapeutic efficacy in the treatment of myocardial fibrosis and heart failure by suppressing the expression of matrix metalloproteinase 9 (MMP9), thereby inhibiting myocardial fibrosis and cell uncoupling.
CONCLUSIONS The study demonstrates the significance of exercise-derived exosomes in cardiac protection, highlighting their role in modulating the protective mechanisms of the cardiovascular system through the transportation of specific miRNA molecules. These results offer valuable insights for the advancement of novel strategies for cardiac protection and set the groundwork for potential clinical implementations.
GW35-e0239
Chen Guo
Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Shaanxi, China
OBJECTIVES The referral, participation, and execution of cardiac rehabilitation in females are comparatively inadequate compared to males. However, the existence of sex differences in responses to cardiac rehabilitation remains uncertain.
METHODS PubMed, Embase, Cochrane Library, and Web of Science databases were searched until February 2024. Studies for evaluating exercise capacity, clinical outcomes, or biological characteristics in female and male participants with coronary artery disease after cardiac rehabilitation were selected, and the endpoints were assessed by random-effects meta analysis with pooled odds ratio (OR) or mean differences (MD) and 95% confidence intervals (95% CI).
RESULTS Twenty-two studies with 27,624 patients comprised of 7441 (27%) females and 20,183 (73%) males were included. Females exhibited lower peak oxygen uptake (MD −4.82, 95% CI −6.30 to −3.34, P < 0.00001), respiration exchange rate (MD −0.05, 95% CI −0.06 to −0.03, P < 0.00001), peak metabolite equivalents and changes, duration, attendance, handgrip strength, quality of life, body mass, and waist circumference compared to males after cardiac rehabilitation. Conversely, no significant differences were observed between sexes regarding all-cause death (OR 0.98, 95% CI 0.57–1.68, P = 0.95), myocardial infarction (OR 0.86, 95% CI 0.50–1.50, P = 0.60), rehospitalization, heart rate, blood pressure, and body mass index.
CONCLUSIONS Exercise capacity and quality of life in females after cardiac rehabilitation were lower than in males, however no sex-based disparities for clinical “hard outcomes”, suggested that female patients with coronary artery disease may benefit more clinically from less functional improvements after cardiac rehabilitation. (CRD42021269222).
GW35-e0408
Haoning Cui, Jian Wu
The Second Affiliated Hospital of Harbin Medical University
OBJECTIVES Return to work is a critical indicator of recovery after acute myocardial infarction (AMI), and accurate identification of patients with low return-to-work rates is critical for timely intervention. The aim of this study was to develop a machine learning (ML) model for predicting the return to work in AMI patients.
METHODS A retrospective study of data from 1473 patients was conducted using the Incidence Rate of Heart Failure After Acute Myocardial Infarction With Optimal Treatment database. Patients were randomly divided into a training cohort and a validation cohort (7:3). A total of five ML models, namely, logistic regression (LR), random forest (RF), support vector machine (SVM), eXtreme gradient boosting (XGBoost), and artificial neural network (ANN) models, were developed based on the training cohort to predict return to work. Model performance was assessed according to numerous learning metrics, including the area under the receiver operating characteristic curve (AUC), accuracy, F1-score, and Brier score.
RESULTS The ML models were constructed using 12 features, including age, occupation, income, anterior wall AMI, hypertension, fasting plasma glucose (FPG), beta-blockers, marriage, aspartate transaminase (AST), body mass index (BMI), TG (triglyceride) and phase II cardiac rehabilitation (CR). Among the five ML models, the LR model achieved the best performance, with an AUC of 0.793 (95% CI, 0.712–0.874), an accuracy of 0.719 (95% CI, 0.642–0.787), an F1 score of 0.800, and a Brier score of 0.135, and was subsequently transformed into a nomogram.
CONCLUSIONS A new return-to-work prediction model was developed based on a machine learning algorithm, which may help identify patients with low return-to-work rates and may become an effective management tool for AMI patients.
GW35-e0412
Bojian Wang1, Pengyu Cao2
1Jilin University
2Changzhou No. 2 People’s Hospital
OBJECTIVES This retrospective study aimed to explore the key factors on long-term prognosis in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI) and establish a multi-dimensional prognostic risk stratification model, that can provide a theoretical basis for the precision of cardiac rehabilitation.
METHODS This study included ACS patients who were hospitalized in the First Hospital of Jilin University from June 2020 to March 2021 and underwent PCI. Based on clinical data and angiography results, the subjects were divided into two groups: acute myocardial infarction (AMI) and unstable angina (UA). Hospitalization data, physical performance, exercise tolerance before discharge, the average number of daily steps, major adverse cardiac events (MACE), and follow-up duration of 18 months were recorded.
RESULTS Our data showed that Weight, Fasting plasma glucose (FPG), Total cholesterol, High-density lipoprotein cholesterol (HDL-C), Low-density lipoprotein cholesterol (LDL-C), White blood cell (WBC), Neutrophile granulocyte, Monocyte, Hemoglobin (Hb), Aspartate aminotransferase (AST), and Alanine aminotransferase (ALT) were significantly higher, while Age and Left ventricular ejection fraction (LVEF) were significantly lower in the AMI group compared to the UA group. WBC (OR: 4.110) and Effective average number of daily steps (ANS) (OR: 2.689) were the independent risk factors for AMI prognosis. WBC (OR: 6.257), VO2 at Anaerobic threshold (AT) (OR: 4.294), and Effective ANS (OR: 4.097) were the independent risk factors for UA prognosis. The total prognostic risk assessment score for AMI is 5 points, with 0 points being low risk, 2–3 points being intermediate risk, and 5 being high risk. The total prognostic risk assessment score for UA is 7 points, with 0–3 being low risk, 4–5 being intermediate risk, and 7 being high risk.
CONCLUSIONS The inflammatory response after onset, physical function and exercise tolerance before discharge, and the average number of daily steps within six months after PCI jointly determine the long-term prognosis in ACS patients.
GW35-e0731
Manyan Wu1, Yefa Liu1, Xiaomian Fan2, Rongjing Ding2, Junxian Song1
1Peking University People’s Hospital
2Peking Union Medical College Hospital
OBJECTIVES The aim of this study is to explore the effects of internet-managed, home-based moderate-intensity aerobic training on cardiopulmonary function, ventricular remodeling and mental health in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI.
METHODS From December 2021 to October 2022, 59 patients with STEMI who were admitted to the Cardiology Department of Peking University People’s Hospital and underwent primary PCI were selected. They were randomly divided into an experimental group of 30 patients and a control group of 29 patients. Both groups received the same in-hospital rehabilitation during their postoperative hospital stay. After discharge, the control group received conventional secondary prevention guidance for coronary heart disease, while the experimental group received an internet-managed, home-based aerobic exercise intervention on top of the control group’s regimen. The exercise prescriptions in the rehabilitation model were based on the anaerobic threshold heart rate determined by cardiopulmonary exercise testing. The cardiopulmonary function, ventricular remodeling, and mental health of the two groups were compared at baseline and at a three-month follow-up.
RESULTS A total of 53 patients completed the follow-up, with 25 in the experimental group and 28 in the control group. At baseline, there were no significant differences between the groups in clinical data, cardiopulmonary function parameters, left ventricular remodeling indices, or scores on the Generalized Anxiety Disorder 7-item scale (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9) (P > 0.05). At the three-month follow-up, the experimental group showed significant improvements over baseline in peak oxygen uptake (Peak VO2), anaerobic threshold oxygen uptake (AT VO2), and exercise duration, and these measures were also superior to those in the control group (P < 0.05). Conversely, only the exercise duration increased in the control group compared to baseline. Compared to baseline, at three months, the experimental group exhibited a significant increase in left ventricular ejection fraction (LVEF) (P < 0.01) and a significant decrease in overall longitudinal strain (GLS) (P < 0.01), with no notable changes in the control group; furthermore, the increases in LVEF and the reductions in left ventricular end-diastolic volume index (LVEDVi) and GLS in the experimental group were significantly greater than in the control group (P < 0.05). Compared to baseline, the scores on the GAD-7 and PHQ-9 significantly decreased in both groups at 3 months (P < 0.05), but the decrease in the GAD-7 score was significantly more pronounced in the experimental group than in the control group (P < 0.05).
CONCLUSIONS Internet-managed, home-based moderate-intensity aerobic training can significantly improve cardiopulmonary function, left ventricular remodeling, and mental health three months post-discharge in patients with STEMI following primary PCI.
GW35-e0809
Haoning Cui, Jian Wu
The Second Affiliated Hospital of Harbin Medical University
OBJECTIVES Currently, non-exercise prediction equations for oxygen uptake in patients with cardiovascular diseases are primarily based on cardiopulmonary exercise test data from international cohorts, which may not be entirely applicable to Chinese patients. Moreover, compared to peak oxygen uptake, anaerobic threshold oxygen uptake may hold more significant clinical relevance for patients with acute myocardial infarction. The aim of this study is to establish a non-exercise prediction equation for anaerobic threshold oxygen uptake for Chinese patients with acute myocardial infarction.
METHODS Cardiopulmonary exercise test data were collected from 2612 patients with acute myocardial infarction treated at the Second Affiliated Hospital of Harbin Medical University from July 2017 to June 2024. The cohort was divided into a development cohort (n = 2090) and a validation cohort (n = 522). In the development cohort, a predictive model was established using regression analysis. This model was then validated and subjected to consistency analysis in the validation cohort. It was also compared with the widely used Wasserman equation and a non-exercise prediction equation for oxygen uptake in cardiovascular patients, established based on the FRIEND database.
RESULTS Age, gender, and weight are significant predictors of anaerobic threshold oxygen uptake. The regression equation is: Anaerobic Threshold VO2 (L/min) = 0.602892 − (0.004309 × Age [years]) − (0.146860 × Gender [Male = 0; Female = 1]) + (0.005983 × Weight [kg]). The adjusted R-squared = 0.4698; Standard Error = 0.1491 L/min. This equation performs better in the population of Chinese patients with acute myocardial infarction compared to the Wasserman equation and the non-exercise prediction equation for oxygen uptake in cardiovascular patients established based on the FRIEND database.
CONCLUSIONS This study established a non-exercise prediction equation for anaerobic threshold oxygen uptake in patients with acute myocardial infarction based on the Chinese population, which is more applicable to the Chinese population compared to non-exercise prediction equations developed based on international cohorts. The equation developed through this study can better guide the exercise prescription for cardiac rehabilitation in patients with acute myocardial infarction.
GW35-e0811
Zixin Chen1, Baiyang You1,2, Jie Zhang1, Jie Dong1, Yuqiong Long1, Wenliang Zhang1,2, Yang Du2,3, Yaoshan Dun1,2, Suixin Liu1,2
1Division of Cardiac Rehabilitation, Department of Physical Medicine & Rehabilitation, Xiangya Hospital of Central South University
2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University
3Department of Neurology, Xiangya Hospital, Central South University
OBJECTIVES The prevalence of sarcopenia increases significantly among older patients with cardiovascular disease. While exercise is a cornerstone of cardiac rehabilitation, it has also emerged as a crucial intervention for improving sarcopenia. The optimal exercise regimen for mitigating sarcopenia remains uncertain. Our previous studies demonstrated high-intensity interval training (HIIT) within cardiac rehabilitation increased body lean mass in older patients with myocardial infarction. This study aimed to investigate the efficacy of HIIT over moderate-intensity continuous training (MICT) in ameliorating sarcopenia.
METHODS We conducted a randomized crossover trial to evaluate plasma proteomic reactions to acute HIIT (four 4-minute high-intensity intervals at 70% maximal capacity alternating with 4-minutes at 30%) versus MICT (constant 50% maximal capacity) in inactive male adults. Further, we explored the relationship between a HIIT-specific protein relative to MICT, eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1), identified via comparative proteomic analysis, and sarcopenia (per the 2019 AWGS standards) in a paired case-control study of elderly individuals (aged over 65). Finally, young (three months old) and aged (20 months old) mice were randomized to sedentary, HIIT, and MICT groups (five sessions/week for four weeks; n = 8 for each group). Measurements included skeletal muscle index, hand grip strength, expression of atrophic markers Atrogin1 and MuRF1, and differentiation markers MyoD, Myogenin, and MyHC-II via western blotting. We examined the impact of EEF1E1 siRNA and recombinant protein on D-galactose-induced myoblasts senescence, measuring senescence-associated β-galactosidase and markers like p21 and p53. Analyses were conducted using ANOVA with Bonferroni multiple comparison test.
RESULTS The crossover trial, including ten sedentary adults (32 yrs old, IQR 31–32) demonstrated significant alterations in the abundance of 21 plasma proteins after HIIT compared with MICT. In the paired case-control study of 84 older adults (84 yrs old, IQR 69–81; 52% female), EEF1E1 was significantly increased in those with sarcopenia compared to those without (14.68 [95% CI, 2.02–27.34] pg/mL, P = 0.03), and was associated with skeletal muscle index (R2 = 0.51, P < 0.001) and hand grip strength (R2 = 0.54, P < 0.001). In the preclinical study, aged mice exhibited higher EEF1E1 mRNA and protein levels in skeletal muscle compared to young mice, accompanied by a lower muscle mass and strength, increased cellular senescence and protein degradation markers, and reduced muscle differentiation efficiency (all P < 0.05). HIIT reduced EEF1E1 expression and mitigated age-related muscle decline and atrophy in aged mice more effectively than MICT. Notably, EEF1E1 downregulation via siRNA significantly counteracted D-galactose-induced myoblasts senescence as evidenced by reduced markers of muscle protein degradation and improved muscle differentiation efficiency (all P < 0.05). Conversely, treatments that increased EEF1E1 levels accelerated the senescence process (all P < 0.05).
CONCLUSIONS This study highlights the potential of HIIT as a promising therapeutic approach to mitigate sarcopenia within cardiac rehabilitation programs. Moreover, EEF1E1 appears to be a potential marker of sarcopenia and intervention target.
GW35-e0815
Xingbo Mu
General Hospital of Northern Theater Command
OBJECTIVES The COVID-19 pandemic has potentially impacted the treatment and rehabilitation of patients with coronary heart disease, particularly those with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study aims to evaluate the impact of the COVID-19 pandemic on cardiopulmonary exercise test outcomes in patients with ACS who underwent PCI. Additionally, we aim to identify predictors of cardiopulmonary function decline in this patient population.
METHODS This cross-sectional study included 4941 ACS patients who underwent PCI at the Northern Theater General Hospital from July 2018 to July 2023. Patients were divided into pre-pandemic, pandemic, and post-pandemic groups based on the COVID-19 pandemic timeline, with January 2020 and February 2023 as cut-off points. We collected patients’ demographic information, personal history, past medical history, laboratory test results, ultrasound findings, clinical assessments, and diagnostic results. Propensity score matching was used to match baseline data of patients in the three groups at a 1:1:1 ratio, with 631 patients in each group. Cardiopulmonary exercise testing and psychological questionnaire assessment were conducted for each patient before discharge. Cardiopulmonary exercise test results, including peak oxygen uptake, peak metabolic equivalents and other parameters, were compared among the three groups. Cardiac function was assessed using the Weber functional classification. The Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9) were used to evaluate patients’ anxiety and depression status. LASSO regression and random forest models were used to adjust for confounding factors and identify key variables affecting cardiopulmonary function. Subsequently, using Weber’s heart function classification AB/CD as the outcome variable, multivariate logistic regression was utilized to evaluate the predictive efficacy of these key variables.
RESULTS The study found significant declines in cardiopulmonary function during the pandemic. The peak oxygen uptake per kilogram (14.89 ± 3.85 mL/min · kg−1) in patients during the pandemic was significantly lower than in pre-pandemic patients (15.84 ± 3.64 mL/min · kg−1, P < 0.05). However, there was no significant difference compared to post-pandemic patients (15.29 ± 4.18 mL/min · kg−1). LASSO regression and random forest models identified 13 key variables: age, sex, smoking, BMI, LEVF, hs-CRP, serum HDL-cholesterol level, maximum voluntary ventilation, forced vital capacity, length of stay, history of myocardial infarction, ACS type, and PHQ-9 score. Multivariate logistic regression analysis indicated that advanced age, female, smoking, poor psychological assessment results, high BMI, severe ACS type, and history of myocardial infarction were associated with poor cardiopulmonary function.
CONCLUSIONS The COVID-19 pandemic adversely affected the cardiopulmonary function of ACS patients after PCI. The impact of increased psychological stress on patients’ cardiopulmonary function should be given attention. This study highlights the need for optimized cardiovascular disease management strategies, particularly during global health crises.
GW35-e0855
Yushan Li, Qiang Ren, Kai Xu, Jian Zhang, Yanchun Liang, Quanyu Zhang, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES The first phase of the ENERGY study showed that moderate-intensity continuous training (MICT) had a positive effect on the cardiopulmonary function and physical capacity of patients after transcatheter aortic valve replacement (TAVR). However, the long-term efficacy and safety of MICT in patients after TAVR are still unclear.
METHODS A total of 66 patients enrolled in the ENERGY study were extended training to 12 months. Patients in the MICT group were scheduled 3 times per week for 12 months in the intervention group. Patients in the control group received one-time advice on physical activity according to the current guideline. Efficacy and Safety of MICT was assessed using the 12-month change in cardiopulmonary exercise testing (CPET) parameters, 6-min walk distance (6MWD), the 12-Item Short Form Health Survey (SF-12), New York Heart Association (NYHA) class, echocardiographic parameters, and laboratory parameters.
RESULTS After 12 months, the change in peak VO2 (1.58 mL/kg/min, 95% CI 0.08–3.09, P = 0.040), peak MET (0.56, 95% CI 0.20–0.93, P = 0.003), VO2AT (1.55 mL/kg/min, 95% CI 0.80–2.30, P < 0.001), METAT (0.35, 95% CI 0.10–0.61, P = 0.007), 6MWD (21.24 m, 95% CI 7.10–35.39, P = 0.004), and mental component summary of SF-12 (10.47, 95% CI 0.48–20.45, P = 0.040) were higher in the MICT group compared with the control group.
CONCLUSIONS Long-term adherence to 12-month MICT is safe and effective for patients after TAVR.
GW35-e0919
Xiaofan Yu, Likun Ma
The First Affiliated Hospital of University of Science and Technology of China
OBJECTIVES To maximize adherence to prescribed treatment and lifestyle, coronary heart disease (CHD) patients should be closely followed up after percutaneous coronary intervention (PCI). Concerning the spatial accessibility of patients, telemedical interventional management may improve better patient care by providing closer follow-up than usual care. However, their impact on clinical outcomes, such as recurrent cardiovascular events and bleeding events, has not been fully elucidated. This study was aimed to determine whether remote patient management directed by health professionals during secondary prevention would reduce clinical outcomes in CHD patients after PCI.
METHODS In this investigator-initiated, open-label, randomized controlled trial, 2086 CHD patients aged between 18 and 79 (including 18 and 79) who had received PCI in The First Affiliated Hospital of University of Science and Technology of China between December 2022 and June 2023 were randomly assigned to the remote patient management (n = 1040) or usual care (n = 1046) group. The usual care group received follow-up calls by healthcare providers at 1, 3, 6, and 12 months after hospital discharge. The remote patient management group received multicomponent interventions delivered on a web-based platform in addition to usual care. The primary outcome was a composite of major adverse cardiac or cerebral events (MACCE, a composite of cardiac death, recurrent myocardial infarction, ischemia-driven target vessel revascularization or stroke) within one year after discharge.
RESULTS During the 1-year follow-up, 55 participants were found with MACCE (5.3%) in the usual care group while 36 MACCE (3.5%) in the remote patient management group. The difference was significant between the two groups (P = 0.044). This significance was mainly a consequence of reduction in cardiac death (1.0% vs. 2.3%, P = 0.017) and myocardial infarction (0.8% vs. 1.8%, P = 0.034) in the remote patient management group compared to the usual care group. Remote patient management was also associated with positive influence on blood-pressure, current drinking (11.7% vs. 16.5%, P = 0.002), adherence rates for heparin (87.8% vs. 84.4%, P = 0.027), angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker/angiotensin receptor neprilysin inhibitor (47.9% vs. 43.5%, P = 0.045) and also BARC 3–5 bleeding events (0.6% vs. 1.6%, P = 0.033).
CONCLUSIONS A well-designed telemedical interventional management package could significantly reduce the risk of cardiovascular death or myocardial infarction in the secondary prevention among CHD patients. Further multicenter and randomized studies are warranted to assess the validity and efficacy of telemedical interventional management systems.
GW35-e0941
Qiang Ren, Yushan Li, Xingbo Mu, Jian Zhang, Yanchun Liang, Quanyu Zhang, Yaling Han
The General Hospital of Northern Theater Command
OBJECTIVES To optimize the Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) score system by adding cardiopulmonary function parameters to predict the risk of ischemic events in patients with coronary artery disease (CAD).
METHODS The present study retrospectively recruited patients who were admitted for CAD and underwent cardiopulmonary exercise testing (CPET) from February 2016 to December 2021. The patients were divided into three groups according to OPT-CAD score, including low risk group (0–90 points), moderate risk group (91–150 points), high risk group (≥151 points). The study endpoint was the first major adverse cardiovascular event (MACE) occurring within one year of discharge, defined as the composite endpoint of all-cause death, myocardial infarction (MI), repeat revascularization, and stroke. Multivariate Logistic regression analysis models were constructed to assess the association between the CPET parameters and MACE in patients with CAD. The area under the curve (AUC) were assessed through receiver operating characteristic (ROC) curve analysis to evaluate the predictive value of the updated model. The C-statistic was calculated and compared by De-Long’s test to evaluate whether introducing the CPET parameters into the OPT-CAD model could improve the predictive value. Additionally, to further evaluate the incremental predictive value of the CPET parameters, the categorical net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were also calculated.
RESULTS A total of 5087 patients with CAD (57.25 ± 8.84 years, 77.4% male) were enrolled. The OPT-CAD score in the present cohort, ranging from 6–159 points, including 4419 patients with low risk (0–90 points), 665 patients with moderate risk (91–150 points), and 3 patients with high risk (≥151 points). MACE occurred in 176 (3.46%) patients, including 65 (1.28%) patients with death, 45 (0.88%) patients with MI, 343 (6.74%) patients with revascularization, and 55 (1.08%) patients with stroke. In multivariate Logistic regression analysis, peak oxygen uptake in Kilograms (peak VO2/kg) and heart rate reserve (HRR) were independent correlative factors of MACE. Compare to OPT-CAD model, adding the peak VO2/kg and HRR to the OPT-CAD model in patients with CAD could contribute to an increase in AUC (0.741 vs. 0.621, P < 0.001), C-statistics (0.738 vs. 0.620, De-Long’s test P < 0.001), NRI (0.224, P < 0.001), and IDI (0.037, P < 0.001).
CONCLUSIONS Among CAD patients, the optimized model with peak VO2/kg and HRR added to OPT-CAD score system was better than original OPT-CAD score system in predicting long-term prognosis.
GW35-e1160
Yu Zhao1,2, Xue Dong1,2, Jianchao Li1,2, Rongjing Ding3
1School of Engineering Medicine, Beihang University
2Beijing Advanced Innovation Center for Biomedical Engineering, China
3Rehabilitation Department of Peking Union Medical College Hospital, Beijing, China
OBJECTIVES The effectiveness and adherence of Virtual Reality (VR) technology in cardiac rehabilitation are still vague. The aim of this study is to evaluate the effectiveness and adherence of VR technology in cardiac rehabilitation, in order to provide patients with more efficient and personalized rehabilitation plans.
METHODS Using [Virtual Reality OR VR] AND [Cardiac Rehabilitation] as the English and Chinese literature retrieval terms, comprehensively retrieve and analyzes the literature in PubMed, Web of Science, and CNKI databases. A total of 17 randomized controlled trial research articles were included.
RESULTS The main research countries in this field include China (7 papers), Brazil (2 papers), and Poland (2 papers). 16 studies conducted experimental analysis on the effectiveness of cardiac rehabilitation, and all found that there was no significant difference in the improvement of cardiovascular function between VR based rehabilitation and conventional rehabilitation. However, VR based rehabilitation has significant advantages in improving quality of life and decreasing anxiety, depression, etc. Four studies compared the adherence of two modes, among which three found that VR based cardiac rehabilitation provided better adherence. The evaluation of the effectiveness of cardiac rehabilitation based on VR technology is mainly carried out through the following parameters, including: (1) Cardiopulmonary function parameters (9 articles): metabolic equivalent (METS), 6-minute walking test, heart rate systolic pressure product (RPP), heart rate variability (HRR), etc. (2) Quality of Life, Anxiety and Stress Parameters (9 articles): Emotional Stress Score, Hospital Anxiety and Depression Scale (HADS score), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Hamilton Anxiety Scale (HAMA index), etc. (3) Blood evaluation parameters (3 articles): left ventricular end diastolic diameter (LVEDD) and serum heart type fatty acid binding protein (H-FABP), N-terminal brain natriuretic peptide precursor (NT-proBNP); lactate dehydrogenase (LDH), aspartate aminotransferase (AST), serum creatine kinase (CK), etc.
CONCLUSIONS Literature research has found that VR based cardiac rehabilitation interventions have significant advantages in improving the quality of life and satisfaction of cardiovascular patients, reducing anxiety and depression, and improving rehabilitation compliance. They are an important and effective supplement to routine cardiac rehabilitation. In the future, VR based rehabilitation models need to be standardized and personalized, and more large scale sample size, multi-center randomized controlled trials need to be conducted.
GW35-e1163
Xue Dong1,2, Yu Zhao1,2, Chunjing Tao1,2, Jianchao Li1,2
1School of Engineering Medicine, Beihang University
2Beijing Advanced Innovation Center for Biomedical Engineering, China
OBJECTIVES Elderly female patients (aged 65 and above) have a heavy disease burden, a high incidence rate, unique rehabilitation barriers, and urgent mental health issues that need to be addressed. The aim of this study is to review the latest progress in the field of cardiac rehabilitation for elderly female in recent years, in order to explore its specificity, challenges, and effective strategies.
METHODS This study retrieved English and Chinese literature from PubMed, Web of Science, CNKI, and Wanfang databases from the inception of database until July 1, 2024. The retrieval formula is: “woman AND elderly AND cardiovascular diseases AND cardiovascular rehabilitation”. A total of 19 articles were included, with a total population of 16,375.
RESULTS The main research countries or regions include Europe, China, Japan, Canada, and the United States, etc. The main content includes: (1) Cardiovascular risk factors (7 articles): 5 articles discussed that female patients have higher obesity rate, prevalence of diabetes, unique gynecological and obstetric history and other risk factors, which lead to increased cardiovascular risk and insufficient control of risk factors during treatment. Two literature points out that the risk of malnutrition in the elderly increases both the incidence and mortality rates. (2) Rehabilitation Exercise (14 articles): The participation rate of elderly female in CR treatment is relatively low, leading to long rehabilitation time and low completion rate, especially in impoverished or rural areas. This may be related to poor adherence and weaker physical strength of elderly female, making it difficult to complete high-intensity rehabilitation training. Five studies have shown that female are more inclined to participate in low-intensity, highly repetitive exercise. Supervised, targeted training, and intelligent device assistance can significantly improve the physical function, cardiovascular adaptability, ineffective ventilation, exercise tolerance, and quality of life of this population. (3) Psychological stress and quality of life (6 articles): Four studies have indicated gender and age differences in the improvement of psychological health and quality of life in patients after CR treatment. Elderly female patients generally have higher psychological pressure and a higher tendency towards disability and depression compared to male, which is related to their physiological characteristics, social roles, and disease cognition. Two studies have pointed out that providing social and psychological support and promoting disease knowledge to these patients is beneficial for enhancing their mental health and improving their quality of life.
CONCLUSIONS Based on the special characteristics of elderly and female in terms of cardiovascular risk factors, rehabilitation exercise, and psychological stress, personalized risk factor management strategies and rehabilitation programs should be developed, and social psychological support should be strengthened, such as supervised training and providing additional psychological treatment, in order to reduce gender age differences, improve rehabilitation effectiveness and quality of life. Exploring the mechanisms and influencing factors of rehabilitation benefits for elderly female in depth, as well as providing precise guidance for clinical practice, is an inevitable trend in the rehabilitation of elderly female.
GW35-e1165
Linyi Liu1,2, Xue Dong1,2, Yu Zhao1,2, Jianchao Li1,2
1School of Engineering Medicine, Beihang University
2Beijing Advanced Innovation Center for Biomedical Engineering, China
OBJECTIVES Quitting smoking involves repeated interventions, and due to severe withdrawal symptoms and high risk of relapse, multiple attempts are often necessary. Therefore, it is crucial to provide smokers with effective intervention methods and services. This study aims to summarize the review literature on digital smoking cessation in recent years, and analyze the effectiveness and development direction of digital smoking cessation.
METHODS This study systematically searched PubMed, The Lancet, Cochrane Library, Web of Science and other authoritative databases, and collected systematic reviews and meta-analyses on digital smoking cessation technology from 2010 to 2024. The search strategy was: “(Smoking cessation OR Tobacco Cessation OR Cigarette Quitting) AND (Smartphone applications OR APP OR Internet OR Mobile OR mHealth) AND Review”. Through literature screening and data extraction, a total of 12 eligible studies involving 163,541 participants were included.
RESULTS The main countries and regions involved in the research include Europe (6 articles), the United States (2 articles), China (3 articles), and LMICs countries defined by the World Bank (1 article). (1) Effectiveness of digital smoking cessation: Nine items explored the effectiveness of digital smoking cessation. The results showed that in seven of the studies, the smoking cessation rate in the experimental group (using a certain or mixed digital smoking cessation intervention) significantly decreased compared to the control group (such as only receiving evaluation or receiving parallel interventions unrelated to smoking cessation). (2) Individual differences: The research on individual differences mainly includes two aspects: different states of patients or different intervention methods. The research on different states of patients includes mental illness (2 articles), low-income population (2 articles), pregnant women (1 article), and retired military personnel (1 article). The results show that mental stress such as anxiety, depression, and postpartum and post-war syndromes often lead to higher smoking rates, while showing higher dropout rates and lower smoking cessation rates during the process of quitting smoking, with smaller RR values and 95% Cl ranges. Regarding different intervention methods, five studies compared the differences in intervention channels such as mobile phone text messages, mobile applications, and online games, of which three studies showed no significant differences between the experimental groups. In two studies, there were significant differences in the results of using text messages and mobile applications.
CONCLUSIONS This study reveals the significant effectiveness of digital smoking cessation technology in improving the success rate of smoking cessation, which can provide support for the promotion of digital smoking cessation in areas such as cardiac rehabilitation prescription and public health. However, there are still shortcomings in existing research, and researches on individual differences have not yet intertwined in two directions. Using artificial intelligence for medical big data analysis should be an important development path.
GW35-e1216
Zhongxing Zhou, Dajun Chai
The First Affiliated Hospital of Fujian Medical University
OBJECTIVES Exercise protects against cardiovascular disease injuries, involving multiple mechanisms. Histone lactylation has recently been described as a novel post-translational modification of histones that links cellular metabolism with epigenetic regulation. Therefore, we aimed to determine whether histone lactylation is involved in exercise-reducing heart damage after myocardial infarction.
METHODS We used a treadmill exercise mouse model and performed anterior descending coronary artery ligation with ventilator-assisted breathing to determine the effect of exercise on reducing pathological damage after myocardial infarction. Single-cell sequencing and flow cytometry, immunofluorescence to determine macrophage polarization, immunoblotting and immunofluorescence to determine histone lactylation, Cut & Tag to identify enrichment of target genes (Arg1, IL-10, and Vegf-a), magnetic bead sorting of macrophages, The increased modification and expression levels of these target genes post-MI were verified by chromatin immunoprecipitation-qPCR and reverse transcription-qPCR.
RESULTS We first confirmed that exercise can induce physiological myocardial growth. Manifested as an increase in mitochondrial density, myocardial cell area, and vascular density, but without an increase in myocardial fibrosis or a decrease in cardiac function. We demonstrated that exercise can effectively prevent myocardial infarction injuries, and improve heart function, and measurement through echocardiographic and hemodynamic evaluation, specifically by reducing fibrosis and apoptosis. Exercise can facilitate M2 polarization, activation repair, and anti-inflammatory and pro-angiogenic genes in macrophages after myocardial infarction. Mechanistically, exercise can enhance glucose metabolism. 18F-FDG myocardial perfusion imaging suggests that exercise promotes a significant increase in myocardial glucose uptake ability and increase lactate production in the infarcted area. The lactate microenvironment induces macrophages to undergo histone H3K18 lactylation through GCN5, promoting downstream Arg1, IL-10, and Vegf-a gene expression, reducing post-myocardial infarction injury, and promoting repair effects.
CONCLUSIONS Lactate promotes M2-like polarization of macrophages through histone H3K18La lactylation, favoring a repair microenvironment which is essential in reducing cardiac injury and improving cardiac function after myocardial infarction through exercise.
GW35-e1237
Yuanyuan Wang
Second Hospital of Lanzhou University, Lanzhou, Gansu
OBJECTIVES Shared decision-making is a patient-centered clinical medical execution process that combines knowledge, communication, and respect. Its purpose is to enable healthcare professionals and patients to jointly enjoy the best empirical medical outcomes before making medical decision. Shared decision-making at home and abroad is of great significance for the long-term prognosis of patients with atrial fibrillation after catheter ablation. Improving the understanding of shared decision-making can help improve the treatment compliance of patients with atrial fibrillation after surgery, thereby improving their health outcomes.
METHODS Retrieve relevant literature on the application of shared decision-making in postoperative patients with atrial fibrillation both domestically and internationally. Introduce the attitudes, influencing factors, and practical application strategies of patients and medical staff participating in shared decision-making before and after home exercise rehabilitation therapy for atrial fibrillation patients undergoing catheter ablation.
RESULTS Relevant evidence shows that shared decision-making helps to increase disease awareness and treatment compliance, reduce decision regret and conflict, and improve patient health outcomes.
CONCLUSIONS Shared decision-making has reached international consensus and received widespread support. Currently, there is little research on shared decision-making in the field of cardiac rehabilitation treatment for AF patients in China, and there is a lack of localized and specialized auxiliary tools, as well as the development of corresponding core competency standards and responsibility norms. Further research and development are needed.
GW35-e1276
Chuang Zhang
Department of Cardiology, The Sixth Medical Center of PLA General Hospital
OBJECTIVES With the rapid development of interventional catheterization in recent years, the number of myocardial revascularization procedures using coronary angioplasty in patients with coronary artery disease has increased dramatically. However, 20–40% of patients still suffer from recurrent angina symptoms during the follow-up after successful percutaneous coronary intervention (PCI). At present, effective interventions for post-PCI angina are still lacking at home and abroad. Though several national and international clinical guidelines recommend patients to participate in exercise rehabilitation after PCI as Class IA, however, the implementation of exercise rehabilitation is always limited by the patient’s clinical symptoms, further seriously increasing the burden on families and society. In recent years, stress myocardial computed tomography perfusion (CTP) has gained increasing recognition as an imaging method which combines both anatomical and functional assessment in a single modality. This study proposes to use CTP categorize patients’ levels of microcirculatory disturbance and utilize it as a guide to personalize their exercise rehabilitation.
METHODS It was a prospective non-randomized intervention trial study including a total of 121 CHD patients after successful PCI between September, 2017 and December, 2020. Patients were assigned to two groups: the myocardial perfusion rehabilitation group (experimental group, n = 47) and the conventional rehabilitation group (control group, n = 74). Based on the cardiopulmonary exercise test data and the clinical data of the patients, the half quantitative index of transmural perfusion ratio (TPR) was used to grade the microcirculation disorder, so as to adjust the exercise intensity program of the patients. We use the VO2max to monitor and evaluation, the change in the VO2max was analyzed by paired t-test among the matched cohort.
RESULTS We found no significant difference in VO2max between different exercise intensity groups in each group. The comparison between the medium-low risk group in myocardial perfusion group and the high-risk group in conventional rehabilitation group shows that: After evaluation by myocardial perfusion, higher intensity training was given, and VO2max increased significantly compared with the traditional rehabilitation program (1.63 ± 0.41 vs. 1.40 ± 0.26, P < 0.05).
CONCLUSIONS Through the study, we believe that for high-risk patients after PCI, myocardial perfusion scan after recurrent angina pectoris can not only further clarify the causes of angina pectoris (residual stenosis, in-stent restenosis, in-stent thrombosis, etc.), but also provide guidance for further exercise rehabilitation programs.
GW35-e1338
Jing Lu1, Guozhen Sun1,2
1School of Nursing, Nanjing Medical University
2Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University
OBJECTIVES The efficacy of exercise rehabilitation in patients with chronic heart failure depends upon their long-term adherence. Exercise adherence is the result of a combination of antecedent conditions, but it is not yet clear how the combination of factors influencing exercise adherence in CHF patients leads to different adherence outcomes. The study aims to investigate the configuration path of influencing factors of exercise adherence in CHF patients based on the Capacity, Opportunity, Motivation-Behavior (COM-B) model.
METHODS Convenience sampling was used to recruit patients with chronic heart failure from 3 tertiary-level hospitals in Nanjing, Taizhou (Jiangsu Province) and Chongqing, China, between January and May 2024. LPA was conducted to identify the different characteristic of exercise adherence in patient with CHF. Fuzzy-set qualitative comparative analysis (fsQCA) was then employed by conducting necessity and sufficiency analysis.
RESULTS In total 219 patient with CHF participated. Based on LPA results, exercise adherence in patients with CHF was categorised into low (28.3%), moderate (54.3%) and high (17.4%) adherence profiles. The necessity analysis of low and high adherence profiles indicated that the perception of benefits was necessary to cause high exercise adherence, and no single factor was necessary to cause low exercise adherence. The sufficiency analysis identified three (Integrated-driven/Opportunity-supportive/Capacity-supportive) and two distinct configuration paths (Opportunity-fear/Isolated opportunity), respectively, that result in high and low exercise adherence.
CONCLUSIONS Patients with CHF exhibit heterogeneous exercise adherence behaviours, which are influenced by multiple antecedent conditions that act synergistically to result in diverse pattern of adherence behaviours. The exercise adherence of patients with CHF demonstrates distinct preferences. It is crucial to enhance intrinsic motivation in order to improve exercise adherence in patients with CHF. Healthcare providers can give targeted interventions based on configuration pathways.
GW35-e1341
Bright Eric Ohene
Northeastern University and Beijing Anzhen Hospital
OBJECTIVES Background: “Con-Men’s syndrome /73–84” superstition; an age-related, oriental numerological “superstitious” belief, characterized by an excessive preoccupation with the fear of death or heightened fear of sickness exhibited by subjects aged 73 through 84 years. Varied modes of presentation when seeking medical attention and/or poor compliance to medical treatment among individuals with this superstitious orientation make them an interesting group to investigate especially in this advent of increasing cases of in-stent restenosis among geriatric patients. To determine the clinical facts of the existence of Con-Men’s syndrome/73–84 superstition among geriatric patients with coronary heart disease.
METHODS A cross-sectional survey of Chinese seniors undergoing repeat percutaneous coronary interventions was undertaken using the Con-Men’s Syndrome Assessment Questionnaires (CSAQ) which comprised of social-demographic information, clinical history, and 16 Likert-like scaled items. Several hypothesized categories of the 73–84 superstitious belief, specifically knowledge/cognitive, perception, behaviour, and emotion were tested. Statistical analyses were carried out using SPSS software (IBM SPSS) version 21 and interpreted on Con-Men’s syndrome perception scale (CSPs).
RESULTS Out of the total 558 participants (mean age, 68.75 ± 7.10 years), 299 (53.6%) were men and 527 (94.4%) were of the Han ethnic group. Also, 463 (83.0%) believe the factuality of 73–84, 393 (70.4%) had undergone percutaneous coronary intervention; 407 (72.9%) had a history of coronary heart disease, and 340 (60.9) had hypertension. Based on the CSPS, the mean score for QB, QC, QE, and QT were 8.63 ± 1.31, 16.78 ± 1.78, 8.43 ± 1.44, and 33.84 ± 2.92, respectively. Only 5 (0.9%) participants had ever been referred for psychological or psychiatric consultation.
CONCLUSIONS Con-Men’s syndrome/73–84 superstition is not uncommon among Chinese septuagenarians and octogenarians undergoing repeat coronary interventions. Psychiatric/psychological referrals and consultation remain low for geriatric cardiology encounters.
GW35-e1357
Liu Yuanyuan1, He Qingyong2, Han Xiaofei3, Zhou Dong2, Sun Ke4, Huang Yuanxun1
1Wuhan University of Engineering Science
2Hubei University of Science Technology
3Hubei Vocational College of Physical Education
4Hubei University
OBJECTIVES Some studies have shown that there is a close relationship between the intensity of exercise training and the production of free radicals, causes the organism tissue cell membrane structure damage as well as the organism fatigue. Epicatechin is a kind of catechin polyphenols, which has many physiological functions. At present, there are not many reports about the antioxidation of Epicatechin in China. Therefore, this paper mainly discusses the effect of epicatechin on the metabolism of free radicals in exercise rats by taking Epicatechin and swimming, this study provides some experimental basis for the later research of Epicatechin.
METHODS Forty Sprague-dawley rats were randomly divided into 4 groups: control group, Exercise Group, DMSO Group and DMSO + EC Group. The rats in each group were fed with routine diet. The Rats in the control group and the exercise group were fed with free food and water every day, while those in the DMSO group were fed with 10 mg/kg.d-1DMSO solution, DMSO + EC Group 10 mg/kg.d-1DMSO + EC solution was perfused for 12 weeks, except the blank control group, the rats in the other three groups were subjected to swimming exercise, the weight of the rats was measured once a week, and the rats in the three groups were subjected to exhaustive exercise after 12 weeks, the time of exhaustion was recorded, and the rats were killed immediately after exhaustive exercise. Blood samples were taken from the rats after decapitation. The activities of Superoxide dismutase and glutathione Peroxidase (GSH-PX) and the content of malondialdehyde (MDA) were measured. The experimental data and indexes were analyzed by mathematical statistics.
RESULTS (1) The time of exhaustive exercise in DMSO group and DMSO-epicatechin group increased significantly, and there was a significant difference between DMSO-epicatechin group and DMSO group, indicating that Epicatechin can promote the exercise ability of rats. (2) DMSO-epicatechin can significantly inhibit the increase of blood lactic acid concentration, indicating that epicatechin can effectively reduce the blood lactic acid concentration and reduce the degree of fatigue. (3) DMSO-epicatechin can effectively inhibit the decrease of serum GSH-Px activity induced by exhaustive exercise, indicating that epicatechin can enhance the activity of GSH-Px, can effectively reduce the high-intensity exercise because of the excessive free radicals on the body tissue damage. (4) The content of MDA in DMSO group and DMSO-epicatechin Group was lower than that in DMSO group, the results indicated that Epicatechin had significant inhibitory effect on MDA activity in rats.
CONCLUSIONS (1) DMSO-epicatechin prolonged the time from swimming exercise to exhaustion and had anti-fatigue effect. (2) DMSO-epicatechin could inhibit the decrease of serum creatine activity during exercise. (3) DMSO-epicatechin can inhibit the decrease of GSH-PX activity in the tissues of rats after exhaustive exercise, indicating that DMSO-epicatechin can enhance the activity of GSH-PX. (4) DMSO-epicatechin inhibited the Superoxide dismutase of SOD in serum, indicating that DMSO-epicatechin has the ability to enhance the antioxidant activity of tissues. (5) DMSO-epicatechin can inhibit the decrease of malondialdehyde, which indicates that DMSO-epicatechin can improve the antioxidation ability of organism.
CLINICAL RESEARCH ON CARDIOVASCULAR DISEASES
CORONARY HEART DISEASE
GW35-e0011
Zhenwei Wang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University
OBJECTIVES To evaluate the association between persistent lipoprotein (a) [Lp(a)] exposure levels and clinical outcomes in patients with acute myocardial infarction (AMI).
METHODS In this large prospective cohort study involving 1131 patients with AMI, the phenotype of persistent Lp(a) exposure was determined by the Lp(a) levels measured at admission and 1-year follow-up. Patients were divided into four groups by the cut-off point of Lp(a) of 300 mg/L: (1) persistent low Lp(a) (lowon admission − low1 year); (2) fortified Lp(a) (lowon admission − high1 year); (3) attenuated Lp(a) (highon admission − low1 year); and (4) persistent high Lp(a) (highon admission − high1 month 1 year). Multivariate Cox regression, subgroup analysis and sensitivity analysis were used to evaluate the risks of clinical outcomes.
RESULTS During a median follow-up of 50 months, 343 (35.70%) patients experienced major adverse cardiovascular and cerebrovascular events (MACCE) and 210 (18.70%) patients died, of which 126 patients (11.20%) died of cardiovascular disease. Compared to the persistent low Lp(a) group, persistent high Lp(a) group demonstrated the higher risks of MACCE (HRadjusted, 1.871; 95% CI: 1.474–2.374; P < 0.001), non-fatal stroke (HRadjusted, 1.647; 95% CI: 1.031–2.632; P = 0.037), unplanned revascularization (HRadjusted, 1.571; 95% CI: 1.008–2.449; P = 0.046), all-cause (HRadjusted, 1.546; 95% CI: 1.134–2.108; P = 0.006) and cardiovascular death (HRadjusted, 2.163; 95% CI: 1.405–3.331; P < 0.001), while persistent high Lp(a) group continued to have higher risks of MACCE, all-cause and cardiovascular death compared with other three groups.
CONCLUSION Persistent high Lp(a) was associated with MACCE, non-fatal stroke, unplanned revascularization, all-cause and cardiovascular death in patients with AMI.
GW35-e0012
Zhenwei Wang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University
OBJECTIVES To assess the synergistic effect of lipoprotein (a) [Lp(a)] and high-sensitivity C-reactive protein (Hs-CRP) on the risk of all-cause and cardiovascular death in patients with acute myocardial infarction (AMI).
METHODS In this large-scale cohort study, 912 patients with AMI were enrolled. Patients were divided into four groups: Group 1 [Lp(a) <30 mg/dL & Hs-CRP <2 mg/L], Group 2 [Lp(a) <30 mg/dL & Hs-CRP ≥2 mg/L], Group 3 [Lp(a) ≥30 mg/dL & Hs-CRP <2 mg/L], and Group 4 [Lp(a) ≥30 mg/dL & Hs-CRP ≥2 mg/L]. Cox regression analysis, Kaplan-Meier survival analysis and sensitivity analysis were used to evaluate the synergistic effect of Lp(a) and Hs-CRP on the risk of all-cause and cardiovascular death.
RESULTS During a median follow-up time of 38.98 months, a total of 217 patients died, of which 137 individuals died of cardiovascular disease. Multivariate Cox regression analysis showed that after adjusting for all confounders, the risk of cardiovascular death in group 4 was 2.346 and 1.878 times higher than that in group 1 and the other three groups, respectively (HR: 2.346, 95% CI: 1.054–5.220; HR: 1.878, 95% CI: 1.284–2.748), but no correlation with all-cause death risk was found. Sensitivity analysis showed that the risk of cardiovascular death in group 4 remained 3.710 and 2.433 times higher than that in group 1 and the other three groups (HR: 3.710, 95% CI: 1.466–9.392; HR: 2.433, 95% CI: 1.620–3.656), and there was also a 235.3% increased risk of cardiovascular death in group 3 compared with group 1 (HR: 3.353, 95% CI: 1.133–9.917).
CONCLUSION Lp(a) and Hs-CRP had a synergistic effect on the risk of cardiovascular death in patients with AMI, but not on the risk of all-cause death.
GW35-e0015
Zhao Jiawei, Wu Tianyu, Tan Jinfeng, Chen Yuzhu, Zhao Rui, Hou Jingbo, Dai Jiannan, Fang Chao, Yu Bo
Second Affiliated Hospital of Harbin Medical University
OBJECTIVES Non-culprit plaque progression is associated with recurrent cardiac ischemic events and worse clinical outcomes. Given that atherosclerosis is a systemic disease, the pancoronary characteristics of patients with rapid plaque progression are unknown. This study aims to identify pancoronary plaque features in patients with ST-segment elevation myocardial infarction (STEMI) with and without rapid plaque progression, focused on the patient level.
METHODS From January 2017 to July 2019, 291 patients underwent 3-vessel optical coherence tomography imaging at the time of the primary procedure and a follow-up angiography interval of 12 months. Lesion progression was characterized by a decrease in MLD ≥0.4 mm at follow-up QCA analysis.
RESULTS The final analysis included 237 patients. Overall, 308 non-culprit lesions were found in 78 STEMI patients with rapid plaque progression, and 465 non-culprit plaques were found in 159 STEMI patients without rapid plaque progression. These patients had a higher pancoronary vulnerability (CLIMA-defined high-risk plaque: 47.4% vs. 33.3%; non-culprit plaque rupture: 25.6% vs. 14.5%) and a significantly higher prevalence of other vulnerable plaque characteristics (i.e., lipid-rich plaque, cholesterol crystal, microchannels, calcification, spotty calcification, and thrombus) at baseline versus those without rapid plaque progression. Lesions with rapid progression were highly distributed at the LAD, tending to be near the bifurcation. In multivariate analysis, age ≥65 years was an independent predictor of subsequent rapid lesion progression at the patient level, whereas microchannel, spotty calcification, and cholesterol crystal were independent predictors for STEMI patients ≥65 years old.
CONCLUSION STEMI patients with subsequent rapid plaque progression had higher pancoronary vulnerability and commonly presented vulnerable plaque morphology. Aging was the only predictor of subsequent rapid plaque progression.
GW35-e0045
Linfeng Xie
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University
OBJECTIVES Although early reperfusion therapy has somewhat improved outcomes in patients with acute ST-elevation myocardial infarction (STEMI), the in-hospital mortality remains as high as 4–12%. The heart and kidney are closely linked, and both renal and cardiac function have been confirmed to be associated with the prognosis of patients with STEMI. This study intends to evaluate the prognostic value of blood urea nitrogen (BUN) to left ventricular ejection fraction (LVEF) ratio (BLR) in STEMI patients undergoing coronary intervention (PCI).
METHODS From January 2015 to January 2023, 2024 consecutive STEMI patients who underwent PCI were enrolled. The endpoint was in-hospital all-cause mortality. The predictive value of BUN, LVEF, creatinine, NT-pro-BNP, troponin, GRACE score, TIMI score and BLR were compared by receiver operating characteristic (ROC) curves. The area under the curve (AUC) of those indexes were further compared by DeLong test. The patients were divided into two groups based on the cut-off value of BLR determined by Youden index and compared the in-hospital all-cause death between the two groups. The association between BLR and in-hospital all-cause mortality was investigated by multivariable Cox regression. Considering that anterior wall myocardial infarction is an independent factor in the poor prognosis of STEMI, patients with anterior wall MI were analyzed separately.
RESULTS Totally 2024 patients were included into our study, and 50 (2.47%) patients died in hospital. The AUC of BUN, LVEF, creatinine, NT-pro-BNP, troponin, GRACE score, TIMI score and BLR were 0.783, 0.752, 0.695, 0.732, 0.626, 0.769, 0.785, and 0.844, which revealed that BLR had the highest prognostic value for in-hospital all-cause mortality. The further DeLong test showed that the predictive value of BLR was significantly higher than BUN, LVEF, creatinine, NT-proBNP, and troponin (P < 0.05) and was comparable to GRACE score and TIMI scores. The optimal cut-off value of BLR was 14.56, with a sensitivity of 72.0%, and a specificity of 81.6%. The in-hospital mortality was significantly higher in high BLR group (9.02% vs. 0.86%, P < 0.001). And after multivariable adjustment, BLR >14.56 was still independently associated with higher in-hospital mortality (HR = 3.435, 95% CI: 1.758–6.715, P < 0.001). In patients with anterior myocardial infarction, the in-hospital mortality was also significantly higher in high BLR group (11.26% vs. 0.77%, P < 0.001). And after multivariable adjustment, BLR >14.56 was still independently associated with higher in-hospital mortality (HR = 3.772, 95% CI: 1.396–10.188, P = 0.009).
CONCLUSION BLR can provide more prognostic information to identify risk groups and make therapeutic strategies than BUN or LVEF alone in STEMI patients, and the prognostic value of BLR was comparable to GRACE score and TIMI score. This easily accessible index might be promising for early risk stratification in STEMI patients and should be taken into consideration for the current risk stratification model.
GW35-e0059
Honghong Zhang1,2, Yuqi Liu1,3, Li Zheng1,4, Haijing Zhao1,2, Yue Zhu1,2, Zhengfeng Wu1,2
1Chinese PLA General Hospital
2Medical School of Chinese PLA
3Department of Cardiology & National Clinical Research Center of Geriatric Disease
4Nankai University
OBJECTIVES Acute coronary syndrome (ACS) and atrial fibrillation (AF) are common cardiovascular diseases in elderly individuals. Patients with comorbidities face increased risks of bleeding and ischemia; however, there is a lack of prognostic models for quantifying these risks in this special population. Our study aimed to develop and externally validate distinct models to predict the probability of bleeding and ischemia in elderly patients with ACS and AF.
METHODS In this retrospective cohort study, 1252 and 284 patients (≥65 years old) with ACS and AF hospitalized at the First and Sixth Medical Center of Chinese PLA General Hospital from January 2015 to December 2019 were included in the development cohort and validation cohort, respectively. All patients underwent one year of follow-up. The primary outcome was the performance of the models in predicting the probability of bleeding and ischemia, measured by the C-index, calibration curve, and clinical decision analysis (DCA).
RESULTS Among 1536 patients with comorbid ACS and AF (median age, 77 [71–83] years; 962 men [62.6%]), thromboembolic events occurred in 222 patients (14.5%), and 78 (5.1%) of the Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding events occurred. In the development cohort, the C-indexes for bleeding at 3, 6, and 12 months were 0.845 (95% CI: 0.753–0.937), 0.742 (95% CI: 0.655–0.828), and 0.737 (95% CI: 0.671–0.803), respectively. The C-indexes for ischemia were 0.777 (95% CI: 0.676–0.877), 0.755 (95% CI: 0.696–0.814), and 0.723 (95% CI: 0.683–0.764). The calibration curve and DCA indicated adequate calibration and clinical practicability. Analogous, the C-indexes varied from 0.679 (95% CI: 0.574–0.785) to 0.777 (95% CI: 0.676–0.877) in the validation cohort. Kaplan-Meier curves demonstrated significant differences (log-rank P < 0.001). Additionally, the models outperformed conventional models in C-indexes, integrated discrimination improvement, and net classification improvement.
CONCLUSION Our study provides two robust prognostic models with easily available clinical factors for predicting bleeding and ischemia in elderly patients with ACS and AF. In addition, we further developed online calculators to facilitate individualized prediction and clinical decision-making.
GW35-e0093
BuChun Zhang
Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
OBJECTIVES Coronary microvascular dysfunction (CMD) assessed by the index of microcirculatory resistance (IMR) is associated with perioperative myocardial injury (PMI). The angiography-derived index of microcirculatory resistance (caIMR) is a novel and accurate alternative of IMR. This study aims to evaluate the predictive value of caIMR on PMI in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI).
METHODS Consecutive stable CAD patients undergoing elective PCI of a single lesion were recruited. caIMR were measured before and after revascularization. Total creatine kinase-MB (CK-MB) and high sensitivity Troponin T (hsTnT) levels were measured before and within 24 hours after PCI.
RESULTS A total of 65 patients were enrolled, twenty-six patients fulfilled the diagnostic criteria of PMI. Post-PCI caIMR values in the PMI group were significantly higher than those in the control group (27.02 ± 3.70 vs. 15.91 ± 3.43U, P < 0.001). Pearson correlation analysis demonstrated that increased post-PCI caIMR values have a significant positive correlation with peak hsTnT (r = 0.803, P < 0.001) and peak CK-MB (r = 0.512, P = 0.001). Multivariate logistic regression analysis showed the post-PCI caIMR was independent predictors of PMI (OR, 1.731; 95% CI: 1.348–2.023; P < 0.001). The ROC analysis suggested that the best cutoff value of post-PCI caIMR was 25.17U to diagnose PMI (AUC = 0.951, sensitivity 88.5%, specificity 97.1%).
CONCLUSION The post-PCI caIMR can accurately predict PMI in stable CAD patients receiving elective PCI, supporting its use in clinical practice.
GW35-e0094
BuChun Zhang
Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
OBJECTIVES The stress hyperglycemia ratio (SHR) is a novel marker that reflects the true hyperglycaemic state of patients with acute myocardial infarction and is closely associated with the poor prognosis in these patients. However, the association between the SHR and vascular function in patients with acute ST-elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) remains unknown.
METHODS This was a post hoc analysis of a multicenter, prospective cohort study. In this study, patients with STEMI who underwent PCI were included, and coronary angiography data were analyzed by Quantitative coronary angiography (QCA) and quantitative flow ratio (QFR). In addition, the SHR was calculated as follows: admission glucose (mmol/L)/(1.59 × HbA1c [%] − 2.59). According to the optimal thresholds for post-PCI QFR predict adverse clinical outcomes, patients were divided into two groups: post-PCI QFR ≤0.89 group and post-PCI QFR >0.89 group. Construction of logistic regression model to explore the relationship between the SHR and post-PCI QFR.
RESULTS A total of 547 STEMI patients were included in this study. Compared with patients in the post-PCI QFR >0.89 group, the SHR was higher in the post-PCI QFR ≤0.89 group. Logistic regression model showed that after adjusting for other confounding factors, the SHR was positively correlated with the risk of post-PCI QFR ≤0.89 (OR = 2.509, 95% CI: 1.369–4.470, P = 0.003). Restricted cubic splines showed the cutoff value of SHR associated with post-PCI QFR ≤0.89 risk was 1.04.
CONCLUSION The SHR was associated with the risk of post-PCI QFR ≤0.89 in STEMI patients. The risk of post-PCI QFR ≤0.89 increased when the SHR exceeded 1.04.
GW35-e0108
Lina Cui1,2, Yibo Guo1,2, Chao Fang1,2, Bo Yu1,2
1Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
2The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
OBJECTIVES The peak incidence of cardiovascular diseases (CVD) usually occurs in the morning. This study aimed to investigate the exact distribution pattern of peak incidence of ST-segment elevation myocardial infarction (STEMI) in the Chinese population, and to explore whether it is associated with the prognosis.
METHODS This study included 7805 patients with STEMI from the multicenter, prospective AMI cohort in China, for whom had a definite time of symptom onset. In the overall population and the predefined subgroup populations, the circadian rhythms of STEMI onset were statistically analyzed. Then patients were divided into four groups based on the time of onset (6-hour interval) to assess the association of symptom onset time and major adverse cardiovascular and cerebrovascular events (MACCE) after discharge.
RESULTS The onset of STEMI had a bimodal distribution: a well-defined primary peak at 8:38 AM (95% confidence interval (CI): 7:49–9:28 AM), and a less well-defined secondary peak at 12:55 PM (95% CI: 7:39 AM–18:10 PM) (bimodal: P < 0.001). A similar bimodal circadian rhythm pattern was observed in subgroups of patients with STEMI defined with respect to day of the week, age, sex, and coronary risk factors. Notedly, the two peaks on Sunday were significantly later than other days, and the secondary peaks became clear and concentrated. In addition, no significant difference was found in MACCE among the four groups (P = 0.905).
CONCLUSION In the Chinese population, the onset of STEMI exhibited a bimodal circadian rhythm pattern, with a clear primary peak and a less clear secondary peak. One-year clinical outcomes were unrelated to the timing of STEMI onset.
GW35-e0112
Yuzhu Chen, Jiawei Zhao, Bo Yu
The Second Affiliated Hospital of Harbin Medical University
OBJECTIVES Pre-CKD, defined as the early stages of metabolic disorder affecting kidney function, is common among patients with AMI. However, the extent to which pre-CKD influences coronary plaque characteristics and the risk of adverse cardiovascular events remains unclear. The aim of this study was to investigate the impact of pre-chronic kidney disease (pre-CKD) on coronary plaque characteristics and clinical outcomes in patients with acute myocardial infarction (AMI).
METHODS This study included patients with AMI who underwent three-vessel quantitative coronary angiography and optical coherence tomography (OCT) after successful percutaneous coronary intervention (PCI). Based on the glomerular filtration rate, patients were divided into three groups: normal renal function (NRF), pre-CKD, and CKD. We performed patient-level and lesion-level analyses to compare the three groups with respect to coronary plaque characteristics and the risk of major adverse cardiovascular events (MACEs), defined as cardiac death, myocardial infarction, and unplanned revascularization related to untreated non-culprit lesions.
RESULTS Among the 883 patients, 430 (48.6%) had NRF, 376 (42.5%) had pre-CKD, and 77 (8.7%) had CKD. Significant differences were observed in the presence of vulnerable plaques on OCT. CKD patients exhibited longer non-culprit lesion lengths (70.9 mm vs. 67.8 mm and 58.4 mm, P < 0.001) and a higher prevalence of lipid-rich plaques (92.9% vs. 85.6% and 81.6%, P = 0.012), macrophages (96.4% vs. 92.0% and 88.9%, P = 0.033), layered tissue (71.4% vs. 66.6% and 57.8%, P = 0.001), and calcified plaques (73.8% vs. 68.4% and 58.9%, P < 0.001) compared to pre-CKD and NRF patients. Lipid index and lipid length increased significantly from NRF to pre-CKD to CKD patients. Minimal lumen area (MLA) decreased significantly, with the incidence of MLA <3.5 mm2 being highest in CKD patients. Although CKD patients had the highest 4-year composite incidence of cardiac death and non-culprit lesion-related MACEs, the difference was not statistically significant.
CONCLUSION Following PCI of all culprit lesions in AMI patients, non-culprit lesions in CKD and pre-CKD patients showed more vulnerable plaque characteristics compared to those in NRF patients, particularly in CKD patients. While CKD-related plaque characteristics may contribute to an increased risk of MACEs, this study did not find a statistically significant difference.
GW35-e0116
Tiantong Yu, Haokao Gao, Kun Lian, Chengxiang Li
Department of Cardiology, First Affiliated Hospital, Air Force Medical University, Xi’an 710032, Shaanxi, China
OBJECTIVES We aimed to compare the efficacy and prognosis of percutaneous coronary intervention (PCI) in complex and high-risk patients with coronary heart disease (CHD) treated with extracorporeal membrane oxygenation (ECMO) combined with intra-aortic balloon pump (IABP) assistance, and explore the application value of combined use of mechanical circulatory support devices (MCS) in complex PCI.
METHODS A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology, the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled. According to the mechanical circulatory support method, the patients were divided into ECMO+IABP group and IABP group. Clinical characteristics, angiographic features, in-hospital outcomes, and complications were collected. The intra-hospital outcomes and major adverse cardiovascular events (MACE) at one month and one year after the procedure were observed. The differences and independent risk factors between the two groups in the above indicators were analyzed.
RESULTS A total of 218 patients undergoing elective PCI were included, of which 66 patients were in the ECMO + IABP group and 152 patients were in the IABP group. The baseline characteristics of the two groups of patients were generally comparable, but the ECMO + IABP group had more complex lesion characteristics. The proportion of patients with atrial fibrillation (6.1% vs. 0.7%, P = 0.03), left main disease (43.9% vs. 27%, P = 0.018), triple vessel disease (90.9% vs. 75.5%, P = 0.009), and RCA-CTO (98.5% vs. 86.8%, P = 0.005) was higher in the ECMO + IABP group compared to the IABP group. The proportion of patients with previous PCI history was higher in the IABP group (16.7% vs. 32.9%, P = 0.014). There was no statistically significant difference in the incidence of in-hospital complications between the two groups (P > 0.05), but the incidence of IABP-related complications after PCI was higher in the ECMO + IABP group (P < 0.01). The rates of 1-month MACE (4.5% vs. 2.6%, P = 0.435) and 1-year MACE (7.6% vs. 7.9%, P > 0.999) were comparable between the two groups. Multivariate analysis showed that in-hospital cardiac arrest (OR = 7.22, 95% CI: 1.28–40.68, P = 0.025) and IABP-related hypotension (OR = 3.61, 95% CI: 1.10–11.87, P = 0.035) were independent risk factors for the occurrence of 1-year MACE.
CONCLUSION Combination use of ECMO + IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI, and achieve satisfactory long-term prognosis.
GW35-e0127
Haoyu Wu, Yiwei Cao, Lei Liang
Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi, China
OBJECTIVES Fractional flow reserve (FFR) has become the gold standard for evaluating coronary lesion-specific ischemia and coronary artery revascularization decisions. However, FFR is an invasive method that may cause possible complications of the coronary artery and requires expensive equipment, which limits its use in clinical practice. The promising noninvasive diagnostic methods, computed tomography angiography–derived FFR (CT-FFR) and quantitative flow ratio (QFR) have been proposed. The objective of this study is to evaluate the difference in diagnostic performance between CT-FFR and QFR in predicting coronary lesion-specific ischemia with FFR as the reference standard.
METHODS This study included 84 subjects (age 59.85 ± 9.36 years; 61.76% were men) with suspected or known CAD who underwent coronary CT angiography (CCTA) revealing 30%–90% stenosis in a main coronary artery (≥2.0 mm reference diameter). CT-FFR was computed based on the CCTA images. FFR and QFR were measured during invasive coronary angiography. FFR ≤0.8 was the reference standard for coronary lesion-specific ischemia.
RESULTS The diagnostic performance CT-FFR ≤0.80 for predicting coronary lesion-specific ischemia demonstrated a good diagnostic sensitivity, and specificity of 90.74%, and 94.74%, respectively, with an area under the receiver-operating characteristics curve (AUC) of 0.958 (P < 0.0001). The diagnostic performance QFR ≤0.80 for predicting coronary lesion-specific ischemia demonstrated a good diagnostic sensitivity, and specificity of 91.00%, and 89.47% respectively, with an AUC of 0.941 (P < 0.0001). However, there was no significant difference in AUC between CT-FFR ≤0.80 and QFR ≤0.80 for predicting coronary lesion-specific ischemia (P = 0.942). There was a good direct correlation of CT-FFR and FFR (Pearson’s correlation coefficient 0.835, P < 0.0001). QFR and FFR also showed a good direct correlation (Pearson’s correlation coefficient 0.804, P < 0.0001).
CONCLUSION CT-FFR and QFR has a good direct correlation with FFR, and can provide high clinical diagnostic performance for coronary lesion-specific ischemia.
GW35-e0128
Qianwen Chen1, Qingqing Gu1, Anwen Yin2, Dabei Cai1, Tingting Xiao1, Yu Wang1, Yuan Ji1, Jun Wei3, Qingjie Wang1, Ling Sun1
1Department of Cardiology, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University
2Department of Cardiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University
3Department of Cardiovascular Surgery, The Affiliated Hospital of Xuzhou Medical University
OBJECTIVES Acute myocardial infarction (AMI), the most serious type of IHD, manifests rapid onset, high morbidity and mortality. Acute kidney injury (AKI), a common secondary renal injury of AMI, brings with various short- or long-term adverse effects, such as immune dysfunction, bleeding, long hospital stay, and mortality. This study aimed to explore the association of preoperative neutrophil percentage (NEUT%) with the risk of AKI in patients with AMI having undergone coronary interventional therapy.
METHODS A single-center, retrospective and observational study was conducted. A total of 3742 hospitalized patients aged 18 years or over and diagnosed with AMI in our hospital between December 2012 to June 2021 were recruited. All enrolled patients received coronary intervention therapy during hospitalization. Collected were patients’ data about baseline demographics, initial vital signs, laboratory tests, angiographic data, and medication administration. The primary endpoint was AKI after AMI, and the secondary outcome was all-cause mortality within about 1 month after AMI. Patients with AMI were enrolled and divided into AKI group and non-AKI group. The NEUT% in the two groups was compared. The association between NEUT% with the risk of post-AMI AKI was analyzed by univariate and multivariable logistic regression. The association of NEUT% with risk of AKI was evaluated on a continuous scale with restricted cubic spline curve. Kaplan-Meier survival curve was drawn to evaluate the prognostic ability of NEUT% for short-term all-cause death following AMI.
RESULTS A total of 3001 consecutive patients were enrolled with an average age of 64.38 years. AKI occurred in 327 (10.9%) patients. The NEUT% was higher in the AKI group than in the non-AKI group ([76.65 ± 11.43]% versus [73.22 ± 11.83]%, P < 0.001). NEUT% was also identified as an independent risk factor for AKI in AMI patients after adjustment (OR = 1.021, 95% CI: 1.010–1.033, P < 0.001). Compared with those at the lowest quartile of NEUT%, the patients at quartiles 2–4 had a higher risk of AKI (P for trend = 0.003). The odds of AKI increased by 29.0% as NEUT% increased by 1 standard deviation (OR = 1.290, 95% CI: 1.087–1.531, P = 0.004) after multivariable adjustment. In the low quartile, the risk of AKI remained basically unchanged, and the OR increased gradually as NEUT% increased, with a cut-off of 76.1%. After a median of 35 days follow-up, 93 patients died. AKI patients presented a higher risk of all-cause death within 1 month after AMI (Log rank: χ2 = 51.293, P < 0.001), and patients with a larger NEUT% had a significantly worse short-term survival after AMI (Log rank: χ2 = 24.753, P < 0.001).
CONCLUSION In AMI patients, the peripheral blood NEUT% was positively associated with the odds of AKI and short-term all-cause mortality. NEUT% may provide physicians with more information about disease development and prognosis.
GW35-e0131
Wu Haoyu, Liu Yang
Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an 710068, China
OBJECTIVES To investigate the clinical effect of Gelanxinning soft capsule in patients with unstable angina pectoris and the expression of insulin-like growth factor-1 (IGF-1).
METHODS A total of 116 patients with unstable angina pectoris confirmed by coronary angiography and requiring conservative treatment were randomly divided into control group and observation group (58 patients respectively) from January 2023 to October 2023. The control group was given conventional western medicine (such as aspirin, clopidogrel, beta-blockers, nitrates and statins, etc.), and the observation group was given Gelanxinning soft capsule based on conventional western medicine, 2 capsules/time, 3 times/day. The course of treatment was 12 weeks. The clinical efficacy and serum IGF-1 level of Gelanxinning soft capsule in patients with unstable angina pectoris were observed.
RESULTS There were no significant differences in the frequency and duration of angina pectoris between the observation group and the control group before treatment (P > 0.05). The frequency and duration of angina pectoris in the observation group were lower than those in the control group after treatment (P < 0.05). There was no significant difference in high-sensitivity C-reactive protein (hs-CRP) level between the observation group and the control group before treatment (14.38 ± 1.51 mg/L vs. 13.91 ± 1.24 mg/L, P > 0.05). After treatment, the level of hs-CRP in the observation group was significantly lower than that in the control group (5.91 ± 0.64 mg/L vs. 8.32 ± 1.16 mg/L, P < 0.05). There was no significant difference in serum IGF-1 level between the observation group and the control group before treatment (52.29 ± 8.26 μg/L vs. 58.21 ± 8.12 μg/L, P > 0.05). The serum IGF-1 level in the observation group was significantly higher than that in the control group after treatment (78.01 ± 9.12 μg/L vs. 65.11 ± 9.34 μg/L, P < 0.05).
CONCLUSION Gelanxinning soft capsule can improve the clinical symptoms of patients with unstable angina pectoris and increase IGF-1.
GW35-e0150
Yachao Li
Langfang People’s Hospital
OBJECTIVES To investigate the impact of different dual antiplatelet therapy (DAPT) regimens on the prognosis of acute coronary syndrome (ACS) patients with dual high risk of ischemia and bleeding after percutaneous coronary intervention (PCI).
METHODS A retrospective analysis was conducted on 1816 ACS patients with dual high risk of ischemia and bleeding who underwent PCI treatment at a single center from January 2017 to November 2022. Patients were divided into intensive treatment group (n = 1046, ticagrelor 90 mg), routine treatment group (n = 611, clopidogrel 75 mg), and de-escalation treatment group (n = 159, ticagrelor 90 mg) based on the type and dosage of P2Y12 receptor inhibitors taken orally three months after surgery. After 3 months of treatment with mg, it was changed to clopidogrel 75 mg or ticagrelor 60 mg. All patients took DAPT, including aspirin, for a duration of ≥12 months after surgery. The definition of dual high risk was based on the criteria of the OPT-BIRISK study, with a follow-up period of 12 months after PCI. The primary endpoint is the net clinical adverse event (NACE) that occurred during follow-up, including the composite endpoint of major adverse cardiovascular and cerebrovascular events (MACCE) and TIMI major bleeding. The secondary endpoint is MACCE, which includes a composite endpoint of cardiogenic death, myocardial infarction, ischemia driven revascularization, and stroke. The primary safety endpoint is defined as major and minor bleeding events by TIMI.
RESULTS Compared with the de-escalation treatment group, the intensive treatment group reduced the incidence of NACE (6.5% vs. 12.6%, P = 0.011) and MACCE during follow-up (4.4% vs. 11.9%, P < 0.001); However, there was no statistically significant difference in the incidence of NACE and MACCE between the routine treatment group, the intensive treatment group, and the de-escalation treatment group. The risk of bleeding in the intensive treatment group was significantly higher than that in the conventional treatment group (21.1% vs. 15.3%, P = 0.003), especially in minor bleeding events (19.5% vs. 14.4%, P = 0.007). Cox regression analysis showed that there was no statistically significant difference in the incidence of NACE among the three DAPT treatment regimens mentioned above. Compared with the de-escalation treatment group, both the intensive treatment group and the routine treatment group reduced the incidence of MACCE (HR = 0.334, HR = 0.508); But compared with the conventional treatment group, the intensive treatment group increased the incidence of bleeding events (HR = 1.426), especially minor bleeding events (HR = 1.395).
CONCLUSION For ACS patients with both high risk of ischemia and bleeding, the dual antiplatelet therapy of aspirin combined with clopidogrel is primary recommended, which not only reduces the incidence of ischemic events but also does not increase the risk of bleeding events; Choosing aspirin combined with ticagrelor to enhance antiplatelet therapy may reduce the risk of ischemic events, but it increases the risk of mior bleeding events. For this type of patient, de-escalation treatment is not recommended.
GW35-e0151
Yachao Li
Langfang People’s Hospital
OBJECTIVES Dual antiplatelet therapy (DAPT) is currently a critical treatment in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). The current guidelines recommend that the duration of DAPT should be at least 12 months for patients with acute coronary syndrome (ACS) undergoing PCI, and strong P2Y12 receptor inhibitors should be prioritized. However, despite receiving standard antiplatelet therapy, patients with AMI still have a higher risk of recurrent ischemic events 1 year after hospitalization. Guidelines recommend the use of DAPT scores for evaluation of these patients but do not explicitly recommend the specific duration of extension. The PEGASUS-TIMI54 study confirmed that the extended DAPT regimen of ticagrelor combined with low-dose aspirin (aspirin <150 mg/day) can reduce major adverse cardiovascular events (MACEs) for 1–3 years in patients with stable coronary heart disease who have a history of old myocardial infarction, while not increasing non-fatal intracranial or fatal bleeding. However, patients with acute ST segment elevation myocardial infarction (STEMI) are a high-risk group among patients with ACS, and no clear evidence is currently available regarding the extension of DAPT. This study aims to discuss the impact of extending DAPT to 18–24 months on the prognosis of patients with STEMI who did not experience bleeding events at 12 months.
METHODS A retrospective investigation were conducted on 757 patients with STEMI from a single center from September 2016 to August 2020. Based on the duration of postoperative DAPT, patients were divided into a standard group (n = 326) and an extended group (n = 431). Those in the standard group received aspirin 100 mg + ticagrelor 90 mg or clopidogrel 75 mg for 12 months, after which the drug regimen was changed to aspirin 100 mg, once per day. Those in the extended group received aspirin 100 mg + ticagrelor 90 mg or clopidogrel 75 mg that was continued for 18–24 months. The duration of DAPT in all patients was ≥12 months, and the follow-up time was 12 months, 18 months, and 24 months after PCI. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during the follow-up period, including composite end points of cardiac death, myocardial infarction, ischemia-driven revascularization, and stroke. The major safety endpoint was bleeding events.
RESULTS The results showed that during follow-up, the difference in the incidence of MACCEs between the two groups (4.6% vs. 3.9%, χ2 = 0.198, P = 0.656) was not statistically significant, but the incidence of bleeding events in the standard group was significantly lower than that in the extended group (5.2% vs. 10.7%. χ2 = 7.242, P = 0.007). The Cox regression analysis showed that an increase in hemoglobin (HR = 0.978) could reduce the incidence of MACCEs, while an old myocardial infarction) (P = 0.022) was an independent predictor of MACCEs. The extension of DAPT (P = 0.003) and hypertension (P = 0.045) were independent predictors of bleeding events.
CONCLUSION For patients with STEMI undergoing PCI, continuing DAPT to 18–24 months did not reduce ischemic events but increased the incidence of bleeding events, especially minor bleeding events.
GW35-e0179
Chen Chang1,2, Qiang Wu3,4, Yanlin Ren2, Yingman Su2, Qiang Su1,2
1Department of Cardiology, Jiangbin Hospital of Guangxi Zhuang Autonomous Region
2Guilin Medical University
3Department of Cardiology, The Sixth Medical Centre, Chinese PLA General Hospital
4Journal of Geriatric Cardiology Editorial Office, Chinese PLA General Hospital
OBJECTIVES The present study investigated the potential underlying mechanism of Shexiang Tongxin Dropping Pill (STDP) against myocardial inflammation caused by coronary microembolization (CME) through network pharmacology and animal experiments.
METHODS The network pharmacology approach was utilized for PPI network analysis of common targets of STDP and CME. The hub genes were further analyzed for GO and KEGG enrichment. Key pathways were screened and molecular docking analysis of partial hub genes involved was performed. The effects of STDP on the myocardium of CME rats were evaluated using ultrasound and HE staining. Western blotting was utilized to detect the expression of TLR4, MyD88, NF-κB, phospho-NF-κB, TNF-α, and IL-1β in myocardial tissue.
RESULTS Overall, 83 targets common to STDP and CME were identified through network pharmacology, of which the hub genes were TNF, IL-6, VEGFA, PTGS2, IL-1β, MMP9, CASP3, AKT1, TLR4, and EGF, which were mainly associated with TNF, IL-17, lipids and atherosclerosis, and TLR signaling pathways (P < 0.05). Molecular docking results revealed the strong binding ability of hub genes TLR4 and TNF with corresponding active ingredients. Ultrasound and HE staining showed that STDP significantly ameliorated myocardial injury caused by CME (P < 0.05). Western blotting showed that STDP significantly inhibited the expression of TLR4, MyD88, phospho-NF-κB, TNF-α, and IL-1β (P < 0.05).
CONCLUSION STDP could alleviate CME-induced myocardial injury via inhibiting the TLR4/MyD88/NF-κB axis and decreasing inflammatory factors expression.
GW35-e0202
Qixin Guo, Xinli Li
Jiangsu Provincial People’s Hospital
OBJECTIVES Ischemic cardiomyopathy arising from myocardial infarction (MI) frequently leads to a cascade of adverse events. However, the lack of prognostically relevant predictive models for MI impedes clinical decision-making. Thus, this study sought to construct a gene-based model that can forecast the incidence of adverse cardiac events subsequent to myocardial infarction, leveraging the integration of gene expression profiles and clinical factors.
METHODS We employed a combined bioinformatics and machine learning approach to identify key genes associated with adverse prognosis following myocardial infarction. Patients admitted to Jiangsu Provincial People’s Hospital and Hangzhou First People’s Hospital between June 2021 and January 2024 were prospectively enrolled, constituting the model-building and validation cohorts, respectively. Cox regression analysis was employed to identify risk factors, which were then integrated into columnar plots. The specificity and sensitivity of the models were assessed using the C-index, calibration curves, and Receiver Operating Characteristic (ROC) curves. To evaluate the model’s performance compared to previous ones, integrated discrimination improvement (IDI) and continuous net reclassification improvement (c-NRI) were calculated. Kaplan-Meier curves were utilized for visualization, and Log-rank tests were conducted for between-group comparisons.
RESULTS A total of 291 patients were included in the model construction cohort, with an additional 100 patients forming the validation cohort for this study. In the model construction cohort, patients had an average age of 63 ± 13 years, and the majority were male (226 patients, 77.7%). Among the 55 patients who reached an endpoint event, 13 experienced cardiovascular death, 20 were readmitted due to heart failure, and 22 underwent re-intervention for chest pain. In the validation cohort, the average age was 65 ± 17 years, with a similar majority of male patients (99 patients, 77.8%). During follow-up, 25 patients encountered major adverse cardiovascular events (MACE). Through biometric analysis and machine learning, four candidate genes – FADS2, FMN1, TMEM176A, and RPS4Y1 – were identified. These genes were categorized using a spline function, revealing statistically significant differences between the groups. A prognostic model was developed based on PCR results combined with clinical factors, achieving a C-index of 0.83. This represented an improvement of at least 0.239 and 0.69 in IDI and c-NRI, respectively, compared to previous models. The internal and external validation C-indexes were 0.864 and 0.723, respectively.
CONCLUSION The prognostic model developed for myocardial infarction demonstrates robust sensitivity and specificity, alongside favorable validation results in external cohorts. Its clinical utility is substantial, providing strong guidance for clinical decision-making. Furthermore, further exploration of the function and mechanism of action of several targets identified in this study is warranted in follow-up research.
GW35-e0236
Guangshuo Zhi, Mengjie Lei, Shuang Qian, Chunyan Zhang, Yachao Li, Zhigang Zhao, Zengming Xue
Langfang People’s Hospital
OBJECTIVES With the continuous development of intervention technology, percutaneous coronary intervention (PCI) through the radial artery approach has become the preferred recommendation for coronary intervention treatment due to its advantages of small trauma, convenient bandaging, fewer complications at the puncture site, no position limitation, and less patient pain. The 2018 European Heart Association guidelines for revascularization also recommend the radial artery approach as the standard approach. At present, the proportion of transradial coronary intervention in China exceeds 80%. The most common complication is forearm hematoma. We have calculated the incidence of forearm hematoma in our ward from 2017 to 2022, and it shows a decreasing trend year by year. Now, we summarize our nursing experience of patients with forearm hematoma after transradial coronary intervention.
METHODS We have innovatively summarized the risk classification of forearm hematoma and the three key time points for preventing hematoma, providing reference for the prevention and management of forearm hematoma in clinical practice.
RESULTS On the basis of reviewing relevant literature and consulting experts, we have independently developed a grading standard for forearm hematoma, which involves multiple aspects such as hematoma range, pain grading, blisters, skin temperature, skin color, peripheral sensation, and pulse. The pain grading is based on verbal rating scale (VRS), and we have also conducted small-scale validation of this hematoma classification standard, which involves comprehensive hematoma symptoms.
CONCLUSION By identifying risk factors and mastering management measures, the incidence of forearm hematoma after intervention can be effectively reduced, and patient comfort can be improved. Meanwhile, strengthening preoperative evaluation, standardized intraoperative procedures, postoperative care, and rational drug treatment are key measures for prevention.
GW35-e0238
Mowei Kong
Ren’an Hospital
OBJECTIVES The latest drug-eluting stents (DES) reduce target lesion failure (TLF) but still pose risks like in-stent restenosis (ISR) and late stent thrombosis. Bioresorbable scaffolds (BRS) emerged to avoid long-term metalization but have shown complications, leading to some being withdrawn. A new generation of domestically produced BRS is being studied for safety, efficacy, and medium-to-long-term outcomes in treating acute myocardial infarction and other conditions.
METHODS Patients with intermediate to low-risk ACS who underwent percutaneous coronary intervention (PCI) with either drug-eluting stents (DES) or BRS, and were continuously recruited from January 2019 to June 2022 at a single center, were analyzed. Baseline data and clinical follow-up were collected for DES implantation (control group) and BRS implantation (observation group) patients, and the survival outcomes and complications during a maximum follow-up period of 3 years were compared. The primary clinical endpoint was device-oriented composite endpoint (DoCE), representing the occurrence of one of the following events: cardiac death, stent thrombosis (ScT), target vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR). Secondary endpoints included coronary artery bypass grafting, target vessel revascularization (TVR), and non-cardiac death.
RESULTS A total of 128 patients were included in this study, with a mean age of (63 ± 10) years, including 95 males (74%). There were 201 treated vessels, with 87 (43%) receiving BRS and 114 (57%) receiving DES. A total of 97 patients completed the full 3-year follow-up, and 5 patients (17%) in the observation group and 7 patients (16%) in the control group reached DoCE. At 1-year follow-up, 7 patients (15%) in the observation group and 6 patients (10%) in the control group reached DoCE, showing a statistically significant difference (P < 0.05). The number of patients with TVR in both groups showed a statistically significant difference at 2-year follow-up (P < 0.05). Eighteen patients (33%) in the observation group underwent coronary angiography re-examination. During the follow-up period, one patient in the observation group was found to have re-narrowing in the proximal and middle segments of the left anterior descending artery, suspected to be due to BRS collapse. Another patient in the observation group developed chronic occlusion of multiple vessels at the 3-year follow-up and underwent coronary artery bypass grafting.
CONCLUSION 1. In patients with intermediate to low-risk ACS, the time to reach DoCE was earlier in patients treated with BRS compared to those treated with DES, but the final number did not show significant differences. 2. In terms of compatibility testing, BRS showed stronger compatibility affinity than DES. 3. In the long-term follow-up of up to 3 years, the types and numbers of complications were similar in both groups. However, there were still individual cases of scaffold collapse and chronic coronary artery occlusion in the BRS group.
GW35-e0295
Ting Tang, Mingwei Wang
Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou
OBJECTIVES Coronary Heart Disease (CHD), primarily caused by atherosclerosis, is one of the most common cardiovascular diseases, a leading cause of cardiovascular-related deaths and chronic disabilities. Previous studies have associated CHD with an increased risk of Cognitive Impairment (CI). While past research has focused on static features of brain activity, there has been less attention on its dynamic changes. This study aims to explore the dynamic characteristics of brain activity in CHD patients using functional magnetic resonance imaging (fMRI).
METHODS Twenty-two CHD patients and 13 control subjects were included. All participants underwent fMRI scans and cognitive assessments at Affiliated Hospital of Hangzhou Normal University. Cognitive assessments were conducted using the Mini-Mental State Examination (MMSE) and the Hamilton Depression Scale (HAMD). The dynamic amplitude of low-frequency fluctuation (dALFF) was calculated for all participants using a sliding window method. A two-sample T-test was used to compare the differences in the temporal variability of dALFF between CHD patients and control subjects. Pearson’s analysis was employed to examine the correlation between participants’ dALFF values and HAMD, MMSE scores.
RESULTS The T-test revealed a significant reduction in the temporal variability of dALFF in the inferior temporal gyrus of CHD patients compared to controls (t = −3.95, GRF correction, P < 0.05). Correlation analysis showed that the temporal variability of dALFF in the inferior temporal gyrus was significantly correlated with MMSE scores (r = 0.57, P < 0.05) and HAMD scores (r = −0.40, P < 0.05) in all participants, and significantly correlated with MMSE scores in the control group (r = 0.67, P < 0.05), but not significantly correlated with the scores of CHD patients.
CONCLUSION The study found abnormalities in dynamic brain activity features in CHD patients. Analyzing the dynamic changes in the brain’s intrinsic activity provides new insights for research into CHD-related CI. However, the non-significant correlation between dALFF and the assessment scales may be due to the small sample size, necessitating the inclusion of more participants to further explore the connection between cognitive status and brain activity in CHD patients.
GW35-e0315
Wittawat Wattanasiriporn
Rajavithi Hospital
OBJECTIVES Bradycardia and heart block are most commonly occurred when performing RA. A previous retrospective cohort showed that Heart block or temporary pacing was more commonly associated with right coronary artery and left-dominant circumflex lesions. Current expert consensus on RA from Japan and Europe provide no standard of care with regard to the use of temporary pacing during these procedures.
METHODS Observational retrospective cohort, we enrolled 128 Patients who underwent rotational atherectomy at Central Chest Institute of Thailand Between 1 June 2020 to 31 June 2022 to analyse Incidence of Heart Block and Outcomes of Patients Who Underwent Rotational Atherectomy with and without Temporary pacemaker.
RESULTS A total of 128 patients were enrolled in this study. The incidence of bradycardia that required atropine or pacemaker activation are showed were 13.3% (17/128). Bradycardia is most common with RCA lesions but occur infrequently when RA is performed to the LAD or Rt dominant Lcx. MACE in 2 groups were not statistical significance.
CONCLUSION The incidence of bradycardia and temporary pacing during rotational atherectomy was very low. Bradycardia is most common with RCA lesions. The role of prophylactic temporary pacemaker should be considered with RA to the RCA and left dominant LCx artery to prevent conduction abnormalities but it is not necessary to use in the case of right dominant LCA.
GW35-e0322
Xiaoyan Bao, Yajuan Lin, Bo Zhang
The First Affiliated Hospital of Dalian Medical University
OBJECTIVES Cardiovascular disease is still one of the diseases with the highest morbidity and mortality worldwide. Increasing evidence shows that insulin resistance may be a common risk factor for diabetes and cardiovascular disease, and its indicators include metabolic score for insulin resistance (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, etc. However, few studies have explored the relationship between METS-IR and chronic coronary artery occlusion (CTO) in patients with type 2 diabetes and coronary heart disease. Therefore, this study aims to explore the association between METS-IR indicators and CTO in patients with coronary heart disease and T2DM.
METHODS This was a retrospective study. Patients who visited the First Affiliated Hospital of Dalian Medical University between January 2010 and October 2023 and were diagnosed with coronary heart disease and type 2 diabetes were collected from the electronic medical record system, and their demographic characteristics, medical history, laboratory test datas, coronary angiography and interventional data were collected; METS-IR = (Ln ((2 × FPG) + TG) × BMI)/(Ln (HDL-C)); Logistic regression was used to evaluate the relationship between METS-IR and CTO, and the OR value and 95% CI were used to express it; at the same time, stratified analysis was used to further explore the association between METS-IR and CTO in different subgroups.
RESULTS A total of 3529 patients were included in the study, of which 65.74% (n = 2320) were male, and 16.46% (n = 581) were CTO patients. Patients in the CTO group showed higher hemoglobin, neutrophil count, uric acid, creatinine, BNP, CK-MB, cTnI, left atrial diameter, METS-IR levels, and lower HDL-C and left ventricular ejection fraction levels. According to the METS-IR level, they were divided into four groups. In the Q4 group, patients had higher systolic blood pressure, glycated hemoglobin, uric acid, and TG, but lower LDL-C and TC values. The proportion of hypertension, smokers, and CTO was higher. Multivariate Logistic regression analysis showed that after correcting for multiple confounding factors (gender, age, smoking history, history of hypertension, creatinine, uric acid), it was still found that compared with patients in the Q1 group, patients in the Q4 group had a higher risk of CTO (OR (95% CI) = 1.36 (1.05, 1.770), P = 0.0221; subgroup analysis showed that in patients aged ≤65, after adjusting for multiple confounding factors, the risk of CTO increased with the increase of METS-IR (Q4 group OR (95% CI) = 1.55 (1.03, 2.31), P = 0.0344); in smoking patients, the higher the METS-IR value, the greater the risk of CTO (Q4 group OR (95% CI) = 1.78 (1.05, 3.02), P = 0.0325)); in non-hypertensive patients, the higher the METS-IR value, the greater the risk of CTO (Q4 group OR (95% CI) = 1.90 (1.10, 3.31), P = 0.0224).
CONCLUSION The above results show that in patients with coronary heart disease and type 2 diabetes, higher METS-IR values indicate a greater risk of coronary CTO, and this association also exists in patients aged ≤65 years, in smokers, and in non-hypertensive patients.
GW35-e0326
Xiaofei Gao, Junjie Zhang, Shaoliang Chen
Nanjing First Hospital, Nanjing Medical University
OBJECTIVES Drug-coated balloon (DCB) angioplasty seems a safe and effective option for specific de novo coronary lesions. However, the beneficial effect of intravascular ultrasound (IVUS)-guided DCB angioplasty in de novo lesions remains uncertain. This study aims to assess the benefits of IVUS guidance over angiography guidance during DCB angioplasty in de novo coronary lesions.
METHODS A total of 260 patients with high bleeding risk who had a de novo coronary lesion (reference vessel diameter 2.0–4.0 mm, and lesion length ≤15 mm) were randomly assigned to either IVUS-guided or angioplasty-guided DCB angioplasty group. The primary endpoint was in-segment late lumen loss (LLL) at 7 months after procedure. The secondary endpoint was target vessel failure (TVF) at 6 months, including cardiac death, target-vessel myocardial infarction, and ischemia-driven target-vessel revascularization.
RESULTS A total of 2 patients in angiography-guided group and 7 patients in IVUS-guided group underwent bailout stent implantation (P = 0.172). The primary endpoint of 7-month LLL was 0.03 ± 0.52 mm with angiography guidance versus −0.10 ± 0.34 mm with IVUS guidance (mean difference 0.14 mm, 95% CI: 0.02–0.26, P = 0.025). IVUS guidance was also associated with a larger 7-month minimal lumen diameter (2.06 ± 0.62 mm vs. 1.75 ± 0.63 mm, P < 0.001) and a smaller diameter stenosis (28.15 ± 13.88% vs. 35.83 ± 17.69%, P = 0.001) compared with angiography guidance. Five TVFs occurred at 6 months, with 4 (3.1%) in angiography-guided group and 1 (0.8%) in IVUS-guided group (P = 0.370).
CONCLUSION This study demonstrated that IVUS-guided DCB angioplasty is associated with a lower LLL in patients with a de novo coronary lesion compared with angiography guidance.
GW35-e0330
Xin Peng, Jian Liu
Peking University People’s Hospital
OBJECTIVES Based on DNA methylation level of PEAR1 gene in Chinese patients with coronary heart disease, and explore the relationship between the DNA methylation level of PEAR1 gene and the clinical prognosis of patients with coronary heart disease.
METHODS This prospective, observational study included patients who were admitted to the Department of Cardiovascular Medicine of Peking University People’s Hospital from December 2020 to August 2022 for suspected coronary heart disease to undergo coronary angiography or coronary CT. In 145 patients who received antiplatelet therapy, DNA methylation levels of PEAR1 gene cites were detected. In patients followed for more than 2 years, the primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, unstable angina pectoris, or ischemic stroke resulting in re-hospitalization, and target vessel revascularization.
RESULTS 1. Finally, 145 patients with coronary heart disease who completed PEAR1 gene DNA methylation level were included, including 41 patients in the myocardial infarction group. There were no significant differences in age, sex, smoking history, comorbidities, other clinical baseline data and other drug treatments between myocardial infarction group and non-myocardial infarction group (P > 0.05), except for statins (94.2% vs. 82.9%, P < 0.05) and proton pump inhibitor (39.4% vs. 65.9%, P < 0.05). Besides, there were significant differences in leukocyte, fibrinogen, total cholesterol, triglyceride and low-density lipoprotein-cholesterol between the two groups (P < 0.05). 2. The results of correlation analysis showed that the correlation between methylation level of CpG sites in the PEAR1 gene and coronary heart disease status showed regular change, and chr1: 156863488–156863504 was the focal region where the methylation level of CpG sites was significantly correlated with coronary heart disease status. 3. Among the 13 CpG sites in the PEAR1 gene, univariate Cox analysis showed that DNA methylation level at the CpG 5 site was significantly associated with major adverse cardiovascular events during follow-up in patients with coronary heart disease. 4. According to the results of univariate Cox regression, age, sex, methylation level at CpG 3 and CpG 5 sites, white blood cells, hemoglobin, platelets, fibrinogen, triglyceride, high density lipoprotein-cholesterol, LDL-C, hypertension, diabetes, hyperlipidemia and myocardial infarction history were included in multivariate Cox regression analysis. The results showed that the DNA methylation level at the CpG5 site was associated with increased risk of primary endpoint events (adjusted HR 1.155, 95% CI: 1.077–1.238, P < 0.001). The level of DNA methylation at CpG5 cite is associated with the risk of revascularization in target vessels (adjusted HR 1.170, 95% CI: 1.072–1.276, P = 0.0004).
CONCLUSION This study suggests that the correlation between methylation level of CpG sites in PEAR1 gene and coronary heart disease status change regularly. In addition, DNA methylation of PEAR1 gene is associated with clinical prognosis of patients with coronary heart disease, and DNA hypermethylation at CpG5 cite is an independent predictor of adverse cardiovascular events.
GW35-e0350
Houyong Zhu1, Xiaoqun Xu2, Tielong Chen1
1Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University
2Hangzhou Red Cross Hospital
OBJECTIVES The interplay between inflammatory markers and cardiovascular outcomes has been a subject of keen interest, particularly amidst the COVID-19 pandemic. This study aimed to delve into the prognostic roles of specific inflammatory markers – neutrophil-lymphocyte ratio (NLR), C-reactive protein-albumin ratio (CAR), and platelet-lymphocyte ratio (PLR) – in patients with coronary artery disease (CAD) who also faced the challenge of COVID-19.
METHODS The investigation encompassed a cohort of 265 subjects. The predictive efficacy of NLR, CAR, and PLR concerning all-cause mortality was initially gauged through a receiver operating characteristic (ROC) curve analysis. The main endpoint was in-hospital mortality from any cause, with secondary endpoints being deaths due to cardiovascular causes and respiratory failure. A Cox proportional hazard model, adjusted for confounding variables, was employed to assess the overall risk associated with the outcomes. Additional analyses were performed to examine the impact of CAD’s acute and chronic phases. The primary endpoint’s reliability was further scrutinized through propensity score matching (PSM).
RESULTS The ROC curve analysis revealed AUC values of 0.686 (95% CI: 0.592–0.781, P < 0.001) for NLR, 0.749 (95% CI: 0.667–0.832, P < 0.001) for CAR, and 0.571 (95% CI: 0.455–0.687, P = 0.232) for PLR. According to the Cox proportional hazard model, neither the NLR nor the PLR trends had a significant impact on the risk of all-cause mortality (P = 0.096 and P = 0.544 for trend, respectively). However, an elevated CAR was associated with an increased risk of all-cause mortality (P < 0.001 for trend). This pattern was mirrored for cardiovascular and respiratory failure-related deaths, with NLR and PLR showing no significant trends, yet a higher CAR indicating a greater risk for these outcomes. The findings from subgroup and PSM analyses aligned with those of the overall study group.
CONCLUSION Among patients with CAD who also contracted COVID-19, elevated CAR levels were linked to a heightened risk of mortality from all causes, as well as from cardiovascular and respiratory failure, while NLR and PLR did not exhibit such associations.
GW35-e0364
Zhulin Zhu, Xiaoli Zhou
The First Affiliated Hospital of Chongqing Medical University
OBJECTIVES Non-ST segment elevation myocardial infarction (NSTEMI) is a common type of acute coronary syndrome (ACS). Epidemiological data show that approximately 70% of ACS patients in the United States have acute NSTEMI. In China, the incidence of NSTEMI has been increasing annually, and the occurrence rate of acute NSTEMI is higher than that of STEMI. NSTEMI patients who undergo percutaneous coronary intervention (PCI) remain at a high-risk state after discharge, with recurrent or sustained myocardial ischemia and major cardiovascular events still posing a challenge. Therefore, accurate and comprehensive risk assessment, the selection of high-risk NSTEMI patients, and optimized treatment decisions are particularly important. Traditional guidelines recommend the use of the Global Registry of Acute Coronary Events (GRACE) score for risk stratification of NSTEMI patients. The GRACE score includes variables such as age, blood pressure, creatinine and so on. However, it does not cover all risk factors for myocardial infarction. Combining other relevant indicators can further improve the GRACE score and enhance its predictive ability for the prognosis of NSTEMI patients.
METHODS This study enrolled a total of 482 NSTEMI patients who underwent PCI at the First Affiliated Hospital of CQMU from September 2016 to May 2022. The PCT levels at admission were collected, and the occurrence of MACE was followed up until February 2023. The general characteristics of patients were compared between the MACE and non-MACE group. Multivariate Cox regression analyses were performed to assess whether PCT is an independent influencing factor for the occurrence of MACE in NSTEMI patients. The ROC curve was used to evaluate whether PCT can enhance the predictive ability of the GRACE score for the prognosis of NSTEMI patients. The optimal cutoff value was calculated, and PCT was divided into two groups. The log-rank test was used to compare the two groups and draw the risk function.
RESULTS During a median follow-up period of 31 months, 124 MACE events (25.7%) occurred. There were differences between the two groups in terms of age, gender, smoking history, diabetes, total cholesterol, creatinine, hypersensitive C-reactive protein (CRP), and PCT (P < 0.05). Univariate and multivariate Cox regression analysis showed that PCT was independent risk factors affecting survival time. ROC curve analysis showed that addition of PCT enhances the predictive ability of the GRACE score for the occurrence of MACE in NSTEMI patients. According to the optimal cutoff value of 0.045 for PCT, the log-rank test showed statistical significance (P = 0.006) when dividing PCT into two groups.
CONCLUSION PCT is an independent influencing factor for the survival time of NSTEMI patients and can better predict the prognosis of NSTEMI patients in combination with the GRACE score. Therefore, the measurement of PCT can serve as an auxiliary indicator for evaluating the prognosis of NSTEMI patients, providing clinicians with a more comprehensive risk assessment and treatment decision-making.
GW35-e0373
Changqing Du
Zhejiang Hospital
OBJECTIVES The selection of fractional flow reserve derived from computed tomography (CT-FFR) calculation locations was of particular importance when determining ischemic lesions for guiding therapeutic strategies. However, there was no prospective research on comparisons of different measured locations of CT-FFR. To compare the diagnostic efficiency of three interpretation methods of CT-FFR prospectively, using invasive FFR as the reference standard.
METHODS Patients with stable coronary heart disease who underwent CCTA examination and met the inclusion criteria at Zhejiang Hospital from January 2019 to June 2021 were prospectively enrolled. All patients underwent invasive coronary angiography and FFR within 60 days after the CCTA examination. The CT-FFR values were computed using a novel CFD-based model (AccuFFRct, ArteryFlow Technology Co., Ltd., Hangzhou, China). Diagnostic performance of vessel-level CT-FFR, lesion-specific CT-FFR and ∆CT-FFR were evaluated with invasive FFR ≤0.8 as the reference standard and multivariate logistic regression was used to further analyze the influencing factors of their inconsistency with FFR.
RESULTS In total, 124 patients with 143 vessels were included in this prospective study. On a per-vessel basis, vessel-level AccuFFRct and lesion-specific AccuFFRct had good correlation with invasive FFR (r = 0.751 and r = 0.665, respectively) and consistency (mean difference was 0.0118 ± 0.0749 and −0.0194 ± 0.0796, respectively). With invasive FFR ≤0.8 as the reference standard for the diagnosis of myocardial ischemia, the sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy and area under the curve (AUC) values of CCTA, vessel-level AccuFFRct, lesion-specific AccuFFRct and ∆AccuFFRct in the diagnosis of myocardial ischemia were 82.0%, 40.2%, 50.5%, 75.0%, 58.0%, 0.611; 93.4%, 89.0%, 86.4%, 94.8%, 90.9%, 0.937; 62.3%, 92.7%, 86.4%, 76.8%, 79.7%, 0.880 and 62.3%, 92.7%, 86.4%, 76.8%, 79.7%, 0.854, respectively. Multivariate logistic regression analyses showed that neither clinical characteristics nor lesion characteristics were independent influencing factors for the inconsistent diagnosis between vessel-level AccuFFRct, lesion-specific AccuFFRct, ∆AccuFFRct and FFR (all P > 0.05).
CONCLUSION Vessel-level AccuFFRct, lesion-specific AccuFFRct and ∆AccuFFRct provided better diagnostic performance compared with CCTA, with vessel-level AccuFFRct being superior in predicting myocardial ischemia, while lesion-specific AccuFFRct and ∆AccuFFRct had higher specificity than vessel-level AccuFFRct.
GW35-e0374
Changqing Du
Zhejiang Hospital
OBJECTIVES We aim to compare with the diagnostic performance of target-position quantitative flow ratio derived from Murray Law (target-μFR) and vessel quantitative flow ratio derived from Murray Law (vessel-μFR) using the fractional flow reserve (FFR) as reference standard. This study may provide more evidence for the novel clinical usage of quantitative flow ratio derived from Murray Law in the diagnosis and treatment of coronary artery disease (CAD).
METHODS Six hundreds and fifty-six patients (685 lesions) with known or suspected coronary artery disease were screened for this retrospective analysis between January 2021 to March 2023. A total of 161 patients (190 lesions) underwent quantitative coronary angiography (QCA) and FFR evaluations. Both of target-μFR and vessel-μFR were compared the diagnostic performance using the FFR ≤0.80 as the reference standard.
RESULTS Both target-μFR and vessel-μFR demonstrated a strong correlation with FFR (R = 0.90, P < 0.001; and R = 0.87, P < 0.001), and both methods showed great agreement with FFR. The area under the receiver operating characteristic curve was 0.937 (P < 0.001) for target-μFR and 0.936 (P < 0.001) for vessel-μFR in predicting FFR ≤0.80. FFR ≤0.80 were predicted with high sensitivity (92.98%), specificity (91.01%), and the Youden index (0.840) using the cutoff value of 0.83 for target-μFR. A good diagnostic performance (sensitivity 86.44%, specificity 88.51%, and Youden index 0.750) was also demonstrated by vessel-μFR which the cutoff value was 0.80.
CONCLUSION The target-μFR has the similar diagnostic performance with vessel-μFR. The accuracy of μFR does not seem to be affected by the selection of the measurement point. Both of the virtual model could be used as computations tools for diagnosing ischemia and to aid clinical decision-making.
GW35-e0391
Tinghao Zhao1,2, Jun Wang1,2, Ruoxi Gu1, Dongyuan Sun1, Lingfei Zheng1, Xiaoxiang Tian1, Xiaozeng Wang1,2
1Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
2The General Hospital of Northern Theater Command Training Base for Graduate, China Medical University, Shenyang, Liaoning 110016, China
OBJECTIVES The consensus on whether acute ST-segment elevation myocardial infarction (STEMI) patients with multivessel coronary artery disease (MVD) benefit from complete revascularization during primary percutaneous coronary intervention (PCI) is unclear. This study aims to assess the impact of multi-vessel PCI (MV-PCI) versus culprit-vessel only PCI (CV-PCI) on in-hospital outcomes in a Chinese population.
METHODS We evaluated STEMI patients with MVD undergoing PCI, registered in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, from November 2014 to December 2019. Using inverse probability of treatment weighting (IPTW) and multivariable Cox regression, we compared the incidence of in-hospital Major Adverse Cardiac Events (MACE) and other adverse clinical outcomes between the MV-PCI and CV-PCI groups. We used subgroup analyses to create sensitivity analyses to primary endpoint events.
RESULTS Among 8138 patients included, 840 (10.3%) underwent MV-PCI, and 7298 (89.7%) underwent CV-PCI. MV-PCI was associated with higher in-hospital MACE (2.0% vs. 0.9%, P = 0.005), all-cause mortality (1.7% vs. 0.7%, P = 0.003), and contrast-induced acute kidney injury (CI-AKI) (13.6% vs. 10.2%, P = 0.002), after IPTW adjustment. The multivariable Cox analysis further validated the increased risks associated with MV-PCI. Subgroup analysis showed that MV-PCI in patients with three or more vascular lesions was associated with a higher incidence of MACE.
CONCLUSION In the Chinese STEMI population with MVD, participating in the CCC-ACS project, MV-PCI during primary PCI was linked to higher in-hospital adverse events including MACE, all-cause death and CIAKI, compared to CV-PCI. These findings advocate for a cautious approach to MV-PCI in this setting, suggesting a potential preference for a staged PCI strategy for non-culprit vessels.
GW35-e0398
Xinxin Zhu1,2, Haibo Jia1,2, Bo Yu1,2
1Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China
2Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, PR China
OBJECTIVES Acute coronary syndrome (ACS), which is result from the sudden thrombotic occlusion of coronary artery. ACS could be divided into three common subtypes according to pathology mechanism: plaque rupture (PR), plaque erosion (PE) and calcified nodule (CN). PR is the most common subtype of ACS, which accounts for about two-thirds of ACS; PE, has been found in approximately one-thirds of ACS. PE shown much difference to PR, such as plaque morphology, treatment strange, cardiovascular risk and predictive factor. Plaque rupture characteristics with a large necrotic lipid core and thin fibrous cap with discontinued endothelial layer, and more likely to stent implanted, patients with plaque rupture more suffer from hypertension, diabetes and chronic kidney disease, and show higher cardiovascular risk than plaque erosion. Autopsy and OCT studies demonstrated that plaque rupture expressed higher “inflammasome state” than plaque erosion. Ruptured plaque contains more macrophages and T lymphocytes than eroded plaque, and cytokine array was used to compared inflammation state ruptured plaque and eroded plaque, the result shown rupture patients expressed higher I-TAC level than erosion patients. As we know, the level of inflammatory factor may influence by others organs, but not only atherosclerosis plaque. At this study, we compared the inflammatory factor mRNA level of white blood cell in different culprit lesion and explore the biomarker for diagnosis erosion and rupture patients.
METHODS Three hundred and six patients with ST-segment–elevation myocardial infarction (STEMI) and who underwent preintervention optical coherence tomography (OCT) examination were enrolled; 119 and 120 patients were categorized as PR and PE, respectively. Eighty patients diagnosed as stable angina pectoris (SAP) and underwent coronary angiogram (CAG) were enrolled as control group. The blood pre-PCI was collected, after separated the white blood cell, total RNA was extracted and reversed transcription into cDNA. The mRNA of IL-4, IL-10, IL-1β and TNFα was evaluated between patients with PE and PR. ROC analysis was used to evaluating the sensitive and specific of biomarker.
RESULTS STEMI patients shown higher IL-4, IL-1β and TNF-α expression than SAP patients. The mRNA level of IL-4, IL-10 and TNFα were high expressed in the white blood cell of patients with PR than PE. The area under the receiver operating characteristic curve for PR versus plaque erosion was 0.93. At the cut off value of 9.865 (ΔCT), TNFα had a sensitivity of 92.98% and specificity of 82.86% in discriminating patients with plaque rupture from plaque erosion.
CONCLUSION The white blood cell in patients with plaque rupture and plaque erosion shown different inflammatory state to each other. TNFα might be a potential biomarker to predicting plaque erosion and plaque rupture.
GW35-e0416
Zhang BuChun
Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
OBJECTIVES Alterations in circulating CCL4 levels have been implicated in coronary artery disease (CAD), but the causal relationship and underlying mechanisms remain unclear. This study aims to analyse the role of CCL4 and its receptor (CCR5) in CAD using Mendelian randomisation (MR) analysis, bulk RNA and single cell RNA sequencing (scRNA-seq).
METHODS The MR analysis was used to determine the causal relationship between 91 circulating inflammatory proteins and CAD. Bulk RNA sequencing data was used to demonstrate the expression profile of CCL4/CCR5. The localisation of CCL4/CCR5 was determined using scRNA-seq data. Functional enrichment analyses were used to infer the potential role of CCL4 in CAD. Additional clinical samples were utilized to validate the results of MR.
RESULTS We identified six circulating inflammatory proteins associated with CAD. Of these, CCL4 was identified as a key inflammatory cytokine associated with CAD risk for MR analysis. The bulk RNA sequencing data from the Gene Expression Omnibus (GEO) datasets showed that CCR4 receptor (CCR5) expression was significantly higher in human atherosclerotic plaques compared to controls. Notably, scRNA-seq analysis revealed CCL4 was highly expressed in T cells, monocytes and macrophages. Clinical specimens confirmed high levels of serum CCL4 expression in CAD patients by ELISA. Functional enrichment analysis revealed that CCL4 was primarily enriched in the cytokines and cytokine receptors, viral proteins with cytokines and cytokine receptors, and chemokine signaling pathways.
CONCLUSION Our study presented a genetic insight into the pathogenetic role of CCL4-CCR5 in CAD, which may provide new insights for further mechanistic and clinical investigations of inflammatory cytokine-mediated CAD.
GW35-e0447
Na Wang
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China
OBJECTIVES Mesenchymal stem cells (MSCs) hold a great promise for reverse acute myocardial infarction. However, the underlying mechanisms remain controversial. Extracellular vesicles (EVs), secreted from MSCs, play an important role in the process of angiogenesis.
METHODS Due to the role of microRNAs in the angiogenesis and existence of microRNAs in EVs, we hypothesized that MSC-derived EVs, via microRNAs, improve infarcted cardiac function by promotion of neoangiogenesis.
RESULTS Our present study found that MSC-EVs could be taken by the human umbilical vein endothelial cells (HUVECs), consequently increase the angiogenesis, determined by matrigel plug assay and capillary-like tube formation assay, by facilitation of HUVEC migration and proliferation. After screening, miR-210 was found to be one candidate, which was supported by the siRNA study. After down-regulation of miR-210 in EVs from MSCs, the MSC-EVs mediated angiogenesis was reduced. Bioinformatics analysis showed that EFNA3 was the target gene of miR-210, the EFNA3 expression was decreased when HUVECs were co-cultured with MSC-EVs. The above-mentioned experiments were of pathophysiological significance, because treatment of mice with myocardial infarction with MSC-EVs, by intravenously injection, improved cardiac function, reduced infarcted area, accompanied with increased neoangiogenesis in infarcted border 4 weeks after cardiac infarction. Knockdown of miR-210 would remarkably reduce the above-mentioned protective effect of MSC-EVs.
CONCLUSION These results collectively demonstrate that miR-210 in MSC-EVs could protect cardiac function by promotion of neoangiogenesis in infarcted heart.
GW35-e0448
Wang Shen, Wang Yue, Sun Shuaifeng, Pang Shuo, Li Fadong, Zhao Wenxin, Li Xinjian, Ye Maomao, Niu Yufei, Wu Xiaofan
Beijing Anzhen Hospital Affiliated to Capital Medical University
OBJECTIVES Thyroid function is closely related to the onset and long-term prognosis of cardiovascular diseases and diabetes. The free triiodothyronine (fT3) to free thyroxine (fT4) ratio has been reported as a poor risk factor for coronary artery disease and diabetes in euthyroid patients, but its prognostic value in euthyroid patients with diabetes and de novo multi-vessel coronary artery disease (MVD) after percutaneous coronary intervention (PCI) remains unclear.
METHODS In our study, 1357 euthyroid patients with diabetes and MVD who successfully underwent PCI were included at Beijing Anzhen Hospital from August 2021 to April 2022. Patients were divided into three groups according to FT3/FT4 ratio tertiles (tertile 1 ≥0.45, n = 451; 0.39 ≤ tertile 2 <0.45; n = 453; tertile 3 <0.39; n = 453). The primary endpoint was major adverse cardiac events (MACE), including all-cause death, nonfatal MI, and revascularization. The associations between FT3/FT4 ratio and outcomes were assessed by applying Cox regression. The median follow-up time was 16 months.
RESULTS During the follow-up of median 1.5 years, 28 all-cause deaths, 19 cardiac deaths and 54 MACEs occurred in cohort study. Compared with the other two group, patients with low level of FT3/FT4 ratio tended to be female, older, as well as higher CR and T4 level and higher prevalence of prior stroke (all P < 0.05). Patients with lower level of FT3/FT4 ratio was negatively associated with the risk of (adjusted HR 2.31, 95% CI: 1.13–4.75, P = 0.022) than those with higher level of FT3/FT4 ratio from Cox regression analysis. In subgroup analyses, the proportional effect of low FT3/FT4 ratio on MACE was consistent across all seven pre-specified subgroups.
CONCLUSION Low level of FT3/FT4 ratio demonstrated an independent association with an increased risk of MACE in euthyroid patients with diabetes and MVD.
GW35-e0466
Haoyu Wang, Kefei Dou
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES The risk of side branch (SB) occlusion is pivotal for decision-making of stenting strategies during unprotected left main (LM) bifurcation percutaneous coronary intervention (PCI). Accordingly, this study aimed to develop a scoring system for predicting SB occlusion during unprotected LM bifurcation PCI.
METHODS A total of 855 consecutive patients undergoing unprotected LM bifurcation PCI with provisional strategy at Fuwai Hospital from January 2014 to December 2016 were recruited. A prediction model was selected by means of all-subsets logistic regression, and a multivariable risk score (LM Visual Estimation for Risk Prediction of Side Branch Occlusion in Coronary Bifurcation Intervention [LM V-RESOLVE]) was then established with incremental weights attributed to each component variable based on its estimate coefficients. SB occlusion was defined as any decrease in Thrombolysis in Myocardial Infarction (TIMI) flow grade or absence of flow in SB after main vessel (MV) stenting.
RESULTS SB occlusion occurred in 19 (2.22%) LM bifurcation lesions. In multivariable model, three variables, including MV/SB diameter ratio, MV plaque ipsilateral to SB, and baseline diameter stenosis of SB, were independent predictors for SB occlusion (model C-statistics, 0.829; 95% confidence interval [CI], 0.735–0.923, with good calibration). The risk score had a C-statistics of 0.830 (95% CI: 0.738–0.923), with good calibration. According to the quintiles of the risk score, lesions were stratified as the non-high-risk and high-risk groups (quintile I to IV [<8 points] and quintile V [≥8 points]), and SB occlusion rates differed significantly between the two groups (7.39% [15/203] vs. 0.61% [4/652], P < 0.001). Notably, there was a consistently higher rate of PMI in the high-risk group compared with that in the non-high-risk group by different definitions of PMI (SCAI, 15.8% vs. 3.0%; ARC-2, 21.1% vs. 4.8%; and fourth UDMI, 21.1% vs. 6.5%, all P < 0.05). Satisfactory discriminative ability of the risk score was also preserved in external validation (C-statistics, 0.794; 95% CI: 0.691–0.896). Satisfactory discriminative ability of the risk score was also preserved in external validation (C-statistics, 0.794; 95% CI: 0.691–0.896).
CONCLUSION The novel LM V-RESOLVE score, leveraging 3 routinely assessed angiographic variables, could help to rapidly discriminate lesions at risk for SB occlusion for LM bifurcation PCI. The score has the potential to improve risk assessment and inform clinical decision making.
GW35-e0518
Wenchang Nie1, Xinyi Zhang2, Xiaoyan Nie2, Jian Liu1
1Department of Cardiology, Peking University People’s Hospital, Beijing 100044, China
2Department of Pharmacy Administration & Clinical Pharmacy, School of Pharmaceutical Science, Peking University, Beijing 100191, China
OBJECTIVES Platelet endothelial aggregation receptor 1 (PEAR1), a recently identified membrane protein localized to platelets, has been implicated in various cellular and plasma inflammatory processes. This study aims to elucidate the role of PEAR1 DNA methylation in the context of coronary heart disease (CHD) status, a chronic inflammatory sign.
METHODS To clarify this question, we conducted a range of analyses, including a clinical cohort study, animal experiment, and In-silico analysis. A cohort of 876 CHD patients were genotyped for methylation level of 16 CpG sites in PEAR1 CpG island 1 (CGI1). Adjudication of CHD status was made by two qualified physicians in accordance with the guidelines. C57BL/6J ApoE−/− mice fed a high-fat diet for 16 weeks were used as an atherosclerosis model compared with their wild-type relatives. Genotyped sequences of mice were aligned with the human, and the progression of atherosclerosis was defined as the proportion of plaque area in the aortic arch. Then, mendelian randomization was conducted to explore the association of genetically-proxied methylation level of CpG sites in PEAR1 CGI1, which were abstracted from the latest methylation quantitative trait Loci (meQTL) database, with coronary atherosclerosis in UK Biobank.
RESULTS This CHD cohort included 235 (26.8%) with chronic coronary syndrome (CCS), 487 (55.6%) with unstable angina (UA), and 154 (17.6%) with acute myocardial infarction (AMI). After adjusting for potential risk factors such as age, sex, prior MI, prior revascularization, smoking, and those variates chosen by univariate regression, the methylation level of CpG4 and CpG5 were found to have an inverse correlation with CHD status (CpG4: odds ratio [OR] = 0.86, 95% confidence interval [CI] = 0.74~0.98, P-value = 0.030, CpG5: OR = 0.84, 95% CI = 0.72~0.98, P-value = 0.024). Regional-specific DNA methylation was identified to be negatively associated with CHD status. The ApoE−/− mice showed significant atherosclerotic plaques in the aortic root compared with the wild-type after 16 weeks fed. CpG sites in Pear1 CGI1 negatively correlated with CHD status likewise. The mendelian randomization reveals methylation level one CpG site was inversely associated with coronary atherosclerosis (OR = 0.95, 95% CI = 0.912~0.999, P-value = 0.047) without evidence of reverse causation (Psteiger = 1.63 × 10−217).
CONCLUSION This study supports the methylation level of PEAR1 CGI1 associated with CHD status. More research is warranted to confirm the potential causal relationship.
GW35-e0525
YF Xiang1,2, Fan Chen1,2, Jialin Liu1,2
1Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China
2Fuzhou University Affiliated Provincial Hospital
OBJECTIVES Adiposity is associated with new-onset coronary heart disease (CHD) and cannot be comprehensively assessed with body mass index (BMI). We explored anthropometric indices in assessing the association of body fat distribution with new-onset CHD in the high-CVD risk population.
METHODS The analysis was based on populations at high CVD risk of Fu-CARE. This study is a cohort study with the goal of preventing cardiovascular diseases through primary prevention measures. The study enrolled 32,410 participants aged 35–75 years at high CVD risk between 2017 and 2021 from nine cities in Fujian Province, China. The study used weight, height, and WC to calculate 6 adiposity indices: BMI, waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI), A Body Shape Index (ABSI), body roundness index (BRI), and Conicity Index (CONI).
RESULTS During a mean follow-up period of 3.44 ± 1.10 years, 405 of the 32,410 participants developed CHD. Multivariate logistic regression revealed a significant association of higher WWI and CONI with an increased risk of new-onset CHD (respectively, OR = 1.616, 95% CI: 1.190–2.221, P = 0.003; OR = 1.343, 95% CI: 1.012–1.796, P = 0.044). The subgroup analysis reported a gender impact on the WWI prediction of new-onset CHD. Moreover, BMI stratification showed that increased WWI and CONI indicated an increased CHD risk at normal weight levels (respectively, OR = 2.143, 95% CI: 1.330–3.512, P = 0.002; OR = 1.808, 95% CI: 1.168–2.832, P = 0.009). Reclassification of BMI in combination with WWI and CONI thresholds further revealed a similar risk of new-onset CHD in the normal-weight participants with high WWI or CONI and in the overweight or obese counterparts with high WWI or CONI.
CONCLUSION Undesirable fat distribution as indicated by high WWI and CONI may better predict the risk of new-onset CHD than BMI. Normal-weight individuals with undesirable fat distribution may have a comparable risk of new-onset CHD with their overweight or obese counterparts. These findings hold great promises for screening individuals at a CHD risk and designing prevention strategies.
GW35-e0565
Qiang Tan
Peking University Third Hospital Qinhuangdao Hospital
OBJECTIVES Hyperinsulinemia impaired cardiovascular system and endothelial function in patients with coronary artery disease. The purpose of this study was to explore the relationship between hyperinsulinemia and coronary collateral circulation in patients with chronic total coronary occlusion.
METHODS Patients with stable angina and at least one total coronary occlusion were enrolled in this study. Collateral grade was determined according to Rentrop’s classification. Patients were divided into good coronary collateral circulation (CCC) group (grade 2 or 3 collateral vessels, n = 223) and poor CCC group (grade 0 or 1 collateral vessels, n = 115). Fasting insulin level (FINS), fasting glucose level (FBS) were measured. Endothelial function evaluated by flow-mediated dilation (FMD).
RESULTS Serum FINS level was significantly increased in poor CCC group (P < 0.01). Patients in poor CCC group had higher levels of FBS, HbA1C, HOMA-IR than patients in good CCC group. Poor CCC group also had lower level of FMD, lower LVEF and higher syntax scores than good CCC group. Hyperinsulinemia (T3, FINS ≥15.22 μIU/mL) increased OR for the incidence of poor CCC (OR 2.419, 95% CI: 1.780–3.287) in multivariate analysis. Multivariate logistic regression also revealed that diabetes, HbA1c, homeostasis model assessment for insulin resistance (HOMA-IR), HDL-C and Syntax score were independent predictors of poor CCC (all P < 0.05).
CONCLUSION Hyperinsulinemia is a valuable predictor of poor collateral formation in patients with chronic total coronary occlusion.
GW35-e0576
Jing Guo, Daqing Zhang
Shengjing Hospital of China Medical University
OBJECTIVES Oxidative stress has been implicated in the differentiations of Ly6Chigh and Ly6Cmid inflammatory monocytes induced by high glucose. Diabetes is known to exacerbate atherosclerosis by promoting inflammation through oxidative stress. Our previous study has shown that probucol, a lipid-lowering agent with antioxidant properties, reversed the differentiation of Ly6Chigh inflammatory monocyte subsets induced by homocysteine probably via reducing oxidative stress mediated by NADPH oxidase. In this study, we aimed to investigate the impacts of probucol on regulating monocyte subset differentiation and atherosclertic process in diabetic apolipoprotein E deficient (apoE−/−) mice.
METHODS Six-week-old male apoe−/− mice were induced with streptozotocin (STZ) at a dose of 55 mg/kg intraperitoneally for 5 consecutive days, and STZ-apoe−/− mice was confirmed if the blood glucose level exceeded 300 mg/dL. The experimental mice were then categorized into three groups: apoe−/− mice on a high-fat diet (HFD) for 4 weeks as high-fat group (n = 8), STZ-apoe−/− mice on HFD for 4 weeks as diabetes group (n = 8), and STZ-apoe−/− mice on a high-fat diet combined with 1% probucol intervention for 4 weeks as probucol group (n = 8). Blood glucose, lipids, plasma inflammatory factors, and atherosclerotic lesions in the aortic sinus area were assessed. Additionally, flow cytometry (BD FACS Calibur) was used to analyze the differentiation of monocyte subpopulations in peripheral blood and spleen single cell suspensions, where monocytes were identified as CD11b + MNC and further categorized into Ly-6Chigh, Ly-6Cmid, and Ly-6Clow subpopulations based on the expression of Ly-6C antigen on their surface.
RESULTS The levels of low-density lipoprotein cholesterol (35.02 ± 8.50 vs. 22.09 ± 4.29, P = 0.008), plasma inflammatory factors IL-6 (40.05 ± 3.70 vs. 34.69 ± 2.71, P = 0.018) and TNF-α (13.20 ± 1.30 vs. 10.23 ± 1.62, P = 0.002), and the atherosclerotic lesions in the aortic sinus area (25.52 ± 7.59 vs. 8.73 ± 2.08, P = 0.0002) were significantly increased in the diabetes group compared to the high-fat group. The Ly6Cmid monocyte subsets in blood (62.1 ± 13.0% vs. 46.4 ± 8.1%, P = 0.003) and spleen (9.1 ± 1.8% vs. 7.7 ± 0.8%, P = 0.015) of diabetic mice was selectively expanded in diabetic group. Moreover, probucol treatment significantly inhibited atherosclerotic lesions with reducing LDL-C (23.44 ± 5.60 vs. 35.02 ± 8.50, P = 0.013), IL-6 (35.29 ± 3.59 vs. 40.05 ± 3.70, P = 0.02), and TNF-α (11.71 ± 1.47 vs. 13.20 ± 1.30, P = 0.049) levels, compared with those in the diabetes group. Probucol treatment significantly modulated monocytes prevented the differentiation of Ly6Cmid monocyte subsets in blood (44.8 ± 6.4% vs. 62.1 ± 13.0%, P = 0.000) and spleen (7.8 ± 1.9% vs. 9.1 ± 1.8%, P = 0.013), while promot the differentiation of Ly6Clow monocyte subsets, peripheral blood (32.0 ± 6.9% vs. 14.7 ± 11.7%), P = 0.000), spleen (10.5 ± 1.8% vs. 9.3 ± 2.3%, P = 0.027).
CONCLUSION Probucol alleviates diabetic atherosclerotic process probably through modulating the differentiation of monocytes and reducing systemic inflammation.
GW35-e0587
Yuling Zha1, Chengshuai Liu2, Baoying Li1, Mi Deng1, Luna Liu1, Lu Jing1
1China Academy of Chinese Medical Sciences Eye Hospital
2Guang’anmen Hospital of the Chinese Academy of Traditional Chinese Medicine
OBJECTIVES In comparison to coronary angiography and coronary computed tomography, the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) offers advantages such as safety, non-invasiveness, absence of ionizing radiation, absence of contrast damage, cost-effectiveness, and convenience in assessing coronary artery disease. This study aims to investigate the utility and prevalence of MHR as a novel biomarker for diagnosing coronary artery disease in clinical settings.
METHODS A search of seven databases including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, CBM, PubMed, Embase, and Cochrane Library was conducted from inception to September 25, 2023. Literature selection criteria were applied and managed using Endnote 20.0. Quality assessment of literature was done using the QUADAS-2 scale. Heterogeneity, sensitivity, and publication bias were assessed using Meta Disc 1.4 and Stata 17.0. The bivariate model was utilized to calculate combined sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) with 95% confidence intervals (CI).
RESULTS This study included a total of 14 articles involving 25,384 patients, with 18,745 in the observation group and 6639 in the control group. Meta-analysis revealed no heterogeneity due to threshold effects, but heterogeneity due to non-threshold effects. The random-effects model analysis showed a combined sensitivity of 0.543 (0.536–0.550), combined specificity of 0.651 (0.640–0.663), positive likelihood ratio of 1.998 (1.732–2.304), negative likelihood ratio of 0.481 (0.412–0.562), and combined AUC of 0.74 (0.69–0.77). The Q-index was 0.6807, and the combined DOR was 4.442 (3.222–6.123).
CONCLUSION MHR demonstrates appropriate sensitivity and specificity as a simple biomarker for early detection of coronary lesions in coronary artery disease, offering a non-invasive alternative to coronary angiography. However, further large-scale, multi-center studies are necessary to explore its clinical relevance.
GW35-e0591
Beizheng Xu1, Xu Yao Han1, Nan Zhang1, Gary Tse1,2, Guangping Li1, Tong Liu1
1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
2School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China
OBJECTIVES The red blood cell distribution width (RDW) to serum albumin ratio (RAR) has emerged as a reliable prognostic marker for mortality in various disease populations. However, the association between RAR and mortality rates in patients with cardiovascular disease (CVD) requires further investigation.
METHODS This population-based cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. The study included participants with complete data on serum albumin concentration, RDW, and cause of death. Kaplan-Meier curves, multivariable-adjusted Cox regression, and restricted cubic splines (RCS) were employed to examine the potential associations between RAR and all-cause mortality as well as cardiovascular mortality in CVD patients. Subgroup analyses and interaction analyses were conducted to explore correlations within different subgroups.
RESULTS The analysis was conducted on a sample of 4275 individuals (mean age: 64.36 ± 0.31 years; male: 54.55%), with 1884 cases of all-cause mortality and 657 cases of cardiovascular mortality, and a median (IQR) follow-up time of 84 (46–133) months. After the adjustment of potential confounders, Kaplan-Meier curves and Cox regression analysis revealed that high RAR values (Quartile4) were statistically significantly associated with increased risks of all-cause mortality (HR, 2.48 [95% CI: 2.03–3.04]) and cardiovascular mortality (HR, 2.40 [95% CI: 1.83–3.15]), compared to low RAR values (Quartile1) (P < 0.0001). Significant interactions were observed between RAR and sex, race, and education level. RCS stratified by sex demonstrated a positive linear association between RAR and all-cause mortality in males (P overall < 0.001, nonlinear P-value = 0.201), while significant non-linear associations were observed in the remainder of the population (P overall < 0.001, nonlinear P-value > 0.05).
CONCLUSION These findings suggest that higher RAR levels may be linked to increased risks of all-cause mortality and cardiovascular mortality in CVD patients. RAR has the potential to serve as a straightforward, reliable, and cost-effective marker for identifying mortality risk in CVD patients.
GW35-e0596
Guzal Sobirova1, Jamol Uzokov1,2, Adiba Usmonkhodjaeva1, Zarnigor Bafoeva1
1Tashkent Medical Academy
2Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation
OBJECTIVES The objective of this study was to evaluate the impact of COVID-19 on endothelial function in patients with coronary artery disease (CAD). Given the known vascular complications associated with COVID-19, we aimed to determine the extent to which endothelial function is affected in this high-risk population and identify potential implications for their cardiovascular health.
METHODS A prospective cohort study was conducted involving 120 patients with established CAD, recruited from cardiology department of the tertiary center. The study group consisted of 60 patients who had recovered from COVID-19 (post-COVID group) and 60 CAD patients with no history of COVID-19 (control group). Endothelial function was assessed using flow-mediated dilation (FMD) of the brachial artery, a non-invasive ultrasound method, at baseline (within two weeks of recovery for the post-COVID group) and six months later. Additional biomarkers, including endothelial progenitor cells (EPCs) and vascular endothelial growth factor (VEGF), were measured via blood samples at both time points. Statistical analysis was performed using SPSS version 27.0. Changes in FMD, EPCs, and VEGF levels were analyzed using paired t-tests within groups and independent t-tests between groups. Multivariate regression analysis was conducted to adjust for potential confounders, including age, sex, and comorbidities. A significance level of P < 0.05 was considered statistically significant.
RESULTS At baseline, the post-COVID group exhibited significantly lower FMD (4.8% ± 1.2%) compared to the control group (7.3% ± 1.4%, P < 0.001). Six months post-baseline, FMD improved slightly in the post-COVID group (5.6% ± 1.3%, P = 0.02) but remained significantly lower than in the control group (7.1% ± 1.3%, P < 0.001). EPC levels were significantly reduced in the post-COVID group at baseline (45 ± 10 cells/μL) compared to the control group (60 ± 12 cells/μL, P < 0.001). After six months, EPC levels in the post-COVID group increased to 50 ± 11 cells/μL (P = 0.04) but were still lower than in the control group (58 ± 11 cells/μL, P < 0.001). VEGF levels were higher in the post-COVID group at baseline (45 ± 8 pg/mL) compared to the control group (35 ± 7 pg/mL, P < 0.001). Six months later, VEGF levels decreased in the post-COVID group (40 ± 7 pg/mL, P = 0.03) but remained elevated compared to the control group (34 ± 6 pg/mL, P < 0.001). Multivariate regression analysis indicated that COVID-19 was an independent predictor of reduced FMD (β = −0.35, P < 0.001), lower EPCs (β = −0.28, P = 0.002), and higher VEGF levels (β = 0.31, P < 0.001) after adjusting for confounders.
CONCLUSION COVID-19 significantly impairs endothelial function in patients with CAD, as evidenced by lower FMD and EPC levels, and higher VEGF levels, even six months post-recovery. These findings highlight the need for ongoing vascular health monitoring and targeted therapeutic strategies in CAD patients recovering from COVID-19. Further research is required to understand the long-term cardiovascular implications and develop interventions to mitigate these effects.
GW35-e0598
Anis Alyavi1, Akbar Abdullaev1, Jamol Uzokov1,2, Igor Vikrov1,2, Sherzod Ashirbaev1,2, Bakhromkhon Alyavi1,2, Sherzod Iskhakov1, Shovkat Muminov1,2
1Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation
2Tashkent Pediatric Medical Institute
OBJECTIVES The objective of this study was to evaluate the accuracy of an artificial intelligence (AI) model in detecting coronary artery stenosis using coronary angiography images. We aimed to assess the model’s performance metrics, including F-score, Area Under the Receiver Operating Characteristic Curve (AUC-ROC), sensitivity, and specificity, using data from 2000 patients.
METHODS This retrospective study analyzed coronary angiography images from 2000 patients diagnosed with varying degrees of coronary artery stenosis at the Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation. The AI model, based on a convolutional neural network (CNN) architecture, was trained and validated on a dataset comprising 70% of the images (1400 patients) and tested on the remaining 30% (600 patients). The ground truth for stenosis was established by expert cardiologists, with stenosis defined as a narrowing of 50% or more in the coronary arteries. The model’s performance was evaluated using standard metrics: F-score, AUC-ROC, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Statistical analysis was conducted using Python’s scikit-learn library. The primary outcome measures were the model’s F-score, AUC-ROC, sensitivity, and specificity, compared to the expert cardiologists’ assessments.
RESULTS The AI model demonstrated high accuracy in detecting coronary artery stenosis. Key performance metrics on the test set (600 patients) were as follows: F-score: 0.89, AUC-ROC: 0.94, sensitivity: 88%, specificity: 90%, positive predictive value (PPV): 87%, and negative predictive value (NPV): 91%. Detailed results showed that the AI model correctly identified stenosis in 528 out of 600 patients (88%), with 72 false negatives and 60 false positives. The high AUC-ROC of 0.94 indicates excellent discrimination ability between stenosis and non-stenosis cases. The confusion matrix revealed: true positives (TP): 528, false positives (FP): 60, true negatives (TN): 540, and false negatives (FN): 72.
CONCLUSION The AI model exhibited a high degree of accuracy in detecting coronary artery stenosis on coronary angiography images, with an F-score of 0.89 and an AUC-ROC of 0.94. Its sensitivity (88%) and specificity (90%) suggest that the model can reliably differentiate between patients with and without significant coronary artery stenosis. These results support the potential of AI as a valuable tool in the diagnostic workflow of coronary artery disease, aiding cardiologists in the accurate and efficient interpretation of coronary angiography. Further prospective studies and real-world validation are recommended to confirm these findings and explore the integration of AI models into clinical practice.
GW35-e0605
Buchun Zhang
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
OBJECTIVES The goal of this study was to investigate whether there was a link between the triglyceride-glucose index (TyG index), monocyte/high-density lipoprotein cholesterol ratio (MHR) and quantitative flow ratio (QFR) measured immediately after emergency percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). The goal of this study was to investigate whether there was a link between the triglyceride-glucose index (TyG index), monocyte/high-density lipoprotein cholesterol ratio (MHR) and quantitative flow ratio (QFR) measured immediately after emergency percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).
METHODS This retrospective study included 137 consecutive STEMI patients who undergoing emergency PCI of culprit lesions and underwent post-PCI QFR from 2022 to 2023. Then patients were divided into high- and low-QFR groups according to the post-PCI QFR cut-off value of 0.89. Univariate and multivariate logistic regression analyses were conducted to investigate the independent the risk factors of TyG index and MHR with post-PCI QFR ≤0.89. Receiver operating characteristic (ROC) curves were generated to determine predictive power of TyG index and MHR. The decision curve analysis (DCA) was performed to assess the relationship between TyG index, MHR, and post-PCI QFR value in STEMI patients.
RESULTS The TyG index and MHR in the post-PCI QFR ≤0.89 group were significantly higher than those in the control group (P < 0.001). Multivariate logistic regression showed that TyG index and MHR were also risk factors for post-PCI QFR ≤0.89 after correction, respectively (P < 0.001). The ROC analysis showed that TyG combined with MHR had a maximum area under the curve of 0.854 for predicting post-PCI QFR ≤0.89. DCA analysis further suggested a good overall net benefit of TyG index combined with MHR in predicting the incidence of post-PCI QFR ≤0.89.
CONCLUSION Elevated TyG index and MHR are associate with QFR ≤0.89 after emergency PCI in STEMI patients, and TyG index combined with MHR have higher diagnostic efficacy.
GW35-e0613
Yang Duan, Yafeng ZHou
The Fourth Affiliated Hospital of Soochow University
OBJECTIVES The early diagnosis of coronary microvascular dysfunction (CMD) in patients percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) has has been and remained a puzzling issue. The computational pressure-fluid dynamics applied to index of microcirculatory resistance, derived from coronary angiography (CPFD-caIMR) is a promising alternative method of IMR to evaluate the prognosis of STEMI patients. The potential of caIMR, in conjunction with microvascular obstruction (MVO), to early and timely identify high-risk individuals and thereby enhance the clinical outcomes of STEMI patients has not yet been explored. This study aim to evaluate the incremental value CPFD-caIMR and MVO in predicting MACE after patients with undergoing primary percutaneous coronary PPCI.
METHODS A total of 292 patients who met the inclusion criteria were selected retrospectively from 1107 STEMI patients from January 2019 to January 2021 in Affiliated Hospital of Xuzhou Medical University in China. All patients with STEMI underwent CPFD-caIMR and MVO assessment. CPFD-caIMR measurements for all participants were obtained off-line post-PPCI using FlashAngio software (Rainmed Ltd., Suzhou, China). MRI parameters were analyzed using cvi42 software (Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada) by two independent experts who were blinded to clinical, surgical, and coronary physiology data. The patients were categorized into four groups based on CPFD-caIMR and MVO presence: 1) CPFD-caIMR ≤40U without MVO; 2) CPFD-caIMR >40U without MVO; 3) CPFD-caIMR ≤40U with MVO; and 4) CPFD-caIMR >40U with MVO. The primary endpoint of the study was MACE, defined as cardiovascular or all-cause deaths, non-fatal MI, revascularization including target vessel reconstruction, heart failure readmission.
RESULTS Within the included 292 patients, a notable proportion of 101 cases (34.6%) revealed discrepancies between CPFD-caIMR and MVO. Among these, 103 patients (35.3%) exhibited CPFD-caIMR values of ≤40 without MVO, while 88 patients (30.1%) displayed CPFD-caIMR values of >40 with MVO on CMR. Both MVO (HR: 2.750 [95% CI: 1.085–6.973, P = 0.033]) and CPFD-IMR >40U (HR: 3.572 [95% CI: 1.639–7.786, P = 0.001]) were predictors of MACE over 12 months. Specifically, for every 1-unit increase in CPFD-IMR >40U, MACE increased by 3.572 units. Furthermore, ROC curve analysis demonstrated that CPFD-caIMR >40U (AUC, 0.724, 95% CI: 0.577–0.757; P < 0.001) and MVO (AUC, 0.667, 95% CI: 0.577–0.757; P = 0.001) were effective in predicting MACE. Notably, combined CPFD-caIMR and MVO increased the area under the curve for MACE to 0.820 (95% CI: 0.747–0.892, P < 0.001). Over 12 month of follow-up, Group 4 (hazard ratio [HR]: 8.765; 95% CI: 2.854–26.912; P < 0.001) but not Group 3 (HR: 3.474; 95% CI: 1.138–10.607; P = 0.029), Group 2 (HR: 3.554; 95% CI: 1.028–12.289; P = 0.045) had worse clinical outcomes compared with those with no significant CMD in Group 1.
CONCLUSION CPFD-caIMR is a novel method for noninvasive detection of microvascular reperfusion failure, and CPFD-caIMR >40U can predict the prognosis of STEMI patients. When combined with CMR, CPFD-caIMR >40U can be used to further stratify the risk of STEMI and to identify high-risk patients who may require more aggressive treatment during follow-up.
GW35-e0617
Feng Lv, Yafeng Zhou
The Fourth Affiliated Hospital of Soochow University
OBJECTIVES Progress has been made in genetic investigations on restenosis for the past 20 years, many studies regarding AGTR1 rs5186 polymorphism and restenosis after percutaneous coronary intervention (PCI) have been published, but the result remains controversial. The study aimed to explore the relationship between rs5186 polymorphism and the risk of restenosis after PCI.
METHODS We performed a systematic search on PubMed, Web of Science, Embase, CNKI, and Wan Fang databases up to December 2021. Two authors individually extracted all useful data of each study involved in this meta-analysis and assessed the study quality using the Newcastle-Ottawa scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were combined in different genetic models for evaluation using a random-effects model or fixed-effect model.
RESULTS There were eventually 8 studies of 1111 cases and 4097 controls eligible for this meta-analysis. Significant associations were found between rs5186 polymorphism and restenosis after PCI. Allelic (OR: 1.31, 95% CI: 1.17–1.47, P < 0.001), homozygous (OR: 1.90, 95% CI: 1.50–2.44, P < 0.001), heterozygous (OR: 1.10, 95% CI: 0.93–1.29, P = 0.27), recessive (OR: 1.80, 95% CI: 1.37–2.36, P < 0.001), dominant genetic model (OR: 1.24, 95% CI: 1.06–1.44, P = 0.006). Subgroup analyses indicated a significant association in Asians.
CONCLUSION The rs5186 polymorphism in the AGTR1 gene increases the risk of restenosis after PCI in Asians significantly.
GW35-e0639
Pengsheng Chen1,2, Jianling Bai3, Tong Wang4, Kun Liu5, Zengguang Chen6, Xiaoyan Wang7, Li Zhu8, Xin Zhao9, Naiquan Yang10, Jun Jiang11, Xiangqing Kong1, Chunjian Li1
1The First Affiliated Hospital of Nanjing Medical University
2XuZhou Central Hospital
3Nanjing Medical University
4The First People’s Hospital of Yancheng
5The First People’s Hospital of Lianyungang
6The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University
7Affiliated Hospital of Jiangnan University
8Taizhou People’s Hospital
9The Second Hospital of Dalian Medical University
10Huai’an Second People’s Hospital Affiliated to Xuzhou Medical University
11Zhejiang University School of Medicine
OBJECTIVES The aim of this study was to determine whether in patients presenting with ST-elevation myocardial infarction (STEMI) a single bolus recombinant staphylokinase (r-SAK) prior to timely percutaneous coronary intervention (PCI) leads to improved patency of the infarct-related artery (IRA) and reduces the infarct size.
METHODS OPTIMA (OPtimal management of anTIthrombotic and throMbolytic Agents)-5 is an open-label, prospective, multicenter, randomized, controlled study approved by the ethics committees of participating centers. We enrolled patients aged 18–75 who were within 12 hours of symptom onset of STEMI and expected to undergo PCI within 120 minutes. Patients were administered loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive 5 mg bolus of r-SAK or normal saline (NS) prior to PCI. The primary endpoint was thrombolysis in myocardial infarction (TIMI) flow grade 2 and 3 or grade 3 in the IRA 60 minutes after thrombolysis. The infarct size was detected by cardiac magnetic resonance (CMR) 5 days after randomization. The safety endpoint was major bleeding (BARC ≥3) during 30-day follow-up. Images of coronary arteriography (CAG) and those from CMR were adjudicated by the event review committee and a core laboratory blinded to treatment allocation.
RESULTS A total of 283 patients were screened from 8 centers, and 200 were randomized (median age 58.5 years, 14% female). The median symptom to thrombolysis time was 252.5 (IQR 142.8–423.8) minutes and thrombolysis to coronary arteriography was 50.0 (IQR 37.0–66.0) minutes. Patients randomized to r-SAK compared with NS more often had TIMI flow grade 2 and 3 (69.0% vs. 29.0%; P < 0.001) and TIMI flow grade 3 (51.0% vs. 18.0%; P < 0.001) and had smaller infarct size (21.91 ± 10.84% vs. 26.85 ± 12.37%; P = 0.016). There was no increase in major bleeding (r-SAK 1.0% vs. control 3.0%; P = 0.246).
CONCLUSION A single bolus r-SAK prior to PPCI for STEMI improves IRA patency and reduces infarct size without increasing major bleeding (OPTIMAL MANAGEMENT OF ANTITHROMBOTIC AND THROMBOLYTIC AGENTS-5 [OPTIMA-5]; NCT05023681).
GW35-e0650
Yu Zhao, Xiaojun Ding, Zeya Li, Rongchong Huang
Capital Medical University Affiliated Beijing Friendship Hospital
OBJECTIVES Acute Coronary Syndrome (ACS) presents with a variable prognosis, posing significant public health challenges. This study investigated the potential link between cerebral small vessel disease (CSVD) burden and outcomes in patients with ACS.
METHODS In this retrospective cohort study, ACS patients admitted to Beijing Friendship Hospital from January 1, 2020, to October 1, 2021, were analyzed. CSVD burden was assessed using magnetic resonance imaging (MRI) markers, including white matter lesions, lacunar infarcts, cerebral microbleeds, and enlarged perivascular spaces. The correlation between CSVD burden and clinical outcomes, including major adverse cardiovascular and cerebrovascular events (MACE), myocardial Infarction (MI), target vessel revascularization (TVR), stroke, and mortality was examined over a one-year follow-up.
RESULTS Out of 248 patients, 216 were categorized into a low score group (LSG-CSVD) and 32 into a high score group (HSG-CSVD). Patients in the HSG-CSVD exhibited significantly worse prognosis, with an elevated risk of MACE, MI, and TVR. After adjusting for age, sex, hypertension, TNT, and eGFR, a significantly higher risk of MI was observed in the HSG-CSVD group [HR 4.51, 95% CI: 1.53–13.26, P = 0.006]. Subgroup analysis by age and sex consistently demonstrated increased adverse outcomes in the HSG-CSVD group.
CONCLUSION The study highlights a direct association between increased CSVD burden and poorer ACS outcomes, particularly in MI risk. These findings underscore the importance of considering CSVD burden as a crucial prognostic factor in ACS management, facilitating risk stratification and guiding personalized treatment strategies.
GW35-e0657
Lan Zhao1,2, Zhichuan Huang1, Jianshuo Wang1, Zhanyu Deng1, Pengzhen Wang1, Shaoheng Zhang1
1GuangZhou Red Cross Hospital Medical College of Ji-Nan University
2Dahua Hospital, Xuhui District, Shanghai
OBJECTIVES Exploring the cardiac repair of renal sympathetic denervation (RD) could be of great clinical significance for treating heart failure (HF) post-myocardial infarct (MI). We investigated whether RD restores cardiac function in a clinically relevant pig model of HF with reduced ejection fraction (HFrEF) via remote effects on the myocardium.
METHODS After the induction of MI, the pigs with ejection fractions (EF) <40% were selected as HFrEF model, and randomly underwent sham-RD (CON) or radiofrequency-RD (RD). Both sets were randomlyallocated to receive either 2 × 1013 empty AAV6 particles or the same dose of AAV6-mirRNA mixparticles with miR-195-3p plus miR-199a-3p, and underwent follow-up for a period of 90 days. Other pigs were used to receive myocardial biopsy and exosomal (Exos) collection.
RESULTS RD therapy significantly enhancedmesenchymal stem cell (MSC) Exos uptake by cardiomyocytes (CMs). Exos secreted from RD-derived MSCs have been shown to enrich miR-195-3p and miR-199a-3p. When cocultured with Exos from MSCs overexpressing miR-195-3p or/and miR-199a-3p, CMs from RD-treated hearts showed dedifferentiation, proliferation, and redifferentiation. RD therapy significantly reduced circulating norepinephrine and epinephrine levels, and increased circulating B-type natriuretic peptide levelswhen compared with sham-treated animals. Following RD, injection of Exos with mixture of miR-195-3p and miR-199a-3p resulted in sustained increase in LV ejection fraction and inhibition of LV remodeling, myocardial regeneration, and angiogenesis. Correspondingly, Oct4 was significantly up-regulated in the pigs receiving RD and mirRNA mix.
CONCLUSION RD and MSC-derived exosomal miRNAs may work synergitically in improving HFrEF post-MI in a clinically relevant model system.
GW35-e0660
Boning Zhou1,2, Xin Zhang1,2,3, Zijie Dang1,2, Jian Shen1,2, Yang Jiao1,2, Henan Liu4, Yongkang Su1,2, Jian Wang1,2,5, Xiaoling Hou1, Zhenhong Fu1
1Senior Department of Cardiology, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100853, China
2Chinese PLA Medical School, Beijing 100853, China
3The 980th Hospital of the PLA Joint Logistical Support Force (Bethune International Peace Hospital), Shijiazhuang 050081, Hebei, China
4The 305 Hospital of PLA, Beijing 100017, China
5Department of Cardiology, Hainan Hospital, Chinese PLA General Hospital, Sanya 572000, Hainan, China
OBJECTIVES Our study aimed to develop a individualized risk prediction model to predict major adverse cardiovascular events (MACEs) of coronary in-stent restenosis (ISR) patients undergoing percutaneous coronary intervention (PCI).
METHODS Three hundred and fifty-six patients with in-stent restenosis who underwent PCI in the Cardiology Department of Chinese PLA General Hospital from 2016 to 2020 were enrolled in the restospective study. Least absolute shrinkage and selection operator (LASSO), random survival forest (RSF) and Cox regression analysis were used to select significant parameters for nomogram. Time-dependent receiver operating characteristic (ROC) curve, Harrell’s concordance index (c-index), calibration curve and decision curve analysis (DCA) were used to evaluate the predictive accuracy and clinical utility of the nomogram to predict major adverse cardiovascular events (MACEs). Bootstrap validation and cross-validation were used to estimate the mean AUC and C-index after bias correction so as to assess the predictive stability of nomogram. The total risk score for each patient was calculated using the nomogram. According to optimal cutoff value of total points obtained by X-tile software, the participants were divided into three risk groups. Kaplan–Meier (KM) curves and log-rank test were used to assess the differences among three risk groups.
RESULTS The nomogram was constructed in 356 participants with ISR, and 133 of whom (37.4%) suffered the MACEs. The significant predictors screened out by the LASSO regression, RSF and Cox regression included uric acid ≥360 umol/L, ST segment deviation ≥0.5 mm, number of vessels diseased, restenosis interval ≤1 year, ostial ISR lesion, left main or multivessel ISR lesion and repeat PCI without stent implantation. After bootstrap validation or cross-validation, the time-dependent area under the curves (AUCs) for MACEs were all over 0.7 and bias-corrected C-index at 365, 730, 1095, 1460, 1825, 2190 days were all over 0.65, suggesting a remarkable accuracy and stability of the nomogram. The calibration curve indicated a good agreement with the observations and decision curve analyses confirmed that the nomogram performed significantly better clinical utility than SYNTAX score, Gensini score, SYNTAX Score II, GRACE score or Mehran type. According to the risk stratification by Xtile, patients were divided into three risk groups: low risk (total points ≤214.12), middle risk (214.12< total points ≤333.90) and high risk (total points >333.90). The KM curve showed great discrimination among the three risk groups (Plog-rank < 0.0001).
CONCLUSION A prognostic nomogram was established and validated for evaluating the MACEs of ISR patients who underwent PCI.
GW35-e0662
Yang Zhang1, Liang Zhang 1, Quan Li1, Yicong Ye1, Xiliang Zhao1, Li Lin1, Yaodong Ding1, Yi Ye1, Jiayi Han1, Chao Zhang2, Chunliang Wang2, Yong Zeng1
1Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
2Escope Ltd, Beijing, China
OBJECTIVES Previous studies have revealed the well diagnostic performance of novel angiography-derived index of microcirculatory resistance (aIMR), yet comparisons between resting and hyperemic conditions are underexplored.
METHODS This prospective, multicenter and self-controlled study was undertaken to evaluate the feasibility and diagnostic accuracy of aIMR in chronic coronary syndrome patients using wire-based functional indices as the reference. The aIMRs were quantified from resting and hyperemic angiograms by calculating the flow rate through the ratio of vessel volume to mean transit time. This data was then integrated into a computational fluid dynamics solver to estimate angiography-derived fractional flow reserve and aIMRs.
RESULTS After exclusions following predefined criteria, 139 vessels were eventually included in the analysis of the present study. Both hyperaemic aIMR (H-aIMR) (r = 0.82, P < 0.001) and resting aIMR (R-aIMR) (R = 0.25, P = 0.003) exhibited positive linear correlations with wire-based IMR. Notably, H-aIMR was associated with a higher diagnostic yield than R-aIMR (AUC 0.95 vs. 0.72; P < 0.001). Significant differences in diagnostic yield between these modalities were observed in vessels with compromised coronary flow reserve (CFR <2.0). In contrast, such differences were not observed in vessels with normal CFR (CFR ≥2.0).
CONCLUSION The aIMRs demonstrated high diagnostic accuracy with wire-based IMR measurements. Nevertheless, discrepancies in diagnostic yield persist between modalities in resting and hyperaemic states, potentially attributable to abnormally reduced CFR.
GW35-e0677
Yanan Zhao, Wenjia Liu, Tao Li
Department of Radiology, The First Medical Center of PLA General Hospital
OBJECTIVES Over the past few decades, left ventricular (LV) dysfunction in ST-segment elevation myocardial infarction (STEMI) patients has been the focus of research. Recently, co-occurring right ventricular (RV) dysfunction has received more attention in clinical practice. We aimed to assess RV function using cardiac magnetic resonance (CMR) imaging and identify factors that may contribute to RV dysfunction in STEMI patients.
METHODS We retrospectively studied 189 patients with STEMI who underwent CMR 1–7 days after successful percutaneous coronary intervention (PCI). The ejection fraction (EF), wall thickening rate (WTR), peak radial strain (RS), circumferential strain (CS) and longitudinal strain (LS) of the LV, interventricular septum (IVS) and RV were measured with cine images. The location and extent of the infarct were determined using late gadolinium enhancement (LGE) imaging. The differences of function between STEMI patients with right ventricular ejection fraction (RVEF) <50% and those with RVEF ≥50% were compared using an independent-sample t-test. Linear regression analyses were used to determine independent predictors of RVEF.
RESULTS RVEF <50% was observed in 32.28% STEMI patients, who also demonstrated significantly lower LVEF (41.4 ± 10.1% vs. 49.2 ± 8.2%; P < 0.001), WTR (38.6 ± 14.6% vs. 46.9 ± 13.1%; P < 0.001), RS (20.0 ± 6.2% vs. 23.9 ± 6.3%; P < 0.001), and larger infarct sizes (30.51 ± 17.92 mL vs. 22.35 ± 15.15 mL; P = 0.001) than those with RVEF ≥50%. Patients with RVEF <50% also demonstrated a higher incidence of RV infarction (32.8% vs. 17.2%, P = 0.020), higher RV end-systolic volume (ESV) index (27.88 ± 9.56 mL/m2 vs. 26.47 ± 6.95 mL/m2; P < 0.001), and lower RV RS (20.3 ± 6.4% vs. 29.7 ± 8.1%; P < 0.001). Multivariable linear regression analysis revealed LV EF, IVS WTR and IVS RS as significant predictors for RVEF, while male gender, the culprit lesion in the right coronary artery (RCA), peak troponin were negative predictors for RVEF. Notably, peak troponin, LV EF, LV RS, LV CS, LV WTR, and IVS WTR demonstrated higher area under the curve values for predicting RV dysfunction.
CONCLUSION RV dysfunction was detected in 32.28% of STEMI patients. Patients with acute STEMI and RVEF <50% had impaired LV and IVS functions. Systolic function of the LV and IVS, peak troponin, and culprit lesions in the RCA were independent predictors of RV dysfunction in STEMI patients.
GW35-e0678
Ziqiang Guo
PLA General Hospital
OBJECTIVES Coronary artery disease (CAD) has become a significant public health issue nowadays. Timely identification of potential risk factors, accurate clinical diagnosis, and appropriate intervention strategies are crucial for preventing disease progression and long-term adverse cardiovascular events. With the widespread use of coronary computed tomography angiography (CCTA), non-obstructive CAD, defined as the presence of mild stenosis or no flow-limiting lesions, has gradually gained attention from researchers due to its high prevalence and potential clinical risks. CCTA can evaluate atherosclerotic lesions from multiple dimensions, including anatomical information such as plaque characteristics, functional information related to hemodynamics, and inflammatory information assessed by the perivascular fat attenuation index (FAI). However, there is currently a lack of comprehensive, accurate, and individualized risk assessment criteria and methods for patients with non-obstructive CAD. In light of the aforementioned background, this study aims to address the issue of identifying individuals and lesions at high risk for non-obstructive CAD using CCTA from anatomy perspective.
METHODS The study was based on a single-center retrospective cohort, including 1241 patients with diabetes complicated by non-obstructive coronary artery disease (CAD), with a median follow-up time of 31 months (interquartile range: 27.6–37.3 months). The study evaluated the correlation between the SIS and Leiden scores and the 3-year risk of major adverse cardiovascular and cerebrovascular events (MACCE) using a multivariate model. Within the population of non-obstructive CAD, the study further stratified the groups by SIS or Leiden scores and compared the 3-year MACCE risk between the high- and the low-score group.
RESULTS The patients with non-obstructive CAD were stratified by SIS score or Leiden score, and it was found that there was a significant increasing trend in the incidence of MACCE events, with a statistically significant difference between the groups (log-rank P < 0.0001). Compared to the low-score groups, the high-score groups had a higher risk of MACCE (SIS ≥3: HR: 2.02, 95% CI: 1.11–3.68, P = 0.021; Leiden ≥5: HR: 1.92, 95% CI: 1.06–3.48, P = 0.032). Both SIS score and Leiden score were associated with the occurrence of 3-year MACCE in both the total population and the non-obstructive CAD group, with the risk increasing as the scores rose.
CONCLUSION Leiden score and SIS score can serve as effective cardiovascular risk stratification tools in patients with diabetes complicated by non-obstructive CAD. They support the risk identification based on anatomical features provided by CCTA, particularly for diabetic patients prone to diffuse lesions in multiple vessels. The assessment of atherosclerotic burden is feasible and reasonable, and a greater burden as quantified by the scores is associated with worse clinical outcomes.
GW35-e0680
Mengkai Lu, Jiaqi Hao, Chao Li
Innovation Research Institute of traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine
OBJECTIVES Aims to analyze the association between low-fiber diet and cardiovascular diseases (CVD), as well as the related trends in health inequality, based on the 1990–2019 Global Burden of Disease (GBD) database.
METHODS We utilized the 2019 Global Burden of Disease data, including annual disability-adjusted life years (DALYs) and age-standardized DALY rates (ASDR) related to cardiovascular diseases associated with low-fiber diets, as well as gender and age information. Disease mapping was employed to visualize the global, regional, and national burden of cardiovascular diseases, and standard measures such as the Slope Index of Inequality (SII) and Concentration Index (CI) were used to assess absolute and relative inequality. Statistical analysis was conducted using R software.
RESULTS The study shows a slight increase in the burden of cardiovascular diseases attributed to low-fiber diets from 1990 to 2019, with higher DALY numbers in males compared to females. In 2019, India, China, and Indonesia had the highest DALY numbers related to cardiovascular diseases caused by low-fiber diets. Additionally, Southeast Asia, South Asia, and East Asia remained at the forefront in terms of the burden of cardiovascular diseases. The study also found that countries with low Socio-demographic Index (SDI) had the lowest ASDR, while high SDI countries effectively controlled their ASDR. In terms of international health inequality, the study indicated a reduction in inequality between low-income and high-income countries in the burden of cardiovascular diseases from 1990 to 2019.
CONCLUSION There is an association between low-fiber diet and cardiovascular diseases, along with significant regional and gender differences. Moreover, there is a gradual reduction in international health inequality related to this disease burden. These findings provide important evidence for the development of targeted strategies for the prevention and intervention of cardiovascular diseases, contributing to the improvement of global cardiovascular health and the reduction of health inequality.
GW35-e0691
Hongbo Huang1, Yuxuan Liu1, Linjie Xu1,2, Zirui Wang1,2, Peili Wang1, Ying Zhang1
1Xiyuan Hospital, China Academy of Chinese Medical Sciences
2Beijing University of Chinese Medicine
OBJECTIVES Previous studies have shown that overweight/obesity is an independent risk factor for cardiovascular disease (CVD). However, overweight/obesity is metabolically heterogeneous, and the relationship between different transitions in the weight-metabolic phenotypes and CVD is unclear.
METHODS Data were derived from 5 waves of the China Health and Retirement Longitudinal Study (CHARLS). Assessment of weight-metabolic phenotypes and their transitions based on body mass index (BMI) and metabolic status at baseline (Wave 1) and the second blood test (Wave 3), including metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obesity (MHOO), and metabolically unhealthy overweight/obesity (MUOO). CVD was defined as the presence of physician-diagnosed heart disease and/or stroke. We used Cox proportional hazards regression models to examine the prospective association between transitions in the weight-metabolic phenotypes and CVD.
RESULTS Seven thousand five hundred and seventy-eight participants were included at baseline, of which 2292 participants (30.25%) were categorized as MHNW, 2093 MUNW (27.62%), 839 MHOO (11.07%), and 2354 MUOO (31.03%). The largest proportion maintained stable phenotypes in the 4 years follow-up. More than half of MHOO (57.62%) experiencing a phenotypic transitions and the majority transitioning into MUOO. Compared with MHNW, the CVD risk of stable MUNW (HR: 2.175, 95% CI: 1.668–2.837, P < 0.05) and stable MUOO (HR: 2.318, 95% CI: 1.820–2.953, P < 0.05) increased. In phenotypic transitions, MHNW to MUNW (HR: 1.718, 95% CI: 1.241–2.380, P < 0.05), MUNW to MUOO (HR: 2.524, 95% CI: 1.770–3.599, P < 0.05), MHOO to MUNW (HR: 2.220, 95% CI: 1.118–4.410, P < 0.05), MHOO to MUOO (HR: 2.220, 95% CI: 1.560–3.158, P < 0.05), and MUOO to MUNW (HR: 2.945, 95% CI: 2.021–4.302, P < 0.05) increased the risk of CVD.
CONCLUSION Compared with metabolically healthy middle-aged and older adults with normal weight, the risk of cardiovascular disease is increased in who with metabolically unhealthy status, regardless of whether BMI is controlled within the normal range.
GW35-e0697
Zhiqiang Zhang
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Prior research has indicated that individuals who suffer from anemia are at a heightened risk for experiencing ischemic and hemorrhagic incidents following percutaneous coronary intervention (PCI). The objective of this study was to assess the in-hospital outcomes of ticagrelor and clopidogrel in Chinese patients with anemic acute coronary syndrome (ACS) undergoing PCI.
METHODS This research involved individuals with ACS who were registered in the CCC-ACS project from November 2014 to December 2019 who received aspirin and a P2Y12 receptor inhibitor within 24 hours of initial medical contact. The primary focus was to evaluate the occurrence of major adverse cardiovascular and cerebrovascular event (MACCE) and major bleeding during hospitalization. To compare the effectiveness and safety of clopidogrel with ticagrelor, inverse probability treatment weighting (IPTW) was utilized, and multivariate logistic models were applied to confirm the accuracy of the findings.
RESULTS Out of 7477 anemic patients, the majority (72.4%) received clopidogrel, while the remaining (27.6%) received ticagrelor. The occurrence of major bleeding was more frequent in the ticagrelor group when compared to the clopidogrel group (2.2% vs. 1.3%, P = 0.003). However, there was no statistically significant difference in the incidence of MACCE between the two groups (2.8% vs. 2.3%, P = 0.282). IPTW analysis and multivariate logistic analysis revealed that the use of ticagrelor increased the risk of major bleeding during hospitalization compared to clopidogrel.
CONCLUSION This study indicates that ticagrelor, had a similar risk of in-hospital MACCE in anemic ACS patients receiving PCI compared to clopidogrel, but a greater rate of major bleeding events during hospitalization.
GW35-e0701
Lingling Zhang
Xiangtan Central Hospital
OBJECTIVES Acute coronary syndrome (ACS) is a serious threat to the life and health of patients, and diagnosis-related grouping (DRG) payment has been widely introduced into the management of ACS patients, but its impact on the medical quality of ACS patients has not been fully studied. This study aims to examine the effect of DRG payment on the quality of care (hospitalization costs, hospitalization days, readmission for heart failure) in patients with ACS.
METHODS This study included 12,760 patients with ACS admitted to our chest pain center from 1 January 2015 to 31 June 2023. After propensity score matching, comparisons was made by logistic regression analysis. Mainly compare the quality of care before and after DRG payment.
RESULTS After the implementation of DRG payment, the proportion of hospitalization expenses for ACS patients (β = −7950.28, 95% CI: −8861.51, −7039.06, P < 0.001), hospitalization days (β = −1.57, 95% CI: −1.77, −1.36, P < 0.001), and heart failure readmission (OR = 0.53, 95% CI: 0.43, 0.65, P < 0.001) all decreased. At the same time, we also found that the implementation of DRG payment and the standard construction of chest pain center had a synergistic effect on the medical quality of ACS patients, which significantly reduced the proportion of hospitalization costs and readmission for heart failure (P < 0.001).
CONCLUSION DRG payment can reduce hospitalization costs, hospitalization days and the proportion of heart failure readmissions in patients with ACS. At the same time, the implementation of DRG payment and the standard construction of chest pain center have a synergistic effect on the improvement of medical quality of ACS patients.
GW35-e0703
Lingling Zhang
Xiangtan Central Hospital
OBJECTIVES Cardiovascular disease (CVD) is the leading cause of death worldwide, with air pollution posing significant risks to cardiovascular health. The effect of air quality on heart failure (HF) readmission in acute myocardial infarction (AMI) patients is unclear. Our study aimed to find evidence of the effect of air quality on readmission for heart failure in patients with myocardial infarction.
METHODS We retrospectively analyzed data from 12,857 acute coronary syndrome (ACS) patients (January 2015–March 2023). After multiple screenings, 4023 AMI patients were included. Cox proportional hazards regression assessed the impact of air quality indicators on admission and outcomes in 4013 AMI patients. A decision tree model identified the most susceptible groups.
RESULTS After adjusting for confounders, NO2 (HR 1.009, 95% CI: 1.004–1.015, P = 0.00066) and PM10 (HR 1.006, 95% CI: 1.002–1.011, P = 0.00751) increased the risk of HF readmission in ST-segment elevation myocardial infarction (STEMI) patients. No significant effect was observed in non-STEMI (NSTEMI) patients (P > 0.05). STEMI patients had a 2.8-fold higher risk of HF readmission with NO2 >13 μg/m3 (HR 2.857, 95% CI: 1.439–5.670, P = 0.00269) and a 1.65-fold higher risk with PM10 >55 μg/m3 (HR 1.654, 95% CI: 1.124–2.434, P = 0.01064).
CONCLUSION NO2 and PM10 are linked to increased HF readmission risk in STEMI patients, particularly when NO2 exceeds 13 μg/m3 and PM10 exceeds 55 μg/m3. Younger, less symptomatic male STEMI patients with fewer underlying conditions are more vulnerable to these pollutants.
GW35-e0704
Lingling Zhang
Xiangtan Central Hospital
OBJECTIVES Background: Early identification of patients at risk of developing severe mechanical complications (SMCs) after acute myocardial infarction (AMI) is crucial for improving patient outcomes. Therefore, the aim of this study was to develop and validate a risk prediction model, named the AMI-SMC Model, using clinical data to enhance the early detection of SMC risk in AMI patients.
METHODS A retrospective cohort study, comprising 12,857 patients diagnosed with acute coronary syndrome and admitted to the Cardiology Department at Xiangtan Central Hospital from January 2015 to June 2023, was conducted. After excluding patients with unstable angina and those missing crucial data, 4023 AMI cases were included in the final analysis. A temporal validation approach was used divide the cohort into a training set of 2756 patients (68.51%) attending the hospital from January 1, 2015, to May 31, 2022, for constructing the AMI-SMC model, and a validation set comprising 1267 patients (31.49%) attending the hospital from June 1, 2022, to June 1, 2023, for validating the predictive ability of the model. The primary endpoint was the occurrence of SMCs. Univariate Logistic regression analysis was conducted to identify the risk factors for SMCs, followed by LASSO regression analysis. A comparative analysis of the min model, 1se model from LASSO regression, Boruta feature selection, and recursive feature elimination (RFE) was performed to determine the most reliable predictive model. The predictive accuracy and reliability of the AMI-SMC model was assessed by generating receiver operating characteristic (ROC) curves, accuracy curves, and conducting Hosmer-Lemeshow goodness-of-fit tests.
RESULTS In this study, 93 cases of SMCs were identified after analysis. Independent risk factors of SMCs identified using the AMI-SMC model included high-sensitivity troponin T (for every 1 ng/mL increase, Odds Ratio [OR] = 2.021; 95% confidence interval [CI]: 1.683–2.539; P < 0.001), creatine kinase-MB (for every 1 IU/L increase, OR = 1.004; 95% CI: 1.003–1.006; P < 0.001), C-reactive protein (for every 1 mg/L increase, OR = 1.017; 95% CI: 1.012–1.022; P < 0.001), and the occurrence of cardiogenic shock (OR = 4.079; 95% CI: 1.911–8.878; P < 0.001). The area under the ROC curve for the model using the training set was 0.993 (with 95% CI: 0.991–0.996 with 500 bootstrap values), and the H-L test P-value was 0.9887. The area under the ROC curve using the validation set was 0.997 (with 95% CI: 0.994–1.000 with 500 bootstrap values), and the H-L test P-value was 0.9916.
CONCLUSION AMI-SMC Model is an effective predictive tool, accurately predicting the risk of SMCs in AMI patients based on clinical data. The clinical application of this model can enhance patient management strategies and enable clinicians to provide personalized treatment, thereby improving clinical outcomes for patients.
GW35-e0705
Lingling Zhang
Xiangtan Central Hospital
OBJECTIVES Our objective was to design diagnostic models to predict initial heart failure hospitalizations in Unstable Angina (UA) patients, and to craft prognostic models for their potential re-hospitalizations due to recurrent or onset heart failure after discharge. The intent is to facilitate early identification of high-risk individuals and enhance patient care strategies.
METHODS We retrospectively analyzed data from 12,857 patients diagnosed with acute coronary syndrome from January 2015 to March 2023. After rigorous screening, 7092 UA patients were selected. This data was randomly allocated into a training (4964 patients) and validation (2128 patients) cohort. Diagnostic and prognostic models were then formulated and assessed. Logistic and Lasso regression were employed to pinpoint risk factors associated with initial heart failure admissions. With these factors, diagnostic models were developed, and their efficacy assessed via ROC curves. Similarly, using the same factors, prognostic models were developed to predict re-hospitalizations due to recurrent or onset heart failure at 1, 2, and 6 months post-discharge.
RESULTS The Lambda.1se criterion in our Lasso regression analysis identified three pivotal risk factors associated with initial heart failure admissions: LVd, NTproBNP, and Ischemic cardiomyopathy. Within the training cohort, the diagnostic model exhibited a strong AUC of 0.938, with a 95% confidence interval spanning from 0.909 to 0.955 after 200 Bootstrap replicates. In the validation cohort, an AUC of 0.931 was observed, with a 95% confidence interval of 0.901–0.956 post 200 replicates. This underscores the model’s consistent and reliable performance in both groups. Moreover, prognostic models for 1, 2, and 6 months post-discharge presented AUC values of 0.770, 0.794, and 0.751, respectively, vouching for their utility in prognostic evaluations.
CONCLUSION We have effectively crafted and validated Unstable Angina Diagnostic and Prognostic Heart Failure models (The UADP-HF Model). Implementing these models can aid in the swift identification of high-risk patients, allowing for prompt and tailored interventions.
Keywords: unstable angina; heart failure, diagnostic models, prognostic models, lasso regression analysis
GW35-e0722
Dan Deng, Yue Feng, Min Zeng, Shuhui Chen, Zhihui Zhang
Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Army Medical University
OBJECTIVES This study aimed to explore the synergistic diagnostic potential of integrating assessments of coronary flow reserve (CFR), fractional flow reserve (FFR), and index of microcirculatory resistance (IMR) in coronary artery disease patients, with the objective of establishing a more precise diagnostic and therapeutic pathway for coronary artery diseases.
METHODS A retrospective analysis was conducted on the records of 301 patients who underwent CFR, FFR, and IMR testing at the First Affiliated Hospital of Army Medical University between March 20, 2022, and November 6, 2023. Patients were categorized into four groups based on test results: CFR and IMR both negative, CFR negative but IMR positive, CFR positive and IMR negative, and both CFR and IMR positive. The proportions of FFR-positive cases within each category were meticulously documented, with particular attention paid to the post-interventional dynamics of IMR in IMR-positive patients.
RESULTS Among 330 examined vessels, 56.3% (186 vessels) were found to have both CFR and IMR negative, of which 48 showed positive FFR. In 25.78% (85 vessels) with CFR negative and IMR positive, 13 concurrently had positive FFR. Additionally, 7.88% (26 vessels) displayed CFR positive and IMR negative, with 8 FFR-positive cases. Lastly, 10.00% (33 vessels) showed positivity for both CFR and IMR, among which 12 were also FFR-positive; notably, post-interventional normalization of initially elevated IMR was observed in 6 vessels.
CONCLUSION Combining CFR, FFR, and IMR markedly improves coronary function assessment, excel in detecting microvascular issues, with IMR revealing unique insights, including FFR issues in normal CFR cases. Post-intervention IMR improvements highlight the need for ongoing functional monitoring during interventions, previewing a novel strategy for optimized coronary disease management via comprehensive physiological indicators.
GW35-e0728
Takumi Nakayama1, Masahiro Suzuki2, Morihiro Matsuda3, Yoichi Ajiro4, Tsuyoshi Shinozaki5, Satoru Sakagami6, Kazuya Yonezawa7, Masatoshi Shimizu8, Junichi Funada9, Takashi Takenaka10, Yukiko Morita11, Toshihiro Nakamura12, Kazuteru Fujimoto13, Hiromi Matsubara14, Toru Kato15, Takashi Unoki1,16, Daisuke Takagi1,17, Kyohma Wada1,18, Miyaka Wada1, Yuka Maeda1, Nobutoyo Masunaga1, Mitsuru Ishii1, Moritake Iguchi1, Kazuhiko Kotani19, Mitsuru Abe1, Masaharu Akao1, Koji Hasegawa1, Hiromichi Wada1
1NHO Kyoto Medical Center
2NHO Saitama Hospital
3NHO Kure Medical Center and Chugoku Cancer Center
4NHO Yokohama Medical Center
5NHO Sendai Medical Center
6NHO Kanazawa Medical Center
7NHO Hakodate National Hospital
8NHO Kobe Medical Center
9NHO Ehime Medical Center
10NHO Hokkaido Medical Center
11NHO Sagamihara National Hospital
12NHO Kyushu Medical Center
13NHO Kumamoto Medical Center
14NHO Okayama Medical Center
15NHO Tochigi Medical Center
16Saiseikai Kumamoto Hospital
17Hirakata Kohsai Hospital
18Japanese Red Cross Kyoto Daini Hospital
19Jichi Medical University
OBJECTIVES Diabetes mellitus (DM) is still significantly associated with the risk of mortality in the general population. Higher circulating fibroblast growth factor 23 (FGF23) levels are associated with the risk of mortality in the general population, in patients with DM, and in those with coronary artery disease (CAD). However, whether FGF23 levels differ according to the diabetic status and whether DM modifies the relationship between FGF23 and mortality in patients with suspected or known CAD are unclear.
METHODS Using data from a multicenter, prospective cohort of 2418 patients with suspected or known CAD, we assessed the association between diabetic status and FGF23 and the impact of DM on the association between FGF23 levels and the risk of all-cause death. FGF23 was measured in 1087 DM and 1331 non-DM patients enrolled in the ANOX Study.
RESULTS The mean age (standard deviation [SD]) of the patients was 70.6 (10.4) years; 67.2% were men. Patients with DM exhibited significantly higher levels of FGF23 compared to those without DM (median [interquartile range], 12.6 [6.7–23.0] vs. 10.8 [5.8–19.1] pg/mL, respectively; P < 0.001). Stepwise multiple linear regression analysis revealed that the log-transformed (Ln-) FGF23 level was independently associated with lower age, DM, lower estimated glomerular filtration rate, lower Ln-Gensini score, anemia, Ln-N-terminal pro-natriuretic peptide, and Ln-high-sensitivity C-reactive protein (P < 0.001 for all). In the entire patient cohort, the FGF23 level was significantly associated with all-cause death after adjusting for potential clinical confounders (hazard ratio per 1-SD increase [HR], 1.09; 95% confidence interval [CI], 1.05–1.14). This association was still significant in patients with DM (HR, 1.13; 95% CI: 1.06–1.20), but not in those without DM (HR, 1.02; 95% CI: 0.88–1.18). Furthermore, FGF23 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in patients with DM, but not in the entire cohort or in those without DM.
CONCLUSION Higher FGF23 levels were independently associated with DM in patients with suspected or known CAD. The prognostic value of FGF23 on mortality was pronounced in patients with DM.
GW35-e0732
Takumi Nakayama1, Tsuyoshi Shinozaki2, Masahiro Suzuki3, Yoichi Ajiro4, Satoru Sakagami5, Morihiro Matsuda6, Junichi Funada7, Masatoshi Shimizu8, Takashi Takenaka9, Yukiko Morita10, Kazuya Yonezawa11, Hiromi Matsubara12, Toshihiro Nakamura13, Kazuteru Fujimoto14, Yujiro Ono15, Toru Kato16, Akiyo Ninomiya17, Takashi Unoki1,18, Daisuke Takagi1,19, Kyohma Wada1,20, Miyaka Wada1, Yuka Maeda1, Nobutoyo Masunaga1, Mitsuru Ishii1, Moritake Iguchi1, Kazuhiko Kotani21, Mitsuru Abe1, Masaharu Akao1, Koji Hasegawa1, Hiromichi Wada1
1NHO Kyoto Medical Center
2NHO Sendai Medical Center
3NHO Saitama Hospital
4NHO Yokohama Medical Center
5NHO Kanazawa Medical Center
6NHO Kure Medical Center and Chugoku Cancer Center
7NHO Ehime Medical Center
8NHO Kobe Medical Center
9NHO Hokkaido Medical Center
10NHO Sagamihara National Hospital
11NHO Hakodate National Hospital
12NHO Okayama Medical Center
13NHO Kyushu Medical Center
14NHO Kumamoto Medical Center
15NHO Higashihiroshima Medical Center
16NHO Tochigi Medical Center
17NHO Nagasaki Kawatana Medical Center
18Saiseikai Kumamoto Hospital
19Hirakata Kohsai Hospital
20Japanese Red Cross Kyoto Daini Hospital
21Jichi Medical University
OBJECTIVES The pre-test probability (PTP) model of obstructive coronary artery disease in Japanese patients with suspected anginal symptoms is not established.
METHODS Using data from two multicenter, prospective cohort studies (the ANOX study and the EXCEED-J study) of 2982 high-risk Japanese patients with chest pain or dyspnea undergoing elective coronary angiography, we calculated the probabilities of obstructive coronary artery disease and compared them to those in the 2019-ESC-PTP model. We also assessed the predictive ability of the 2019-ESC-PTP, alone and in combination with known clinical likelihood determinants of obstructive coronary artery disease (i.e., hypertension, diabetes, dyslipidemia, smoking, chronic kidney disease, previous stroke, history of peripheral artery disease, etc), and/or high-sensitivity cardiac troponin I.
RESULTS The probabilities of obstructive coronary artery disease were much higher than those in most subgroups of the 2019-ESC-PTP model, and the differences seemed to be partly explained by the accumulation of known clinical likelihood determinants. The 2019-ESC-PTP alone significantly predicted obstructive coronary artery disease. The addition of known clinical likelihood determinants markedly improved its prediction, which was further improved by that of high-sensitivity cardiac troponin I.
CONCLUSION We first demonstrated the probabilities of obstructive coronary artery disease based on sex, age, and type of symptoms in high-risk Japanese patients with chest pain or dyspnea. The 2019-ESC-PTP model appears to be useful for relative risk assessment in combination with clinical likelihood determinants and high-sensitivity cardiac troponin I in high-risk Japanese patients.
GW35-e0757
Ning Yan, Wu Wu, Jia Jia
Heart Centre & Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan 750004, People’s Republic of China
OBJECTIVES Stress hyperglycemia ratio (SHR), an index of relative stress hyperglycemia, is linked to the poor clinical outcomes in patients with coronary artery disease (CAD). Nonetheless, the exploration of SHR’s relationship with the prognosis of Acute Myocardial Infarction (AMI) remains scant. Therefore, this study aims to elucidate the connection between SHR and the 1-year clinical outcomes following AMI through a large cohort design analysis.
METHODS This investigation enrolled a cohort of 6219 patients with Acute Coronary Syndrome (ACS), admitted to the General Hospital of Ningxia Medical University. Individuals with severe valvular heart disease, decompensated heart failure, non-ischemic dilated cardiomyopathy, severe renal or hepatic disease, acute infection and/or inflammation, malignancy, hematologic disease, autoimmune disease, those having incomplete medical records or missing follow-up information were systematically excluded. Consequently, the study comprised 4012 participants for final analysis. These patients were stratified into three distinct groups according to the tertiles of the SHR: Group T1 (SHR <0.90, n = 1337), Group T2 (0.90 ≤SHR <1.11, n = 1337), and Group T3 (SHR ≥1.11, n = 1338). The primary outcome measure was the incidence of Major Adverse Cardiac Events (MACE) and all-cause mortality within one year. A Cox regression model was utilized to investigate the relationship between SHR levels and one-year clinical outcomes. Further, the non-linear relationship between SHR and clinical outcomes within one year was delineated utilizing restricted cubic splines (RCS), leading to the establishment of a two-segment Cox proportional hazards model on either side of the determined inflection point.
RESULTS During a 1-year follow-up, a total of 229 all-cause mortalities were record, resulting in an all-cause mortality rate of 5.71% (n = 229). Additionally, 861 MACE were recorded, yielding a MACE rate of 21.46%. After adjusting for covariates, SHR was found to be significantly associated with 1-year MACE [hazard ratio (HR) = 2.18; 95% confidence interval (CI) = 1.64–2.89; P < 0.001] and all-cause mortality (HR = 3.11; 95% CI: = 1.77–5.46; P < 0.001) in patients with AMI, and the T3 group exhibited a higher risk of 1-year MACE (HR = 1.67; 95% CI: = 1.34–2.09; P < 0.001) and all-cause mortality (HR = 1.67; 95% CI: = 1.02–2.73; P = 0.042) compared with T1 group. A U-shaped association was observed between SHR and 1-year MACE as well as all-cause mortality, with inflection points of 0.87 for poor prognosis in both outcomes.
CONCLUSION SHR is significantly and positively associated with one-year clinical outcomes in patients with AMI. Furthermore, there is a specific non-linear association between SHR and MACE and all-cause mortality (both inflection point 0.87). Interventions aimed at reducing SHR levels below 0.87 through medication management have the potential to significantly improve outcomes.
GW35-e0763
Peng Wu1, Ning Yan2, Shaobin Jia2
1First Clinical College, Ningxia Medical University
2Heart Centre & Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University
OBJECTIVES To assess the predictive value of the age, creatinine, and ejection fraction (ACEF) score in determining cardiovascular outcomes in STEMI patients undergoing primary percutaneous coronary intervention (PCI).
METHODS We conducted a retrospective cohort study involving 2971 patients with STEMI undergoing primary PCI for the present analyses. The primary endpoint was major adverse cardiocerebrovascular events (MACCEs) within 1 year, encompassing all-cause death, nonfatal myocardial infarction, rehospitalization for angina, rehospitalization for heart failure, and nonfatal stroke. Patients were divided into tertiles according to the ACEF score levels. Kaplan-Meier analysis curve was performed for survival time. A multivariate regression model was developed to analyze the association between baseline ACEF score and MACCEs. The linear association between baseline ACEF score and MACCEs was explored using smooth curve fitting with parallel subgroup analyses. Receiver operating characteristic (ROC) curve were generated to determine predictive power of ACEF score.
RESULTS Among the 2971 STEMI patients, 471 incident patient cases of MACCEs were ascertained. A multivariate logistic regression analysis indicated that the ACEF score stood out as an independent risk factor for the occurrence of MACCEs [OR = 2.45, 95% CI: 2.05–2.94, P < 0.001]. Furthermore, the likelihood of experiencing the MACCEs showed a steady rise with each increasing ACEF score tertile interval (P < 0.001), as revealed by a gradual escalation in the smooth curve fitting. Subgroup analyses further reinforced this positive correlation. The area under the ROC curve (AUC) for the ACEF score in predicting MACCEs occurrence was 0.702 (95% CI: 0.675–0.729; P < 0.01).
CONCLUSION The elevated ACEF score was independently associated with an increased risk of cardiovascular outcomes and served as a predictor of MACCEs in STEMI patients undergoing primary PCI. This suggests that the ACEF score maybe a valuable marker for risk stratification and prognosis in STEMI patients undergoing primary PCI.
GW35-e0771
Yang Ling
Yijishan Hospital Affiliated to Wannan Medical College
OBJECTIVES New-onset atrial fibrillation (NOAF) in the setting of ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (PCI) is correlated to poor prognosis. Naples prognostic score (NPS), which is a combination of inflammatory and nutritional parameter, has been proven to predict adverse outcomes in STEMI patients. We aim to investigate the relationship between NPS and NOAF in patients with STEMI following PCI.
METHODS A single-centre analysis at the Department of Cardiology of Yijishan Hospital, affiliated to Wannan Medical College in Anhui province. In total, 683 consecutive STEMI patients after PCI were recruited. All patients had been classified as NOAF group and sinus rhythm (SR) group. Both multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the predictability of NPS for NOAF development. Additionally, the comparison of all-cause mortality between two groups was evaluated by the Kaplan-Meier curve.
RESULTS Fifty-one (7.5%) patients of the present study developed NOAF during hospitalization. NPS was found to be independently predictive of NOAF (NPS as continuous variable, odds ratio [OR], 2.207; 95% confidence interval [CI], 1.305–3.732; P < 0.05; NPS as categorical variable, OR, 5.616; 95% CI: 1.252–25.198; P < 0.05). The optimal NPS value in estimating NOAF development in STEMI patients following PCI was >2, with a sensitivity of 72.5% and a specificity of 55.9%, respectively (area under curve (AUC): 0.662, 95% CI: 0.625–0.697, P < 0.001). In addition, the all-cause mortality in NOAF cases is significantly higher in comparison with that in SR group over a median of 44-month follow-up (Log-rank P < 0.001).
CONCLUSION NPS has been proposed to be independently predictive of NOAF in STEMI patients underwent PCI during hospitalization. Furthermore, NOAF is strongly linked to a poor prognosis after discharge.
GW35-e0814
Yue Li, Yan Liu, Tienan Zhou, Junxian Qi, Lei Zhang, Xiaozeng Wang
Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 receptor inhibitor is the standard antithrombotic treatment for patients with coronary atherosclerotic heart disease (CHD) undergoing percutaneous coronary intervention (PCI). However, long-term use of aspirin increases the risk of bleeding, particularly in CHD patients with gastrointestinal disease (GID). In Asia, low-dose rivaroxaban (10 mg/day) has been widely prescribed for patients with atrial fibrillation. The efficacy and safety of rivaroxaban plus P2Y12 inhibitor in CHD patients with GID undergoing PCI are still uncertain.
METHODS This study was a prospective, single-center, randomized controlled trial conducted in China (ChiCTR2100044319). Eligible patients with CHD and GID undergoing PCI were randomly assigned to either the dual pathway inhibition (DPI) group (rivaroxaban 10 mg plus clopidogrel 75 mg daily) or the dual antiplatelet therapy (DAPT) group (aspirin 100 mg plus clopidogrel 75 mg daily) in a 1:1 ratio. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2–5 bleeding requiring medical intervention at 6 months. The secondary endpoint was the incidence of major adverse cardiovascular or cerebrovascular events (MACCE) at 6 months, including cardiac death, nonfatal myocardial infarction, ischemia-driven target vessel revascularization, all-cause death, stent thrombosis, and stroke.
RESULTS A total of 1042 eligible patients were randomized, with 522 in the DPI group and 520 in the DAPT group. BARC type 2–5 bleeding at 6 months was non-inferior for the use of rivaroxaban plus clopidogrel versus aspirin plus clopidogrel [8 (1.5%) vs. 6 (1.2%), absolute risk difference 0.38%, 95% confidence interval (CI) (−1.02–1.78), P < 0.0001 for non-inferiority]. There were no significant differences between the DPI group and the DAPT group in the incidences of 6-month MACCE [11 (2.1%) vs. 10 (1.9%), hazard ratio (HR) 1.10, 95% CI: (0.47–2.59), P > 0.05] and 6-month BARC type 3–5 bleeding [1 (0.2%) vs. 4 (0.8%), HR 0.25, 95% CI: (0.03–2.22), P > 0.05]. The incidence of each component of the MACCE at 6 months, including cardiac death, nonfatal myocardial infarction, ischemia-driven target vessel revascularization, all-cause death, stent thrombosis, and stroke, was similar in the two groups (all P > 0.05). The incidence of abdominal pain was significantly lower in the DPI group than in the DAPT group [25 (4.8%) vs. 50 (9.6%), HR 0.53, 95% CI: (0.33–0.85), P < 0.05]. There were no significant differences in other types of abdominal discomfort and gastrointestinal bleeding events (all P > 0.05).
CONCLUSION In Asian patients with CHD and GID undergoing PCI, the efficacy and safety of rivaroxaban plus clopidogrel were found to be non-inferior to DAPT.
GW35-e0826
Min Zeng, Dan Deng, Shuhui Chen, Zhihui Zhang
Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Army Medical University
OBJECTIVES To investigate the potential association between myocardial bridging (MB) and coronary microvascular disease (CMD), aiming to provide a basis for clinical identification and management of such patients.
METHODS A retrospective analysis was conducted on patients who exhibited myocardial ischemic symptoms, had angiographically confirmed luminal narrowing not exceeding 50%, and underwent either myocardial perfusion imaging or contrast echocardiography at the First Affiliated Hospital of Army Medical University from August 2021 to June 2023.
RESULTS Of the 309 enrolled patients, the median age was 60.0 years (IQR: 54.0–69.0), and 59.8% (185) were male. CMD was diagnosed in 69.6% (215) of the population. After adjusting for conventional cardiovascular risk factors such as gender, age, hypertension, diabetes, and hyperlipidemia via a multivariate logistic regression model, the odds ratio (OR) for the link between MB and CMD was 1.817, hinting at an increased CMD risk associated with MB presence (95% CI: 0.988–3.472); however, this association did not reach statistical significance (P = 0.061).
CONCLUSION While the relationship between MB and CMD did not attain statistical significance (with a P-value closely approaching but not less than 0.05), the OR value suggests a possible trend. Given the near-significant P-value, we propose that future studies with larger cohorts should be conducted to further validate any potential link between MB and CMD, thereby refining our understanding of MB’s role in CMD pathogenesis.
GW35-e0832
Mekhman Mamedov
National Research Center for Therapy and Internal Nedicine
OBJECTIVES The aim of the study was to assess the one-year survival rate of patients with type 2 diabetes (T2DM) with acute and chronic forms of coronary artery disease (CAD) against the background of invasive intervention and complex drug correction.
METHODS The study included 202 people (140 men and 62 women) with acute (non-ST segment elevation myocardial infarction (MI), unstable angina) or chronic (stable exertional angina, post-infarction cardiosclerosis form of CAD and with or without T2DM, which were divided into 4 groups. Most patients (76%) underwent coronary artery revascularization according to indications, and they underwent complex drug therapy 1 year after inclusion in the study, the occurrence of end points was assessed.
RESULTS One year after discharge, the number of cardiovascular complications, assessed by composite endpoints in patients with diabetes, was 2 times higher compared to patients without diabetes (<0.001). To analyze survival, two types of endpoints were formed: hard (death and/or myocardial infarction and/or cerebral stroke) and combined (death and/or myocardial infarction, and/or cerebral stroke and/or revascularization, and/or hospitalization). The survival curves for patients with T2DM and patients without T2DM for the hard end point were statistically significantly different (P = 0.044). At the same time, the survival curves for the hard point in patients with different forms of CAD did not differ (P = 0.62). The Cox proportional hazards model was used to assess the association of risk factors and important clinical variables with endpoints. Seven indicators were used as indicators that may influence the association (covariates): gender, age in years, ejection fraction (EF) less than 50%, high-density lipoprotein cholesterol less than 1 mmol/L for men and 1.2 mmol/L for women, triglycerides above 1.7 mmol/l, a history of PICS and total SYNTAX scores above 25. Taking into account the inclusion of covariates, the presence of diabetes significantly increases the risk of the composite endpoint by 2.96 (1.52–5.76, CI 95%) times. Age also statistically significantly increased the risk of developing the composite endpoints when adjusted for other predictors. At the same time, an EF value of less than 50% tends to increase the risk of developing the analyzed complications.
CONCLUSION In patients with T2DM after a year of observation, regardless of the form of CAD, composite end points were registered 2 times more often than in persons without diabetes. Independent predictors of cardiovascular complications in the studied group of patients were the presence of type 2 diabetes and age. The results highlight the need for effective control of glycemia and other clinical parameters during the outpatient treatment of patients with diabetes and various forms of CAD.
GW35-e0839
Chao Fang1,2,3, Lina Cui1,2,3, Jiawei Zhao1,2,3, Yuzhu Chen1,2,3, Jiaqing Guo1,2,3, Yini Wang1,2,3, Jiannan Dai1,2,3, Bo Yu1,2,3
1Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University
2State Key Laboratory of Frigid Zone Cardiovascular Disease (SKLFZCD)
3The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
OBJECTIVES Existing evidence has identified that high-risk plaque (HRP) characterized by a thin-cap fibroatheroma (TCFA) and/or a minimal lumen area ≤3.5 mm2 were indicative of future cardiovascular events. Diffuse coronary artery disease also contributes to the poor prognosis. The present study aims to investigate the relationship between diffuse high-risk plaque detected by using three-vessel optical coherence tomography (OCT) and long-term clinical outcomes in patients with acute myocardial infarction (AMI).
METHODS A total of 674 patients with AMI who underwent OCT examination of three major epicardial arteries between January 2017 and December 2018 were consecutively studied. Among 2843 nonculprit lesions detected by OCT, 1375 (48.4%) HRPs were identified and divided into diffuse HRP group (lesion length >20 mm, n = 443) and focal HRP group (lesion length ≤20 mm n = 932). Patients were followed up for a median period of 5 years. Major adverse cardiovascular event (MACE) was defined as the composite of cardiac death, nonculprit lesion-related nonfatal myocardial infarction, and unplanned coronary revascularization.
RESULTS The average age of all enrolled patients is 56.7 ± 11.4 years, with 74.9% of male. As compared with focal HRP group, diffuse HRP group had longer lesion length [25.8 (23.0, 30.8) mm vs. 13.2 (9.8, 16.1) mm, P < 0.001], longer lipid length [18.6 (12.3, 24.9) mm vs. 7.0 (4.5, 10.5) mm, P < 0.001], and thinner minimal fibrous cap thickness [73.3 (53.3, 106.7) μm vs. 93.3 (60.0, 130.0) μm, P < 0.001], whereas mean lipid arc was comparable between the two groups. The prevalence of nonculprit plaque rupture (14.2% vs. 7.8%, P < 0.001) was significantly higher in diffuse HRP group than that in the focal HRP group. Nonculprit lesions in diffuse HRP group had higher incidence of macrophage accumulation, microvessels, cholesterol crystals, calcification, and layered plaque phenotype than those in focal HRP group (all P < 0.001). The incidence of nonculprit lesion-related MACE was 4.7% in diffuse HRP group and 1.7% in focal HRP group [HR: 3.155, 95% confidence interval: 1.579–6.301, P = 0.002].
CONCLUSION In patients with AMI, diffuse HRP at nonculprit segment has higher levels of plaque vulnerability and is predictive of future adverse cardiovascular events. Further studies are warranted to investigate the individual treatment strategy of diffuse and focal HRP.
GW35-e0888
Jingyi Yang
Jinzhou Central Hospital
OBJECTIVES Background: Routine dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) increases the risk of upper gastrointestinal bleeding (UGIB) in patients with acute coronary syndromes (ACS). Once UGIB occurs, patients have a poor prognosis. Therefore, it is particularly important to predict the occurrence of UGIB events early and effectively. Purpose: To explore the risk factors for UGIB received DAPT after PCI, and establish and validate a prediction model for preventing UGIB events in these patients for individualized anti-thrombotic strategies formulation.
METHODS One thousand five hundred and ninety patients with ACS who received PCI treatment in Jinzhou Central Hospital from January 1, 2019 to June 30, 2022 were randomly divided into the modeling group (n = 1114) and the validation group (n = 476) in a ratio of 7:3. Based on the independent risk factors screened by logistic regression analysis, a prediction model was developed and visualized to predict the risk of UGIB events in patients with dual DAPT. The validation group was used for verification, and the discrimination, calibration, and clinical practicability of the nomogram were verified using receiver operating characteristic (ROC) curve analysis, Hosmer-Lemeshow (H-L) test, and decision curve analysis (DCA), respectively.
RESULTS The incidence of UGIB in the modeling group was 3.9%. Multivariate logistic analysis indicated that age (OR = 1.06, 95% CI: 1.03~1.09, P < 0.001), history of gastrointestinal ulcer/bleeding (OR = 3.03, 95% CI: 1.39~6.62, P = 0.005), HF (OR = 3.73, 95% CI: 1.88~7.40, P < 0.001), drinking (OR = 2.43, 95% CI: 1.22~4.82, P = 0.011) and Cr (OR = 1.02, 95% CI: 1.02~1.03, P < 0.001) were the independent risk factors for UGIB in these patients. ROC curve analysis showed that the area under the curves were 0.806 (95% CI: 0.739~0.872) and 0.838 (95% CI: 0.737~0.945) in the modeling and validation groups, respectively. The model was well fit according to the calibration curve and the H-L goodness of fit test (modeling group: P = 0.846, validation group: P = 0.326). DCA curve showed that the Nomogram’s net benefit was higher than both extreme curves when the threshold probability greater than 0.02 in the modeling group and validation group, suggesting potential clinical benefits provided by this Nomogram.
CONCLUSION Age, history of gastrointestinal ulcer/bleeding, drinking, HF and Cr are independent determinants for UGIB. The prediction model established by these factors can effectively predict the probability of UGIB events in patients with DAPT after PCI.
GW35-e0920
Li Lin1, Tingfeng Xu2, Yaodong Ding1, Yang Zhang1, Jichao Wang3, Yaxin Zuo3, Minxian Wang2, Yong Zeng1
1Capital Medical University Affiliated Beijing Anzhen Hospital
2Beijing Institute of Genomics, Chinese Academy of Sciences (National Bioinformatics Center)
3Xinglong County People’s Hospital
OBJECTIVES We aim to develop and validate an artificial intelligence model for the diagnosis of coronary artery disease based on facial photos.
METHODS This study prospectively enrolled participants from the coronary artery disease center of Beijing Anzhen Hospital and the cardiovascular department of Beijing Daxing Hospital from August 2022 to November 2023. Before the the coronary angiography, facial photos were taken (including four angles: frontal, left and right 60° lateral faces, and head). 70% participants were randomly divided into the training group and the validation group, with the remaining 30% being as the test group. Firstly, the base model was trained using 2 million facial photos obtained from the publicly available VGGFace dataset, and adjusted by our facial photo dataset (training group and the validation group). In terms of model pre-training, we adopted Masked Autoencoder (MAE), one of the advanced architectures in the current unsupervised pre-training field, and then evaluated the performance of the model on new samples using a test dataset. Based on the evaluation results, the model was adjusted and optimized to improve its performance and generalization ability. Using coronary angiography results as the gold standard, we used the area under the receiver operating curve (ROC) of the artificial intelligence model to evaluate its performance.
RESULTS This study included a total of 5974 participants with 84,964 facial photos. In the training and validation sets, there were 3822 patients with coronary artery disease, with 79,140 facial photos. In the test set, there were 239 patients with coronary heart disease, with 5824 facial photos. The performance of the generative artificial intelligence model based on pre-trained facial photos (MAEimage Net az) reaches the best AUC of existing methods at 0.841, while the model without pre-training based on facial photos (ViT imagenet) has an AUC of 0.824. However, all methods based on the ResNet architecture are weaker than MAE and ViT. Among them, we trained our dataset based on the previous approach of imitating three angles (i.e. front face, left face, and right face) and found that the results obtained from training were weaker than those of ViT architecture, whether in pre-trained (resnet_ehj_image net) or randomly initialized (resnet_ehj_random) model architectures. We further adopted ResNet trained from any angle, and whether in-pre training or random initialization, the model performance was not significantly different from the three angle methods.
CONCLUSION The artificial intelligence model based on facial photos performs well in the diagnosis of coronary artery disease, and is expected to further achieve early diagnosis and treatment of coronary artery disease.
GW35-e0927
Hongkui Chen, Liwei Zhang, Yansong Guo
Fujian Provincial Hospital
OBJECTIVES Estimated glucose disposal rate (eGDR) was proposed as an alternative measure of insulin resistance (IR) and demonstrated a good correlation with clamp studies. The objective of our study was to investigate the association between eGDR and both all-cause and cardiovascular mortality within the general population.
METHODS This study incorporated 49,424 National Health and Nutrition Examination Survey (NHANES) participants aged >18 years from 1999 to 2018. The primary outcome of interest was all-cause mortality, while the secondary outcome focused on cardiovascular mortality. The study employed the restricted cubic spline (RCS) method with three nodes to visually represent the relationships between eGDR and all-cause and cardiovascular mortality. Furthermore, a survey-weighted Cox regression analysis was utilized to investigate the association between eGDR and both all-cause and cardiovascular mortality. Subgroup analysis was conducted to explore potential variations in the association between eGDR and mortality across different subgroups.
RESULTS The average age of study participants was 46.19 years, and 49.11% were male. Over a follow-up period of 483,495 person-years, 6939 deaths have occurred from all causes and 2177 from cardiovascular diseases. The RCS model based on COX regression revealed negative and linear correlations between eGDR and all-cause mortality as well as cardiovascular mortality. After adjusting for potential confounders, multivariable COX regression indicated that the highest eGDR group (Q4) was associated with a 32% decreased risk of all-cause mortality (full adjusted HR = 0.68; 95% CI: 0.58–0.80) and 44% decreased risk of cardiovascular mortality (full adjusted HR = 0.56; 95% CI: 0.40–0.78). Besides, Subgroup analysis revealed that the association between eGDR and death was particularly prominent in younger, non-diabetic and non-CVD participants.
CONCLUSION This study provided evidence from the US that a relatively high eGDR was inversely associated with all-causes.
GW35-e0931
Pengfei Liu
First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES Serum uric acid (SUA) levels are strongly associated with cardiovascular disease (CVD). The objective of this study was to investigate the correlation between the recently updated cardiovascular health (CVH) indicator, Life Essential 8 (LE8), and SUA levels in US adults.
METHODS Cross-sectional analysis was conducted on data extracted from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 in this study. Associations were evaluated through the application of weighted multiple linear, weighted multivariate logistic, and restricted cubic spline models.
RESULTS Among 21,155 participants aged ≥20 years, the mean SUA level was 5.42 ± 0.02 mg/dL. After adjusting for potential confounders, the LE8 score exhibited a negative association with both SUA levels (β: −0.02; 95% CI: −0.022 to −0.019). Participants with moderate and high CVH had lower SUA levels compared to those with low CVH, with corresponding β values (95% CI) of −0.32 (−0.39 to −0.24) and −0.79 (−0.88 to −0.71). The multivariate-adjusted restricted cubic spline analysis indicated a significant nonlinear relationship between LE8 scores and SUA levels (P for nonlinearity < 0.05. In subgroup analyses, there was an interaction between LE8 and age, race, and sex for SUA levels (P < 0.05 for interaction) (−0.39 to −0.24) and −0.79 (−0.88 to −0.71). The multivariate-adjusted restricted cubic spline analysis indicated a significant nonlinear relationship between LE8 scores and SUA levels (P for nonlinearity < 0.05. In subgroup analyses, there was an interaction between LE8 and age, race, and sex for SUA levels (P < 0.05 for interaction).
CONCLUSION A significant negative correlation was observed between LE8 scores and SUA levels in US adults. Maintaining a high CVH level may be beneficial for SUA control.
GW35-e0968
Zhijie Lin, Yansong Guo, Linchuan Chen, Hongkui Chen
Shengli Clinical Medical College of Fujian Medical University, Department of Cardiology, Fuzhou, China
OBJECTIVES The Naples Prognostic Score (NPS) constitutes an innovative metric devised to evaluate the nutritional and inflammatory statuses of patients. This investigation seeks to elucidate the associations between NPS and both contrast-associated acute kidney injury (CA-AKI) and mortality after elective percutaneous coronary interventions (PCI).
METHODS In this retrospective study, we evaluated 5841 subjects who underwent elective PCI. The primary endpoint was CA-AKI, delineated as an escalation in serum creatinine by at least 50% or 0.3 mg/dL within 48 hours following exposure to contrast media. The secondary endpoint encompassed all-cause mortality. Subjects were stratified into groups based on NPS: low (NPS 0–2) and high (NPS 3–4). Employing multivariable logistic regression, we scrutinized the relationship between NPS and CA-AKI, while the impact of NPS on mortality was assessed through Cox proportional hazards regression combined with Kaplan–Meier survival analysis.
RESULTS CA-AKI was manifest in 6.53% of participants (n = 354). Multivariate logistic regression underscored that an elevated NPS significantly augments the risk of CA-AKI (odds ratio = 1.29, 95% CI: 1.09–1.52, P = 0.003). During a median follow-up of 2.85 years, there were 500 fatalities (8.56%). Kaplan-Meier survival analysis demonstrated markedly inferior outcomes in the high NPS group (P < 0.001). Adjusted Cox regression analyses confirmed that a higher NPS robustly predicts increased mortality (hazard ratio = 1.59, 95% CI: 1.28–1.98, P < 0.001).
CONCLUSION NPS serves as a reliable independent prognosticator of both CA-AKI and mortality in patients undergoing elective PCI. Given these findings, the prognostic value of NPS for CA-AKI in particular warrants further validation through prospective studies.
GW35-e0976
Lei Bi, Yu Geng, Yintang Wang, Ou Zhang, Ping Zhang
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
OBJECTIVES The efficacy of optimal medical therapy (OMT) with or without revascularization therapy in patients with stable coronary artery disease (SCAD) remains controversial. We performed a meta-analysis of randomized controlled trials (RCTs) that compared OMT with or without revascularization therapy for SCAD patients.
METHODS Studies were searched in PubMed, EMBASE, and the Cochrane Central Register of Clinical Trials from January 1, 2015, to December 30, 2023. The main efficacy outcome was a composite of all-cause death, myocadiac infarction, revascularization, and cerebrovascular accident. Results were pooled using random effects model and fixed effects model and are presented as odd ratios (ORs) with 95% confidence intervals (CI).
RESULTS Ten studies involving 12,790 participants were included. The arm of OMT with revascularization compared with OMT alone was associated with decreased risks for MACE (OR 0.55 [95% CI: 0.38–0.80], I2 = 93%, P = 0.002), CV death (OR 0.84 [95% CI: 0.73–0.97], I2 = 36%, P = 0.02), revascularization (OR 0.32 [95% CI: 0.20–0.50], I2 = 92%, P < 0.001), and MI (OR 0.85 [95% CI: 0.76–0.96], I2 = 45%, P = 0.007). While there was no significant difference between OMT with revascularization and OMT alone in the odds of all-cause death (OR 0.94 [95% CI: 0.84–1.05], I2 = 0%, P = 0.30).
CONCLUSION The current updated meta-analysis of 10 RCTs shows that in patients with stable CAD, OMT with revascularization would reduce the risk for MACE, cardiovascular death, and MI. However, the invasive strategy does not decrease the risks for all-cause mortality when comparing with OMT alone.
GW35-e0980
Rui Yan, Shaobin Jia, Guangzhi Cong, Bo Shi, Congyan Ye, Shizhe Fu, Kairu Wang, Haowei Li, Baotong He, Zefeng He
General Hospital of Ningxia Medical University
OBJECTIVES Mechanical circulatory support (MCS) devices have been widely used for managing acute myocardial infarction complicated by cardiogenic shock (AMI-CS). However, their use additionally elevates acute ischemic stroke (AIS) risk. There is insufficient data on the risk of AIS associated with early versus late initiation of MCS in AMI-CS cases. Therefore, this study aimed to assess the timing of MCS initiation associated with the risk of AIS in patients with AMI-CS.
METHODS A retrospective of the National Inpatient Sample data analysis (January 2016–December 2020) identified AMI-CS hospitalizations: categorized into early MCS initiation (<48 h) and late MCS initiation (>48 h). The primary outcome was AIS; the secondary outcomes included in-hospital mortality, acute kidney injury (AKI), cardiac arrest, major bleeding, and blood transfusion. The outcomes were compared using logistic multivariate regression and 1:1 propensity score-matching analyses between the groups.
RESULTS From 2016 to 2020, the use of IABP decreased from 35.89% to 30.21%, whereas Impella use increased from 8.49% to 15.27% and ECMO use increased from 2.05% to 2.90%. The incidence of AIS in patients with AMI-CS receiving MCS remained stable over the study period; 3.55% in 2016 and 4.54% in 2020 (P trend = 0.277). Among 78,405 weighted patients with AMI-CS receiving MCS, 82.77% (n = 64,895) and 17.23% (n = 13,510) underwent early and late MCS initiation, respectively. Patients receiving late initiation of MCS were older (67.85 years vs. 66.14 years, P < 0.001), were more of female sex (32.68% vs. 29.95%, P = 0.007), and had a higher burden of Elixhauser comorbidities (comorbidity index >4, 50.74% vs. 31.97%, P < 0.001). The patients with late MCS initiation had higher risks of AIS (5.74% vs. 3.60%; adjusted odds ratio [aOR] 1.46; 95% confidence interval [CI], 1.19–1.79; P < 0.001), AKI (61.73% vs. 50.40%; aOR, 1.41; 95% CI: 1.27–1.55; P < 0.001), and major bleeding (43.19% vs. 29.72%; aOR, 1.12; 95% CI: 1.01–1.23; P = 0.028). There were no significant differences between the groups in terms of incident cardiac arrest, blood transfusion, and in-hospital mortality (all P > 0.050). A propensity-matched cohort, adjusted for risk factors indicated that late MCS initiation remained associated with increased risks of AIS (5.70% vs. 4.14%; aOR, 1.39; 95% CI: 1.08–1.78; P = 0.010), AKI (61.69% vs. 53.55%; aOR, 1.37; 95% CI: 1.23–1.53; P < 0.001), and major bleeding (43.27% vs. 38.50%; aOR, 1.14; 95% CI: 1.02–1.28; P = 0.027). Furthermore, subgroup analysis revealed that an AMI-CS hospitalization with late MCS was consistently associated with a high AIS risk among all subgroups.
CONCLUSION Among patients with AMI-CS, late initiation of MCS was associated with increased risks of AIS, AKI, and major bleeding. Further studies are needed to decipher the optimal timing of MCS initiation to improve outcomes in this critically ill population.
GW35-e0995
Ying Hu, Yitian Chen, Zeya Li, Rongchong Huang
Beijing Friendship Hospital, Capital Medical University
OBJECTIVES The association between hearing problem and cardiovascular disease (CVD) is inconsistent and paradoxical, especially lacking of the study of the Chinese population. We aimed to investigate the association of hearing problem and CVD among a middle aged and elderly Chinese population.
METHODS Data were obtained from the China Health and Retirement Longitudinal Studay (CHARLS) in 2015, including 14,590 Chinese aged over 45 years old. Hearing problem is divided into two categories based on whether you have hearing problems or not, which is self-reported by the patient. Propensity score matching was performed for age, gender, residence, education and married status. Logistic regression models were used to estimate the odds ratios (ORs) of CVD in relation to hearing loss. Subgroup analyses were used to determine whether there were statistically significant differences between groups for age, sex, smoking, hypertension, diabetes etc.
RESULTS After propensity score matching, of the all participants, 47% were male, 51.1% were range 45–65 years. After adjusting for the potential confounders, hearing problem is closely associated with increased cardiovascular events (OR, 2.31; [95% confidence intervals (CI), 1.73–3.09], P < 0.001), hypertension (OR, 1.29; [95% CI: 1.04–1.61], P = 0.022), diabetes (OR, 1.72; [95% CI: 1.19–2.50], P = 0.004), obesity (OR, 1.46; [95% CI: 1.03–2.07], P = 0.004). To reduce obvious differences between groups, we performed subgroup analyses for age, sex, smoking, hypertension, diabetes, stroke etc., however this did not alter the association between the relationship (all P value for interaction > 0.05). Corrected multivariate logistic regression for cardiovascular risk factor indicates that hearing loss may be an independent risk factor for CVD (OR, 1.99; [95% CI: 1.52–2.59], P < 0.001), in addition to traditional risk factors. The association could be explained by ischemia and psychiatric psychological problems.
CONCLUSION There may be a positive correlation relationship between hearing problem and CVD prevalence, and remained unchanged after subgroup analysis of age, sex, smoking, hypertension, diabetes etc. In addition, hearing problem may also be positively associated with hypertension and diabetes.
GW35-e1000
Ho Ying Edwina Sze, Kaihang Yiu
University of Hong Kong
OBJECTIVES Computational pressure-flow dynamics derived fractional flow reserve (caFFR) is an angiographic-derived index to determine the fractional flow reserve (FFR) without invasive pressure wire and hyperaemic stimulus. Although the safety of FFR-guided deferral of revascularization in non-ischemic lesions is well-established, physicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because the LAD often supplies a large territory of myocardium. It has been suggested that due to the relatively large area of myocardium at risk, only hyperaemia-based indexes can be trusted for decision-making in the LAD. Whether caFFR guided deferral of LAD lesions is safe compared to non-LAD lesions is unclear. The aim of the study is to investigate the prognostic implications of caFFR for non-ischemic deferred LAD compared to non-LAD lesions in stable coronary artery disease (CAD) patients.
METHODS This was a retrospective cohort study of patients from Queen Mary Hospital, Hong Kong with a clinical diagnosis of coronary artery disease who underwent coronary angiography between January 1, 2014, and December 31, 2017. Patients underwent PCI according to the angiographic and clinical data available at the time. Among the 1665 stable CAD patients who were recruited from 2014–2017, 650 of the stable CAD patients (mean age = 63.3 ± 12.2, 65.2% male) had non-ischemic lesions defined by caFFR ≥0.80 and did not undergo PCI for said lesions. The primary endpoint was the vessel-oriented composite endpoint (VOCE), defined as vessel-related cardiovascular mortality, vessel-related myocardial infarction (MI) and any unplanned revascularisation at median follow-up time of 4.4 years. Survival curves were constructed using Kaplan-Meier estimates and differences between groups were tested using the log-rank test. Cox proportional hazards model was also used to evaluate the association between an LAD artery and the risk of VOCE, with parameters with P < 0.1 upon univariate analysis entered into multivariable Cox model.
RESULTS A total of 430 (23.1%) LAD and 1434 non-LAD (76.9%) non-ischemic lesions that had not undergone PCI were studied. Mean caFFR was 0.90 ± 0.04 amongst LAD lesions and 0.92 ± 0.04 for non-LAD lesions (P < 0.001). LAD lesions had significantly higher incidence rates than non-LAD lesions in terms of VOCE (6.0% vs. 3.0%; P = 0.003), MI (2.1% vs. 0.6%; P = 0.007), and unplanned revascularisation (4.9% vs. 2.4%; P = 0.009). After multivariate adjustment, LAD lesions had a significantly higher risk than non-LAD lesions in terms of VOCE (HR 1.80; 95% CI: 1.10–2.95; P = 0.019), vessel-related MI (HR 3.54; 95% CI: 1.36–9.20; P = 0.010), and unplanned revascularisation (HR 1.82; 95% CI: 1.06–3.14; P = 0.031).
CONCLUSION In stable CAD patients, caFFR-based deferral has superior prognostic durability in non-LAD lesions compared to LAD lesions during long-term follow up. This novel index could enhance risk stratification of non-ischemic vessels in stable CAD patients for LAD and non-LAD lesions.
GW35-e1006
Jilang Zeng1, Kaiyang Lin2, Yansong Guo2, Yao Zhang1
1Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
2Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
OBJECTIVES Inflammatory response is involved in the development and progression of coronary atherosclerotic heart disease (CHD), and it’s closely linked to poor clinical outcomes. The lactate dehydrogenase-to-albumin ratio (LAR) has recently emerged as a novel inflammatory biomarker. We aim to explore the prognostic significance of LAR in CHD patients undergoing percutaneous coronary intervention (PCI).
METHODS We consecutively enrolled 5435 CHD patients treated with elective PCI from January 2012 to December 2018. The optimal cutoff value (4.14) for the LAR was based on the maximally selected rank statistics. Accordingly, patients were stratified into two groups: the low- (LAR ≤4.14, n = 2697) and high- (LAR >4.14, n = 2738) LAR groups. The primary outcome was all-cause mortality.
RESULTS Over a median follow-up period of 3.0 years, 460 (8.8%) deaths occurred. Restricted cubic spline (RCS) analysis indicated a positive correlation between LAR and all-cause mortality (P for nonlinearity < 0.001). Meanwhile, time-dependent receiver operated characteristic (ROC) analysis demonstrated the good diagnostic value of LAR for all-cause mortality, with an area under the curve (AUC) of 0.638 [95% confidence interval (CI): 0.592–0.684] at 1 year, 0.676 (95% CI: 0.647–0.707) at 3 years, and 0.676 (95% CI: 0.640–0.711) at 5 years. The fully-adjusted COX regression further indicated that the high-LAR group had a 2.1 times higher risk of all-cause mortality compared to low-LAR group [fully-adjusted hazard ratio (HR): 2.10, 95% CI: 1.63–2.70, P < 0.001]. Similarly, Kaplan-Meier curves revealed significant differences in survival rates between the two groups (log-rank test, P < 0.001).
CONCLUSION Among CHD patients undergoing elective PCI, LAR is independently associated with an increased risk of all-cause mortality. Overall, LAR may serve as a promising biomarker for prognostic stratification in this patient group.
GW35-e1020
Biyi Xu1,2, Haibo Jia1,2
1Department of Cardiology, Second Affiliated Hospital of Harbin Medical University
2National Key Laboratory of Frigid Zone Cardiovascular Disease, Harbin Medical University
OBJECTIVES Acute coronary syndrome (ACS), which is result from the sudden thrombotic occlusion of coronary artery. ACS could be divided into three common subtypes according to pathology mechanism: plaque rupture (PR), plaque erosion (PE) and calcified nodule (CN). PR is the most common subtype of ACS, which accounts for about two-thirds of ACS; PE, has been found in approximately one-thirds of ACS. PE shown much difference to PR, such as plaque morphology, treatment strange, cardiovascular risk and predictive factor. Plaque rupture characteristics with a large necrotic lipid core and thin fibrous cap with discontinued endothelial layer, and more likely to stent implanted, patients with plaque rupture more suffer from hypertension, diabetes and chronic kidney disease, and show higher cardiovascular risk than plaque erosion. Autopsy and OCT studies demonstrated that plaque rupture expressed higher “inflammasome state” than plaque erosion. Ruptured plaque contains more macrophages and T lymphocytes than eroded plaque, and cytokine array was used to compared inflammation state ruptured plaque and eroded plaque, the result shown rupture patients expressed higher I-TAC level than erosion patients. As we know, the level of inflammatory factor may influence by others organs, but not only atherosclerosis plaque. At this study, we compared the inflammatory factor mRNA level of white blood cell in different culprit lesion and explore the biomarker for diagnosis erosion and rupture patients.
METHODS We prospectively enrolled consecutive STMEI patients who underwent OCT examination in the second hospital of Harbin medical university, the study was approved by the Harbin medical university ethics committee. STEMI was defined as continuous chest pain lasting >30 minutes, ST-segment–elevation >0.1 mV in at least 2 contiguous leads or new left bundle-branch block on the 18-lead ECG, and an elevated troponin I level. The patients cardiac shock, congestive heart failure, end-stage renal disease, and coronary artery bypass graft were excluded. All of the patients provided written informed consent. The patients were divided into two groups (Plaque rupture and erosion) according to OCT image. Thre hundred and six STEMI patients were included in the study, 63 patients were excluded because of the poor quality of white blood cell (hemolysis, chloremia, fail of RNA extraction). The blood samples were collected pre-PCI, and white blood cell was separated by Lymphocyte Separation Medium kit (Solarbio, Beijing, China) according to specification. And add 500 μl trizol (Thermo Scientific) into the WBC for RNA extraction, the RNA concertation was evaluated by BioSpec-nano. The RNA quality which out of the rang (OD260/280, 1.6–2.2; OD260/230, 1.6–2.2) was excluded, and Reverse transcription kit (Roche, Switzerland) was used to reverse RNA to cDNA. The PCRs were amplified for 40 cycles (95 °C for 10 seconds, 61 °C for 30 seconds) on a 96-well CFX96 Real-Time System (BIO-RAD). mRNA analyzed for proinflammatory factor (IL-8, IL-1β and TNF-α) and anti-inflammatory factor (IL-4, and IL-10).
RESULTS For anti-inflammatory cytokine, rupture patients show higher expression of IL-4 and IL-10 than erosion patients (P < 0.05), and for proinflammatory cytokine, rupture patients show higher expression of TNFα than plaque erosion (P < 0.001); to our surprise, plaque erosion show higher expression of IL-1β than rupture patients (P < 0.05). And there was no significant difference in IL-8 expression between plaque rupture and plaque erosion (P > 0.05).
CONCLUSION The white blood cell in rupture patients show higher anti-inflammatory and proinflammatory cytokine than erosion patients. IL-1β was higher expressed in erosion patients, which suggested that IL-1β plays an important role in the progress of plaque erosion.
GW35-e1038
Haoyu Wang
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Few large-scale studies have evaluated the effectiveness of percutaneous coronary intervention (PCI) technological advances in the treatment of patients with unprotected left main coronary artery disease (LM-CAD). We aim to identify independent factors that affect the prognosis of PCI in patients with unprotected LM-CAD, and to assess the impact of PCI technological advances on long-term clinical outcomes.
METHODS Four thousand five hundred and twelve consecutive patients who underwent unprotected LM-CAD PCI in Fuwai Hospital from 2004 to 2016 were enrolled. Multivariable Cox proportional hazards model was used to identify which techniques can independently affect the incidence of major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction, or target vessel revascularization).
RESULTS The incidence of 3-year MACE was 9.0% (406/4512). By multivariable Cox proportional hazards regression, nine independent risk factors that associated with the incidence of MACE were identified. Five were inherent risk factors, including lower EF (adjusted hazard ratio [aHR]: 0.98, 95% CI: 0.96–0.99 for every 1% reduction in EF), prior PCI (aHR: 1.45, 95% CI: 1.15–1.82), COPD (aHR: 2.77, 95% CI: 1.29–5.96), higher SYNTAX score (aHR: 1.03, 95% CI: 1.01–1.05 for each 1 point increase in the SYNTAX score), and number of stents implanted (aHR: 1.13; 95% CI: 1.00–1.28 for each additional stent implanted). On the other hand, four new techniques were protective factors for MACE, including 2nd-generation DES (aHR: 0.61, 95% CI: 0.37–0.99), post-dilatation (aHR: 0.75, 95% CI: 0.59–0.94), final kissing balloon inflation (FKBI, aHR: 0.78; 95% CI: 0.62–0.99), and IVUS (aHR: 0.78, 95% CI: 0.63–0.97). The MACE rate of at 3 years was significantly lower in patients treated with all four techniques versus those without using any four techniques (4 techniques vs. 0 techniques: 5.8% vs. 10.9%; aHR: 0.53, 95% CI: 0.32–0.87, P = 0.011). For the components of MACE, implantation of 2nd-generation DES was associated with lower occurrence of cardiac death, whereas the reduced risk of MI was mainly associated with the use of post-dilatation, FKBI and IVUS. Of note, post-dilatation and FKBI reduced the risk of peri-procedural MI, while there was lower rate of spontaneous MI with IVUS guidance. However, none of four techniques had an impact of 3-year risks of TVR. Landmark analysis was performed to determine whether the effects of using new techniques on both short-term and long-term prognosis. We found that the beneficial impact of use of all 4 new techniques was prominent within 30 days after LM-CAD PCI, but continued divergence was not observed throughout the long-term period. Experienced operators had a significant higher rate of using all four techniques (21.8% vs. 13.0%, P < 0.001) and a marginally lower rate of 3-year MACE (8.3% vs. 9.8%, P = 0.088), compared to operators with low annual volume.
CONCLUSION PCI technological advances including post-dilatation, 2nd-generation DES, FKBI, and IVUS guidance were associated with improved clinical outcomes of patients who underwent unprotected LM-CAD PCI.
GW35-e1054
Galina Kukharchik, Daria Nedbaeva
Almazov National Medical Research Centre
OBJECTIVES Objective was to assess the impact of frailty on platelet function in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS).
METHODS The study included 126 patients with NSTE-ACS, who underwent standard laboratory and instrumental evaluations. Functional deficits and the frailty index were assessed using a questionnaire based on M. Hoover et al. On days 1 and 7–10, P-selectin expression and the number of GPIIb-IIIa receptors on thrombocytes (measured by mean fluorescence intensity, MFI) were analyzed before and after activation with 10 μM ADP. This was done using flow cytometry with fluorescently labeled monoclonal antibodies CD61-FITC and CD62P-PE on a CYTOMICS FC 500 flow cytometer.
RESULTS Based on the frailty index values, patients with NSTE-ACS were divided into three groups: 49 patients with frailty syndrome (38.9%), 47 patients with pre-frailty syndrome (37.3%), and 30 patients without frailty syndrome (23.8%). Chronic anemia (30.6%) and a glomerular filtration rate below 60 mL/min/1.73 m2 (46.9%) were more prevalent in frail patients compared to non-frail patients (6.6% and 16.6%, respectively, P < 0.05). Acute heart failure (Killip class II and above) was more frequent in frail patients (16 patients) than in pre-frail or non-frail patients (P = 0.016). Cardiogenic shock was only observed in frail patients (2 cases). Histories of myocardial infarction, hypertension, stroke, and chronic obstructive pulmonary disease were similarly common across all groups. The most frequent geriatric syndromes in older patients included impaired vision, hearing, memory, urinary function, and cognitive deficits. The most significant increase in GPIIb-IIIa receptor numbers was observed in frail patients, both before ADP exposure (8.31 [6.49; 9.17]) and after (12.5 [11.45; 14.05], P = 0.04), compared to non-frail patients (before ADP: 6.27 [5.24; 6.89]; after ADP: 6.34 [6.05; 9.61], P = 0.02). P-selectin expression was significantly higher in frail patients after ADP induction (10.65 [4.04; 15.77]) compared to pre-frail (5.92 [1.23; 16.45]) and non-frail patients (2.48 [1.10; 5.35], P = 0.01). During hospitalization, frail patients experienced higher rates of mortality, bleeding, rhythm disturbances, and early post-infarction angina compared to pre-frail and non-frail patients (36.7%, 10.6%, and 3.3%, respectively; P = 0.01).
CONCLUSION Patients with frailty syndrome frequently have comorbid conditions and acute heart failure in NSTE-ACS. Additionally, they exhibit higher platelet functional activity (increased P-selectin expression and GPIIb-IIIa receptor numbers), suggesting a greater thrombogenic potential and higher risk of adverse outcomes.
GW35-e1055
Jinxing Liu, Xiaorong Han, Yingzhen Gu, Yifan Li, Jiangshui Wang, Wei Zhang, Naqiang Lv, Aimin Dang
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES To investigate the correlation between triglyceride (TG) and high-sensitivity C-reactive protein (hsCRP) levels and the risk of adverse cardiovascular events in a cohort of patients with coronary artery disease (CAD) to provide clues for the secondary prevention of CAD.
METHODS In patients aged ≥18 years who were diagnosed with CAD between January 2016 and November 2019 were included. The exclusion criteria were as follows: (1) history of malignant tumor; (2) severe hepatic or renal dysfunction (aminotransferase level >10 times the upper limit of normal, serum creatinine level >442 μmol/L); (3) acute infection at the time of hospitalization; (4) active autoimmune disease or treatment with glucocorticoid drugs; and (5) severe cardiac insufficiency (left ventricular ejection fraction <30%). Demographic data, medical history, drug treatment, and biochemical indicators were collected. The primary endpoint of the study was major adverse cardiovascular events (MACEs), a composite endpoint consisting of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization. The secondary endpoint was all-cause death.
RESULTS During a median follow-up of 4.88 years, 354 MACEs occurred, including 67 all-cause deaths, 36 nonfatal myocardial infarctions, 33 strokes, and 218 unplanned revascularizations. Preliminary statistical analysis suggested that hsCRP was independently associated with the risk of all-cause death [hazard ratio (HR) = 1.083, 95% CI: 1.022–1.147]. The level of hsCRP increased the risk of MACEs (HR = 1.026, 95% CI: 0.993–1.060) but did not reach statistical significance (P = 0.123). TG was not independently associated with MACEs or all-cause death. Restricted cubic spline (RCS) analysis indicated that TG and hsCRP were nonlinearly correlated with MACE, and the potential target point of TG was 3.81 mmol/L. TG concentration ≥3.9 mmol/L and hsCRP level were included in the multivariate regression model, and the results suggested that TG concentration ≥3.9 mmol/L was significantly associated with an increased risk of MACEs (HR = 1.624, 95% CI: 1.022–2.582). hsCRP tended to increase the risk of MACEs (HR = 1.025, 95% CI: 0.92–1.059), but the difference was not statistically significant. Propensity score matching was used to match sex (male), age, current smoking status, systolic blood pressure, BMI, and PCI history at a 1:2 ratio (TG ≥3.9 mmol/L vs. TG <3.9 mmol/L). The survival results of the matched cohort suggested that TG ≥3.9 mmol/L was associated with an increased risk of MACEs (P = 0.022) but was not significantly associated with the risk of all-cause death (P = 0.4).
CONCLUSION hsCRP was independently associated with the risk of all-cause death in CAD patients. When TG ≥3.9 mmol/L, regardless of the level of hsCRP, an increase in TG is independently associated with the risk of major adverse cardiovascular events in CAD patients. Therefore, when TG ≥3.9 mmol/L after receiving effective statin treatment, it may be necessary to actively apply TG-lowering drugs to further reduce the residual risk in CAD patients.
GW35-e1056
Shandong Yu1, Yanpeng Chu2
1Beijing Friendship Hospital
2Dazhou Central Hospital
OBJECTIVES Cardiovascular disease (CVD) is the leading cause of death globally, and its prevalence is significantly rising in China. While traditional risk factors such as hypertension, diabetes, and hyperlipidemia account for a substantial portion of CVD risk, residual risk remains unexplained. Concurrently, the global incidence of both depression and obesity is increasing, with potential implications for CVD risk. This study aims to investigate the combined and interactive effects of body mass index (BMI) and depression on the incidence of CVD among Chinese adults, using data from the China Health and Retirement Longitudinal Study (CHARLS).
METHODS We analyzed data from 9925 participants in the CHARLS database collected between 2015 and 2020. Participants were categorized based on their BMI as normal weight (<24.0 kg/m2), overweight (24.0–27.9 kg/m2), and obese (≥28.0 kg/m2). Depression levels were assessed using the CESD-10 (Center for Epidemiologic Studies Depression Scale), categorizing participants into no depression, mild/moderate depression, and severe depression. Cox proportional hazards models were employed to estimate hazard ratios (HRs) for CVD incidence, adjusting for potential confounders such as age, sex, smoking status, physical activity, and existing comorbidities. Subgroup analyses were also conducted to explore variations in CVD risk by age, gender, and diabetes status.
RESULTS Over the follow-up period, 1644 participants developed CVD. Overweight and obesity were associated with a higher risk of developing CVD, with HRs of 1.17 (95% CI: 1.02–1.34) and 1.22 (95% CI: 1.05–1.42), respectively. Similarly, mild/moderate depression and severe depression were linked to increased CVD risk, with HRs of 1.43 (95% CI: 1.24–1.64) and 1.82 (95% CI: 1.54–2.15), respectively. Notably, there was a significant joint effect of severe depression and obesity on CVD risk (HR 2.72, 95% CI: 2.02–3.67), indicating a compounded risk when both conditions are present. An antagonistic interaction between severe depression and overweight was also observed (HR 0.65, 95% CI: 0.43–0.99), suggesting a complex interplay between these factors. Subgroup analyses: revealed that non-diabetic individuals showed significant CVD risks across all BMI and depression groups, particularly in the severely depressed obese group, which had an HR of 2.84 (95% CI: 1.62–4.98). Among participants aged 45–55 years, the highest risk was observed in the severely depressed obese group, with an HR of 4.77 (95% CI: 2.24–10.1), highlighting the significant impact of these factors in this age group. Gender-specific analysis indicated that both males and females exhibited similar risk patterns, with substantial risks in the severely depressed obese groups. However, in diabetic participants, none of the associations between BMI, depression, and CVD risk reached statistical significance, suggesting that the combined effects of BMI and depression on CVD risk might be less pronounced in this subgroup due to other overriding factors related to diabetes.
CONCLUSION The study findings underscore the significant independent and combined effects of high BMI and depression on CVD risk. These effects are particularly pronounced in non-diabetic individuals and specific age subgroups, emphasizing the need for integrated prevention strategies that address both physical and mental health to effectively reduce CVD risk. Further research is warranted to elucidate the underlying mechanisms and develop tailored interventions for these high-risk populations.
GW35-e1059
Daria Nedbaeva, Valeria Mikhaleva, Galina Kukharchik
Almazov National Medical Research Centre
OBJECTIVES Patients with non-ST elevation acute coronary syndrome (NSTE-ACS) represent a heterogeneous group, including both clinical, laboratory and angiographic characteristics as well as the course of the disease. The available prognostic scales for risk assessment in NSTE ACS present a number of advantages and limitations, which makes it essential to search for more accurate predictors of unfavourable prognosis. Therefore, the objective of this study is to determine the significance of angiographic data for predicting hospital mortality in patients with NSTE-ACS.
METHODS The present study analysed retrospective data pertaining to 2348 patients admitted to hospital with a diagnosis of NSTE-ACS. The characteristics of the disease course, the presence of risk factors, and data from laboratory and instrumental investigations were included in this analysis. A total of 62 indicators were available. The outcome of interest, hospital mortality, was registered in 172 of the 2348 patients included in the analysis. The statistical methods included the Mann-Whitney test, the chi-square test and the logistic regression method.
RESULTS A number of indicators were associated with an unfavourable course of acute coronary syndrome. These included such well-established risk factors as age, comorbidity, and anaemia. Among the angiographic parameters, multivessel disease (P = 0.006, RR = 1.5 (1.1; 2.0)), chronic occlusions (P = 0.0001, RR = 1.7 (1.2; 2.3)), and left main stem lesions (P = 0.042, RR 1.4 (1.1; 1.8)) were found to be associated with hospital mortality. The association between inflammatory markers and hospital mortality has been investigated. Both leukocytes and complex hematological parameters have been found to be associated with mortality. It is highly significant to highlight the correlation between hospital mortality and lymphocyte/monocyte ratio (LMR), systemic inflammation index (SII) and systemic inflammation response index (SIRI), P = 0.0001. Adding these parameters to the angiographic data model resulted in a notable improvement in its prognostic significance (AUC 0.80 vs. 0.68). The newly developed prognostic model exhibited 75% sensitivity and 76% specificity, in comparison to the 64% sensitivity and 63% specificity observed in the angiographic model.
CONCLUSION The integration of inflammatory markers with angiographic data increases the accuracy of hospital mortality prediction model in patients with NSTE-ACS.
GW35-e1074
Yipu Ding1,2, Zinuan Liu1,3, Ran Xin1,2, Ziqiang Guo1,3, Yundai Chen1, Junjie Yang1
1Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital
2School of Medicine, Nankai University
3Medical School of Chinese PLA
OBJECTIVES Traditionally, women are known to have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Coronary computed tomography angiography–derived fractional flow reserve (CT-FFR), as a newly emerged functional assessment, could increase the specificity of the diagnosis of stable angina over anatomic assessment with coronary computed tomographic angiography (CCTA) alone, irrespective of sex. Whether CT-FFR improves sex-based patient management decisions compared to CCTA alone is unknown. This study aims to determine the management and clinical outcomes of patients investigated with CT-FFR according to sex.
METHODS The Effect of On-site CT-derived Fractional Flow Reserve on the Management of Decision Making for Patients with Stable Chest Pain (TARGET) trial enrolled 1216 patients with stable coronary artery disease and an intermediate stenosis of 30% to 90% on CCTA who were randomized to an on-site CT-FFR care pathway using machine learning or to standard care in 6 Chinese medical centers. Demographics, symptom status, CCTA parameters, CT-FFR values, and management plans were recorded. The primary endpoint was the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease who did not undergo intervention within 90 days. Secondary endpoints included major adverse cardiovascular events (MACE), quality of life, symptoms of angina, and medical expenditure at 1 year.
RESULTS Among both groups, women were older (standard care group: 62 ± 9 years vs. 58 ± 12 years; CT-FFR care group: 62 ± 8 years vs. 59 ± 9 years, both P < 0.001) and had a lower prevalence of current smoker and alcohol usage. The prevalence of other risk factors such as hypertension, dyslipidemia, diabetes mellitus, and family history of CAD was similar in both sexes. A total of 421 out of 608 patients (men: 280/398; women: 141/210) in the CT-FFR care group and 483 of out 608 patients (men: 310/387; women: 173/221) in the standard care group underwent invasive coronary angiography. Compared to standard care, the proportion of men undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease not undergoing intervention was significantly reduced in the CT-FFR care group (51.9% [161/310] vs. 26.8% [75/280], P < 0.001), whereas this reduction was not significant for women (35.8% [62/173] vs. 31.2% [44/141], P = 0.388). Overall, more men underwent revascularization in the CT-FFR care group than in the standard care group (51.5% [205/398] vs. 38.5% [149/387], P < 0.001), while this increase was not significant among women (46.2% [97/210] vs. 50.2% [111/221], P = 0.402). Notably, MACE at 1 year did not differ between men and women in both groups (Log-rank P = 0.656).
CONCLUSION CT-FFR demonstrates sex-specific differences in its impact on patient management, which reduces the number of men undergoing unnecessary invasive coronary angiography without obstructive disease or intervention within 90 days and increases revascularization rates among men. However, this benefit was not observed in women, where CT-FFR does not significantly alter the rates of invasive procedures or revascularizations.
GW35-e1081
Liang Chen1, Yawei Xu2
1School of Medicine, Tongji University
2Department of Cardiology, The Tenth People’s Hospital of Tongji University
OBJECTIVES To investigate the impact of AdipoQ polymorphisms, and their additional interactions with smoking and drinking on coronary heart disease (CHD) risk based on Chinese population.
METHODS Hardy–Weinberg equilibrium (HWE) was performed using SNPStats (available online at http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) model was used to screen the best gene–gene and gene–environment interaction combinations. Logistic regression was performed to investigate association between four single-nucleotide polymorphisms (SNPs) and CHD and the interaction effect between rs1501299 and smoking.
RESULTS Logistic analysis showed that CHD risks were higher in carriers with homozygous mutant of rs1501299 and rs2241766 than those with wild-type homozygotes, odds ratio (ORs) (95% CI) were 1.49 (1.19– 1.95) and 1.71 (1.33–2.24), respectively, but CHD risks were lower in carriers with homozygous mutant of rs7649121 than those with wild-type homozygotes, OR (95% CI) was 0.72 (0.51–0.96). GMDR model indicated that there was a significant two-locus model (P = 0.0107) involving rs1501299 and current smoking, indicating a potential gene–environment interaction between rs1501299 and current smoking. Overall, the cross-validation consistency of this model was 9/10, and the testing accuracy was 60.11% (P = 0.0010). T-allele carriage had 42% prevalence, and one-quarter of them were current smokers. Smokers with rs1501299-GT or TT genotype have the highest CHD risk, compared to never-smokers with rs1501299-GG genotype, OR (95% CI) was 3.56 (1.91– 5.42), after adjustment for gender, age, alcohol status, and body mass index. But we did not find any significant gene–gene and gene–drinking interaction combinations in GMDR models.
CONCLUSION Polymorphisms in rs1501299 and rs2241766, and their additional interactions between rs1501299 and smoking were associated with increased CHD risks: polymorphism in rs7649121 was associated with decreased CHD risks.
GW35-e1084
Zhijie Lin, Linchuan Chen, Hongkui Chen, Yansong Guo
Shengli Clinical Medical College of Fujian Medical University, Department of Cardiology, Fuzhou, China
OBJECTIVES Post-acute myocardial infarction (AMI) late left ventricular (LV) remodeling, an insufficiently recognized pathologic transformation in ventricular morphology, is intricately linked to the anatomical and functional synergy between the LV and the arterial system. Consequently, this investigation ascertains the prognostic significance of compromised ventricular-arterial coupling (VAC) for predicting late LV remodeling in AMI patients subjected to percutaneous coronary intervention (PCI).
METHODS This retrospective cohort study encompassed 829 successive AMI patients undergoing PCI at Fujian Provincial Hospital from 2012 to 2020. In assessing VAC, we quantified the arterial to ventricular end-systolic elastance ratio (Ea/Ees) through echocardiographic determination, computed as end-systolic volume divided by stroke volume (ESV/SV). The principal outcome was late LV remodeling, delineated as a decrement in left ventricular ejection fraction (LVEF) to less than 50% between 3 and 12 months after AMI, while additional outcomes encompassed all-cause mortality and major adverse cardiovascular events (MACE).
RESULTS Documented in 6.1% of participants (n = 121), late LV remodeling demonstrated a robust association with the Ea/Ees ratio through multivariate logistic regression analysis (Odds Ratio = 11.17, Confidence Interval: 5.70–23.59, P < 0.001). Further analysis using Receiver operating characteristic (ROC) curves determined an optimal Ea/Ees threshold of 0.86, which exhibited an area under the curve (AUC) of 0.77 (95% CI: 0.71–0.82, P < 0.001). Additionally, integrating the Ea/Ees ratio with a comprehensively adjusted logistic regression model markedly augmented the predictive accuracy for late LV remodeling, evidenced by a C-statistic increase from 0.774 to 0.828 (P < 0.001), continuous net reclassification improvement of 0.704 (P < 0.001), and integrated discrimination improvement of 0.075 (P < 0.001).
CONCLUSION Given these findings, compromised ventricular-arterial coupling serves as an independent prognosticator for late LV remodeling in AMI patients undergoing PCI, highlighting its potential utility in clinical assessments and interventions.
GW35-e1095
Marianne Therese Punsalan, Jose Paolo Prado, Kristine Coup Macapagal
The Medical City - Pasig, Manila, Philippines
OBJECTIVES The study aimed to determine the incidence of in-hospital bleeding in acute coronary syndrome (ACS) patients admitted in a private tertiary hospital and investigate its relationship with in-hospital, 7-day, and 30-day mortality.
METHODS This retrospective cohort study utilized the Acute Myocardial Infarction Clinical Care Program (AMI CCP) registry of a private tertiary hospital in Manila, Philippines. All patients diagnosed with ACS admitted during the 12-month period of April 2023 to March 2024 were included in the study. Patients were classified according to the Bleeding Academic Research Consortium (BARC) bleeding definition.
RESULTS Among 140 ACS patients, the incidence of overall in-hospital bleeding was 26.4%, while the incidence of major bleeding events as represented by BARC type 3 was 1.4%, which involved gastrointestinal bleeding and pericardial effusion. Comparing patients with vs. without bleeding events, female sex (P = 0.01), non-smoker status (P = 0.01), use of left radial (P = 0.02) and right femoral (P = 0.001) access sites were significantly associated with in-hospital bleeding. Overall, the in-hospital mortality among ACS patients was 5.7% (n = 8). The proportion of mortality among those with bleeding events was 10.8% vs. 3.9% among those without bleeding (P = 0.21). Patients with in-hospital bleeding events had an increased risk of in-hospital mortality (RR 2.78, 95% CI: 0.73–10.57, P = 0.13), though no deaths were documented during the 7-day and 30-day follow-up.
CONCLUSION The rate of major in-hospital bleeding BARC 3–5 was relatively low among ACS patients but may still increase the risk of in-hospital mortality hence close care should be taken especially if with identified predictors of bleeding.
GW35-e1104
Yixuan Duan, Miaohan Qiu, Jing Li, Yi Li, Yaling Han
Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES The purpose of this study was to investigate the prognosis of patients with acute coronary syndrome (ACS) with high bleeding risk (HBR) at different levels of inflammation undergoing percutaneous coronary intervention (PCI).
METHODS Patients with ACS (n = 6957) who underwent PCI between March 2016 and March 2019 in the Department of Cardiology of the General Hospital of Northern Theater Command were included in this study. Included patients were stratified according to ARC-HBR criteria and hsCRP during hospitalization. The primary endpoint was ischemic events at 12 months, composed of cardiac death, myocardial infarction, and/or stroke. Secondary endpoints included the independent component of ischemic events at 12 months, all-cause death, all bleeding events, and Bleeding Academic Research Consortium type 2 to 5 and 3 to 5 bleeding.
RESULTS Among the primary outcome events, the risk of ischemic events was significantly higher in the high hs-CRP group of non-HBR patients (HR 1.68, 95% CI: 1.13–2.51, P = 0.0101), whereas there was no significant difference in the risk of ischemic events between the different hs-CRP groups in patients with HBR. Among the secondary endpoints, the 12-month risk of all-cause mortality was significantly higher in the high hs-CRP group than in the low hs-CRP group (HR 1.83, 95% CI: 1.26–2.66, P = 0.0016). Similarly, in non-HBR patients, the risk of all-cause mortality was significantly higher in the high hs-CRP group than in the low hs-CRP group (HR 1.64, 95% CI 1.01–2.64, P = 0.0441). In terms of cardiac death, the risk of high hs-CRP was higher in HBR patients than in the low hs-CRP group (HR 1.56, 95% CI: 1.02–2.40, P = 0.0422), and high hs-CRP levels in non-HBR patients significantly increased the risk of stroke (HR 2.79, 95% CI 1.06–7.34, P = 0.0376). In contrast, for bleeding-related outcomes, including all bleeding events, BARC type 2 to 5 and 3 to 5 bleeding, the risk of outcome events was no difference between patients with HBR and non-HBR.
CONCLUSION Regardless of whether HBR population or not, high hs-CRP levels were associated with an increased risk of all-cause mortality after PCI in ACS patients, and an increased risk of ischemic events in non-HBR population was associated with high hs-CRP levels.
GW35-e1105
Jia Liao, Miaohan Qiu, Jing Li, Yi Li, Yaling Han
Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Residual risk assessment for acute coronary syndrome (ACS) patients after optimal revascularization and medical management remain challenging. Usefulness of measuring high-sensitivity C-reactive protein (hsCRP) and remnant cholesterol (RC) in assessing level of residual inflammation risk (RIR) and residual cholesterol risk (RCR) for risk stratification in these patient needs to be evaluated.
METHODS Patients admitted for ACS undergoing percutaneous coronary intervention between March 2016 and March 2019 were included in the study. The enrolled patients were divided based on the concentration of hsCRP and RC at discharge. The primary outcome was ischemic events at 12 months, defined as a composite of cardiac death, myocardial infarction, or stroke. The secondary outcomes included 12-month all-cause death and cardiac death.
RESULTS Of 6378 patients, the median hsCRP concentrations was 2.70 mg/L (interquartile range, 1.10–7.50) and the median RC concentrations was 24.98 mg/dL (interquartile range, 17.89–34.98). RIR was significantly associated with all-cause death (highest hsCRP tertile vs. lowest hsCRP tertile, adjusted hazard ratio [HR]: 2.06, 95% confidence interval [CI], 1.35–3.12, P = 0.0007) and cardiac death (adjusted HR: 1.66, 95% CI: 1.04–2.65, P = 0.03). The relationship of RCR was significantly associated with cardiac death (highest RC tertile vs. lowest RC tertile, adjusted HR: 1.78, 95% CI: 1.13–2.81, P = 0.01) and of low magnitude for all-cause death (adjusted HR: 1.32, 95% CI: 0.89–1.95, P = 0.16). Risks of ischemic events (adjusted HR: 2.05, 95% CI: 1.34–3.14, P = 0.0009), cardiac death (adjusted HR: 2.64, 95% CI: 1.55–4.49, P = 0.0004), and all-cause death (adjusted HR: 2.13, 95% CI: 1.32–3.44, P = 0.002) were significantly higher in patients with both RIR and RCR (highest hsCRP and RC tertile) than in patients with neither RIR nor RCR (lowest hsCRP and RC tertile).
CONCLUSION Among ACS patients receiving optimal medical management strategy, both high risk of residual inflammatory and cholesterol was still strongly associated with increased risks of ischemic events, cardiac death, and all-cause mortality.
GW35-e1106
Kun Na, Miaohan Qiu, Jing Li, Yi Li, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Acute coronary syndrome (ACS) is a major cause of morbidity and mortality globally. The prognostic value of high-sensitivity Troponin T (hsTnT) in patients with varying renal functions undergoing percutaneous coronary intervention (PCI) remains understudied. This retrospective study aims to investigate the long-term outcomes associated with hsTnT levels in ACS patients post-PCI, stratified by renal function.
METHODS A total of 14,208 ACS patients undergoing PCI were included in this study. All participants had at least one serum creatinine measurement and one post-PCI hsTnT test. Patients were categorized into two groups based on renal function: impaired renal function (eGFR <60 mL/min/1.73 m2, n = 1206) and normal renal function (eGFR ≥60 mL/min/1.73 m2, n = 13,002). The primary endpoints were one-year all-cause mortality and ischemic events, analyzed using Cox regression models and restricted cubic spline regression.
RESULTS Patients with impaired renal function were older, more likely to be female, and had a higher prevalence of baseline cardiovascular risk factors compared to those with normal renal function. Elevated hsTnT levels (≥5 times the 99th percentile URL) were observed in 25.2% of patients with impaired renal function and 17.8% of those with normal renal function. One-year all-cause mortality was significantly higher in the impaired renal function group (6.88% vs. 1.06%, P < 0.0001), with similar trends observed for ischemic events (6.63% vs. 1.78%, P < 0.0001). High hsTnT levels were associated with increased mortality in both renal function groups, but the risk was more pronounced in patients with impaired renal function (aHR: 3.63; 95% CI: 2.04–6.49) compared to those with normal renal function (aHR: 1.40; 95% CI: 0.85–2.29). RCS regression analysis revealed a nonlinear correlation between hsTnT levels and one-year all-cause mortality in patients with impaired renal function (P for overall < 0.0001 and P for non-linearity = 0.0004), while a linear correlation was observed in those with normal renal function (P for overall = 0.0307 and P for non-linearity = 0.2647).
CONCLUSION Elevated hsTnT levels post-PCI are significantly associated with increased one-year all-cause mortality and ischemic events in ACS patients, with a more pronounced effect in those with impaired renal function. These findings suggest the importance of considering renal function when evaluating hsTnT levels for prognostic assessment in ACS patients post-PCI.
GW35-e1107
Haofu Tian, Miaohan Qiu, Jing Li, Yi Li, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES To compare the safety and efficacy of ticagrelor and clopidogrel in the treatment of CYP2C19 allele-deficient acute coronary syndrome (ACS) complicated with diabetes mellitus (DM).
METHODS Seven hundred and fifty patients with ACS and DM with CYP2C19 allele loss admitted to the Department of Cardiovascology of General Hospital of Northern Theater Command from March 2016 to March 2017 to the type of P2Y12 inhibitor used. Patients were divided into clopidogrel group (n = 439) and ticagrelor group (n = 311) according to the type of P2Y12 inhibitor used. Baseline data, surgical data, discharge medication, and endpoint events within 12 months were recorded and compared between the two groups. Kaplan-Meier survival analysis was used to plot the risk curve of the end event.
RESULTS Before propensity score matching, age, hypertension and previous stroke rates in Ticagrelor group were lower than those in clopidogrel group, and the proportions of male, left main branch, left anterior descending branch and creatinine clearance were higher than those in clopidogrel group, with statistical significance (P < 0.05). There was statistical significance in smoking status between the two groups (P < 0.05). After matching propensity score, there was no significant difference in baseline data between ticagrelor group and clopidogrel group (P > 0.05). After matching the propensity score, the incidence of ischemic events (0.78% vs. 4.71%, P = 0.007), all-cause death (0.78% vs. 4.31%, P = 0.012) and stroke (0 vs. 1.96%, P = 0.025) in ticagrelor group was lower than that in clopidogrel group, and the incidence of BARC type 3–5 hemorrhage (3.53% vs. 0.39%, P = 0.011) was higher than that in clopidogrel group, with statistical significance (P < 0.05). Kaplan-Meier survival curve showed that after matching the propensity score, the incidence of ischemic eventsin ticagrelor group was lower than that in clopidogrel group (0.78% vs. 4.71%, P = 0.007), and the incidence of BARC type 3–5 bleeding events was higher than that in clopidogrel group (3.53% vs. 0.39%, P = 0.011), with statistical significance (P < 0.05).
CONCLUSION Compared with clopidogrel, the incidence of ischemic events is reduced and the incidence of bleeding events is increased in patients with ACS and DM who are treated with CYP2C19 allele loss using ticagrelor.
GW35-e1127
Yan Tang1, Suxin Deng1,2, Jiamin Zhou1, Yuan Wen1, Liang Wang1, Xiaoping Peng1
1Department of Cardiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, P.R. China
2Department of Cardiology, Gaoxin Branch of The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China
OBJECTIVES The optimal intravenous fluid volumes (IFV) control is essential to prognosis in patients with RVMI. However, the role of initial IFV in the long-term prognosis of RVMI and the influence of emergency reperfusion on IFV–risk association have yet been unclear.
METHODS We performed a multi-center retrospective study with 1120 RVMI patients between January 2017 and December 2019. The last date of the follow-up was December 31, 2023. The IFV in the first 24-hour of hospitalization was categorized into 1000 mL increments. The primary and secondary outcomes were all-cause death and cardiovascular death at the end of follow-up, respectively. Cox regression models, subgroup tests, and restricted cubic splines were used to evaluate the association of outcomes with IFV during hospitalization and the impact of emergency reperfusion on this association. The sensitivity analysis was used to confirm the relationship between the initial IFV and outcomes.
RESULTS After a median follow-up duration of 5 (IQR 4–6) years, 142 patients had experienced death. The relationship between IFV in the first 24-hour of hospitalization followed a U-shaped curve association with 5-year mortality. All-cause mortality was higher in patients with lower IFV (≤1000 mL) (adjusted hazard ratios (HRs) 6.739, 95% confidence interval (CI) 2.282–19.898; P = 0.001) and higher IFV (>4000 mL) (HR 2.949, 95% CI: 1.297–6.701; P = 0.010) [reference: 2000< IFV ≤3000 mL]. However, we observed that IFV was associated with all-cause and cardiac mortality (P < 0.001) in RVMI patients without emergency reperfusion, but not in those with emergency reperfusion (P = 0.180).
CONCLUSION Controlling the IFV from 1000 to 4000 mL in the first 24-hour of hospitalization may be conducive to RVMI patients specific to without reperfusion in the long run.
GW35-e1140
Xinya Dai, Tong Liu
Second Hospital of Tianjin Medical University
OBJECTIVES High-sensitive C-reactive protein (hsCRP) to high-density lipoprotein cholesterol (HDL-C) ratio (CHR) is associated with coronary artery disease (CAD), but its predictive value for long-term adverse outcomes in patients with CAD following percutaneous coronary intervention (PCI) remains unexplored and is the subject of this study.
METHODS Patients with CAD undergoing PCI were included in the Korea University Guro Hospital-Percutaneous Coronary Intervention Registry (KUGH-PCI) since 2004. Patients were categorized into tertiles of CHR. The endpoints were all-cause mortality (ACM), cardiac mortality (CM) and major adverse cardiac events (MACEs). Kaplan-Meier, multivariable Cox regression (hazard ratios (95% confidence intervals)), restricted cubic splines (RCS) and sensitivity analyses were performed.
RESULTS A total of 3260 patients were included and divided into Group 1 (CHR <0.830, N = 1089), Group 2 (CHR = 0.830–3.782, N = 1085), and Group 3 (CHR >3.782, N = 1086). Higher CHR tertiles were associated with progressively higher risks of ACM, CM, and MACEs (log-rank, P < 0.001). Multivariable Cox regression showed that patients in the highest tertile showed higher risks of ACM (HR: 2.13 [1.45, 3.12]), CM (HR: 3.58 [1.94–6.59]) and MACEs (HR: 1.34 [1.09–1.64]) compared to those in the lowest tertile. RCS analyses did not reveal a significant non-linear relationship between CHR and ACM, CM or MACES. The significant associations remained significant on sensitivity analyses, RCS analyses with or without extreme values, subgroup analyses and multiple imputations for missing data.
CONCLUSION Elevated CHR is a novel, independent risk factor for long-term ACM, CM and MACEs in CAD patients following PCI.
GW35-e1150
Wang Fengxia1,2, Ma Yitong1
1The First Clinical College of Xinjiang Medical University
2Cardiovascular medicine department, Center for cardiac and panvascular Medicine, People’s Hospital of Xin jiang Uygur Autonomous Region
OBJECTIVES Clinical practice guidelines have categorized patients with either a history of one or more “clinical atherosclerotic cardiovascular disease (ASCVD)” events or “coronary heart disease (CHD) risk equivalency” to be at “very high risk” for a recurrence or a first event, respectively. Extreme risk, a descriptor for even higher morbidity and mortality potential, defines a 30% or greater 10-year 3-pointnon-fatal MACE of myocardial infarction (MI), non-fatal stroke, or cardiovascular death risk. Extreme risk particularly applies to those with progressive or multiple clinical ASCVD events in the same artery, same arterial bed, or polyvascular sites, including unstable angina and transient ischemic events. The TCB index (triglycerides × total cholesterol × body weight), a novel simply calculated nutritional index based on serum triglycerides (TGs), serum total cholesterol (TC), and body weight (BW), was recently reported to be a useful prognostic indicator in patients with coronary artery disease. Thus, this study aimed to investigate the relationship between TCBI and long-term mortality in acute decompensated ASCVD patients.
METHODS We concluded 1478 participants with extreme ASCVD risk from the First Affiliated Hospital of Xinjiang Medical University from June 2017 to April 2021. TCBI was calculated using the formula TG (mg/dL) × TC (mg/dL) × BW (kg)/1000. Patients were divided into two groups according to the median TCBI value. An association between admission TCBI and mortality was assessed using univariable and multivariable Cox proportional hazard analyses.
RESULTS Overall, 1478 eligible patients were enrolled, and 333 (22.5%) patients died during a median follow-up period of 3.2 years. The cumulative survival rate with respect to all-cause, cardiovascular, and cancer-related mortalities was worse in patients with low TCBI than in those with high TCBI. In the multivariable analysis, although TCBI was not associated with cardiovascular and cancer mortalities, the association between TCBI and reduced all-cause mortality (hazard ratio: 0.59, 95% confidence interval: 0.40–0.91, P = 0.020) was observed. We computed net reclassification improvement (NRI) when TCBI or Geriatric Nutritional Risk Index (GNRI) was added on established predictors such as hemoglobin, serum sodium level, and both. TCBI improved discrimination for all-cause mortality (NRI: 0.40, P < 0.001; when added on hemoglobin and serum sodium level). GNRI can improve discrimination for cancer mortality (NRI: 0.90, P = 0.002; when added on hemoglobin and serum sodium level).
CONCLUSION TCBI, a novel and simply calculated nutritional index, can be useful to stratify patients with ASCVD who were at risk for worse long-term overall mortality.
GW35-e1151
Wang Fengxia1,2, Ma Yitong1
1The First Clinical College of Xinjiang Medical University
2Cardiovascular medicine department, Center for cardiac and panvascular Medicine, People’s Hospital of Xin jiang Uygur Autonomous Region
OBJECTIVES We aim to investigate the predictive ability of PCE (Pooled Cohort Equations), QRISK2 and SCORE (Systematic COronary Risk Estimation) scoring systems for atherosclerotic cardiovascular disease (ASCVD) risk prediction in XinJiang, a province with one of the highest ASCVD event rates in China.
METHODS Five-year risk estimates were calculated in risk score-specific subsets of the XinJiang cohort. Calibration was assessed by standardised incidence ratios (SIRs) and discrimination by Harrell’s C-statistics. In addition, a head-to-head comparison of the scores was performed in the intersection of the three score-specific subcohorts.
RESULTS PCE, QRISK2 and SCORE risk estimates were calculated for 1056, 1191 and 887 eligible individuals from the First Affiliated Hospital of Xinjiang Medical University, respectively. During the 5-year follow-up, 124 hard ASCVD events (PCE outcome), 371 ASCVD events (QRISK2 outcome) and 61 ASCVD deaths (SCORE outcome) occurred among the score-specific subsets of the cohort. While PCE (SIR 1.13, 95% CI: 0.90–1.18) and SCORE (SIR 0.91, 95% CI: 0.81–1.21) were calibrated well for the cohort, QRISK2 underestimated the risk by 48% (SIR 0.52, 95% CI: 0.48–0.56). In terms of discrimination, PCE (C-statistic 0.748) was inferior to QRISK2 (C-statistic 0.792) and SCORE (C-statistic 0.825). All three risk scores performed at similar level in the head-to-head comparison.
CONCLUSION Of three widely used ASCVD risk scores, PCE and SCORE performed at acceptable level, while QRISK2 underestimated ASCVD risk markedly. These results highlight the need for evaluating the accuracy of ASCVD risk scores prior to use in high-risk populations.
GW35-e1153
Zaixin Jiang, Haiwei Liu, Miaohan Qiu, Yi Li, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research institute and Department of Cardiology, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
OBJECTIVES This study aims to explore the long-term outcomes and identify independent prognostic factors associated with adverse clinical outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) without traditional modifiable cardiovascular risk factors (CVRFs).
METHODS This study used data from Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) registry study. Clinical characteristics and outcomes of adult patients (≥18 years) with and without traditional modifiable CVRFs were examined. The primary outcomes were major adverse cardia-cerebrovascular events (MACCE). The long-term (5 fives) outcomes were compared between the without and with CVRFs group in such cohort. An exploratory multivariable Cox proportional hazards regression analysis was performed to identify the independent demographic and clinical predictors of the adverse clinical outcomes in the CVRFs-absent cohort.
RESULT Among 5688 patients with ACS undergoing PCI, 392 (6.9%) were in the absence of CVRFs and 5296 (93.1%) were in the presence of CVRFs. Age, sex, body mass index (BMI), family history and type of coronary artery disease (CAD), smoking status, and lipid levels differed significantly between two cohorts. Utilization rates of β-blocker, angiotensin-converting enzyme inhibitor (ACEI), and angiotensin receptor blockade (ARB) at discharge were lower, while use of statins was higher in the CVRFs-absent cohort. Patients had increased number of target vessels, stents, stent length, and left circumflex (LCX) and diffuse lesions in the CVRFs-present cohort. There were no significant differences in MACCE rates between the two cohorts (9.44% vs. 9.76%, log-rank P = 0.90). Patients with MACCE were older, more total occlusion, RCA lesions, and thrombus lesions when compared with those without MACCE in the CVRFs-absent cohort. Multivariable Cox proportional hazards regression analysis indicated that age (HR, 1.06; 95% CI, 1.03–1.10; P = 0.001) and thrombus lesions (HR, 2.58; 95% CI, 1.24–5.40; P = 0.011) were independently associated with MACCE in the CVRFs-less cohort.
CONCLUSIONS Among patients with ACS undergoing PCI, CVRFs-absent patients had a similar MACCE rates when compared with those with one or more CVRFs at 5 years. Discovery of novel biomarkers/makers of ACS beyond traditional modifiable CVRFs may identify high-risk individuals and provide valuable preventive strategies.
GW35-e1154
Ping Jin1, Juan Ma2, Shaobin Jia2, Qiangsun Zheng1
1The Second Affiliated Hospital of Xi’an Jiaotong University
2General Hospital of Ningxia Medical University
OBJECTIVES Homocysteinemia (HHcy) has been confirmed as a risk factor for atherosclerosis, closely related to the severity of coronary lesions and the instability of atherosclerotic plaques. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new target in the field of lipid-lowering in recent years, and its inhibitors can significantly reduce plasma low-density lipoprotein cholesterol levels, stabilize or even reverse plaques, and improve poor cardiovascular prognosis. Our previous studies have found that homocysteine (Hcy) increases macrophage PCSK9 expression, leading to lipid accumulation and inflammatory activation in macrophages, and increases the instability of aortic sinus plaques in ApoE−/− mice. However, the correlation between PCSK9 and plasma Hcy levels, and whether the correlation between homocysteine and the severity of coronary lesions is mediated by PCSK9 have not been reported. The purpose of this study is to explore the mediating effects of PCSK9 on the correlation between Hcy and the severity of coronary lesions in patients with acute coronary syndrome.
METHODS In this cross-sectional study, 730 patients who presented with initial acute chest pain to our department of cardiology and underwent coronary angiography were enrolled in December 2022 to December 2023. Based on the angiography results, 617 patients were ultimately diagnosed with acute coronary syndrome (ACS) and included in the study. Informed consent was obtained from the patients, and the study was approved by our hospital’s ethics committee. Baseline characteristics, plasma Hcy and interventional indicators were collected. Plasma PCSK9 levels were measured using ELISA before coronary angiography in patients after admission. Patients were divided into non-severe stenosis group (Syntax score ≤22, n = 502) and severe stenosis group (Syntax score >22, n = 115) based on their Syntax scores. The correlation between Hcy and PCSK9 was examined using Pearson correlation analysis. The association between Hcy or PCSK9 and severe stenosis was examined using multiple logistic regression. In order to determine whether PCSK9 mediated the association between Hcy and severe stenosis, a mediation analysis was performed.
RESULTS Individuals in severe stenosis group had significantly higher levels of Hcy and PCSK9 than those in non-severe stenosis group (P < 0.05). After adjusting covariates, the multivariate linear regression analysis showed that Hcy was positively associated with PCSK9. That was, for every unit increase in Hcy, PCSK9 increased by 1.17 pg/mL (β = 1.17, 95% CI: 1.00, 1.34). Multiple logistic regression analysis indicated that Hcy (OR = 1.04, 95% CI: 1.02, 1.05) and PCSK9 (OR = 1.02, 95% CI: 1.01, 1.02) were positively associated with severe stenosis. The mediation analysis showed that Hcy had a direct, significant effect on severe stenosis (β = 0.0379, 95% CI: 0.0120, 0.0646), and PCSK9 partially mediated the indirect effect of Hcy on severe stenosis (β = 0.0197, 95% CI: 0.0161, 0.0350). PCSK9 contributed to 34.19% of Hcy-related severe stenosis.
CONCLUSIONS Findings suggest a mediation link between Hcy and PCSK9 and the risk of severe stenosis. The significance of PCSK9 as a mediator deserves recognition and consideration.
GW35-e1174
Yanbo Wang, Lifang Su, Changchang Liu, Qing Zhou, Jia Tian, Xiaohui Zhao, Xinshun Gu
The Fifth Department of Cardiology, Second Hospital of Hebei Medical University
OBJECTIVES To compare the different doses of ticagrelor on the efficacy and safety in patients with STEMI based on propensity score matching (PSM).
METHODS The patients with STEMI who underwent PPCI and antiplatelet therapy with ticagrelor at the Cardiovascular Department of the Second Hospital of Hebei Medical University from June 2019 to May 2021 were selected consecutively. According to the different maintenance doses of ticagrelor, patients were divided into a reduced dose group (n = 60) and a standard group (n = 180), using ticagrelor 60 mg2/day and 90 mg2/day, respectively. The PSM method was used to perform a 1:1 match between two groups, with matching variables including gender, age, medical history, Killip grade at admission, and intervention related parameters. Finally, 54 patients were included in the each group. Follow-up was conducted on both groups at 1 month, 3 months, and 6 months after discharge, and platelet parameters as well as clinical events were recorded and compared between the two groups of patients.
RESULTS There was no statistically significant difference in baseline data, intervention treatment parameters, and incidence of major adverse cardiovascular events (MACEs) during hospitalization between the two groups after PSM (P > 0.05). There was no statistically significant difference in the levels of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet aggregation rate (PAR) between baseline and 1 month after discharge (P > 0.05). The level of MPV in the reduced dose group was higher than that of the standard group at discharge, and the level of PDW was lower than that of the standard group (P < 0.05). The level of PDW in the reduction group was higher than that of the standard group after 3 months of discharge (P < 0.05). The level of MPV in the reduction group was higher than that of the standard group after 6 months of discharge (P < 0.05). There was no statistically significant difference in the level of PLT between the two groups before and after discharge (P > 0.05). The levels of MPV in the two groups were higher than baseline at discharge, while the levels of PDW and PAR were lower than baseline (P < 0.05). The level of MPV in the reduction group was lower than that at discharge at 1 month, 3 months, and 6 months, while the levels of PDW and PAR were higher than those at discharge (P < 0.05). There was no statistically significant difference in the incidence of MACEs and severe bleeding events between the two groups during the follow-up (P > 0.05).
CONCLUSIONS Reduced dose of ticagrelor treatment is safe and effective for STEMI patients undergoing PPCI.
GW35-e1184
Xieyire Hamulati1, Qian Zhao1, Xiaomei Li1,2
1Department of Cardiology, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
2Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of Xinjiang Medical University, Urumqi, China
OBJECTIVES Rapid economic development has led to lifestyle changes characterized by higher calorie intake and reduced physical activity, causing energy imbalance, obesity, and disturbances in glucose and lipid metabolism. Consequently, the prevalence of MetS in Chinese residents has increased from 24.2% to 31.1% over the past decade, becoming a significant public health issue. We aimed to analyze the prevalence of metabolic syndrome (MetS) and to assess the joint association of diet quality (DQ) and physical activity (PA) with MetS in urban areas of Xinjiang.
METHODS In this population based, cross sectional study, a total of 10,192 participants aged 30–74 years old were recruited from Urumqi and Korla, conducted between July 2019 and September 2021 Completed and validated questionnaires were employed to evaluate the DQ and PA, physical examinations and laboratory tests were recorded with Standard methods. MetS was diagnosed according to the 2009 Joint Interim Statement for China (JIS 2009). DQ was assessed by the Food Frequency Questionnaire (FFQ), to obtain the intake frequency of each dietary term, and divided into three groups (poor, intermediate and good) according to the dietary score. PA was calculated using the formulas in the IPAQ and grouped according to the values: low, moderate and high. Multivariate logistic regression was used to calculate the odds ratios (ORs) of MetS, as well as the joint association of DQ and PA.
RESULTS Of 10,192 participants, 5251 (51.5%) were men, and the mean (SD) age was 47.53 (8.98) years. The prevalence of MetS was 30.9%, with men significantly higher than women (77.1% vs. 22.9%, P < 0.001). The prevalence of high waist circumference (WC), high blood pressure (BP), elevated fasting plasma glucose (FPG), elevated triglycerides (TG) and low high-density-lipoprotein-cholesterol (HDL-c) were 59.5%, 46.8%, 22.1%, 35.0% and 18.4%, men had a higher prevalence of each of the MetS components than women (P < 0.001). 22.0% (7.7% in men and 25.2% in women) of the participants had none of the metabolic component, and over 18.7% of the participants (27.0% of men, and 13.6% of women) had three or more metabolic components, which is the definition of metabolic syndrome. The multiplicative interaction between DQ and PA is associated with MetS (P for interaction < 0.05). In high PA, poor DQ was associated an increased odds of MetS. In good DQ, less PA was also associated an increased odds of MetS.
CONCLUSIONS The MetS situation in urban areas of Xinjiang is relatively severe. Maintaining good diet quality time along with increasing physical activity might be an important strategy for preventing the metabolic disorder and easing the burden of premature deaths and cardiovascular disease (CVD).
GW35-e1190
Yuxin Yang
School of Public Health, Inner Mongolia Medical University, Hohhot, China
OBJECTIVES The ratio of small and dense low-density lipoprotein cholesterol (sdLDL-C) to low-density lipoprotein cholesterol (LDL-C) is closely associated with the risk of Atherosclerotic Cardiovascular Disease (ASCVD) but has received limited research attention. Therefore, this study aims to investigate the correlation between sdLDL-C/LDL-C ratio and ASCVD, thus providing insights for ASCVD prevention and the identification of new therapeutic targets.
METHODS Data were collected from ASCVD patients and non-ASCVD patients at Inner Mongolia Medical University Affiliated Hospital between January 2019 and July 2023. Univariate and multivariate logistic regression analyses were conducted after adjusting for demographic and vascular risk factors to examine the relationship between sdLDL-C/LDL-C ratio and ASCVD risk. Additionally, the diagnostic efficacy of sdLDL-C/LDL-C ratio and sdLDL-C in predicting ASCVD was evaluated using ROC curve analysis.
RESULTS The study included 8924 subjects with an average age of (59.42 ± 11.77) years. Multivariate logistic regression analysis revealed that compared to the lowest quartile of sdLDL-C/LDL-C ratio, the risk of ASCVD increased by 1.428, 3.616, and 9.395 times in quartile groups 2, 3, and 4, respectively (OR values: 2.428 [95% CI 1.932–3.051], 4.616 [95% CI 3.678–5.794], 10.395 [95% CI 8.093–13.351]; P < 0.001). This increasing trend was also observed in stratified analyses by age, hypertension, and sex. ROC curve analysis demonstrated that sdLDL-C/LDL-C ratio and sdLDL-C predicted ASCVD with area under the curve (AUC) values of 0.668 and 0.605, respectively. The sensitivity of sdLDL-C/LDL-C ratio was higher (73.6%), while the specificity of sdLDL-C was higher (66.7%).
CONCLUSIONS Elevated sdLDL-C/LDL-C ratio is associated with an increased risk of ASCVD, particularly among individuals aged 55 years or older, men, and those with hypertension. The predictive ability of sdLDL-C/LDL-C ratio for ASCVD occurrence (AUC = 0.668, 95% CI: 0.655–0.681, P < 0.001) surpasses that of sdLDL-C alone, suggesting its potential as an effective predictor for ASCVD development.
GW35-e1191
Tianyu Wu
Second Affiliated Hospital of Harbin Medical University
OBJECTIVES There is limited evidence regarding the effects of gender on coronary plaque features by optical coherence tomography (OCT) and none regarding assessment of non-culprit plaques in the context of ST-elevation myocardial infarction (STEMI).
METHODS Between July 2016 and June 2018, 583 patients (449 men and 134 women) who were treated emergently including OCT imaging of all three major epicardial coronary arteries were included with another 103 patients excluded from analysis because of in-stent restenosis, imaging of the culprit vessel after pre-dilation, poor image quality, or incomplete imaging.
RESULTS A total of 583 culprit lesions and 1419 non-culprit plaques were analyzed. Both patient-based (16.7% vs. 7.5%, P = 0.008) and plaque-based (8.1% vs. 3.2%, P = 0.004) analyses showed that non-culprit plaque rupture (NC-PR) was more prevalent in men vs. women, especially in older patients (>50 years of age: 9.7% vs. 3.4%, P < 0.001) along with more high-risk OCT features and wider distribution of high-risk plaques. Multivariate analysis showed that culprit plaque rupture, age ≥50 years, and higher TC/HDL-C ratio were independent predictors of NC-PR in men (OR: 2.004, 95% CI: 1.147–3.641, P = 0.015; OR: 2.811, 95% CI: 1.093–7.229; P = 0.032; and OR: 1.227, 95% CI: 1.027–1.464; P = 0.024); and culprit plaque rupture was an independent predictor of patients with ≥1 non-culprit high-risk OCT characteristics in men (OR: 2.680, 95% CI: 1.747–4.113; P < 0.001). None of these findings were seen in women.
CONCLUSIONS In patients with STEMI, men more pan-coronary plaque vulnerability compared to women and was predictable by culprit plaque rupture, age ≥50 years, and higher TC/HDL-C ratios. Conversely, even in women ≥50 years of age, pan-coronary plaque vulnerability was less common and less widespread.
GW35-e1203
Qian Zhao1,2, Dingshan Zhang1, Yining Yang2
1First Affiliated Hospital of Xinjiang Medical University
2People’s Hospital of Xinjiang Uyghur Autonomous Region
OBJECTIVES Acute myocardial infarction (MI) is the leading cause of cardiac mortality worldwide. Recent clinical studies have found that AMI patients without standard modifiable cardiovascular risk factors (SMuRF), including hypertension, diabetes, hypercholesterolemia, and smoking, had higher in-hospital mortality rates and more severe symptoms. Nutritional status has been shown in several studies to be a good predictor for prognosis. This study aims to investigate the prognostic value of Prognostic Nutritional Index (PNI) in ST-elevation MI (STEMI) patients who do not have traditional cardiovascular risk factors.
METHODS A single-center, prospective cohort study designed to assess whether PNI could predict long-term clinical outcomes in SMuRF-less patients. We consecutively recruited adult patients with STEMI attended the Department of Cardiology, the First Affiliated Hospital of Xinjiang Medical University during the period of January 2013 to June 2023 and underwent percutaneous coronary intervention (PCI) within 12 h after onset of chest pain. The exposure variable was defined as having at least one of the following SMuRFs: current smoker status, hypercholesterolemia, diabetes, or hypertension. The primary endpoints were in-hospital mortality and major adverse cardiovascular events (MACE) during follow-up period. Restricted Cubic Splines (RCS) were used to explore the relationship between PNI and MACE. Kaplan-Meier and Cox-proportional hazard models analysis for long-term outcomes.
RESULTS Among 2368 STEMI patients with primary PCI, 260 (10.9%) had no SMuRFs. Compared with those with SMuRF, SMuRF-less patients have a higher in-hospital mortality rate (5.0% vs. 7.5%; P < 0.001). SMuRF-less patients who died in the hospital had a significantly lower PNI in comparison to those who survived (44.1 ± 7.0 vs. 48.1 ± 5.9, P = 0.007). During the 4.2-year follow-up, 79 (38.9%) patients developed MACE. After adjustment for patient characteristics and treatment, low PNI (≤48) was significantly associated with a high risk of MACE (HR: 1.14; 95% CI: 1.012–1.289; P = 0.031). The incidence of MACE decreased with an increase in the PNI (P overall < 0.05).
CONCLUSIONS A higher PNI level is an independent predictor for long-term MACE in SMuRF-less patients. It is necessary to monitor patients’ immunonutritional status and use it as an auxiliary indicator to predict short-term prognosis.
GW35-e1222
Chengqing Jiang, Ziang Li, Haiyan Xu, Yongjian Wu
State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
OBJECTIVES Cardiovascular disease (CVD) is the leading cause of non-cancer mortality among cancer survivors. Despite the known benefits of physical activity on cardiovascular health in the general population, evidence regarding post-diagnosis physical activity and CVD risk among cancer survivors is limited. To explore the associations of wearable device-measured moderate-to-vigorous intensity physical activity (MVPA) with CVD risk in long-term cancer survivors.
METHODS The retrospective analysis involved a prospective cohort of 6109 cancer survivors without CVD, aged 40–80 years old from the UK Biobank accelerometry subsample. Cancer diagnoses were obtained from national cancer registries (International Classification of Diseases-10 [ICD-10], C00-C97, except for non-melanoma skin cancer, in situ, and non-well-defined cancers), and participants were followed up through December 31, 2022. A machine-learning algorithm was utilized to categorize MVPA into four groups based on guideline-recommend MVPA duration (0–75 min/week, 75–150 min/week, 150–300 min/week, ≥300 min/week).
RESULTS Over a median follow-up of 7.88 years, there were 539 incident CVD events, including 361 incident CAD events, 155 incident HF events, and 109 incident stroke events. A clear inverse linear dose-response relationship between MVPA volume and the incidence of CVD was observed (P for nonlinear = 0.49), with no maximal threshold for the benefits. Adjusted CVD incidence rates (95% confidence intervals [CIs]) across MVPA groups (0–75 min/week, 75–150 min/week, 150–300 min/week, ≥300 min/week) were 15.30 (12.90, 18.10), 13.50 (11.00, 16.40), 12.00 (10.20, 14.10), and 9.86 (8.35, 11.6) per 1000 person-years, respectively. Adjusted hazard ratios (95% CI) for CVD, CAD, HF, and stroke in the highest MVPA group (≥300 min/week) compared with those with the lowest MVPA group (0–75 min/week) were 0.63 (0.49, 0.80), 0.68 (0.51, 0.91), 0.66 (0.42, 1.06), 0.72 (0.42, 1.23), respectively.
CONCLUSIONS Findings from the UK Biobank study suggest that longer durations of MVPA are associated with reduced incident CVD risk in cancer survivors, particularly in CAD risk reduction, underscoring the potential for physical activity to serve as a key component in cardio-oncology care.
GW35-e1229
Xuelin Wang1,2, Xuyu He1
1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
2Shantou University Medical College, Shantou, Guangdong, China
OBJECTIVES Left ventricular thrombus formation is a feared complication of myocardial infarction. Previous studies on blood urea nitrogen to serum albumin (BUN/ALB) ratio have showed that an association with the severity and prognosis of cardiovascular diseases. However, its role in predicting the long-term prognosis of left ventricular thrombus remains unclear. The aim of this study was to investigate the associations between BUN/ALB ratio and long-term outcomes among patients with left ventricular thrombus.
METHODS Patients diagnosed with left ventricular thrombus between January 2011 and December 2018 in Guangdong Provincial People’s Hospital were included. The primary endpoint was all-cause mortality within 5 years. Clinical characteristics, biomarker profiles, and echocardiographic parameters of patients with left ventricular thrombus were collected on admission. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal cutoff value and predictive performance of the BUN/ALB ratio. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between BUN/ALB ratio and 5-year all-cause mortality.
RESULTS We retrospectively included 335 patients diagnosed with LVT who underwent ultrasound examination. During a 5-year follow-up, mortality occurred in 48 (14.3%) patients. The ROC curve showed that the area under the curve (AUC) of BUN/ALB ratio was 0.705 (95% confidence interval [CI] 0.628–0.728), the best cut-off value to discriminate survivors from non-survivors was 5.905, with a sensitivity of 58.3%, a specificity of 79.4%, and a Youden’s index of 0.377. Kaplan-Meier curves indicated that patients with BUN/ALB ratio ≥5.905 had a significantly higher mortality rate (32.2% vs. 7.7%, P < 0.001) compared to those with BUN/ALB ratio <5.905. The BUN/ALB ratio ≥5.905 was an independent predictor of long-term all-cause mortality (hazard ratio [HR]: 3.34, 95% CI 1.75–6.34, P < 0.001 in a multivariate Cox regression analysis).
CONCLUSIONS An elevated BUN/ALB ratio was independently associated with a higher risk of all-cause mortality in patients with LVT, indicating that the BUN/ALB ratio serves as a biomarker for identifying long-term prognosis in these patients.
GW35-e1240
Xinyi Zhang1, Wenchang Nie2, Jian Liu2, Xiaoyan Nie1
1School of Pharmaceutical Science, Peking University
2Peking University People’s Hospital
OBJECTIVES PEAR1, a protein expressed in platelets and endothelial cells that plays a role in platelet aggregation. Previous cohort studies suggested that PEAR1 genetic polymorphisms might influence platelet reactivity after antiplatelet therapy. However, the effect of PEAR1 genetic polymorphisms on the long-term efficacy of antiplatelet treatment is controversial. Whether PEAR1 protein affects the long-term therapeutic efficacy of antiplatelet treatment is unclear. The aim of our study was to explore the impact of PEAR1 protein on the long-term therapeutic efficacy of antiplatelet treatment in patients with coronary artery disease (CAD).
METHODS CAD patients treated with dual antiplatelet therapy (aspirin plus clopidogrel) were enrolled and followed up for one year. By analyzing protein quantitative trait loci (pQTL) significantly associated with PEAR1 plasma protein levels from INTERVAL, deCODE, and UKB-PPP studies, a polygenic risk score was developed to represent genetic-predicted plasma PEAR1 protein levels. A COX proportional risk model was then utilized to assess the relationship between genetic-predicted plasma PEAR1 protein levels and the long-term therapeutic efficacy of antiplatelet therapy in CAD patients.
RESULTS A total of 1073 CAD patients with dual antiplatelet therapy were enrolled in this study, and 49 patients experienced the major adverse cardiac events during one-year follow-up. There were four cis-pQTLs (rs12566888, rs4661012, rs12137505, and rs11264581) included in the polygenic risk score. The patients were stratified into two groups based on their PEAR1 protein polygenic risk score, with 162 patients classified in the high score group and 911 patients in the low score group. After adjusting clinical factors including age, gender, diagnose of myocardial infarction, hypertension, chronic kidney disease, left main coronary artery and CYP2C19 phenotype, the multivariate COX analysis showed that PEAR1 protein polygenic risk score was an independent risk predictor of major adverse cardiac events within one year (Hazard Ratio: 2.04, P-value: 0.04). The incidence of major adverse cardiac events was significantly higher in the high score group compared to the low score group.
CONCLUSIONS The findings suggest that genetic-predicted plasma PEAR1 protein levels was an independent predictor of major adverse cardiac events in CAD patients undergoing antiplatelet therapy, highlighting the potential influence of PEAR1 protein on long-term antiplatelet treatment efficacy.
GW35-e1270
Zhijie Lin, Junhan Chen, Hongkui Chen, Yansong Guo
Shengli Clinical Medical College of Fujian Medical University, Department of Cardiology, Fuzhou, China
OBJECTIVES Metallic elements have been implicated in the pathogenesis of cardiovascular disorders, yet research delineating their specific contribution to mortality rates among patients suffering from myocardial infarctions is conspicuously absent.
METHODS In this longitudinal study at Fujian Provincial Hospital, China, we recruited 1315 myocardial infarction patients undergoing percutaneous coronary intervention (PCI). We measured plasma concentrations of 25 metal (loid)s using inductively coupled plasma mass spectrometry (ICP-MS) and stratified participants into quartiles for detailed analysis. Our research focused on the correlation between metal levels and long-term PCI outcomes, particularly all-cause mortality. We utilized Kaplan-Meier analysis, Cox proportional hazards models, and Fine-Gray competing risk models to evaluate survival trends. Additionally, we investigated dose-response relationships with restricted cubic spline (RCS) analysis and assessed the synergistic effects of metal combinations and their cumulative impacts using quantile g-computation (qgcomp). We also performed stratification analysis for hypertensive individuals to explore differential impacts.
RESULTS A total of 104 incidents of all-cause mortality were documented throughout the study. Multivariate Cox regression analysis identified significant correlations between increased plasma levels of copper, lead, and strontium and augmented all-cause mortality. Specifically, the hazard ratios (HRs) were 4.32 for copper (95% CI 2.24–8.33, P < 0.001), 2.53 for lead (95% CI 1.47–4.35, P < 0.01), and 2.54 for strontium (95% CI 1.48–4.36, P < 0.001). Further analysis using the adjusted Fine-Gray model, which accounted for non-cardiovascular death as a competing risk, substantiated the independent prognostic significance of elevated plasma levels of these metals for cardiovascular mortality. The hazard ratios were notably high for copper at 7.60 (95% CI 3.77–15.32, P < 0.001), while lead and strontium also showed significant impacts with HRs of 1.33 (95% CI 1.07–1.66, P < 0.01) and 3.73 (95% CI 2.40–5.83, P < 0.001), respectively. Additionally, the analysis revealed that hypertension modified the influence of these metal exposures across all measurements. Lastly, the quantile g-computation regression confirmed a significant association between exposure to multiple metals and an increase in all-cause mortality (HR 2.01, 95% CI 1.56–2.59, P < 0.001), highlighting the complex interactions within metal mixtures.
CONCLUSIONS The study revealed a pronounced correlation between heightened plasma concentrations of copper, lead, and strontium and an increased risk of all-cause mortality among myocardial infarction patients. These findings emphasize the critical need to monitor harmful metal exposures rigorously. By identifying these associations, we can facilitate the development of targeted interventions designed to mitigate these risks. This approach not only promises to improve patient outcomes but also supports broader public health initiatives aimed at reducing exposure to toxic metals.
GW35-e1280
Qiang Xu, Jaisheng Yin, Li Shen, Junbo Ge
Zhongshan Hospital, Fudan University
OBJECTIVES To observe the 5-year long-term follow-up results of the Xinsorb scaffold, we conducted a comprehensive analysis of the final clinical outcomes of 985 patients from both the randomized controlled trial and the registry study.
METHODS We performed a statistical analysis of the clinical outcomes of 985 patients who received the Xinsorb scaffold. The clinical outcome endpoints included patient-oriented clinical endpoints (PoCE), target vessel failure (TVF), major adverse cardiovascular events (MACE), target lesion failure (TLF), target vessel myocardial infarction (TV-MI), and their components. We also conducted statistical analyses on drug use and the related factors of clinical outcomes during the 5-year follow-up period.
RESULTS The incidence of clinical endpoint events among the 985 patients was as follows: PoCE 10.66%, TVF 5.79%, MACE 3.96%, and TLF 3.76%. For individual endpoints, the all-cause mortality rate was 1.52%, the target vessel-related myocardial infarction rate was 0.91%, the device thrombosis rate was 0.81%, and the incidence of intervention-required or fatal bleeding was 1.62%. The dual antiplatelet therapy (DAPT) adherence rates at 4 and 5 years were 80.81% and 63.76%, respectively. Logistic regression analysis indicated that a history of diabetes was a risk factor for PoCE, while BMI and fasting blood glucose (FBG) were protective factors.
CONCLUSIONS The 5-year follow-up results show that the clinical outcome incidence of the Xinsorb scaffold is acceptable, with good adherence to antiplatelet therapy during the degradation period of the scaffold. A history of diabetes is an important risk factor for clinical events associated with the Xinsorb scaffold.
GW35-e1288
Man Li, Boling Yi, Shuangtong Shao, Wentao Wang, Sining Hu, Haibo Jia
Department of Cardiovascular Medicine, The Second Affiliated Hospital of Harbin Medical University
OBJECTIVES Clonal hematopoiesis, which refers to the phenomenon of clonal expansion of hematopoietic stem cells in the bone marrow due to somatic mutations, is closely related to myocardial infarction. Among the common driver genes that cause clonal hematopoiesis, the JAK2V617F mutation has the strongest ability to cause myocardial infarction. Previous pathologic studies have shown that a large number of NETs accumulate on the surface of plaque erosion, and the change of neutrophil metabolism pattern is the key factor regulating the formation of NETs. This study aims to clarify the role of JAK2V617F mutation-induced neutrophil metabolic reprogramming in promoting plaque erosion by mediating NETs production through the release of lactic acid.
METHODS This study analyzed 528 patients with plaque erosion who underwent emergency coronary angiography and OCT due to acute coronary syndrome and were divided into 37 JAK2V617F patients and 491 non-mutated patients based on peripheral blood JAK2V617F gene testing. The influence of JAK2V617F mutation on lactic acid content was studied by excluding cardiogenic shock, sepsis, severe liver disease and other factors affecting lactic acid metabolism. The transcriptome of JAK2V617F mutated and non-mutated patients was analyzed by database to clarify the gene expression of key glycolytic enzymes. Glycolytic related enzymes and neutrophil extracellular traps (NETs) expression of mutated and non-mutated neutrophils were evaluated by western blotting and qPCR combined with glycolytic inhibitors. And lactic acid was detected by lactic acid kit.
RESULTS Analysis of patients with JAK2V617F gene mutation group and non-mutation group showed no significant differences in gender, age and other general clinical characteristics between the two groups (P > 0.01), while the lactic acid count in the mutant group was higher than that in the non-mutant group [2.1 (1.3–2.75) mmol/L vs. 1.6 (1.1–2.2) mmol/L, P < 0.05], suggesting that the mutation may cause metabolic changes. Further analysis of the transcriptome revealed that the expression of genes regulating key enzymes in glycolysis was all upregulated, and qPCR and Western blot confirmed the enhanced glycolysis in JAK2V617F mutated neutrophils. We found that the expression level of NETs in JAK2V617F mutated neutrophils increased, while nets decreased after glycolysis was inhibited.
CONCLUSIONS These results indicate that clonal hematopoietic JAK2V617F mutation mediates NETs generation by regulating neutrophil metabolic reprogramming. From a new perspective on metabolic regulation, this study systematically elucidates the role of JAK2V617F mutation in promoting plaque erosion, providing important scientific evidence for precision diagnosis and treatment of patients with plaque erosion.
GW35-e1309
Ying Pan, Tingting Wu, Changjiang Deng, Yingying Zheng, Xiang Xie
Department of Cardiology, Xinjiang Medical University Affiliated First Hospital, Urumqi, China
OBJECTIVES Kings score (KS) was a traditional prediction model in patients with liver diseases. Liver disease was reported to be independently associated with coronary artery disease (CAD). However, the prognostic significance of KS in patients with CAD has not been investigated.
METHODS We prospectively analyzed 12,686 CAD patients and divided them into two groups [low KS: <6.6 (n = 7434), high KS: ≥6.6 (n = 5252)]. Admission data were collected to calculate the KS [age × aspartate aminotransferase (AST) × international normalized ratio (INR)/platelet count (PC)]. We reported long-term mortility as the primary outcome, including all-cause mortility (ACM) and cardiac mortality (CM). Multivariate Cox regression models were performed to assess the association between KS and adverse outcomes in patients with CAD.
RESULTS During a median follow-up period of 24 months, a total of 376 ACMs, 278 CMs, 967 MACEs and 1062 MACCEs were recorded. The incidences of these adverse outcomes were significant different between two groups (all Ps < 0.001). Kaplan-Meier analyses showed that high KS was significantly related to poor prognosis (log-rank Ps < 0.001). After adjusting the traditional confounders, multivariate Cox regression analysis revealed KS as an independent prognostic factor for long-term mortality. Compared to those in low KS group, the risk of ACM and CM in high KS group increased 69.5% [adjusted HR: 1.695, 95% CI: 1.265–2.271, P < 0.001] and 48.7% [adjusted HR: 1.487, 95% CI: 1.068–2.069, P < 0.019], respectively.
CONCLUSIONS This study revealed that high KS was associated with long-term mortality and was an independent predictor of long-term mortality in CAD patients.
GW35-e1311
Chengpeng Liu1,2, Jiasheng Yin1,2, Li Shen1,2
1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China
2National Clinical Research Center for Interventional Medicine, Shanghai, China
OBJECTIVES There is a dearth of optical coherence tomography (OCT)-based comparative research between drug-eluting stents (DES) and XINSORB bioresorbable scaffolds (BRS). The association between plaque characteristics and scaffolds expansion and eccentricity remains limited to small-scale studies.
METHODS This study consecutively enrolled patients treated with DES and XINSORB BRS undergoing post-PCI OCT pullback at Zhongshan Hospital (Shanghai, China) from January 2021 to December 2023. Evaluation of stent immediate performance through coronary angiography and OCT. Characterization of Fibrous Plaque (FP) and Calcified Plaque (CP) Features. Patients were stratified into two groups based on the median values of plaque characteristics for subsequent statistical analysis.
RESULTS This study analyzed 314 lesions in 314 patients, with 178 patients in the BRS group and 136 patients in the DES group. Propensity score (PS) matching identified 65 pairs of patients with similar baseline characteristics. After PS matching, the two groups displayed comparable lumen and scaffold dimensions; the mean and minimal scaffold eccentricity index (SEC) in the BRS group were found to be lower than those in the DES group. OCT analysis revealed that the SEC and SEI of BRS, as well as the SEI of DES, are influenced by the composition, morphology, and burden of CP and FP. The SEC of DES is unaffected by FP but is constrained by larger CP burden.
CONCLUSIONS The XINSORB BRS appears to have reduced SEC, when compared to DES. Through OCT evaluation, the expansion and eccentricity of DES and BRS are influenced by plaque characteristics.
GW35-e1314
Zhennan Li
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES There is still limited data on predictive value of coronary computed tomography angiography (CCTA)-derived fractional flow reserve (CT-FFR) for long term outcomes, incorporating functional CT-FFR into the comprehensive CCTA anatomical risk score may further optimize patients management and risk stratification. We aim to investigate the potential added prognostic value of CT-FFR over the traditional CCTA risk score, and to establish prediction models for long term clinical outcomes.
METHODS We performed a retrospective pooled analysis of individual patient data, including baseline clinical and CT characteristics. Deep-learning-based CT-FFR and Leiden CCTA risk score were calculated. All patients enrolled were followed up for at least 5 years. The primary outcome was a composite of all-cause mortality, nonfatal myocardial infarction, unstable angina requiring hospitalization and any revascularization. The secondary outcome was major adverse cardiovascular events (MACE). Predictive abilities for outcomes were investigated and compared among 3 models (model 1: constructed using clinical variables; model 2: model 1 + CCTA − derived anatomic parameters; model 3: model 2 + CT-FFR).
RESULTS A total of 2667 patients [median age: 60 (53–65) years; 56.6% males] with suspected coronary artery disease (CAD) were included. During a median follow-up time of 2194 (2124 – 2382) days, 338 patients (12.7%) experienced the primary outcomes. In multivariate-adjusted Cox models, the CT-FFR ≤0.80 (HR: 4.99; 95% CI: 3.74–6.66; P < 0.001) showed robust and independent predictive value. Compared with model 1, discriminant ability in predicting primary outcome was higher of model 2 (C-index: 0.82 vs. 0.63; P < 0.001), and further promoted by adding CT-FFR to model 3 (C-index: 0.85 vs. 0.82; P < 0.001). Time-dependent ROC curve showed similar trends across 1-year, 3-year, and 5-year AUC. Net reclassification improvement (NRI) was 0.33 (P < 0.001) for model 2 beyond model 1. Of note, adding CT-FFR to model 3 also exhibited improved reclassification compared with model 2 (NRI = 0.06; P = 0.014). In decision curve analysis, the model 3 provided incremental net benefits within a reasonable threshold probability compared with the other two models. Similar findings were also revealed using the secondary outcome of MACE.
CONCLUSIONS CT-FFR provides strong and incremental prognostic information for patients with suspected CAD. Prediction models including baseline clinical and CT-derived anatomic and physiologic parameters allow improved prediction of long-term outcomes. The proposed models are helpful for risk estimates and decision making.
GW35-e1316
Qian Zhao1,2, Maimaitiyiming Jiamule1, Yining Yang2
1First Affiliated Hospital of Xinjiang Medical University
2People’s Hospital of Xinjiang Uyghur Autonomous Region
OBJECTIVES Carotid Intima-Media Thickness (cIMT) serves as a robust indicator for the development of atherosclerotic cardiovascular disease (ASCVD), and implementing interventions has the potential to decelerate or even reverse the progression of cIMT thickening. In contemporary societies, both inadequate sleep and lack of physical activity are prevalent and have been individually linked to ASCVD. Nevertheless, the combined impact of these factors on the progression of cIMT trajectories remains uncertain.
METHODS This longitudinal prospective cohort study was conducted in the Xinjiang Uygur Autonomous Region, China, between July 2019 and September 2021. Baseline data was established during this period, with annual follow-up measurements of cIMT were conducted from 2020 to 2023. Self-reported sleep behaviors were assessed with the Pittsburgh Sleep Quality Index questionnaire. The International Physical Activity Questionnaire (IPAQ) was employed to assess and quantify PA. Group-based trajectory models (GBTM) were employed to identify trajectories patterns of cIMT: progression, no progression and declining. Multinomial logistic regression models were used to examine the associations between sleep quality and physical activity and cIMT trajectories with adjustment for age, sex, educational status, BMI, and smoking.
RESULTS A total of 1475 participants were included in the study, with an average follow-up period of 3 years. Of these, 107 (7.3%) were classified in the declining group, 1188 (80.5%) in the no progression group, and 180 (12.2%) in the progression group. The progression group exhibited a higher percentage of males, older individuals, individuals who were overweight and smoked, and individuals with poor sleep quality compared to the regression group. Compared with declining trajectory, poor sleep quality was significantly associated with higher risk of progression trajectory (OR = 1.39, 95% CI: 1.012~1.917). Poor sleep quality and physical inactivity were jointly associated with an increased progression of cIMT (OR = 0.484, 95% CI: 0.270~0.867). Good sleep quality can mitigate the negative impact of insufficient physical activity on cIMT thickening.
CONCLUSIONS Public health awareness and strategies concurrently targeting both sleep quality and physical activity should be encouraged to mitigate or reduce the formation of carotid atherosclerosis.
GW35-e1320
Tingting Wu, Ying Pan, Changjiang Deng, Yingying Zheng, Xiang Xie
Department of Cardiology, Xinjiang Medical University Affiliated First Hospital, Urumqi, China
OBJECTIVES Hematocrit (HCT) is an important indicator of anemia and blood oxygen-carrying capacity. However, evidence is scarce on the long-term prognostic value of HCT in coronary artery disease (CAD) patients. This study was to clarify this issue.
METHODS We did a large prospective cohort study in Xinjiang Medical University Affiliated First Hospital, from December 2016 to October 2021. Fifteen thousand and two hundreds thirty seven CAD patients, including 11,271 males and 3966 females, were divided into four groups based on HCT quartile and received regularly follow-up. The longest duration was 60 months. We evaluated the incidence of all-cause mortality (ACM), cardiac mortality (CM) as the primary endpoints.
RESULTS A U-shaped relationship was observed between HCT levels and long-term adverse outcomes, with a lower risk of a poor long-term prognosis when values of HCT ranged from 40 to 50% in males and 35 to 45% in females. Higher and lower HCT may increase the risk of all cause mortality (ACM), cardiovascular mortality (CM), major adverse cardiovascular events and major adverse cardiovascular and cerebrovascular events. After covariates adjustment, HCT >50% could be an independent risk factor for the occurrence of ACM (adjusted HR = 2.841, 95% CI: 1.712–4.716, P < 0.001) and CM (adjusted HR = 3.493, 95% CI: 1.963–6.214, P < 0.001) in males. A similar trend was observed in females with HCT >45% for ACM (HR = 2.257, 95% CI: 0.968–5.265, P = 0.060).
CONCLUSIONS This study identified that HCT level had a powerful prediction for long-term mortality in males with CAD, with the greater risk at higher HCT level.
GW35-e1334
Bo He1,2,3, Zhixing Guo1,2,3, Chuanyu Gao1,2,3
1Zhengzhou University People’s Hospital
2Henan Provincial People’s Hospital
3Central China Fuwai Hospital
OBJECTIVES To investigate whether coronary CTA-derived fractional flow reserve (FFR-CT) can identify patients requiring revascularization by comparing its use in the diagnosis and treatment of suspected coronary artery disease (CAD) patients with invasive coronary angiography (ICA) as the decision-making guide.
METHODS A total of 712 suspected CAD patients treated at Fuwai Huazhong Cardiovascular Hospital from December 2017 to December 2020 were included. Coronary CT angiography (CCTA) was performed first, followed by ICA within 14 days. CCTA results were categorized as normal, mild, moderate, or severe. ICA results were jointly analyzed by two cardiovascular interventional physicians to determine the degree of stenosis, with the average value taken. CCTA data were uploaded to the FFR-CT software (DeepVessel FFR by Keya Medical) powered by an artificial intelligence deep learning algorithm. Baseline patient data and CCTA, ICA, and FFR-CT results for the three major vessels were recorded. Patients’ past treatment methods were retrospectively grouped, and major adverse cardiovascular events (MACE) and secondary endpoints were recorded during follow-up. Survival differences between groups were analyzed, and the impact of patients’ medical history and various risk factors on prognosis was assessed.
RESULTS Patients were grouped based on previous imaging and treatment methods: FFR-CT-guided revascularization group (n = 189), FFR-CT-guided medical treatment group (n = 168), ICA-guided revascularization group (n = 191), and ICA-guided medical treatment group (n = 164). The number and rate of MACE events in the FFR-CT-guided revascularization group and the ICA-guided revascularization group were 31 (16.40%) and 43 (22.51%), respectively, with median follow-up times of 47 months and 45 months. Kaplan-Meier survival curves showed no significant statistical difference (Log Rank [Mantel-Cox], P = 0.133). The number and rate of MACE events in the FFR-CT-guided medical treatment group and the ICA-guided medical treatment group were 7 (4.17%) and 29 (17.68%), respectively, with median follow-up times of 55 months and 46 months. Kaplan-Meier survival curves showed significant statistical differences (Log Rank [Mantel-Cox], P < 0.001). For the FFR-CT-guided revascularization group, analysis at the vascular level indicated that 238 vessels with FFR-CT values ≤0.80 underwent percutaneous coronary intervention (PCI). Only one patient was hospitalized for PCI due to acute myocardial infarction 35 months post-enrollment, with an average repeat revascularization time of over 16 months. A subgroup analysis of patients with negative CCTA and FFR-CT results and no initial PCI (84 cases) showed that 1 patient had an acute myocardial infarction 6 months later, and 2 patients underwent revascularization at 16 and 24 months post-enrollment, respectively, with a MACE incidence rate of 3.57%. For patients with positive CCTA and FFR-CT results and no initial PCI (130 cases), there were 3 deaths, 1 myocardial infarction at 18 months post-enrollment, and 20 target vessel revascularizations, with a MACE incidence rate of 18.46%.
CONCLUSIONS FFR-CT has good predictive value for medium- and low-risk patients and similar efficacy and outcome predictive value to ICA in guiding revascularization decisions. Combined with CCTA stenosis severity and FFR-CT results, this approach may improve patient prognosis. As a non-invasive functional examination, FFR-CT has potential clinical decision-making value and may reduce risks and costs in the diagnosis and treatment process of suspected CAD patients.
GW35-e1346
Bright Eric Ohene
Northeastern University & Beijing Anzhen Hospital
OBJECTIVES Patients with ischemic heart disease as result of imbalance between myocardial oxygen demand and supply can present with stable angina, acute coronary syndromes, or even myocardial infarction with non-obstructive coronary arteries on angiography or invasive computer tomographic imaging and even without electrocardiographic or elevated biomarker evidence. Omega phenomenon (OP) is an angiographic observation, conceptualized and defined as systolic, exaggerate excursion of epicardial artery segment resulting in aberrant looping/kinking (producing inlet and outlet eccentric angulation) with transient partial luminal obliteration. This entity may be part of the causes of myocardial ischemia in non-obstructive coronary arteries, and it is so called due to its resemblance of the last Greek alphabet.
METHODS Following a meticulously planned percutaneous coronary intervention of a patient with inexplicable myocardial ischemia/infarction, where angiographic imaging, intracoronary physiological studies including Fractional flow reserve before intervention was 0.73; B: FFR after intervention was 0.94; Coronary flow reserve (CFR) before intervention was 1.4, and index of microcirculation resistance (IMR) was 46; After intervention CFR improved to 2.6; however, IMR remained unchanged. Computational fluid dynamics (CFD) and simulation was done after idealized 3D geometric models of the culprit coronary vessels (LAD, ramus intermedius, and obtuse marginal) of this omega phenomenon assuming the absence of any artery stenosis. A peak parabolic flow of 0.5 m/s was applied at the inlet. Blood was simulated as a Newtonian fluid with a density of 1060 kg/m3 and a viscosity of 0.0035 Pa.; and simulation was done during both systole and diastole. Pressure drop (∆P), wall shear stress (WSS), and flow velocity were analysed to identify flow disturbance.
RESULTS OP accounted for a sharp pressure drop and increase in velocity at the angle of (proximal) while minor changes (distal to the OP) that was not present when the angles were (proximal) and (distal). It appears that kinetic motion of the coronary arteries and eccentric tandem luminal obliteration or “knotting” induced by the proximal and distal angulations may play roles as resistors with high impedance to blood flow.
CONCLUSIONS Omega phenomenon (OP) may offer an alternative explanation for patients with myocardial infarction with non-obstructive coronary arteries (MINOCA).
HYPERTENSION
GW35-e0110
Xinrui Qi1, Yuting Wu1, Peng Yu1, Xiao Liu2
1Department of Endocrinology Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
2Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
OBJECTIVES Hypertension is one of the key risk factors driving the growing incidence of heart failure. Despite the prevalence of hypertension in young is increasing, the systematic analyses of hypertensive heart disease (HHD) global burden and attributable risk factors in young populations remains underexplored.
METHODS We obtained data from the Global Burden of Disease database for the years 1990 to 2019, focusing on adolescents and young adults (aged 15–39 years) with HHD. The dataset encompassed indictor such as prevalence, disability-adjusted life years (DALY), mortality, and disease-attributable risk factors stratified by regional, national, age, and sex.
RESULTS In 2019, the global prevalence cases stood at 278,096 (compared to 192,094 in 1990) with an age-standardized rate (per 100,000 population) of 9.15 (9.47 in 1990). High-income North America, specifically the United States of America, recorded the highest prevalence rate (per 100,000 population) of 64.45 in 2019. In 2019, there were 15,478 deaths cases globally (as opposed to 14,459 in 1990), with an age-standardized rate (per 100,000 population) of 0.51 (0.7 in 1990). Countries with low sociodemographic indices had higher DALY and mortality burden. Region Oceania, and more specifically the Cook Islands, reported the highest age-standardized mortality rate (per 100,000 population) of 3.98 in 2019. Notably, high body-mass index, alcohol use, and diet high in sodium emerged as the top three attributable risk factors.
CONCLUSIONS The global burden of the early onset HHD is on the rise due to prevalence cases growth. Countries with high socioeconomic index countries had higher prevalence and incidence burden, while low socioeconomic index countries had higher DALY and mortality burden. Effective interventions should target these regions, addressing gender disparities, socioeconomic factors, and health-care accessibility to effectively combat the growing global burden.
GW35-e0212
Shuaiwei Song, Xintian Cai, Junli Hu, Nanfang Li
Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES Obesity, especially visceral obesity, plays an important role in the progression of cardiovascular disease (CVD). The body roundness index (BRI) is a new measure of obesity that is considered to reflect visceral obesity more comprehensively than other measures. This study aims to evaluate the relationship between BRI and CVD risk in hypertensive patients with obstructive sleep apnea (OSA) and explore its superiority in predicting CVD.
METHODS The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD. The area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to assess which measures of obesity had the best predictive value for CVD risk.
RESULTS During a median follow-up period of 6.8 years, 324 participants suffered a CVD event. After multivariable adjustment, compared with the reference group (the first tertile), the HRs (95% CI) of CVD were 1.25 (95% CI, 0.93–1.70) and 1.74 (95% CI, 1.30–2.33) for subjects in the tertile 2 and tertile 3 groups, respectively. Compared with other measurement indicators, BRI has the highest predictive value for CVD risk [AUC: 0.627, 95% CI: 0.593–0.661]. The addition of the BRI to the fully adjusted multivariate model improved the predictive power for CVD, which was validated in the continuous NRI and the IDI (all P < 0.05).
CONCLUSIONS BRI was significantly associated with the risk of CVD in hypertensive patients with OSA. Furthermore, BRI may improve CVD risk prediction in hypertensive patients with OSA.
GW35-e0214
Taotao Wei, Xin Lin, Jing Yu
Department of Cardiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
OBJECTIVES The weight-adjusted-waist index (WWI) is an innovative measure of obesity that appears to surpass body mass index (BMI) in assessing lean body mass and fat mass. This study aimed to evaluate the relationship between WWI and arterial stiffness in hypertensive adults in the United States.
METHODS This study included 9753 adults diagnosed with hypertension from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. The WWI was computed by dividing waist circumference (WC) by the square root of body weight, with arterial stiffness (represented by estimated pulse wave velocity, ePWV) as the outcome. Weighted multiple linear regression and smooth curve fitting were used to test for linear and nonlinear associations. Threshold effects were determined using a two-part linear regression model. Additionally, subgroup analyses and interaction tests were conducted.
RESULTS Among the participants included, the mean WWI was 11.32 ± 0.76. After multivariable adjustment, WWI showed a significant nonlinear association with ePWV. A U-shaped association between WWI and ePWV was observed. Specifically, WWI below the threshold (WWI <10.41) was negatively associated with arterial stiffness [β = −0.50, 95% CI: (−0.57, −0.43)], while WWI above the threshold (WWI >10.41) was positively associated with arterial stiffness [β = 0.09, 95% CI: (0.07–0.11)].
CONCLUSIONS Our study indicates a U-shaped association between WWI and arterial stiffness among hypertensive adults in the United States. Also observed in both male and female populations. However, this needs to be confirmed in large clinical trials.
GW35-e0278
Lihua Hu, Yan Zhang, Jianping Li
Peking University First Hospital
OBJECTIVES Data regarding the association of the triglyceride-glucose (TyG) index, a marker of insulin resistance (IR), with the risk of hypertension are limited and inconsistent. Therefore, we aimed to assess the relationship between the TyG index and hypertension and examine any possible effect modifiers.
METHODS A total of 7.862 US adults from NHANES 2015–2018 were analyzed. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or diagnosed by a physician or taking antihypertensive drugs. Logistic regression analyses, a generalized additive model and smooth curve fitting and a two-piecewise logistic regression models were used to evaluate the association between TyG index and hypertension.
RESULTS Overall, the mean TyG index was 8.14 (1.25) and 2507 (31.89%) participants had hypertension. Compared with the reference group, there was an increased prevalence of hypertension for participants in the first and fourth quartiles of the TyG index. We further found a U-shaped association between the TyG index and hypertension in the overall population and both sexes. The inflection point for the curve was found at a TyG index of 7.88. The ORs (95% CI) for hypertension were 0.88 (0.82, 0.95) and 1.29 (1.16, 1.43) to the left and right of the inflection point, respectively. When the TyG index was ≥7.88, a significantly stronger positive association between the TyG index and hypertension was observed in participants with BMI <25 kg/m2 (OR = 1.80, 95% CI: 1.32–2.44) than in those with BMI ≥25 kg/m2 (OR = 1.22, 95% CI: 1.07–1.40; Pinteraction = 0.013).
CONCLUSIONS There was a U-shaped association between TyG index and hypertension in US adults, with an inflection point at approximately 7.88. Our findings emphasized the importance of maintaining an optimal TyG index for the primary prevention of hypertension.
GW35-e0286
Junwen Wang, Yuyang Ye, Xuefeng Chen, Xinru Hu, Yong Peng
Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China
OBJECTIVES Although hypertension is highly prevalent among the elderly and significantly contributes to cardiovascular disease risk, studies focusing on male elderly individuals over 85 years old are relatively scarce. This study investigated ABPM characteristics in male hypertensive patients aged over 85 years.
METHODS This research included male elderly hypertensive patients with stable vital signs experiencing internal medicine conditions who were admitted to the Department of Geriatric Medicine and Cardiology at the General Hospital of Western Theater Command of the People’s Liberation Army from January 1, 2018, to September 31, 2023. The inclusion criteria were: confirmed primary hypertension diagnosis, age over 65 years, male gender, and complete ABPM. This included demographic characteristics, antihypertensive drug use, values of 24-hour ABPM, diabetes, coronary heart disease, sleep disorders, smoking history, and drinking history, analyzing the differences in ABPM between the age groups over and under 85 years old.
RESULTS A total of 585 elderly hypertensive patients were included. The mean systolic blood pressure in individuals aged over 85 years was significantly higher throughout the day (131.57 ± 12.52 mmHg vs. 123.75 ± 2.74 mmHg, P < 0.001). In the age group over 85 years, the nighttime variability coefficient of SBP was lower at 7.84 ± 2.9 than the under 85 years age group 8.92 ± 3.13 (P < 0.001). The age group of individuals over 85 years exhibited a significantly higher standard deviation of ABPM (13.2 ± 3.19 vs. 12.47 ± 3.05, P = 0.005) compared to those under the age of 85 years. In the age group over 85 years, the proportion of individuals with the reverse dipper pattern was higher (48.15% vs. 38.31%, P = 0.017) than under 85 years age group.
CONCLUSIONS This study found that elderly male hypertensive patients over 85 years old have higher average blood pressure levels. They also have less variability in nighttime blood pressure compared to younger elderly groups. Older hypertensive individuals are more likely to have a reverse-dipper blood pressure pattern.
GW35-e0317
Jinyu Sun, Wei Sun, Xiangqing Kong
The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES This study aims to ascertain whether abdominal fat accumulation evaluated by waist circumference increases the risk of hypertension using the nationwide populations.
METHODS We enrolled 47,037 participants from the China Health and Nutrition Survey (CHNS), China Health and Retirement Longitudinal Study (CHARLS), and National Health, and Nutrition Examination Survey (NHANES). The adjusted logistic regression model was used to examine the relationship between waist circumference and prevalent hypertension. Nine thousaund four hundred and forty-five participants without baseline hypertension from the CHNS and CHARLS were followed up to investigate the association between waist circumference and onset hypertension. The association was evaluated using a Cox regression model and restricted cubic spline. Furthermore, Mendelian randomization was employed to explore causal inferences.
RESULTS In the baseline survey, waist circumference demonstrated a notable correlation with hypertension, presenting an odds ratio (with 95% confidence intervals) of 1.34 (1.28~1.40). After a mean follow-up of 3.8 years for participants without baseline hypertension, 2592 (27.5%) developed hypertension. In the pooled analysis, the Cox regression showed that every 10 cm increment in waist circumference amplified the hypertension risk by 21% (95% CI: 14%~28%). Restricted cubic splines indicated a pronounced linear dose-response relationship. A sensitivity analysis affirmed the persisting association between waist circumference and hypertension onset even in those with normal BMI. The Mendelian randomization method revealed a significant causative association between waist circumference and hypertension.
CONCLUSIONS Elevated waist circumference stands as an independent risk factor for hypertension, even in those with normal BMI.
GW35-e0336
Bin Liu, Xinyu Zou, Qiang She
Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University
OBJECTIVES Whether an increase in epicardial adipose tissue (EAT) is a risk factor for primary hypertension remains controversial. The aim of this study was to conduct a meta-analysis to investigate the association of increased EAT with primary hypertension.
METHODS Published English articles in PubMed, EMBASE, and Cochrane databases assessing the association of EAT thickness (EAT-t) and volume (EAT-v) with primary hypertension were systematically reviewed and conducted by meta-analysis.
RESULTS There were 41 studies and 9211 subjects included in the analysis. The comparison between primary hypertension with respect to normotensive individuals showed that EAT-t (standard mean difference (SMD) = 0.64, 95% confidence intervals (CI): 0.46–0.83, P < 0.001) and EAT-v (SMD = 0.45, 95% CI: 0.18–0.72, P = 0.002) were both higher in primary hypertension group. In addition, higher EAT-t and EAT-v were associated with a 1.7- and 1.9-fold higher odds of primary hypertension (EAT-t, OR: 1.71, 95% CI: 1.19–2.47, P < 0.001; EAT-v, OR: 1.84, 95% CI: 1.29–2.62, P = 0.001). We also found higher EAT-t and EAT-v in non-dipper hypertensive patients. However, we didn’t find significant difference in EAT-t among patients with different grades of hypertension. We investigated the association of EAT with complications in hypertensive patients, and EAT-t was increased in patients with cardiac hypertrophy and dysfunction.
CONCLUSIONS Increased EAT is associated with the development of essential hypertension, circadian blood pressure changes, and hypertension-related complications.
GW35-e0377
Xinru Hu1, Guangzhi Liao1, Junwen Wang1, Yuyang Ye1, Xuefeng Chen1, Lin Bai1, Fanfan Shi2, Kai Liu1, Yong Peng1
1Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, PR China
2Department of Clinical Research and Management, Center of Biostatistics, Design, Measurement and Evaluation (CBDME), West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China
OBJECTIVES The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient-specific factors predicting the RDN response.
METHODS We focused on hypertensive individuals who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the GRADE approach to assess the overall quality of evidence.
RESULTS Fifty studies were ultimately included in this systematic review, among which 17 studies were for meta-analysis. Higher baseline heart rate (HR) and lower pulse wave velocity (PWV) were shown to be associated with significant antihypertensive efficacy of RDN on 24-hour systolic blood pressure (SBP) reduction (WMD = −4.05, 95% CI = −7.33 to −0.77; WMD = −7.20, 95% CI = −9.79 to −4.62). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension (OHTN), impaired baroreflex sensitivity (BRS), and several biomarkers are also reported to be associated with significant BP reduction after RDN.
CONCLUSIONS In hypertensive patients treated with the RDN, higher HR, and lower PWV were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with OHTN, BP variability, impaired cardiac BRS, and some biomarkers are also reported to be associated with a better BP response to RDN.
GW35-e0413
Wei Zhang1, Jin Zhang1, Jie Yan3, Qian Ge1, Xiaohong Lu1, Shaoxing Chen1, Wenjie Xu3, Jingchao Sun3, Jinfeng Li3, Zichen Liu3, Qiang Wang3, Xiangnan Zhou3, Yan Li1, Jiguang Wang1,2
1Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2National Research Centre for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
3Shenzhen Salubris Pharmaceuticals Co., Ltd. Shenzhen, Guangdong, China
OBJECTIVES The prevalence of hypertension still increases with the very rapidly increasing longevity in some countries, such as China. The control rate remains low. This randomized, double-blind, phase 3 study assessed the efficacy and safety of sacubitril/allisartan, compared with olmesartan in Chinese patients with mild to moderate hypertension.
METHODS Eligible patients aged 18–75 years (n = 1197) with mild to moderate hypertension were randomized to receive sacubitril/allisartan 240 mg (n = 399), sacubitril/allisartan 480 mg (n = 399), or olmesartan 20 mg (n = 399) once daily for 12 weeks. Patients who completed the 12-week treatment then received another 12-week extended treatment (n = 1084) and 28-week prolonged treatment (n = 189). The primary end point was a reduction in clinic mean sitting systolic blood pressure (msSBP) from baseline at 12 weeks.
RESULTS Sacubitril/allisartan 240 mg/day provided a greater reduction in msSBP than olmesartan at 12 weeks (between-group difference: −1.9 mmHg [95% confidence interval −4.2 to 0.4 mmHg], P = 0.0007, for non-inferiority). Sacubitril/allisartan 480 mg/day provided a significantly greater reduction in msSBP than olmesartan at 12 weeks (between-treatment difference: −5.0 mmHg [95% confidence interval −7.3 to −2.8 mmHg], P < 0.001, for superiority). Greater reductions in 24-h, daytime and nighttime systolic and diastolic blood pressure were also observed with both doses of sacubitril/allisartan compared with olmesartan (P ≤ 0.001 for 480 mg/day). The blood pressure reductions tended to be dose-dependent for sacubitril/allisartan. Sacubitril/allisartan was well tolerated, and no cases of angioedema or death were reported.
CONCLUSIONS Sacubitril/allisartan is effective for the treatment of hypertension and well tolerated in Chinese patients.
GW35-e0441
Yujie Zuo, Hui Dong, Hongwu Li, Wentao Ma, Yubao Zou, Xiongjing Jiang
National Center for Cardiovascular Diseases and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Multiple randomized controlled trials have demonstrated that renal denervation (RDN) was effective and safe for the treatment of hypertension. However, there were few reports on long-term outcomes, particularly on the impact of ablation approaches towards the long-term efficacy and safety. This study is to evaluate the long-term efficacy and safety of transfemoral access (TFA) versus upper extremity access (UEA) for RDN based on vascular morphology.
METHODS This study retrospectively enrolled all patients with resistant hypertension who underwent RDN treatment via TFA and UEA (brachial, radial and ulnar artery) based on vascular morphology at the Fuwai Hospital between February 2012 and November 2019. Follow-up was conducted at 6 months, 1 year, and 3 years after RDN, and the last visit was June 2023. The procedure parameters of RDN were compared between two approaches. The data on baseline, blood pressure (BP), heart rate, antihypertensive drugs, renal function, and major adverse events were recorded during followup.
RESULTS Total 85 patients were enrolled, 58 (68.2%) of them were treated via TFA, and 27 patients (31.8%) were treated via UEA. The fluoroscopy time was less in the TFA group (12.2 ± 5.7 minutes vs. 15.2 ± 7.2 minutes; P = 0.038). The procedure time (40.8 ± 14.9 minutes vs. 38.6 ± 11.7 minutes; P = 0.506), contrast volume (78.2 ± 25.9 mL vs. 91.9 ± 39.7 mL; P = 0.061) were similar between two groups, and there were no procedure-related complications. Fifty-eight participants (41 participants in TFA group and 17 participants in UEA group) completed the last follow-up with a 3–12 year of followup (9.5 ± 1.3 years). Compared with baseline, there were not significant difference in the change of office systolic BP (−12.6 ± 21.6 mmHg vs. −13.1 ± 22.8 mmHg; P = 0.933), 24-hour mean systolic BP (−11.9 ± 14.2 mmHg vs. −11.3 ± 15.3 mmHg; P = 0.899), the number of antihypertensive drug, and renal function between two groups. There were three adverse events in TFA group (3 of 58 patients, 5.2%) vs. one (1 of 27 patients, 3.7%) in UEA group, without significant difference between two groups.
CONCLUSIONS The study showed RDN via UEA was feasible using a special designed catheter, particularly in the patients with illegal vascular morphology via TFA.
GW35-e0467
Yujie Dang1, Nanfang Li1, Qing Zhu1, Mulalibieke Heizhati1, Lin Gan1, Wen Wen2, Delian Zhang1, Jing Hong1, Qin Luo1
1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region “Hypertension Research Laboratory”, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases
2School of Graduate Studies, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China
OBJECTIVES Statins have cardiovascular protective effects in addition to lipid-lowering effects. However, no human studies have examined whether statins prevent aortic dissection in hypertensive patients. This study aimed to explore the association between statins and aortic dissection.
METHODS This nested case–control study was based on data extracted from the UHDATA (Hypertension Database at Urumchi) in Xinjiang of China. Cases (patients who developed aortic dissection) and controls (patients without aortic dissection; matched for age, sex, and date of aortic dissection diagnosis) were selected from among the 52,146 adult patients with hypertension and hyperlipidemia or high-risk hypertension registered in the database between January 1, 2006, and December 31, 2018. Follow-up data were collected up to April 30, 2022. Multivariable logistic regression analysis was used to assess the relationship between statin use and aortic dissection.
RESULTS A total of 7049 patients (75.6% men; mean age, 54.6 years) were selected for the study: 647 patients who developed aortic dissection during the follow-up period and 6402 patients who did not develop aortic dissection. The proportion of patients using statins was lower in the case group than in the control group (21.2% vs. 29.9%, P < 0.001). However, in multivariable logistic regression analysis, statin use was independently associated with decreased risk for aortic dissection (adjusted OR = 0.538, 95% CI: 0.418–0.692, P < 0.001).
CONCLUSIONS Statins appear to reduce risk of aortic dissection, and clinicians should consider early use of statins in hypertensive patients, especially those with hyperlipidemia and multiple risk factors.
GW35-e0566
Zeya Li1, Yu Zhao1, Weihua Chen1, Dongjie Du1, Shanshan Wu2, Xianzhong Gu3, Rongchong Huang1
1Department of Cardiology, Beijing Friendship Hospital, Capital Medical University
2National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital
3Beijing Tongzhou Yongshun Community Health Service
OBJECTIVES Serum uric acid (SUA) has been demonstrated as a risk factor for decline in kidney function; however, the impact of cumulative SUA (cumSUA) in patients with hypertension remains unclear.
METHODS The cohort study enrolled 2472 hypertensive patients without a history of without chronic kidney disease (CKD), and these participants underwent a 3-year follow-up of kidney function during 2016 to 2021. CumSUA over 3-year follow-up was derived by calculating the means of SUA values between consecutive examinations and multiplying by time intervals between visits. Participants were classified by cumSUA tertiles. Logistic regressions and restricted cubic spline analysis were used to explore the association between the cumSUA and the endpoint. The primary endpoint was defined as the new-onset of CKD, and the secondary endpoint was the decline in kidney function, which defined as the slope of estimated glomerular filtration rate (eGFR) ≤−3 mL/min/1.73 m2/year.
RESULTS During a 3-year follow-up, 84 incident CKD and 386 secondary endpoints occurred. In the multivariable-adjusted model, a higher risk of CKD was observed in participants with the highest tertiles versus the lowest tertiles of cumSUA [OR (95% CI) 4.53 (2.4–8.55), P < 0.001]. Restricted cubic spline analysis revealed a linear association of cumSUA with risk of CKD. Similarly, participants with the highest tertiles also had higher risk of decline in kidney function versus the lowest tertiles of cumSUA [OR (95% CI) 1.93 (1.48–2.52), P < 0.001].
CONCLUSIONS The risk of CKD and decline in kidney function increased with higher cumSUA in patients with hypertension.
GW35-e0568
Zeya Li1, Shanshan Wu2, Xianzhong Gu3, Rongchong Huang1
1Department of Cardiology, Beijing Friendship Hospital, Capital Medical University
2National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University
3Beijing Tongzhou Yongshun Community Health Service
OBJECTIVES The role of uric acid (UA) in chronic kidney disease (CKD) remains controversial. In this study, the effects of UA levels on risk of kidney function (KF) decline in patients with normal or mildly decreased KF at baseline were investigated.
METHODS Data were extracted from the community-based Tongzhou Cohort Study (ClinicalTrials.gov Identifier: NCT05156580). The cohort of 4246 patients was divided into the normal KF group (estimated glomerular filtration rate [eGFR] ≥90 mL/min/1.73 m2) or mildly decreased KF group (60≤ eGFR <90 mL/min/1.73 m2). The primary endpoint was the risk of kidney function decline, which defined as a composite of a ≥30% decrease in eGFR from baseline or new onset of CKD diagnosed during the annual checkups.
RESULTS A total of 284 participants reached the primary endpoint during the 5-year follow-up period. There was a significant interaction between UA levels and baseline eGFR (P < 0.001). Restricted cubic spline analysis revealed a U-shaped association between baseline UA levels and the risk of decreased KF for participants with normal KF (cut-off value = 5.0 mg/dL; Pnonlinear = 0.025) and a linear association for participants with mildly decreased KF (Pnonlinear = 0.384). The odds ratio of an increase in UA levels by 1 mg/dL was 1.15 [95% confidence interval (CI) 1.02–1.31, P = 0.028] for the primary endpoint and 1.15 (95% CI = 1.01–1.31, P = 0.037) for new onset of CKD for participants with mildly decreased KF.
CONCLUSIONS The association between uric acid and risk of KF decline was U-shaped in participants with normal KF while linear in participants with mildly decreased KF.
GW35-e0569
Zeya Li1, Weihua Chen1, Yu Zhao1, Dongjie Du1, Shanshan Wu2, Xianzhong Gu3, Rongchong Huang1
1Department of Cardiology, Beijing Friendship Hospital, Capital Medical University
2National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital
3Beijing Tongzhou Yongshun Community Health Service
OBJECTIVES Serum uric acid (SUA) has been demonstrated as a risk factor for decline in kidney function; however, whether the change of SUA could alter kidney outcomes in patients with hypertension remains unclear.
METHODS The cohort study enrolled 3964 hypertensive patients without a history of without chronic kidney disease (CKD). These participants underwent at least two annual examination for SUA and kidney function during 2016 to 2021. Participants were categorized based on SUA change patterns, including stable normal pattern (<7.0 mg/dL at both baseline and follow-up), normal to hyperuricemia pattern (<7.0 mg/dL at baseline and ≥7.0 mg/dL at follow-up), stable hyperuricemia pattern (≥7.0 mg/dL at both baseline and follow-up), hyperuricemia to normal (above target) pattern (≥7.0 mg/dL at baseline and 6.0–7.0 mg/dL at follow-up), and hyperuricemia to normal (below target) pattern (≥7.0 mg/dL at baseline and <6.0 mg/dL at follow-up). The primary endpoint was the risk of new-onset of CKD.
RESULTS During a median follow-up of 4 years, 145 incident CKD occurred. Compared with participants with stable normal SUA, those transitioning from normal to hyperuricemia category had a 5.91-fold higher risk of CKD (OR 6.91, 95% CI 4.58–10.43, P < 0.001). Stable hyperuricemia was also consistently linked with an increased risk of CKD (OR 7.14, 95% CI 4.09–12.47, P < 0.001). However, patients transitioning from hyperuricemia to normal (above target) had a 54% lower risk of CKD (OR 0.46, 95% CI 0.22–0.95, P = 0.035), and those transitioning from hyperuricemia to normal (below target) had a 66% lower risk of CKD (OR 0.34, 95% CI 0.12–0.93, P = 0.036).
CONCLUSIONS Stable hyperuricemia and transitioning from normal to hyperuricemia were associated with increased risks of CKD. However, transitioning from hyperuricemia to normal could significantly reduce this risk.
GW35-e0571
Zeya Li1, Yu Zhao1, Weihua Chen1, Dongjie Du1, Shanshan Wu2, Xianzhong Gu3, Rongchong Huang1
1Department of Cardiology, Beijing Friendship Hospital, Capital Medical University
2National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital
3Beijing Tongzhou Yongshun Community Health Service
OBJECTIVES Serum uric acid (SUA) has been demonstrated as a risk factor for decline in kidney function; however, the impact of variability of SUA in patients with hypertension remains unclear.
METHODS The cohort study enrolled 2472 hypertensive patients without a history of without chronic kidney disease (CKD) Variability of SUA over 3-year follow-up was derived by calculating the average real variability (ARV) (primary index), standard deviation (SD) and coefficient of variation (CV) of SUA values between consecutive examinations. Participants were classified by ARV tertiles. Logistic regressions and restricted cubic spline analysis were used to explore the association between the SUA variability and the endpoint. The primary endpoint was the risk of new-onset of CKD, and the secondary endpoint was the decline in kidney function, which defined as the slope of estimated glomerular filtration rate (eGFR) ≤−3 mL/min/1.73 m2/year.
RESULTS During a 3-year follow-up, 84 incident CKD and 386 secondary endpoint occurred. In the multivariable-adjusted model, a higher risk of CKD was observed in participants with the highest variability tertiles versus the lowest variability tertiles [OR (95% CI) 7.29 (3.45–15.40), P < 0.001]. Restricted cubic spline analysis revealed a linear association between variability of SUA and the risk of CKD. Similarly, participants the highest variability tertiles also had higher risk of decline in kidney function versus the lowest tertiles [OR (95% CI) 2.17 (1.66–2.85), P < 0.001].
CONCLUSIONS The risk of CKD and decline in kidney function increased with higher variability of SUA in patients with hypertension.
GW35-e0663
Yuanyuan Kang1, Jianzhong Xu1, Xiongjing Jiang2, Jiguang Wang1
1Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2Department of Cardiology, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
OBJECTIVES Fibromuscular dysplasia (FMD) is a noninflammatory arterial disease that predominantly affects women. The arterial manifestations may include beading, stenosis, aneurysm, dissection, or tortuosity. This study compared the frequency, location, and outcomes of FMD patients with aneurysm and/or dissection to those of patients without.
METHODS Consecutive hypertensive patients with renal artery stenosis caused by FMD underwent catheter-based angiography, followed at two Chinese referral centers in China between January 2000 and October 2023.
RESULTS Aneurysm occurred in 72 patients (24.9%) and dissection in 14 patients (4.8%); in total, 85 patients (29.0%) had an aneurysm and/or a dissection by the time of FMD diagnosis. The extracranial carotid, renal, and intracranial arteries were the most common sites of aneurysm; dissection most often occurred in the renal arteries. FMD patients with dissection were elder at presentation (37.6 vs. 26.5 years of age, respectively; P < 0.0001) and experienced more headache symptoms and renal infarction events than those without dissection. One-fifth of aneurysm patients (14 of 72) underwent therapeutic intervention for aneurysm repair.
CONCLUSIONS Chinese patients with renal artery FMD had a lower prevalence of dissection at the time of FMD diagnosis than Caucasians, but similar prevalence of aneurysm. Patients with dissection and aneurysm had high prevalence of renal infarction. Because of the high prevalence and associated morbidity in patients with FMD who have an aneurysm and/or dissection, it is recommended that every patient with FMD undergo one-time cross-sectional imaging from head to pelvis with computed tomographic angiography or magnetic resonance angiography.
GW35-e0694
Jia Shanshan, Liu Lu, Huo Xingwei, Sun Lirong, Chen Xiaoping
West China Hospital of Sichuan University
OBJECTIVES Several cohort studies underscored significant associations between novel anthropometric indices, such as the body roundness index (BRI) and a body shape index (ABSI), and the onset of hypertension. However, studies on the relationship between ABSI and BRI and mortality in people with hypertension have been inconclusive.
METHODS The study included adults with hypertension in the 2007–2018 National Health and Nutrition Examination Survey (NHANES). We used a weighted multivariate Cox regression analysis to assess the association between BRI and ABSI and all-cause mortality. We further evaluated the potential non-linear association between BRI and ABSI and mortality using restricted cubic spline (RCS) analysis. Receiver operating characteristic curve (ROC) analysis was used to assess the predictive power of BRI and ABSI for survival. Our study used R software (version 4.2.1) for visualization and statistical analysis.
RESULTS After a median follow-up of 79 months, a total of 813 participants died. The average age of all participants was 55.06 ± 0.27 years, with males constituting 52.95%. Our study indicated that mortality risk increased by 49% and 75% for each 1-unit and 0.01-unit increase in BRI and ABSI, respectively. Additionally, compared to the reference group, the highest BRI and ABSI groups exhibited a significantly elevated mortality risk by 91% and 107%, respectively. RCS analysis revealed no significant nonlinear association between BRI and ABSI and mortality. The ROC curve confirmed that ABSI was superior to BRI in predicting 10-year mortality.
CONCLUSIONS Our study confirmed a positive association between BRI and ABSI and mortality in hypertensive patients. Our finding further underscores the importance of assessing fat distribution in hypertensive patients for prognostic evaluation.
GW35-e0723
Zhang Yingying, Cai Xintian, Li Nanfang
Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES This study aimed to examine the association between plasma aldosterone concentration (PAC) and the prevalence of peripheral vascular disease (PAD) in hypertensive patients.
METHODS A total of 13,860 subjects with hypertension were included in the final study. PAD was defined as either side of the ankle-brachial index (ABI) ≤0.90. A multivariate logistic regression model was employed to investigate the association between PAC and PAD prevalence. To elucidate potential non-linear relationships and to graphically represent the dose-response curve, restricted cubic splines were employed. Furthermore, sensitivity and subgroup analyses were performed.
RESULTS The study revealed a significant non-linear (J-shaped) association between PAC and PAD prevalence (P for non-linearity = 0.024), with a critical threshold identified at 14.00 ng/dL. The prevalence of PAD was notably lower in participants with PAC below this threshold (per 5 ng/dL: odds ratio [OR], 0.63; 95% confidence interval [CI], 0.43–0.93) and higher in those with PAC at or exceeding this level (per 5 ng/dL: OR, 1.13; 95% CI, 1.01–1.26). Quartile analysis indicated a higher PAD prevalence in the first and fourth quartiles of PAC compared to the intermediate quartiles.
CONCLUSIONS The findings of this study suggest a J-shaped association between PAC and PAD prevalence in hypertensive patients, with an optimal PAC level for PAD risk at approximately 14.00 ng/dL. These results highlight the need for further large-scale, prospective studies to validate these findings and explore the potential clinical implications for PAD prevention and management in hypertensive individuals.
GW35-e0739
Rui Ma, Xintian Cai, Qin Luo, Nanfang Li
Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES The effects of visceral fat on osteoporosis have attracted considerable attention. The Chinese visceral adiposity index (CVAI) has been demonstrated to respond more effectively than conventional measures in reflecting visceral fat characteristics in the Chinese population. This study aimed to explore the relationship between CVAI and bone mineral density (BMD), FRAX scores and osteoporosis in Chinese elderly individuals with hypertension.
METHODS The datasets from the People’s Hospital of Xinjiang Uygur Autonomous Region from January 2021 to December 2023 were utilized in a cross-sectional investigation. The Chinese version of FRAX scores was employed to assess the probability of a major osteoporotic fracture (MOF) or hip fracture (HF) over a 10-year period in participants. Furthermore, linear and logistic regression models were employed to investigate the relationship between CVAI and BMD, FRAX scores, and osteoporosis, while adjusting for potential confounding variables.
RESULTS A total of 850 elderly participants with hypertension, with a mean age of 67.21 ± 6.17 years, were included in the final analysis. The results of the multivariate linear regression analysis indicated a significant positive association between CVAI and BMD and a negative association between CVAI and FRAX scores. In contrast, logistic regression analysis indicated that CVAI was negatively correlated with the risk of osteoporosis.
CONCLUSIONS The results of this study demonstrated a significant correlation between elevated CVAI and increased BMD, reduced FRAX scores, and diminished a risk of osteoporosis in elderly participants with hypertension. Further research is necessary to determine the causal relationship between CVAI, BMD, and the risk of fracture and osteoporosis.
GW35-e0743
Xintian Cai1,2,3, Nanfang Li1,2,3
1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region
2Xinjiang Hypertension Institute
3NHC Key Laboratory of Hypertension Clinical Research
OBJECTIVES Cardiovascular disease (CVD) remains the leading cause of mortality globally, with hypertension identified as a critical risk factor. Plasma aldosterone concentration (PAC) has emerged as a significant and modifiable risk factor for CVD; however, most studies have relied on single measurements of PAC, potentially overlooking the impact of long-term PAC patterns. This cohort study aimed to delineate the long-term trajectories of PAC and investigate their association with the risk of CVD in hypertensive patients.
METHODS We conducted a longitudinal analysis of 2254 hypertensive adults from the People’s Hospital of Xinjiang Uygur Autonomous Region, China. Participants underwent three surveys between 2010 and 2016. Latent mixed modeling was utilized to identify PAC trajectory patterns during this period, and the association between these trajectories and the risk of CVD was examined using Cox regression analysis.
RESULTS Over a median follow-up of 4.10 years, 82 incident CVD cases were identified. Three distinct PAC trajectory patterns were observed: low-stable, moderate-stable, and high-stable. The high-stable PAC pattern was associated with the highest risk of CVD, with hazard ratios (HRs) of 2.19 for the moderate-stable and 2.56 for the high-stable pattern compared to the low-stable pattern after adjusting for covariates. Subgroup and sensitivity analyses confirmed these findings, suggesting that a persistently high PAC level is a significant predictor of CVD risk in hypertensive patients.
CONCLUSIONS This study provides the first longitudinal evidence linking PAC trajectory patterns with CVD risk in a Chinese hypertensive population. The findings underscore the importance of monitoring PAC levels over time as a potential strategy for identifying individuals at increased risk of CVD. While the study’s strengths include its longitudinal design and robust analytical methods, limitations such as the observational nature and potential residual confounding factors should be considered. Further research is warranted to validate these findings and explore the mechanisms underlying the observed associations.
GW35-e0753
Pan Zhou, Xintian Cai, Nanfang Li
People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES Limited studies have examined the relationship between plasma aldosterone concentration (PAC) and arterial stiffness progression. The objective of this study was to investigate the longitudinal association between baseline PAC and arterial stiffness progression in hypertensive patients.
METHODS A total of 1138 hypertensive patients were enrolled in the study. PAC was measured using standard techniques while in a sitting position. Arterial stiffness was quantified using brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness that is non-invasive in nature. Progression of baPWV was assessed using the baPWV change rate (the absolute difference between baseline and follow-up baPWV, divided by the follow-up time in years). Multivariate linear regression models were employed to idenitify the associations between baseline PAC and the baPWV change rate. Additionally, multivariable restricted cubic splines were utilized to investigate the dose-response relationship between baseline PAC and baPWV change rate.
RESULTS Multivariate linear regression analyses revealed that an increase of one unit in PAC at baseline was associated with a 1.96 cm/s/year increase [95% confidence interval (CI), 0.99, 2.92] in baPWV change rate. Furthermore, RCS demonstrated a significant dose-response relationship between baseline PAC and the baPWV change rate.
CONCLUSIONS This study found that higher levels of PAC were associated with a faster progression of arterial stiffness. This study is the first to establish an association between baseline PAC and the rapid arterial stiffness progression in hypertensive patients, thereby increasing the risk of arteriosclerosis and vascular disease. These findings suggest that controlling PAC levels could represent a novel approach to delaying the onset of arterial stiffness.
GW35-e0764
Weihong Chang1,2, Boda Zhou1,2
1Beijing Tsinghua Changgung Hospital
2Tsinghua University
OBJECTIVES VEGF inhibition may elevate blood pressure by reducing the bioavailability of vasodilator nitric oxide, and by increasing the activity of the vasoconstrictor endothelin-1. Studies have examined the relationship between HTN and clinical outcome among patients treated with bevacizumab. In a correlative study involving 4599 non small cell lung cancer (NSCLC) patients, patients with bevacizumab-induced HTN experienced significantly longer overall survival (OS) than patients without bevacizumab-induced HTN. A significant improvement in treatment response and time to progression has also been reported for patients with metastatic colorectal cancer (CRC) who required antihypertensive medication during treatment with bevacizumab. Thus, there is hypothesis that the onset of bevacizumab-induced HTN during treatment involves successful inhibition of the VEGF pathway. Of note, VEGF-A has been reported as a useful marker for predicting the effects of bevacizumab. As CCB and angiotensin II receptor blocker (ARB) are the most commonly used antihypertensive medicine, we asked whether CCB or ARB may have different antihypertensive, cardioprotective and anticancer effects in the treatment of bevacizumab induced HTN. Unfortunately, to our best knowledge, there was no published clinical study or RCT on this topic.
METHODS This is a single-center pilot study on patients with Bevacizumab induced HTN. Inclusion criteria were adult patients from 18 to 70 year-old, in sinus rhythm and normal echocardiographic LV ejection fraction (LVEF ≥50%), diagnosed of solid tumors who were on Bevacizumab treatment and developed HTN after Bevacizumab treatment.
RESULTS In general, 11 patients with Bevacizumab induced HTN were enrolled, 4 were randomized into ARB treatment group, the other 7 were randomized into non-ARB (6 treated with CCB, 1 treated with β-blocker) treatment group. The change of serum VEGF levels before and after treatment were compared between ARB and non-ARB groups. ARB treatment tend to increase serum VEGF level comparing with non-ARB treatment, with P value 0.092.
CONCLUSIONS ARB treatment tend to increase serum VEGF level comparing with non-ARB treatment. Non-ARB is better than ARB for patients treated with bevacizumab.
GW35-e0805
Di Shen, Xintian Cai, Nanfang Li
Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES Metabolic-dysfunction-associated fatty liver disease (MAFLD), a prevalent condition that affects approximately one-quarter of the global adult population, represents a significant health and economic burden across all societies, with a notable impact on the Asian demographic. However, MAFLD, a new definition for metabolic fatty liver disease, has not yet been studied in relation to plasma aldosterone concentration (PAC), and the link between the two remains unclear. This study is designed to explore the correlation between PAC and MAFLD, with the intent of contributing novel insights into the prevention and therapeutic intervention of metabolic fat accumulation in the context of hypertensive patients.
METHODS Between January 1, 2014, and December 31, 2023, a total of 41,131 hospitalized patients were included in the study. Multivariate logistic regression models are used to test associations. We further confirmed our findings using threshold analysis. To reinforce the robustness of our findings, subgroup and sensitivity analyses were also conducted.
RESULTS Overall, in the original model, for every 5-unit increase in PAC, the risk of developing MAFLD increases by 1.57 times. This relationship remains reliable in the fully adjusted model. Compared to the Q1 group, the OR values for the Q2, Q3, and Q4 groups are 1.21, 2.12, and 3.14 respectively, showing an increasing trend. Notably, threshold effect analysis identified a pivotal threshold at 14 ng/dL. Subgroup and sensitivity analyses yielded consistent results with these findings.
CONCLUSIONS This study has uncovered a robust positive association between increased PAC levels and the prevalence of MAFLD in hypertensive patients. It is imperative to undertake larger-scale prospective studies to substantiate these findings.
GW35-e0963
Yuhang Yang, Tongshuai Chen, Peili Bu
Department of Cardiology, National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China
OBJECTIVES Atrial fibrosis, which is considered an important mechanism contributes to the occurrence and recurrence of atrial fibrillation (AF), is apparent in AF patients with hypertension. Low-voltage areas (LVAs) are an important marker of atrial fibrosis. However, the mechanism of hypertension-induced atrial fibrosis is not clear. This study aimed to investigate the characteristics of atrial substrate in AF patients with hypertension and how hypertension affects atrial substrate.
METHODS From June 2022 to June 2023, we evaluated the relationship between the distribution of LVAs in the left atrium (LA) and the three-dimensional CT image measurements of ascending aorta and LA such as aortic sinus, aorta-LA angle and aorta-left ventricular angle in 82 patients who underwent catheter ablation for AF. All patients were followed-up at our outpatient clinic or by phone at 12 months after the procedure.
RESULTS Forty-five AF patients (54.9%) suffered from hypertension. For CT features, the hypertensive group (vs. normotensive group) had a smaller aorta-LA angle (mean, 22.2° vs. 26.2°; P < 0.001), greater aorta-left ventricular (LV) angle (mean, 131.7° vs. 128.0°; P < 0.001), larger noncoronary cusp (NCC) diameter (20.34 ± 0.85 mm vs. 19.28 ± 0.76 mm; P < 0.001) and smaller left coronary cusp (LCC)-right coronary cusp (RCC) distance (28.84 ± 2.43 mm vs. 31.11 ± 3.06 mm; P < 0.001). For LVAs, a larger total LVAs area (37.4 cm2 vs. 27.6 cm2; P < 0.01), especially LVAs area in the anterior wall (15.6 cm2 vs. 10.2 cm2; P < 0.001) was observed in AF patients with hypertension. There was a correlation between CT features and LVAs features. The aorta-LA angle correlated negatively with the LVAs in anterior wall, and the aorta-LV angle correlated positively with the LVAs. A cut-off of 21.8° for aorta-LA angle and 129.4° for aorta-LV angle are significant for prediction of AF recurrence.
CONCLUSIONS Expansion of aortic sinus especially NCC and narrow angle between the ascending aorta and LA are obvious in the hypertensive group, which may relate to LVAs in AW. Mechanical pressure by the ascending aorta on the LA may contribute to atrial fibrosis in AF patients with hypertension.
GW35-e1009
Hui Wang1,2,3,4,5, Nanfang Li1,2,3,4,5, Mulalibieke Heizhati1,2,3,4,5, Lin Gan1,2,3,4,5, Mei Li1,2,3,4,5, Ling Yao1,2,3,4,5, Amaiaomiao Liu1,2,3,4,5, Adalaiti Maitituersun1,2,3,4,5
1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region
2Xinjiang Hypertension Institute
3NHC Key Laboratory of Hypertension Clinical Research
4Key Laboratory of Xinjiang Uygur Autonomous Region “Hypertension Research Laboratory”
5Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases
OBJECTIVES Statins, a kind of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are first-line cholesterol-lowering drugs that are widely used in the primary and secondary prevention of coronary atherosclerotic heart disease (CAD). However, the safety of statins has been in the spotlight as recent studies have shown that statins may increase the incidence of diabetes.
METHODS We conducted a retrospective cohort study using data from the Urumchi Hypertension Database (UHDATA), including patients aged ≥18 years diagnosed with hypertension and obstructive sleep apnoea treated at our Hypertension Centre between 2015 and 2019. The study was followed until November 2023 and the primary endpoint was new-onset diabetes during the follow-up period. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using the Cox proportional hazards model. Sensitivity analysis were performed to adjust for confounders.
RESULTS The prevalence of diabetes is higher in patients with OSA and hypertension, in addition, the risk of diabetes is significantly higher in patients who continue to take statins (HR 1.77, 95% CI 1.34, 2.34, <0.001), and the results remain significant in sensitive analysis.
CONCLUSIONS In patients with OSA and hypertension, continuous statin use increases the risk of diabetes. It is suggested that in future clinical work, these patients should monitor their blood glucose levels when using statins.
GW35-e1047
Weijing Feng1, Jiajing Chen2, Jianwu Zhang1, Yintong Teng2, Hui Huang3, Caiwen Ou2
1Department of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Nanfang Hospital, Southern Medical University, Guangzhou, China
2The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Southern Medical University, Dongguan, China
3Cardiovascular Department, The Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
OBJECTIVES Hypertensive disorders of pregnancy (HDP) is associated with an earlier onset and increased susceptibility to hypertension, a significant risk factor for cardiovascular disease (CVD). Nevertheless, it remains uncertain whether achieving normal consistent levels of blood pressure (BP) can ameliorate the excess CVD risk associated with HDP history. This study aimed to assess HDP history and long-term individual BP patterns after pregnancy associated with myocardial structure and function in women, a manifestation of cardiac remodeling, and predictor of adverse clinical outcomes, particularly heart failure.
METHODS This study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort study conducted at multiple centers across the United States that consisted of young Black (50%) and White adults aged 18–30 years at baseline (1985–1986). The sample included 1080 women without hypertension at baseline, who had one or more singleton births during follow up, and HDP status were assessed. BP was determined up to 9 visits over a 30-year interval (1986–2016). Latent class modeling was used to identify long-term BP trajectories. Echocardiographic indices of myocardial structure and function were measured at year 30 (2015–2016). Multivariable general linear models were utilized to estimate the association of HDP status and identified trajectories with the following echocardiographic assessments of myocardial structure and function.
RESULTS Of the 1080 included women, 820 (75.9%) had normotensive pregnancies and 260 (24.1%) reported HDP, and the mean (SD) age was 28.5 ± 4.7 years. Compared to women with normotensive pregnancies, those with HDP history did not have significant change in echocardiographic indices of myocardial structure and function after multivariable adjustment (all P > 0.05). A total of 3 distinct SBP trajectories were identified: Low-Stable (445 individuals [41.2%]), Moderate-Gradual (512 individuals [47.4%]), and Elevated-Increasing (123 individuals [11.4%]). After full adjustment for demographic and clinical variables, there were significant differences in left ventricular (LV) mass by SBP trajectory group (mean [SE] LV mass: HDP/Elevated-Increasing, 90.4 (5.1) g/m2; HDP/Moderate-Gradual, 77.0 (2.1) g/m2; HDP/Low-Stable 73.0 (1.9) g/m2; No HDP/Elevated-Increasing, 84.8 (2.2) g/m2; No HDP/Moderate-gradual 76.1 (1.1) g/m2; No HDP/Low-Stable, 70.4 (1.3) g/m2; P < 0.001). Significant differences by trajectory group were also observed in LV longitudinal strain, e′ tissue velocities, and estimated LV filling pressures. Similar trends were also noted in other BP (DBP and MAP) trajectories.
CONCLUSIONS Women with a history of HDP across all subsequent levels of BP trajectories have significant differences in LV structure and function over a 30-year span after pregnancy. These differences were predominantly driven by long-term BP trajectories after pregnancy, irrespective of HDP history, suggesting that the established long-term risk of CVD after HDP may primarily result from longitudinal changes in BP trajectories.
GW35-e1122
Xue Tian1,2, Qin Xu1, Xue Xia1, Anxin Wang1
1Department of Epidemiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University
2Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University
OBJECTIVES The protective role of systolic blood pressure (SBP) time in range over months on the risk of cardiovascular disease (CVD) has been confirmed by data from randomized controlled trials. Evidence on hour TTR in real-world setting was scarce. This study aimed to investigate the association of 24-hour, daytime, nighttime ambulatory SBP TTR with the risk of CVD and mortality in real-world settings.
METHODS Data were obtained from the Kailuan study during 2006 and 2021. SBP TTR was calculated using linear interpolation, with 110–140 mmHg as the target range. Cox regressions were performed to assess the associations of SBP TTR with outcomes.
RESULTS Among 5099 participants in this analysis, 396 (7.77%) cases of CVD and 490 (9.61%) cases of all-cause mortality occurred during a median follow-up of 6.96 years. After multivariable adjustment, each 1-SD increment in 24-hour SBP TTR was associated with an 11% lower risk of CVD (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.79–0.99) and all-cause mortality (HR, 0.89; 95% CI, 0.81–0.98). Consistently, each 1-SD increment in daytime SBP TTR was associated with 14% lower risk of CVD (HR, 0.86; 95% CI, 0.78–0.95) and 13% lower risk of all-cause mortality (HR, 0.87; 95% CI, 0.79–0.95). However, the associations for nighttime SBP TTR did not reach statistically significant levels.
CONCLUSIONS Higher SBP TTR associated with lower risk of CVD and mortality in the real-world settings. Efforts to attain SBP within 110–140 mmHg over time may be an effective strategy to prevent CVD.
GW35-e1130
Junli Hu
Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Hypertension Research Laboratory, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, China
OBJECTIVES The objective of this study was to ascertain the relationship between the weight-adjusted waist index (WWI) and the risk of stroke in an elderly hypertensive population, a relationship that has not been previously elucidated.
METHODS The Cox regression model was employed to assess the correlation between baseline WWI measurements and the incidence of stroke. To further elucidate the shape of the association between baseline WWI and stroke, restricted cubic splines were employed. Furthermore, subgroup analyses and interaction tests were conducted to explore potential heterogeneities in the data.
RESULTS Our study cohort comprised 4962 hypertensive individuals aged 60 years or older with no prior history of stroke. Over a median follow-up period of 3.2 years, we identified 547 cases of new-onset stroke. After adjusting for confounding variables, the Cox regression analysis revealed a positive association between baseline WWI and the risk of stroke, with hazard ratios (HRs) escalating progressively as WWI values increased. When compared to the lowest quartile of WWI, the highest quartile demonstrated an HR of 1.87 (95% CI, 1.44–2.42) for stroke. Subgroup analyses confirmed the consistency of this relationship across different demographic and clinical strata.
CONCLUSIONS The study findings indicate that an elevated WWI is significantly associated with an increased risk of new-onset stroke among elderly patients with hypertension. These results underscore the importance of WWI as a potential risk stratification tool. Further research is warranted to validate these findings and investigate the causal pathways underlying the observed association.
GW35-e1195
Shuanghui Gong1, Yuanyuan Wang2, Yatin Lin1, Yumeng Rao1, Yongmei Bao1, Meixia Ren3
1Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Key Laboratory of Geriatric Diseases, Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
2College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
3Department of Geriatric Medicine, Fujian Provincial Center for Geriatrics, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fujian Medical University, Fuzhou 350000, China
OBJECTIVES A recent genome-wide association study identified a novel gene locus, splicing factor 3a subunit 3 (SF3A3), as significantly related to blood pressure (BP). This study aims to characterize the biological role of SF3A3 in BP regulation and the possible mechanism.
METHODS Using an angiotensin II (AngII)-induced mouse model, we examined the expression of SF3A3 in the aorta of hypertensive mice. We generated both systemic SF3A3−/+ knockout (sf3a3KO) and endothelial-specific sf3a3 knockout (sf3a3−/+-ecKO) mouse. Blood pressure and cardiac function were monitored using non-invasive blood pressure measurement techniques and echocardiography from 8–36 weeks. To investigate the functional mechanisms of SF3A3, we knocked down the SF3A3 gene expression in human umbilical vein endothelial cells (HUVECs) via lentiviral transfection and performed RNA sequencing to obtain differentially expressed genes (DEGs) followed with the disease ontology (DO), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Moreover, we conducted a series of cell function experiments to assess the effects of SF3A3 knockdown in HUVECs, including cell viability by CCK8 assay, and cell cycle by flow cytometry, etc.
RESULTS Sf3a3 expression was significantly up-regulated in the aorta of AngII-induced hypertensive mice compared to wild-type mice. Non-invasive blood pressure monitoring revealed a significant increase in systolic blood pressure in both sf3a3KO and sf3a3−/+-ecKO mice at 24 weeks. Echocardiography showed that sf3a3−/+ ecKO mice exhibited diastolic dysfunction, with a significant increase in the E/e′ ratio, compared with control group, whereas the changes were not observed in the sf3a3KO mice. In the transcriptome analysis, a total of 1568 DEGs were identified, comprising 575 up-regulated genes and 993 down-regulated genes. DO enrichment analysis suggested differential expression of SF3A3 associated with hypertension. Functional enrichment analyses demonstrated that SF3A3 alterations were related to pathways such as cell cycle, ferroptosis, and pyroptosis. CCK8 assay indicated that SF3A3 knockdown suppressed HUVECs viability with or without AngII treatment. Flow cytometry showed that SF3A3 knockdown induced G0/G1 phase arrest in HUVECs.
CONCLUSIONS This study suggests SF3A3 plays a role in blood pressure regulation and subsequent diastolic dysfunction, which might be involved with endothelial G0/G1 cell cycle arrest.
GW35-e1299
Minglei Zhang, Zongbin Li
The First Medical Center of the Chinese PLA General Hospital
OBJECTIVES The main factor that restricts the combat effectiveness of stationed training units and causes non combat casualties is acute mountain sickness (AMS). The important characteristic of low pressure and low oxygen in high-altitude environments is a significant cause of AMS. Extensive research has been conducted on the genetic pathogenesis of acute mountain sickness so far, mainly including studies on adaptive genes in high-altitude populations and susceptibility genes in plain populations. Apart from nuclear genes, researches based on mitochondrial genes also has achieved certain progress. The mitochondrial MT-ATP6 gene encodes the subunit ATP6 of complex V, and this mutation can cause a change from threonine to alanine. Previous studies have reported that the mitochondrial MT-ATP6 gene 8923A → G point mutation is associated with acute mountain sickness, but the specific mechanism is still unclear. Therefore, we further searched for evidence of the correlation between mitochondrial MT-ATP6 gene 8923A → G point mutation and AMS by conducting whole genome sequencing of mitochondria and analyzing physiological indicators such as dynamic blood pressure and electrolytes in volunteers under acute high-altitude exposure.
METHODS In our experiment, we began by recruiting 84 young male volunteers who depart simultaneously from the plains (altitude <100 meters) and reach the plateau area at an altitude of 4000 meters within 40 hours. Collecting peripheral blood samples from volunteers for mitochondrial DNA whole genome sequencing. Preceding to collect dynamic blood pressure, dynamic electrocardiogram, blood biochemistry and other related examinations in both high-altitude and low-pressure oxygen chamber environments. Next, we analyze the differences in various physiological indicators between volunteers with and without mitochondrial MT-ATP6 gene 8923A → G point mutations related to AMS, and explore the correlation between mitochondrial MT-ATP6 gene 8923A → G point mutations and acute mountain sickness.
RESULTS There was no statistically significant difference in age, height, and weight between the two groups of volunteers. The mitochondrial MT-ATP6 DNA gene point mutation at position 8923A → G was found in 15 cases among 84 volunteers. After entering the plateau, their average systolic blood pressure was lower than that of the non mutated volunteers at 24 hours [115.8 ± 6.7 mmHg vs. 120.5 ± 8.0 mmHg, P < 0.05], and their average systolic blood pressure at night was lower than that of the non mutated volunteers [107.9 ± 6.9 mmHg vs. 113.4 ± 7.4 mmHg, P < 0.05]. Their C-reactive protein levels were lower than those of the non mutated volunteers [0.04 (0.03, 0.04) mg/dL vs. 0.07 (0.03, 0.13) mg/dL, P < 0.05], and their high-density lipoprotein cholesterol levels were higher than those of the non mutated volunteers [1.5 ± 0.4 mmol/L vs. 1.3 ± 0.3 mmol/L, P < 0.05]. The number of white blood cells in the low-pressure oxygen chamber was lower than that in volunteers without mutations [5.4 (4.5, 6.7) × 109/L vs. 6.6 (5.7, 7.6) × 109/L, P < 0.05].
CONCLUSIONS The point mutation of mitochondrial MT-ATP6 gene 8923A → G is a protective factor for AMS. Volunteers with gene mutations have lower systolic blood pressure after entering high altitude, especially at night. Simultaneously accompanied by lower levels of C-reactive protein and white blood cell, as well as higher levels of high-density lipoprotein cholesterol. The mechanism chances are that relate to the enhanced blood pressure regulation ability and inhibition of inflammatory response in the body after entering the plateau.
GW35-e1313
Miaomiao Yang1, Jianwu Zhang1, Jiajing Chen2, Yintong Teng2, Caiwen Ou2, Weijing Feng1
1Department of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Nanfang Hospital, Southern Medical University, Guangzhou, China
2The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Southern Medical University, Dongguan, China
OBJECTIVES Hypertension is a significant risk factor for the development of aortic aneurysm (AA) and frequently coexists with it. However, the efficacy of various antihypertensive agents in the management of AA remains a contentious issue. Here we aimed to investigate the potential effects of different antihypertensive drug classes on AA.
METHODS Genetic instruments for expression of antihypertensive drug target genes were identified with expression quantitative trait loci (eQTL) in blood, which should be associated with systolic blood pressure to proxy for the effect of antihypertensive drug. The association between genetic variants and different types of AA risk were obtained from the FinnGen study. Participants involved a total of 344,901 controls and 8125 patients with AA, including 3880 patients with thoracic aortic aneurysm (TAA) and 3869 patients with abdominal aortic aneurysm (AAA). Blood eQTL levels were measured in 31,684 individuals from 37 cohorts (eQTLGen consortium). The summary-based MR was employed to estimate the drug effects on different types of AA risk. We further performed sensitivity analyses to validate the identified MR associations, including assessment of horizontal pleiotropy and colocalization.
RESULTS The association of AA risk was observed with the expression of SLC12A3 (thiazide-sensitive NaCl cotransporter) gene at a Bonferroni-corrected threshold. A 1-SD lower expression of the SLC12A3 gene in blood was associated with lower systolic blood pressure of 1.53 (95% CI, 0.57–2.60) mmHg, and decreased risk of AA (odds ratio [OR], 0.55; 95% CI, 0.38–0.79; P = 1.13 × 10−3). This signal was further observed for AAA (OR, 0.35; 95% CI, 0.20–0.60; P = 1.35 × 10−4) rather than TAA. We detected no evidence of horizontal pleiotropy for these associations and the probability of the causal variants being shared between the gene expression and AAA risk was 97.5%.
CONCLUSIONS We found that genetically proxied long-term SLC12A3 inhibition, a thiazide diuretic targeting gene, were significantly associated with reduced AAA risk. These findings warrant greater pharmacovigilance and further exploration of the role of SLC12A3 inhibitor use in patients with hypertension who are at high-risk of AAA.
ARRHYTHMIA
GW35-e0060
Gege Zhang
People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES Frequent premature ventricular complexes (PVCs) are associated with cardiac remodeling. Different origins of PVCs may also affect cardiac function. The purpose of this study was to evaluate the effects of different origins and frequency of PVCs on cardiac remodeling.
METHODS Literature searches were performed using CENTRAL, Embase, Pubmed and the Cochrane Central Register of Controlled Trials to assess the effects of different origins and frequency of PVC on cardiac remodeling. Articles on the relations of origin or frequency of PVCs and cardiac remodeling were included in our study. Only studies in English were included. Studies of non-PVC-induced cardiac structure changes were excluded.
RESULTS A total of 625 articles were obtained from the preliminary search, and finally 9 articles were included in the meta-analysis. Three of them were about the study of cardiac remodeling at different origins of PVCs, and the other six were about the study of cardiac remodeling with different frequency of PVCs. The weighted mean difference (WMD) of the left ventricle ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left-ventricular end-systolic dimension (LVESD) and left atrial dimension (LAD) in the frequent PVCs compared to the control group were LVEF = −3.66 (P = 0.007), LVEDD = 3.17 (P = 0.0006), LVESD = 3.27 (P = 0.03) and LAD = 1.59 (P = 0.03), respectively. The WMD of LVEF and LVEDD of the PVCs originating from the outflow tract was LVEF = −0.16 (P = 0.84) and LVEDD = 6.28 (P = 0.29), respectively.
CONCLUSIONS Frequent PVCs could induce cardiac remodeling more likely to occur, while whether the PVC originating from the outflow tract or not had no significant effect on cardiac remodeling.
GW35-e0068
Huasheng Lyu
The First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES The pathogenesis of age-related atrial fibrillation (AF) remains not fully elucidated and is believed to be complex and multifactorial. Gene expression profiling and bioinformatic analysis are helpful to discover the molecular changes in the development of disease. The aim of this study was to explore the potential mechanism of age-related AF.
METHODS We employed a comprehensive analysis approach to study the common genes expression signature present in the atria of AF patients and the senior population. Specifically, we conducted gene ontology (GO) analysis, pathway enrichment analysis, and protein-protein interaction analysis on the identified common differentially expressed genes (DEGs). This multi-faceted analysis aimed to gain a deeper understanding of the underlying mechanisms and pathways associated with age-related atrial fibrillation.
RESULTS Altogether, 112 differentially expressed genes (DEGs) were selected. By GO enrichment analysis, result of cellular component showed that collagen-containing extracellular matrix, basement membrane and ion channel complex accounted for a great part of the DEGs. Correspondingly, extracellular structure organization, atrial cardiac muscle membrane repolarization and calcium-mediated signaling also displayed significant changes in biological process. Circadian entrainment, oxytocin signaling, PI3K-Akt signaling calcium signaling and focal adhesion were significantly enriched in KEGG analysis.
CONCLUSIONS Our study manifested focal adhesion and circadian entrainment may be critical in the development of aging-related AF.
GW35-e0069
Huasheng Lyu
The First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES To explore the constituent ratio, gender difference and risk factors of complications after the first PVI in patients with nonvalvular AF.
METHODS We retrospectively selected AF patients who underwent PVI at our hospital’s heart center from 2018 to 2021. A total of 1092 patients were included and divided into male and female groups. Using a 1:1 propensity score matching analysis, we matched 362 pairs of patients for inclusion in this study. We collected clinical data from the patients, calculated the incidence rates of complications in the male and female groups, and performed univariate and multivariate conditional logistic regression analysis to explore the relationship between gender and complications.
RESULTS There were significant statistical differences in the complications of pericardial effusion, micro and small amounts of pericardial effusion and Vagus nerve hyperfunction in the female group. Multivariate logistic regression found that women, RFA, and intraoperative left atrial appendage occlusion (LAAO) were independent risk factors for overall and mild complications after PVI in non valvular AF patients, while overweight and obesity were protective factors for overall and mild complications; Non-PV triggered ablation is an independent risk factor for major complications after PVI in patients with nonvalvular AF.
CONCLUSIONS There is a gender difference in complications between the male and female groups; The main risk factors for postoperative complications were women, RFA, intraoperative LAAO during operation and non-PV triggered ablation. Overweight and obesity may be protective factors for complications.
GW35-e0096
Jiachen Luo
Shanghai Tenth People’s Hospital
OBJECTIVES New-onset atrial fibrillation (NOAF) is an independent predictor of poor survival in patients with acute myocardial infarction (AMI), and adequate risk stratification may facilitate the clinical-decision making in this high-risk population. Greater AF burden has been associated with detrimental outcomes in AF individuals, but the optimal metrics to characterize the AF burden remain to be determined.
METHODS We used the New-Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in ShangHai (NOAFCAMI-SH) registry to examine the association between NOAF burden metrics and major adverse cardiac events (MACE). All-cause death and heart failure hospitalization were recorded as MACE. The NOAF burden metrics included the longest NOAF duration (the longest duration of a single NOAF episode), total NOAF duration, and NOAF proportion (proportion of time spent in AF).
RESULTS A total of 278 patients (mean age: 74.3 ± 10.5 years, 66.9% man) with post-MI NOAF were included. MACE occurred in 146 patients (52.5%) during a median follow-up of 30.6 (interquartile range: 18.4–45.2) months. Multivariable Cox regression analyses showed that it was the NOAF proportion (hazard ratio for per 1 SD increment: 1.306, 95% confidence interval [CI]: 1.115–1.528, P = 0.001) rather than the longest NOAF duration and total NOAF duration that was an independent predictor of MACE. Comparison of predictive performance demonstrated that adding NOAF proportion, but not NOAF durations, to the Global Registry of Acute Coronary Events (GRACE) score significantly improve its reclassification ability, as evidenced by continuous net reclassification indexes and 95% CIs of 0.202 (0.089–0.294), 0.223 (0.086–0.336), and 0.214 (0.068–0.329); integrated discrimination improvements and 95% CIs of 0.030 (0.006–0.058), 0.034 (0.008–0.060), and 0.032 (0.004–0.066), at 1-, 2-, and 3-year follow-up, respectively.
CONCLUSIONS Post-MI NOAF burden measured by NOAF proportion has the greatest prognostic impact and adds to risk stratification beyond the GRACE score.
GW35-e0097
Jiachen Luo
Shanghai Tenth People’s Hospital
OBJECTIVES New-onset atrial fibrillation (NOAF) is a common finding after acute myocardial infarction (AMI) and is independently associated with poor survival. However, the association of NOAF burden with outcomes among patients with post-MI NOAF is poorly understood. We aimed to examine the relationship between AF burden and long-term outcomes in AMI patients with NOAF.
METHODS This multicenter retrospective cohort study included 812 AMI patients without preexisting AF who developed the first documented paroxysmal AF and underwent continuous electronic monitoring throughout hospitalization between January 2014 and January 2022. AF burden was evaluated as the percentage of time in AF (%). The association between AF burden and the composite outcomes of cardiovascular death, reinfarction, heart failure hospitalization or ischemic stroke, its component, and all-cause death was examined using Cox regression analyses.
RESULTS The median burden of AF was 8.16% (IQR: 2.39%–29.47%) and an AF burden of 15.29% was identified as the optimal cut-off value. During a median 4.2 years of follow-up, 663 patients with complete follow-up data were classified into the low burden (AF burden <15.29%; N = 447) and high burden (AF burden ≥15.29%; N = 216) groups. After multivariable adjustment, high AF burden was independently associated with an increased risk of the composite outcomes (HR: 1.66, 95% CI: 1.30–2.12, P < 0.001), which was primarily driven by cardiovascular death (HR: 1.54, 95% CI: 1.12–2.12, P = 0.009), heart failure hospitalization (HR: 1.79, 95% CI: 1.29–2.48, P < 0.001), and ischemic stroke (HR: 2.91, 95% CI: 1.59–5.32, P = 0.001). When measured as a continuous scale, increasing AF burden remained an independent predictor of the composite outcomes (HR: 1.06 per 10% AF burden, 95% CI: 1.02–1.09, P = 0.004), as well as HF hospitalization (HR: 1.07 per 10% AF burden, 95% CI: 1.03–1.13, P = 0.002) and ischemic stroke (HR: 1.20 per 10% AF burden, 95% CI: 1.11–1.29, P < 0.001).
CONCLUSIONS Among AMI patients with NOAF, increasing AF burden is significantly with adverse cardiovascular outcomes.
GW35-e0113
Yifan Wu1, Huilei Zhao1, Lin Li2, Peng Yu3, Xiao Liu4
1Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
2College of Medicine, The Fujian Medical University, Guangzhou, Guangdong, China
3Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China
4Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
OBJECTIVES Alcohol is a known risk factor for the risk of developing atrial fibrillation (AF), but whether alcohol abstinence reduces the incidence of AF is less clear. In light of this gap in the literature, we conducted a meta-analysis of prospective studies to investigate the association between abstinence from alcohol and the incidence of AF.
METHODS PubMed, EMBASE, and the Cochrane Library were searched to identify prospective studies that reported the association between alcohol abstinence and AF up to September 2023. The effect size was pooled by using the random-effects model. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system assesses evidence quality.
RESULTS Eleven prospective cohorts with 429,429 participants and 58,863 AF cases were included. The summary results showed alcohol abstinence was not statistically significantly associated with a decreased incidence of AF (Hazard ratio [HR] 0.88, 95% CI 0.72–1.08) compared with current drinkers. Alcohol abstinence was not associated with the incidence of AF (HR 1.00, 95% CI 0.94–1.06) compared with never-drinkers. All studies obtained scores ranging from 7 to 9, signifying a medium to high level of quality. The GRADE indicated a moderate level of certainty. Meta-regressions analyzing follow-up time, region, mean age, and alcohol consumption dosage, revealed no significant sources of heterogeneity.
CONCLUSIONS Alcohol abstinence might be linked to a reduction in AF incidence among current drinkers, although this outcome did not reach significance. The benefits of abstinence concerning the amount of alcohol consumed and the duration of the abstinent period merit further study.
GW35-e0119
Wanqian Pan, Tingbo Jiang, Weixiang Chen
The First Affiliated Hospital of Soochow University
OBJECTIVES Atrioventricular block (AVB) is a prevalent bradyarrhythmia that can result in life-threatening rhythm disorders. Observational studies have highlighted the association between senescence and AVB. Epigenetic aging derived from DNA methylation profiles has been acknowledged as an excellent predictor of biological aging and concomitant health implications. However, their causal relationship remains uncertain. This study aimed to investigate the causal effects of epigenetic aging (GrimAge, PhenoAge, HannumAge, and HorvathAge) on AVB by Mendelian randomization (MR) analysis.
METHODS Genetic instruments for epigenetic aging and AVB were adopted from the Genome-wide association study data of the Edinburgh DataShare and FinnGen biobank. Univariate and multivariable MR analyses were conducted to evaluate the causal associations. In addition, we employed quality control analysis to assess the robustness of MR findings.
RESULTS The MR analysis showed that genetically predicted GrimAge acceleration was significantly associated with a higher risk of AVB (IVW: P = 0.010, 95% CI = 1.024–1.196; WM: P = 0.031, 95% CI = 1.009–1.215). In the reverse MR analysis, no evidence supported the causal relationship from AVB to epigenetic aging. The causality of epigenetic aging and AVB remained significant in multivariable MR analysis after adjusting myocardial infarction, coronary heart disease, serum potassium, hypertrophic cardiomyopathy, dilated cardiomyopathy, and endocarditis. Quality control analysis confirmed the reliability and robustness of our results.
CONCLUSIONS Our findings suggested a causal association between the epigenetic aging of GrimAge and the risk of AVB, emphasizing the importance of curbing epigenetic aging for primary prevention of AVB.
GW35-e0175
Di Zhou, Minjie Lu
Department of Magnetic Resonance Imaging, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Approximately 30% of patients undergoing cardiac resynchronization therapy (CRT) per Class I recommendation (COR I) do not benefit from the procedure, and the effectiveness of CRT in patients with Class II recommendation remains uncertain, necessitating additional evaluation tools. We sought to refine risk stratification in patients with reduced ejection fraction and prolonged QRS using cardiac magnetic resonance (CMR) imaging, and to enhance the selection of CRT candidates by incorporating CMR factors beyond the current guideline criteria.
METHODS We retrospectively enrolled 711 patients with reduced ejection fraction and prolonged QRS who underwent CMR imaging. The primary endpoint was a composite of cardiac-related death, heart transplantation, and left ventricular (LV) assist device implantation. Outcomes were compared in CRT-eligible patients with and without CRT.
RESULTS Over a median follow-up of 4.8 years, LGE and LV strains emerged as independent risk factors for survival in 547 patients without CRT. Stratified by COR I, late gadolinium enhancement (LGE)-negative, LGE of 0–8.0%, global longitudinal strain (GLS) ≥−5.9%, global circumferential strain (GCS) ≥−6.3%, or global radial strain (GRS) ≤8.0%, patients without CRT experienced significantly shorter event-free survival for the primary endpoint compared to CRT recipients. Among COR I patients with LGE ≥8.0%, GLS <−5.9%, GCS <−6.3%, or GRS >8.0%, survival outcomes were comparable regardless of undergoing CRT or not. In COR IIa subgroup, GLS ≥−5.9% (HR [95% CI]: 3.204 [1.339–7.670]), GCS ≥−6.3% (HR [95% CI]: 3.050 [1.194–7.788]), and GRS ≤8.0% (HR [95% CI]: 2.743 [1.070–7.029]) independently correlated with worse outcomes in patients without CRT compared to those with CRT.
CONCLUSIONS LGE and LV strains played a crucial role in determining the suitability for CRT implantation. Impaired LV strains provided additional value in patient selection for CRT among those meeting COR IIa criteria.
GW35-e0184
Sergey Zenin, Olga Pyataeva
GBUZ NSO Novosibirsk Regional Clinical Cardiology Dispensary, Novosibirsk, Russia
OBJECTIVES Electrical cardioversion, according to the literature, is effective in patients with persistent fibrillation, atrial flutter, with success rate about 90%. Arrhythmia relief is limited by the duration of the arrhythmia, the patient’s high weight, organic changes in the heart, and concomitant diseases. The modern Russian antiarrhythmic drug Refralon (Cavutilide) has shown a high relief effect, including when used after unsuccessful CV.
METHODS One hundred and seventy-nine patients were treated: 105 men and 74 women aged from 39 to 83 years (69.9 ± 5.82); body mass index – 31.5 ± 7.8 kg/m2, duration of arrhythmia – 6.9 ± 5.19 (2–25) months. Refralon (class III antiarrhythmic drug) was administered under cardiac monitoring in the intensive care unit. ECG, blood pressure and heart rate were continuously recorded throughout the observation period. The drug was administered at a dose of 10 mcg/kg body weight according to the instructions. To assess intervals (QRS, QT), dynamic ECG recording was performed.
RESULTS In 89.2% of cases, the effect of rhythm conversion was obtained. In 19 patients (10.8%) there was no effect from the administration of the drug Refralon: of these, in 9 cases (47.4%) the calculated dose of the drug was used without restoring sinus rhythm, in 10 patients (52.6%) the administration of the drug was stopped for against the background of the appearance of ventricular extrasystole (group), prolongation of the QT interval.
CONCLUSIONS Refralon showed high effectiveness in patients with persistent fibrillation, atrial flutter of varying duration and arrhythmia, statistically comparable with electrical cardioversion. The study of the effectiveness of the drug Refralon continues.
GW35-e0198
Sergey Zenin1,2, Oksana Kononenko1, Olga Pyataeva1, Artem Fedoseenko1, Anastasia Zvonkova1
1GBUZ NSO Novosibirsk Regional Clinical Cardiology Dispensary, Novosibirsk
2Novosibirsk Medical University
OBJECTIVES Drug and interventional treatments for atrial fibrillation are not always effective. Currently, the first publications have appeared on the positive effect of dapagliflazine on the course of supraventricular arrhythmias.
METHODS The results of 5 cases of dapagliflazine therapy in patients with drug-resistant, frequently recurrent paroxysmal and persistent atrial fibrillation without signs of congestive CHF and the absence of the possibility of surgical treatment of arrhythmia are presented. In all patients, the secondary nature of atrial fibrillation and electrolyte disturbances were excluded. Antiarrhythmic drugs of class I and III without effect. All patients had previously been implanted with dual-chamber pacemaker systems for various indications. At the start of observation, the patients were chosen to control heart rate with the prescription of beta-blockers and digoxin, and according to the indications of CKD, dapagliflazin 10 mg/day was added to all patients. The patients were then observed after 2, 6 and 12 months; patients were interviewed with memory data from permanent pacemakers.
RESULTS By the time of the first visit, two patients had established stable sinus rhythm with no recurrences of atrial fibrillation during a year of observation. In one patient, the burden of atrial fibrillation decreased from 8% to 1.8% within 6 months and to 1.7% over the next 6 months. In the fourth patient, the burden of atrial fibrillation decreased from 5% to 0.8% within 6 months and was maintained for a year. In the fifth patient, the burden of atrial fibrillation decreased by the time of the first visit from 29% to 5%, after 6 month to 1.2% and remained 1.3% by the third visit.
CONCLUSIONS SGLT2i are associated with a significant reduction in the risk of atrial arrhythmias and sudden cardiac death. Further prospective studies are needed to confirm the antiarrhythmic effect of SGLT2i and whether this is a class effect.
GW35-e0221
Li Feng
The Second Affiliated Hospital of Soochow University
OBJECTIVES Obstructive sleep apnea (OSA) is an independent and modifiable risk factor in the initiation and maintenance of atrial fibrillation (AF). However, the effective of the continuous positive airway pressure (CPAP) on AF patients with OSA after ablation is elusive. Obstructive sleep apnea (OSA) is an independent and modifiable risk factor in the initiation and maintenance of atrial fibrillation (AF). However, the effective of the continuous positive airway pressure (CPAP) on AF patients with OSA after ablation is elusive.
METHODS Cochrane Library, PubMed, Embase, and Web of Science were systematically searched up to 1 February 2023. Studies comprising the AF recurrence rate between the CPAP therapy group and non-CPAP therapy group for the AF patients with OSA were included. Meanwhile, trial sequential analysis (TSA) was conducted to adjust the lower statistical power and random error in this study. Subgroup analysis identified the potential determinants for the AF recurrence rate with CPAP therapy.
RESULTS A total of eight studies including 1231 AF patients with OSA were eligible. Compared with non-CPAP treatment group, CPAP treatment group was statistically associated with a lower AF recurrence rate (risk ratio [RR], 0.58; P = 0.000). TSA indicated the firm evidence favoring CPAP group for AF recurrence risk. Three significant intervention-covariate interactions for AF recurrence was identified, including study design, non-paroxysmal AF (PAF) proportion, and CPAP treatment strategy.
CONCLUSIONS Our study suggests that CPAP therapy might be an effective strategy on reducing AF recurrence post-ablation for AF patients with OSA. The CPAP treatment strategy and the non-PAF proportion might be the possible determinants on AF recurrence for AF patients with OSA after ablation.
GW35-e0222
Li Feng
The Second Affiliated Hospital of Soochow University
OBJECTIVES Conduction system pacing (CSP) has been reported to improve clinical outcomes in comparison of right ventricular pacing (RVP). However, the performance between CSP and RVP on the risk of new-onset atrial fibrillation (AF) remains elusive. Conduction system pacing (CSP) has been reported to improve clinical outcomes in comparison of right ventricular pacing (RVP). However, the performance between CSP and RVP on the risk of new-onset atrial fibrillation (AF) remains elusive.
METHODS Four online databases were systematically searched up to December 1st 2023. Studies comprising the rate/risk of new-onset AF between CSP and RVP group were included. Subgroup analysis was performed to screen the potential determinants for the new-onset AF risk for CSP therapy. The pooled risk of new-onset AF based on ventricular pacing burden (Vp) between CSP and RVP group were evaluated.
RESULTS A total of five studies including 1491 patients requiring pacing therapy were eligible. The pooled new-onset AF rates for CSP and RVP group were 0.09 and 0.26, respectively. Compared with RVP group, CSP group showed a lower pooled risk (risk ratio [RR] 0.38, P = 0.000) and adjusted risk (hazard ratio [HR] 0.33, P = 0.000) of new-onset AF. Meanwhile, a significant intervention-covariate interaction for the adjusted risk of new-onset AF between CSP and RVP group was identified with Vp <20% and Vp ≥20%.
CONCLUSIONS Our study suggests that CSP significantly reduces the new-onset AF risk compared with RVP. The Vp ≥20% may be the key determinant on the lower risk of new-onset AF with CSP therapy.
GW35-e0227
Zhixiang Dong, Yanyan Song, Shihua Zhao
MR Center, Fuwai Hospital
OBJECTIVES Cardiac magnetic resonance (CMR) has demonstrated promising potential in the prognosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to develop and validate a novel CMR-based nomogram score to predict adverse outcomes in patients with ARVC over a long follow-up period.
METHODS A total 327 (median age, 40 [IQR, 30–52] years; 212 male, 115 female) consecutive ARVC patients were retrospectively enrolled for analysis. Comprehensive clinical evaluation and CMR imaging assessment were obtained, including late gadolinium enhancement (LGE) and biventricular global strain analysis. The primary outcome was defined as a composite of major adverse cardiac events (MACE) including cardiovascular death and heart transplantation. All the patients were randomly divided into development and validation cohort (7:3). The LASSO regression and multivariable Cox regression analysis were used for feature selection, and the nomogram was then used to estimate 1-, 3- and 5-year survival probability of ARVC patients.
RESULTS MACE occurred in 25 (10.9%) out of 229 patients in the development cohort, and in 13 (13.3%) out of 98 patients in the validation cohort. Left ventricular ejection fraction (LVEF), extent of LV LGE, RVEF and RV global longitudinal strain were identified as independent prognostic factors and integrated for the construction of the nomogram. The nomogram achieved good discrimination, with C-indexes of 0.88 and 0.80 for the development and validation cohort, respectively. Calibration plots showed favorable consistency between the nomogram predicted and actual probability for 5-year MACE in both the development and validation cohort. Decision curve analysis indicated that the nomogram was of significant clinical use. Moreover, in the subgroup analysis of patients with LV involvement, the probability of MACE significantly differed between nomogram-determined low-risk group and high-risk group.
CONCLUSIONS A CMR-based predictive nomogram for MACE in ARVC was constructed and validated, providing a convenient tool for the individual risk evaluation in patients with ARVC.
GW35-e0233
Yankai Mao
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, China
OBJECTIVES Left bundle branch pacing (LBBP) has emerged as a more physiological alternative to right ventricular pacing. However, capturing the pre-divisional LBB is not easy to accomplish. This study investigates if left fascicular pacing (LFP), defined as the capture of one of the LBB fascicles, could achieve comparable left ventricular (LV) mechanical synchronicity and cardiac function compared to LBBP.
METHODS Thirty-one patients with pacing indication for bradycardia were retrospectively collected: LBBP was successfully performed in 13 patients and 18 achieved LFP. All patients underwent echocardiography before and after implantation and at one-year follow-up. Left ventricular (LV) volumes, ejection fraction (EF) and global longitudinal strain (GLS) were measured. The lateral-septal (LW-SW) work difference was used as a measure of mechanical dyssynchrony. Septal flash, apical rocking and septal strain patterns were also assessed.
RESULTS Although LW-SW work difference were significantly higher in the LBBP groups than that in the LFP group at baseline (272 ± 269 mmHg*% vs. 25 ± 279 mmHg*%, P = 0.02), a similar increase in LW-SW work difference was observed during follow-up (199 ± 342 mmHg*% vs. 371 ± 384 mmHg*%, P = 0.21). In addition, both LFP and LBBP induced septal flash or apical rocking in some patients, and resulted in subtle changes in strain patterns, which were not significantly different between groups. At one year follow-up, LV ejection fraction (EF) remained almost unchanged in both LBBP and LFP patients (ΔLVEF: 1.1 + 3.1% vs. −0.3 ± 4.8%, P = 0.35), and global longitudinal strain (GLS) was slightly and equally decreased in LFP compared to LBBP (ΔLVGLS: −1.6 ± 2.3% vs. −1.2 ± 2.7%, P = 0.69).
CONCLUSIONS LFP and LBBP did not differ in mechanical dyssynchrony or LV remodelling.
GW35-e0242
Huaiyang Chen
Hunan Children’s Hospital
OBJECTIVES Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary cardiomyopathy characterized by the substitution of right ventricular myocardial tissue by fibrous and adipose tissue. This leads to structural remodeling, functional abnormalities and ultimately malignant ventricular arrhythmias and sudden cardiac death (SCD). The estimated prevalence of ARVC is 1:1000–1:5000, and it is a familial autosomal dominant disease with variable penetrance. Pathologically, the early stages of the disease may be asymptomatic or characterized by subtle structural changes localized to the right ventricle, progressing to widespread left ventricular disease involving the left ventricle. ARVC is a progressive genetic disease that is not limited to the right ventricle and mainly determined by genes, such as JUP, PKP2, DSG2, DSC2, TMEM43 and so on. This study aimed to identify compound heterozygous variants of DSC2 (c.394C > T (p.R132C) and c.448G > A (p.G150S)) as a disease-causing mutation for ARVC.
METHODS Whole exome sequencing, sanger sequencing and online prediction tools were used to identify the pathogenicity of DSC2 (c.394C > T (p.R132C) and c.448G > A (p.G150S)) mutation in DSC2.
RESULTS The proband with ARVC has compound heterozygous variants of DSC2 (c.394C > T (p.R132C) and c.448G > A (p.G150S)), which were inherited from his parents through Whole-exome sequencing and Sanger sequencing. Meanwhile, c.394C > T (p.R132C) and c.448G > A (p.G150S) mutations in DSC2 were predicted to be deleterious using online computational prediction tools.
CONCLUSIONS This study identified the presence of presented compound heterozygous mutations (c.394C > T (p.R132C) and c.448G > A (p.G150S)) in DSC2 gene of a pediatric ARVC patient.
GW35-e0270
Liting Zhang
The Second Affiliated Hospital of Nanchang University
OBJECTIVES Mid-upper arm circumference (MUAC) is a simple, convenient anthropometric indicator. Evidence on the relationship between MUAC and atrial fibrillation (AF) is limited. The aim of this study is to explore the association between MUAC and AF in Chinese hypertensive patients.
METHODS The data of our cross-sectional study is from the China H-Type Hypertension Project, a long-term prospective cohort study consisting of hypertensive patients in southern China. A total of 15,753 participants were included in this study. Measure all participants’ MUAC by a tape measure. The outcome was AF. Among 15,753 hypertensive participants, 633 (4.02%) developed AF. Odds ratios of AF concerning MUAC were calculated using multivariate logistic regression models.
RESULTS Multivariate logistic analyses showed that MUAC was negatively correlated with the prevalence of AF (per SD decrement; adjusted OR, 1.59; 95% CI, 1.32, 1.92). Compared with participants in Q4, the odds ratios (95% CI) for those in the Q3 (26.6–28.5), Q2 (24.6–26.5), and Q1 (16.2–24.5) were 1.31 (0.91, 1.89), 1.85 (1.26, 2.72) and 2.59 (1.63, 4.12), respectively. This negative correlation remains stable in each subgroup. In addition, although MUAC had no additional predictive value in predicting the risk of AF, its AUC is the highest compared to other body circumference indicators.
CONCLUSIONS MUAC, an alternative index of malnutrition, were independently associated with a lower risk of AF among Chinese hypertensive population. Importantly, further research is needed to help understand the relationship between subcutaneous fat and muscle of upper arm and AF.
GW35-e0280
Qing Li1, Tingting Lv2, Yifei Wang2, Qiuyu Wang1, Bin Wang2, Ping Zhang2
1School of Clinical Medicine, Tsinghua University, Beijing, China
2Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
OBJECTIVES Long QT syndrome (LQTS) is a life-threatening cardiac ion channel disorder characterized by prolongation of the QT interval on the electrocardiogram, leading to an elevated risk of arrhythmias and sudden cardiac death. Left cardiac sympathetic denervation (LCSD) has been identified as an supplementary therapy for patients with LQTS who remain at increased risk despite conventional treatment.
METHODS A systematic review was conducted until March 2024 using PubMed, Embase, Web of Science, and Cochrane Library databases to identify relevant studies on LCSD with LQTS. Inclusion criteria required studies with primary data, a sample size of at least five, and a focus on safety and efficacy outcomes, particularly cardiac events and sudden cardiac death. The review followed PRISMA 2020 guidelines.
RESULTS A total of 11 studies involving 743 patients were evaluated, with 63% being female and an average age of 17.8 ± 11.7 years at surgery. Genotype distribution was as follows: LQT1 (35%), LQT2 (24%), LQT3 (6%), and other subtypes (35%). The preoperative QTc interval was 520.1 ± 64.6 ms and 521 patients undergoing LCSD treatment for secondary prevention. Following the procedure, there was a mean reduction in QTc duration of 35.9 ± 65.3 ms. After an average follow-up period of 26.3 ± 35.4 months, the proportion of patients free from cardiac events was 53% (95% CI: 0.42~0.65) and sudden cardiac death occurring in 26 patients at an incidence rate of 4% (95% CI: 0.02~0.06). The predominant postoperative complications observed in the study population included Horner syndrome in 4 patients, left eyelid ptosis in 11 patients, neuropathic pain in 23 patients, and pneumothorax in 8 patients. Most postoperative complications resolved within 6 months, with only 3 cases of permanent left eyelid ptosis.
CONCLUSIONS LCSD has been shown to significantly decrease the occurrence of cardiac events and reduce QTc duration in patients with LQTS without resulting in severe adverse effects.
GW35-e0294
Ting Tang, MingWei Wang
Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou
OBJECTIVES The effect of sodium intake on atrial fibrillation (AF)/atrial flutter (AFL), with respect to sex and age, has yet to be elucidated. This study aims to compare long-term trends in AF/AFL death and disability due to high sodium intake in China from 1990 to 2019.
METHODS Data for China in the Global Burden of Disease (GBD) 2019 study were primarily sourced from the Chinese surveillance systems and the KaiLuan Study. Trends in death and disability related to AF/AFL due to high sodium intake (>5 g/d) were assessed via Join-point regression and age–period–cohort methods, with adjustments for age, sex, period, and cohort.
RESULTS In 2019, the number of AF/AFL deaths and disability-adjusted life years attributable to high sodium intake were 4,209,944 (95% CI: [125,069–8,718,238]) and 235,484,586 (95% CI: [89136783–428566694]), with males comprising 44.81% and 51.95% of cases, respectively. The age-standardized mortality rates (ASMRs) and age-standardized disability rates (ASDRs) of AF/AFL attributable to high sodium intake exhibited downward trends from 1990 to 2019 in China. The average annual percentage change (AAPC) was 0.221 (95% CI: −0.321 to −0.121) and −0.631 (95% CI: −0.816 to −0.446) for AF/AFL, respectively. An upward trend was observed in ASMRs for AF and AFL, attributable to high sodium intake due to high salt intake at ages 30–34, 35–39, and 40–44. With an increase in age, the (AAPC) for ASMRs increased correspondingly, and the AAPC for ASDRs exhibited a decreasing trend.
CONCLUSIONS Our findings provide strong evidence that high sodium levels in China significantly affect standard ASMRs and ASDRs for AF and AFL. Notably, different patterns of change are identified across various age groups, emphasizing the pronounced effect of salt reduction on AF and AFL.
GW35-e0393
Xiaodi Tang, Rong He
Beijing Tsinghua Changgung Hospital affiliated with Tsinghua University
OBJECTIVES Heart rate variability (HRV) is an autonomic nervous system marker of the heart, which has predictive value in cardiac patients. Ultra-short heart rate variability (usHRV) can be measured on a large scale using standard and wearable electrocardiogram devices. The relationship between atrial fibrillation and the autonomic nervous system is multifaceted and is an important area of current research into cardiac arrhythmias. Our aim is to obtain ultra-short heart rate variability (usHRV) measurements from ≤10-second electrocardiograms (using SDNN, SDSD, pNN50, RMSSD, LF, HF, LF, HF, LF/HF) to explore its relationship with the risk of atrial fibrillation.
METHODS We conducted a case-control study, which included a total of 2970 patients from the MIMIC-IV and MIMIC-ECG databases. Following a 1:1 matching principle, 1485 of the samples were atrial fibrillation patients, while another were non-atrial fibrillation patients matched based on age, gender, race, MAP, BMI, previous use of Beta blocker, history of previous myocardial infarction, congestive heart failure, and diabetes. All patients in the study had complete 10-second electrocardiogram (ECG) records, and the ECGs of all patients in the exposed group were collected before the onset of atrial fibrillation. We used a univariate and multivariate logistic regression model to calculate the correlation between usHRV and the risk of atrial fibrillation. We further examined linearity using restricted cubic splines to explore the shape of the dose-response relationship. Additionally, we conducted stratification and interaction analyses to determine the stability of relationships between different subgroups.
RESULTS Of all subjects, the mean age was 71.5 ± 12.6 years, and 54.4% was male. After matching, there were no statistically significant differences between the case group and the control group in terms of age, gender, race, MAP, BMI, history of previous myocardial infarction, diabetes, and previous use of β-blockers. The effect of usHRV on the risk of atrial fibrillation was evaluated using multivariate logistic regression models (SDSD OR, 1.05 and 95% CI, 1.03–1.08; RMSSD OR, 1.05 and 95% CI, 1.03–1.08). A linear relationship was found between usHRV (SDSD, RMSSD) and the risk of atrial fibrillation according to a restricted cubic spline model. Further exploratory subgroup analysis showed there were no significant interactions (P values for interaction were >0.05).
CONCLUSIONS This analysis of MIMIC-IV and MIMIC-IV-ECG data has demonstrated that the usHRV is significantly associated with the risk of incident atrial fibrillation, independent of confounders. The findings of this study warrant attention. These results revealed that underscoring usHRV may play a role as a risk factor for atrial fibrillation and usHRV may be a relevant biomarker. As the potential for confounding may exist, further studies are warranted.
GW35-e0417
Yan Yin1, Yanguang Li1, Yunlong Wang1
1Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Long-term outcomes following catheter ablation for long-standing persistent atrial fibrillation (LSPAF) remain unsatisfactory. This study sought to report a novel ablation strategy exclusively guided by anatomical considerations [Ethanol infusion into the vein of Marshall (EI-VOM), pulmonary vein isolation (PVI), posterior wall isolation (PWI), and mitral isthmus (MI) blockage, namely “POEM” approach] in LSPAF patients with dilated atrium.
METHODS From October 2021 and April 2023, 187 LSPAF patients were enrolled in the single center and underwent the “POEM” procedure. The primary endpoint was freedom from atrial fibrillation, atrial flutter, or atrial tachycardia (>30 s) within 12 months. The secondary endpoint was patients’ symptom status during follow-up.
RESULTS In 187 LSPAF patients with a median age of 62.0 (IQR 57.0–67.0) years, successful EI-VOM, PWI, and MI block rates were 89.3%, 73.3%, and 92.5%, respectively. Complications included one transient ischemic attack (0.5%) and two cases of mild to moderate pericardial effusion (1.0%). During a median follow-up of 17.5 months (IQR 12.7–23.8), 145 patients (78.1%) maintained sinus rhythm (SR), with 152 patients (81.3%) free of atrial arrhythmia (ATA) recurrence within 12 months. Higher left atrial diameter (HR: 1.18; 95% CI: 1.09–1.27) and longer Diagnosis-to-Treatment time (HR: 1.01; 95% CI: 1.00–1.02) were linked to ATA recurrence. Successful PWI (HR: 0.37; 95% CI: 0.19–0.72) and MI block (HR: 0.29; 95% CI: 0.12–0.70) were beneficial for sustaining SR.
CONCLUSIONS The “POEM” ablation procedure demonstrates feasibility and safety, correlating with a satisfactory rate of sinus rhythm maintenance in LSPAF patients with dilated atrium. The “POEM” ablation procedure demonstrates feasibility and safety, correlating with a satisfactory rate of sinus rhythm maintenance in LSPAF patients with dilated atrium. In this series of prospective, consecutive patients with persistent AF treated with the POEM ablation strategy, we reported that: (1) a full “POEM” lesion set (VOM ethanol infusion, PVI, PWI, and MI block) with confirmed blockage was achieved in >60% of patients, resulting in a 89.8% success rate of remaining free from ATA recurrence; (2) the rate of major complications was no higher than conventional PVI; (3) the rate of arrhythmia-free survival at 12 months was satisfied, with an overall SR maintenance rate of 81.3%; (4) “POEM” procedure did not negatively impact quality of life and often led to improvements; (5) both PWI and MI block could improve SR maintenance.
GW35-e0419
Xin Zheng1,2, Fenfang Zhang2, Leigang Wang1,3, Bin Liang1,3
1Shanxi Medical University
2Yangquan First People’s Hospital
3Second Hospital of Shanxi Medical University
OBJECTIVES Serum calcium (SC) derangements affect over half of hospitalized patients and are linked to increased in-hospital mortality. Atrial fibrillation (AF) is the most common arrhythmia in the intensive care unit (ICU), affecting around 6% of critically ill patients. However, the significance of the relationship between SC levels and in-hospital mortality in these patients remains unclear. This study aimed to examine the correlation between SC levels and in-hospital mortality in ICU patients diagnosed with AF.
METHODS Patients with atrial fibrillation were selected from the MIMIC-IV database. The study targeted in-hospital mortality as the outcome, employing multivariable-adjusted Cox regression, curve fitting, and threshold effects analysis to assess the association between SC levels and in-hospital mortality.
RESULTS The cohort comprised 11,621 patients diagnosed with AF, with an average age of 75.6 ± 11.7 years, and 42.6% were male. The in-hospital mortality rate was 8.9% (1031 out of 11,621). The relationship between SC levels and in-hospital mortality demonstrated a nonlinear pattern. Effect sizes on either side of the inflection point were 0.79 (HR: 0.79, 95% CI 0.67–0.94, P = 0.006) and 1.12 (HR: 1.12, 95% CI 1.01–1.25, P = 0.029), respectively. Sensitivity analysis results were consistent.
CONCLUSIONS The findings indicate a nonlinear association between SC levels and in-hospital mortality in critically ill patients with AF. Specifically, a SC level of approximately 8.56 mg/dL is linked to the lowest risk of in-hospital mortality. Risks increase as levels deviate below or above this point, underscoring a critical concern for ICU physicians.
GW35-e0422
Huasheng Lyu
The First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES This study explored the relationship between weight control and atrial fibrillation (AF) recurrence after catheter ablation in overweight and obese patients.
METHODS We prospectively enrolled consecutive 333 overweight and obese patients aged 28–87 years old, who underwent catheter ablation for AF in The First Affiliated Hospital of Xinjiang Medical University between October 2019 and February 2020. Data of patients’ characteristics, laboratory examination and treatment were collected at baseline. Each patient was followed up at 3, 6 and 12 months after ablation to collect information on weight, AF recurrence, stroke, major bleeding, hospitalization for cardiovascular reasons and death, etc. Patients were divided into weight controlled group (BMI <−1 kg/m2) and weight uncontrolled group (BMI ≥−1 kg/m2), according to the changes in the most recent exposure BMI before AF recurrence in patients with recurrence or the BMI at 12 months’ follow up in patients without recurrence and the BMI at baseline. Multivariate logistic regression was performed to adjust other known risk factors of AF recurrence and to explore the association between weight control and AF recurrence after catheter ablation.
RESULTS There were 54 and 279 patients in the weight-controlled and uncontrolled groups, respectively. There were no significant differences in age, gender, education, left atrial size, or hypertension history. The proportion of using ACEI/ARB was higher in the weight-controlled group. There was no significant difference in the proportion of obesity, paroxysmal AF, and AF duration. The AF recurrence rate was lower in the weight-controlled group. Multivariable logistic regression analysis shows that weight control is associated with a lower recurrence rate.
CONCLUSIONS Weight control is strongly associated with a lower AF recurrence rate after catheter ablation in overweight and obese patients.
GW35-e0424
Qinchao Wu, Yanguang Li, Yunlong Wang
Beijing Anzhen Hospital Affiliated to Capital Medical University
OBJECTIVES Mitral regurgitation (MR) is the most common valvular heart disease in the population and one of the most common comorbidity of atrial fibrillation (AF). Nonetheless, the prognosis of MR in AF patients remains unelucidated. This study aims to systematically evaluate the clinical outcomes of MR in AF patients.
METHODS In total, 1368 participants with echocardiographic records of MR severity in CABANA trial were included in the final analysis. Patients with no or mild MR (group 1, n = 1233) were compared with those with moderate or severe MR (group 2, n = 135). The primary end point of CABANA trial was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Secondary endpoint included all-cause mortality alone, heart failure hospitalization, and the composite of all-cause mortality and heart failure hospitalization. Quality of life assessment was achieved using 3 different scores at baseline, 3 and 12 months, and annually until 60 months.
RESULTS Patients in group 2 were significant older, more frequently men and longstanding persistent AF and had a history of heart failure compared with group 1. Additionally, patients in group 2 tended to have lower left ventricular ejection fraction and higher CHA2DS2-VASc score. The primary end point occurred in 7.2% (n = 89) of patients in group 1 vs. 14% (n = 19) in group 2 (hazard ratio, 1.97 [95% CI, 1.20–3.25]; P = 008). As for secondary end points, outcomes group 1 vs. group 2, respectively, were 4.7% vs. 8.8% for all-cause mortality (HR, 1.73 [95% CI, 0.92–3.25]; P = 0.089), and 10.8% vs. 15.5% for the composite of death and heart failure hospitalization (HR, 1.25 [95% CI, 0.78–1.99]; P = 0.357). There were not significant differences between the 2 groups in quality of life from baseline to the follow-up of 60 months.
CONCLUSIONS Our findings demonstrate that moderate or severe MR is associated with adverse clinical outcomes in AF patients. Further independent trials are warranted to verify these results.
GW35-e0430
Li Yanguang, Wang Lili, Wang Yunlong
Beijing Anzhen Hospital
OBJECTIVES Frailty was highly prevalent in patients with atrial fibrillation (AF) and is associated with adverse outcomes compared to robust individuals. However, it remains uncertain whether frailty modifies the effect of ablation and drug therapy on clinical outcomes and Quality of life (QoL).
METHODS The study is a post hoc analysis of the Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial. The Frailty index was calculated using 30 items, with a frailty index ≥0.21 defined as frailty. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included all-cause death and heart failure (HF) hospitalization. QoL was assessed periodically over 60 months using the Mayo AF-Specific Symptom Inventory (MAFSI) and Euro-QoL five dimensions questionnaire (EQ-5D). The analysis was based on the per-protocol (PP) set, in which the drug therapy arm consisted of patients randomized to drug therapy without crossover to ablation. Drug arm patients who crossed over to catheter ablation were censored at the time of the ablation. The catheter ablation arm consisted of patients randomized to ablation who received the procedure within a 12-month window following randomization.
RESULTS A total of 2070 patients (mean age, 66.2 ± 8.2 years; female, 37.2%), 1378 (66.6%) of whom had frailty, were included in the final analysis. Among them, 983 (47.5%) received catheter ablation, and 1087 (52.5%) received drug therapy. Catheter ablation was associated with a 34% reduction in the primary endpoint for patients with frailty (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.46–0.94). For patients without frailty, catheter ablation was not associated with a significant difference in the primary endpoint (HR, 0.78; 95% CI, 0.38–1.60). Among frail patients, the primary endpoint incidence was significantly lower for those who received catheter ablation (log-rank P = 0.019). For frail patients, the mean QoL score was more favorable in the catheter ablation group. Over the entire 60-month follow-up, the adjusted mean difference was −1.59 (95% CI, −2.11 to −1.06) for the MAFSI frequency score, −1.28 (95% CI, −1.71 to −0.86) for MAFSI severity score, and 3.30 (95% CI, 1.88 to 4.71) for EQ-5D score. There was no significant difference in QoL scores between the catheter ablation group and the drug therapy group among patients without frailty.
CONCLUSIONS In AF patients with frailty, catheter ablation significantly reduces the risk of adverse clinical outcomes and improves QoL compared to drug therapy. Our results indicate a potential benefit of catheter ablation for frail AF patients.
GW35-e0434
Huasheng Lyu
The First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES To investigate the impact of history of hypertension and blood pressure levels on the thromboembolism risk in the setting of nonvalvular atrial fibrillation (NVAF).
METHODS A total of 25,512 patients with atrial fibrillation were included. After excluding patients with valvular atrial fibrillation, hypertrophic cardiomyopathy, and those who received anticoagulation or catheter ablation at baseline, a total of 7757 patients were finally included in the study. The endpoint of follow-up was thromboembolic events, including ischemic stroke and systemic embolism. A multivariate Cox regression model was used to analyze whether a history of hypertension and blood pressure levels were independent risk factors for thromboembolic events in patients with NVAF.
RESULTS During a mean follow-up of (35 ± 25) months, 455 (5.9%) thromboembolic events occurred. The crude incidence rate of thromboembolism in patients with hypertension was higher than that in patients without (2.38 vs. 1.35 per 100 patient-years, χ2 = 16.8, P < 0.001). According to SBP levels, the incidence rate of thromboembolism increased with SBP (χ2 = 17.9, P < 0.001), while there was no difference in DBP groups (χ2 = 0.6, P = 0.907). Multivariable regression analysis showed that hypertension was associated with a 27% higher risk of thromboembolism (HR = 1.27, 95% CI 1.01–1.61, P = 0.045). SBP ≥140 mmHg was associated with a 36% higher risk of thromboembolism (HR = 1.36, 95% CI 1.02–1.82, P = 0.036), while SBP 120–129 mmHg or 130–139 mmHg was not (SBP 120–129 mmHg: HR = 1.23, 95% CI 0.90–1.67, P = 0.193; SBP 130–139 mmHg: HR = 1.30, 95% CI 0.95–1.77, P = 0.098). DBP was not associated with thromboembolism.
CONCLUSIONS A history of hypertension and SBP ≥140 mmHg are independent predictors of thromboembolism risk in patients with NVAF. These results indicate that intensive efforts to lower SBP below 140 mmHg might be an important strategy to reduce the risk of stroke in patients with NVAF.
GW35-e0465
Haoyu Wang
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES The association between bleeding and subsequent major adverse cardiac and cerebrovascular events (MACCE) remains poorly characterized. We aimed to evaluate the impact of hemorrhagic events in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI).
METHODS A total of 1877 consecutive patients with AF and ACS or undergoing PCI were prospectively recruited. The primary endpoint was MACCE, including all-cause death, myocardial infarction, ischemic stroke, systemic embolism or ischemia-driven revascularization during follow-up. Post-discharge bleeding was graded according to TIMI criteria. Associations between bleeding and subsequent MACCE were examined using time-dependent multivariate Cox regression after adjusting for baseline covariates and the time from bleeding.
RESULTS During a median follow-up of 34.2 months, 341 (18.2%) had TIMI major or minor bleeding events, of whom 86 (25.2%) also experienced MACCE. The risk of MACCE was significantly higher in patients with bleeding than those without (8.85% versus 6.99% per patient-year; HR, 1.568, 95% CI, 1.232–1.994). In patients who had both bleeding and MACCE, 65.1% (56 of 86) bleeding events occurred first. Temporal gradients in MACCE risk after major bleeding was highest within 30 days (HRadj, 23.877; 95% CI, 12.810–44.506) and remained significant beyond 1 year (HRadj, 3.640; 95% CI, 1.278–10.366). Minor bleeding was associated with increased risk of MACCE within 1 year.
CONCLUSIONS In patients with AF and ACS or PCI, major and minor bleeding were associated with subsequent MACCE with time-dependency. Our findings may aid in better defining net clinical benefit of optimal antithrombotic therapy.
GW35-e0473
Rui Zhang
Tsinghua Changgung Hospital
OBJECTIVES Atrial Fibrillation (AF) is one of the most common Atrial arrhythmias in clinical practice. It has a high disability rate and high mortality rate. It has been shown that left ventricular hypertrophy (LVH) is closely related to AF, and hypertension (HTN) is a risk factor for LVH. Therefore, it is important to identify the risk factors of AF in LVH (HTN-LVH) patients combined with HTN. We aimed to describe the clinical characteristics of HTN-LVH and to explore the relationship between HTN-LVH and AF, so as to identify the high risk population of AF as early as possible.
METHODS We conducted a retrospective cohort study to collect clinical data of patients who underwent thoracic echocardiography from January 2017 to December 2021 at Tsinghua Changgeng Hospital in Beijing, China. According to left ventricular mass index (LVH) (male ≥115 g/m2, female ≥95 g/m2), and inclusion and exclusion criteria, 2903 patients with LVH were selected. The data of patients were collected and analyzed for atrial fibrillation in Left ventricular hypertrophy patients and atrial fibrillation in hypertensive Left ventricular hypertrophy patients. We used the eXtreme Gradient Boosting (XGBoost) prediction model for classification problem analysis to classify the importance of each variable.
RESULTS Among them, 2124 patients with HTN-LVH were divided into HTN-LVH with AF group (HTN-LVH-AF) and HTN-LVH without AF group (HTN-LVH-non AF) according to whether they were complicated with AF or not. One hundred and eighty-nine patients with HTN-LVH-AF had an incidence of AF of 8.9%. By analyzing clinical data, laboratory tests and echocardiography indicators of the patients, we showed that there were significant differences between HTN-LVH-AF group and HTN-LVH-nonAF group in sex, age, systolic blood pressure, diastolic blood pressure, c-reactive protein, absolute lymphocyte, platelet, creatinine, glomerular filtration rate, total cholesterol, low-density lipoprotein, internal diameter of ascending aorta, left atrial anteroposterior diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction and left ventricular mass index (P < 0.05). Multiple Logistic regression analysis showed that these factors including the diameter of ascending aorta (OR 1.088, P < 0.001), left atrial anteroposterior diameter (OR 1.181, P < 0.001), left atrial upper and lower diameter (OR 1.192, P < 0.001), left atrial right diameter (OR 1.133, P < 0.001), left ventricular end-diastolic diameter (OR 1.094, P < 0.001), left ventricular end-systolic diameter (OR 1.090, P < 0.001), left ventricular ejection fraction (OR 0.934, P < 0.001), left ventricular mass index (LVMI, OR 1.011, P = 0.005), were all closely related to AF in HTN-LVH patients. The area under the receiver operating characteristic (ROC) curve of left atrial anteroposterior diameter was the largest (0.746), followed by left ventricular ejection fraction (0.724). Analyzing through XGBoost model, we found that LVMI was the most important predictor of AF in HTN-LVH (weight = 925), followed by left atrial anteroposterior diameter (weight = 562), internal diameter of ascending aorta (weight = 469), left ventricular ejection fraction (weight = 372) and left ventricular end-diastolic diameter (weight = 331).
CONCLUSIONS In conclusion, we found that left atrial anteroposteior diameter and left ventricular ejection fraction may be the main risk factors of AF occurrence in HTN-LVH patients; furthermore, the importance of left ventricular mass index deserved attention, which required further investigation.
GW35-e0534
Ying Zhang, Ming Ming
General Hospital of Northern Theater
OBJECTIVES The function of cardiac autonomic nervous system is closely related to the occurrence of arrhythmia. Stellate ganglion plays a vital role as an important target of sympathetic regulation. The research is to investigate the effect of stellate ganglion block in the treatment of arrhythmia.
METHODS Stellate ganglion block is the injection of local anesthetics into the surrounding and nearby tissues of the stellate ganglion, thereby blocking the sympathetic nerve of the preganglionic and postganglionic fibers and their innervating areas to regulate the sympathetic nerve tone. It is widely used in a variety of pain and non-pain diseases. In recent years, it has been more widely used in cardiovascular system diseases, especially in the treatment of arrhythmia. SGB procedures include anterolateral block puncture (paratracheal approach) and high lateral puncture, a successful block is marked by ipsilateral Horner syndrome, which is characterized by reduced pupil, eyeball invagination, ptosis, and absence of perspiration on the affected side. Increased skin temperature in the ipsilateral upper limb is considered the gold standard for successful sympathetic block. From June 2023 to June 2024, patients with ventricular tachyelectrical storm, rapid atrial fibrillation and frequent ventricular premature were enrolled in the General Hospital of Northern Theater. The patient received unilateral or bilateral stellar ganglion block with 100 mg 1% lidocaine. The use of antiarrhythmic drugs, the occurrence of arrhythmia, the frequency of electrocardioversion before and after block were recorded, and the follow-up discharge and clinical outcome were also recorded.
RESULTS A total of 25 patients with electrical storm, rapid atrial fibrillation, and frequent ventricular premature with poor drug treatment admitted to the cardiovascular department of our hospital from June 2023 to June 2024 were included in the study. The patients ranged in age from 41 to 82 years, including 18 males. The types of arrhythmias included ventricular tachyelectrical storm (21 cases), rapid atrial fibrillation (1 case), and frequent ventricular premature (3 cases). Basic heart diseases include coronary heart disease, valvular heart disease, idiopathic cardiomyopathy, and neoplastic heart disease. Ventricular tachycardia was terminated in patients with electrical storm after block, atrial fibrillation after block, and premature beat disappeared in patients with frequent ventricular premature after block. None of the 25 patients had operation-related complications.
CONCLUSIONS Ventricular tachyelectric storm, rapid atrial fibrillation, and frequent ventricular premature stellate ganglion block that do not respond to drug therapy is a safe and effective treatment. As an extracardiac autonomic intervention, SGB has been proven to be safe and effective in the treatment of arrhythmias, but its specific mechanism and optimal indications are still unclear, and further clinical studies are needed in the future to provide more powerful theoretical support for the treatment of common clinical arrhythmias with SGB.
GW35-e0608
Jun Shen, Baopeng Tang
The First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES This study evaluates the global impact of atrial fibrillation/flutter (AF/AFL) from 1990 to 2021 and predicts trends up to 2030. It highlights risk factors and demographic differences to guide health policies and enhance patient care, informing future global health strategies to tackle the growing issue of AF/AFL.
METHODS Using standardized GBD methods, we aimed to improve understanding of the health impact and risk factors of AF/AFL. We examined incidence, prevalence, mortality, and DALYs, providing estimates with uncertainty intervals. Population attributable fractions were used to assess the impact of key risk factors on mortality rates of AF/AFL. Trends from 1990 to 2021 were analyzed using Joinpoint regression to calculate annual percentage change (APC) and average annual percentage change (AAPC) with 95% confidence intervals. Bayesian Age-Period-Cohort model (BAPC) analysis informs our projections for the global burden of AF/AFL and its risk factors from 2020 to 2030.
RESULTS Globally, the age-standardized prevalence rates (ASPR), age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALYs rates (ASDR) for AF/AFL in 2021 were 620.507 per 100,000 persons (95% UI: 511.357–768.875), 52.116 per 100,000 persons (95% UI: 41.854–66.231), 4.363 per 100,000 persons (95% UI: 3.691–4.752), and 101.398 per 100,000 persons (95% UI: 84.890–122.412), respectively. Regional differences were observed, with regions with high sociodemographic index having the highest rates and those with low index having the lowest rates. Sweden and Turkey had the highest and lowest rates nationally. Older age groups, especially those over 85 years old, had higher rates of AF/AFL. Females had higher ASPR and ASIR in the 80+ age group but lower in the 30–79 age group. Risk factors like high body mass index, alcohol use, smoking, high sodium diet, and lead exposure were consistent across all SDI quintiles. The GBD 2021 highlighted that high systolic blood pressure was the main risk factor for AF/AFL-related deaths and DALYs from 1990 to 2021. Joinpoint analysis revealed that the global ASPR (APC = 0.711%; 95% CI: 0.285%–1.138%; P = 0.002) and ASIR (APC = 0.790%; 95% CI: 0.557%–0.926%; P < 0.001) increased between 2019 and 2021, ASDR decreased (APC = −0.190%; 95% CI: −0.500% to −0.063%; P = 0.079), and there was a significant decrease in ASMR from 2018 to 2021 (APC = −0.886%; 95% CI: −1.534% to −0.233%; P = 0.010). The BAPC model shows a rise in age-standardized rates from 1990 to 2030 for both sexes. Mortality is decreasing, especially in males, but DALYs burden is increasing and expected to continue.
CONCLUSIONS The study shows that AF/AFL is becoming more common worldwide, especially in older populations and regions with high socio-demographic index. While mortality rates are decreasing, the impact on health systems is increasing. It is important to focus on reducing modifiable risk factors like high blood pressure to lessen this burden.
GW35-e0615
Hezi Jiang, Yafeng Zhou
The Fourth Affiliated Hospital of Soochow University
OBJECTIVES The treatment of atrial fibrillation (AF) has made significant progress, but the prevention of AF has not received the attention it deserves. A few recent large-sized studies have conducted dose response analysis and reported different conclusions from previous studies on alcohol consumption and AF risk. The aim of this study is to examine the potential non-linear association between alcohol consumption and risk of AF and explore the potential differences of gender.
METHODS In this updated dose-response meta-analysis, PubMed, Embase and Cochrane databases were searched until June 2022. Risk estimates were reported as relative risk (RR) with 95% confidence intervals (CIs). The random effects restricted cubic spline models are used to evaluate the potential non-linear association between alcohol consumption and AF risk.
RESULTS A total of 10,151,366 participants with 214,365 cases of AF enrolled in 13 prospective studies. The overall meta-analysis showed that a 1 drink/day increase in alcohol consumption increased the risk of AF by 6% (RR: 1.06; 95% CI: 1.03–1.08). In gender subgroup analysis, pooled results were different between men (RR: 1.08; 95% CI: 1.05–1.11) and women (RR: 1.05; 95% CI: 0.96–1.14). A linear relationship between alcohol consumption and risk of AF was found in men (P = 0.87) while a J-shaped curve was observed in women (P = 0.00). Regional subgroup analysis yielded broadly comparable results in Americas (RR: 1.07; 95% CI: 1.03 1.12), Europe (RR: 1.04; 95% CI: 0.99–1.1) and Asia (RR: 1.07; 95% CI: 0.99–1.14).
CONCLUSIONS The relationship between AF risk and alcohol consumption is linear in men, while a potential non-linear J-shaped relationship is shown in women.
GW35-e0619
Zhenghao Liu, Yafeng Zhou
The Fourth Affiliated Hospital of Soochow University
OBJECTIVES The influence of left atrial appendage volume (LAAV) on the recurrence of atrial fibrillation (AF) following radiofrequency catheter ablation remains unclear. We performed a meta-analysis to assess whether LAAV is an independent predictor of AF recurrence following radiofrequency catheter ablation.
METHODS The PubMed and the Cochrane Library databases were searched until March 2022 to identify publications evaluating LAAV in association with AF recurrence after radiofrequency catheter ablation. Seven studies that fulfilled the specified criteria of our analysis were found. We used the Newcastle-Ottawa Scale to evaluate the quality of the studies. The pooled effects were evaluated depending on standardized mean differences (SMDs) or hazard ratios (HRs) with 95% confidence intervals (CIs). P values < 0.05 were considered statistically significant.
RESULTS A total of 1017 patients from 7 cohort studies with a mean follow-up 16.3 months were included in the meta-analysis. Data from 6 studies (943 subjects) comparing LAAV showed that the baseline LAAV was significantly higher in patients with AF recurrence compared to those without AF (SMD: −0.63; 95% CI: −0.89 to −0.37; all P values < 0.05; I2 = 62.6%). Moreover, higher LAAV was independently associated with a significantly higher risk of AF recurrence after radiofrequency catheter ablation (HR: 1.10; 95% CI: 1.02 to 1.18).
CONCLUSIONS The meta-analysis showed that there is a significant correlation between LAAV and AF recurrence after radiofrequency catheter ablation, and the role of LAAV in AF patients should not be ignored in clinical practice.
GW35-e0637
Kun Li
Beijing Tsinghua Changgung Hospital
OBJECTIVES Genotypes and phenotypes of congenital long QT syndrome (LQTS) may be variable among different population groups and they have not yet been well studied in Chinese population. We sought to evaluate the current outcomes of LQTS in China.
METHODS Genotype and phenotype data of LQTS patients (65 families) were retrospectively reviewed from 3 specialty centers from 2006 to 2021. Patients were included if they met any of the following diagnostic criteria for LQTS using the 2015 European Society of Cardiology guidelines.
RESULTS A total of 115 patients (74 female patients) were included and had median QTc 511 (472, 570) ms. Thirty-four (52%) probands experienced a delay in diagnosis, including epilepsy 8 (12%), hypoglycemia 2 (3%), myocarditis 4 (6%) or no definite diagnosis 20 (31%). Long QT syndrome type 2 (LQT2, 53%) was the most common subtype, followed by long QT syndrome type 1 (LQT1, 28%) and long QT syndrome type 3 (LQT3, 5%). Age of onset was genotype specific. Seventeen (100%) symptomatic LQT1 patients and 4 (80%) symptomatic LQT3 patients have their first BCE before 15 years old, whereas 30 (70%) long QT syndrome type 2 (LQT2) patients and 6 (67%) other LQTS patients have their first BCE after 15 years old. Patients with long QT syndrome type 3 (LQT3) had a significantly longer median QTc interval when compared with the rest of LQTS patients (577 [565, 595], P = 0.006). Individualized treatment strategies ranged from nontreatment (53%) to triple therapy that involved a combination of pharmacotherapy, left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillator (ICD). Totally 39 (55%) patients experienced ≥1 LQTS-triggered BCE during follow-up, including 23 (32%) patients with only a single BCE, 12 (17%) patients with 2 to 5 BCEs, 3 (4%) patients with 6 to 10 BCEs, and 1 (1%) patient with >10 BCEs. After the patients’ evaluation and treatment, the total number of BCEs dropped from 4 (2, 7) to 1 (0, 1) (P < 0.001) and annual BCEs dropped from 1.125 (0.5, 3) to 0.083 (0, 0.244) (P < 0.001). The BCE-free survival for the symptomatic cohort was 72% at 1 year, 54% at 5 years, and 32% at 10 years. Further analysis showed there was a sex-specific risk associated with treatment outcomes. Female patients had a higher percentage of BCE recurrence compared with male LQTS patients (44% vs. 24%; P = 0.024). The BCE-free survival for female patients was 79% at 1 year, 62% at 5 years, and 48% at 10 years, whereas the BCE-free survival for male patients was 89% at 1 year, 81% at 5 years, and 60% at 10 years.
CONCLUSIONS This study sheds light on number of important facets of patients with LQTS in China. Further optimization of diagnosis and treatment strategies is still needed given that the initial diagnosis rate and BCE-free survival is low compared to western countries.
GW35-e0642
Yan Yin1, Yanguang Li1, Shaomin Chen2
1Beijing Anzhen Hospital, Capital Medical University
2Peking University Third Hospital
OBJECTIVES The predictive efficacy of echocardiographic abnormalities for incident atrial fibrillation (AF) in elderly remains under-investigated.
METHODS From January 2015 to May 2023, 2615 elderly inpatients (>65 years) were studied. Using LASSO Cox regression to identify independent risk factors. Patients were then divided into two groups based on age: Young-old Elderly and Middle-to-Oldest Elderly, with an age cutoff of 75 years. The left atrial diameter (LAD) and Echocardiographic diastolic parameter (E/A ratio) were integrated into both a restricted cubic spline (RCS) model and a Cox model for subsequent survival assessment based on individual measurements. Furthermore, these variables were incorporated into the CHA2DS2-VASc score model.
RESULTS The most regularized and parsimonious model included three variables, Age, LAD and E/A ratio (P < 0.001). Nonlinear relationships between LAD and E/A ratio with incident AF events were identified (Pnonlinear < 0.05), showing a U-shaped RCS curve for E/A ratio. Age showed a nonlinear interaction with the two variables (Pnonlinear < 0.05). With increasing age, the hazard ratio (HR) of the E/A ratio demonstrates a U-shaped pattern, while the HR of LAD exhibits an inverted U-shaped trend. Higher LAD (adjusted HR [aHR]: 3.31 [95% CI: 1.64–6.68] in Young-old Elderly, 3.28 [95% CI: 2.02–5.34] in Middle-to-Oldest Elderly) and E/A ratio (adjusted HR [aHR]: 1.85 [95% CI: 1.08–3.17] in Young-old Elderly, 2.46 [95% CI: 1.66–3.64] in Middle-to-Oldest Elderly) were associated with incident AF events. The predictive ability of the CHA2DS2-VASc score for incident AF improved from an AUC of 0.585 (95% CI: 0.544–0.630) to 0.753 (95% CI: 0.715–0.790) after integrating the LAD and E/A ratios.
CONCLUSIONS Transthoracic echocardiography is indispensable for predicting incident AF in elderly hospitalized patients, with higher LAD and E/A ratios were associated with incident AF. As age progresses, its predictive efficacy for incident AF intensifies. Incorporating them into the CHA2DS2-VASc score can significantly improve its accuracy and specificity in predicting incident AF.
GW35-e0665
Yulai Yan
General Hospital of Northern Theatre Command
OBJECTIVES To investigate the impact of different catheter ablation strategies on the left atrial structure and function of patients with atrial fibrillation postoperatively.
METHODS A retrospective analysis was conducted on the clinical data of 384 patients with atrial fibrillation who underwent catheter ablation treatment at the Northern War Zone General Hospital from January 2022 to December 2023. Among them, 217 patients had paroxysmal atrial fibrillation, and 167 patients had persistent atrial fibrillation. Based on the choice of different ablation strategies, patients with paroxysmal atrial fibrillation were divided into the radiofrequency group (N = 138) and the cryoablation group (N = 79). Patients with persistent atrial fibrillation were divided into the double-loop group (N = 56) and the double-loop with additional linear ablation group (N = 111). Follow-up was conducted for 6 months postoperatively. Cardiac structural and functional indicators (left atrial diameter, right atrial diameter, left ventricular diameter, right ventricular diameter, left ventricular ejection fraction, and NT-proBNP) were collected at admission, postoperative day 1, postoperative month 1, month 3, and month 6, and their differences were analyzed.
RESULTS According to the 6-month follow-up results, each group was compared for baseline vs. postoperative day, baseline vs. 1 month postoperatively, baseline vs. 3 months postoperatively, and baseline vs. 6 months postoperatively for left atrial diameter (LAD), right atrial diameter (RAD), left ventricular diameter (LVD), right ventricular diameter (RVD), left ventricular ejection fraction (LVEF), and NT-proBNP. In patients with paroxysmal atrial fibrillation, the radiofrequency group showed a significant reduction in left atrial diameter postoperatively, with statistically significant differences at 1 month, 3 months, and 6 months postoperatively compared to baseline (P < 0.05). The other cavity diameters and LVEF remained consistent with baseline levels postoperatively, while NT-proBNP showed a similar decreasing trend to left atrial diameter, significantly decreased at 1 month, 3 months, and 6 months postoperatively (P < 0.05). In the cryoablation group, all observed indicators showed no significant differences between pre- and postoperative measurements (P > 0.05). In patients with persistent atrial fibrillation, the double-loop group showed an increase in left atrial diameter postoperatively on the day of the procedure (42.25 ± 3.98 to 43.16 ± 3.77), with a statistically significant difference (P < 0.05), and a decrease at 3 and 6 months postoperatively compared to baseline (P < 0.05). The other cavity diameters remained consistent with preoperative conditions, while LVEF significantly increased at 3 and 6 months postoperatively compared to baseline (P < 0.05), and NT-proBNP decreased significantly from the day of the operation to 6 months postoperatively (P < 0.05). In the additional linear ablation group, the left atrial diameter and right atrial diameter decreased at 1 month, 3 months, and 6 months postoperatively compared to baseline (P < 0.05), while LVEF significantly increased at 1 month, 3 months, and 6 months postoperatively compared to baseline (P < 0.05), and NT-proBNP decreased significantly from the day of the operation to 6 months postoperatively (P < 0.05).
CONCLUSIONS Catheter ablation for paroxysmal atrial fibrillation improved left atrial structure but did not significantly improve heart function. Radiofrequency ablation had a more significant impact on left atrial improvement than cryoablation. For patients with persistent atrial fibrillation, catheter ablation resulted in a significant improvement in cardiac structure and function, and adding linear ablation appropriately on the basis of bilateral pulmonary vein isolation can expedite the improvement of atrial structure and function.
GW35-e0719
Jing Yang, Ping Zhang
Beijing Tsinghua Changgung Hospital
OBJECTIVES Long QT syndrome (LQTS) is a potentially fatal cardiac channelopathy and contributes to an increased risk of life-threatening arrhythmic events (LAEs) of teenagers. Few study reported the predictive model for the risk assessment of life-threatening arrhythmic events (LAEs) in diagnosed Chinese LQTS patients.
METHODS Baseline demographic features, personal presentation, family history, 12-lead resting electrocardiograms (ECGs), 24-hour ambulatory Holter recordings, exercise stress tests, echocardiographic data and genetic tests were performed. Follow-up data were obtained from our hospital electronic medical recording system. The primary outcome was life-threatening arrhythmic events (LAEs). LQTS-LAEs related risk predictors were identified by univariate Cox regression analysis, which were fit in multivariate Cox analysis to establish the risk prediction model for LQTS patients.
RESULTS The study cohort included 297 LQTS patients with prolonged QTc interval of 507.9 ± 54.0 ms. Sixty-five patients (65/297, 21.9%) experienced LAEs at 26.4 ± 28.1 months. Risk factors of LAEs were identified by Univariate Cox regression including: proband, female, young age of onset, first symptoms (sudden death/syncope), family history of LQTS, and Schwartz score; bradycardia, QTc interval ≥500 ms, Tdp/VF recorded by Holter electrocardiograms; different genotypes. A multimodal risk prediction model for LAEs with female, age of onset ≤20 years, family history of LQTS, QTc interval, Tdp/VF recorded by Holter electrocardiograms, and genotype was established by multivariate Cox regression analysis. A scoring FAGQA risk prediction system was formulated based on the β coefficient and risk ratio in multivariate Cox regression. The incidence of 5-year LAEs with different FAGQA scores were calculated to stratify LQTS patients and propose precise treatment options.
CONCLUSIONS A score-type FAGQA risk prediction system in Chinese LQTS patients was formed, which would bring convenience for clinical evaluation. LQTS patients at high risk of sudden death could be identified, and effective treatment methods would be implemented to reduce the incidence of sudden cardiac death.
GW35-e0736
Qiaoyuan Li1, Yanguang Li1, Zhuo Liang1, Tao Zhang1, Xu Liu1, Dongping Fang1, Jin Bai2, Jian Li3, Fengxiang Zhang4, Yunlong Wang1
1Beiing Anzhen Hospital, Department of Cardiology, Arrhythmia Center
2Peiking University Third Hospital, Department of Cardiology
3Chinese PLA General Hospital, Department of Cardiology
4Jiangsu Province Hospital, Department of Cardiology
OBJECTIVES The ablation treatment for persistent atrial fibrillation still challenges, particularly ablation at the mitral isthmus. Ablation in conjunction with the Vascular of the Mitral Isthmus (VOM) combined with endocardial ablation at the mitral isthmus can enhance the blockage rate at the mitral isthmus. However, some patients remain refractory to blockage at the mitral isthmus even after VOM and endocardial ablation at the mitral isthmus. This article analyzes the distal coronary sinus potential to rapidly determine the location of the mitral isthmus gap, thereby guiding ablation at the mitral isthmus.
METHODS This study included a total of 114 patients with persistent atrial fibrillation. After the routine completion of CPVI and VOM alcohol ablation, the pentaray electrode was placed at the left atrial appendage (LAA) position. If the mitral isthmus was not blocked during LAA pacing, the distal coronary sinus potential (CSd) characteristics were analyzed.
RESULTS This study found that in 43.9% of patients with unblocked mitral isthmus during LAA pacing, 84% of those patients (42/50) was recorded double potentials at CSd, 16% of those patients (8/50) was recorded one single potential at CSd. There was a high-frequency near-field potential (NFP) and a low-frequency far-field potential (FFP) with those who could be recorded double potentials at CSd. 52.4% (22/42) of those double potentials showed FFP was earlier while 47.6% of them showed NFP was earlier.
CONCLUSIONS For patients with an unblocked mitral isthmus, if two potentials can be recorded from the distal coronary sinus beneath the left atrial appendage during pacing, it can help in rapidly determining the location of the mitral isthmus gap, thereby guiding ablation and achieving blockage at the mitral isthmus.
GW35-e0737
Haonan Deng
National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
OBJECTIVES Globally, diabetes prevalence is increasing, along with a significant rise in atrial fibrillation (AF) cases linked to diabetes. Managing diabetes symptoms while reducing AF risk is a critical issue. This study compares the preventive effects of various oral hypoglycemic medications, including single and combination therapy regimens, on AF.
METHODS We thoroughly searched several databases, including CBM, CNKI, Wanfang, Embase, PubMed, and Cochrane. The scope of the search was restricted to research that was published before June 2023. With an emphasis on type 2 diabetes patients, we searched for cohort studies and randomized controlled trials (RCTs) that examined the use of oral antidiabetic medications and evaluated the incidence of AF as an outcome measure. Two independent researchers reviewed the literature, retrieved data, and assessed study bias. STATA 14.0 and R were used for network meta-analysis.
RESULTS In 20 RCTs and 4 cohort studies, an aggregate of 321,050 patients took part. Overall AF frequency was lower in dipeptidyl peptidase-4 inhibitor and metformin combined treatment (OR 0.12, 95% CI: 0.03, 0.43) and in thiazolidinedione and sulfonylureas combined therapy (OR 0.24 and 95% CI: 0.07 and 0.86) when compared to placebo. When compared to other drugs, thorough research revealed that the combination of Dipeptidyl-peptidase IV inhibitors and metformin had the greatest impact on lowering AF occurrences.
CONCLUSIONS The oral antidiabetic drug regimen that reduces the incidence of AF the most effectively is the combination of Dipeptidyl-peptidase IV inhibitors and metformin.
GW35-e0781
Sanbao Chen, Zulu Wang, Ming Liang, Jie Zhang, Wenqing Yang, Yaling Han
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research institute and Department of Cardiology, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
OBJECTIVES Aims: Cryoballoon ablation (CB-A) has been well recognized as a safe and effective strategy for atrial fibrillation (AF) in several observational and prospective randomized trials. Despite that PV occlusion is thought to be necessary for circumferential, transmural lesions produced by cryoballoon ablation, there is increasing evidence in performing segmental non-occlusive cryoballoon ablation (NOCA) in combination with pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF). In the present study, lesion formation under different conditions during NOCA were assessed.
METHODS NOCA was simulated in an ex vivo model in which a circulating water pump was used to produce and adjust flow across the CB (simulating blood leakage) and a funnel was attached to the outlet of the pump (simulating PV-antrum junction). Fresh canine hearts were obtained from dogs under general anesthesia and the left ventricles were sectioned into strip-shaped pieces. We conducted experiments to evaluate the effects of (1) flow rate (0, 1, and 1.5 L/min) and freezing time (120-sec, 150-sec and 180-sec) on lesion dimensions during segmental NOCA and (2) overlapping manners between two sequential cryoablations (overlaps of half and two-thirds the balloon area) on lesion continuity during linear NOCA. Inner balloon temperature and tissue-balloon surface temperature were recorded and lesion formation was assessed after 3–5 hours using tetrazolium chloride staining.
RESULTS (1) Experiments of segmental NOCA: Inner balloon temperature was significantly lower in no-flow group (flow rate = 0 L/min) compared with flow groups (−57.92 ± 2.83 °C for 0 L/min vs. −44.67 ± 4.73 °C for 1 L/min vs. −42.87 ± 5.95 °C for 1.5 L/min, P < 0.001), while no differences were found in tissue-balloon surface temperature among different flow rates (−50.14 ± 6.35 °C for 0 L/min vs. −47.11 ± 6.51 °C for 1 L/min vs. −48.93 ± 7.97 °C for 1.5 L/min, P = 0.488). No differences were observed in maximal lesion depths among different flow rates across cryoballoon. For ablation duration, 120-sec cryotherapy was able to penetrate to a maximal lesion depth of 6.45 ± 0.80 mm, significantly smaller than those for 150-sec and 180-sec (P < 0.001). (2) Experiments of linear NOCA: Maximal lesion depths of 2 × 120-sec linear NOCA were similar between two-thirds and half-size overlaps (P = 0.192). However, non-transmural lesions were more frequently observed in half-size than two-thirds overlaps (56.3% vs. 6.3%, P = 0.002).
CONCLUSIONS When performing NOCA, lesion depths did not vary significantly with convective flow around the CB. 120-sec cryoapplication seemed to yield enough lesion depth and longer cryotherapy should be applied cautiously considering risk of esophageal injury. Additionally, a series of sequential applications in a half-size overlapping manner might lead to non-transmural lesions in the ablation line.
GW35-e0850
Yangyang Wang1, Yang Shao2, Qiming Dong3, Yunfei Gu1, Hao Wang1
1Luoyang Central Hospital Affiliated to Zhengzhou University
2Sahlgrenska University Hospital
3Greater Baltimore Medical Center, Towson
OBJECTIVES The efficacy of angiotensin receptor-neprilysin inhibitor (ARNI) in reducing recurrence risk of atrial fibrillation (AF) after ablation remains uncertain. To systematically evaluate the effect of ARNI in decreasing the recurrence risk of atrial fibrillation following ablation, we conducted this meta-analysis.
METHODS We summarized the results of randomized controlled trials (RCTs) and cohort studies on ARNI, separately – specifically Sacubitril/Valsartan in preventing AF recurrence after radiofrequency ablation. Two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. The random effect model was used to merge the effect sizes, and the results were reported separately depending on whether the study was a RCT or a cohort study and on the follow-up duration. We further conducted subgroup analysis by comparing the effect of ARNI in reducing AF recurrence to that of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) and to that of the Blank group. Publication bias was conducted by using Egger’s test and Begg’s test. Sensitivity was analyzed by excluding one study at a time using Stata version 18.0 (StataCorp, College Station, TX, USA).
RESULTS Whether in RCTs or in cohort studies, continuous use of ARNI for 6 and 12 months partly reduced the AF recurrence after ablation (using 3-month ARNI in RCTs: RR = 0.58; 95% CI = 0.38–0.88; P = 0.01; using 6-month ARNI in RCTs: RR = 0.58; 95% CI = 0.40–0.83; P = 0.004; using 12-month ARNI in RCTs: RR = 0.54; 95% CI = 0.35–0.84; P = 0.007; using 6-month ARNI in cohort studies: RR = 0.49; 95% CI = 0.37–0.64; P < 0.001). Subgroup analysis showed that, compared to angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) or Blank, both in RCTs and cohort studies, ARNI was more effective in reducing the recurrence rate of atrial fibrillation after ablation.
CONCLUSIONS The using of ARNI may be effective in preventing the recurrence of AF after ablation, with ARNIs being shown to be more effective than ACEI/ARBs in the present Meta-analysis.
GW35-e0957
Pengze Xiao, Yunlin Chen, Zhiyu Ling
The Second Affiliated Hospital of Chongqing Medical University
OBJECTIVES Background: The process of the Atrial Fibrillation Centers (AFCs) construction in China has begun since 2016. The Atrial Fibrillation Better Care (ABC) pathway was formally proposed in 2020. The purpose of this study was to evaluate the impact of Atrial Fibrillation Center construction on the implementation of ABC pathway in a Chinese large teaching hospital, and to further assess the changes and time trends at the hospital-wide level and across different medical disciplines, in order to clarify the practical significance in providing optimal integrated care for atrial fibrillation (AF).
METHODS We obtained data from the de-identified electronic medical records of a large teaching hospital in Chongqing, China from October 2018 to February 2023. Data from 18,942 patients with atrial fibrillation who hospitalized in The Second Affiliated Hospital of Chongqing Medical University were included. To assess the ABC pathway implementation trend among patients, the data of the patients were aggregated monthly. We calculated the monthly ABC pathway implementation rates, used interrupted time-series model, performed tests for first-order autocorrelation, fitted a linear regression model, and plotted time-series graphs to present the changes and time trends before and after the AFC construction.
RESULTS A total of 18,942 patients were included, with 8106 (42.8%), 7600 (40.1%), and 3236 (17.1%) in the cardiology, internal medicine and surgical departments. In the first month after the completion of the atrial fibrillation center construction, the hospital-wide implementation rate of the ABC pathway significantly improved with an absolute increase of 11.82% (95% CI [8.21%, 15.44%], P < 0.01). The subsequent slope increased by 0.27% (95% CI [0.05%, 0.5%], P = 0.01). Meanwhile, the implementation rate of the “A” and “B” criterion increased significantly at the hospital-wide level, with absolute increases of 12.19% (95% CI [8.41%, 15.97%], P < 0.01) and 6.45% (95% CI [2.88%, 10.01%], P < 0.01), respectively. However, there was no statistically significant improvement of the “C” criterion.
CONCLUSIONS The process of the AFC construction resulted in a significant increase of the implementation of the ABC pathway following the completion of the atrial fibrillation center. And this intervention was effective in stroke prevention and symptom control. However, it remained deficient in rhythm control and comorbidities management. These results demonstrate a need for further consolidation of the comprehensive management for atrial fibrillation, especially focusing on enhancing rhythm control and management of risk factors and comorbidities.
GW35-e1008
Jiawei Chen1, Zhe Wang2, Yingwei Chen1, Jianzeng Dong1,2
1The First Affiliated Hospital of Zhengzhou University
2Beijing Anzhen Hospital
OBJECTIVES Emerging evidence suggests that remnant cholesterol (RC) is strongly associated with an increased incidence of atrial fibrillation (AF). However, the causality has not been confirmed. We aimed to evaluate the causal associations of RC with AF and risk factors by using Mendelian randomization (MR) methods.
METHODS A two-sample MR study was conducted to explore the bidirectional causal relationship between RC (n = 115,082) and AF (n = 138,994) using publicly available genome-wide association study data. The inverse variance weighted (IVW), weighted median, and MR-Egger were used to obtain the causal estimates. Findings were verified through extensive sensitivity analyses. Multivariable MR (MVMR) analysis was performed to estimate the direct causal effects with adjustment of potential confounders. Two-step MR technique was then conducted to explore the mediators in the causal effects of RC on AF.
RESULTS Univariate MR analysis showed that genetically predicted RC was causally associated with a higher risk of atrial fibrillation (OR: 1.165, 95% CI: 1.020–1.310, P = 0.038), but the opposite relationship was not established (OR: 0.990, 95% CI: 0.973–1.007, P = 0.244). The MVMR analysis indicated that the causal relationships remained significant after adjusting for the potential confounding factors. Mediation analysis revealed that hypertension was significantly mediated the causal effects of RC on AF (44%). These results remained robust across sensitivity analyses.
CONCLUSIONS MR findings provide genetic evidence for causal link between RC and AF, which suggesting that targeted RC-lowering therapies may be effective for the primary prevention of AF.
GW35-e1017
Kong Lingcong, Wang Xinhua
Department of Cardiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES The electrocardiogram-based algorithm for predicting para-septal atrial tachycardia (PSAT) is limited by the significant overlaps in the P-wave morphology originating from various para-septal sites. The aim of this study was to investigate the endocardial activation characteristics of PSAT and to seek an endocardial activation-derived predictor for the ablation site.
METHODS Forty-four patients (11 males, average 62.6 ± 14.7 years) with PSAT ablation in four tertiary medical centers were assigned into three groups according to the ablation site: right atrial (RA) para-Hisian region (Group 1, n = 10), the noncoronary cusp (NCC) (Group 2, n = 13) and left atrial (LA) para-septal areas (Group 3, n = 21). Multiple-chamber activation mapping was performed guided by a 3D navigation system. The discrepancies in the earliest activation time between two of three chambers (ΔRA-LA, ΔRA-NCC and ΔLA-NCC) were calculated in each group and used for pairwise comparisons.
RESULTS There was significant difference in ΔRA-LA, ΔRA-NCC, and ΔLA-NCC compared among three groups. ΔRA-LA was the only parameter which could consistently predict the ablation site of PSAT with good accuracy (AUC 1.000, sensitivity 100%/specificity 100%, and cut-off value 7 ms for predicting right para-Hisian or NCC ablation; AUC 0.974, sensitivity 92.3%/specificity 95.2%, and cut-off value −4 ms for predicting NCC or left para-septal ablation). Based on two cut-off values, A two-step algorithm was developed to predict the ablation site of PSAT with positive predictive value of 95.4% and negative predictive value of 97.0%.
CONCLUSIONS ΔRA-LA is a useful endocardial activation-derived parameter for predicting the successful ablation site of PSAT.
GW35-e1022
Guanzhi Chen, Ligang Ding
Peking Union Medical College, National Center for Cardiovascular Diseases, Fuwai Hospital, Beijing, China
OBJECTIVES Cardiac conduction block (CCB) is a common bradyarrhythmia that significantly increases cardiovascular and mortality risk. Each 5 kg/m2 increase in BMI raises the CCB risk by over 20%. While high BMI is linked to higher CCB risk in the general population, no studies have examined weight changes’ impact on CCB risk in hypertensive patients. We hypothesized that BMI changes affect CCB risk in individuals with hypertension. To test this, we used data from the Kailuan Study cohort in China to explore BMI changes and CCB incidence in hypertensive patients.
METHODS The follow-up period began immediately after the 2010 health examination, during which a total of 38,907 observations were made, until a CCB event occurred or December 31, 2021. Poisson regression within a generalized linear model was used to calculate the relative risk (RR) and 95% confidence interval (95% CI) for CCB that was associated with BMI changes. Participants with normal BMIs in both 2006 and 2010 were used as the reference group.
RESULTS We studied 38,907 individuals with a mean age of 56.11 ± 11.31 years. The median duration of follow-up was 10.06 years. Poisson regression analysis of the generalized linear model, after adjustment for confounding factors, showed that the Overweight/obesity-to-normal weight, Normal weight-to-overweight/obesity, and Overweight/obesity-to-overweight/obesity groups had higher risks of CCB (relative ratio: 1.33, 95% confidence interval: 1.32–1.34; 1.76, 1.73–1.79; and 1.74, 1.70–1.77; respectively) vs. the Normal weight-to-normal weight group.
CONCLUSIONS In hypertensive populations, changes in BMI are closely linked to the incidence of CCB. Patients with high BMI have an increased CCB risk. Reducing BMI from overweight/obese to normal lowers but doesn’t eliminate this risk. Increasing BMI from normal to overweight/obese raises CCB risk more than the reduction achieved by losing weight. Notably, the CCB risk increase from gaining weight is higher than maintaining a high BMI continuously.
GW35-e1025
Kong Lingcong, Wang Xinhua
Department of Cardiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES Pulmonary vein isolation (PVI) usually results in abolishment of PV potentials (PVP) rather than concomitant termination of non-paroxysmal atrial fibrillation (non-PAF). It is unclear whether ongoing fibrillation in isolated PVs (OFIP) might co-exist with AF in non-PAF ablation. This study sought to explore the prevalence of OFIP in non-PAF ablation and to develop a concise discriminating algorithm to distinguish between OFIP and isolation failure, thereby minimizing excessive ablation and associated risks.
METHODS Non-PAF patients undergoing first-time ablation were divided into retrospective induction cohort (IC) and prospective validation cohort (VC). In case of ongoing PV fibrillation after PV ablation, PVI completion was assessed based on unique PVP phenomena and after systemic gaps mapping and ablation.
RESULTS Twenty (3.55%) of 563 had OFIP, including 9/300 from the IC and 11/263 from the VC. No significant predictors of OFIP were identified in terms of baseline characteristics or procedural factors. Based on 3 right-sided, 5 left-sided, 1 bilateral OFIP cases in the IC, either spontaneous or bumping-induced PVP disappearance, or a combination of bipolar voltage reduction >80%, local activation time later than PV recordings and no response to carina ablation were adopted as the major criteria for developing a discriminating algorithm. In 20 patients with ongoing PV fibrillation in the VC, the algorithm identified true OFIP in 11, false OFIP in 3 and true incomplete PVI in 6. The sensitivity, specificity, positive and negative predictive value was 100%, 66.7%, 78.6% and 100%, respectively.
CONCLUSIONS OFIP was not negligible in non-PAF ablation procedures for achieving efficient and safe PVI. A novel four-step algorithm was developed to discriminate OFIP with good predictive value.
GW35-e1037
Huiyuan Qin, Jiuzhou Chen
The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES Atrial fibrosis is a precursor to atrial cardiomyopathy and stroke in patients with atrial fibrillation (AF). This study aims to identify plasma metabolites predictive of atrial fibrosis and assess the potential of specific dietary interventions to prevent atrial fibrosis.
METHODS The study enrolled 354 patients, divided into a discovery cohort of 251 and a validation cohort of 103. Plasma samples were analyzed for metabolomics, and atrial fibrosis biomarkers were identified and prioritized using bioinformatics. Cardiac fibroblast function was assessed through Western blot, quantitative real-time PCR (qRT-PCR), and cellular immunofluorescence. Interventions involving fatty acid metabolites, particularly Suberic acid, were tested at cellular and animal levels.
RESULTS Metabolites such as Suberic acid, Palmitic amide, 10Z-Nonadecenoic acid, 8,11,14-Eicosatrienoic acid, and 2,2-Dimethylglutaric acid independently predicted atrial fibrosis and recurrence of AF, beyond clinical predictors like hypertension and diabetes. A multivariate regression model using differential fatty acid metabolites yielded receiver operating characteristic (ROC) areas of 0.822 in the discovery cohort and 0.802 in the validation cohort. The expression patterns of these metabolites in the validation cohort mirrored those in the discovery cohort. Furthermore, Suberic acid significantly promoted fibroblast proliferation and differentiation into myofibroblasts by activating the cAMP/Akt pathway in vitro. A diet containing 0.2% Suberic acid significantly increased atrial fibrosis and the incidence of atrial fibrillation in CS-CREM mice in vivo.
CONCLUSIONS The plasma metabolite Suberic acid was identified as a crucial predictor of atrial fibrosis. Dietary interventions targeting this metabolite provide a novel approach to slow the progression of atrial fibrosis in AF patients.
GW35-e1168
Yijie Liu, Li Yanguang, Wang Yunlong
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Mitral regurgitation (MR) has been associated with atrial fibrillation (AF). This article aims to determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in atrial fibrillation patients with/without MR.
METHODS The CABANA trial randomized 2204 patients (ablation 1108, drug 1096) with AF who were ≥65 years old or <65 years old with ≥1 risk factor for stroke. Of these, 1375 had an transthoracic echocardiography (TTE) with MR documentation and form the subject of this article. Per-protocol (PP) analysis was used and the relative risks were expressed as hazard ratios (HRs) with associated 95% CIs derived using the Cox proportional hazards model. The CABANA trial’s primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest.
RESULTS A total of 1116 patients with MR in TTE documentation met the requirements for PP analysis, of which 107 had a moderate/severe MR and 1009 had no/mild MR. AF patients with no/mild MR in the ablation arm had a 51% relative reduction in the primary composite end point (hazard ratio, 0.49 [95% CI, 0.31–0.76]) and a 58% relative reduction in all-cause mortality (hazard ratio, 0.42 [95% CI, 0.24–0.74]) compared with drug therapy alone. Treatment-related strategy differences in the primary outcomes of CABANA were not seen in AF patients with moderate/severe MR.
CONCLUSIONS The CABANA trial results support catheter ablation as an effective treatment strategy for patients with no/mild MR, which achieves clinically important improvements in survival relative to drug therapy.
GW35-e1175
Yheng Yang
First Hospital of Dalian Medical University
OBJECTIVES Sick sinus syndrome (SSS) patients with pacemaker who experienced atrioventricular block that subsequently results in increased ventricular pacing ratio. The association between high ventricular pacing ratio or the pacing site and new onset ischemic stroke in SSS patients remains unclear.
METHODS Patients with SSS diagnosis and pacemaker implantation were continuously admitted to the First affiliated hospital of Dalian medical university between January 2011 and January 2022. Exclusion criteria included: 1) Atrial flutter (AFL)/atrial fibrillation (AF); 2) New onset atrial flutter/atrial fibrillation during the follow-up 3) Tachycardia-bradycardia syndrome; 4) Lost of follow-up or missing data. A high ventricular pacing ratio is defined as pacing ratio ≥40% in any programming report after implantation. The correlation between the high ventricular pacing ratio and incident ischemic stroke was analyzed using Cox multivariate regression analysis. Statistical analysis was completed using the R software package.
RESULTS Totally 679 cases were included in this study as the final sample. The average age was 66.97 ± 11.21 years and 42.71% were males. 17.3% (N = 118) were identified to the high ventricular pacing ratio group. After a mean of 4.02 years follow-up of, 63 cases (9.28%) experienced a new symptomatic ischemic stroke. Multivariate Cox regression indicated high ventricular pacing ratio significantly increased the risk of ischemic stroke in SSS patients (HR 1.72, 95% CI 1.01–2.95, P = 0.046). In the subgroup without previous stroke, the high ventricular pacing ratio remained significant (HR 2.24, 95% CI 1.14–4.42, P = 0.02). Association between different pacing site (105 in septal and 15 in apex) and incident stroke were further analyzed, Risk of ischemic stroke in septal pacing group was significantly higher than that of the control group (HR 2.47, 95% CI 1.45–4.22, P = 0.001). No significant difference were found in the incidence of new ischemic stroke between the apex pacing group and control group (P Log-rank = 0.62). Different pacing sites (septal or apex pacing) may not related to new onset ischemic stroke (P Log-rank = 0.051).
CONCLUSIONS Among patients with SSS implanted a dual chamber pacemaker in the absence of atrial fibrillation/flutter, high ventricular pacing ratio with right ventricular septal pacing is an independent risk factor for new onset ischemic stroke. There is no difference in incidence of ischemic stroke among SSS patients with septal pacing or apical pacing.
GW35-e1178
Rongqian Xu
First Affiliated Hospital of Dalian Medical University
OBJECTIVES QT prolongation was known as a marker associated to poor prognosis and common in left bundle branch block (LBBB) patients. Identification of QT prolongation in LBBB patients is confused. Several QT correction formulas for LBBB have been generated and its predictive value for prognosis in LBBB patients is unknown.
METHODS LBBB patients were continuously enrolled from 2011 to 2021. Patients with continuous atrial fibrillation/flutter, atrioventricular block, right ventricular pacing, atypical LBBB and malignant tumor were excluded. Electrocardiographic, biochemical tests and clinical characteristics were collected to analyze the effect on all-cause mortality. 5 QT correction formulas (Rautaharju, Yankelson, Wang, Bogossian and Colunga formula) were used to calculate the QTc under LBBB.
RESULTS After the median time of 5.1 ± 2.9-year-follow-up, 21.50% (106/493) patients died, with a mortality rate of 18.32% (74/404) among the cardiology and 35.96% (32/89) in non-cardiology. Potential clinical factors in multi-variable regression, age, left ventricular ejection fraction, diabetes and coronary heart disease were significantly associated to all cause death after adjustment. Cardiac resynchronization therapy treatment showed protective effect in LBBB patients in all 5 models. Further, increased corrected QTc by 5 formulas associated with all cause death in multi-variable regression model. Rautaharju formula has the best prediction value for all cause death (AUC = 0.812, cut-off = 416.59 ms).
CONCLUSIONS Mortality of patients with LBBB is relatively high and needs to be focused, especially in non-cardiology. Rautaharju formula shows the best efficacy to predict all cause death after QT correction for LBBB patients.
GW35-e1258
Fanchao Meng, Nian Liu
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Pulsed field ablation (PFA) is increasingly being used in clinical practice due to its unique selectivity and safety profile. However, some findings indicate that PFA procedures may lead to intravascular hemolysis in patients, which in severe cases, could result in acute kidney injury. This study aims to explore the effects of clinical ablation-level electrical pulses on red blood cells (RBCs) at the cellular level and to investigate the impact of different pulse parameters on RBCs.
METHODS Isolated atrial myocytes from C57BL/6 mice were subjected to pulse stimulation under conditions simulating good, moderate, and poor contact typically seen in clinical settings. This allowed for the determination of acute atrial myocyte death parameters. Using these parameters, C57BL/6 mouse RBCs located at the center of the electric field were stimulated. The morphology and quantity of the RBCs were analyzed, and the levels of Free Hemoglobin (Free Hb) in the RBCs suspension were measured. Different parameters were applied to stimulate the RBCs, and the levels of Free Hb in the suspension were measured to analyze the effects of the various parameters.
RESULTS As the distance between the electrode plane and the cell plane increased, the number of pulses required for acute myocardial cell death increased exponentially (1 mm – 5 groups, 3 mm – 20 groups, 5 mm – 60 groups). When RBCs were stimulated using the above pulse parameters, their morphology and number showed no significant changes under light microscopy (P > 0.05). Although there appeared to be an increase in cell size, it was not statistically significant (P = 0.0589). In the cases of good, moderate, and poor contact, the release of Free Hb in the suspension increased, and curve fitting suggested an exponential relationship between the number of pulses and Free Hb release (R2 = 0.8691). When the number of pulses was kept constant and the voltage (500V–1500V), duration (5 μs–15 μs), and frequency (2 kHz–10 kHz) were varied, changes in Free Hb release were observed. The frequency (2 kHz–10 kHz) had no significant impact on Free Hb release. Voltage was positively correlated with red blood cell hemolysis, while duration exhibited a threshold effect; when the electric field strength exceeded 1000 V/cm, duration was positively correlated with red blood cell hemolysis. Additionally, it was found that monophasic square wave pulses had a stronger effect on myocardial cell damage and hemoglobin release compared to biphasic square wave pulses.
CONCLUSIONS The application of clinical-level pulses can lead to red blood cell hemolysis. As the distance between the electrode plane and the cell plane increases, the number of pulses required to induce acute myocardial cell death increases exponentially, resulting in a corresponding exponential increase in the degree of red blood cell hemolysis. Therefore, in clinical practice, it is best to ensure close contact between the electrode and the tissue, while also minimizing the total number of pulses applied during a single procedure. Additionally, using biphasic square wave pulses, moderately reducing the voltage, and increasing the pulse frequency and duration can help reduce hemolysis.
GW35-e1274
Yijiang Zhao, Rong He
Beijing Tsinghua Changgung Hospital
OBJECTIVES Hypertension and atrial fibrillation (AF) are major global health concerns. Hypertension can activate RAAS, induce left ventricular hypertrophy (LVH), and remodel the atrium, potentially triggering AF by affecting heart muscle electrical activity. ARB can not only lower blood pressure, but also inhibit atrial electrical and structural remodeling, thereby reducing the occurrence of AF. Azilsartan is a new ARB that is superior in reducing blood pressure compared to other ARBs. It can reduce LV mass index in dialysis patients with hypertension. Whether Azilsartan can reduce the risk of AF in patients with hypertension and its mechanism remain unclear. Accordingly, the investigators designed this study (AZAF) intending to evaluate the effect of Azilsartan on the incidence of AF in hypertensive patients combined with LVH, and to explore the possible mechanism.
METHODS AZAF adopts a practical, randomized controlled study method. It will recruit 195 patients with hypertension and LVH (UCG shows left ventricular wall thickness is ≥11 mm, or the left ventricular mass index (LVMI) is >95 g/m2 in female, 115 g/m2 in male). The patients were randomly divided into an azilsartan group (109 cases) and a conventional treatment group (86 cases) and followed up for 12 months. The occurrence of AF events was determined by wearing a flexible intelligent ECG monitoring system every 3 months (14 days each time) and by 24-hour Holter monitoring every 6 months. The patient’s blood pressure was measured 3 days a week to determine its control status, and an echocardiogram was performed every 6 months to determine LVH and left atrial function. The primary outcome was the incidence of atrial fibrillation outcome events, and the secondary outcomes were blood pressure target achievement rate, the incidence of adverse cardiovascular events, and LVH.
RESULTS A total of 195 patients were included in this study, with an average age of 57 ± 15 years, an average blood pressure of 155 ± 10/88 ± 13 mmHg, and an average LV wall thickness of 11.29 ± 0.94 mm. There was no significant difference between the two groups (SBP P = 0.737, DBP P = 0.053, LV wall thickness P = 0.104). A total of 4 patients developed AF, 3 in the conventional group (3.49%) and 1 in the azilsartan group (0.92%), and the difference between the two groups was not significant (P = 0.209). The blood pressure control rate in the azilsartan group (64.22%) was significantly better than that in the conventional group (50.00%) (P = 0.046). After 1 year of follow-up, UCG showed that the average LV wall thickness in both groups did not change significantly, with the conventional group being 11.69 ± 1.10 mm (P = 0.352) and the azilsartan group being 10.85 ± 0.69 mm (P = 0.083). The incidence of adverse cardiovascular events in the azilsartan group (5.50%) was significantly lower than that in the conventional group (22.09%) (P < 0.001).
CONCLUSIONS Azilsartan has a good antihypertensive effect and provides a new solution for reducing adverse cardiovascular events and improving prognosis. However, whether it can improve the incidence of AF in patients with hypertension and LVH still requires further follow-up studies (ClinicalTrials.gov number, NCT05841654).
GW35-e1360
Yangxun Wu, Caiyi Lu
Barcelona Heart Center of the Fifth Affiliated Hospital of Guangzhou Medical University, Guangdong Province, P.R. China
OBJECTIVES This study aimed to assess the efficacy and safety of employing the simplified diaphragmatic equidistant line positioning method to guide left bundle branch region pacing operations for the first time.
METHODS A retrospective analysis was conducted on patients admitted to the Barcelona Heart Center at the Fifth Affiliated Hospital of Guangzhou Medical University from September 1st, 2022, to June 30th, 2024. Patients with indications for dual-chamber pacemaker implantation who underwent left bundle branch pacing treatment were included. Clinical baseline data, arrhythmia-related clinical diagnoses, electrocardiographic parameters, and pacemaker implantation surgery details were collected. The diaphragmatic equidistant line positioning method was employed for lead placement (In the 30° RAO view, the fluoroscopic image captures key anatomical landmarks. A vertical line is drawn from the midpoint of the diaphragm baseline to 1.5 cm above it, marking the pacing lead positioning point near the left bundle branch, which serves as a reference for lead placement), and complete the implantation of the 3830 pacemaker electrode. Intraoperative documentation include venous access technique, surgical duration, sheath positioning, fluoroscopy time for lead implantation, number and duration of pacemaker target localization, electrode parameters, peak time of paced QRS, immediate postoperative ECG parameters, recording of left bundle branch block (LBBB), surgical success rate and complications. Successful pacing was defined as single-pole pacing with a right bundle branch block morphology and a QRS wave peak time <90 ms; effective pacing rhythm was characterized by a QRS duration <120 ms; ineffective pacing was indicated by a QRS duration >120 ms or heart rate <60 bpm without evidence of pacing rhythm. Follow-up of patient survival and pacing complications was performed 3–6 months after discharge.
RESULTS A total of 44 patients were included, with an average age of 72.6 ± 10.7 years, 27 (61.4%) were male. BMI was 23.9 ± 2.3 kg/m2. Among the clinical diagnoses of cardiac arrhythmia, sinus bradycardia syndrome was observed in 21 patients (47.7%), atrial fibrillation with RR long interval in 12 patients (27.3%), and second-degree II or higher AV block or bundle branch block in 19 patients (43.2%). Among the coexisting cardiac comorbidities, valvular heart disease was found in 9 patients (20.5%), hypertension in 35 patients (79.5%), coronary heart disease in 32 patients (72.7%), diabetes in 15 patients (34.1%), and heart failure in 19 patients (43.2%). The preoperative QRS wave width was 116.32 ± 42.34 ms. All patients were implanted via subclavian vein access. No infections, pericardial effusion, pneumothorax, pacemaker threshold elevation, or electrode displacement occurred during the operation. Eleven patients (25.0%) had a positive LBBB electrogram, the targeting time for pacemaker implantation was 3.9 ± 0.8 s, the fluoroscopy time for sheath placement and lead implantation was 3.5 ± 0.8 min, and the operation time was 64.3 ± 6.3 min. The LBBB pacing parameters were: threshold of 0.72 ± 0.27 volts, sensing of 10.53 ± 4.02 mV, and impedance of 910.64 ± 258.96 ohms. The LBBB pacing effect was: a postoperative QRS wave width of 103.07 ± 18.18 ms, a peak time of the pacing QRS wave of 71.70 ± 15.11 ms, and an R wave amplitude of 0.49 ± 0.14 mV and width of 67.84 ± 6.02 ms in lead V1. All 44 patients (100%) completed follow-up, with a mean follow-up duration of 4.73 ± 0.76 months. All patients survived, and the electrode parameters remained stable without any complications.
CONCLUSIONS The utilization of diaphragmatic equidistant line positioning method for guiding left bundle branch region pacing demonstrated notable advantages including operational simplicity, precise localization accuracy, as well as safety and efficacy within the study’s cohort. Clinical prospects, benefits, and limitations require validation through large-scale controlled studies.
HEART FAILURE
GW35-e0033
Siling Peng1, Xiaojiao Huang1, Zhengqi Hu1, Yaoyuan Xiao1, Zhibin Liu1, Haoran Zhong1, Wenyu Zhu1, Sisi Liu1, Jianqiang Peng2, Yi Tang2, Hongwei Pan2
1Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha 410005
2Department of Cardiology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Normal University, Changsha 410005, China
OBJECTIVES The prognostic value of human epididymal protein-4 (HE4) in patients with acute heart failure (AHF) is not clear. This study aims to investigate the prognostic value of HE4 in patients with AHF.
METHODS Patients with AHF admitted to the cardiovascular Department of Hunan Provincial People’s Hospital from February 2019 to September 2022 were prospectively included. Serum HE4 levels were detected by chemiluminescence particle immunoassay. Patients were followed up and endpoint events were recorded.
RESULTS A total of 567 patients were included in the analysis, among them 246 patients experienced endpoint events. The median follow-up time was 671 days (503–1161). With the increase of NYHA classification, the level of HE4 increased gradually. Multivariate Cox regression analysis revealed that the log2 transformed HE4 [HR = 1.274 (95% CI: 1.097–1.478), P < 0.001], age [HR = 1.039 (95% CI: 1.026–1.052), P < 0.001], NYHA classification [HR = 1.284 (95% CI: 1.067–1.545), P < 0.05] and NT-proBNP [HR = 1.000 (95% CI: 1.000–1.000), P < 0.05] were independent predictors of endpoint events. The Receiver Operating Characteristic (ROC) Curve analysis found that the area under the ROC curve (AUC) of the clinical model increasing from 0.7750 to 0.7878 when the log2 transformed HE4 and the log2 transformed NT-proBNP was included in the clinical model. Kaplan-Meier survival curve showed that patients with high level of HE4 (HE4 ≥100.3 pmol/L) had a higher risk of endpoint events [log rank: χ2 = 76.41, HR = 3.107 (95% CI: 2.412–4.003), P < 0.001], compared with patients with low level of HE4 (HE4 <100.3 pmol/L). After adjusting for age and gender, the HR was 2.570 (95% CI: 1.936–3.414, P < 0.001).
CONCLUSIONS HE4 levels are associated with AHF severity and are independent predictors of heart failure re-hospitalization and cardiovascular death in patients with AHF.
GW35-e0055
Di Shen, Xintian Cai, Nanfang Li
Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES The association of the metabolic score for insulin resistance (METS-IR) with heart failure (HF) risk in hypertensive patients remains uncertain. This study aimed to examine the relationship of the METS-IR with incident HF in hypertensive patients.
METHODS A total of 12,066 patients, free of prior HF, were enrolled. Using multivariable Cox regression models, hazard ratios (HRs) and 95% confidence intervals (CIs) for HF were calculated.
RESULTS Four hundred sixty-four incident HF events were identified over a median follow-up of 5.00 years. Increases in METS-IR per SD were linked to a higher risk of HF (adjusted HR: 1.17; 95% CI: 1.07, 1.28). When METS-IR was evaluated as quartiles, compared with those in the first quartile, the adjusted HRs (95% CI) of incident HF in participants in the second, third, and fourth quartiles were 1.02 (0.77, 1.35), 1.26 (0.97, 1.64), and 1.43 (1.10, 1.85), respectively. Each 1 SD increase in METS-IR was significantly associated with a 17% increase in HF incidence after multivariate adjustment using Model 3. However, restricted cubic spline analysis showed no dose-response connection between METS-IR and HF risk (P for non-linearity = 0.113).
CONCLUSIONS In summary, the current investigation has discovered that elevated METS-IR is associated with an increased risk of HF in hypertensive patients. If more research supports our findings, METS-IR might be a helpful and practical indicator for the early identification of hypertensive patients at high risk of HF.
GW35-e0095
Jiachen Luo
Shanghai Tenth People’s Hospital
OBJECTIVES Improvement in left ventricular ejection fraction (impEF) often presents in contemporary acute myocardial infarction (AMI) patients. New-onset atrial fibrillation (NOAF) during AMI is an important predictor of subsequential heart failure (HF), while its impact on the trajectory of post-MI left ventricular ejection fraction (LVEF) and prognostic implication in patients with and without impEF remains undetermined. We aimed to investigate the prognostic impacts of NOAF in AMI patients with and without impEF.
METHODS Consecutive AMI patients without a prior history of AF between February 2014 and March 2018 with baseline LVEF ≤40% and had ≥1 LVEF measurement after baseline were included. ImpEF was defined as a baseline LVEF ≤40% and a re-evaluation showed both LVEF >40% and an absolute increase of LVEF ≥10%. Persistently reduced EF (prEF) was defined as the second measurement of LVEF either ≤40% or an absolute increase of LVEF <10%. The primary endpoint was a major adverse cardiac event (MACE) that was composed of cardiovascular death and HF hospitalization. Cox regression analysis and competing risk analysis were performed to assess the association of post-MI NOAF with MACE.
RESULTS Among 293 patients (mean age: 66.6 ± 11.3 years, 79.2% of males), 145 (49.5%) had impEF and 67 (22.9%) developed NOAF. Higher heart rate (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.73–0.97; P = 0.015), prior MI (OR: 0.25, 95% CI: 0.09–0.69; P = 0.008), and STEMI (OR: 0.40, 95% CI: 0.21–0.77; P = 0.006) were independent predictors of post-MI impEF. Within up to 5 years of follow-up, there were 22 (15.2%) and 53 (35.8%) MACE in patients with impEF and prEF, respectively. NOAF was an independent predictor of MACE in patients with impEF (hazard ratio [HR]: 7.34, 95% CI: 2.49–21.59; P < 0.001) but not in those with prEF (HR: 0.78, 95% CI: 0.39–1.55; P = 0.483) after multivariable adjustment. Similar results were obtained when accounting for the competing risk of all-cause death (subdistribution HR and 95% CIs in impEF and prEF were 6.47 [2.32–18.09] and 0.79 [0.39–1.61], respectively).
CONCLUSIONS The NOAF was associated with an increased risk of cardiovascular outcomes in AMI patients with impEF.
GW35-e0105
Jitao Ling1, Changchang Fang1, Ruoyun Fan1, Peng Yu1, Xiao Liu2
1Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
2Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
OBJECTIVES Inflammation and immune are linked to the prognosis of HF. This study aims to investigate the predictive value of systemic immune inflammation index (SII) in patients with chronic heart failure (HF).
METHODS We assessed the role of SII index (platelet × neutrophil/lymphocyte ratio) in two independent chronic HF cohorts (HF in Zigong [ZIG-HF] and medical information mart for intensive care HF [MIMIC-HF] database). Association between SII and all-cause death and admission were analyzed by Cox regression. The predictive ability of SII for outcomes evaluated by C-index, net reclassification improvement (NRI), and discrimination improvement (IDI) were tested in ZIG-HF cohort and validated in MIMIC-HF dataset.
RESULTS A total 1937 patients with HF in the ZIG-HF study were included for association analysis, with 808 of them (41.71%) being female. High SII index (≥700) were associated with mortality at 28 days (HR = 2.78, 95% CI: 1.19, 6.46), 3 months (HR = 2.56, 95% CI: 1.15, 5.69), and 6 months (HR = 2.26, 95% CI: 1.15, 5.69) compared to the low SII group (SII <700) after age, sex, pulse rate, potassium, hemoglobin, estimated glomerular filtration rate, moderate to severe chronic kidney disease, diabetes, chronic obstructed pulmonary disease, cerebrovascular disease, peripheral vascular disease, diastolic blood pressure, systolic blood pressure, low density lipoprotein cholesterol, β-blockers, ACEI/ARB, diuretics, BNP adjustments and inverse probability of treatment weighting analysis in patients with chronic HF. SII index had a moderate predictive ability for the mortality both in ZIG-HF (C-index: 0.654, 95% CI: 0.571–0.736) and MIMIC-HF cohort (C-index: 0.680, 95% CI: 0.632–0.725). Addition by SII index into the baseline model significantly improve the predictive performance of all-cause mortality (C-index 0.738, NRI 0.285) in ZIG-HF cohort. The predictive ability of SII addition was valeted in MIMIC-HF cohort (C-index 0.732, NRI 0.087).
CONCLUSIONS In patients with chronic HF, a high SII was associated with all-cause death. The inclusion of the SII index improved reclassification of in traditional predictor for death in patients with chronic HF.
GW35-e0115
Yi Wang
Sichuan Provincial People’s Hospital
OBJECTIVES Hypercontractile phenotype of the left ventricle (LV) is an actionable therapeutic target in patients with chronic coronary syndromes (CCS), but its clinical recognition remains elusive. The aim of this study is to assess the clinical variables associated with the hypercontractile phenotype of the LV, identified with supernormal values of an index of LV contractility such as LV force, also known as ventricular elastance.
METHODS In a prospective, observational, multicenter study, we recruited 5122 patients (age 65 ± 11.1 years, 2974 males, 58%) with CCS referred for resting transthoracic echocardiography with technically successful volumetric echocardiography in 17 accredited laboratories. We measured systolic blood pressure (SBP) with a cuff sphygmomanometer. We assessed semi-quantitatively wall motion score index (WMSI), and quantitatively LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), force (SBP/ESV), stroke volume (SV), arterial elastance (SBP/SV), ventricular-arterial coupling (VAC, as SV/ESV), and cardiac output (CO = SV*heart rate). Univariable and multivariable logistic regression analysis assessed independent factors associated with the highest force sextile. Odds ratios (ORs) with the corresponding 95% confidence interval (CI) were estimated.
RESULTS For all the studied patients, EF was 59 ± 11%. Force was 4.51 ± 2.11 mmHg/mL, with reference sextile = 3.50–4.26 mmHg/mL, lowest sextile (Group 1) <2.60 mmHg/mL and highest sextile (Group 6) >6.36 mmHg/mL. The correlation between the log of EF and the log of Force was significant with linear regression (r = 0.73, P < 0.001). Patients in the highest sextile of force showed lower values of WMSI, SV, EDV, and ESV, and higher values of arterial elastance and VAC. By multivariable logistic regression model, the highest sextile of force was associated with age >71 years (OR 4.35, 95% CI 3.06–6.18, P < 0.001), female sex (OR 4.48, 95% CI 3.62–5.54, P < 0.001), absence of beta-blocker therapy (OR 1.56, 95% CI 1.27–1.91), rest SBP >159 mmHg (OR 6.86, 95% CI 5.03–9.35, P < 0.001), high heart rate (OR 1.03, 95% CI 1.02–1.04, P < 0.001), absence of prior MI (OR 1.31, 95% CI 1–1.72, P = 0.049), and higher LV EF at rest (OR 1.24, 95% CI 1.22–1.26, P < 0.001).
CONCLUSIONS A hypercontractile phenotype of the LV with high force is associated with a small heart, reduced SV, and higher arterial elastance. It was clinically associated with advanced age, female sex, history of hypertension, absence of beta-blocker therapy, and high resting SBP.
GW35-e0139
Leyi Zhu, Jian He, Jing Xu, Wenjing Yang, Shihua Zhao, Minjie Lu
Department of Magnetic Resonance Imaging, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Left atrial (LA) booster function plays a critical role in the pathophysiological progression of heart failure with preserved ejection fraction (HFpEF). However, previous studies yielded inconsistent findings regarding the associations between LA booster function and adverse outcomes in patients with HFpEF. Cardiac magnetic resonance feature-tracking (CMR-FT) has shown the potential to detect subtle atrial dysfunction in multiple cardiovascular diseases; therefore, it might gain novel insights into the relationship between LA pathophysiology and clinical outcomes. The purpose of this study is to evaluate the prognostic value of LA strain parameters derived from CMR-FT and a novel index – LA contractile index in patients with HFpEF.
METHODS This retrospective study included 883 participants, comprising 803 consecutive patients with HFpEF who underwent CMR from January 2010 to December 2018 (age 54.8 ± 11.9 years; 225 females, 28.0%), and 80 healthy controls (age 52.9 ± 10.1 years; 23 females, 28.8%). Left ventricular (LV) and LA strain parameters were obtained using FT strain analysis. LA contractile index was calculated as the percentage of LA booster strain relative to LA reservoir strain. The primary endpoints were cardiovascular death or heart failure hospitalization. Cox proportional hazard regression models were used to explore the associations between variables and clinical outcomes. Due to the nonlinear relationship between LA contractile index and adverse outcomes, restricted cubic spline analysis was performed to categorize this new continuous variable, using hazard ratio (HR) = 1 as the cutoff value. The prognostic value was evaluated using Chi-square statistics and receiver operating characteristic analysis.
RESULTS Patients with HFpEF had significantly higher LA contractile indices than healthy controls (53.7 ± 11.6% vs. 46.4 ± 8.0%; P < 0.001). LA contractile index showed a moderate association with age (r = 0.454; P < 0.001). Over a median follow-up of 7.3 years, 309 (38.5%) patients reached the primary endpoints. LA contractile index exhibited a J-shaped relationship with adverse outcomes, leading to the categorization of the HFpEF cohort into normal (33.9–51.7%) and abnormal LA contractile index group (<33.9% or >51.7%). In multivariable Cox regression analysis, both impaired LA conduit strain (<14.9%) (HRadj: 1.62 [95% CI: 1.26–2.08]; P < 0.001) and abnormal LA contractile index (HRadj: 3.37 [95% CI: 2.52–4.51]; P < 0.001) were independently associated with the primary endpoints. Improvements in outcome prediction were observed when impaired LA conduit strain (chi-square test = 80.84) and abnormal LA contractile index (chi-square test = 140.93) were respectively added to the baseline model (chi-square test = 60.18; both P < 0.001), which already included clinical and conventional imaging variables. The receiver operating characteristic analysis indicated that the model incorporating LA contractile index had the highest prognostic accuracy compared to other models with an area under the curve of 0.754 (all P < 0.001).
CONCLUSIONS LA conduit strain and LA contractile index based on CMR-FT were independent predictors of adverse outcomes in patients with HFpEF, and the incremental prognostic value of LA contractile index was more pronounced than that of LA conduit strain.
GW35-e0148
Mengjie Lei, Jingyao Wang, Xiao Wang, Xue Sun, Cairong Li, Yanli Yang, Yachao Li, Zhigang Zhao, Zengming Xue
Langfang People’s Hospital
OBJECTIVES To investigate the impact of guideline-directed medical therapy (GDMT) during hospitalization on the prognosis of heart failure patients with a preserved ejection fraction after acute myocardial infarction.
METHODS From May 2017 to September 2022, 527 heart failure patients at a single medical center who had preserved ejection fraction after acute myocardial infarction were retrospectively investigated and analyzed. Based on whether GDMT during hospitalization for preventing ventricular remodeling was used in patients undergoing percutaneous coronary intervention, the patients were divided into two groups: the GDMT group (n = 379) and the non-GDMT group (n = 148), with a follow-up period of 12 months after percutaneous coronary intervention. The primary endpoint was the composite endpoint of all-cause death and all-cause readmission during follow-up, while the secondary endpoints were the composite endpoints of cardiac death and cardiac readmission, all-cause death, cardiac death, all-cause readmission, and cardiac readmission.
RESULTS During the follow-up period, the incidence of all-cause mortality and all-cause readmission composite events (7.9% vs. 18.9%, P < 0.001), cardiac mortality and cardiac readmission composite events (5.5% vs. 15.5%, P = 0.002), all-cause readmission events (7.1% vs. 18.9%, P < 0.001), and cardiac readmission events (5.0% vs. 13.5%, P = 0.001) in the GDMT group were lower than those in the non–GDMT group. Cox regression analysis revealed that the incidence of all-cause mortality and all-cause readmission composite events, cardiac death and cardiac readmission composite events, all-cause readmission events, and cardiac readmission events in patients treated with GDMT during hospitalization were 0.266 times (HR 0.266; 95% CI 0.146–0.487; P < 0.001), 0.282 times (HR 0.282; 95% CI 0.137–0.581; P = 0.001), 0.251 times (HR 0.251; 95% CI 0.136–0.464; P < 0.001) and 0.262 times (HR 0.262; 95% CI 0.125–0.551; P < 0.001), respectively, compared to patients treated without GDMT. The incidence of cardiac death and cardiac readmission composite events and cardiac readmission in patients with a history of atrial fibrillation was 4.644 times greater (HR 4.644; 95% CI 1.398–15.426; P = 0.012) and 4.787 times greater (HR 4.787; 95% CI 1.438–15.934; P = 0.011), respectively compared to patients without a history of atrial fibrillation.
CONCLUSIONS For heart failure patients who undergo percutaneous coronary intervention with a preserved ejection fraction after acute myocardial infarction, the use of GDMT during hospitalization in order to prevent ventricular remodeling reduces the incidence of all-cause death and all-cause readmission composite endpoints, cardiac death and cardiac readmission composite endpoints, and all-cause readmission and cardiac readmission. For such patients, it is important to actively initiate GDMT as early as possible.
GW35-e0154
Rui Li, Feng Liu, Feng Lei, Shunlin Guo
The First Hospital of Lanzhou University
OBJECTIVES The noninvasive diagnosis of heart failure with preserved ejection fraction (HFpEF) continues to present significant clinical challenges. This investigation was designed to elucidate the clinical manifestations and to analyze cardiovascular magnetic resonance (CMR) derived myocardial strain metrics and tissue characteristics in a cohort exhibiting the HFpEF-Hypertension phenotype.
METHODS This retrospective analysis incorporated a sequentially enrolled cohort comprising 128 patients diagnosed with hypertensive heart failure with preserved ejection fraction (HFpEF-HTN), 78 individuals with hypertensive heart disease (HHD), 89 subjects with hypertension (HTN), and 60 normotensive healthy controls, selected based on predefined clinical criteria. All participants underwent laboratory examinations and 3.0 T CMR. The study involved comparisons of clinical features and CMR-derived structural and functional parameters among the different groups. Receiver operating characteristic (ROC) analysis was utilized to identify HFpEF-HTN. Spearman correlation was employed to analyze the relationship between myocardial strain parameters and left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) parameters.
RESULTS Patients diagnosed with (HFpEF-HTN) were characterized by an older demographic profile, higher prevalence of smoking history, elevated systolic and diastolic blood pressures, increased levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and more advanced New York Heart Association (NYHA) functional class when compared to other studied groups. In terms of myocardial deformation, individuals with HFpEF-HTN exhibited pronounced impairments in both left ventricular (LV) and right ventricular (RV) function, as evidenced by significantly reduced longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) across LV and RV, relative to those with HTN, HHD and the control cohort (all P < 0.001). Additionally, LV global circumferential strain (LVGCS) emerged as a superior diagnostic indicator, demonstrating greater diagnostic accuracy (area under the curve, AUC = 0.85, P < 0.001) in differentiating HFpEF-HTN patients from those with HHD, compared to extracellular volume (ECV). Moreover, a robust correlation was observed between myocardial strain metrics and ventricular ejection fractions.
CONCLUSIONS The myocardial strain, T1 mapping, and ECV parameters hold significant potential in the diagnosis of HFpEF-HTN.
GW35-e0155
Xiao Wang, MengJie Lei, Jingyao Wang, Xue Sun, Cairong Li, Yanli Yang, Yachao Li, Zhigang Zhao, Zengming Xue
People’s Hospital of Langfang City
OBJECTIVES To investigate the impact of guideline-directed medical therapy (GDMT) during hospitalization on the prognosis of heart failure patients after acute anterior myocardial infarction.
METHODS From May 2017 to September 2022, 317 heart failure patients treated at a single center after acute anterior myocardial infarction were retrospectively investigated and analyzed based on whether guideline-directed medical therapy during hospitalization for preventing ventricular remodeling (using at least one type of RAAS inhibitor, β receptor blocker, MRA, or SGLT2 inhibitor) was used. Patients who underwent percutaneous coronary intervention (PCI) were divided into two groups: the GDMT group (n = 236) and the non-GDMT group (n = 81), with a follow-up period of 12 months after percutaneous coronary intervention. The primary endpoint was the composite endpoint of all-cause death and all-cause readmission during follow-up, while the secondary endpoints were the composite endpoints of cardiac death and cardiac readmission, all-cause death, cardiac death, all-cause readmission, and cardiac readmission.
RESULTS During the follow-up period, the incidence of all-cause mortality and all-cause readmission composite events (10.2% vs. 19.8%, P = 0.025), cardiac mortality and cardiac readmission composite events (7.2% vs. 14.8%, P = 0.013), all-cause readmission events (9.3% vs. 19.8%, P = 0.013), and cardiac readmission events (6.4% vs. 14.8%, P = 0.019) in the GDMT group were lower than those in the non-GDMT group. Cox regression analysis revealed that the incidence of all-cause mortality and all-cause readmission composite endpoint events; cardiac mortality and cardiac readmission composite endpoint events; all-cause readmission events; and cardiac readmission events in patients in the GDMT group were 0.397 times (HR 0.397; 95% CI 0.207–0.759; P = 0.005), 0.348 times (HR 0.348; 95% CI 0.162–0.746; P = 0.007), 0.377 times (HR 0.377; 95% CI 0.195–0.730; P = 0.004) and 0.320 times (HR 0.320; 95% CI 0.146–0.700; P = 0.004), respectively, than that in patients in the non-GDMT group. Additionally, the left ventricular ejection fraction was an independent predictor of all-cause mortality and all-cause readmission composite events (HR 0.944; 95% CI 0.917–0.973; P < 0.001), cardiac mortality and cardiac readmission composite events (HR 0.933; 95% CI 0.904–0.962; P < 0.001), all-cause readmission (HR 0.952; 95% CI 0.921–0.983; P = 0.003), and cardiac readmission (HR 0.940; 95% CI 0.908–0.973; P < 0.001).
CONCLUSIONS For heart failure patients who undergo PCI with acute anterior myocardial infarction, the use of GDMT during hospitalization for preventing ventricular remodeling reduces the incidence of readmission. For such patients, it is important to actively initiate guideline-directed medical therapy as early as possible.
GW35-e0166
Yanhong Dong1, Nicole Chen1, Lijun Zuo2
1National University of Singapore
2Department of Neurology, Beijing Tiantan Hospital
OBJECTIVES Vascular diseases, such as stroke and heart failure (HF), are associated with cognitive decline. Vascular cognitive impairment (CI) is commonly found in patients who had a stroke and with HF, ranging from mild CI to dementia. Early detection of CI is crucial for effective management and rehabilitation. This study aimed to develop the VasCog Screen test, a screening tool to detect CI in patients who had a stroke and with HF.
METHODS Four hundred and twenty-seven patients who had a stroke and with HF were assessed using cognitive measures including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a formal neuropsychological battery. The short-MoCA was derived and combined with Symbol Digit Modalities Test (SDMT) to create the VasCog Screen. The discriminatory ability of different tests for CI was compared, establishing optimal cut-off points. Variants of short-MoCA including the SDMT were also evaluated.
RESULTS Similar prevalence rates of CI were found in stroke and HF cohorts. The most prevalent neuropsychological impairment was visuomotor speed, followed by visual memory and visuoconstruction. More than half of the patients were found to have CI. The VasCog Screen outperformed MMSE, MoCA and short-MoCA in detecting CI. The addition of SDMT to variants of the short-MoCA increased diagnostic accuracy.
CONCLUSIONS The VasCog Screen test offers a cognitive screening tool, which is sensitive to cognitive deficits characteristically found in patients who had a stroke and with HF. It was found to have good sensitivity, specificity and classification accuracy. It is easy to administer in busy clinics, enabling early detection of CI and facilitating appropriate interventions.
GW35-e0191
Yihang Wu1,2, Yuhui Zhang2, Jian Zhang2
1Interventional Center of Valvular Heart Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
2Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
OBJECTIVES Several hemodynamic parameters related to right heart (RH) function have demonstrated a strong impact on the survival of heart failure with preserved ejection fraction (HFpEF) patients. However, no study has compared all these parameters, and the most powerful hemodynamic parameters for risk stratification in HFpEF remain unknown.
METHODS We prospectively studied 132 HFpEF patients with pulmonary arterial wedge pressure (PAWP) ≥15 mmHg. Eight right heart catheterization-derived hemodynamic parameters (right atrial pressure [RAP], RAP/PAWP, pulmonary artery pulsatility index, right ventricular stroke work, pulmonary effective arterial elastance [Ea], pulmonary arterial proportional pulse pressure, pulmonary vascular resistance, and pulmonary arterial compliance) and two echocardiographic indexes (tricuspid annular plane systolic excursion [TAPSE] and TAPSE/pulmonary artery systolic pressure [PASP]), were analyzed for prognostic value. The primary outcome was event-free survival.
RESULTS Sixty-four patients reached the primary endpoint during a median follow-up of 353 (166–603) days. By multivariate adjustment, RAP (hazard ratio [HR] 1.052, P = 0.013), Ea (HR 1.685, P = 0.045), and TAPSE/PASP (HR 0.156, P = 0.025) remained significantly associated with primary outcomes. Patients with high-RAP/high-Ea had much lower rates of event-free survival than those with low-RAP/low-Ea (P < 0.001), high-RAP/low-Ea (P = 0.016), and low-RAP/high-Ea (P < 0.001). Moreover, patients with high-RAP/high-Ea were more likely to show right ventricular-pulmonary arterial uncoupling defined as TAPSE/PASP <0.36 mm/mmHg (OR 28.846, P < 0.001).
CONCLUSIONS Several hemodynamic parameters of RH function were identified, of which RAP and Ea were the strongest predictors of poor outcomes. Coupling RAP with Ea could be a comprehensive approach to assessing RH function and identifying HFpEF patients at risk for adverse outcomes.
GW35-e0245
Sihan Jia1, Yanjie Lian2, Sinai Li3, Hongxu Liu1, Juju Shang1
1Beijing Hospital of Traditional Chinese Medicine
2Capital Medical University
3Beijing Institute of Traditional Chinese Medicine
OBJECTIVES This study aimed to conduct a visual analysis of the relevant literature on mitochondrial dynamics in heart failure, explore the research progress, frontier topics, and development trends in this field, and provide references for the study concerning mitochondrial dynamics in the prevention and treatment of heart failure.
METHODS The Web of Science was searched from inception to October 1, 2023 to identify relevant English literature on mitochondrial dynamics in heart failure. Bibliometric methods were utilized to statistically analyze the eligible literature, and CiteSpace 6.2.R5 software was employed to visualize data such as countries of publication, institutions, authors, and keywords.
RESULTS A total of 1755 SCI articles were included. The global publication volume showed an increasing trend year by year, with China and the United States having the most publications, and the United States displaying the highest centrality in publications. As revealed by keyword and citation analyses, the research hotspots and frontiers in this field mainly included the pathogenesis of heart failure, mitochondrial dynamics markers, mitochondrial quality control, and potential therapeutic targets for heart failure.
CONCLUSIONS Research on mitochondrial dynamics in heart failure is under vigorous development. It is a development trend in this research field to explore the differential gene expression and molecular mechanisms of targeted treatment in the mitochondrial dynamics in heart failure, which will contribute to the formulation of new strategies for the prevention and treatment of heart failure.
GW35-e0410
Qiongling Wang, Ruijie Li
Wang Qiongling
OBJECTIVES Heart failure is the final stage of various cardiovascular diseases, and there are about 64.3 million patients with heart failure worldwide. There are about 13.7 million heart failure patients in China; “Vulnerable period” refers to the period of high incidence of death and readmission in patients with heart failure within 2–3 months after discharge. China reported that the mortality and readmission rates in vulnerable period within 1 month after discharge of heart failure were 15% and 30%, respectively. Previous studies have confirmed that EMAT has an excellent correlation with left ventricular ejection fraction, and is also correlated with BNP, HR, and body weight. In out-of-hospital patients with heart failure, wearing wearable non-invasive echocardiogram devices to collect echocardiogram data every day and combined with laboratory examination to analyze whether it can early predict the appearance of decompensation of heart failure, find the threshold value, and reduce the readmitted hospital admission to heart failure.
METHODS For patients with heart failure who met the inclusion criteria, we improved cardiac sound-ECG monitoring data, blood test (BNP, electrolyte, blood routine, liver and kidney function), heart color ultrasound (Simpson determination of heart function), heart rate, body weight and other indicators on the day of discharge. Patients with standardized heart failure treatment should wear wearable devices and turn on Bluetooth every day to upload heart-sound and ECG monitoring data to the data center for storage through mobile wechat mini program within 1 month after discharge, and combined with telephone follow-up (telephone contact to inquire about patients’ condition according to the range of 15% and 30% increase and fluctuation of EMAT%) and record weight and symptom scale every day. After discharge monitoring for 1 month, return visit to improve blood drawing and heart color ultrasound and other related examinations.
RESULTS SPSS software was used for correlation analysis of the data, and it was found from the figure that EMAT and EMAT% in the ECG data were correlated with blood pressure and heart rate, EMAT% was positively correlated with heart rate and body weight, and EMAT was negatively correlated with heart rate and body weight. Combined with the results of correlation coefficient R2, Compared with EMAT, EMAT% has a stronger correlation with heart rate and body weight, and the changes of heart rate and body weight are often the early changes in the decompensation stage of heart failure, so EMAT% can better predict the occurrence of heart failure decompensation and reduce the readmission of heart failure. SPSS software analysis, in the process of ECG monitoring, according to the telephone follow-up, we found that when the fluctuation trend of EMAT% was large, the proportion of events increased, indicating that the change of EMAT% independently predicted the occurrence of events.
CONCLUSIONS The monitoring parameters EMAT% and EMAT are correlated with heart rate and body weight. Combined with the results of correlation coefficient R2, EMAT% can better predict the occurrence of decompensation of heart failure after discharge, and greatly reduce the readmitted heart failure. EMAT% of ECG monitoring parameters independently predicted the occurrence of events.
GW35-e0436
Teruhiko Imamura, Koichiro Kinugawa
Second Department of Internal Medicine, University of Toyama
OBJECTIVES Vericiguat, a soluble guanylate cyclase stimulator known for augmenting cyclic guanosine monophosphate production, has garnered substantial clinical attention in patients with systolic heart failure. Despite its proven efficacy, discerning the specific subset of individuals who can enjoy clinical advantages from vericiguat therapy in contemporary real-world clinical practice, particularly among the individuals undergoing “quadruple medical therapy” comprising a beta-blocker, angiotensin receptor neprilysin inhibitor, mineralocorticoid receptor antagonist, and sodium-glucose co-transporter 2 inhibitor, remains an unresolved query. This study encompassed patients maintaining a three-month vericiguat therapy alongside complete quadruple medical therapy in contemporary real-world clinical practice.
METHODS Baseline characteristics associated with the primary outcome – defined as a reduction in serum NT pro-B-type natriuretic peptide (BNP) levels over the three-month therapeutic duration – were scrutinized.
RESULTS A cohort of 24 patients (median age: 66 years; 20 males) were included. All participants diligently adhered to the three-month vericiguat therapy in conjunction with the quadruple medical regimen. A higher baseline systolic blood pressure emerged as an independent factor linked to the primary outcome, yielding an adjusted odds ratio of 1.31 (95% confidence interval: 1.03–1.65, P = 0.026) at a threshold of 105 mmHg. This threshold notably stratified the trajectories of serum NT pro-BNP levels during the three-month vericiguat therapy.
CONCLUSIONS Preservation of baseline systolic blood pressure emerges as a pivotal determinant for reaping the clinical benefits from mid-term vericiguat therapy among patients with systolic heart failure receiving quadruple medical therapy.
GW35-e0462
Chendie YANG, Xiaoqun WANG
Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine
OBJECTIVES Patients with type 2 diabetes mellitus (T2DM) are predisposed to poor cardiovascular outcomes after ST-segment elevation myocardial infarction (STEMI). Left ventricular adverse remodeling (LVAR) triggered upon myocardial infarction is recognized as the predominant pathological process in the development of heart failure. In the present study, we sought to investigate whether visit-to-visit fasting plasma glucose (FPG) variability is a potential predictor of LVAR in T2DM patients after STEMI.
METHODS From January 2014 to December 2018 in Ruijin Hospital, T2DM patients with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for ~12 months. The changes in left ventricular geometric and functional parameters between baseline and 12-month follow-up were assessed by echocardiography. The incidence of LVAR, defined as 20% increase in indexed left ventricular end-diastolic volume (LVEDV), and its relationship with visit-to-visit FPG variability were analyzed. Multivariate regression models were constructed to test the predictive value of FPG variability for post-infarction LVAR.
RESULTS A total of 437 patients with type 2 diabetes and STEMI were included in the final analysis. During a mean follow-up of 12.4 ± 1.1 months, the incidence of LVAR was 20.6% and mean enlargement of indexed LVEDV was 3.31 ± 14.4 mL/m2, which was significantly increased in patients with higher coefficient variance (CV) of FPG (P = 0.002) irrespective of baseline glycemic levels. In multivariate analysis, FPG variability was independently associated with incidence of post-infarction LVAR after adjustment for traditional risk factors, baseline HbA1c as well as mean FPG during follow-up (OR: 3.021 [95% CI: 1.081~8.764] for highest vs. lowest tertile of CV of FPG). Assessing FPG variability by two measures, including standard deviation (SD) and variability independent of the mean (VIM), yielded similar findings.
CONCLUSIONS This study suggests that visit-to-visit FPG variability is an independent predictor of incidence of LVAR in T2DM patients with STEMI.
GW35-e0463
Chendie YANG, Xiaoqun WANG
Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine
OBJECTIVES Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (EF, HFrEF) have experienced partial or complete recovery of EF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in patients with type 2 diabetes mellitus (T2DM).
METHODS A total of 385 T2DM patients with HFrEF were consecutively enrolled. Follow-up echocardiogram was performed after 6 to 12 months, which classified patients into HFrecEF or persistent HFrEF. Clinical outcomes of cardiovascular (CV) death and HF rehospitalization were analyzed during a mean of 3.3 years follow-up.
RESULTS T2DM patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.4% [IQR 5.8%~7.1%] vs. 6.8% [IQR 6.1%~7.8%], P = 0.001), especially in HF of ischemic etiology. After multivariate adjustment, every 1% increase in HbA1c conferred a 21.3% (OR: 0.787 [95% CI 0.658~0.933]) lower likelihood of HFrecEF. Compared to patients with good glycemic control (HbA1c ≤6%), those with poor glycemic control (HbA1c >8%) had higher risk of CV death or HF rehospitalization (HR: 2.778 [95% CI 1.470~5.251]). T2DM Patients with HFrecEF exhibited significantly better clinical outcomes than those with persistent HFrEF.
CONCLUSIONS This study demonstrates that T2DM patients with uncontrolled HbA1c levels were associated with compromised development of HFrecEF and worse clinical outcomes.
GW35-e0532
Zhijun Lei, Wenhui Peng
Shanghai Tenth People’s Hospital
OBJECTIVES Both acute kidney injury (AKI) and left ventricular ejection fraction (LVEF) recovery are associated with prognosis in patients with acute myocardial infarction (AMI), while the link between AKI and LVEF recovery is still unknown. Hence, we aimed to explore the association between AKI and LVEF recovery in STEMI patients with depressed LVEF.
METHODS This was a single-center, observational, and retrospective study. We included STEMI patients presenting with depressed LVEF (<50%) after undergoing primary percutaneous coronary intervention (PCI). AKI was defined as an increase in serum creatinine (Scr) by ≥0.3 mg/dL within the first 48 h or a ≥50% increase in Scr from baseline within 7 days. LVEF recovery was defined as a follow-up LVEF ≥50% over 3–12 months. The univariate and multivariate logistic regression analyses were used to assess the association between AKI and LVEF recovery. The long-term impact of LVEF recovery on all-cause mortality and heart failure (HF) hospitalization was assessed by Kaplan-Meier analysis and Cox proportional hazards models.
RESULTS A total of 436 individuals were enrolled, of whom 81 (18.6%) developed AKI during their stay in hospitalization, and 194 (45.5%) experienced LVEF recovery over a median follow-up period of 6.1 months. The incidence rate of LVEF recovery in patients with AKI was lower than that in patients with non-AKI (22.2% vs. 49.6%, P < 0.001). After full adjustment, AKI was independently associated with LVEF non-recovery (adjusted OR 2.21, 95% CI: 1.09–4.62, P = 0.031). Besides, patients with LVEF non-recovery had a higher risk of all-cause mortality (HR 3.15, 95% CI: 1.19–8.38, P = 0.021) and HF rehospitalization (HR 7.33, 95% CI: 3.52–15.27, P < 0.001) compared with patients with LVEF recovery after adjustment of GRACE risk score.
CONCLUSIONS Our study demonstrated that AKI was independently associated with LVEF non-recovery in STEMI patients with depressed LVEF. In addition, LVEF non-recovery identified patients with poor prognosis.
GW35-e0558
Yuxin Hou1, Qing Cao2, Tao Wu1,3,4, Jiaqi Li1, Zi Zeng2, Gang Lv2, Jingsheng Lin2
1School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
2Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
3Centre for Collaborative Research, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
4China Hospital Development Institute of Medical Intelligence Development, Shanghai Jiao Tong University School, Shanghai 200025, China
OBJECTIVES Early detection of reduced left ventricular ejection fraction (LVEF) is crucial in effectively managing the progression and decreasing death rates of heart failure. In this research, we developed an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm to identify patients with low LVEF and provide precise estimations of LVEF.
METHODS This study utilized a dataset consisting of 136,775 electrocardiogram (ECG) data collected from 136,775 patients at a tertiary hospital in Shanghai throughout the period from 2013 to 2021. The dataset was divided into training, validation, and test sets at a ratio of 6:1:3, respectively. The ECG data were used as input, and the algorithm produces a probability (ranging from 0 to 1) of the patient having a low ejection fraction or a continuous value representing the estimated LVEF. Furthermore, this study performed a 5-year follow-up trial to evaluate the likelihood of developing a low ejection fraction in a cohort that initially had a normal LVEF.
RESULTS The average age of patients in the test set was 56.4 ± 15.7 years, with 48.9% of patients being female. The mean LVEF was 66.4 ± 6.9%. The algorithm’s performance on the test set yielded an area under the curve (AUC) of 0.965 for detecting LVEF ≤50%. The algorithm had a sensitivity of 88.8%, specificity of 92.9%, positive predictive value of 25.9%, negative predictive value of 99.7% and accuracy of 92.8%. For LVEF regression, the method showed a mean absolute error (MAE) of 5.19% (95% CI: 5.11%–5.26%) for the validation set and 5.28% (95% CI: 5.23%–5.33%) for the testing set. In the follow-up analysis, patients who got false-positive results had a significantly greater likelihood of developing a low ejection fraction compared to patients who received true-negative results (26.2% vs. 2.0%, P < 0.0001).
CONCLUSIONS The AI-ECG algorithm has the ability to precisely detect low ejection fraction in patients and estimate the value of LVEF. It is expected to operate as an efficient, timely, and cost-effective screening tool for early heart failure.
GW35-e0593
Beizheng Xu1, Xu Yao Han1, Nan Zhang1, Gary Tse1,2, Guangping Li1, Tong Liu1
1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
2School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China
OBJECTIVES Sarcopenia is recognized as being closely linked to heart failure. The SARC-F questionnaire serves as an effective screening tool for sarcopenia. We aimed to determine the relationship between SARC-F and heart failure (HF).
METHODS This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) in 1999–2020. HF was defined using a standardized medical condition questionnaire administered through self-reported and proxy-reported personal interviews. The SARC-F questionnaire, a straightforward tool for detecting sarcopenia, encompasses five items: strength, assistance with walking, rising from a chair, stair climbing, and falls. A SARC-F score of ≥4 marks the threshold for identifying those at risk of sarcopenia. Weighted logistic regression and restricted cubic splines (RCS) were applied to assess the association between the SARC-F and HF. Stratified and interaction analyses were performed to explore the variability of correlations across subgroups.
RESULTS Representing 9.71 million noninstitutionalized U.S. civilians, 3853 individuals (mean age: 70.73 ± 0.21 years; male: 44.52%) were analyzed, of whom 549 (12.93%) had SARC-F ≥4. After controlling for potential confounders, a statistically significant positive nonlinear dose-response relationship emerged between SARC-F and HF (odds ratio per 1-point increase: 19.57; 95% CI: 11.84–32.33, P < 0.0001). Participants with SARC-F ≥4 showed a multivariable-adjusted odds ratio (OR) for HF of 4.26 (95% CI 3.11–5.84) compared to those with SARC-F <4. An interaction between SARC-F score and gender was observed (P = 0.011), with the multivariable-adjusted OR for CHF in female participants with SARC-F ≥4 being 8.66 (95% CI 5.20–14.43).
CONCLUSIONS These findings imply that a higher SARC-F score may correlate with a greater incidence of HF. Assessing SARC-F is instrumental not only in identifying and reducing sarcopenia but also in evaluating heart failure.
GW35-e0614
Ziying Huang, Yafeng Zhou
The Fourth Affiliated Hospital of Soochow University
OBJECTIVES Heart failure with preserved ejection fraction (HFpEF) is associated with disrupted intestinal epithelial function, resulting from intestinal congestion. Intestinal congestion changes the morphology and permeability of the intestinal wall, and it becomes easy for the gut microbiota to change and transfer. Intervention on gut microbiota may become a new target for HFpEF treatment. However, the characteristics of gut microbiota in patients with HFpEF remain unknown. This preliminary report aims to detect the structure of gut microbiota in HFpEF patients so as to explore their characteristic changes, thereby providing a theoretical basis for future research.
METHODS This research recruited 30 patients diagnosed with HFpEF and 30 healthy individuals. Stool specimens of research subjects were collected separately, and the microarray analyses of gut microbiota were conducted by Illumina high-throughput DNA sequencing. The differences in gut microbiota composition, alpha diversity, and beta diversity between the two groups were finally obtained.
RESULTS The composition of gut microbiota was significantly different between the two groups. At the phylum classification level, the abundance of Synergistetes tended to be higher in the HFpEF group (P = 0.012). At genus classification level, the abundance of Butyricicoccus (P < 0.001), Sutterella (P = 0.004), Lachnospira (P = 0.003), and Ruminiclostridium (P = 0.009) in the HFpEF group were lower, while the abundance of Enterococcus (P < 0.001) and Lactobacillus (P = 0.005) were higher. According to the Chao index of alpha diversity analysis, HFpEF patients showed a nominally significant lower species richness when compared with controls (P = 0.046). However, there was no statistical difference in the Shannon index (P = 0.159) and Simpson index (P = 0.495), indicating that there was no difference in species diversity between the two groups. Beta diversity analysis revealed a highly significant separation of HFpEF patients and controls.
CONCLUSIONS An imbalance in the gut microbiota of HFpEF patients was observed. Patients with HFpEF have an increased abundance of microbiota associated with inflammation and a decreased abundance of microbiota associated with anti-inflammatory effects in the gut environment. In line with that, the species richness of gut microbiota in HFpEF patients tended to be lower.
GW35-e0616
Ying Xie, Yu Geng, Yintang Wang, Siyuan Li, Lei Bi, Ping Zhang
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University
OBJECTIVES The patients with return of spontaneous circulation post cardiac arrest have a mortality rate of up to 30–50%. Hemodynamic support is a key component of out-of-hospital cardiac arrest (OHCA) management and is essential to ensure survival. The meta-analysis was performed to investigate the optimizing blood pressure targets in survivors of OHCA.
METHODS Studies were searched in electronic databases from January 1, 2015 to January 13, 2023. Results were pooled using random effects model and fixed effects model and are presented as odd ratios (ORs) with 95% confidence intervals (CI). The primary outcome was all-cause death and the secondary outcome were severe bleeding, arrhythmia, renal replacement therapy, cerebral performance category (CPC) score ≥3, modified Rankin Scale (mRS) score ≥4 and the level of serum norepinephrine, neuron-specific enolase (NSE), troponin T. This study was registered with INPLASY 2022120065.
RESULTS Four studies involving 1327 participants were included. No significant differences of the risk of all-cause death were found between the low-target blood pressure and high-target blood pressure strategy (OR 0.93 [95% CI 0.73–1.17], I2 = 0%, P = 0.55). Meanwhile, the low-target blood pressure therapy had a higher proportion of mRS score ≥4 (OR 0.43 [95% CI 0.20–0.94], I2 = 0%, P = 0.03) ≥4 compared with the high-target blood pressure therapy. No significant between-group differences were identified among patients in the level of the serum NSE (SD 0.82 [95% CI −1.50 to 3.13], I2 = 28%, P = 0.49), troponin T (SD 0.54 [95% CI −0.03–1.12], I2 = 0%, P = 0.07), renal replacement therapy (OR 1.09 [95% CI 0.71–1.69], I2 = 49%, P = 0.69), severe bleeding (OR 1.18 [95% CI 0.85–1.65], I2 = 0%, P = 0.33) and arrhythmia (OR 0.84 [95% CI 0.57–1.24], I2 = 0%, P = 0.38).
CONCLUSIONS The higher mean arterial pressure (MAP) is not associated with improved outcome when compared to conventional target, but may be associated with worse neurological outcome.
GW35-e0621
Junyi Zhang, Yafeng Zhou
The Fourth Affiliated Hospital of Soochow University
OBJECTIVES The relationship between liver stiffness (LS) and HFpEF remains unclear. The purpose of this study was to explore the correlation between LS and the severity of HFpEF.
METHODS We performed a prospective observational study. After accepting liver transient elastography on admission, consecutive 150 hospitalized HFpEF patients were divided into three groups based on their liver elasticity value: first-third quartiles. Left ventricular diastolic function, left ventricular hypertrophy degree, right cardiac function and short-term prognosis (≤1 year) were compared among the three groups, and the correlation between liver elasticity and each indicator was analyzed.
RESULTS The elasticity of the liver was abnormally high in more than two-thirds of cases. In terms of diastolic function and left ventricular hypertrophy, the ventricular septal e′ (5.01 ± 2.69 vs. 6.48 ± 2.29, P = 0.025), lateral wall e′ (6.63 ± 3.50 vs. 8.62 ± 2.73, P = 0.013), mean E/e′ (20.06 ± 7.53 vs. 13.20 ± 6.05, P = 0.001), left atrial volume index (43.53 ± 10.94 vs. 35.78 ± 13.86, P = 0.008), tricuspid regurgitation (TR) peak flow rate (3.16 ± 0.44 vs. 2.75 ± 0.50, P < 0.001), left ventricular mass index (LVMI) in male (163.2 ± 47.6 vs. 131.3 ± 38.0, P = 0.015) and in female (147.4 ± 48.6 vs. 110.6 ± 24.3, P = 0.036) was significantly different between the third quartile and the first quartile. The proportion of patients with diastolic dysfunction in the third quartile was significantly higher than that in the first quartile (70 vs. 36%, P = 0.017). In terms of right cardiac function, right ventricular fractional area change (RVFAC) (30.3 ± 5.4 vs. 36.5 ± 6.8, P < 0.001), tricuspid annular plane systolic excursion (TAPSE) (7.7 ± 5.2 vs. 14.8 ± 5.9, P = 0.010), pulmonary systolic pressure (38.0 ± 10.5 vs. 32.4 ± 10.3, P = 0.005), TR peak flow rate (3.16 ± 0.44 vs. 2.75 ± 0.50, P < 0.001), and inferior vena cava diameter (2.53 ± 0.51 vs. 1.98 ± 0.41, P < 0.001) were significantly different between the third quartile and the first quartile. More than half of HFpEF patients were combined with right ventricular dysfunction (RVD). In terms of short-term prognosis, the incidence of adverse cardiovascular events was significantly higher in the third quartile than in the first quartile (P = 0.003) and the second quartile (P = 0.008). Multivariate Cox proportional hazard analysis showed that adverse cardiovascular events were independently associated with NYHA class, atrial fibrillation, lgNT-proBNP and liver elasticity value (HR = 1.208, 95% CI 1.115–1.352, P = 0.002).
CONCLUSIONS Increase of liver stiffness is common in HFpEF patients. Increased LS in HFpEF patients was significantly associated with worsen left diastolic function, left ventricular hypertrophy, and the right cardiac function. Atrial fibrillation, poorer NYHA class, higher NT-proBNP, and increased liver elasticity value were independent predictors of poor short-term prognosis of HFpEF patients.
GW35-e0730
Zhuang Guo1,2, Hongwei Xie1, Chenxi Lu2, Ke Xu1,2, Meixia Dai1,2, Ke Peng2, Xiaoying Liu2, Yichong Li2, Yu Shi2, Guiyuan Han2
1School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, People’s Republic of China
2National Clinical Research Center for Cardiovascular Diseases, Heart Failure Ward, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, P.R. China
OBJECTIVES We aim to explore the causal relationship between non-alcoholic fatty liver disease (NAFLD) and heart failure (HF) in individuals with normal BMI.
METHODS The study used data from the UK Biobank, which recruited over 500,000 participants aged from 37 to 73 years between 2006 and 2010. Among 157,298 individuals with normal BMI, with the exclusion of 13,618 with missing FLI data and 3123 with cardiovascular conditions, we finally included 140,557 participants. NAFLD was assessed using the fatty liver index (FLI), calculated from BMI, waist circumference, triglycerides, and gamma-glutamyl transferase. Participants were categorized into non-NAFLD with FLI less than 60 and NAFLD with FLI more than or equal to 60. We classified FLI according to quartile distribution with the lowest quartile group as the reference group and the other three quartile group as exposure groups. HF was identified using ICD – 10 code I50 based on self-reports, primary care records, death registrations, and hospital admissions with a censoring date of June 2023. We used Poisson regression models and Kaplan-Meier methods to calculate HF incidence rates per 1000 person-years and 14-year cumulative incidence of HF. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HF incidence were analysed using multivariable Cox proportional hazard models. We developed different multivariable models with the adjustment of different covariates combinations. We also did subgroup analyses based on age, sex, alcohol and smoking status, diabetes, and hypertension. Additional analyses were conducted with the exclusion of HF cases within 1 or 2 years of baseline and cases of alcoholic liver disease in the main results as sensitivity analyses.
RESULTS Of these 140,557 participants, the mean age was 55.56 ± 8.21 years, and 33.8% were male. During Over 2,007,192.7 person-years follow-up, 8232 HF events were diagnosed. The cumulative HF incidence was 4.10 per 1000 person-years. The 14-year cumulative HF incidence for FLI quartiles 1 to 4 were 3.83%, 5.51%, 6.72%, and 8.57%. NAFLD participants had a 20% higher HF risk than non-NAFLD participants (HR = 1.20, 95% CI: 1.06–1.36). Compared to the lowest quartile of FLI, the risk of HF was 22% (HR = 1.22, 95% CI: 1.13–1.32), 32% (HR = 1.32, 95% CI: 1.21–1.43), and 48% (HR = 1.48, 95% CI: 1.35–1.62). The results were generally consistent across different subgroups, with significant interactions for age (P < 0.001), sex (P = 0.017), and type 2 diabetes (P < 0.001). But in the subgroups of those with diabetes or no drinking. Excluding HF events within 1 and 2 years of baseline and ALD cases confirmed similar results.
CONCLUSIONS NAFLD was associated with an increased risk of HF, even among individuals with a normal BMI. Therefore, it is essential to focus on liver health in individuals with a normal BMI to prevent the onset of NAFLD and subsequently reduce the risk of HF.
GW35-e0863
Rui Li1, Yijun Liu2, Conghui Zhang1, Zhen Zhao2, Jun Gao1, Yu Qi1, Wenyue Dong3, Shuangquan Ma4, Baoxia Chen1, Haihui Fan2, Xiaoyan Gu2, Xinwei Hua1, Yida Tang1
1Department of Cardiology, Institute of Vascular Medicine, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University Third Hospital, Peking University, Peking University, Beijing 100191, China
2Institute of Information Engineering, Chinese Academy of Sciences, Beijing 100080, China
3School of Basic Medical Sciences, Peking University, Beijing 100091, China
4School of Biological Science and Medical Engineering, Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing 100083, China
OBJECTIVES Heart failure (HF) with preserved ejection fraction (HFpEF) represents over 50% of HF cases. Despite the poor quality of life and adverse long-term outcomes experienced by HFpEF patients, effective pharmacotherapy remains scarce, primarily due to the heterogeneity of this clinical syndrome. Improved phenotyping is needed for developing personalized treatments. This study aimed to identify distinct phenotypic subgroups of HFpEF patients in a well-characterized electronic medical record-based cohort of HFpEF patients in China, and to compare clinical characteristics, treatment responses, and prognosis across identified phenogroups.
METHODS The study included 852 hospitalized patients diagnosed with HF and left ventricular ejection fraction (LVEF) ≥50% at Peking University Third Hospital between 2014 and 2022. A DeepCluster model was used to identify three distinct phenogroups based on 106 demographic and clinical variables, including medical history, clinical biomarkers, and echocardiographic measures. Kaplan-Meier curves and Cox proportional hazard models were used to assess the differences in treatment responses and prognoses. In addition, our phenotyping model was internally validated using the leave-one-out cross-validation approach, and was externally validated using the clinical data from TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial).
RESULTS We identified three distinct HFpEF phenogroups. Phenogroup 1 (n = 254) consisted of predominantly older females, with higher prevalence of atrial fibrillation and structural heart disease, left and right atrial enlargement, diastolic dysfunction, and tricuspid regurgitation. Phenogroup 2 (n = 310) had increased burdens of metabolic-related co-morbidities (such as obesity, diabetes, and hyperlipidemia) and coronary heart disease, with highest burden of diastolic functional impairment. Phenogroup 3 (n = 288) exhibited higher burden of cardiomyopathy, with higher circulating levels of heart damage biomarkers. Over a median follow-up of 2.62 years, phenogroup 2 had the worst prognosis (Log-rank P value = 0.01). In multivariate-adjusted Cox proportional hazard models, we observed no overall survival benefit among prescribed medications. After stratifying by phenogroups, we observed that use of beta-blockers was significantly associated with a lower risk of all-cause mortality in phenogroup 2 (adjusted Hazard Ratio [HR], 0.49; 95% CI, 0.29–0.83, P = 0.011). The deep neural network phenotyping model was internally validated with 91.0% consistency (κ = 0.86). External validation in TOPCAT identified three phenogroups with similar clinical characteristics and prognosis profiles: phenogroup 2 having the highest risk of all-cause mortality (Log-rank P value for all-cause mortality = 0.007; adjusted HR, 1.65; 95% CI, 1.07–2.54, phenogroup 2 vs. phenogroup 3).
CONCLUSIONS Deep learning-based phenotyping of HFpEF patients can identify phenogroups with distinct clinical characteristics, treatment response, and prognosis. Beta-blockers therapy is demonstrated to be effective in reducing all-cause mortality among HFpEF patients characterized by higher burdens of metabolic comorbidities and overt diastolic dysfunction.
GW35-e0914
Chenxi Lu1,2, Zhuang Guo2, Meixia Dai2, Guiyuan Han2, Ke Peng2, Xiaoying Liu2, Yichong Li2, Yu Shi2
1School of Public Health, Shenzhen University Medical School, Shenzhen, P.R. China
2National Clinical Research Center for Cardiovascular Diseases, Heart Failure Ward, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, P.R. China
OBJECTIVES Ketone bodies (KB) are an important alternative metabolic fuel source for the myocardium. However, the association between KB and the risk of heart failure development remains unclear. This study aimed to examine the association of plasma total KB and individual KB (β-hydroxybutyrate, acetoacetate, and acetone) with incident heart failure (HF).
METHODS Based on UK Biobank, 268,928 participants free of HF with the measurement of plasma levels of β-hydroxybutyrate, acetoacetate, and acetone levels measured were included at baseline. The exposure factors included β-hydroxybutyrate, acetoacetate, acetone, and the sum of these substances defined as plasma total KB. Multivariable Cox proportional hazard models were used to examine the association of plasma total KB and individual KB with the development of HF.
RESULTS During a median follow-up of 13.8 years, a total of 10,194 HF events occurred. According to the quartiles of plasma total KB level, the incidence rates were 1.85/1000, 2.70/1000, 3.31/1000, and 3.29/1000 person-years in Q1, Q2, Q3, and Q4 groups, respectively. In multivariable Cox models, per 1-standard deviation increase in total KB was associated with an 8% [adjusted hazard ratio (aHR), 1.08; 95% confidence interval (CI), 1.06–1.09] higher risk of HF. Compare to Q1 group, the aHR (95% CI) for Q2, Q3, and Q4 were 1.08 (1.01–1.15), 1.10 (1.04–1.17), and 1.23 (1.16–1.31). This association was consistent for incident HF and individual KB. Specifically, β-hydroxybutyrate showed aHR of 1.12 (1.05–1.19), 1.17 (1.10–1.24), 1.28 (1.20–1.36) for Q2, Q3, and Q4 versus Q1. Acetoacetate exhibited aHR of 1.07 (1.00–1.14), 1.09 (1.03–1.16), 1.22 (1.15–1.29) for Q2, Q3, and Q4 versus Q1. Acetone presented aHR of 1.03 (0.97–1.09), 1.05 (0.99–1.11), 1.19 (1.12–1.26) for Q2, Q3, and Q4 versus Q1.
CONCLUSIONS This study found that elevated plasma KB is independently associated with a higher rate of HF. Ketone bodies could serve as a potential biomarker for the risk of heart failure development.
GW35-e0978
Shaunglei Zhao, Ming Gong
Beijing Anzhen Hospital, Capital Medical University, Beijing, China
OBJECTIVES Renal function is a crucial factor affecting the prognosis of patients with end-stage heart failure. The differential impact of heart transplantation and left ventricular assist device (LVAD) implantation on renal function is unclear. Therefore, we compared the perioperative renal function changes in patients undergoing heart transplantation and LVAD implantation.
METHODS The study included 77 patients who underwent heart transplantation and 59 patients who received LVAD implantation from five hospitals between January 2019 to December 2023. Patients were divided into heart transplantation and LVAD implantation groups based on the type of surgery. Estimated glomerular filtration rates (eGFR) before surgery and on postoperative day (POD) 1, 7, 30 were compared. A subgroup analysis was conducted on patients with preoperative renal dysfunction, using paired t-tests to compare renal function changes before and 1 month after the surgery.
RESULTS Patients in the LVAD group were older (56.4 vs. 44.4, P < 0.001) and had lower preoperative eGFR (72.5 vs. 91.3, P = 0.001) compared with patients in the heart transplantation group. On POD1 and POD7, eGFR levels in the LVAD patients continued to be lower than that in the heart transplantation group. The baseline eGFR levels showed no significant difference (63.3 vs. 60.4, P = 0.438) in patients with preoperative renal dysfunction (eGFR <90 mL/min/1.73 m2). However, on POD 1, 7 and 30, eGFR levels in the LVAD group were significantly higher than that in the heart transplantation group. By POD30, renal function in the LVAD group recovered to near-normal levels (60.4–87.6), while in the heart transplantation group the eGFR remained close to preoperative levels (63.3–63.4). In the LVAD group, eGFR significantly increased on POD30 with 84.7% (50/59) of the LVAD patients showing varying degrees of renal function improvement. In the heart transplantation group, eGFR levels on POD30 were comparable to preoperative levels, with more than half of the patients showing decreased eGFR. Among patients with preoperative renal dysfunction, 10 patients without preoperative continuous renal replacement therapy (CRRT) underwent postoperative CRRT in the heart transplantation group, and 9 died within 3 months after transplantation. In the LVAD group, 3 patients without preoperative CRRT support required CRRT postoperatively, with 1 early mortality.
CONCLUSIONS For patients with end-stage heart failure and concurrent renal dysfunction, LVAD implantation with this new device resulted in significantly improved renal function when compared to heart transplantation. The device operated in a safe and effective manner with no malfunctions and was successfully managed to improve renal function.
GW35-e1030
Jia Shi1,2, Xiang Zhang3, Ya Wen3, Mengjiao Shao4, Yanmei Lu1,2, Baopeng Tang1,2
1Cardiac Pacing and Physiological Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
2Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
3Department of Physiology and Pharmacology, Karolinska Institutet, Sweden
4Department of Cardiology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
OBJECTIVES Heart failure is a leading global cause of mortality, with the subtype Heart Failure with Reduced Ejection Fraction (HFrEF) being particularly prevalent. However, only 43–52% of HFrEF patients experience left ventricular reverse remodeling (LVRR) despite guideline-directed medical therapy (GDMT). Peripheral blood mononuclear cells (PBMCs) are implicated in cardiac inflammation and fibrosis in HFrEF patients, but their role in LVRR and underlying mechanisms require further investigation.
METHODS We conducted a comparative whole transcriptomic analysis to investigate molecular differences in PBMCs between HFrEF patients with and without LVRR after 6 months of GDMT. Cellular deconvolution analysis unveiled LVRR-specific cell type composition of PBMCs. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression modules, as well as module-correlated clinical traits, cell type composition, and non-coding RNAs. Competitive endogenous RNA (ceRNA) regulatory axes were constructed with network hub genes of each module and correlated non-coding RNAs after database searching.
RESULTS Comparative whole transcriptomics showed reduced systemic inflammation and capacity of organizing extracellular matrix but increased natural killer cell and platelet activity and abundance in the LVRR compared to the non-LVRR group. These molecular differences were correlated with clinical traits such as serum phosphorus, activated partial thromboplastin clotting time (APTT), and albumin. The progression of LVRR may be influenced by key genes (e.g., FOS, JUN, MMP9, LCN2, FASLG, SPARC) and their potential ceRNA regulatory axes.
CONCLUSIONS Our findings, which include LVRR-specific clinical traits, cell type composition of PBMCs, molecular signatures and potential regulatory mechanisms, may aid clinicians in developing personalized therapeutic approaches.
GW35-e1040
Chengjian Guan, Angwei Gong, Yan Zhao, Hangtian Yu, Shuaidan Zhang, Bing Xiao
Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, People’s Republic of China
OBJECTIVES This study aims to identify different phenotypes of heart failure (HF) patients admitted to the ICU and to explore optimal fluid balance ranges for different phenotypes.
METHODS Data from the Intensive Care Medical Information Market (MIMIC) database served as the training set and eICU Collaborative Research Database (eICU) data as external validation. Clustering and validation were performed using the k-prototypes algorithm, and risk ratios for in-hospital mortality for different fluid balance strategies during hospitalization for different phenotypes of HF patients were derived using the parameter g-formula. Finally, the Extreme Gradient Boosting (XGBoost) model was used to construct a classification learner to help clinicians quickly identify phenotypes.
RESULTS We identified four phenotypes that differed significantly in clinical characteristics and prognosis. Phenotype A had the highest proportion of mechanical ventilation; phenotype B had the youngest age and relatively mild disease; phenotype C had the oldest age, more complications and poor prognosis and phenotype D had severe renal dysfunction, acid-base imbalance, and the worst prognosis. The fitting results of parameter g-formula showed that the optimal fluid balance range of patients with different phenotypes was different, with phenotype A ranging from −1000 mL to 500 mL per day, while phenotype B had no apparent optimal range, phenotype C from −1500 mL to 500 mL per day, and phenotype D had the strictest limit, from −2000 mL to −500 mL per day. A user-friendly interface was developed to help clinicians quickly identify the different phenotypes.
CONCLUSIONS We found that there were HF phenotypes that respond differently to fluid balance, and future large-scale prospective experiments are needed to confirm our findings.
GW35-e1043
Wang Qiong Ling, Li Ruijie, Sun Huang, Liu Wenjie, Li Yiming
Department of Cardiology, the First Affiliated Hospital of Kunming Medical University
OBJECTIVES Heart failure is the final stage of various cardiovascular diseases, and there are about 13.7 million patients with heart failure in China; The “fragile period” refers to the period of high incidence of death and readmission in heart failure patients within 2–3 months after discharge from hospital. In China, the reported mortality and readmission rates within 1 month after discharge from hospital for heart failure are 15% and 30%, respectively. Previous studies have confirmed that EMAT has a good correlation with left ventricle. At present, we included 13 patients with heart failure in this study. Involved daily monitoring of heart sound and ECG, weight, and symptom scales after discharge, Combined with the results of correlation coefficient R2, EMAT% can better predict the occurrence of decompensation of heart failure after discharge, EMAT% of ECG monitoring parameters independently predicted the occurrence of events, and reduce the readmitted heart failure.
METHODS We included 13 patients discharged from hospital with standardized treatment of heart failure who met the criteria of natrification. On the day of discharge, body weight, heart rate, BNP, heart sound-ECG monitoring data, heart color ultrasound and other examinations were completed. After discharge, patients wear the wearable device for a few minutes or hours every day, turn on Bluetooth, upload the cardiac and ECG monitoring data to the data center for storage through the wechat mini program on the mobile phone, follow up the patient’s condition by phone, and record the weight and symptom scale every day. Return to the hospital one month after discharge, improve blood drawing, heart color ultrasound and other related examinations.
RESULTS SPSS software was used to conduct correlation analysis of the data. EMAT and EMAT% were correlated with blood pressure and heart rate, EMAT% was positively correlated with heart rate and body weight, and EMAT was negatively correlated with heart rate and body weight. Combined with the correlation coefficient R2, compared with EMAT, EMAT% is more strongly correlated with heart rate and body weight, and the changes of heart rate and body weight are often the early changes in the decompensation stage of heart failure, so EMAT% can better predict the prognosis of heart failure. SPSS software analysis, through telephone follow-up and ECG monitoring, we found that when the EMAT% fluctuation trend was large, the incidence of events increased, indicating that the change of EMAT% independently predicted the occurrence of events.
CONCLUSIONS Combined with the results of correlation coefficient R2, EMAT% can better predict the occurrence of decompensation of heart failure after discharge, EMAT% of ECG monitoring parameters independently predicted the occurrence of events, and reduce the readmitted heart failure.
GW35-e1058
Yanbing Pan, Yihui Kong
The First Affiliated Hospital of Harbin Medical University
OBJECTIVES To analyze the arrhythmia characteristics of three types of heart failure (HF) combined with sleep-disordered breathing (SDB).
METHODS This study is a cross-sectional observational study. The study included HF patients who were hospitalized in the Department of Cardiology of the First Affiliated Hospital of Harbin Medical University from April 2023 to December 2023. Clinical data were collected during the patient’s hospitalization. Based on left ventricular ejection fraction (LVEF), patients were divided into heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). According to the type of arrhythmia, it is divided into atrial fibrillation (AF) and premature ventricular contractions (PVC). They were divided into AF group and non-AF group according to whether AF was combined, and PVC group and no PVC group according to whether PVC was combined. The logistic regression model was used to analyze the related factors affecting the occurrence of arrhythmia and correct the confounding factors.
RESULTS A total of 245 patients with HF were included. Thirty-two percent of patients had AF and 25 percent had PVC. (1) The AF event was used as the dependent variable, Multivariate logistic regression model 1 analysis of AF events showed that HF type and SDB severity were the influencing factors for the occurrence of AF in patients with HF and SDB. For the HF group, the risk of AF in patients with HFpEF was 3.246 times higher than that in patients with HFrEF (95% CI: 1.310–8.042, P = 0.011), and for the SDB severity group, the risk of AF in patients with severe SDB was 3.086 times higher than that in patients with mild to moderate SDB (95% CI: 1.475–6.455, P = 0.003). Multivariate logistic regression model 2 analysis showed that HF type and SDB type were the influencing factors for the occurrence of AF in patients with HF and SDB. The risk of AF in HFpEF patients was 3.380 times higher than that in HFrEF patients (95% CI: 1.381–8.274, P = 0.008), and 2.754 times higher than that in OSA patients (95% CI: 1.032–7.355, P = 0.043) in SDB group. (2) The PVC event was used as the dependent variable, Multivariate logistic regression model 1 analysis showed that HF type and SDB severity were not statistically significant for the occurrence of PVC in patients with HF and SDB (P > 0.05). Similarly, the analysis of multivariate logistic regression model 2 showed that SDB type was the influencing factor for the occurrence of PVC in HF patients with SDB. For the SDB group, the risk of PVC in patients with CSA was 3.469 times higher than that in patients with OSA (95% CI: 1.391–8.653, P = 0.008). At the same time, HF type was not statistically significant for the occurrence of PVC in patients with HF and SDB (P > 0.05).
CONCLUSIONS (1) Compared with HFrEF, patients with HFpEF and SDB have a higher risk of AF. (2) Compared with OSA, patients with HF and CSA have a higher risk of AF. (3) Compared with mild to moderate SDB, patients with HF and severe SDB have a higher risk of AF. (4) Compared with OSA, patients with HF and CSA have a higher risk of developing PVC. (5) The type of HF and the severity of SDB were not significantly correlated with the occurrence of PVC in patients with HF and SDB.
GW35-e1065
Nene Takahashi1, Yuto Kawase1, Yuta Hirako1, Ryuya Naruta1, Masafumi Funamoto2, Yoichi Sunagawa1,3, Yasuhumi Katanasaka1,3, Toshihide Hamabe1,3, Koji Hasegawa2, Tatsuya Morimoto1,2,3
1Department of Molecular Pathophysiology, Faculty of Pharmaceutical Sciences, University of Shizuoka
2Department of Deployment Medicine, NHO Kyoto Medical Center
3Shizuoka General Hospital
OBJECTIVES Since heart failure has an extremely poor prognosis, noble therapeutic strategies for heart failure are required. Compound X, an extract of the natural compound Sansho, has various actions such as analgesic, anti-inflammatory, and antioxidant effects, but its effects on heart failure are not yet known. In this study, we investigated whether Compound X inhibits cardiomyocyte hypertrophy and heart failure in mice.
METHODS Primary cultured cardiomyocytes prepared from neonatal rat hearts were treated with 0.1, 0.3, and 1 μM Compound X and then stimulated with the α1-adrenergic receptor agonist phenylephrine (PE). After 48 hours, fluorescent immunostaining with an anti-α-actinin antibody was performed and cell area was measured. mRNA levels of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), which are hypertrophy-related genes, were measured by quantitative PCR. Histone H3K9 acetylation was examined by the western blot (WB). Next, 8-week-old C57BL/6 male mice underwent aortic constriction surgery (TAC) to induce heart failure. One day after the surgery, TAC mice were randomly divided into two groups and orally administered with solvent (0.5% CMC-Na) or 30 mg/kg of Compound X for 4 weeks. Echocardiography was performed to evaluate the systolic function.
RESULTS Fluorescent immunostaining revealed that Compound X suppressed PE-induced cardiomyocyte hypertrophy in cultured cardiomyocytes. Quantitative PCR demonstrated that Compound X significantly reduced PE-induced increase in hypertrophy-related gene transcription. WB showed that Compound X inhibited PE-induced H3K9 acetylation. Moreover, Echocardiography demonstrated that Compound X suppressed TAC-induced systolic dysfunction in mice. Moreover, Compound X suppressed the TAC-induced increases in the heart weight to body weight ratio, heart weight to tibia length ratio, and ANF and BNP mRNA expression levels.
CONCLUSIONS These results indicated that Compound X suppressed PE-induced cardiomyocyte hypertrophy and pressure overload-induced cardiac dysfunction, at least partially by inhibiting the p300 HAT activity. Further examination of the inhibitory mechanism of Compound X on cardiac function may lead to the development of a novel therapeutic agent for heart failure.
GW35-e1116
Guanqi Zhao1, Weimin Li2
1Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
2Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China
OBJECTIVES Due to the stereotyped image that heart failure (HF) predominantly affects older individuals and the assumption that younger patients are less likely to develop this condition, resources, research, and targeted interventions may primarily focus on addressing the unique challenges faced by elderly individuals with heart failure. Consequently, there is a limited emphasis on early detection, intervention, and treatment for younger individuals with heart failure.
Therefore, we would comprehensively evaluate the characteristics, treatment, and outcomes of HF patients based on the China Cardiovascular Association Database-Heart Failure (CCA Database-HF) Center Registry, to improve early detection, develop targeted interventions, and ultimately enhance the overall management and outcomes for young HF patients.
METHODS Between January 2017 and June 2021, 282,168 hospitalized HF patients from 481 CCA Database-HF Center certified secondary and tertiary hospitals across overall 31 provinces of mainland China were included in this study. Age was divided into five categories: <45 years, 45–54 years, 55–64 years, 65–74 years and ≥75 years, to compare characteristics, treatment and in-hospital outcomes. To determine the association between age and in-hospital mortality, modified Poisson regression was performed.
RESULTS Among all included HF patients, patients aged under 45 accounted for 4.68%, aged 45–54 and 55–64 years accounted for 9.08% and 17.28%, respectively. The proportion of LVEF ≤40% was highest in patients under 45 years (53.7%) and then decreased by age, and was only 21.6% in patients ≥75 years. In the young, the most common investigator-reported etiology of HF was dilated cardiomyopathy (37.9%), followed by coronary heart disease (CHD) (22.0%) and hypertension (13.6%). Although in the univariate analysis, the risk of mortality increased with age, the risk of in-hospital mortality was similar among those under 75 years after multivariate adjustment. A total of 280,084 HF patients survived at discharge. The medication use rate of different age groups was compared at different LVEF levels. For patients with LVEF ≤50%, the utilization rates of β-blockers, aldosterone receptor antagonist, ACEI/ARB/ARNI, and SGLT2 inhibitors tend to decrease with advancing age. However, SGLT2 inhibitors are less utilized in all age groups no matter LVEF levels.
CONCLUSIONS Patients with age <65 years account for nearly one-third of all HF hospitalized patients. A distinct clinical profile was identified in the young HF patients. Unexpectedly, the younger HF patients did not show a lower risk of in-hospital mortality, indicating HF prevention is more important in young people.
GW35-e1156
Ping Jin
The Second Affiliated Hospital of Xi’an Jiaotong University
OBJECTIVES Congestive Heart Failure (CHF) is a complex clinical syndrome characterized by the heart’s inability to meet the body’s blood and oxygen demands, predominantly caused by myocardial injury and structural cardiac alterations. CHF’s global impact is significant, particularly among the elderly, where it is a leading cause of morbidity and mortality. This highlights the need for reliable prognostic markers, especially as liver function abnormalities, which can be indicative of reduced hepatic perfusion or congestion, are common in these patients. The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT), or AST/ALT ratio, has been suggested as a potential biomarker for prognostication in CHF. However, its utility as a prognostic indicator in CHF patients, especially those in the ICU, remains to be fully explored.
METHODS This retrospective cohort study utilized the eICU Collaborative Research Database for over 200,000 ICU admissions from >200 US hospitals (2014–2015). Adult CHF patients (ICD-9 410) were included, with AST and ALT levels from initial labs within 24 hours of admission used to calculate the AST/ALT ratio. Descriptive statistics characterized the cohort, while multivariable logistic regression analyzed AST/ALT’s association with 28-day mortality, adjusting for confounders. Adjustments were stratified into minimal and full models, and GAMs assessed nonlinear relationships. Survival was evaluated using Kaplan-Meier curves and log-rank tests. Statistical significance was set at P < 0.05. Data analysis was conducted using R version 3.6.1 and Empower Stats.
RESULTS Our study evaluated a cohort of 5230 patients diagnosed with CHF, among whom 450 (8.6%) succumbed within 28 days of ICU admission. Statistical analysis highlighted that the AST/ALT ratio serves as a significant predictor of mortality. Specifically, when comparing mortality rates across tertiles of AST/ALT, patients in the highest tertile exhibited a significantly increased risk of death compared to those in the lowest tertile, with a fully adjusted odds ratio (OR) of 2.22 (95% CI: 1.58–3.11, P < 0.0001). The dose-response relationship between AST/ALT and mortality was further explored using generalized additive models (GAM), which identified a nonlinear association. The risk of mortality increased sharply with AST/ALT values up to 1.97, beyond which the increase in risk plateaued. This suggests a threshold effect, indicating that AST/ALT values beyond 1.97 still confer additional risk stratification benefit. Kaplan-Meier survival analysis showed significant differences in 28-day survival probability among the three groups (Log rank test: P < 0.0001), with the high AST/ALT group exhibiting the lowest survival probability. These analyses confirmed that the predictive value of AST/ALT was not significantly affected by these factors, highlighting its potential utility as a clinical tool in the management of CHF.
CONCLUSIONS This study confirms the significant prognostic utility of the AST/ALT in predicting 28-day mortality for CHF patients in intensive care settings. The findings reveal that a high AST/ALT is an indicator of severe metabolic distress and a reliable predictor of adverse outcomes, supporting its inclusion in the clinical evaluation toolkit for AST/ALT. Given these results, AST/ALT can enhance risk stratification and potentially guide more targeted interventions in the management of CHF. Future research should focus on prospective validations of these findings and on elucidating the physiological pathways linking AST/ALT to mortality in CHF patients.
GW35-e1183
Zhenyan Xu1, Zixi Huang2, Ying Huang3
1Department of Cardiovascular Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University
2Department of General Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University
3Department of Rehabilitation, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University
OBJECTIVES Fibrinogen, a biomarker of thrombosis and inflammation, is related to a high risk for cardiovascular diseases. However, studies on the prognostic value of blood fibrinogen concentrations for heart failure (HF) patients are few and controversial.
METHODS We performed a retrospective analysis among acute or deteriorating chronic HF patients admitted to a hospital in Sichuan, China, between 2016 and 2019, integrating electronic health care records and external outcome data (N = 1532). During 6 months of follow-up, 579 HF patients were readmitted within 6 months, and 46 of them died.
RESULTS We found an inverted U-shaped association of blood fibrinogen levels with risk of readmission within 6 months but not with risk of death within 6 months. It was found that HF patients had the highest risk for readmission within 6 months after reaching the turning point for blood fibrinogen (2.4 g/L). In HF patients with low fibrinogen levels <2.4 g/L, elevated fibrinogen concentrations were still significantly associated with a higher risk for readmission within 6 months [OR = 2.3, 95% CI (1.2, 4.6); P = 0.014] after controlling for relevant covariates. There was no significant association between blood fibrinogen and readmission within 6 months [(OR = 1.0, 95% CI (0.9, 1.1); P = 0.675] in HF patients with high fibrinogen (>2.4 g/L). The effect difference for the two subgroups was significant (P = 0.014). However, we did not observe any association between blood fibrinogen and death within 6 months stratified by the turning point, and the effect difference for the stratification was not significant (P = 0.380).
CONCLUSIONS We observed an inverted U-shaped association between blood fibrinogen and rehospitalization risk in HF patients for the first time. Additionally, our results did not support that elevated blood fibrinogen was related to increased death risk after discharge.
GW35-e1215
Lina Feng1,2, Cao Hongshuai2, Jiang Liu1,2, Lina Su2, Jingyi Ren2
1Peking University China-Japan Friendship School of Clinical Medicine
2Department of Cardiology (Heart Failure Center), China-Japan Friendship Hospital
OBJECTIVES Dyspnea is a common complaint in the emergency department and half of the patients have congestive heart failure as the primary diagnosis. Approximately 20% of patients presenting with dyspnea are initially misdiagnosed. Noninvasive Remote Dielectric Sensing (ReDS) could rapidly and quantitatively detect pulmonary edema. To assess the accuracy of ReDS in detecting acute heart failure in a large Chinese real-world cohort.
METHODS This was a prospective, single-center, observational study evaluating the accuracy of ReDS in detecting acute heart failure (AHF) in patients with dyspnea. Patients were consecutively enrolled from the Emergency, Respiratory and Cardiology Departments in China-Japan Friendship Hospital. All patients underwent ReDS (within 45–90s), NT-proBNP, Chest imaging (chest CT or X-Ray), echocardiography testing. ReDS values above 35% were defined as positive for pulmonary edema (positive ReDS). AHF was diagnosed by cardiologists according the medical history and examination data but irrespective of ReDS values.
RESULTS From November 2023 to March 2024, there were 507 patients with dyspnea, 61% for men and 39% for women, the mean age was 65 ± 14 years. A total of 152 patients (29.9%) were positive ReDS, 17.9% patients were AHF. In patients with AHF, the mean ReDS values was 41 ± 8%, LVEF was 44 ± 14%, NT-proBNP was 5218 (IQR 1523–10,788) ng/mL. The AUC of ReDS to detect AHF was 0.837 (95% CI 0.792–0.883), with 86.8% sensitivity and 74.4% specificity. The high accuracy of ReDS was similar to NT-proBNP (AUC 0.838, 95% CI 0.799–0.877, P < 0.001).
CONCLUSIONS ReDS is capable of rapidly and accurately identifying acute heart failure in patients with dyspnea, with performance comparable to that of NT-proBNP. It is conceivable that in the future, ReDS will become a fundamental element in the diagnosis of acute heart failure.
GW35-e1355
Hongxiang Wu1,2, Ruobing Wang1,2, Wenda Gu1,2, Jian Liu1,2, Huiming Guo1,2
1Department of of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Guangzhou, China
2Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangzhou, China
OBJECTIVES Large language models (LLMs) are increasingly prevalent in various sectors, with numerous high-tech companies, including leading smartphone manufacturers in China, introducing their models. These LLMs enhance users’ access to healthcare information via smartphones, yet their effectiveness in addressing heart failure (HF) inquiries remains be determined. This study aims to assess the performance of 13 LLMs from prominent Chinese tech companies in answering questions related to HF.
METHODS Between July 1, 2024 and July 14, 2024, we presented 50 objective questions from the Chinese professional physician test database to the 13 LLMs: Zhipu AI, Tiangong, Bai Xiao Ying, Kimi, Yuanbao, ERNIE Bot, iFLYTEK Spark, Qwen, Xiaoyi from Huawei, YOYO from Honor, BlueLM from Vivo, XiaoAi from Mi, and Xiaobu from Oppo. These questions were also answered by two postgraduate students specializing in cardiovascular surgery. Only three subjective questions were sourced from the top 10 cardiology/cardiovascular surgery centers’ official websites. Thus, they were not employed in this study.
RESULTS Qwen exhibited the highest accuracy, correctly answering 90% of the questions, followed by Yuanbao at 86%, Zhipu at 85%, Bai Xiao Ying at 83%, Oppo at 81%, ERNIE Bot at 80%, Vivo at 78%, Kimi at 77%, iFLYTEK Spark at 76%, Mi at 75%, Honor at 73%, Tiangong at 72%, and Huawei at 60%. Notably, Qwen, Yuanbao, Zhipu, and Bai Xiao Ying outperformed the postgraduate students regarding accuracy.
CONCLUSIONS This study highlights the capability of many LLMs developed in China to provide accurate information on HF, showcasing their potential as valuable resources for medical and patient education. Further investigations are warranted to evaluate the LLMs’ proficiency in addressing subjective inquiries.
GW35-e1362
Peipei Li, Weiwei Chen, Yue Yang, Beibei Du, Ping Yang
China-Japan Union Hospital of Jilin University
OBJECTIVES Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel oral hypoglycemic drugs and are strongly recommended in the guidelines for the treatment of heart failure due to their cardioprotective effects. Despite many researches in recent years, the effects of SGLT2 inhibitors on atrial fibrillation (AF) remain unclear. Here we performed a systematic review and meta-analysis to thoroughly assess the long-term effects of SGLT2 inhibitors on arrhythmias.
METHODS We searched PubMed, EMBASE, Web of Science, and ClinicalTrials.gov online databases by computer to identify clinical randomized controlled trials (RCTs) with follow-up time at least 52 weeks from the time of database creation to June 29, 2023. The primary outcome of the meta-analysis was AF, and the secondary outcomes were atrial flutter (AFL), ventricular tachycardia (VT), ventricular fibrillation (VF) and sinus bradycardia. Combined relative risk (RR) with 95% confidence intervals (CI), Mantel-Haenszel calculation (M-H), and fixed-effect model were used to evaluate the long-term effects of SGLT2 inhibitors on arrhythmias.
RESULTS Thirty-four RCTs involving 90,656 participants were included. The results of meta-analysis showed that patients treated with SGLT2 inhibitors had a reduced risk of AF compared with placebo (RR 0.85; 95% CI, 0.75–0.96; I2 = 0%; P = 0.008). There was no significant difference in the risk of AF between the high-dose SGLT2 inhibitors group and the low-dose SGLT2 inhibitors group (RR 0.78; 95% CI, 0.57–1.06; I2 = 0%; P = 0.11), but a decreasing trend in high-dose SGLT2 inhibitors group was observed. The risk of AFL in the SGLT2 inhibitors group was not significantly different from that in the placebo group (RR 0.79; 95% CI, 0.61–1.03; I2 = 0%; P = 0.08) with a decreasing trend observed. There was no significant difference in VT (RR 0.98; 95% CI, 0.79–1.22; I2 = 2%; P = 0.87), VF (RR 1.07; 95% CI, 0.72–1.60; I2 = 0%; P = 0.73) and sinus bradycardia (RR 1.31; 95% CI, 0.63–2.75; I2 = 0%; P = 0.47) models between the SGLT2 inhibitors group with the placebo group.
CONCLUSIONS SGLT2 inhibitors could reduce the risk of AF. It had no significant effect on the risk of AFL, VT, VF and sinus bradycardia. And high-dose SGLT2 inhibitors did not exert better effects on the risk of AF.
GW35-e1372
Furong Yang1, Zhe Wang2, Jie Li3, Shuwen Zheng1, Wenjing Wu4, Mengwen Yan4, Wanmu Xie5, Yiong Sun2,6
1Beijing University of Chinese Medicine China-Japan Friendship School of Clinical Medicine, Beijing 10029, China
2Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 10020, China
3Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
4Department of Cardiology, China-Japan Friendship Hospital, Beijing 100029, China
5National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
6Institute of Heart Lung and Blood Vessel Diseases, Beijing 10020, China
OBJECTIVES Elevated levels of the circulating carbohydrate antigen 125 (CA125) serve as a biomarker for congestion in heart failure (HF). However, its diagnostic value in patients with diuretic resistance, when compared to natriuretic peptides, remains unclear.
METHODS To investigate the association between CA125 levels and clinical outcomes in comparison with NT-proBNP levels among patients exhibiting diuretic resistance, as well as those without. Patients with acute decompensated HF were retrospectively selected from 2022 to 2023 in one teaching hospital. A multivariable analysis was conducted to explore the relationship between CA125 levels and diuretic resistance, which was defined as a urine volume increase of less than 1000 mL within the initial 48 hours following the administration of 40 mg torsemide or an equivalent dosage of other loop diuretics. The primary outcome was all-cause death or HF re-hospitalization (HHF).
RESULTS Among the 107 patients included, the median age was 74 years; 57.9% were males and 47.4% exhibited HF with preserved ejection fraction. Compared to patients having good response to diuretics, those with diuretic resistance had significantly higher median CA 125 level (23.3 U/mL vs. 39.9 U/mL, P = 0.035). However, no significant difference in NT-proBNP levels was observed between the two groups. CA-125 levels revealed a moderate but statistically significant association with serum creatinine levels (r = 0.216, P = 0.026), pulmonary artery systolic pressure (PASP) (r = 0.286, P = 0.033), and right atrial diameter (r = 0.272, P = 0.011). During a median follow-up of 2 years, the incidence of primary outcome was higher in patients with diuretic resistance compared to those without (19.11% vs. 14.01%). The multivariable Cox analysis showed that elevated CA125 (≥35 U/mL) but not NT-proBNP (≥2766 pg/mL) was independently associated with an increased risk of primary endpoint (HR = 2.48, 95% CI: 1.23–5.0, Log-rank P < 0.001). For patients with diuretic resistance, CA125 demonstrated superior predictive accuracy, as indicated by an area under the Receiver Operating Characteristic (ROC) curve of 0.80 with specificity of 100% and sensitivity of 66.7% compared to NT-proBNP.
CONCLUSIONS CA125 is a useful marker for identifying patients with poor response to diuretics and superior to NT-proBNP for predicting mortality and HHF in decompensated HF patients.
BLOOD LIPIDS AND ATHEROSCLEROSIS
GW35-e0034
Lu Geng1, Lu’an Zhao2, Kexin Chen1, Jingchao Lu1
1The Second Hospital of Hebei Medical University
2The Sixth Clinical Medical College of Hebei University
OBJECTIVES Statins have the effect of reducing blood lipids and stabilizing plaque, and are common drugs of cardiovascular disease. Observational studies suggested that statins are associated with the risk of narcolepsy. Thus, we performed this Mendelian randomization (MR) study to provide genetic evidence to support the association between different type of statins and the risk of narcolepsy.
METHODS We employed the two-sample MR analysis to explore the statins use on narcolepsy (daytime dozing/sleeping), including atorvastatin, pravastatin, rosuvastatin and simvastatin. The summary statistics for statins and narcolepsy were obtained from public Genome-wide association studies (GWASs), and cohorts of statins (n = 462,933), narcolepsy (n = 336,082) were obtained. We used Inverse Variance Weighed Method (IVW) and Weighted Median and MR-Egger to study the causal relationship between statins and narcolepsy, in which IVW was the main method. Besides, we applied the odds ratios, P-values, and confidence intervals to estimate the strength and significance of the associations. The robustness of our study were ensured by sensitivity analyses, including MR-PRESSO, Cochran’s Q test, “leave-one-out”, and the MR-Egger method.
RESULTS The results suggested that atorvastatin (OR 1.22, 95% CI [1.07, 1.39], P < 0.01), and simvastatin (OR 1.09, 95% CI [1.03, 1.16], P < 0.01) were associated with an increased risk of narcolepsy, while no causal associations between rosuvastatin or pravastatin and narcolepsy were found.
CONCLUSIONS In summary, our MR study shows there may be a positive causal relationship between atorvastatin, simvastatin and narcolepsy. Specific mechanism needs further investigation in future studies.
GW35-e0103
Qian Xie, Xiaomei Li
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES Atherosclerosis and metabolic syndrome are the main causes of cardiovascular events, but their underlying mechanisms are not clear. In this study, we focused on identifying genes associated with diagnostic biomarkers and effective therapeutic targets associated with these two diseases.
METHODS Transcriptional data sets of atherosclerosis and metabolic syndrome were obtained from GEO database. The differentially expressed genes were analyzed by RSTUDIO software, and the function-rich and protein-protein interactions of the common differentially expressed genes were analyzed.
RESULTS A total of 1242 differential genes (778 up-regulated genes and 464 down-regulated genes) were screened from GSE28829 data set. A total of 1021 differential genes (492 up-regulated genes and 529 down-regulated genes) were screened from the data set GSE98895. Then 23 up-regulated genes and 11 down-regulated genes were screened by VENN diagram. Functional enrichment analysis showed that cytokines and immune activation were involved in the occurrence and development of these two diseases. Through the construction of PPI network and Cytoscape software analysis, we finally screened 10 HUB genes. The immune infiltration analysis was further improved. The results showed that the infiltration scores of 7 kinds of immune cells in GSE28829 were significantly different among groups (Wilcoxon Test <0.05), while in GSE98895, the infiltration scores of 4 kinds of immune cells were significantly different between groups (Wilcoxon Test <0.05). Spearman method was used to analyze the correlation between the expression of 10 key genes and 22 kinds of immune cell infiltration scores in two data sets. The results showed that there were 42 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE28829 (|Cor| >0.3 & P < 0.05). There were 41 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE98895 (|Cor| >0.3 & P < 0.05). Finally, our results identified 10 small molecules with the highest absolute enrichment value, and the three most significant key genes (CX3CR1, TLR5, IL32) were further verified in the data expression matrix and clinical blood samples.
CONCLUSIONS We have established a co-expression network between atherosclerotic progression and metabolic syndrome, and identified key genes between the two diseases. This may be helpful to provide new research ideas for the diagnosis and treatment of atherosclerosis complicated with metabolic syndrome.
GW35-e0178
Yicheng Wu1, Huixin Wang2
1Zhongshan Hospital, Fudan University (Xiamen Branch)
2Zhongshan Hospital, Fudan University
OBJECTIVES The purpose of the current study was to determine the correlation between the apnea hypopnea index (AHI) and ambulatory arterial stiffness index (AASI) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS).
METHODS A total of 201 patients with OSAHS admitted to Zhongshan Hospital, Fudan University (Xiamen Branch) from January 2021 to October 2023 were selected and divided into two groups based on the AHI (mild-to-moderate and severe groups). All patients completed the general data collection, polysomnography, and dynamic blood pressure monitoring. One-way analysis of variance was used to compare the general clinical characteristics between groups with OSAHS of different severity. Correlation analysis was used to compare the correlation between AASI and polysomnography parameters. Multiple linear regression analysis was used to determine the correlation between AASI and polysomnography parameters.
RESULTS The results showed that body mass index, uric acid level, and AASI were higher in patients with severe OSAHS than patients with mild-to-moderate OSAHS, while the high-density lipoprotein (HDL) level was lower in patients with severe OSAHS than patients with mild-to-moderate OSAHS. Correlation analysis showed that the AASI was positively correlated with age, the AHI, and the percentage of total time with oxygen saturation level <90% (T90), and negatively correlated with the estimated glomerular filtration rate (eGFR) and average pulse oxygen saturation (SpO2). While other factors remained unchanged, for every year increase in age, the AASI increased by 0.375 and the AHI increased by 0.177. For every 1% increase in the T90, the AASI increased by 0.213.
CONCLUSIONS There was a correlation between OSAHS severity and the AASI, and the degree of arteriosclerosis in OSAHS patients increased with an increase in the AHI.
GW35-e0187
Dilare Adi, Aibibanmu Aizezi, Yitong Yitong
Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES Familial hypercholesterolemia (FH) is the most important genetic risk factor for ASCVD. The detection rate, individualized treatment rate, and socioeconomic burden of FH patients from different ethnic groups in Xinjiang have not been reported yet. The aim of this study is to describe the detection rate, clinical characteristics and treatment status of FH in different ethnic groups in Xinjiang China.
METHODS A total of 37,988 patients who attended the First Affiliated Hospital of Xinjiang Medical University between January 2010 and January 2023, aged between 18–80 years old, and diagnosed with hyperlipidemia with LDL-C greater than 3.5 mmol/L were selected. A retrospective cross-sectional study was conducted according to the diagnostic criteria of the Dutch Clinical Lipid Network Criteria (DLCN), the Modified Chinese Lipid Network Criteria (MDLCN), and the Chinese Expert Consensus on the Screening and Treatment of FH (CEC) separately to describe the detection rate of FH in different ethnic groups in Xinjiang, and to explore the rate of lipid-lowering treatment for patients with FH and its influencing factors using Logistic Regression Model.
RESULTS (1) The detection rate of clinically confirmed FH according to the DLCN was 11.47% (4358 patients), 41% (1858 columns) of males, 59% (2653 patients) of females, 58% (2612 patients) of Han Chinese, 30% (1370 patients) of Uyghurs, and 11% (512 patients) of Kazakhs. FH detection rate was 2.12 times higher than that of Uyghurs and 6 times higher than that of Kazakhs. (2) The detection rate of FH by MDLCN was 83.96% (31,893 cases), 47% in men (14,953 columns), 53% in women (16,940 cases), 60% in Han Chinese (19,272 cases), 27% in Uyghurs (8551 cases), and 13% in Kazakhs (3993 cases). The detection rate of FH in Han Chinese was 2 times higher than that of Uyghurs and 5 times higher than that of Kazakhs. (3) The detection rate of FH by CEC was 4.17% (1584 cases), 42% (663 cases) for men and 58% (921 cases) for women; 60% (947 cases) for Han Chinese, 29% (456 cases) for Uyghurs, and 10% (161 cases) for Kazakhs, and the detection rate of FH in the Han Chinese group was twice as high as that in the Uyghur and five times as high as that of the Kazakhs (4) The proportion of FH patients receiving low/moderate/high-intensity statin, moderate-intensity statin + ezetimibe, high-intensity statin + ezetimibe, and statin + combined with PCSK9 inhibiters for lipid lowering were 1.0%, 40.7%, 6.9%, 25.0%, 3.4%, and 2.7%, respectively.
CONCLUSIONS (1) The use of MDLCN may be more applicable to the national population; the detection rate of FH in the Han population is higher than that of Uyghurs and Kazakhs, This study initially fills the gaps in the prevalence, diagnosis, phenotypic characterization, and treatment of FH in different ethnic groups in Xinjiang, and provides a strong basis for early screening, diagnosis, prevention, and treatment of FH in Xinjiang.
GW35-e0253
Xing Yu1, Yuhong Liu2, Liangdi Xie1
1Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
2Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
OBJECTIVES The aim of this study is to analyze the correlation between serum uric acid (SUA) and cystatin C (Cys-C) levels and the occurrence of peripheral artery, carotid artery, and coronary artery atherosclerosis in elderly patients with primary hypertension. We aim to explore the diagnostic value of SUA and Cys-C in predicting the development of atherosclerosis.
METHODS Middle-aged and elderly patients admitted to the Department of Cardiovascular Medicine at the First Affiliated Hospital of Guangdong Pharmaceutical University from October 2021 to March 2023 and diagnosed with primary hypertension were selected for this study. All patients underwent carotid artery color Doppler ultrasound, non-invasive arterial stiffness detection of the four limbs, and coronary angiography examinations. Arterial stiffness was assessed using brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (cIMT), carotid Crouse scores, and Gensini scores as indicators of atherosclerosis severity. Patient data including age, height, weight, systolic blood pressure, diastolic blood pressure, blood lipids, serum uric acid (SUA), and cystatin C (Cys-C) levels were collected. Based on their SUA and Cys-C levels, the study population was divided into high-level SUA group, low-level SUA group, high-level Cys-C group, and low-level Cys-C group according to the median values. Statistical methods such as t-test, Spearman correlation analysis, and univariate and multivariate logistic regression analysis were used to analyze the relationship between different SUA and Cys-C levels and atherosclerosis.
RESULTS A cross-sectional study was conducted on 338 patients. Multivariate logistic regression analysis revealed that age, hypertension lasting more than 20 years, and high levels of Cys-C were statistically significant in relation to carotid atherosclerosis and peripheral arterial stiffness (P < 0.05). Additionally, age, pulse pressure (PP), high-density lipoprotein cholesterol (HDL-C), duration of hypertension, and Cys-C levels had significant associations with coronary atherosclerosis (P < 0.05). Correlation analyses indicated that Cys-C and SUA were positively correlated with peripheral arterial stiffness (baPWV), carotid atherosclerosis (cIMT, Crouse scores), and coronary atherosclerosis (Gensini scores). ROC curve analysis suggested that the cutoff values for Cys-C in predicting peripheral arterial stiffness, carotid atherosclerosis, and coronary atherosclerosis were 0.78 mg/L, 0.81 mg/L, and 0.76 mg/L, respectively.
CONCLUSIONS Elevated levels of Cys-C and SUA are associated with peripheral, carotid, and coronary atherosclerosis in middle-aged and elderly patients with primary hypertension. As the levels of Cys-C and SUA increase, the risk and severity of atherosclerosis also rise.
GW35-e0277
Lihua Hu, Jianping Li
Peking University First Hospital
OBJECTIVES Statins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy.
METHODS A quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the “Up to standard” (US) group and the “Below standard” (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites.
RESULTS A total of 10 US and 10 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-β-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism.
CONCLUSIONS The findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins.
GW35-e0283
Deng Yifan1,2, He Shenghu1, Zhang Jing2, Zhu Li1
1Taizhou People’s Hospital Affiliated to Nanjing Medical University
2Northern Jiangsu People’s Hospital
OBJECTIVES The emergence of novel lipid-lowering medications, such as PCSK9 inhibitors, has provided a new avenue for intensifying lipid-lowering therapy. Currently, PCSK9 inhibitor use is primarily indicated for patients whose LDL-C levels remain above target levels 4–6 weeks after statin therapy, often in combination with cholesterol absorption inhibitors. The early use of PCSK9 inhibitors in ACS patients is a topic of considerable debate, and whether it can provide clinical benefits remains uncertain.
METHODS A systematic search of PubMed, Web of Science, and Embase databases was conducted for studies involving the use of PCSK9 inhibitors in ACS patients from inception to October 2023. Two independent researchers screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was performed using STATA 16.0 software.
RESULTS Nine studies, involving a total of 2896 ACS patients, were included. Among them, 1866 patients received high-intensity statin therapy, and 1003 patients received PCSK9 inhibitors within 72 hours of hospital admission. The meta-analysis results showed that compared to high-intensity statin monotherapy, PCSK9 inhibitors were more effective in lowering LDL-C [Standardized Mean Difference (SMD) = −1.904, 95% CI (−2.31, −1.05), P < 0.01], TC [SMD = −0.85, 95% CI (−1.71, 0.02), P < 0.05], and Non-HDL-C [SMD = −1.60, 95% CI (−2.02, −1.18), P < 0.01] levels while increasing HDL-C [SMD = 0.189, 95% CI (0.05, 0.32), P < 0.05] levels. The magnitude of LDL-C reduction within the short term was also significant [Weighted Mean Difference (WMD) = −39.6, 95% CI (−49.49, −29.43), P < 0.01], and a higher proportion of patients achieved target LDL-C levels within 2 months [Odds Ratio (OR) = 37.23, 95% CI (18.63, 74.41), P < 0.01]. Regarding the occurrence of Major Adverse Cardiovascular Events (MACEs), ACS patients who received early in-hospital PCSK9 inhibitors, as compared to statin drugs, may have a lower risk of Coronary revascularization [Relative Risk (RR) = 0.78, 95% CI (0.62, 0.98), P < 0.05], Recurrent ACS [RR = 0.62, 95% CI (0.42, 0.94), P < 0.05], and Stroke [RR = 0.31, 95% CI (0.09, 1.04), P = 0.058]. The risk of adverse drug events, including ALT increase >3× ULN [RR = 1.05, 95% CI (0.55, 2.01), P = 0.878], local injection site reactions [RR = 2.136, 95% CI (0.97, 4.71), P = 0.06], and musculoskeletal pain [RR = 1.34, 95% CI (0.81, 2.23), P = 0.26], was not significantly increased.
CONCLUSIONS Early in-hospital use of PCSK9 inhibitors in ACS patients can rapidly reduce LDL-C levels to target levels, potentially reducing the short-term risk of coronary revascularization, recurrent ACS, and stroke without increasing the risk of adverse drug events such as ALT abnormalities and musculoskeletal pain. However, further research is needed to explore the long-term benefits for patient prognosis.
GW35-e0314
Jianhua Fan1, Qiong Wu1, Cun Xu1, Zhaochen Xia1, Licheng Lu1, Haixiang Xu1, Xiaogang He2, Wen Pan1
1Department of Cardiology, Kunshan Hospital of Traditional Chinese Medicine
2Department of Neurology, Kunshan Hospital of Traditional Chinese Medicine
OBJECTIVES To assess the clinical efficacy of Jiangzhi Mai’an Granules (JZMA) in treating stable angina pectoris and carotid atherosclerotic plaques associated with phlegm and blood stasis obstruction.
METHODS One hundred twenty patients with stable angina pectoris and carotid atherosclerotic plaques of the phlegm and blood stasis obstruction type were randomly assigned to two groups. The control group (n = 60) received standard Western medical treatment, while the treated group (n = 60) received additional JZMA treatment based on the control group’s regimen. Both groups underwent a 3-month treatment period. Outcomes assessed included carotid intima-media thickness (CIMT), carotid plaque thickness and area, Traditional Chinese Medicine (TCM) syndrome score, blood lipids (TC, TG, LDL-C, HDL-C), lipoprotein-related phospholipase A2 (Lp-PLA2), and TCM syndrome scores before and after treatment.
RESULTS The treated group achieved a total effective rate of 93.3% (56/60) compared to 78.3% (47/60) in the control group. Post-treatment CIMT, carotid plaque thickness, and area were significantly reduced in the treated group compared to baseline (P < 0.05) and were lower than those in the control group (P < 0.05). Lipid levels, including TC, TG, LDL-C, and Lp-PLA2, were significantly decreased in both groups post-treatment (P < 0.05), with the HDL-C level increased in the treated group (P < 0.05). The treated group had lower lipid levels compared to the control group post-treatment (P < 0.05). TCM syndrome scores were significantly improved in both groups post-treatment (P < 0.05), with the treated group showing lower scores than the control group (P < 0.05). The incidence of adverse reactions was not statistically significant between the two groups.
CONCLUSIONS JZMA treatment has been shown to effectively lower CIMT, reduce carotid plaque size, and improve lipid profiles by decreasing TC, TG, LDL-C, and Lp-PLA2 levels in patients with stable angina pectoris and carotid atherosclerotic plaques, while also alleviating clinical symptoms.
GW35-e0329
Na Sun1, Wenjing Li1,2, Xintong Li1, Daye Liu1, Yujia Zhai1, Tianmin Xu1, Chenliang Song1, Wei Sun1,3, Hao Su1,4, Daqing Zhang1
1Shengjing Hospital of China Medical University
2Binzhou People’s Hospital
3The Third People’s Hospital of Dalian
4The People’s Hospital of Liaoning Province
OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) has been recognised as an emerging risk factor for atherosclerotic cardiovascular disease (ASCVD). Recent serial evidence has shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively treat fatty liver, slow fibrosis, and reduce cardiovascular metabolic risk. GLP-1RAs have been recently approved for the indication of biopsy-proven non-alcoholic steatohepatitis (NASH).
METHODS We searched PubMed, Embase, and the Cochrane Library from database inception until September 2023 for randomised controlled trials (RCTs) comparing GLP-1RAs with placebo or any other active comparator in patients with NAFLD. Primary outcomes included improvement in liver histopathology and hepatic enzyme parameters, including liver fat content (LFC) and liver stiffness. We assessed 15 secondary efficacy outcomes of cardiovascular metabolic indicators in total. We synthesised the data using weighted mean differences (WMD), risk ratios (RR), and 95% confidence intervals (CI).
RESULTS We included 14 studies with 1161 participants. GLP-1RA treatment improved liver histopathology, reducing NASH (RR = 2.67, 95% CI = 1.87, 3.81), LFC (WMD = −3.36; 95% CI = −4.79, −1.92). It also improved hepatic enzyme levels and decreased cardiovascular metabolic indicators, such as body weight, body mass index (BMI), waist circumference, subcutaneous and visceral adipose tissue. Additionally, it lowered post-load blood glucose (PBG), fasting blood glucose (FBG), glycosylated haemoglobin (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR).
CONCLUSIONS GLP-1RA treatment improved liver dysfunction and histopathological abnormalities, reduced SAT and VAT, and modified some cardiovascular metabolic risk factors in patients with NAFLD, aiding in ASCVD risk control.
GW35-e0446
Na Wang
Department of Cardiology, Chongqing Institute of Cardiology, Daping Hospital, Third Military Medical University
OBJECTIVES Infection is thought to be involved in artheroclerosis. Recent studies showed the close relationship between helicobacter pylori (H. pylori) and coronary artery disease in patients. It is interesting to find H. pylori DNA and CagA protein in atherosclerotic plaques.
METHODS As one kind of bacteria in the stomach, how H. pylori escapes from the defensive system and goes to atherosclerotic plaque keeps unknown. Besides of bacterium itself, H. pylori has the ability to secret outer membrane vesicles (OMVs), which were thought to play some roles in the organ or tissue in long-distance. We wonder whether or not OMVs from H. pylori are involved in the pathogenesis of atherosclerosis.
RESULTS Our present study found that the treatment of Apol E−/− mice with OMVs accelerated the artherosclerosis; OMVs decreased the viability of human umbilical vein endothelial cells (HUVECs), an endothelial cell line, while increased its apoptosis, accompanied by increased NF-κB expression. Considering of the complex of OMV compounds, we made the nucleotide degradation by RNase. It resulted that RNase treatment had no effect on OMVs-mediated effects in HUVECs, indicating that proteins, rather than nucleotides, play a key role in the pathogenesis of atherosclerosis. After remove of lipopolysaccharide (LPS) or neutralization of CagA, two well-known proteins, by corresponding antibodies, the OMVs-mediated effects were reduced.
CONCLUSIONS Our present study indicated that OMVs from H. pylori, via LPS and CagA, accelerated artherosclerosis by injured endothelial cells.
GW35-e0577
Raisa Surkova1,2, Elizaveta Marasaeva2, Dmitry Kashirskikh1,2, Tatiana Kovyanova2, Igor Sobenin2,3, Alexander Orekhov1,2
1Institute for Atherosclerosis Research, Moscow, Russian Federation
2Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
3V.N. Smirnov Institute of Experimental Cardiology, E.I. Chazov National Medical Research Center of Cardiology, Moscow, Russian Federation
OBJECTIVES The development of atherosclerosis begins with the accumulation of circulating modified low density lipoproteins (LDL) in the subendothelial space of the arterial wall. One of the most well-known atherogenic modifications of LDL is desialylation, that is, the loss of terminal sialic acid by glycoconjugates that are part of LDL. Proteins that have sialidase activity can circulate in human blood, i.e., they can cleave sialic acid residues from the two-antennary polysaccharide chains of proteoglycans. Desialylated LDL is highly immunogenic and induces the production of IgG autoantibodies, which bind to LDL to form circulating immune complexes (CIC). The aim of this study was to establish associations between the levels of sialic acid in LDL, sialidase activity and the cholesterol content of lipid-containing CIC in the blood serum of patients with atherosclerosis.
METHODS Measurement of sialidase activity in blood serum was carried out using commercial kits Abcam ab138888 Neuraminidase Assay Kit Fluorimetric-Blue (Abcam, USA). LDL was isolated using KBr density gradient ultracentrifugation. LDL sialic acid content was measured using the modified Warren method. To determine the cholesterol content in lipoprotein-containing CIC, immune complexes were precipitated from serum using PEG 6000. Cholesterol content was measured using a commercial enzymatic kit for determining the concentration of total cholesterol in serum and blood plasma (Vector-Best, Russia). Statistical data processing was carried out using the IBM SPSS Statistics 23 statistical software package using the Pearson correlation coefficient. The significance level was set at 0.05.
RESULTS We analyzed 51 blood serum samples from patients with atherosclerosis and LDL isolated from it. As a result of the correlation analysis, a significant positive relationship was revealed between the cholesterol content of CIC and sialidase activity in the blood serum (r = 0.305 at P = 0.029). At the same time, no correlation was found between the content of sialic acid in LDL and sialidase activity in the blood serum, as well as between the cholesterol content of CIC in the blood serum and sialic acid in LDL.
CONCLUSIONS It should be assumed that increased sialidase activity in the blood serum leads to the formation of desialylated immunogenic LDL with the subsequent production of autoantibodies and the formation of CIC. This study was supported by the Russian Science Foundation (Grant #23-65-10014).
GW35-e0578
Raisa Surkova1,2, Elizaveta Marasaeva1, Natalia Elizova1, Tatiana Kovyanova1, Igor Sobenin1,3, Alexander Orekhov1,2
1Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
2Institute for Atherosclerosis Research, Moscow, Russian Federation
3V.N. Smirnov Institute of Experimental Cardiology, E.I. Chazov National Medical Research Center of Cardiology, Moscow, Russian Federation
OBJECTIVES Proteins that have neuraminidase (sialidase) activity may circulate in human blood and can cleave sialic acid residues from the biantennary polysaccharide chains of proteoglycans. Desialylation of native low-density lipoproteins (LDL) leads to the acquisition of atherogenic properties. It is unclear how known intracellular neuraminidases can enter the bloodstream and exhibit enzymatic activity. We previously established that extracellular vesicles have sialidase activity, i.e. can transport proteins that can cleave sialic acids from LDL. The aim of this study was to study the influence of extracellular vesicles on the atherogenic properties of LDL and proinflammatory cell activation.
METHODS Blood serum from patients with coronary heart disease was used as biological material to obtain vesicles. Vesicles were isolated from blood serum using a 6% PEG 6000 solution. To assess the ability of vesicles to modify the atherogenic properties of LDL, vesicles and LDL were incubated with THP-1 cell cultures for 24 hours, intracellular lipids were extracted, and intracellular cholesterol content was measured. To study the effect of vesicles on proinflammatory activation, THP-1 cells were incubated under control conditions and under the influence of LPS (Sigma) for 24 hours. The content of TNF-α и IL-1β in the culture medium samples was determined by ELISA. Statistical data processing was carried out using the IBM SPSS Statistics 23 statistical software package using the Mann-Whitney test. The significance level was set at 0.05.
RESULTS When vesicles were incubated with THP-1 cells in the presence of LDL, a statistically significant increase in cholesterol content was observed compared to the control (cells without added substances). LDL was able to cause a statistically significant intracellular accumulation of cholesterol when incubated with cells, i.e. were atherogenic. When comparing the intracellular cholesterol content after incubation of vesicles and LDL with cell cultures and incubation of cells with vesicles, no statistically significant accumulation of cholesterol was observed. When vesicles were incubated with cells in the presence of LPS, no statistically significant changes in the content of TNF-α и IL-1β in the culture medium compared to incubation with LPS (caused a statistically significant increase in the content of TNF-α и IL-1β).
CONCLUSIONS Thus, the extracellular vesicles do not have atherogenic properties. This study was supported by the Russian Science Foundation (Grant #22-65-00005).
GW35-e0580
Raisa Surkova1,2, Dmitry Kashirskikh1,2, Tatiana Kovyanova1, Igor Sobenin1,3, Alexander Orekhov1,2
1Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
2Institute for Atherosclerosis Research, Moscow, Russian Federation
3V.N. Smirnov Institute of Experimental Cardiology, E.I. Chazov National Medical Research Center of Cardiology, Moscow, Russian Federation
OBJECTIVES Proteins that have neuraminidase (sialidase) activity can circulate in human blood, i.e., they can cleave sialic acid residues from biantennary polysaccharide chains of proteoglycans. If such cleavage occurs with apoproteins of low-density lipoproteins (LDL), then native LDL acquires atherogenic properties. It is unclear how the known intracellular neuraminidase can enter the circulation and induce serum neuraminidase activity. The purpose of this study was to determine whether proteins responsible for LDL desialylation in serum could circulate in an exosome-associated state.
METHODS Human serum samples with high sialidase activity were selected using commercially available kits (Abcam ab138888 Neuraminidase Assay Kit Fluorimetric-Blue, Abcam, USA). Serum samples were filtered (0.45 μm pore diameter) and then large extracellular vesicles were precipitated with PEG 6000. The pellet was reconstituted with PBS and ultracentrifuged at 115,000 g. Sialidase activity was measured in all supernatant and pellet fractions at each stage.
RESULTS Low levels of sialidase activity were found in precipitates of PEG 6000 filtered serum samples, while most of the activity remained in the supernatant. In exosomes isolated by ultracentrifugation, the remaining sialidase activity was distributed approximately equally between the supernatant and pellet.
CONCLUSIONS The hypothesis that most proteins with sialidase activity circulate in the form of a protein complex with exosomes seems unlikely. However, it should be assumed that the majority of proteins with sialidase activity circulate in the blood in free form, but a minority of them may be non-covalently associated with the exosome membrane. This study was supported by the Russian Science Foundation (Grant #22-65-00005).
GW35-e0602
Nikolai Orekhov1,2, Elizaveta Pleshko1,2, Andrey Omelchenko1, Tatiana Kovyanova1, Igor Sobenin1,3
1Institute of General Pathology and Pathophysiology
2Lomonosov Moscow State University
3National Medical Research Center of Cardiology
OBJECTIVES In our previous studies, the prognostic value of low-density lipoprotein-containing circulating immunecomplexes (LDL-CIC) was assessed in asymptomatic patients with increased carotid intima media thickness (cIMT) taken as the ultrasonographic characteristic of extracoronary atherosclerosis. Elevated LDL-CIC level appeared to be a predictor for cIMT progression, along with the increased levels of total and LDL cholesterol; the low level of LDL-CIC was the only biochemical parameter that predicted the absence of cIMT progression. However, the interplay between LDL-CIC and other risk factors of cardiovascular disease was not assessed. To fill this gap, the study was undertaken to analyze in-depth the possible prognostic significance of LDL-CIC, employing the novel developed mathematical algorithms.
METHODS The data on cIMT progression in 101 asymptomatic men over 12 months of follow-up were analyzed using methods of computer modeling and bioinformatics.
RESULTS We had at our disposal the data on the characteristics of patients and biochemical lipidparameters, such as total, low-density and high-density lipoproteins cholecterol, triglycerids, Cho-CIC, obtained during observation of patients for 3–12 months. None of the indicators had prognostic significance regarding the development of carotid atherosclerosis assessed by intima-media thickness. Only the combination of age and Cho-CIC demonstrated 94.1% accuracy and 98.9% specificity for predicting the progression of carotid atherosclerosis over twelve months.
CONCLUSIONS Thus, the results of the present study demonstrate that Cho-CIC may be employed as a candidate prognostic marker for clinical implications if combined with other factors, such as age. This work was financially supported by the Russian Science Foundation, grant #23-65-10014.
GW35-e0656
Lihua Hu, Long Zhang, Fangfang Fan, Yan Zhang, Jianping Li
Peking University First Hospital
OBJECTIVES Familial hypercholesterolemia (FH), among the commonest inherited metabolic disorders, is due to a group of genetic disorders that result in abnormally high LDL cholesterol (LDL-C) levels that cause atherosclerotic plaque deposition in arteries and a markedly increased risk of coronary heart disease (CHD) at a young age. In most cases, inheritance is autosomal codominant with homozygotes having double the LDL-C levels of heterozygotes; therefore, the phenotype of heterozygous FH (HeFH) is relatively obscure. Moreover, HeFH is often undetected and undertreated. The Dutch Lipid Clinical Network (DLCN) FH criteria is a commonly used diagnostic standard in European countries; however, the diagnostic standard of HeFH in China is unknown. Giving that genetic testing is the gold standard for FH diagnosis, we aimed to estimate the screening, and diagnosis of HeFH among Chinese general population.
METHODS We conducted a large-scale, multicenter, observational study from “National Key Research and Development Program of China”. Patients with dyslipidemia are included in the project. In our study, patients with DLCN ≥6 scores or LDL-C ≥4.9 mmol/L were further subjected to FH gene testing by whole exome sequencing. The main exclusion criteria include abnormal cholesterol elevation caused by secondary causes. A total of 3948 patients (mean age: 53.2 ± 12.6 years; 41.5% males) with hypercholesterolemia and genetic testing data were ultimately included in the analysis.
RESULTS There was a total of 796 (20.2%) HeFH patients. The proportion of single gene mutations in LDLR, ApoB, PCSK9, and ABCG5 was 649 (82%), 94 (12%), 15 (2%), and 15 (2%), respectively. Compared with non FH patients, HeFH patients were more likely to be younger, to have high value in LDL-C levels, to have higher rates of fatty corneal arch, family history of early onset CHD, signs of skin lipid deposition, early onset CHD, and lipid-lowering drugs used. Based on univariate and multivariate logistic regression analysis, the variables of age, BMI, family history of FH, Skin/Achilles tendon xanthoma/fatty corneal arch within first degree relative, fatty corneal arch (<45 years), Premature CAD, LDL-C and using lipid-lowering drugs were associated with the prevalence of HeFH. The area under the curve was 0.75, which was better than DLCN FH criteria. The sensitivity and specificity which predicted the presence of HeFH were 0.60 and 0.77, respectively. Using machine learning and HeFH risk attribution, we obtained a screening and diagnostic model for HeFH. A total score of 10 or above is considered definite-HeFH; A total score of 6–9 is probable-HeFH; and A total score of 3–5 is possible-HeFH.
CONCLUSIONS A set of screening and diagnostic criteria for HeFH suitable for the Chinese population was developed based on genetic testing. Further research is warranted to explore of the accuracy of the model.
GW35-e0692
Raisa Surkova1,2, Elizaveta Marasaeva1, Dmitry Kashirskikh1,2, Igor Sobenin1,3, Tatiana Kovyanova1, Alexander Orekhov1,2
1Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
2Institute for Atherosclerosis Research, Moscow, Russian Federation
3V.N. Smirnov Institute of Experimental Cardiology, E.I. Chazov National Medical Research Center of Cardiology, Moscow, Russian Federation
OBJECTIVES Atherogenic low density lipoprotein (LDL) circulating in the blood of patients with atherosclerosis has various modifications. One of the primary atherogenic modifications of LDL is desialylation, that is, the loss of terminal sialic acid by glycoconjugates that are part of LDL. Galactosylation is the addition of galactose to the protein or lipid portion of LDL. The aim of the study was to test the hypothesis that resialylation and reglycosylation of LDL from patients with coronary artery disease (CAD) may affect the atherogenic potency of LDL.
METHODS Human LDL was treated with recombinant sialyltransferase and galactosyltransferase. The resialylation effect was monitored by measuring LDL sialic acid levels using the modified Warren’s method. The atherogenic potential of LDL was assessed by the ability to induce cholesterol accumulation in THP-1 cells when incubated with LDL.
RESULTS LDL taken from CAD patients was able to induce statistically significant intracellular cholesterol accumulation, i.e. was atherogenic. The mean increase in cellular cholesterol level accounted for 2.4-fold as compared to control cells (P < 0.001). LDL resialylation by sialyltransferase resulted in moderate but statistically significant increase in LDL sialic acid content by 14% above the initial value (P = 0.006). Resialylation of LDL resulted in incomplete but statistically significant decrease in LDL atherogenicity by the mean of 44% of initial value (P < 0.001). Regalactosylation of LDL by galactosyltransferase did not lead to a statistically significant change in the atherogenic properties of LDL. Combined resialylation and regalactosylation of LDL also did not lead to a statistically significant change in the atherogenic properties of LDL.
CONCLUSIONS Low-density lipoprotein resialylation in vitro leads to a decrease in the atherogenic potential of LDL. These results may indicate that LDL resialylation is a possible target for the prevention and treatment of atherosclerosis. This study was supported by the Russian Science Foundation, Grant #20-15-00264.
GW35-e0729
Takumi Nakayama1, Tsuyoshi Shinozaki2, Masahiro Suzuki3, Yoichi Ajiro4, Satoru Sakagami5, Morihiro Matsuda6, Junichi Funada7, Masatoshi Shimizu8, Takashi Takenaka9, Yukiko Morita10, Kazuya Yonezawa11, Hiromi Matsubara12, Toshihiro Nakamura13, Kazuteru Fujimoto14, Yujiro Ono15, Toru Kato16, Akiyo Ninomiya17, Takashi Unoki18, Daisuke Takagi19, Kyohma Wada20, Miyaka Wada1, Yuka Maeda1, Nobutoyo Masunaga1, Mitsuru Ishii1, Moritake Iguchi1, Kazuhiko Kotani21, Mitsuru Abe1, Masaharu Akao1, Koji Hasegawa1, Hiromichi Wada1
1NHO (National Hospital Organization) Kyoto Medical Center, Kyoto, Japan
2NHO Sendai Medical Center, Sendai, Japan
3NHO Saitama Hospital, Wako, Japan
4NHO Yokohama Medical Center, Yokohama, Japan
5NHO Kanazawa Medical Center, Kanazawa, Japan
6NHO Kure Medical Center and Chugoku Cancer Center, Kure, Japan
7NHO Ehime Medical Center, Toon, Japan
8NHO Kobe Medical Center, Kobe, Japan
9NHO Hokkaido Medical Center, Sapporo, Japan
10NHO Sagamihara National Hospital, Sagamihara, Japan
11NHO Hakodate National Hospital, Hakodate, Japan
12NHO Okayama Medical Center, Okayama, Japan
13NHO Kyushu Medical Center, Fukuoka, Japan
14NHO Kumamoto Medical Center, Kumamoto, Japan
15NHO Higashihiroshima Medical Center, Higashihiroshima, Japan
16NHO Tochigi Medical Center, Utsunomiya, Japan
17NHO Nagasaki Kawatana Medical Center, Higashisonogi-gun, Japan
18Saiseikai Kumamoto Hospital, Kumamoto, Japan
19Hirakata Kohsai Hospital, Hirakata, Japan
20Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
21Jichi Medical University, Shimotsuke, Japan
OBJECTIVES A recent study demonstrated that very high high-density lipoprotein cholesterol (HDL-C) levels (>80 mg/dL) were associated with higher mortality risk in patients with coronary artery disease (CAD). However, the study included only a small number of Asian patients. The association between very high HDL-C levels and mortality in high-risk Japanese men and women should be confirmed.
METHODS Using data from two multicenter, prospective cohort studies of 5397 Japanese patients with suspected or known CAD (2327 from the ANOX Study and 3070 from the EXCEED-J Study), we assessed the association between HDL-C levels and all-cause death in 3714 men (mean [SD] age, 69.3 [10.7] years) and 1683 women (mean [SD] age, 72.5 [9.6] years). Patients were divided into 5 categories of HDL-C: 30 mg/dL or less, 30–40 mg/dL, 40–60 mg/dL, 60–80 mg/dL, and greater than 80 mg/dL.
RESULTS Kaplan-Meier curves for all-cause death by HDL-C categories in men and women. In unadjusted models, compared with the reference category with HDL-C levels of 40–60 mg/dL, those with low HDL-C levels (≤30 mg/dL) and those with very high HDL-C levels (>80 mg/dL) had higher risks of all-cause death (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.33–3.18 for HDL-C ≤30 mg/dL; HR, 1.68; 95% CI, 1.07–2.65 for HDL-C >80 mg/dL) in men, but not in women (HR, 2.37; 95% CI, 0.95–5.92 for HDL-C ≤30 mg/dL; HR, 0.45; 95% CI, 0.19–1.04 for HDL-C >80 mg/dL). Even after adjustment for potential clinical confounders, those with low HDL-C levels (≤30 mg/dL) had a higher risk of all-cause death (HR, 1.96; 95% CI, 1.25–3.08), but those with very high HDL-C levels (>80 mg/dL) did not (HR, 1.43; 95% CI, 0.89–2.28).
CONCLUSIONS High-risk Japanese men with very high HDL-C levels (>80 mg/dL) tended to have, but did not have a statistically significant higher risk of all-cause death. These findings warrant the need for larger and/or longer follow-up studies in high-risk Asian populations.
GW35-e0807
Lihua Hu, Yan Zhang, Jianping Li
Peking University First Hospital
OBJECTIVES Statins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy.
METHODS A quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the “Up to standard” (US) group and the “Below standard” (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites.
RESULTS A total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-β-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism.
CONCLUSIONS The findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins.
GW35-e1102
Ying Xu, Miaohan Qiu, Zizhao Qi, Jing Li, Yi Li, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Diseases, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Recent studies found that the use of drugs to raise high density lipoprotein cholesterol (HDL-C) levels did not reduce or even increase the risk of cardiovascular disease (CVD) in people, and research also suggested that elevated levels of HDL-C may be related to an increased risk of CVD. However, it is not clear whether this is the case in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI), and whether this association is affected by gender.
METHODS A total of 7747 CHD patients undergoing PCI were selected from the Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study, including 5861 men and 1886 women. The primary outcomes were ischemic events including the composite of cardiac death, myocardial infarction (MI), and/or ischemic stroke at 5 years. The secondary outcomes were independent components of ischemic events and all-cause mortality, bleeding events as defined by Bleeding Academic Research Consortium (BARC), including BARC 2–5 and BARC 3–5 bleeding at 5 years. The restricted cubic splines (RCS) were used to test the nonlinear relationship between continuous HDL-C levels and outcomes.
RESULTS Patients were divided into quartile groups based on HDL-C levels. The average age of male patients was 59.10 years old, with 1369 diabetes mellitus (DM) (23.36%), 3264 hypertension (55.69%), 1672 hyperlipidemia (28.53%), and 3101 smoking (52.91%), while female patients were 65.26 years old, with 586 DM (31.07%), 1331 hypertension (70.57%), 623 hyperlipidemia (33.03%) and 189 smoking (10.02%). Ischemic events and MI were statistically different between groups in male patients, with HDL-C in the range of 0.98 mmol/L–1.18 mmol/L having the lowest incidence (P < 0.05). All bleeding events decreased considerably with increasing HDL-C levels (P < 0.001). There was no statistical difference in the ischemic and bleeding events for women. The ischemic events were connected with HDL-C in a U-shaped relationship in CHD patients undergoing PCI, and in male patients, ischemic events and all-cause mortality were U-shaped with HDL-C, outcomes risk increased at both high and low levels of HDL-C (P nonlinearity = 0.007). However the nonlinear relationship did not hold in females.
CONCLUSIONS This study revealed a U-shaped association between ischemic events, all-cause mortality and HDL-C in male patients with CHD who underwent PCI, but no nonlinearity was observed in females.
GW35-e1167
Aikedan Maimaiti
Department of Epidemiology, School of Public Health, Fudan University, Shanghai 20032, China
OBJECTIVES Being a complex disease, CAD is caused by genetic and environmental factors as well as the interactions between these factors. Relative to the traditional CAD predictor LDL cholesterol (LDL-C), epidemiologic studies and clinical trials have demonstrated that low-density lipoprotein particle (LDL-P) is an alternative indicator and clinical target for the treatment of dyslipidemia as well as CAD, even accurate and stronger than LDL-C and apolipoprotein-B. However, it’s unknown if the role of LDL-P subclasses in causing CAD is innately different or formed by acquired pathophysiological mechanisms is not clear. There are few studies regarding the genetic locus of LDL-P and the causal relationship with CAD, which requires us to combine more standard approaches and utilize large populations with enough power to explore, and validation studies in later stages are essential.
METHODS The study included 214,793 unrelated white British population from UK Biobank. Five genome-wide association studies were performed which related to Nuclear Magnetic Resonance (NMR) spectroscopy measured total LDL-P concentration, average diameter of LDL-P, and Large-size, Medium-size, Small-size LDL-P concentration, to identify LDL-P subclasses associated single nucleotide polymorphisms (SNPs). BOLT-LMM and PLINK, etc. software was used to select significant SNPs under the P-value < 5 × 10−8, loci that remained significant after LD clumping (r2 < 0.001, 100 kb) were entered into the screening of instrumental variables (IVs), and loci present after comparison with previously reported loci in the Global Lipids Genetics Consortium (GLGC) and GWAS catalog were defined as novel. Univariable and multivariable MR analysis were conducted through the Inverse-variance weighted (IVW), MR-egger, MR-PRESSO, CAUSE and MR-LASSO etc. for obtain robust conclusions. PRS was calculated for the remaining prominent LDL-P trait(s) in multi-MR, converted ICD-10 to PHECODE, and utilized the PHESANT package to conduct PheWAS analysis.
RESULTS Of the 214,793 individuals included in the study, the mean age of men and women was 57.2 years and 56.9, and of whom 54% were women. The GWAS identified multiple SNPs associated with significant P-values for total LDL-P (41), Ad LDL-P (27), large-size LDL-P (40), medium-size LDL-P (37), and small-size LDL-P (41). Assessed individually using univariable MR, total LDL-P concentration (odds ratio [OR] 1.69; 95% CI 1.52–1.96; P < 1.28 × 10−21), Ad LDL-P (OR 1.23; 95% CI 0.99–1.53; P < 2.00 × 10−2), large-size LDL-P (OR 1.83; 95% CI 1.68–2.01; P < 1.05 × 10−41), medium-size LDL-P (OR 1.82; 95% CI 1.64–2.01; P < 1.05 × 10−30), small-size LDL-P (OR 1.78; 95% CI 1.61–1.96; P < 2.62 × 10−31), except for Ad LDL-P, all other four LDL-P traits had effect estimates consistent with a higher risk of CAD. All sensitivity analysis using different methods were consistent with the above results. In multivariable MR, excluding Ad LDL-P and total LDL-P concentration, only small-size LDL-P still retained a significant effect (OR 2.52; 95% CI 1.16–5.49; P < 1.92 × 10−02) after multiple tests, with large-size LDL-P (OR 1.78; 95% CI 1.61–1.96; P < 2.62 × 10−31) and medium-size LDL-P (OR 1.78; 95% CI 1.61–1.96; P < 2.62 × 10−31) reversing. We screened 81 phenotype outcomes (excluded cases <200) for pheWAS analysis with the established small-size LDL-P’s PRS, and after multiple testing, small-size LDL-P was further found to be significantly associated with 7 categories of circulatory system diseases, i.e. Abdominal aortic aneurysm, Vascular insufficiency of intestine, etc.
CONCLUSIONS The findings of this study suggest that small-size LDL-P concentration can be a predominant etiological trait that plays a better prediction role in CAD, our findings also revealed that circulatory system outcomes such as Aortic aneurysm, Aneurysm of iliac artery were associated with PRS of small-size LDL-P concentration.
GW35-e1185
Aoming Jin1, Jing Xue1, Zhiyuan Feng1,2, Yongjun Wang1,2, Jie Xu1,2
1China National Clinical Research Center for Neurological Diseases
2Department of Neurology, Beijing Tiantan Hospital, Capital Medical University
OBJECTIVES Lipoprotein(a) (lp(a)) concentrations is an independent risk factor of atherosclerotic cardiovascular disease (ASCVD). The association between lp(a) and long-term prognosis of ischemic stroke patients is uncertain. The study is aimed to investigate the shape and the association of the risk of long-term stroke recurrence across the distribution of lp(a) concentrations, and explore whether combining ASCVD risk has an influence on the association.
METHODS Patients with acute ischemic stroke within 7 days in the Third China National Stroke Registry (CNSR-III) having lp(a) measurements were included in the study. ASCVD risk included diabetes mellitus, stroke history and early onset. Based on ASCVD risk and lp(a) concentrations, there were four groups: lp(a) <30 mg/dL, lp(a) 30–70 mg/dL without ASCVD risk, lp(a) 30–70 mg/dL with ASCVD risk, and lp(a) >70 mg/dL without ASCVD risk. To display the shape of the relationship between lp(a) and stroke recurrence within two years, lp(a) concentrations were modeled using natural cubic splines with median concentration serving as the reference adjusted by confounders. And the association was assessed using Cox proportional hazards models and Kaplan-Meier curves. The interaction between Lp(a) and ASCVD risk with stroke recurrence was evaluated.
RESULTS Among 9952 included patients with the mean age of 63 years and 69% of male, the median lp(a) concentrations was 18.06 (inter-quartile range, 8.85–35.66) mg/dL. The relationship between lipoprotein(a) and stroke recurrence appeared linear across the distribution. Compared to patients with lp(a) <50 mg/dL, lp(a) ≥50 mg/dL was associated with a higher risk of stroke recurrence (adjusted HR: 1.21, 95% CI: 1.04–1.40, P = 0.01). Compared to patients with lp(a) <30 mg/dL, lp(a) 30–70 mg/dL combined with ASCVD risk was associated with a higher risk of stroke recurrence (adjusted HR: 1.21, 95% CI: 1.04–1.42, P = 0.03), but no increased risk was found in patients with lp(a) >70 mg/dL without ASCVD risk (adjusted HR: 0.90, 95% CI: 0.65–1.26, P = 0.55).
CONCLUSIONS Lipoprotein(a) concentrations was associated with long-term prognosis of ischemic stroke, with a linear risk gradient across the distribution. ASCVD risk influenced the association between lp(a) and stroke recurrence.
GW35-e1208
Xin Ouyang
The Second Affiliated Hospital of Nanchang University
OBJECTIVES Residual cholesterol (RC) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), but there are discrepancies in the correlation with anxiety disorders and depression, and the aim of our study was to investigate the causal relationship between RC levels and anxiety disorders and depression by combining retrospective analyses and Mendelian randomization (MR) studies.
METHODS Residual cholesterol (RC) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), but there are discrepancies in the correlation with anxiety disorders and depression, and the aim of our study was to investigate the causal relationship between RC levels and anxiety disorders and depression by combining retrospective analyses and Mendelian randomization (MR) studies.
RESULTS A total of 1724 patients with anxiety disorders were included in this study. In logistic regression results, RC concentration was negatively associated with anxiety [0.785 (0.663, 0.929), P = 0.005] for individuals with residual cholesterol concentration >0.90 mmol/L. In MR analysis, there is no causal effect of RC on most psychiatric disorders, but RC had a positive effect on Lewy body dementia [IVW: OR = 1.45, 95% CI (1.19–1.77, P = 0.0002)] and Lewy body dementia carrying APOE gene [IVW: OR = 2.64, 95% CI (1.64–4.28), P = 0.000073]. In addition, most psychiatric disorders had no effect on RC concentrations.
CONCLUSIONS Retrospective studies indicated that residual cholesterol concentrations were negatively correlated with anxiety disorders. However, MR analysis showed no causal association of residual cholesterol with most of the psychiatric disorders such as anxiety and depression, except for high residual cholesterol levels which showed a positive causal association with Lewy body dementia and Lewy body dementia carrying the APOE gene. This finding suggests a potential link between RC and Lewy body dementia. As the understanding of blood lipids continues to grow, medications aimed at lowering blood lipids are being developed. Whether lowering RC levels will have an effect on the onset and development of dementia with Lewy bodies requires further study.
GW35-e1318
Tingting Wu, Ying Pan, Changjiang Deng, Yinhgying Zheng, Xiang Xie
Department of Cardiology, Xinjiang Medical University Affiliated First Hospital, Urumqi, China
OBJECTIVES Evidence is scarce on the effect of free fatty acid (FFA) level in the prognosis of coronary artery disease (CAD) patients with hypertension. This study aims to investigate this issue.
METHODS A large prospective cohort study with a follow-up period of average 2 years was conducted at Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. A total of 10,395 CAD participants were divided into groups based on FFA concentration and hypertension status, and then primary outcome mortality and secondary endpoint ischemic events were assessed in the different groups.
RESULTS A total of 222 all-cause mortality (ACMs), 164 cardiac mortality (CMs), 718 major adverse cardiovascular events (MACEs) and 803 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during follow-up period. A nonlinear relationship between FFA and adverse outcomes was observed only in CAD patients with hypertension. Namely, a “U-shape” relationship between FFA levels and long-term outcomes was found in CAD patients with hypertension. Lower FFA level (<310 μmol/L), or higher FFA level (≥580 μmol/L) at baseline is independent risk factors for adverse outcomes. After adjustment for confounders, excess FFA increases mortality (ACM, HR = 1.957, 95% CI (1.240–3.087), P = 0.004; CM, HR = 2.704, 95% CI (1.495–4.890, P = 0.001) and MACE (HR = 1.411, 95% CI (1.077–1.848), P = 0.012), MACCE (HR = 1.299, 95% CI (1.013–1.666), P = 0.040) prevalence. Low levels of FFA at baseline can also increase the incidence of MACE (HR = 1.567, 95% CI (1.187–2.069), P = 0.002) and MACCE (HR = 1.387, 95% CI (1.070–1.798), P = 0.013).
CONCLUSIONS Baseline FFA concentrations significantly associated with adverse outcomes could be a better and novel risk biomarker for prognosis prediction in CAD patients with hypertension.
GW35-e1321
Zheng Yin1, Yongjian Wu2, Naqiong Wu1
1Cardiometabolic Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College, Beijing
2Coronary Artery Disease Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College, Beijing
OBJECTIVES For acute coronary syndrome (ACS) patients, proprotein convertase subtilisin/Kexin type 9 monoclonal antibody (PCSK9mAb) could be used only when low-density lipoprotein cholesterol (LDL-C) is still not up to target level on the treatment with the maximum tolerable dose of statins and/or cholesterol absorption inhibitor during the first 8–12 weeks. There is no evidence that immediate initiation of PCSK9mAb in the acute stage of ACS further reduces the incidence of cardiovascular events. In patients with ACS undergoing percutaneous coronary intervention (PCI), early initiation of PCSK9mAb intensive lipid-lowering therapy (LLT), rapidly reducing LDL-C level and achieving the LDL-C target early, will be expected to further reduce the incidence of cardiovascular events.
METHODS We conducted a national, multicenter, randomized controlled study, involving 3684 patients undergoing PCI with non-ST-segment elevation ACS with the baseline LDL-C levels between 1.8 mmol/L and 3.4 mmol/L. Patients will be randomly assigned to experimental group (Group 1, G1, n = 1842), receiving intensive LLT with Tafolecimab (PCSK9mAb, 150 mg every 2 weeks) on the background of statin with or without cholesterol absorption inhibitor, or control group (Group 2, G2, n = 1842), receiving conventional LLT (statin with or without cholesterol absorption inhibitor) in a clinical follow-up setting. The primary endpoint is major adverse cardiovascular and cerebrovascular events (MACCEs) after 104 weeks, composited of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization due to unstable angina, and coronary revascularization. The key secondary endpoint is MACCEs after 26 weeks. In this abstract, we analyzed the baseline characteristics of the 393 patients enrolled in the EMPACT trial.
RESULTS A total of 393 patients are currently enrolled in the trial, with 324 males and 69 females. Forty-nine patients were diagnosed as Non-ST-segment elevation myocardial infarction (NSTEMI) and 344 patients were diagnosed as unstable angina. The baseline levels of total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were 4.19 mmol/L, 2.43 mmol/L and 1.15 mmol/L in the experimental group and 4.05 mmol/L, 2.31 mmol/L and 1.14 mmol/L in the control group, with no significant differences between groups. After 4 weeks, the reduction of low-density lipoprotein cholesterol in the experimental group was significantly higher than that in the control group (−1.00 mmol/L vs. −0.60 mmol/L, P < 0.001). After receiving intensive LLT at week 4, rate of LDL-C reaching normal target (<1.8 mmol/L, 91.6% vs. 67.7%, P < 0.001) and strict target (<1.4 mmol/L, 80.4% vs. 36.4%, P < 0.001) were significantly higher compared with conventional LLT. Furthermore, the percentage change in lipoprotein (a) at 4 weeks was significant greater in the experimental group compared with control group (−41.45% vs. −2.11%, P < 0.001).
CONCLUSIONS This early analysis concurs with previous studies that the use of PCSK9mAb can rapidly improve the plasma lipid profiles of NSTE-ACS patients receiving PCI including lipoprotein (a) at week 4. This trial will finally investigate the effect of early initiation of Tafolecimab on ACS patients undergoing PCI. The finding of this study will provide clinical evidence for the optimized strategy of “early initiation of intensive LLT with PCSK9mAb in ACS patients undergoing PCI”.
STRUCTURAL HEART DISEASE
GW35-e0049
Bowen Lin1, Ying Shen2, Pengfei Zhang1, Yunli Shen1, Yuying Gu1, Xiaoyan He1, Jimin Li1, Ke Yang2, Weifeng Shen2, Qi Zhang1, Yuanfeng Xin1, Yehong Liu1
1Shanghai East Hospital, Shanghai Tongji University School of Medicine
2Ruijin Hospital, Shanghai Jiaotong University School of Medicine
OBJECTIVES Robust evidence has demonstrated that Aortic valve sclerosis (AVSc) shares strikingly similar pathophysiology with atherosclerosis. Several traditional risk factors for coronary artery disease (CAD), such as dyslipidemia and hypertension, also affect the incidence of AVSc. Tissue plasminogen activator (t-PA) induces clot dissolution by converting plasminogen to plasmin, and acts as an in vivo marker of endothelial cell injury. Circulating t-PA has been shown to correlate with the presence and severity of CAD and plays an important role in plaque instability. We sought to investigate the relationship between circulating tissue plasminogen activator (t-PA) level and long-term outcomes in stable coronary artery disease patients with or without aortic valve sclerosis (AVSc).
METHODS A total of 805 patients diagnosed as CAD by coronary angiography in the Department of Cardiovascular Medicine, Shanghai Ruijin Hospital were consecutively recruited. Patients with acute coronary syndrome or stroke (n = 62), cancer (n = 10), infectious disease (n = 5), severe renal impairment [estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 or requiring hemodialysis] (n = 11), anticoagulation treatment (n = 26), hypertrophic or dilated cardiomyopathy (n = 17), atrial fibrillation (n = 30), pulmonary heart disease (n = 6), hematological (n = 3), or rheumatic disease (n = 3) were excluded. According to the echo result, we also excluded patients with valve stenosis (n = 12), congenital aortic valve malformation (n = 9), previous aortic valve replacement (n = 8), and congenital heart disease (n = 11). Furthermore, 11 patients refused to participate in the study. The remaining 347 patients were included in the final analysis. AVSc and non-AVCs were identified in 183 and 164 patients, respectively. Patients were followed until death or the last visit. Outcomes were prospectively recorded as planned clinic evaluations every 6 months up to 7 years after enrollment. The primary endpoint was a composite of cardiovascular death or rehospitalization due to heart failure, and the second endpoint included cardiovascular death, rehospitalization due to heart failure, and all-cause mortality.
RESULTS Serum levels of t-PA were determined in 347 consecutive stable angina patients with (n = 183) or without (n = 164). AVSc. Serum t-PA was significantly higher in AVSc than in non-AVSc patients (2131.22 pg/mL vs. 1495.85 pg/mL, P < 0.001). For patients with AVSc, those with t-PA level above the median (>1840.68 pg/mL) were more likely to meet the primary and secondary endpoints (all P < 0.001). After adjusting for potential confounding factors, serum t-PA level remained significantly predictive for each endpoint in the Cox proportional hazard models. The prognostic value of t-PA was good, with an AUC-ROC of 0.753 (P < 0.001). The combination of t-PA with traditional risk factors improved the risk reclassification of AVSc patients, with a net reclassification index of 0.857 and an integrated discrimination improvement of 0.217 (all P < 0.001). However, for patients without AVSc, both primary and secondary endpoints were similar, irrespective of t-PA levels.
CONCLUSIONS Elevated circulating t-PA confers an increased risk for poor long-term clinical outcomes in stable coronary artery disease patients with AVSc.
GW35-e0071
Jianrui Ma1,2, Haiyun Yuan1,2, Jimei Chen1,2
1Guangdong Cardiovascular Institute
2Guangdong Provincial People’s Hospital
OBJECTIVES There is ongoing immense controversy regarding whether atrial isomerism (AI) is associated with impaired outcomes in Fontan circulation, particularly in long-term results, the difference of which may be partially explained by the frequent presence of complex cardiac malformation. The purpose of this study was to compare both early and late outcomes between Fontan patients with and without AI.
METHODS 323 patients with (n = 56) or without (n = 267) AI undergoing Fontan procedure at our institution from January 2004 to December 2021 were retrospectively reviewed. With propensity score matching to reduce the heterogeneity of associated cardiac malformation, we matched AI and non-AI Fontan patients in a 1:2 ratio and compared outcomes between the two groups.
RESULTS Significantly higher postoperative mean or maximum vasoactive-inotropic scores in hospital were noted in the matched AI group than that in the matched non-AI group (P < 0.05). The mean period of follow-up was 7.34 ± 4.74 years in the matched AI group and 8.41 ± 3.98 years in the matched non-AI group. The 5-year and 10-year transplantation-free survival rates were estimated to be 85.9% (95% CI, 73.9%–99.8%) and 81.6% (95% CI, 68.1%–97.8%) in the matched AI group, significantly lower than 96.2% (95% CI, 91.1%–100%) and 91.2% (95% CI, 83.1%–100%) in the matched non-AI group, respectively (P < 0.05). In addition, the estimated freedom from Fontan failure at 5 years and 10 years was 85.9% (95% CI, 73.9%–99.8%) and 70.1% (95% CI, 52.8%–93.0%) in the matched AI group, significantly lower than 92.4% (95% CI, 85.5%–99.8%) and 89.7% (95% CI, 81.3%–98.8%) in the matched non-AI group, respectively (P < 0.05). There were no significant differences regarding the cumulative incidence of arrhythmia and atrioventricular valve regurgitation ≥ moderate between the two groups (P > 0.05). In the Cox multivariable analysis, AI (HR, 2.120; 95% CI, 1.107–4.060) and preoperative SpO2 (HR, 0.953; 95% CI, 0.922–0.985) were identified as independent risk factors for Fontan failure.
CONCLUSIONS Both the early and late outcomes of Fontan circulation with AI were inferior compared with those without AI. AI was an independent risk factor associated with postoperative Fontan failure.
GW35-e0072
Jianrui Ma1,2, Haiyun Yuan1,2, Jimei Chen1,2
1Guangdong Cardiovascular Institute
2Guangdong Provincial People’s Hospital
OBJECTIVES There is a lack of evidence guiding the surgical timing selection in pulmonary atresia with ventricular septal defect. This study aims to compare the long-term outcomes of different initial rehabilitative surgical ages in patients with pulmonary atresia with ventricular septal defect (PAVSD).
METHODS From January 2011 to December 2020, a total of 101 PAVSD patients undergoing the initial rehabilitative surgery at our center were retrospectively reviewed. Receiver-operator characteristics curve analysis was used to identify the cutoff age of 6.4 months and therefore to classify the patients into two groups. Competing risk models were used to identify risk factors associated with complete repair. The probability of survival and complete repair were compared between the two groups using the Kaplan-Meier curve and cumulative incidence curve, respectively.
RESULTS The median duration of follow-up was 72.76 months. There were similar ΔMcGoon ratio and ΔNakata index between the two groups. Multivariate analysis showed that age ≤6.4 months (hazard ratio (HR) = 2.728; 95% confidence interval (CI): 1.122–6.637; P = 0.027) and right ventricle-to-pulmonary artery connection (HR = 4.196; 95% CI = 1.782–9.883; P = 0.001) were associated with increased probability of complete repair. The cumulative incidence curve showed that the estimated complete repair rates were 64% ± 8% after 3 years and 69% ± 8% after 5 years in the younger group, significantly higher than 28% ± 6% after 3 years and 33% ± 6% after 5 years in the elder group (P < 0.001). There was no significant difference regarding the estimated survival rate between the two groups.
CONCLUSIONS Compared with those undergoing the initial rehabilitative surgery at the age >6.4 months, PAVSD patients at the age ≤6.4 months had an equal pulmonary vasculature development, a similar probability of survival but an improved probability of complete repair.
GW35-e0205
Bin Zhang, Hongliang Zhang, Ziang Li, Haiyan Xu, Yongjian Wu
Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College
OBJECTIVES The C-reactive to albumin ratio (CAR) integrates the pro-inflammatory and nutritional status of patients, which may provide superior prognostic information over either parameter alone in valvular heart disease (VHD). We aim to examine the association between CAR and mortality and its ability as biomarker to guide risk stratification in VHD patients.
METHODS A total of 5519 patients (age ≥18 years) with moderate or severe VHD underwent echocardiography and CAR measurement. VHD examined included aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation; tricuspid regurgitation, and multivalvular heart disease. An optimal threshold was defined based on penalized splines and receiver operating characteristic curves.
RESULTS The cohort had a mean age of 61.9 ± 13.7 years, and 2997 (54.3%) were men. At two-year follow-up, 482 (8.7%) deaths occurred. Penalized splines showed a monotonic increase of relative hazards with greater CAR for death. Higher CAR was independently associated with mortality (overall adjusted hazard ratio [aHR]: 1.89; 95% confidence interval [CI]: 1.56–2.28; P < 0.001) and major adverse cardiovascular events (aHR: 1.40; 95% CI: 1.30–1.82; P < 0.001). Different subtypes of VHD incurred excess mortality with elevated CAR. Results remained consistent in patients under medical care. The CAR threshold combined with NT-proBNP amplified the stratification of patients at risk (log-rank, P < 0.001). The addition of CAR to a prediction algorithm including traditional risk factors improved outcome prediction (continuous net reclassification index [NRI]: 0.57; likelihood ratio test P < 0.001) and reclassified better in patients both with and without events (absolute NRI: 1.8%).
CONCLUSIONS CAR provides incremental prognostic information for mortality in various VHD. It could aid in risk stratification as a pragmatic and versatile biomarker in VHD patients.
GW35-e0206
Wence Shi, Hongliang Zhang, Bin Zhang, Moyang Wang, Yongjian Wu
Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
OBJECTIVES The rapid increase in the number of transcatheter aortic valve replacement (TAVR) procedures in China and worldwide has led to growing attention to hypoattenuating leaflet thickening (HALT) detected during follow-up by 4D-CT. It’s reported that HALT may impact the durability of prosthetic valve. Early identification of these patients and timely deployment of anticoagulant therapy are therefore particularly important.
METHODS We retrospectively recruited 234 consecutive patients who underwent TAVR procedure in Fuwai Hospital. We collected clinical information and extracted morphological characteristics parameters of the transcatheter heart valve (THV) post TAVR procedure from 4D-CT. LASSO analysis was conducted to select important features. Three models were constructed, encapsulating clinical factors (Model 1), morphological characteristics parameters (Model 2), and all together (Model 3), to identify patients with HALT. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were plotted to evaluate the discriminatory ability of models. A nomogram for HALT was developed and verified by bootstrap resampling.
RESULTS In our study patients, Model 3 (AUC = 0.738) showed higher recognition effectiveness compared to Model 1 (AUC = 0.674, P = 0.032) and Model 2 (AUC = 0.675, P = 0.021). Internal bootstrap validation also showed that Model 3 had a statistical power similar to that of the initial stepwise model (AUC = 0.723, 95% CI: 0.661–0.786). Overall, Model 3 was rated best for the identification of HALT in TAVR patients.
CONCLUSIONS A comprehensive predictive model combining patient clinical factors with CT-based morphology parameters has superior efficacy in predicting the occurrence of HALT in TAVR patients.
GW35-e0207
Wence Shi, Hongliang Zhang, Bin Zhang, Moyang Wang, Yongjian Wu
Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
OBJECTIVES The mechanism for hypoattenuating leaflet thickening (HALT) after transcatheter aortic valve replacement (TAVR) is still not well elucidated, and the role of biochemical indicators has rarely been studied. This study sought to test the hypothesis that the risk of HALT is associated with elevated level of lipoprotein(a) [lp(a)] or high sensitive C reactive protein (hs-CRP).
METHODS Total of 234 consecutive individuals from Fuwai Hospital who underwent TAVR procedure were included to evaluate potential association of biochemical markers with risk of HALT. All patients received first postoperative CT scans with 6 months and raw data were analyzed on 3mensio. HALT was defined as visually identified increased leaflet thickness with typical meniscal appearance at least two different multiplanar reformation projections.
RESULTS The incidence of HALT within 6-month after TAVR in this study is 36.3%, and the risk of HALT is associated with higher baseline lp(a) [the multivariable adjusted OR for every 100 mg/L change was 1.14 (95% CI: 1.03–1.26)] and hs-CRP level [the multivariable adjusted OR for every 1 mg/L change was 1.10 (95% CI: 1.05–1.20)]. Compared with individuals out of the top 25th percentiles for both lp(a) and hs-CRP, the multivariable adjusted OR for HALT was 3.47 (95% CI: 1.06–11.53) for the top 25th percentiles. This result remained consistent after excluding patients receiving anticoagulant therapy.
CONCLUSIONS Top 25th percentiles of lipoprotein(a) level (≥400 mg/L) combined top 25th percentiles of hs-CRP level (≥4 mg/L) conferred a 3.47-fold risk of HALT.
GW35-e0226
Yusi Chen
The Second Xiangya Hospital of Central South University
OBJECTIVES Pulmonary arterial hypertension (PAH) is a leading cause of right heart failure worldwide. Rapid and accurate diagnosis and prognosis are crucial for timely treatment options. tRNA-derived small RNA (tsRNA) is a noninvasive marker of cellular injury. Its significance in PAH is unknown.
METHODS Plasma tsRNA was measured in 2 PAH cohorts (Discovery cohort, n1 = 41; Verification cohort, n2 = 254) and controls (n1 = 27; n2 = 70). Data were collected for REVEAL 2.0 (Registry to Evaluate Early and Long-Term PAH Disease Management) scores and clinical event determinations. Candidate tsRNAs expression level were compared among controls and PAH by students’ t-test analysis. Areas under the receiver operating characteristic curve were estimated from logistic regression models. Log-rank tests compared event-free survival between tsRNA quartiles and REVEAL risk groups. To explore the tissue origins of the tsRNA in plasma, in situ hybridization was conducted in lung and right ventricular tissues of PAH patients and controls. Additionally, two PAH rat models, namely the monocrotaline and sugen-hypoxia were established, and quantitative assessments were performed on the lung tissues and right ventricles of these rats.
RESULTS In discovery cohort, median (interquartile range) age was 41 years (27–54), with 65.9% female, and median (interquartile range) REVEAL 2.0 was 7 (6–8). In verification cohort, median (interquartile range) age was 36 years (31–52), with 63.4% female, and median (interquartile range) REVEAL 2.0 was 6 (4–7). In discovery cohorts, i-tRF-15:31-Lys-CTT-1 expression level differed among patients with idiopathic PAH and exhibited the largest fold change among the three candidate tsRNAs (t-test P < 0.0001). i-tRF-15:31-Lys-CTT-1 levels varied different REVEAL risks and controls (analysis of variance P ≤ 0.002) and were lower in the high-risk compared with the low-risk category (P ≤ 0.002). The receiver operating characteristic curve analysis based on logistic regression showed that the area under the curve (AUC) of i-tRF-15:31-Lys-CTT-1 in idiopathic PAH diagnosis was 0.90 in discovery cohort and 0.81 in verification cohort. The AUC of i-tRF-15:31-Lys-CTT-1 in heritable and congenital heart disease-associated PAH diagnoses were 0.85 and 0.80 in verification cohort. In verification cohort, clinical events occurred in 19 of 64, 26 of 63, 11 of 63, and 17 of 64 patients in the lowest, second, third, and highest tsRNA quartiles, respectively. i-tRF-15:31-Lys-CTT-1 levels stratified as quartiles (log-rank: P = 0.033) predicted event-free survival. The addition of i-tRF-15:31-Lys-CTT-1 to REVEAL improved discrimination (AUC, 0.67–0.75; P < 0.0001). Compared with controls, the overall signal intensity of i-tRF-15:31-Lys-CTT-1 in lung tissue of PAH patients was significantly decreased compared with healthy controls in situ hybridization. The result was certified by real-time polymerase chain reaction in lung tissue in two PAH models.
CONCLUSIONS Circulating i-tRF-15:31-Lys-CTT-1 is reduced in patients with PAH, correlates with disease severity, and predicts worse survival. The source of decreased i-tRF-15:31-Lys-CTT-1 in PAH was determined damage originating from lung tissue.
GW35-e0234
Cai Xianzhen
Second Affiliated Hospital of Shantou University Medical College
OBJECTIVES With the aging of populations, aortic stenosis (AS) has become the most common heart valve disease. It causes morbidity and mortality when severe, and appropriately timed aortic valve replacement (AVR) can reduce the associated mortality rate. EUROSCORE II has been used extensively to evaluate the perioperative mortality of patients with severe AS who undergo AVR. However, it is unclear whether EUROSCORE II has prognostic value with respect to the long-term all-cause mortality of Chinese patients with moderate-to-severe AS. Therefore, we evaluated the relationship between EUROSCORE II and the all-cause mortality of patients with moderate-to-severe AS and determined whether AVR affects this.
METHODS A total of 544 consecutive patients with moderate-to-severe AS that was diagnosed using echocardiography were enrolled. We performed a multi-centre study at the Second Affiliated Hospital of Shantou University Medical College, the First Affiliated Hospital of Sun Yat-sen University, and the Affiliated Hospital of Guangdong Medical University. The recruited patients were allocated to four groups according to their EUROSCORE II, using a cut-off value of 4% (2017 ESC/EACTS guidelines), and whether or not AVR was performed. The study started in January 2014 and ended on July 31, 2023. The primary outcome was all-cause mortality during the follow-up period. The baseline data, the Kaplan–Meier method, and a Cox regression model (generating a hazard ratio and 95% confidence interval) were used to analyse the relationship between EUROSCORE II and all-cause mortality in the participants. Furthermore, receiver operating characteristic (ROC) and Kaplan–Meier curves were used to identify the optimal cut-off value of EUROSCORE II for the prediction of all-cause mortality.
RESULTS During a median follow-up period of 41.4 months, a total of 177 (21.5%) participants reached the endpoint. Notably, the participants with higher risks (EUROSCORE II ≥4%) who did not undergo AVR exhibited a significantly higher incidence of all-cause mortality than those in the other groups (55.4% vs. 6.5%, 13.4%, and 32.7%; P < 0.001). The Kaplan–Meier curves also showed that these participants had a significantly lower survival rate than the other participants (log-rank test P < 0.001). In addition, Cox regression analysis showed that participants who did not undergo AVR and had high EUROSCORE II were at a 2.3-fold higher risk than those with a lower EUROSCORE II) (hazard ratio, 2.312; 95% confidence interval 0.924–5.784; P = 0.006). The adjusted model (P < 0.01) and subgroup analyses indicated that the prognostic value of EUROSCORE II for all-cause mortality remained after adjustment for potential confounders (without AVR P = 0.001; with AVR P = 0.029). Finally, the ROC curve for EUROSCORE II showed that the most suitable cut-off value for the prediction of moderate-to-severe AS in participants who had not undergone AVR was 2.23% (area under the curve 0.675), rather than 4%.
CONCLUSIONS Both EUROSCORE II (cut-off value 4%) and AVR are independently associated with the long-term prognosis of patients with moderate-to-severe AS. Moreover, the optimal cut-off value of EUROSCORE II for the prediction of all-cause mortality in patients who do not undergo AVR is proposed to be 2.23%.
GW35-e0418
Xin Zheng1,2, Fenfang Zhang2, Leigang Wang1,3, Bin Liang1,3
1Shanxi Medical University
2Yangquan First People’s Hospital
3Second Hospital of Shanxi Medical University
OBJECTIVES Observational studies have suggested that the skin microbiota is a significant risk factor for endocarditis. Despite this, the specific causal relationships and potential mediators remain understudied. Our study aims to apply Mendelian randomization (MR) to validate the correlation between skin microbiota and endocarditis and to explore whether circulating inflammatory proteins can act as inflammatory mediators in regulating the associated inflammation.
METHODS Initially, we conducted a two-sample MR study to investigate the causal links between skin microbiota, circulating inflammatory proteins, and endocarditis. We used the Inverse Variance Weighted (IVW) method as the primary outcome measure. Subsequent analyses involved a two-step MR approach to identify circulating inflammatory proteins that might serve as inflammatory mediators. We then used the coefficient product method to determine the exact mediating effects and the proportions of these inflammatory mediators. We also refined our sensitivity analysis to verify the reliability of our findings.
RESULTS In our study exploring the causal relationship between skin microbiota and endocarditis, we observed that certain types of skin microbiota, such as ACF_ASV016, FH_ASV008, class ACF_BPB, and order ACF_Lact, might increase the risk of endocarditis. Conversely, other skin microbiota, such as FH_ASV015, family DF_CIS XI, genus DF_Strep, and genus ACF_Ehb, exert a protective effect against endocarditis. We also investigated the causal relationship between circulating inflammatory proteins and endocarditis, identifying eight proteins with direct causal links. PD-L1, IL-6, NT-3, MCP-1, and IL-10 were found to increase the risk of endocarditis, whereas TNF, FGF21, and IL-2 have protective effects. Through mediated MR analysis, we found that IL-10 and FGF21 can act as inflammatory mediators in the relationship between ACF_ASV016 in skin microbiota and endocarditis.
CONCLUSIONS This study contributes new evidence to the understanding of the causal relationships between skin microbiota, circulating inflammatory proteins, and endocarditis and highlights specific circulating inflammatory proteins as potential inflammatory mediators. However, these findings require further validation through more comprehensive clinical studies to confirm their implications.
GW35-e0433
Teruhiko Imamura, Ryuichi Ushijima, Mitsuo Sobajima, Nobuyuki Fukuda, Hiroshi Ueno, Koichiro Kinugawa
Second Department of Internal Medicine, University of Toyama
OBJECTIVES Impaired gastric motility in the form of constipation may often occur in patients with chronic heart failure. The clinical implication of a history of constipation in patients receiving trans-catheter aortic replacement (TAVR) remains unknown. We in this study investigated the prognostic impact of the presence of constipation on TAVR candidates.
METHODS Patients who underwent TAVR at a large academic center between 2015 and 2022 were eligible. The prognostic impact of laxative type and number, which was assumed as the severity of constipation, on the incidence of death or heart failure readmission two years after index discharge was investigated.
RESULTS A total of 344 patients were included. Median age was 85 years and 99 were men. Patients with any laxatives (N = 166) had higher systolic blood pressure, higher plasma B-type natriuretic peptide levels, and lower prescription rate of renin-angiotensin system inhibitors at the time of index discharge after TAVR (P < 0.05 for all). The number of laxative types was independently associated with the composite primary outcome with an adjusted hazard ratio of 1.83 (95% confidence interval 1.27–2.63, P = 0.001) with a cutoff of one type of laxative use, which significantly stratified the 2-year cumulative incidence of the primary outcome (18% versus 7%, P = 0.001).
CONCLUSIONS The presence of constipation was associated with worse clinical outcomes following TAVR. Further studies are warranted to evaluate the prognostic impact of aggressively managing constipation in TAVR candidates.
GW35-e0488
Yi Fang
General Hospital of Northern Theater Command
OBJECTIVES To assess the potential predictive value of computed tomography angiography (CTA)-derived fractional flow reserve (CT-FFR) and high risk plaque characteristics (HRPC) in patients with aortic stenosis (AS) and coronary artery disease (CAD) before transcatheter aortic valve (TAVR).
METHODS This was a post hoc analysis from a multicenter TAVR registry. The AS patients with obstructive CAD who underwent successful TAVR treatment were enrolled in the present study. CT-FFR and HRPC were measured for each CTA showing ≥50% coronary stenosis. Subsequently, patients were grouped according to CT-FFR (≤0.8 vs. >0.8) and HRPC (Yes vs. No). The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiac death, nonfatal MI and ischemia-driven revascularization. To assess the added prognostic value of CT-FFR and HRPC to OPT-CAD risk score for prognosis, receiver operator characteristic curve with the area under the curve (AUC) were performed.
RESULTS A total of 213 patients were enrolled in this study with a mean age of 74.34 years old; among them, there were 125 males (58.4%). In the CT-FFR group, the incidence of MACE was higher in higher CT-FFR group (>0.8) compared to lower group (2.3% vs. 11.9%, P = 0.011). However, there was no significant difference between HRPC and MACE. The optimal threshold value for predicting MACE using CT-FFR was determined to be 0.79. The prognostic accuracy was improved when clinical risk score combined with CT-FFR and HRPC to yield a 11% increment for the discrimination of MACE (AUC: from 0.63 to 0.74).
CONCLUSIONS Pre-procedure CTA assessment could enhance the identification of high-risk patients with AS and CAD receiving TAVR.
GW35-e0510
Ruiyan Wang1, Mengyu He1, Jing Zhou1, Zhenyue Chen1, Feng Wang1, Dayi Hu2
1The First Affiliated Hospital of Bengbu Medical University
2Peking University First Hospital
OBJECTIVES Currently, TAVR (Transcatheter Aortic Valve Replacement) is becoming more and more popular and widely used in clinical practice. However, its high mortality rate is still a serious problem to be faced in clinical practice, and the early identification of the risk of death after TAVR is currently an important challenge. Although a number of tools have been developed, however, there is still some controversy about the true value of mortality risk identification. Therefore, we conducted this meta-analysis to discuss the early prediction of mortality risk after TAVR by previously developed mortality risk identification tools and newly developed prediction models, and to provide evidence-based evidence for subsequent tool development and research.
METHODS We systematically searched PubMed, Web of Science, Embase, and Cochrane Library for studies on TAVR mortality risk assessment tools up to September 2023. We used the Predictive Model Risk of Bias Assessment Tool (PROBAST) to assess the risk of bias of the included original studies, and performed subgroup analyses based on different predictive models as well as different time to death during meta-analysis.
RESULTS This systematic review ultimately included 33 original studies covering 243,959 post-TAVR patients and included 6 major scoring tools 48 newly developed machine learning models. Meta-analysis showed that the c-index for validation of EuroSCORE I was 0.610 (0.588–0.632), that for validation of EuroSCORE II was 0.613 (0.585–0.641), that for validation of France II was 0.578 (0.531–0.625), and that for validation of France II was 0.613 (0.585–0.641). Index was 0.613 (0.585–0.641), c-index for validation France II was 0.578 (0.531–0.625), c-index for validation OBSERVANT was 0.594 (0.554–0.633), c-index for validation STS was 0.645 (0.617–0.673), the c-index for validating ACC - TAVR is 0.632 (0.616–0.648); the c-index for validating the aggregated machine learning model is 0.696 (0.663–0.729).
CONCLUSIONS The results of the study show that the accuracy of existing models for mortality prediction is still challenging, but further improvement and refinement is needed. New machine learning models should be actively developed to explore more efficient predictors in the future.
GW35-e0527
Xu Jing
Shanghai East Hospital, Shanghai, Tongji University School of Medicine
OBJECTIVES Relationship between systemic inflammation and aortic valve stenosis (AVS) has been well demonstrated. This investigation aimed to evaluate the link between various inflammation hematological ratios and patients with AVS.
METHODS Patients with AVS (n = 229) and control (n = 1716) were identified. Propensity score matching (PSM) was performed with the proportion of 1:1 using logistic regression based on the variables of age, sex, hypertension, diabetes, creatinine (Cr) and glutamate transpeptidase (γ-GT). The receiver operating characteristic (ROC) analysis was used to estimate the performance of inflammation hematological ratios for distinguishing AVS. Univariate and multivariate analysis were performed to identify the independent risk factors of AVS. In addition, restricted cubic splines (RCS) regression analysis revealed the non-linear correlation between inflammation hematological ratios and AVS.
RESULTS After PSM, 392 patients (196:196) were included. Univariate analysis showed monocyte/high density lipoprotein ratio (MHR) and neutrophil/lymphocyte ratio (NLR) were significantly higher in AVS group (MHR, 0.49 ± 0.23 vs. 0.32 ± 0.20, P < 0.001, NLR, 3.52 ± 2.52 vs. 2.87 ± 1.89, P < 0.001) while lymphocyte/monocyte ratio (LMR) was significantly lower (3.27 ± 1.72 vs. 4.08 ± 1.76, P < 0.001). But the level of platelet/lymphocyte ratio (PLR) and systemic inflammation index (SII) (PLR, 146.27 ± 82.68 vs. 143.27 ± 66.95, P = 0.927, SII, 690.22 ± 602.69 vs. 610.58 ± 403.33, P = 0.100) did not differ significantly between the two groups. However, in multivariate logistic regression models, only MHR remained to be an independent risk factor of AVS (OR 6.199 with 95% CI 3.631–10.583, P < 0.001). Besides MHR, atrial fibrillation (AF), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and hemoglobin (Hgb) were also performed to be independent risk factors of AVS. ROC analysis showed that the cut-off value of MHR (0.2750) predicted AVS with 85.2% sensitivity and 51.5% specificity (95% confidence interval [CI] = 0.691–0.788, the area under the curve [AUC] = 0.740, P < 0.001). Further, RCS revealed the non-linear correlation between MHR and AVS (P for non-linearity < 0.001).
CONCLUSIONS Elevated MHR was independently associated with the presence of AVS. MHR was superior to other inflammation hematological ratios such as SII, NLR, PLR and LMR in AVS prediction.
GW35-e0553
Jingnan Zhang1,2, Kaihang Yiu1,2
1The University of Hong Kong–Shenzhen Hospital
2The University of Hong Kong, Queen Mary Hospital
OBJECTIVES Congenital aortic valve anomalies predominantly present as bicuspid aortic valves (BAV), while quadricuspid aortic valves (QAV) are considerably less frequent. The clinical presentation and consequence of QAV remain largely unknown when compared to BAV. The current study sought to compare the mortality and morbidity burden between BAV and QAV.
METHODS Consecutive patients with QAV and BAV were retrospectively identified from 436,588 exams from two tertiary hospitals. A total of 139 QAV patients [age 55 (46–64) years, male 61%] were included and were 1:5 matched to 695 BAV patients according to age and sex.
RESULTS The 5-year survival rate for QAV patients was comparable to BAV patients (95.1% vs. 93.4%, P = 0.26). Regarding the lifetime morbidity burden (from birth to age 80), QAV patients showed a similar incidence of aortic valve surgery (80% vs. 75.7%, P = 0.17), but lower incidences of aorta surgery (5.5% vs. 33.8%, P < 0.001) and endocarditis (0% vs. 9.6%, P = 0.012) compared to BAV patients. The cumulative incidence of aortic dissection was relatively low for both QAV and BAV patients (0.9% vs. 3.6%, P = 0.57). In contrast, QAV exhibited a higher risk of heart failure hospitalization with a hazard ratio of 1.83 (95% CI: 1.16–2.87, P = 0.009) compared to BAV patients. This increased risk persisted even among patients without significant valve dysfunction (P < 0.001).
CONCLUSIONS The burden for aortic valve surgery was similar for BAV and QAV patients. However, differential outcomes were observed, with BAV patients requiring more aorta surgery and QAV patients experiencing a higher burden of heart failure.
GW35-e0600
Makhmudjon Khaydarov, Shukhrat Salakhitdinov
Republican Scientific Center for Emergency Medical Care
OBJECTIVES The objective of this study was to evaluate the effectiveness of an improved balloon valvuloplasty technique for patients with critical mitral stenosis in emergency situations. The study aimed to compare the outcomes of the modified procedure with the traditional technique, focusing on procedural success, complication rates, and hemodynamic improvements.
METHODS This prospective study involved 85 patients with critical mitral stenosis who underwent emergency balloon valvuloplasty at the Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation. Of the 85 patients, 47 were women. Patients were randomly assigned to two groups: the intervention group (n = 43), which received the improved balloon valvuloplasty technique, and the control group (n = 42), which underwent the traditional procedure. The improved technique included a novel balloon design and modified inflation protocol to enhance valve dilation and reduce procedural risks. Baseline and post-procedural assessments included echocardiographic measurements of mitral valve area (MVA), mean transmitral gradient (MTG), and pulmonary artery pressure (PAP). Procedural success was defined as an increase in MVA by at least 50% and a reduction in MTG by at least 30%. Complications such as mitral regurgitation, atrial septal defect, and procedural mortality were recorded. Statistical analysis was conducted using SPSS version 27.0. Comparisons between groups were made using paired t-tests for within-group changes and independent t-tests for between-group differences. A significance level of P < 0.05 was considered statistically significant.
RESULTS The intervention group showed significant improvements in all hemodynamic parameters compared to the control group. Key results included: Mitral Valve Area (MVA): The intervention group had an increase from 0.8 ± 0.2 cm2 to 1.6 ± 0.3 cm2 (P < 0.001), while the control group increased from 0.8 ± 0.2 cm2 to 1.3 ± 0.3 cm2 (P < 0.001). The between-group difference was significant (P < 0.001). Mean Transmitral Gradient (MTG): The intervention group showed a reduction from 20 ± 5 mmHg to 8 ± 3 mmHg (P < 0.001), compared to the control group’s reduction from 21 ± 5 mmHg to 12 ± 4 mmHg (P < 0.001). The between-group difference was significant (P < 0.001). Pulmonary Artery Pressure (PAP): The intervention group showed a decrease from 60 ± 10 mmHg to 40 ± 8 mmHg (P < 0.001), while the control group decreased from 62 ± 11 mmHg to 45 ± 9 mmHg (P < 0.001). The between-group difference was significant (P = 0.02). Procedural success was achieved in 93% of patients in the intervention group compared to 76% in the control group (P = 0.02). The intervention group had a lower complication rate, with mitral regurgitation occurring in 5% of patients versus 15% in the control group (P = 0.04), and no cases of procedural mortality in either group.
CONCLUSIONS The improved balloon valvuloplasty technique demonstrated superior efficacy and safety in patients with critical mitral stenosis in emergency situations compared to the traditional method. Significant improvements in MVA, MTG, and PAP, coupled with a higher procedural success rate and lower complication rate, suggest that the modified technique offers a valuable advancement in the management of this high-risk patient population.
GW35-e0679
Yang Chen1,2, Qingrong Liu1,3, Bin Zhang1, Hongliang Zhang1, Guannan Niu1, Moyang Wang1, Xiangming Hu1, Runlin Gao1, Yongjian Wu1
1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
2Department of Cardiology, Peking University People’s Hospital, Beijing, China
3Department of Cardiology, Beijing Aerospace General Hospital, Beijing, China
OBJECTIVES As transcatheter aortic valve replacement (TAVR) is progressively being applied to low surgical-risk patients, the total number of TAVR procedures is expected to increase considerably. Therefore, a novel TAVR device designed for these patients is needed. This study aimed to evaluate the safety and efficacy of a novel, short-frame self-expanding valve (ScienCrown transcatheter aortic valve system) in the treatment of patients with symptomatic, severe, calcified aortic stenosis in China.
METHODS This is a prospective, multicenter, single-arm study including sixteen centers in China. We enrolled 128 consecutive patients with symptomatic, severe, calcified aortic stenosis undergoing TAVR using the ScienCrown valve. Patients underwent attempted implant of a ScienCrown transcatheter aortic valve. The valve size was determined based on annular measurements or multiplanar measurements above the annulus. The primary endpoint was all-cause mortality at 1 year. The secondary outcomes included procedural complications, valve hemodynamics, and quality of life assessment.
RESULTS From September 2021 to September 2022, 128 patients were enrolled [63.28% bicuspid aortic valve, mean Society of Thoracic Surgeons score (5.40%)]. The perioperative device success rate was high at 99.20% (124/125), and the procedure success rate was 96.88% (124/128). One-year mortality in 128 patients (follow-up rate, 100%) was 5.47% (95% confidence interval: 1.53%–9.41%), which was significantly lower than the performance goal of 25% (P < 0.0001). Stroke, myocardial infarction, paravalvular leak ≥ moderate, and new pacemaker implantation occurred in 3.91%, 4.69%, 2.34%, and 7.03% of patients, respectively, at 1 year. Hemodynamic performance (mean transaortic valve gradient 10.51 ± 5.63 vs. 56.63 ± 20.00 mmHg, effective orifice area 1.88 ± 0.52 vs. 0.61 ± 0.25 cm2, and peak velocity 2.16 ± 0.52 vs. 4.76 ± 0.79 m/s) and quality of life scores (82.93 ± 11.62 vs. 61.09 ± 19.02) also improved significantly. Patients with a different type of bicuspid valve had similar outcomes to those with a tricuspid aortic valve in the non-matched subgroup analysis.
CONCLUSIONS The 1-year clinical outcomes confirm the safety and efficacy of the ScienCrown transcatheter aortic valve system in the treatment of patients with symptomatic, severe, calcified tricuspid and bicuspid aortic stenosis.
GW35-e0871
Rutao Wang, IAyuan HCeng, Rongzhen Zhang, Doudou Lou, Ling Tao
Xijing Hospital
OBJECTIVES Due to the unique anatomical characteristics among patients with pure severe native aortic valve regurgitation (NAVR), transcatheter aortic valve replacement (TAVR) for NAVR is challenging and remains an “off-label” indication. The safety and efficacy of TAVR with Chinese domestic self-expandable valve in a real-world Chinese cohort of patients with NAVR has not been fully investigated. We aimed to investigate the safety and efficacy of TAVR with domestic self-expanding valves for NAVR.
METHODS Consecutive patients with NAVR underwent TAVR with domestic available devices (including VitaFlow, Venus) were prospectively enrolled in a high volume Chinese single center from October 2018 to December 2023. Clinical, procedural and follow-up data were collected. Outcomes were defined according to the Valve Academic Research Consortium-3 definition.
RESULTS A total of 107 patients were included. Mean age was 67.3 ± 7.9 years and mean STS score was 2.8% ± 2.0%. Technical and device success rates were both 74.8%. Rates of valve migration, need for a second valve, new permanent pacemaker implantation were 5.8%, 17.3% and 12.3%, respectively. At 30-day follow-up, all-cause mortality, acute kidney injury, moderate paravalvular leak, major vascular complications and major bleeding were 5.6%, 1.9%, 2.8%, 5.6%, and 6.5%, respectively. At a median follow-up of 1.8 years, all-cause mortality was 7.0% and one patient had an acute cerebral infarction (1.0%).
CONCLUSIONS In this real-world Chinese cohort of patients with NAVR, TAVR with Chinese domestic self-expandable valve showed acceptable safety and efficacy. Despite relatively moderate device success, Chinese domestic self-expandable TAVR may be an alternative strategy in selected patients with NAVR who have no surgical options.
GW35-e0873
Rutao Wang, Rongzhen Zhang, Aiyuan Cheng, Doudou Lou, Ling Tao
Xijing Hospital
OBJECTIVES Neutrophil-Lymphocyte Ratio (NLR) has been demonstrated as a new inflammation marker and associated with adverse outcomes in patients with cardiovascular disease. However, the impact of NLR on clinical outcomes in patients with native aortic valve regurgitation (NAVR) underwent transcatheter aortic valve replacement (TAVR) has not been fully elucidated. We aimed to evaluate the impact of NLR on all-cause mortality in patients with NAVR underwent TAVR.
METHODS Consecutive patients with NAVR underwent TAVR with domestic available devices (including VitaFlow, Venus) were prospectively enrolled in a high-volume Chinese single center from 2018 October to 2023 December. Clinical, procedural and follow-up data were collected. The patients were divided into two groups according to the median value of NLR. Cox proportional hazards models were performed to determine the association between NLR and all-cause mortality.
RESULTS The present study included 107 patients. The mean age was 67.3 ± 7.9 years and mean STS score was 2.8% ± 2.0%. Patients were stratified to higher NLR group (n = 54) and lower NLR group (n = 53) according to the median value of NLR (2.68). At the median follow-up of 22 months (interquartile range: 10–40), patients with higher NLR had a higher risk of all-cause mortality than those with lower NLR (18.5% vs. 3.7%, HR: 4.62, 95% CI: 1.01–21.10, P = 0.048). After adjustment for sex, age, body mass index, coronary artery disease, and STS scores, higher NLR remained an independent risk factor of all-cause mortality (HR: 5.57, 95% CI: 1.19–26.21, P = 0.03).
CONCLUSIONS Higher admission NLR was an independent risk factor of all-cause mortality in patients with NAVR underwent TAVR. Our findings need to be validated in larger sample size trials in future.
GW35-e0874
Rutao Wang, Aiyuan Cheng, Rongzhen Zhang, Doudou Lou, Ling Tao
Xijing Hospital
OBJECTIVES The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance (IR). Some studies have found that higher TyG index was associated with a higher risk of all-cause mortality in patients with moderate and severe AS. However, whether the TyG index has prognostic value in patients with pure native aortic regurgitation (PNAR) underwent transcatheter aortic valve replacement transcatheter (TAVR) remains unclear.
METHODS This study enrolled 107 patients with PNAR underwent TAVR in a Chinese single center from October 2018 to December 2023. The patients were grouped according to the cut-off value of the TyG index which was derived from the Maximally Selected Rank Statistics analysis. The TyG index was calculated as ln (TG [mg/dL] × FBG [mg/dL]/2). Data of clinical, laboratory, procedure and outcomes were collected. Outcomes were defined according to the Valve Academic Research Consortium-3 definition. The Kaplan-Meier method was conducted to assess the association between the TyG index and all-cause mortality, and differences between groups were assessed using the log-rank test.
RESULTS A total of 107 patients were included with mean age of 67.3 ± 7.9 years and mean STS score of 2.8% ± 2.0%. The Maximally Selected Rank Statistics analysis showed that the optimal cutoff point of the TyG index was 8.3. Patients were divided into >0.83 group and ≤0.83 group accordingly. Compared to patients with a lower TyG index (≤0.83), patients with a higher TyG index (>0.83) had a numerically but not statistically significant higher all-cause mortality (6.8% vs. 14.3%, HR: 2.54, 95% CI: 0.68–0.94, P-value = 0.163) during a median follow-up of 1.8 years.
CONCLUSIONS Higher TyG index was associated with a numerically but not statistically significant higher risk of all-cause mortality in patients with PNAR who underwent TAVR. Our findings need to be validated in larger sample size trials in future.
GW35-e0926
Zheng Zheng1, Yining Yang2
1First Affiliated Hospital of Xinjiang Medical University
2People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES Aortic valve calcification is a significant predictor of poor prognosis in aortic stenosis; however, its prognostic role in patients undergoing transcatheter aortic valve replacement (TAVR) remains unclear. This study aimed to analyze the influence of severe aortic valve calcification on mortality following TAVR.
METHODS By following the PRISMA guidelines, all relevant articles with no design restrictions from PubMed, Scopus, Cochrane, and Embase databases were screened for inclusion. Studies were included if they reported clinical endpoints for TAVR, with the severity of calcification on aortic valve. Odds ratio and Cohen’ D were considered as effect size measurements for qualitative and quantitative variables, respectively.
RESULTS A total of seven studies involving 3638 patients were included in the analysis, with 60.7% (n = 2207) reporting severe aortic valve calcification. However, these patients did not exhibit a higher risk of all-cause mortality during the one-year follow-up after TAVR (OR = 0.86, 95% CI: 0.68–1.07). The included studies showed no significant heterogeneity (I2 = 0.0%, P = 0.31). In subgroup analysis, there was no significant difference in the incidence of stroke during the one-year follow-up between the severe calcification group and the non-severe calcification group (OR = 0.8, 95% CI: 0.51–1.26) either. During the 30-day follow-up post-procedure, patients with severe aortic valve calcification exhibited a similar risk of all-cause mortality and stroke compared to those with non-severe calcification (OR = 0.86, 95% CI: 0.58–1.26 and OR = 0.76, 95% CI: 0.46–1.23, respectively). However, the risk of paravalvular leak (PVL) was markedly elevated in the severely calcified group (OR = 2.17, 95% CI: 1.50–3.15).
CONCLUSIONS This study indicates that the severity of aortic valve calcification may not serve as a sole predictor for assessing short-term or long-term mortality risk after TAVR. However, a more comprehensive assessment is necessary, considering the risk of stroke and/or death, as well as the prediction of PVL occurrence in patients with severe calcification.
GW35-e1004
Haowei Li1,2,3,4,5, Guangzhi Cong1,2,3,4,5, Jingjing Wang1,2,3,4,5, Xueping Ma1,2,3,4,5, Bo Shi1,2,3,4,5, Congyan Ye1,2,3,4,5, Shizhe Fu1,2,3,4,5, Rui Yan1,2,3,4,5, Kairu Wang1,2,3,4,5, Baotong He1,2,3,4,5, Zefeng He1,2,3,4,5
1Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
2School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, China
3Institute of Cardiovascular Medicine, General Hospital of Ningxia Medical University, Ningxia, China
4Department of Cardiology, General Hospital of Ningxia Medical University, Ningxia Medical University, Ningxia, China
5NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Ningxia, China
OBJECTIVES Ischemic stroke poses a significant risk for hospitalized patients undergoing transcatheter aortic valve replacement (TAVR). However, the association between malnutrition and the incidence of ischemic stroke after TAVR remains unclear. This study aims to investigate the relationship between malnutrition and ischemic stroke incidence following TAVR using National Inpatient Sample (NIS).
METHODS We conducted a retrospective observational study utilizing data extracted from the National Inpatient Sample spanning the years 2012 to 2021. Our analysis focused on identifying patients who underwent TAVR and were diagnosed with malnutrition based on ICD-9 and ICD-10 codes. Exclusion criteria comprised patients under 18 years of age, those with a history of stroke, or those afflicted with both ischemic and hemorrhagic stroke. After adjusting for influential covariates, logistic regression was used to determine the association between malnutrition and ischemic stroke risk. Stratified analysis and propensity score matching were used to perform sensitivity analyses of the primary outcome.
RESULTS A total of 74,662 TAVR patients were included, of which 2144 (2.87%) were diagnosed with malnutrition. Malnourished patients were older (78.18 ± 11.08 vs. 77.49 ± 9.85), predominantly white (85.54%) and exhibited a higher incidence of ischemic stroke (11.33% vs. 7.32%, P < 0.001). After adjusting for common ischemic stroke risk factors, malnutrition significantly raised the incidence of ischemic stroke (aOR: 1.51; 95% CI: 1.31–1.74) in TAVR patients. These relationships persisted in the propensity-matched cohort. Subgroup analysis stratified by age, sex, race, selective admission, hospital geographic distribution, and comorbidities consistently revealed associations between malnutrition and ischemic stroke risk.
CONCLUSIONS Malnutrition is associated with an elevated incidence of ischemic stroke following TAVR. Further research and practical clinical interventions are essential for mitigating the increased risk of ischemic stroke in patients undergoing TAVR with malnutrition.
GW35-e1032
Ying Yang
Yichang Central People’s Hospital
OBJECTIVES Patent foramen ovale (PFO) is closely associated with migraine. However, the mechanism remains unclear. Diffusion tensor imaging (DTI) is widely used to study microstructural changes of the whole brain, we aimed to use DTI to investigate microstructure changes of the whole brain in migraineurs with PFO.
METHODS A total of 20 migraineurs enrolled in PFO group, and 20 TCD-negative migraineurs matched with gender and similar age were included in control group. All patients underwent brain DTI. DSI-studio software was used to complete the preprocessing.
RESULTS There was no significant difference in their baseline clinical characteristic. The whole brain tissue is divided into 98 brain regions. PFO group showed significantly decreased fractional anisotropy (FA) in 11 brain regions, and significantly increased FA in 1 brain region. There are 14 brain regions with significantly increased mean diffusion (MD) and radial diffusion (RD) in PFO group, and in which most brain regions are consistent. In terms of axial diffusion (AD), 12 brain regions were significantly increased in PFO group. The RD of the corpus callosum body in the PFO group was significantly increased, and MD of the left inferior longitudinal fasciculus and right corticospinal tract, and the AD of the left thalamic radiation were significantly increased in PFO group. Correlation analysis revealed that the MD, RD and AD of the fusiform are significantly positively correlated with the PFO diameter.
CONCLUSIONS The microstructure of the brain is significantly changed in migraineurs with PFO, and fusiform damage may be associated with migraine caused by PFO.
GW35-e1033
Ying Yang
Yichang Central People’s Hospital
OBJECTIVES PFO is a prevalent disease and an independent risk factor for migraine. However, the mechanism remains unclear. Using SBM and VBM to investigate changes in brain microstructure in patients with PFO.
METHODS Patients with migraine who had undergone TCD in our hospital were collected and divided into the PFO group and control group. Patients with a positive TCD result were confirmed PFO by TE. A total of 40 patients were enrolled, including 20 in the PFO group and 20 in the control group. All patients underwent brain MRI.
RESULTS There was no significant difference between the PFO and control patients regarding age, sex, hypertension, diabetes mellitus, hyperlipidemia, and migraine duration (all P > 0.05). VBM results showed that there were no significant differences in TIV, GM volume, WM volume, and CSF volume between the two groups (all P > 0.05). Compared with the control group, WM volume decreased in 6 nuclear groups in the PFO group, including declive, extra-nuclear in the right cerebrum, and superior temporal gyrus, parahippocampal gyrus, cingulate gyrus, postcentral gyrus in the left cerebrum, and GM volume of the parahippocampal gyrus of the bilateral cerebrum was significantly smaller in PFO group (all P < 0.05). Furthermore, SBM results showed differences in CT, SD, and FD between the two groups, but the differences were not significant and could not pass FDR correction.
CONCLUSIONS Using the structural MRI to study brain structure helps explore the mechanism and subtle changes of nervous system abnormalities in patients with PFO.
GW35-e1036
Yimin Li, Ruijie Li, Huang Sun, Tao Yang, Qingling Wang
The First Affiliated Hospital of Kunming Medical University
OBJECTIVES Dilatation and angulation of the ascending aorta are common in patients with severe aortic stenosis (AS). In this study, we aimed plan to explore the impact of mechanical stress changes in aortic stenosis on the pathologic and structural changes of aorta.
METHODS Patients with severe aortic stenosis and planed for TAVR were included in this study. Preoperative intra-aortic CT, echocardiogrpahy and intra-aortic pressure were collected to build a computational Fluid Dynamics (CFD) framework model. MIMICS (Materialize’s interactive medical image control system) software was used to construct a 3D model of the aorta; the FLUENT software was used to perform CFD simulation under flow boundary conditions; wall sheer pressure (WSS) and wall pressure stress (WPS) of the blood flow in the aorta were analyzed with post-processing software () as a whole and at multiple different locations. Correlation analysis was performed between the obtained data and the structural changes of the patients’ aorta.
RESULTS In 4 patients with severe AS included, dilatation and bending of ascending aorta were found in all patients. Ascending aorta bending occurred in the area opposite to aortic valve where maximum WPS was detected. The WPS was significantly increased in the dilation area compared to the descending aorta area without dilation (P = 0.043). Aortic valve area positively correlated to WPS gradient with aorta (R2 = 0.916, P = 0.043).
CONCLUSIONS In patients with severe aortic stenosis, aortic dilation and angulation occurred in the area where the highest WPS existed. Increased wall pressure stress due to increased aortic velocity might be an important mechanism of aortic dilation in these patients.
GW35-e1063
Yao Ma, Chang Liu, Yuan Wang, Dengfeng Gao
Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University
OBJECTIVES Metabolic syndromes and type 2 diabetes are strongly associated with atrial fibrillation and multiple cardiovascular disease incidence. However, there is limited evidence on their effects on the left atrium (LA). This study broadly investigated whether adverse glucose and lipid metabolism levels are causally associated with LA structural, functional, and electrical remodeling.
METHODS Significant variants of glucose and lipid metabolism obtained from the genome-wide association studies (GWAS) in the Global Lipid Genetics Consortium (n = 188,577) and the diabetes consortium (n = 108,577) were used as instrumental variables in this study, including insulin resistance (IR), fasting insulin, fasting glucose, HbA1c, total cholesterol, triglycerides (TG), high-density lipoproteins (HDLC), low-density lipoproteins (LDLC), and lipoprotein(a). GWAS summary statistics for LA morphology and function based on cardiac magnetic resonance (n = 16,923) were used as outcome sources, with additional consideration of P-wave duration and PR interval based on electrocardiogram. Causality was investigated using two-sample Mendelian randomization (MR) analyses with the inverse variance weighted method as the primary estimation method. Sensitivity analyses were performed using Multivariate MR methods. Cross-sectional correlations were tested in 26,506 European individuals from UK Biobank with blood biochemistry and LA measurements.
RESULTS Per 1-standard deviation increase in genetically predicted IR was associated with smaller LA passive emptying fraction (β = −0.21%, 95% confidence interval [CI] −0.33 to −0.08%, P = 0.001), and longer PR intervals (β = 2.45 ms, 95% CI: 0.64 to 4.26 ms, P = 0.008). High genetically predicted TG resulted in reduced atrial volume (LA max volume, β = −0.07 mL, 95% CI: −0.13 to −0.005 mL, P = 0.03; LA min volume, β = −0.07 mL, 95% CI: −0.13 to −0.008 mL, P = 0.03) and shorter P wave duration (β = −5.89 ms, 95% CI: −9.05 to −2.72 ms, P = 0.0003). Multivariate MR supported an independent effect of TG on reduced LA volume and increased LA function, additionally pointed to a slight positive effect of LDLC with increased LA volume. Lipoprotein(a), as a predictor of risk for atrial fibrillation independently of all other lipid markers, was not found to have a significant causal association with LA remodeling. Observational analyses yielded partially consistent results.
CONCLUSIONS This study highlights the significant role of genetic susceptibility to IR, TG and LDLC in LA remodeling, especially the pioneering role in TG-dominated metabolic disorders, which may enhance our understanding of metabolic disorders affecting cardiovascular disease development.
GW35-e1187
Congyan Ye, Bo Shi, Shizhe Fu, Rui Yan, Kairu Wang, Shaobin Jia, Guangzhi Cong
General Hospital of Ningxia Medical University
OBJECTIVES Acute kidney injury (AKI) complicates transcatheter aortic valve replacement (TAVR), leading to higher mortality. Incidence and effect of AKI on clinical outcomes in patients undergoing TAVR without chronic kidney disease (CKD) is unclear. We aimed to determine the association between AKI and in-hospital outcomes in patients with TAVR using propensity score matching (PSM).
METHODS Using International Classification of Diseases-10th Revision codes, we queried the National Inpatient Sample for TAVR performed between 2016 and 2021. Patients were divided into two groups according to perioperative AKI development. We excluded patients with CKD or those on permanent hemodialysis at baseline. We conducted 1:1 PSM to assemble a cohort of patients with similar baseline characteristics. Multivariate logistic regression analyses assessed the association between AKI and in-hospital outcomes. Sensitivity analyses evaluated the robustness of our inferences.
RESULTS Of 47,372 unweighted patient admissions for TAVR, 1617 (3.41%) had a concomitant diagnosis of AKI. AKI incidence decreased from 4.82% to 3.18% (P-trend < 0.01). Before PSM, patients with AKI had a significantly higher rate of in-hospital mortality compared with those without AKI (6.12% vs. 0.48%, respectively; odds ratio [OR] 8.59, 95% confidence interval [CI] 6.32–11.68). Using the PSM algorithm, 1579 well-matched patients were included in each group. After PSM, an association was observed between patients with TAVR and concomitant AKI and a higher risk of in-hospital mortality (6.21% vs. 1.08%, respectively; OR: 5.96; 95% CI: 3.54–10.04). In subgroup analyses stratified according to age (≤80 and >80 years), sex (male/female), and hypertension status, consistent associations were observed between AKI and the risk of in-hospital mortality. AKI patients were at higher risk for acute myocardial infarction (OR: 1.78, 95% CI: 1.35–2.34), major bleeding (OR: 1.62, 95% CI: 1.13–2.33), blood transfusion (OR: 1.65, 95% CI: 1.28–2.11), and cardiogenic shock (OR: 3.73, 95% CI: 2.77–5.01). No significant between-group differences were observed concerning stroke (P = 0.12).
CONCLUSIONS AKI was a strong predictor of in-hospital mortality in patients with TAVR without CKD and was associated with higher post-procedure complication rates.
GW35-e1192
Maoxiang Zhao1, Guangyuan Song1, Hao Xue2, Shouling Wu3
1Department of Interventional Center of Valvular Heart Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
2Department of Cardiology, the Sixth Medical Center, Chinese People’s Liberation Army Hospital, Medical School of Chinese People’s Liberation Army, Beijing, China
3Kailuan Hospital, Tangshan, China
OBJECTIVES Although several studies have investigated the relationship between obesity and aortic valve calcification (AVC), the associations of long-term obesity, recent obesity, and weight change with AVC risk remain uncertain, and longitudinal studies among Chinese population are still lacking.
METHODS Briefly, from June 2006 to December 2023, 201,985 individuals aged ≥18 years were enrolled to biennially participate in questionnaire interview, clinical examinations and laboratory test at 11 hospitals affiliated with the Kailuan Group. Among them, 45,720 underwent standard transthoracic echocardiography and Doppler flow imaging. Aortic valve calcification cases were ascertained through linkage with hospitals electronic medical record system. For the present study, participants were included if they underwent repeated standard transthoracic echocardiography and Doppler flow imaging during follow-up. The date of the first echocardiography was considered as the baseline. Of the 10,420 participants who met these criteria for assessing the associations of current BMI with AVC. Of these participants, 4401 underwent three consecutive surveys within 6 years prior to the baseline and were used to study the associations of changes in BMI and its change with the AVC. Data were analysed using Cox proportional hazards regression.
RESULTS During a median follow-up of 4.62 years, 2655 participants developed AVC. In multivariable Cox proportional hazards regression models, the hazard ratios for AVC were as follows: 1.34 (95% CI, 1.20–1.49; P for trend < 0.01) for current BMI level, 1.40 (95% CI, 1.09–1.81; P for trend < 0.01) for time weighted average (TWA) BMI level, 1.22 (95% CI, 1.03–1.45; P for trend < 0.01) for cumulative BMI level, and 0.79 (95% CI, 0.67–0.93; P for trend < 0.01) for BMI time in target range (TTR). In contrast, no association was found between BMI variability and AVC. Compared with metabolically healthy normal-weight individuals, both metabolically healthy obesity and metabolically healthy overweight were associated with increased AVC risk. In comparison to participants with stable normal weight (NW), participants with stable overweight/obesity (OW/OB) were at the highest AVC risk (HR: 1.29, 95% CI: 1.07–1.55). No significant association between changes in weight status and AVC risk was observed in participants who NW to OW/OB and participants with OW/OB to NW.
CONCLUSIONS In this population-based study, obesity is a significant risk factor of AVC, even without metabolic disorder. With repeated measurements of weight and height, long-term obesity was associated with increased AVC risk, but not variability. Additionally, this study identifies that TTR might be a useful metric of body weight management for population-based quality assessment. Taken together, these findings highlight the potential for population-wide weight control strategies to mitigate the emerging epidemic of AVC.
GW35-e1226
Wang Jianming
General Hospital of Shenyang Military Region, Shenyang, China
OBJECTIVES In the past, most of the patients with atrial septal defect (ASD) and atrial fibrillation (AF) were only treated for ASD. However, ASD patients with AF need to take anticoagulants for life. The use of antiarrhythmic drugs and oral anticoagulants has a low control rate and a high risk of bleeding. Left atrial appendage closure (LAAC) with simultaneous interventional occlusion for ASD has become a new therapy. To report long-term safety and efficacy of simultaneous percutaneous LAA and ASD closure in comparison with ASD closure alone.
METHODS A retrospective study of 101 consecutive patients. Data were compared between 51 cases with simultaneous percutaneous procedures of LAAC and ASD closure (group I) undergoing LAAC procedures using the LAmbre or LACBES LAA occluders and 50 cases only with ASD closure (group II). All clinical events were obtained by telephone, outpatient visit or case histories, and the follow-ups, including medical treatment and TEE imaging, etc.
RESULTS There were no statistical differences in the patient characteristics of the two groups. During the follow-up period, there were no significant differences between the two groups in cardiac death (1.98% vs. 3.9%, P = 0.495). There were significant differences between the two groups, group I had lower embolism events (3.9% vs. 18%, P = 0.028) and major bleeding events (0% vs. 15.7%, P = 0.003). Compared with group II, the probability of all thromboembolic events was decreased in group I (HR = 4.295, CI: 1.317–14.01, P = 0.0409), and the observed annual rate of bleeding was decreased in group I (HR = 7.311, CI: 1.828–29.23, P = 0.0049) either by Kaplan–Meier analysis.
CONCLUSIONS Simultaneous percutaneous LAAC combined with ASD closure might be an ideal choice to prevent stroke and other thrombotic complications, especially for preventing major bleeding in patients with both non-valvular atrial fibrillation and ASD.
GW35-e1254
Xueqing Xing
First Hospital of Shanxi Medical University
OBJECTIVES Recent studies have shown that right atrial (RA) function are important predictors of cardiovascular morbidity and mortality. However, the study data about RA phasic function in obstructive sleep apnea syndrome (OSAS) patients are scarce, especially based on the left ventricular geometry. So, we aimed to assess the influence of left ventricular geometry on RA phasic function in OSAS patients via a multimodal echocardiographic approach.
METHODS Total of 235 OSAS patients were enrolled in this cross-section study and underwent complete clinical, polysomnography, echocardiography examinations. The OSAS patients were divided into four groups based on left ventricular mass index (LVMI) and relative wall thickness (RWT): normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). RA phasic function was evaluated via multimodal echocardiography approach (two-dimensional echocardiography biplane method, 2DE; two-dimensional speckle tracking echocardiography, 2D-STE and three-dimensional echocardiography, 3DE). The multiple linear regression analysis was used to determine the relationship between left ventricular geometry and RA phasic function.
RESULTS The RA volume and indices increased from NG to CR to EH to CH. RA total emptying fraction (RA TotEF) and RA strain during systole (RAS-S) decreased from NG to CR to EH to CH. RA passive emptying fraction (RA PassEF) and RA strain during early diastole (RAS-E) similarly decreased. RA active emptying fraction (RA ActEF) and RA strain during late diastole (RAS-A) also gradually increased similarly. In analyses that adjusted for gender, age, body mass index, systolic blood pressure (SBP), apnea-hypopnea index (AHI), LVMI, systolic pulmonary artery pressure and right ventricular free wall thickness, concentric hypertrophy was associated with RA reservoir and conduit function via 2DE area-length method, whereas concentric hypertrophy and eccentric hypertrophy were associated with RA reservoir and conduit function via 2D-STE and 3DE method. Further, concentric hypertrophy was associated with RA booster pump funtion via 2DE area-length method, 2D-STE and 3DE method.
CONCLUSIONS The RA volumes and phasic function varied with left ventricular geometry via multimodal echocardiography approach. Concentric hypertrophy had the apparent negative effect on RA phasic function.
GW35-e1307
Kairi Wang, Shizhe Fu, Guangzhi Cong, Shaobin Jia
General Hospital of Ningxia Medical University
OBJECTIVES Transcatheter aortic valve replacement (TAVR) has witnessed significant advancements in the treatment of aortic stenosis over the past decade, surpassing surgical aortic valve replacement (SAVR) as the primary intervention in 2019. While TAVR offers significant advantages, including lower invasiveness and quicker recovery, it is not without risks. Serious complications, such as aortic dissection, remain a concern and can significantly impact patient outcomes. Despite its clinical importance, there is a notable gap in research focusing on intraoperative complications of TAVR, particularly regarding gender differences in aortic dissection incidence. This study aimed to investigate gender-specific differences in the incidence of intraoperative aortic dissection during TAVR procedures using a comprehensive dataset from the National Inpatient Sample (NIS) database.
METHODS This retrospective study utilized data from the NIS covering the period from 2012 to 2021. The study included 84,275 inpatients who underwent TAVR. Patients were stratified by gender into male and female groups. The primary outcome was to assess the incidence of in-hospital aortic dissection, with secondary outcomes on in-hospital mortality. Additionally, the temporal trend of this complication in recent years was analyzed.
RESULTS Between 2012 and 2021, the total number of patients undergoing TAVR surged from 1332 to 16,604, showing a steady upward trend for both genders. Notably, more TAVR procedures were performed on males (55.06%) compared to females (52.03%). The incidence of aortic dissection did not differ significantly between male and female patients (OR: 0.92 [95% CI: 0.71, 1.19], P = 0.51). Conversely, in-hospital mortality was significantly lower in male patients compared to female patients (OR: 0.78 [95% CI: 0.69, 0.88], P < 0.05).
CONCLUSIONS These findings suggest that while the incidence of aortic dissection does not significantly vary between genders, male patients undergoing TAVR have a significantly lower in-hospital mortality compared to their female counterparts. This highlights the need for further research to understand the underlying factors contributing to these gender differences in outcomes.
GW35-e1312
Qinghao Zhao1, Wenchang Nie1, Shenda Hong2, Jian Liu1
1Department of Cardiology, Peking University People’s Hospital
2National Institute of Health Data Science, Peking University
OBJECTIVES Disorders of mineral metabolism, including elevated levels of serum calcium, phosphate, 25-hydroxyvitamin D (25OH-VitD), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), have been reported in patients with calcific aortic valve stenosis (CAVS). However, evidence of the causal role of mineral metabolism in CAVS is still lacking. We aimed to investigate the causality between mineral metabolism and CAVS.
METHODS A systematic pipeline combining Mendelian randomization (MR), Steiger directionality test, colocalization analysis, protein-protein network, and enrichment analysis was applied to investigate the causal effect. Genome-wide association study (GWAS) and protein quantitative trait loci data for mineral metabolism markers were extracted from large-scale meta-analyses. Summary statistics for CAVS were obtained from two independent GWAS datasets as discovery and replication cohorts (n = 374,277 and 653,867).
RESULTS In MR analysis, genetic mimicry of serum FGF23 elevation was associated with increased CAVS risk [ORdiscovery = 3.081 (1.649–5.760), Pdiscovery = 4.21 × 10−4; ORreplication = 2.280 (1.461–3.558), Preplication = 2.82 × 10−4] without evidence of reverse causation (Psteiger = 7.21 × 10−98). Strong colocalisation association with CAVS was observed for FGF23 expression in the blood (PP.H4 = 0.96). Additionally, we identified some protein-protein interactions between FGF23 and known CAVS causative genes. Serum calcium, phosphate, 25OH-VitD, and PTH failed to show causal effects on CAVS at Bonferroni-corrected significance (all P > 0.05/5 = 0.01).
CONCLUSIONS Elevated serum FGF23 level is a causal risk factor for CAVS, and its mechanism of action in CAVS development may be independent of its function in regulating mineral metabolism. Hence, FGF23 may serve as a circulating marker and a promising preventive target for CAVS, warranting further investigation.
GW35-e1330
Shizhe Fu1,2, Kairu Wang1,2, Bo Shi1,2, Congyan Ye1,2, Rui Yan1,2, Haowei Li1,2, Shaobin Jia1,3,4, Guangzhi Cong1,3,4
1Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
2School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, China
3Institute of Cardiovascular Medicine, General Hospital of Ningxia Medical University, Ningxia, China
4Department of Cardiology, General Hospital of Ningxia Medical University, Ningxia Medical University, Ningxia, China
OBJECTIVES Patients with aortic stenosis and atrial fibrillation face a higher risk of stroke during Transcatheter aortic-valve replacement (TAVR). It is unclear whether providing cerebral embolic protection (CEP) can effectively reduce the risk of stroke during or after surgery in such patients.
METHODS This study analyzed data from the Nationwide Inpatient Sample (NIS) from 2017 to 2021, which included 23,648 patients with atrial fibrillation who underwent TAVR. The primary endpoint was the incidence of stroke during hospitalization. We utilized rigorous statistical methods typical of real-world research, including multivariate regression, inverse probability weighting (IPTW), and propensity score matching (PSM), to enhance the reliability of the analysis.
RESULTS Out of the 23,648 patients, 2034 received CEP-assisted therapy. There was no significant difference in the risk of stroke (aOR: 0.95, 95% CI: 0.68–1.34) or transient ischemic attack (aOR: 1.12, 95% CI: 0.51–2.45) during hospitalization between the CEP group and the control group. However, the CEP group experienced a lower risk of death (aOR: 0.58, 95% CI: 0.35–0.96) and cardiac arrest (aOR: 0.49, 95% CI: 0.27–0.91) during hospitalization compared to the control group. These findings were consistent even after IPTW and PSM of baseline characteristics.
CONCLUSIONS Among patients with atrial fibrillation undergoing transfemoral TAVR, the use of CEP had no significant effect on the incidence of periprocedural stroke, but based on the 95% confidence interval for this finding, the results may not rule out a benefit of CEP in TAVR among Patients with atrial fibrillation.
CARDIOMYOPATHY
GW35-e0145
Gang Fan, Hong Zuo
Xianyang Central Hospital
OBJECTIVES There is a scarcity of studies investigating the relationship between NAFLD and cardiomyopathy, and the available observational studies may be biased. We aimed to investigate the causal effect of NAFLD on cardiomyopathy using Mendelian randomization (MR) analysis.
METHODS The summary-level data for NAFLD and cardiomyopathy of European ancestry were extracted from publicly available genome-wide association studies (GWAS). The sample size for NAFLD as an exposure variable was 37,799 and the sample sizes for dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) as outcome variables were 355,381 and 489,727, respectively. The main analysis used was the random inverse variance weighted (IVW) method, weighted median and the MR-Egger method as supplementary evidence for IVW results. Horizontal pleiotropy and heterogeneity tests were performed to assess the stability of the results.
RESULTS Seven SNPs were retrieved by means of the SNP screening criteria. However, our study found no significant association between NAFLD and DCM (OR = 1.00, 95% CI: 0.86–1.16; P = 0.9892) or HCM (OR = 1.02, 95% CI: 0.77–1.34; P = 0.8923). Horizontal pleiotropy and heterogeneity tests confirmed the robustness of the MR findings with respect to horizontal pleiotropy (P > 0.05).
CONCLUSIONS There is no evidence to support that NAFLD is a direct causal risk factor for cardiomyopathy. Other factors are likely to mediate previous observational associations between NAFLD and cardiomyopathy.
GW35-e0186
YanPeng Li, Dilara Adi, YiTong Ma
Department of Cardiology Heart disease, The First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES To explore the serum levels of lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC) in patients with dilated cardiomyopathy (DCM) and their significance.
METHODS 250 patients with dilated cardiomyopathy, admitted to the Heart Center of the First Affiliated Hospital of Xinjiang Medical University from September 2022 to August 2023, were selected as the research object (DCM group), and 250 patients with non-dilated cardiomyopathy admitted in the same period were selected as the control group. Serum LPA and LPC levels were measured by enzyme linked immunosorbent assay (ELISA). Univariate and multivariate logistic regression were used to evaluate the diagnostic significance of LPA and LPC levels in DCM. According to the LPA and LPC levels, the cardiac function of patients in different levels was analyzed, and the predictive value of LPC and LPA levels and their combination with NT-proBNP on DCM was analyzed by ROC curve.
RESULTS The serum LPA level in DCM group was higher than that in control group, and the serum LPC level was lower than that in control group, with statistical significance (P < 0.05). Spearman correlation analysis showed that serum LPA level was positively correlated with NT-proBNP level and negatively correlated with LVEF level, which could be used as a predictor of prognosis and severity of DCM. Serum LPC level was positively correlated with LVEF level and negatively correlated with NT-proBNP level. Logistic regression analysis showed that serum LPA and LPC levels were independent influencing factors for the risk and severity of DCM (P < 0.001). ROC curve analysis shows that LPA combined with NT-proBNP is better than NT-proBNP alone in predicting DCM events.
CONCLUSIONS Serum LPA and LPC levels are independent related factors of DCM, and are closely related to the severity of DCM patients. Serum LPA level combined with NT-proBNP can be used to predict DCM more accurately.
GW35-e0195
Xiaolei Li, Dilare Adi, Yitong Ma
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES To investigate the metabolic profile characteristics of dilated cardiomyopathy (DCM) using combined multi-omics analysis and to establish a metabolic-genetic model for the diagnosis and prognostic assessment of DCM.
METHODS Thirty cases each of ethnicity, gender, and age-matched DCM patients and healthy individuals were screened for non-targeted metabolomics analysis, differential metabolites were screened using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and signature markers were screened and early diagnostic model for DCM was established using machine learning methods. Combined with transcriptomics data, key pathway enrichment analysis was performed to screen key pathway signature genes, and signature gene scores were established for the assessment of DCM disease progression.
RESULTS One hundred and thirty differential metabolites were screened compared to healthy controls. Among them, dysfunctional glycerophospholipid metabolism (GPL) was identified and validated as a characteristic metabolic pathway in DCM. By LASSO regression, we identified the seven most important GPL metabolites. The established diagnostic models based on these seven metabolites were all able to identify DCM patients well (AUC were all greater than 0.90). Further, we screened five GPL-associated signature genes, namely CDIPT, LPCAT3, BCHE, DGKD, and DDHD2, and calculated GPL scores for predicting DCM disease progression. The area under the ROC curve for the training and test sets were: 0.84 and 0.78, respectively. Transcription factors GATA2 and has-mir-26b-5p may be the regulators of the characterized genes. Mitochondrial energy metabolism and autoimmune-related pathways were significantly enriched in patients with higher GPL scores. We combined clinical information and GPL scores to construct a Nomogram model for assessing the progression of DCM, and the results showed that the model had good diagnostic (corrected C-index = 0.80) and calibration capabilities (Hosmer-Lemeshow test, χ2 = 5.27, P = 0.73), while the DCM curve analysis suggested that the patients could also derive Clinical benefits.
CONCLUSIONS GPL metabolism may play a contributing role in the pathophysiological mechanisms of DCM, and the metabolic-gene model we established can help in the early diagnosis of DCM and the prediction of disease progression, which has some clinical translational value.
GW35-e0196
Xiaolei Li, Dilare Adi, Yitong Ma
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES Dilated cardiomyopathy (DCM) is a common primary cardiomyopathy with a high risk of mortality and a poor prognosis. Our aim was to develop validated tools for assessing the prognostic risk of DCM for later management.
METHODS A total of 1105 patients with DCM from the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed between 2015 and 2020 and randomly divided into development and validation groups by 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) and recursive feature elimination with cross-validation (RFECV) was used in the selection of variables. We developed traditional linear regression models [Cox proportional hazards (CoxPH) and Cox proportional hazard with elastic net penalty (CoxNet)] and machine learning (ML) algorithmic models [random survival forest (RSF), survival trees (ST), gradient boosting (GB), extra survival trees (EST) and survival support vector machine (SSVM)] based on 10 simple variables. We use Harrell’s concordance index (C-index), integrated brier score (IBS) and the time-dependent area under the curve (AUC) to evaluate and compare the predictive performance of the models. The SHapley Additive exPlanations (SHAP) method was applied to the optimal model to certify its interpretability.
RESULTS During a median follow-up of 44 months, 197 patients who died in the subsequent period. Through variable screening, eight variables, including ethnic, age, systolic blood pressure (SBP), left ventricular ejection fraction (LVEF), hemoglobin (Hb), albumin (ALB), creatinine (Cr) and N-terminal precursor B-type diuretic peptide (NT-proBNP) were finally used to develop the prediction models. In all six prediction models, EST performed much better than other models (C-index: 0.808, IBS: 0.085). The time-dependent AUC of EST was the highest at most times (mean AUC = 0.803). Our EST model accurately classifies DCM patients into three risk groups: high, medium and low (P < 0.05).
CONCLUSIONS The EST model can provide a reliable prognostic prediction for DCM patients. Moreover, the model can accurately distinguish high-risk groups, which may help in clinical medical decision making.
GW35-e0372
Yahui Lu1,2
1Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
2Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China
OBJECTIVES Hypertrophic cardiomyopathy (HCM), the predominant inherited cardiovascular disorder, poses a significant health burden globally. Chest pain, a common initial symptom in HCM patients, is closely linked to myocardial ischemia, despite the absence of significant coronary arteries stenosis. This study explored microvascular dysfunction in HCM patients, employing angiography-derived microcirculatory resistance (AMR) as a novel, non-invasive tool for comprehensive assessment.
METHODS This retrospective analysis included HCM patients with chest pain as the primary symptom and control patients without cardiac hypertrophy during the same period. AMR was computed through angiography, providing a wire-free and adenosine-free index for evaluating microcirculatory function. Propensity score matching ensured balanced demographics between groups. This study also investigated the correlation between AMR and clinical outcomes, utilizing echocardiography and follow-up data.
RESULTS After propensity score matching, 76 HCM patients and 152 controls were analyzed. While epicardial coronary stenosis showed no significant difference, AMR on three epicardial coronary was markedly higher in HCM patients, indicating widespread microcirculatory dysfunction. A criterion of AMR ≥250 mmHg*s/m identified 65.7% of HCM patients experiencing coronary microvascular dysfunction (CMD), which was significantly higher than normal controls (OR = 5.77, 95% CI: 3.17–10.50, P < 0.001). Independent risk factors for CMD included increased left ventricular (LV) wall thickness (OR = 1.209, 95% CI: 1.013–1.443, P = 0.036). Furthermore, AMR_LAD ≥250 mmHg*s/m had an increased cumulative risk of the endpoint (log-rank P = 0.023) and was an independent risk factor for the endpoint (HR = 11.64, 95% CI: 1.13–120.03, P = 0.039), providing valuable prognostic insights.
CONCLUSIONS AMR is a useful tool for assessing microcirculatory dysfunction in HCM patients, providing a non-invasive and adenosine-free option. The increased AMR levels in HCM patients, especially those with chest pain, indicate a high prevalence of CMD. The prognostic value of AMR highlights its potential for guiding treatment decisions and risk assessment in HCM patients.
GW35-e0439
Teruhiko Imamura, Toshihide Izumida, Koichiro Kinugawa
Second Department of Internal Medicine, University of Toyama
OBJECTIVES Remote dielectric sensing (ReDS) systems can quantify the degree of pulmonary congestion rapidly and non-invasively. However, the clinical implications of ReDS-guided medication adjustment remain uncertain.
METHODS Patients hospitalized to treat cardiovascular diseases, including heart failure, valvular disease, and coronary artery disease, and underwent ReDS measurement before index discharge between 2021 and 2022 were included. According to our institutional protocol, ReDS values were blinded to the attending clinicians until February 2022 (blind period). After the period, ReDS values were timely opened to the attending clinicians and medication such as diuretics were adjusted according to the ReDS values (target value between 20% and 35%) before index discharge (open period). A composite primary outcome of all-cause death and heart failure readmissions was compared between the two groups.
RESULTS A total of 183 patients were included (median 79 years, 101 men), consisting of 138 patients in the blind period and 45 patients in the open period. During a median of 646 (401, 818) days after the index discharge, 33 patients experienced the primary outcome. Management during the open period, where medications were adjusted according to ReDS values, was independently associated with a lower incidence of the primary outcome with an adjusted hazard ratio of 0.22 (95% confidence interval 0.05–0.94, p = 0.041), as compared with those of the blind period.
CONCLUSIONS According to the findings of the present retrospective study, ReDS-guided management may have the potential to reduce the risk of mortality and heart failure admission in individuals hospitalized for cardiovascular diagnoses. Further prospective randomized control trials involving those with a variety of background etiologies and clinical scenarios are warranted to validate our findings and establish optimal ReDS-guided management.
GW35-e0507
Yuan Huang1, Qiang Su1, Chun Gui2
1Jiangbin Hospital of Guangxi Zhuang Autonomous Region
2The First Affiliated Hospital of Guangxi Medical University
OBJECTIVES D-dimer is a biomarker of coagulation and fibrinolytic system activation in response to the hypercoagulable state of the body. The research aimed to analyze the value of D-dimer in the prognosis of patients with dilated cardiomyopathy (DCM).
METHODS Patients admitted to our center for the first time with DCM were enrolled consecutively. The clinical characteristics variables were obtained from the electronic medical record system, and the prognostic information was obtained using telephone return visits and a review of repeated hospitalization records. Univariate and multivariate Cox regression was used to explore the association of D-dimer with all-cause mortality. Smooth curve fitting, threshold saturation effect analysis, and subgroup analysis were performed.
RESULTS Ultimately, 534 patients were included. After a follow-up of the enrolled patients, 485 patients obtained prognostic information, of which 159 died from all causes, and the main cause of death was heart failure (89/159), the sudden death accounted for about 17%. The independent positive association between D-dimer and all-cause mortality remained unchanged in both unadjusted and adjusted Cox regression models. In the fully adjusted model, each standard deviation increase in D-dimer was associated with a 14% increase in all-cause mortality (HR = 1.14; 95% CI: 1.02~1.27; P < 0.05). Curve fitting and threshold effect analysis showed an inflection point in the relationship between D-dimer and all-cause mortality (non-linear test: P = 0.03). When D-dimer was equal to 362 ng/mL, HR = 1; and as the value increased, the risk of all-cause mortality increased by 34.7% for every 2-fold increase in D-dimer gradually (HR = 1.347; 95% CI: 1.069~1.697; P = 0.012). In subgroup analysis, D-dimer and BMI had a significant interaction on all-cause mortality, with a significantly increased risk of all-cause mortality in subjects with BMI ≥25 kg/m2 (HR = 1.99; 95% CI: 1.34~2.97; P < 0.01). The ROC curve showed that D-dimer was a good predictor of all-cause mortality, and the areas under the curve at 1-, 3-, and 5-year were 0.71, 0.64, and 0.59, respectively. In addition, D-dimer improved the predictive performance of the MAGGIC heart failure score in patients with DCM.
CONCLUSIONS D-dimer is not only independently associated with all-cause mortality in DCM patients, but also has good predictive value, suggesting that D-dimer may be an early and useful marker for improving the management of DCM patients.
GW35-e0676
Yanan Zhao, Wenjia Liu, Tao Li
The First Medical Center of PLA General Hospital
OBJECTIVES Systemic sclerosis (SSc) is a rare autoimmune systemic heterogeneous connective tissue disease with a high prevalence of SSc-primary cardiac involvement (SSc-pHI) at autopsy, however, many subclinical SSc-pHI are missed clinically because they have no cardiac symptoms. We aimed to detect and characterize subclinical SSc-pHI by cardiovascular magnetic resonance (CMR), and explored the relationship between serology and CMR characterization.
METHODS We retrospectively studied 50 SSc patients without a history of cardiovascular disease or pulmonary hypertension and 20 age and sex matched HCs underwent 3T CMR, with measurements including native T1, extracellular volume (ECV), late gadolinium enhancement (LGE), T2 mapping, and left ventricular volumes and function. Serology such as erythrocyte sedimentation rate (ESR), N-terminal pro b-type natriuretic peptide (NT-proBNP), C-reaction protein (CRP), complement protein 3 (C3), and complement protein 4 (C4) were also measured. According to the LeRoy classification, SSc patients were divided into diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc).
RESULTS Although LV volume and function were comparable between the HCs and SSc participants, and the means were within normal limits, the LV ejection fraction [54.38 (9.86) vs. 60.47 (6.12), P = 0.03] of dcSSc patients were lower than lcSSc patients. A total of 31 (62%) SSc patients had LGE and 30 (60%) patients had ECV greater than 29% in our study. Compared with lsSSc patients, dsSSc patients had higher native myocardial T1 value [1334.48 ms (46.29) vs. 1306.97 ms (50.56), P = 0.37], and ECV [33.78% (6.23) vs. 31.48% (4.31), P = 0.001]. Receiver-operating characteristic curves were plotted to assess the ability of serum cardiac biomarkers to identify myocardial LGE. The area under the curve (95% CI) of NT-proBNP and ESR for identifying LGE was significant at 0.83 (0.65–1.00), P = 0.01 and 0.79 (0.58–1.00), P = 0.04, respectively. Logistic regression confirmed an association between LGE and ESR [odds ratio (OR) = 1.33, P = 0.04]. Multivariate analysis confirmed native T1 value was associated with CRP, NT-proBNP and the types is dsSSc (R2 = 0.72). T2 value was positively correlated with NT-proBNP and negatively correlated with complement C3 (R = −0.38; P = 0.008) and C4 (R = −0.38; P = 0.009).
CONCLUSIONS CMR can well detect subclinical SSc-pHI in SSc patients, and serology were associated with CMR characterization of subclinical SSc-pHI. These data will help us better understand and manage subclinical SSc-PHI.
GW35-e0893
Lutong Pu1, Mengdi Yu1, Jie Wang1, Yucheng Chen1,2
1Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
2Center of Rare Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
OBJECTIVES Alpha-protein kinase 3 (ALPK3) was recently identified as a candidate gene associated with Hypertrophic cardiomyopathy (HCM), however, there is a scarcity of clinical data available regarding carriers of ALPK3 variants. The aim of this study is to evaluate the prevalence of heterozygous ALPK3 variants in adult patients with HCM through whole-exome sequencing, and to elucidate the phenotype and prognosis of individuals harboring these variants.
METHODS DNA samples obtained from consecutive patients diagnosed with HCM and who underwent cardiac magnetic resonance imaging (cardiac MRI) were subjected to whole-exome sequencing (WES). Index cases harboring at least one rare missense variant (MAF < 0.0005) or truncating variant in the ALPK3 gene were considered genotype positive.
RESULTS A total of 574 patients with HCM (65.0% male, mean age 49 ± 15 years) were included. 36 patients (63.9% male, mean age 49 ± 15 years) were identified with ALPK3 variants (prevalence, 6.27%), including 16 with truncating variant, 20 with missense variant. In total, we identified 32 non-synonymous ALPK3 variants, including 13 stop-gained and 14 missense variants. Compared to patients without ALPK3 variants, those with ALPK3 variants had a higher prevalence of apical HCM (33.3% vs. 21.2%), particularly among those with truncated variants (50%). Sarcomere-positive patients carrying ALPK3 variants exhibited lower LA function compared to other genotype subgroups (LA reservoir strains 17.61 ± 7.81%, LA conduit strains 8.2 ± 4.79%, and LA booster strains 9.41 ± 3.54%). Over a median follow-up period of 34 months. 4 (11.4%) patients harboring ALPK3 variants experienced composite endpoint (new-onset AF, n = 2; hospital admission related to HF, n = 2).
CONCLUSIONS Heterozygous ALPK3 variants are associated with HCM. The clinical phenotype of individuals harboring these variants exhibits distinct characteristics, and the prognosis appears to be relatively poor.
GW35-e0961
Yun Tang
Fuwai Hospital, National Center for Cardiovascular Diseases
OBJECTIVES This study aims to investigate the progression of myocardial fibrosis assessed with serial cardiac magnetic resonance (CMR) imaging in patients with hypertrophic cardiomyopathy (HCM), as well as its associated clinical factors and prognostic value.
METHODS A total of 381 consecutive patients with HCM who underwent two CMRs (median interval 4.1 years) for assessment of myocardial fibrosis, quantified by late gadolinium enhancement (LGE), were retrospectively included. Primary endpoint included all-cause mortality, heart transplantation, aborted sudden cardiac death, appropriate implantable cardioverter defibrillator discharge, hospitalization for heart failure, stroke and new-onset atrial fibrillation. Secondary endpoint included all-cause mortality and heart transplantation.
RESULTS Among the study cohort, 75 of 109 patients without myocardial fibrosis on initial CMR developed new fibrosis on the latest CMR. No fibrosis regression was seen in any of the patients. LGE mass increased from a median of 2.88 g (IQR: 0.00–8.04 g) to 8.54 g (IQR: 3.38–16.59 g). On multivariable analysis, LGE mass progression was highly correlated with time interval, the LGE mass and left ventricular (LV) mass index on the initial CMR (all P < 0.02). During an average follow-up of 6.3 years from initial CMR, the primary endpoint occurred in 120 patients, of whom 4.5% reached the secondary endpoint (n = 17). Fibrosis progression was significantly associated with increased hazards for primary (HR: 2.5, P < 0.001, 95% CI: 1.1–4.0) and secondary endpoint (HR: 2.3, P < 0.001, 95% CI: 1.1–3.9) after adjustment for clinical and CMR covariates including age, LV ejection fraction and end-diastolic volume index.
CONCLUSIONS Given the prognostic value of myocardial fibrosis progression, a CMR enhancement scan is recommended as routine monitoring in HCM patients.
GW35-e1115
Zhixiang Dong, Yanyan Song, Shihua Zhao
Fuwai Hospital, Chinese Academy of Medical Sciences
OBJECTIVES A novel risk-prediction model based on clinical data and imaging tests was developed to provide an individualized estimate of sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), but it was recently shown to potentially underestimate the risk when left ventricle (LV) was involved. It remains unclear whether LV cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) provides additional value in prognosis. This study sought to explore whether LV LGE could serve as an independent predictor of the first episode of SVA, thus further improving the risk stratification of ARVC.
METHODS A total of 217 consecutive patients (median age, 38 [IQR, 27–50] years; 134 male) with a definite ARVC diagnosis, no history of sustained VA at diagnosis, and CMR performed at baseline were retrospectively enrolled for analysis. The novel 5-year ARVC risk score was retrospectively calculated based on the patients’ baseline characteristics. The primary outcome was defined as the first episode of sustained VA (sustained ventricular tachycardia, ventricular fibrillation/flutter, sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention). Univariable and multivariable Cox regression analysis was used to evaluate the impact of LV LGE on sustained VA. Restricted cubic spline was used to flexibly model the association between LV LGE and adverse outcome. Additional prognostic value of LV LGE beyond 5-year ARVC risk score was evaluated using Kaplan-Meier curves, calibration plot and likelihood ratio test.
RESULTS Of the 217 definite ARVC patients, LV LGE was observed in 141 (65%) subjects. Over a median follow-up of 35.9 months, 61 (28%) patients experienced sustained VA. LV LGE remained an independent predictor after multivariable adjustment, including the 5-year ARVC risk score (HR, 1.07 [1.04–1.10]; P < 0.001). The restricted cubic spline analysis indicated that the risk of sustained VA was relatively flat until LV LGE reached approximately 10%, after which it started to increase rapidly (P for non-linearity = 0.0324). At Kaplan-Meier analysis, patients with both a higher 5-year ARVC risk score and LV LGE ≥10% had the highest risk of sustained VA. Notably, even among those with a 5-yeaer ARVC risk score <25% or 50%, patients with LV LGE ≥10% had a worse prognosis than those with LV LGE < 10% (Log-rank P = 0.04 and P < 0.001, respectively). In patients with LV LGE >10%, the 5-year ARVC risk score showed underestimation of risk in the low and medium risk groups. The likelihood ratio test demonstrated a significant incremental prognostic value of LV LGE (P < 0.001) over the existing 5-year ARVC risk model.
CONCLUSIONS LV LGE was an independent predictor of the first episode of sustained VA in ARVC patients, and could help improve the 5-year prediction of arrhythmic outcomes after diagnosis, especially for those with low or intermediate arrhythmic risk according to the ARVC risk calculator.
GW35-e1166
Ruoxuan Li, Jing Wang, Bo Wang, Shengjun Ta, Bo Shan, Liwen Liu
Department of Ultrasound, The First Affiliated Hospital of Air Force Medical University (Xijing Hospital)
OBJECTIVES The purpose of this study was to construct a plasma metabolite screening diagnostic model for HCM based on untargeted metabolomics detection and machine learning (ML) algorithm to improve the diagnostic rate of HCM and make up for the deficiency of the existing diagnostic methods.
METHODS A total of 76 HCM patients and 35 nomal participants were enrolled in the untargeted plasma metabolomics analysis. Univariate statistical analysis methods include fold change analysis and T-test/nonparametric test; multivariate statistical analysis methods include partial least squares discrimination analysis (PLS-DA) and orthogonal partial least-squares discriminant analysis (OPLS-DA). Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathogenic pathway analysis. The data was split to discovery set and validation set with the ratio of 7: 3. Random forest (RF) and support vector machine (SVM) algorithm were used to select the feature combination contributed most to prediction results by combining cross-validation and recursive feature elimination (RFE). Stepwise linear regression analysis was performed to identify the potential key marker compounds related to the clinical indicators of the left ventricular wall thickness including left ventricular mass index (LVMI), RV5 + SV1 and left atrial volume index (LAVI).
RESULTS A total of 1481 metabolites were identified including 240 significant differential metabolites. There were significant differences between the two cohorts and both R2Y and Q2 achieved satisfactory values (PLS-DA model R2Y = 0.700, Q2 = 0.456; OPLS-DA model R2Y = 0.700, Q2 = 0.462). The results of 200 permutations proved that the model was reliable and there was no overfitting (PLS-DA model positive ion mode R2 = 0.3501, Q2 = −0.3524, negative ion mode R2 = 0.3189, Q2 = −0.4141; OPLS-DA model positive ion mode R2 = 0.5084 Q2 = −0.4511, negative ion mode R2 = 0.3231, Q2 = −0.3556). In the metabolic pathway analysis, compared with the control cohort, 2 pathways of HCM showed a significant up-regulated trend including central carbon metabolism in cancer and protein digestion and absorption, which were connected by alanine, aspartate and glutamate metabolism pathway. ML analysis of 240 significantly different metabolites and 3 important demographic indicators including gender, age and BMI, 10 metabolites were selected as candidate traits for RFE by LASSO regression after excluding the complete linear correlation features, while these three indicators were excluded. The same feature combinations were screened out by SVM and RF algorithms including 7-keto-8-aminopelargonic acid (KAPA), γ-linolenoyl ethanolamid, nitrilotriacetic acid, D-Quinovose and N-acetyl-l-aspartic acid (NAA). Using the dataset with the above 5 features, the SVM model and the RF model were constructed in discovery set and the mean misclassification error in 5-fold cross-validation were 0.036 and 0.028, respectively. The AUROC of the SVM model in discovery set and validation set were 0.996 and 0.985, respectively. And the accuracy were 96.1% and 97.1%, respectively. The AUROC of the RF model in discovery and validation sets was both 1.000 and the accuracy was 94.8% and 100.0%, respectively. Then univariate and multivariate linear regression analysis was performed on the 5 substances in the model and 3 key clinical indicators. The results showed that KAPA was independently associated with LAVI (P = 0.001). NAA was independently associated with RV5 + SV1 (P = 0.001). KAPA and NAA were independently associated with LVMI (P = 0.020; P = 0.001).
CONCLUSIONS Through comprehensively analyze the data of plasma metabolomics of HCM patients and normal participants, we established a screening diagnostic model of HCM, which does not depend on the experience of physicians with a good application prospect. Meanwhile, we have identified the possible metabolic pathways leading to the occurrence of HCM, which provides a new perspective for further exploring disease regulatory targets.
GW35-e1181
Zhenyan Xu1, Jiaxing Huang1, Hualong Liu1, Zixi Huang2
1Department of Cardiovascular Medicine, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University
2Department of General Medicine, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University
OBJECTIVES Hypertrophic cardiomyopathy (HCM) is an inherited heart disease that can lead to sudden cardiac death. Impact of genetic testing for the prognosis and treatment of patients with HCM needs to be improved. We conducted a systematic review and meta-analysis to investigate the characteristics and outcomes associated with sarcomere genotypes in index patients with HCM.
METHODS A systematic search was conducted in Medline, Embase, and Cochrane Library up to Dec 31, 2023. Data on clinical characteristics, morphological and imaging features, outcomes and interventions were collected from published studies and pooled using a random-effects meta-analysis.
RESULTS A total of 30 studies with 10,825 HCM index patients were included in the pooled analyses. The frequency of sarcomere genes in HCM patients was 41%. Sarcomere mutations were more frequent in women (P < 0.00001), and were associated with lower body mass index (26.1 ± 4.7 versus 27.5 ± 4.3; P = 0.003) and left ventricular ejection fraction (65.7% ± 10.1% vs. 67.1% ± 8.6%; P = 0.03), less apical hypertrophy (6.5% vs. 20.1%; P < 0.0001) and left ventricular outflow tract obstruction (29.1% vs. 33.2%; P = 0.03), greater left atrial volume index (43.6 ± 21.1 mL/m2 vs. 37.3 ± 13.0 mL/m2; P = 0.02). Higher risks of ventricular tachycardia (23.4% vs. 14.1%; P < 0.0001), syncope (18.3% vs. 10.9%; P = 0.01) and heart failure (17.3% vs. 14.6%; P = 0.002) were also associated with sarcomere mutations.
CONCLUSIONS Sarcomere mutations are more frequent in women, and are associated with worse clinical characteristics and poor outcomes.
GW35-e1199
Mengdi Yu, Lutong Pu, Jie Wang, Yucheng Chen
West China Hospital, Sichuan University
OBJECTIVES The current guidelines suggested patients with hypertrophic obstructive cardiomyopathy (HOCM) be treated with septal reduction therapy, including surgical septal myectomy and septal ablation. However, there is still a lack of the comparison of cardiac hemodynamic changes and prognosis between the two approaches. The study aimed to compare the changes of cardiac hemodynamics before and after surgical septal myectomy and septal ablation, by LV hemodynamic force (HDF) assessment based on cardiac magnetic resonance (CMR) and to evaluate the prognosis of these two subgroups.
METHODS This study recruited patients with HOCM who underwent surgical septal myectomy or septal ablation. All patients underwent CMR before and after septal reduction therapy. The LV HDF assessment was performed on 2-, 3- and 4-chamber CMR deformation imaging by measurement of mitral and aortic in/outflow valve width. LV HDF was reported as a percentage of gravitational acceleration to represent the distribution of force vectors that drive blood acceleration within the ventricles. All patients were followed up regularly. The clinical outcome was defined as a composite of all-cause mortality, heart failure-related hospitalization, new-onset atrial fibrillation (AF) and reoperation for left ventricular outflow tract obstruction. The prognosis were evaluated by the Kaplan–Meier survival analysis and compared with log-rank test.
RESULTS A total of 52 patients with HOCM were enrolled, including 24 patients with surgical septal myectomy (14 males; age 39 ± 16 years) and 28 patients with septal ablation (8 males; age 54 ± 14 years) (sex P = 0.03; age P = 0.001). Patients after surgical septal myectomy had decreased global HDF in longitude direction (IQR 14.56–26.87 vs. 12.96–17.67, P = 0.007) and systolic function, assessed by systolic peak (50.80 ± 27.36% vs. 36.62 ± 15.83%, P = 0.020), systolic impulse (31.48 ± 16.88% vs.21.68 ± 8.1%, P = 0.011). However, there was no significant differences in diastolic period in patients with HOCM after surgical septal myectomy. Besides, no significant differences were observed in hemodynamic force assessment in patients with HOCM after septal ablation. There were greater differences in global HDF in longitude direction after septal reduction therapy in patients with surgical septal myectomy than patients with septal ablation (−8.61% vs. −0.65%, P = 0.008). Among patients with surgical septal myectomy, during a median follow-up of 65 months, 4 (17%) patients developed new onset AF and 1 patient had heart failure-related hospitalization. Among patients with septal ablation, during a median follow-up of 67 months, 1 patients died, 9 (32%) patients had heart failure-related hospitalization, 4 (14%) patients were re-operated for left ventricular outflow tract obstruction, and 4 (14%) patients developed new onset AF. There was a significant difference in the prognosis of these two subgroups (P = 0.036).
CONCLUSIONS Compared with septal ablation, patients with HOCM after septal myectomy have greater changes in cardiac hemodynamics and appear to have a better prognosis.
GW35-e1218
Tao Liu1, Xiaokun Gao1, Xihan Fan1, Peihong Guo1, Lingjiao Wu1, Tianfu Qi1, Wei Zhao1, Yu Wang2, Wei Chen1
1Department of Medical Imaging, the First Hospital of Kunming Medical University, Kunming 650032, China
2Department of Ultrasound, The First Affiliated Hospital of Kunming Medical University Kunming 650032, China
OBJECTIVES Myocardial fibrosis is one of the main pathological features of dilated cardiomyopathy (DCM). This study aims to quantitatively assess myocardial fibrosis using cardiac magnetic resonance (CMR) and to explore CMR predictors of left ventricular reverse remodeling (LVRR) in DCM patients after standardized heart failure drug treatment.
METHODS This study included 48 patients diagnosed with DCM. All patients underwent baseline CMR examinations, which included cine sequences to evaluate cardiac function parameters: left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). T1 mapping was used to assess diffuse myocardial fibrosis, measuring native T1 values and extracellular volume fraction (ECV). Late gadolinium enhancement (LGE) was employed to evaluate replacement myocardial fibrosis, expressed as the percentage of left ventricular myocardial mass (%LV). All patients received standardized heart failure medication therapy. Baseline and follow-up cardiac ultrasound examinations were conducted to evaluate parameters including LVEF and left ventricular end-diastolic diameter index (LVEDDi). Laboratory tests included B-type natriuretic peptide (BNP) levels. Based on the baseline and follow-up LVEF and LVEDDi measurements, DCM patients were categorized into two groups: LVRR(+) and LVRR(−).
RESULTS The median follow-up duration was 10.5 months (interquartile range: 6–15.8 months). LVRR occurred in 14 patients (29%) and did not occur in 34 patients (71%). There was no statistically significant difference in baseline LVEF between the two groups. In the LVRR(+) group, the following CMR parameters were all lower compared to the LVRR(−) group: Native T1 value [1048 ms (1031, 1069 ms) vs. 1071 ms (1039, 1098 ms), P = 0.047], ECV (27.2 ± 3.5% vs. 30.1 ± 4.2%, P = 0.028), and LGE [1.6% (1.0, 3.2%) vs. 3.7% (2.1, 6.1%), P = 0.004]. Multivariate logistic regression analysis identified the severity of baseline LGE as the only independent predictor of LVRR in DCM patients. Baseline LGE predicted LVRR with a sensitivity of 74% and specificity of 71%, with an area under the ROC curve (AUC) of 0.765 and an optimal threshold of 2.35% (P = 0.004).
CONCLUSIONS The severity of LGE at baseline is an independent predictor of LVRR in DCM patients after standardized heart failure drug treatment.
GW35-e1263
Jie Lin1,2
1The Third People’s Hospital of Yunnan Province
2The First Affiliated Hospital of Kunming Medical University
OBJECTIVES Myocardial iron overload (MIO) in patients with secondary iron overload can lead to subclinical left ventricular (LV) dysfunction, manifested by abnormal strain parameters before the decline of ejection fraction (EF). Cardiovascular magnetic resonance (CMR)-t2* is the gold standard for the diagnosis of myocardial iron overload, it is essential for the early detection of MIO. In this study, CMR feature tracking (FT) strain was applied to evaluate whether myocardial strain parameters were related to t2*, and to explore early predictors of myocardial systolic dysfunction in patients with MIO.
METHODS Forty patients with secondary iron overload and LVEF >50% were included. All patients underwent CMR examination, film sequence, and evaluation of cardiac function, including: left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume index (LVESVI), left ventricular ejection fraction (LVEF), left ventricular global radial strain (GRS), left ventricular global circumferential strain (GCS), left ventricular global longitudinal strain (GLS), and t2* mapping technology. Laboratory test indicators include: serum ferritin (SF) and ferritin. The patients were divided into two groups according to whether there was cardiac iron overload. The first group was patients without MIO (t2* >20 ms) and the second group was patients with MIO (t2* <20 ms). A total of 15 healthy people without cardiovascular disease were included as the control group.
RESULTS Forty patients with secondary iron overload (mean age 48.79 years, 25 males) underwent CMR. There were 7 cases (17.5%) in group 1, 33 cases (82.5%) in group 2, and 15 cases in the control group. Combined with correlation analysis, GRS, GCS and GLS had no statistical correlation with t2* value. The difference analysis showed that GRS and GCS in group 2 were significantly lower than those in group 1: GRS value (25.98 ± 3.65 vs. 31.18 ± 5.22, P = 0.012), GCS value (−16.18 ± 1.64 vs. −18.43 ± 1.99, P = 0.005), and GRS and GCS in group 2 were also significantly lower than those in the control group: GRS value (25.98 ± 3.65 vs. 29.84 ± 3.66, P = 0.025), GCS value (−16.18 ± 1.64 vs. 17.59 ± 1.39, P = 0.040).
CONCLUSIONS FT-CMR can early identify subtle myocardial systolic dysfunction in patients with MIO, it can be used as an effective auxiliary index for Mio patients except CMR t2*.
GW35-e1268
Peihong Guo, Xihan Fan, Wei Chen
The First Affiliated Hospital of Kunming Medical University
OBJECTIVES At present, the International criteria for diagnosis multiple myeloma (MM) do not specifically highlight the use of cardiac magnetic resonance (CMR) to detect abnormal myocardial infiltration in patients at different clinical stages of MM. To detect whether myocardial involvement in patients with MM at different clinical stages based on CMR T1 mapping.
METHODS This study recruited a cohort of 32 patients diagnosed with MM and 30 sex- and age-matched controls. All participants underwent CMR examination to assess native T1 and extracellular volume (ECV). The MM patients were categorized into three groups according to the International Staging System (ISS): Stage I (G1; n = 5), Stage II (G2; n = 9), and Stage III (G3; n = 18). The diagnosis of cardiac amyloidosis (CA) was based on clinical presentation and tissue biopsy. The primary endpoints were all-cause mortality and hospitalization due to heart failure.
RESULTS Among patients with MM, 13 (40.63%) were diagnosed as CA. Distribution across the staging groups was as follows: none in Group 1 (G1), four in Group 2 (G2), and nine in Group 3 (G3), though these differences were not statistically significant (P > 0.05). The ECV in G3 (44.48 ± 11.78%) was significantly higher compared to G1, G2, and the control group (26.18 ± 3.57%, 34.09 ± 8.91%, and 25.40 ± 2.52% respectively) (all P < 0.05). During the follow-up period, which had a median duration of 8.0 months (interquartile range 6.0–12.0 months), 9 patients died and 10 were hospitalized due to heart failure. Among them, there were 3, 4, and 12 in G1, G2, and G3 respectively. The receiver operating characteristic (ROC) curve analysis indicated that an ECV of ≥40.24% is the optimal cutoff for predicting the composite endpoint, demonstrating a sensitivity of 68%, a specificity of 92%, and an area under the curve (AUC) of 0.83 (95% CI: 0.70–0.97). Moreover, an ECV of 40.24% was also identified as the best threshold for predicting CA (sensitivity 92.3%, specificity 89.5%, AUC: 0.915, P < 0.0001). Kaplan-Meier survival analysis showed that patients with an ECV ≥40.24% had a significantly higher probability of adverse outcomes compared to those with an ECV < 40.24% (P < 0.05).
CONCLUSIONS ECV, derived from CMR T1 mapping, shows promise in identifying amyloid accumulation that progressively worsens as disease stages advance in patients with MM. Additionally, ECV serves as a predictor of adverse outcomes in MM patients and effectively identifies CA secondary to MM. We recommend that as part of the treatment strategy for MM, patients diagnosed with ISS Stage II and III should undergo CMR imaging.
GW35-e1342
Zhenzhen Wang1, Wei Liu1, Wei Li1, Xiaopei Lin2, Wensheng Tao1
1Zhejiang Provincial People’s Hospital
2The First Affiliated Hospital of Xi’an Medical College
OBJECTIVES Although left ventricular global longitudinal strain (LV-GLS) is valuable in explaining impaired LV contractility in hypertrophic cardiomyopathy with preserved LV ejection fraction (LVEF), its clinical significance in assessing diastolic dysfunction is poorly explored. This study aimed to determine the independent association between LV-GLS and diastolic dysfunction in hypertrophic obstructive cardiomyopathy (HOCM) patients.
METHODS A total of 145 consecutive patients (56 females and 89 males, 46 ± 14 years old) with symptomatic HOCM (NYHA II-IV) who presented to our cardiothoracic surgery center between November 30, 2021, and July 31, 2023, were enrolled. The LV diastolic function, ejection fraction, and LV-GLS were evaluated according to guidelines. Patients were divided into two groups (diastolic dysfunction grade II–III versus grade I). Patient baseline clinical data, echocardiographic parameters, and brain-type natriuretic peptide (BNP) were compared.
RESULTS There were 109 HOCM patients with grade II–III diastolic dysfunction, and 36 with grade I. The incidence of grade II–III diastolic dysfunction was more common in females (49 cases vs. 7 cases, P = 0.006). No differences were found in age, physical examination, comorbidities, and active medications. Wall thickness, LV-GLS, and BNP were associated with diastolic dysfunction, whereas loading conditions and LVEF were not. ROC curve showed that LV-GLS had an area under the curve (AUC) of 0.728 in judging diastolic dysfunction grade (P = 0.001). In stepwise forward multivariable regression analysis, LV-GLS might be an independent indicator of diastolic dysfunction after adjusting for gender, septal e′, mean E/e′, and left atrial volume index. A 1% absolute decrease in GLS was associated with a 1.20-fold increased risk of advanced diastolic dysfunction (OR = 1.20, 95% CI: 1.18–1.22, P = 0.018).
CONCLUSIONS Impaired LV-GLS was found independently associated with the severity of diastolic dysfunction in symptomatic HOCM patients with preserved ejection fraction and might add incremental value in risk stratification of heart failure with preserved LVEF (HFpEF) in patients with HOCM, thereby contributing to clinical management of patients at a higher risk of HFpEF.
CARDIOVASCULAR SURGERY
GW35-e0073
Jianrui Ma1,2, Haiyun Yuan1,2, Jimei Chen1,2
1Guangdong Cardiovascular Institute
2Guangdong Provincial People’s Hospital
OBJECTIVES The impact of dominant ventricular morphology on the outcomes of Fontan patients remains highly disputed. We aimed to report long-term outcomes of right ventricle (RV) dominance versus left ventricle (LV) dominance in Fontan circulation using propensity score analysis to minimize heterogeneity.
METHODS A total of 323 patients who underwent Fontan operation at our center were retrospectively reviewed. To minimize the pre- and intra-Fontan heterogeneity, we matched 55 dominant RV patients with 55 dominant LV patients using propensity score matching and compared outcomes between groups.
RESULTS The mean period of follow-up was 6.5 ± 4.2 years in the dominant RV and 7.4 ± 4.9 years in the dominant LV group (P > 0.05). The cumulative incidence of atrioventricular valve regurgitation ≥ moderate was also comparable between the two groups (P > 0.05). What’s more, the freedom from death or transplantation at 5 and 10 years after the Fontan operation were 90% and 87% in the dominant RV group, similar to 84% and 81% in the dominant LV group, respectively (P > 0.05). The 5-year and 10-year freedom from Fontan failure was 85% and 82% in the dominant RV group, also similar to 76% and 65% in the dominant LV group, respectively (P > 0.05).
CONCLUSIONS The RV dominance appears not to adversely influence the long-term outcomes of Fontan patients. It showed a similar likelihood of AVVR, transplantation-free survival, and Fontan failure in contrast to LV dominance in the same pre- and intra-Fontan context.
GW35-e0197
Jiaxin Cheng1,2, Zhiqiang Zhang2, Y Wang2, Dujuan Meng2, Tinghao Zhao2, Xuan Wu2, Xiaozeng Wang2
1College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning, China
2National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
OBJECTIVES To explore the impact of abdominal aortic aneurysm (AAA) combined with bilateral renal cysts (BRC) on the prognosis.
METHODS This study continuously screened and retrospectively analyzed 278 patients who were diagnosed with AAA in the General Hospital of Northern Theater Command from January 2017 to May 2023. According to whether the patients were complicated with BRC during their first computer tomography angiography examination, they were divided into an BRC group (N = 75) and a control group (N = 203). Kaplan-Meier survival analysis and uni-variate and multi-variate COX proportional risk models were used to compare the impact of BRC on prognosis in patients with AAA. Subgroup analysis was conducted in patients who did not receive endovascular repair (EVAR) treatment to confirm the sensitivity of this study.
RESULTS Among the 278 patients included in this study, 239 (86.0%) were male, with an average age of (67.97 ± 9.32) years. Among them, 75 (27.0%) died within 5 years after the diagnosis of AAA. The incidence of all-cause death within 5 years in the BRC group (37.3% vs. 23.2%, P = 0.018) was significantly higher than that in the control group. Kaplan–Meier survival analysis showed that the cumulative incidence of all-cause death (Log rank P = 0.016) within 5 years in the BRC group was higher than that in the control group. The results of the uni-variate COX hazard regression proportional model showed that BRC were associated with an increased risk of all-cause death within 5 years in patients with AAA [HR (95% CI): 1.764 (1.104–2.818), P = 0.018], it is still statistically significant after age and gender adjustment [HR (95% CI): 1.816 (1.136–2.903), P = 0.013]. Subgroup analysis results suggested the incidence of all-cause death within 5 years in patients with AAA in the BRC group was significantly higher than that in the control group (45.7% vs. 25.2%, P = 0.012), which was confirmed in Kaplan–Meier survival analysis (Log rank P = 0.012). Uni-variate COX risk regression proportional model [HR (95% CI): 2.042 (1.159–3.597), P = 0.013], after adjustment for age and sex [HR (95% CI): 1.970 (1.117–3.474), P = 0.019], and patients with BRC and AAA who did not receive EVAR were associated with an increased risk of all-cause death within 5 years.
CONCLUSIONS BRC can increase the incidence of all-cause death in patients with AAA within 5 years. For patients with AAA combined with BRC, active intervention and management should be performed to reduce their mortality.
GW35-e0228
Samire Mutailifu, Qing Zhu, Nanfang Li
Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region
OBJECTIVES Admission hyperglycemia plays a significant role in the adverse outcome of cardiovascular and cerebrovascular diseases. This study aimed to evaluate the relationship between admission hyperglycemia and in-hospital mortality in hypertensive patients with AAD.
METHODS We retrospectively collected electronic medical records of hypertensive patients diagnosed with acute aortic dissection admitted to our hospital and patients were divided into hyperglycemia group and normoglycemia group based on their blood glucose levels at admission (BGA). The outcome was all-cause mortality during hospitalization. Logistic regressions used to calculate the odds ratio (OR) and 95% confidence intervals (CIs) for incident in-hospital mortality.
RESULTS Totally, 1239 patients were enrolled between January 1, 2010, and March 1, 2023, with 77.1% men, mean age of 53.0 years and median BGA of 6.1 mmol/L. The logistic regression analysis showed the in-hospital mortality for individuals with hyperglycemia was 2.53 times greater compared to the normoglycemia group (95% CI: 1.68–3.80, P < 0.001), significant in adjusted model (adjusted OR: 2.49; 95% CI: 1.56–3.85, P = 0.005). Stratified analysis and sensitivity analysis did not change the relationship of the two. In addition, insulin use during hospitalization appears to be associated with reduced in-hospital mortality.
CONCLUSIONS Admission hyperglycemia found to be correlation with an elevated risk of in-hospital mortality in hypertensives with AAD. And insulin treatment seems associated with a lower risk of in-hospital mortality. Blood glucose management is very important for the prognosis of these patients.
GW35-e0355
Songhao Jia, Wenjian Jiang, Hongjia Zhang, Jie Han
Beijing Anzhen Hospital, Capital Medical
OBJECTIVES Not all patients with rheumatic mitral valve disease are suitable for mitral valve repair surgery. This study aimed to explore the influencing factors on the outcome of rheumatic mitral valve repair, in order to guide clinical doctors in selecting suitable patients for rheumatic mitral valve repair.
METHODS A total of 876 patients who planned to undergo rheumatic mitral valve repair between January 2016 and March 2022 were included in the study. Preoperative echocardiography and cardiac CT imaging were used to evaluate mitral valve disease in patients. Successful completion of rheumatic mitral valve repair without over mild stenosis or regurgitation was defined as satisfactory repair. Univariate and multivariate logistic regression analyses were conducted to identify the influencing factors on the outcome of rheumatic mitral valve repair.
RESULTS Four hundred and ninety-three patients (56.2%) completed satisfactory rheumatic mitral valve repair surgery. BMI, NYHA classification, left atrial diameter, degree of mitral stenosis, degree of mitral regurgitation, Agatston score, and papillary tendon fusion were the independent influencing factors on the outcome of rheumatic mitral valve repair.
CONCLUSIONS Nearly 60% of patients with rheumatic mitral valve disease could complete satisfactory rheumatic mitral valve repair, and the degree of mitral valve calcification was an independent risk factor affecting the outcome of rheumatic mitral valve repair.
GW35-e0542
Zhou Liu1, Yeting Lou1, Longfei Wang1, Yuyong Liu2, Ming Gong1, Hongjia Zhang1, Wenjian Jiang1
1Beijing Anzhen Hospital, Capital Medical University
2The First Affiliated Hospital of Anhui Medical University
OBJECTIVES Organ malperfusion significantly impacts the prognosis of patients suffering from acute type A aortic dissection (ATAAD). This study aims to pinpoint radiographic markers that can identify malperfusion syndrome (MPS) by specifically evaluating preoperative aortic computed tomography angiography (CTA) in ATAAD patients.
METHODS A retrospective study was conducted on ATAAD patients who underwent total arch replacement and stented elephant trunk procedures at Beijing Anzhen Hospital, Capital Medical University, between January 1, 2016, and December 31, 2020. Exclusion criteria comprised patients with unavailable preoperative aortic CTA data, those under 18 years of age, those with isolated ascending aortic dissection, and pregnant patients, resulting in a total inclusion of 432 patients. A retrospective analysis of aortic CTA data was performed, evaluating dissection characteristics (entry tear location, false lumen thrombus, and ascending aortic circumference), branch vessel involvement (percentage of involvement of intercostal arteries >50%, and involvement of major branches including the coronary arteries, innominate artery, left common carotid artery, left subclavian artery, celiac trunk artery, superior mesenteric artery, renal arteries, and iliac arteries), and dissection severity (tear length ratio, and false lumen tear arc length ratio at five levels: ascending aorta (2 cm above the sino-tubular junction), descending aorta (the level of aortic annulus, diaphragm, celiac trunk artery, and renal arteries)). Branch vessel involvement was defined as branches supplied by the false lumen or branches with both true and false lumen supply. False lumen tear arc length ratio (FL%) was defined as the false lumen arc length/aortic circumference × 100%.
RESULTS Out of 432 patients, 340 (78.7%) were male with a mean age of 47.5 years. Preoperative MPS was observed in 155 (35.9%) patients. Those with preoperative MPS exhibited markedly more severe dissection and experienced higher postoperative MPS occurrence rates (38.7% vs. 24.5%, P = 0.002), as well as elevated 30-day postoperative mortality rates (17.4% vs. 6.5%, P < 0.001). Branch vessel involvement did not independently influence preoperative or postoperative MPS occurrence. Age (OR: 1.05; 95% CI: 1.03–1.08, P < 0.001), stroke (OR: 3.90; 95% CI: 1.03–14.83, P = 0.046), preoperative renal (OR: 3.30; 95% CI: 1.57–6.95, P = 0.002) and cardiac (OR: 3.41; 95% CI: 1.59–7.33, P = 0.002) malperfusion, FL% at the ascending aorta (OR: 2.64; 95% CI: 1.35–5.16, P = 0.005), and operative time (OR: 1.65; 95% CI: 1.40–1.95, P < 0.001) were identified as independent risk factors for postoperative MPS.
CONCLUSIONS Indices of aortic dissection severity are significantly correlated with MPS in ATAAD surgery patients, with the FL% at the ascending aorta being an independent risk factor for postoperative MPS occurrence.
GW35-e0543
Zhou Liu, Jie Han, Wenjian Jiang, Hongjia Zhang
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Due to complex pathological features and intricate repair techniques, patients with rheumatic mitral valve disease exhibit a relatively high incidence of residual mild regurgitation following repair. This study aims to investigate the influencing factors and midterm outcomes of residual mild regurgitation following rheumatic mitral valve repair.
METHODS In our institution, 822 patients underwent mitral valve repair due to rheumatic heart disease between January 2016 and August 2022. Cardiac CT was employed to reconstruct and analyze preoperative mitral valve calcification. Surgeons with fewer than 150 repair cases of surgical experience were excluded. According to the last echocardiographic evaluation before discharge, 511 patients were finally included in the study, including 189 cases (37.0%) with residual mild regurgitation and 322 cases (63.0%) with successful mitral valve repair. Univariate and multivariate logistic regression were performed to identify the influencing factors of residual mild regurgitation after rheumatic mitral valve repair.
RESULTS Both groups had similar baseline characteristics and mitral valve disease severity. The mean age of the entire cohort was 57.84 ± 7.51 years, and the mean EuroSCORE II was 2.86 ± 1.77. Patients with residual mild regurgitation had a higher prevalence of mitral valve calcification (57.7% [109/189] vs. 46.0% [148/322], P = 0.011). Preoperative atrial fibrillation (OR, 2.47; 95% CI, 1.50–4.09; P < 0.001), systolic pulmonary artery pressure (OR, 1.02; 95% CI, 1.00–1.03; P = 0.035), and anterior commissural calcification (OR, 1.99; 95% CI, 1.20–3.28; P = 0.007) were identified as independent risk factors for residual mild regurgitation after rheumatic mitral valve repair. The mean follow-up time was 4.2 ± 1.8 years (range 1.2–8.1 years). Between the two groups, survival rates did not differ significantly (96.9% vs. 97.2%, P = 0.79). However, the group with mild residual regurgitation had a lower 5-year rate of free progression to moderate or severe mitral valve regurgitation (86.6% vs. 91.1%, P = 0.037).
CONCLUSIONS Patients with residual mild regurgitation following rheumatic mitral valve repair are significantly more likely to progress to moderate or severe regurgitation in the midterm, despite no increased mortality rate. Patients with atrial fibrillation, pulmonary hypertension, and anterior commissural calcification should be carefully selected for repair to reduce residual regurgitation after repair.
GW35-e0876
Dujuan Meng, Yasong Wang, Zhiqiang Zhang, Tinghao Zhao, Xiaozeng Wang
General Hospital of Northern Theater Command
OBJECTIVES This study is to examine the factors associated with short-term aortic-related adverse events in patients with acute type B aortic intramural hematoma (IMH). Additionally, we develop a risk prediction nomogram model and evaluate its accuracy.
METHODS This study included 197 patients diagnosed with acute type B IMH by computed tomography angiography from July 2015 to June 2023 in the Emergency and Cardiovascular Department of the Northern Theater General Hospital. The primary endpoint event was defined as an aortic-related adverse event within 30 days in patients with acute type B IMH. The patients were divided into stable group (n = 125) and exacerbation group (n = 72) based on the occurrence of aortic-related adverse events. Logistic regression and the Least Absolute Shrinkage and Selection Operator (LASSO) method for variables based on baseline assessments with significant differences in clinical and image characteristics were employed to identify independent predictors. A nomogram risk model was constructed based on these independent predictors. The model’s diagnostic performance was assessed using the receiver operating characteristic curve, while the accuracy was evaluated using the calibration curve. The goodness of fit of the model was determined through the Hosmer-Lemeshow test. Additionally, the clinical benefit was observed using the decision analysis curve (DCA), and the clinical practicability of the model was verified using the clinical impact curve. Internal validation was performed using the Bootstrap method.
RESULTS Among the 197 patients with type B IMH, 72 patients experienced aortic-related adverse events, resulting in an exacerbation rate of 36.5%. The risk prediction model was established using Logistic regression analysis and LASSO regression analysis, and it included the following four variables: diabetes (OR = 0.053, 95% CI: 0.005–0.580, P = 0.016), anemia (OR = 6.814, 95% CI: 1.761–26.364, P = 0.005), maximum descending aorta diameter (MDAD) (OR = 1.149, 95% CI: 1.066–1.238, P < 0.001), and ulcer-like projection (ULP) (OR = 8.941, 95% CI: 3.708–21.561, P < 0.001). A nomogram risk prediction model was established based on four variables: absence of diabetes, anemia, MDAD, and ULP. The model demonstrated a discriminative ability with an area under the curve (AUC) of 0.813. The calibration curve indicated a good agreement between the predicted probabilities and the actual probabilities. The Hosmer-Lemeshow goodness of fit test showed no significant difference (χ2 = 7.040, P = 0.532). DCA revealed that the nomogram model provided the highest net benefit when the risk threshold was set between 0.01 and 0.7.
CONCLUSIONS This study introduces a nomogram prediction model that integrates four important risk factors: ULP, MDAD, anemia, and absence of diabetes. The model allows for personalized prediction of patients with type B IMH.
GW35-e0964
Kaifan Niu1,2, Zhixiang Wang1, Xinyun Wang1, Xian Jin1
1Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
2Tongren Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES Ondansetron (OND), a commonly used antiemetic, has garnered interest for its potential protective effects in critically ill patients. This study aimed to investigate the impact of OND on risks of mortality and its potential regulation in critically ill patients undergoing cardiopulmonary Bypass (CPB).
METHODS Clinical data of CPB patients were extracted from the MIMIC-IV database. Data analysis was conducted via R, including Cox proportional hazards regression, Kaplan–Meier survival analysis, and interaction analysis. Additionally, network pharmacology analysis was performed to explore the underlying pharmacological mechanisms of OND.
RESULTS Baseline characteristics showed no significant differences between CPB patients with and without early OND administration. OND significantly reduced in-hospital mortality (OR: 0.49 [0.25–0.90], P = 0.032), 30-day mortality (HR: 0.53 [0.28–0.97], P = 0.041) and 90-day mortality risks (HR: 0.58 [0.37–0.92], P = 0.020) in critically ill CPB patients. Higher baseline white blood cell (WBC) counts were associated with increased risk of mortality (HR: 1.09 [1.06–1.12], P < 0.001). Interaction analysis revealed that, compared to OND patients with normal baseline WBC counts, those with high baseline WBC counts who did not receive OND had significantly higher mortality risks (HR for in-hospital mortality: 3.51 [1.56–9.37], P < 0.005; HR for 30-day mortality: 2.89 [1.19–7.02], P = 0.019; HR for 90-day mortality: 3.19 [1.66–6.10], P < 0.001). Network pharmacology analysis suggested that OND may exert its effects primarily through involvement of pathways related to inflammatory response, including TNF, IL-17, and NF-κB signaling, in the context of CPB.
CONCLUSIONS Early administration of ondansetron demonstrated potential protective effects in CPB patients, particularly those with elevated baseline WBC counts, possibly mediated through anti-inflammatory properties. This finding provided novel insights on early pharmacological intervention in critically ill CPB patients.
GW35-e0975
Shuanglei Zhao1,2, Ming Gong1,2
1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
2Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
OBJECTIVES The Association between D-dimer with morphologic features and surgical outcomes of Acute Type A Aortic Dissection (ATAAD) is still unclear.
METHODS A total of 430 ATAAD patients who underwent surgery in Beijing Anzhen Hospital of Capital Medical University between January 2016 and December 2020 were enrolled in the present study. The last preoperative D-dimer values were collected. Patients were divided into higher D-dimer (>2307 ng/mL) group and lower D-dimer (≤2307 ng/mL) group based on the median value of D-dimer. Compared the extent of dissection and branch artery perfusion patterns between two groups. As continuous variable, we first perform a logarithmic conversion of the D-dimer base natural constant. Then the restricted cubic spline (RCS) was performed to assess the association between D-dimer with the extent of dissection and major adverse events after surgery.
RESULTS Among 430 patients, there was 45 in-hospital mortality and 156 major adverse events. Patients with D-dimer >2307 ng/mL had bigger dissection extension length and false lumen perimeter in ascending aorta, thoracic descending aorta, diaphragmatic, coeliac trunk and renal artery level compared to patients with D-dimer ≤2307 ng/mL. For the branch artery perfusion patterns, Patients with D-dimer >2307 ng/mL had higher proportion of malperfusion among innominate artery, right renal artery and both side iliac artery, a higher proportion of dissected intercostal artery/all intercostal artery >0.5 (43.46% vs. 29.63%, P = 0.003) compared to patients with D-dimer ≤2307 ng/mL. The RCS linear regression model revealed a nonlinear association between lnD-dimer with extension length and false lumen perimeter (all P for overall and P for nonlinearity < 0.001, except false lumen perimeter in ascending aorta level). The RCS logistic regression model revealed a linear association between lnD-dimer with major adverse events (P for overall < 0.001, P for nonlinearity = 0.637). The association between lnD-dimer and major adverse events was still significant in the fully adjusted logistic regression model with CTA characteristics (OR (95% CI) = 1.388 (1.137, 1.695), P = 0.001).
CONCLUSIONS D-dimer strongly and positively correlates with extent of dissection and major adverse events of ATAAD after surgery. D-dimer seems to be a supplement of Indicating the severity of aortic dissection to aortic CTA.
GW35-e0977
Shaunglei Zhao, Ming Gong
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
OBJECTIVES Lipoproteins and insulin resistance are associated with the prognosis of cardiovascular disease, with strong evidence supporting causality for some. Whether the lipoproteins and insulin resistance have prognostic value in infective endocarditis patients after valve surgery remains unclear.
METHODS Retrospective analysis of observational data from 278 consecutive patients with a definite diagnosis of IE and underwent valve surgery from January 2010 to December 2022. Mortality was analyzed in relation to lipid profile and insulin resistance. Patients were divided into higher high-density lipoprotein (>0.905 mmol/L) group and lower high-density lipoprotein (≤0.905 mmol/L) group based on the cut-off value of the high-density lipoprotein. The Kaplan–Meier survival analysis of patients in two groups was conducted. Subgroup analysis and restricted cubic splines regression of the association between baseline high-density lipoprotein and incident all-cause mortality were conducted.
RESULTS Among 278 patients (mean age 44.96 years, 28.1% female), there was 36 all-cause mortality during a median 60.98 months follow-up. Kaplan–Meier survival analysis showed lower twelve years mortality in patients with high-density lipoprotein >0.905 mmol/L (HR = 0.125, P < 0.001). There were no significant interactions in all subgroups. The negative effect of high-density lipoprotein on all-cause mortality was consistent after adjusting for the confounders across all subgroups. The restricted cubic splines regression model revealed a linear association between high-density lipoprotein and the risk of all-cause mortality (P for nonlinearity = 0.477), and this linear association is more pronounced in women.
CONCLUSIONS High-density lipoprotein is protective against mortality in infective endocarditis patients after valve surgery particularly in female patients.
GW35-e1113
Sichong Qian, Haiyang Li, Hongjia Zhang
Beijing Anzhen Hospital
OBJECTIVES Acute type A aortic dissection (ATAAD) is a catastrophic cardiovascular disease with high morbidity and mortality rates. Evidence-based studies have demonstrated that proximal repair was associated with lower early mortality risk. It has also been reported that with the improvement of surgical techniques, more extensive repair did not increase early mortality significantly. The objectives of this study were to evaluate the impact of proximal repair versus extensive repair on operative mortality and how this impact is influenced by patient characteristics.
METHODS Of 5510 patients with acute type A aortic dissection from 13 Chinese hospitals (2016–2021) categorized by proximal repair versus extensive repair, 4038 patients were used for model derivation using XGBoost and 1472 patients for model validation.
RESULTS Patients underwent extensive repair showed higher operative mortality compared with proximal repair group (10.4% vs. 2.9%; OR, 3.833; 95% CI, 2.810–5.229; P < 0.001) with a number needed to harm of 15 (95% CI, 13–19). Seven top characteristics of significance were selected to develop an alphabet risk model (age, body mass index, platelet-to-leucocyte ratio, albumin, hemoglobin, serum creatinine, and preoperative organ malperfusion), with an area under the curve (ROC) of 0.767 (95% CI, 0.733–0.800) and 0.727 (95% CI, 0.689–0.764) in the derivation and validation cohorts, respectively. The absolute rate differences in mortality between the 2 strategies increased progressively as predicted risk rose; however, it did not become statistically significant until the predicted risk exceeded 4.5%. Extensive repair was associated with similar risk of mortality (OR, 2.540; 95% CI, 0.944–6.831) for patients with a risk probability <4.5% but higher risk (OR, 2.164; 95% CI, 1.679–2.788) for patients with a risk probability >4.5% compared with proximal repair.
CONCLUSIONS Extensive repair is associated with higher mortality than proximal repair; however, a higher risk of mortality was not of significance until the predicted probability exceeded a certain threshold. Suitable strategy should be chosen according to individualized risk stratification and treatment effect.
GW35-e1157
Yumeng Ji, Juntao Qiu
Fuwai Hospital
OBJECTIVES To assess the effects of unilateral versus bilateral antegrade cerebral perfusion (u-B-ACP) on postoperative complications and mid-term follow-up results in Asian patients with acute type A aortic dissection (ATAAD) having total arch replacement (TAR).
METHODS We gathered clinical baseline data and postoperative complications of 702 ATAAD patients who had complete arches replaced at China Cardiovascular Centre Fuwai Hospital between January 2019 and December 2022. Patients were divided into two groups for antegrade cerebral perfusion: unilateral (n = 402) and bilateral (n = 300). We matched propensity scores for 217 pairs of patients, analyzed mid-term and perioperative surgical complications, and assessed baseline characteristics between the two groups.
RESULTS The matched cohort showed similar 30-day mortality rates for u-ACP and b-ACP: 4.15% and 3.23%, respectively (P = 0.61). The rates of postoperative permanent neurologic dysfunction (PND) were similar between groups (2.76% for u-ACP and 3.23% for b-ACP, P = 0.76). However, u-ACP had 14.29% postoperative transient neurologic deficit (TND) compared to 6.91% for b-ACP (P = 0.01). The logistic regression models indicate that u-ACP and cardiopulmonary bypass (CPB) time were independent risk factors for TND. The mid-term survival was similar in the two groups (5-year survival: 90.29% vs. 93.67%, P = 0.133).
CONCLUSIONS Both u-ACP and b-ACP are regarded as effective brain protection techniques for ATAAD patients receiving total arch replacement. Notably, there is a significant decrease in the frequency of TND when b-ACP is used.
CLINICAL DRUG DEVELOPMENT AND DEVICE DEVELOPMENT
GW35-e0333
Siqi Hu1,2
1Affiliated Hospital of Hangzhou Normal University
2Hangzhou Normal University
OBJECTIVES Unexpected cardiovascular events are likely to occur within a short period following acute myocardial infarction (AMI). The sodium-glucose cotransporter 2 inhibitor (SGLT2-I) is a recently recommended drug for the treatment of acute myocardial infarction, and its role in the risk of AMI endpoint events, including all-cause death and heart failure readmission, remains controversial. Therefore, in this study, we explored the effect of SGLT2-Is on cardiovascular outcomes after AMI.
METHODS PubMed, Web of Science, and Embase were searched without language restrictions to retrieve case-control studies published before April 2024. Citations were independently screened by two authors, and the studies meeting the predefined inclusion criteria were retained. Data on author names, year of publication, location of the study group, gender and age of participants, outcome assessment, adjusted odds ratios (ORs) and 95% confidence intervals (CIs), and the follow-up period were extracted.
RESULTS Eight studies were eligible for inclusion, and the studies demonstrated that the use of SGLT2-Is after AMI was significantly associated with reduced hospitalization for heart failure (OR: 0.65, 95% CI 0.55–0.77, P < 0.01) and major cardiovascular adverse events (OR: 0.74, 95% CI 0.60–0.91, P < 0.01) but not with a decrease in all-cause mortality (OR: 0.84, 95% CI 0.69–1.02, P = 0.07).
CONCLUSIONS Compared with placebo, SGLT2-I therapy following AMI can reduce the risk of heart failure hospitalization and the incidence of major cardiovascular adverse events, but the therapy has no effect on all-cause mortality.
CARDIOVASCULAR DISEASES IN SPECIAL GROUPS (CHILDREN, WOMEN, ETC.)
GW35-e0030
Hongbiao Huang1,2
1Children’s Hospital of Soochow University
2Fujian Provincial Hospital
OBJECTIVES To analyse the research history, development trends and current status of relevant literature in the field of Kawasaki disease (KD), and to provide the basis for future directions in the Kawasaki disease research.
METHODS Literature on KD published between January 1974 and December 2022 was searched for in the Web of Science database, and CiteSpace was used to perform visual analyses.
RESULTS The search yielded a total of 6950 articles. The number of publications related to KD showed an increasing trend. Collaborative network analysis shows that the United States, Japan and mainland China are the most influential countries in this field. University of California system contributed the most publications and the journal with the most publications is Circulation. Newburger JW is an authoritative author in this field. “Coronary artery lesion”, “Intravenous immunoglobulin (IVIG)” and “Risk factor” were three prominent keywords. Keyword bursts changed from “TNF” and “IVIG”, which focused on aetiology and treatment, to “Long term management” that emphasized the recovery period, and to “Kawasaki-like disease” and “Multisystem inflammatory syndrome” during the novel coronavirus pandemic. Trends of highly cited references indicated that landmark articles in different periods focused on KD guidelines, gene polymorphisms and multisystem inflammatory syndrome caused by the novel coronavirus.
CONCLUSIONS The aetiology of KD remains unclear, but viral infection is likely to play an important role. The combination of evolving sequencing technologies, large-scale epidemiological investigations and prospective cohort studies is likely to be important in exploring KD and improving its prognosis in future.
GW35-e0182
Xihang Fu1, Lin Wang2, Hua Peng2, Jing Wu1
1Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, Hubei 430030, China
2Department of Paediatric, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
OBJECTIVES Paediatric dilated cardiomyopathy (PDCM) is a heterogeneous disease, and its clinical management is still considered challenging. This study aimed to establish clinically relevant PDCM subtypes to evaluate prognosis and guide its treatments.
METHODS Multidimensional data (like demographics, clinical symptoms, laboratory data, and imaging phenotypes) of study participants were derived from electronic hospital records based on a multicentre retrospective cohort in China. Six clustering models for heterogeneous data were adopted to identify PDCM subtypes, and multiple indices were used to select the best model. Multivariable Cox models were adopted to evaluate the association between PDCM subtypes and the risk of adverse clinical events with the adjustment of several common clinical markers. Then, the additive prognostic value of PDCM subtypes was evaluated by the comparison between clinical model (age, sex, cardiac function classification, indexed LV diastolic diameter by body surface area [LVDd_index], LV ejection fraction [LVEF], and natriuretic peptide [NP] levels) by including or not including PDCM subtypes through the likelihood ratio test (LRT), and the corresponding area under the curve (AUC) values of the above models were compared by the DeLong’s test. Finally, a clinical classifier was constructed for clinical application.
RESULTS A total of 280 primary PDCM cases were included in this study, and two phenotypes developed by the Kamila model were recognized as optimal. Group II was mainly infants and toddlers (agemedian: 7.00 months) with larger dimensions (group II: LVDd_indexmedian = 99.43 mm/m2; group I: LVDd_indexmedian = 53.33 mm/m2) but mild LV systolic dysfunction (group II: LVEFmedian = 34.00%; group I: LVEFmedian = 30.00%) while group I was older children (agemedian: 111.88 months) with severe LV systolic dysfunction, reduced LV wall thickness expressed by the indexed interventricular septal thickness during diastole by body surface area (IVSd_index) (group II, IVSd_indexmedian = 11.20 mm/m2; group I, IVSd_indexmedian = 5.24 mm/m2), higher prevalence of abnormal valvular regurgitation (mitral regurgitation with over mild degree: group II vs. group I = 51.25% vs. 70.83%; tricuspid regurgitation with over mild degree: group II vs. group I = 28.12% vs. 47.50%; artery regurgitation with mild and above degree: group II vs. group I = 31.88% vs. 65.00%), and higher burden of arrhythmia (group II: 34.38%; group I: 65.83%). Moreover, group I had a significantly lower event-free survival probability than group II after adjusting for all covariates (HR = 8.864, P = 0.001). The developed PDCM subtypes also showed additional prognostic values beyond common clinical markers (AUC: from 0.628 to 0.692, P = 0.010; LRT: P < 0.001). The conditional interference tree model with five parameters could accurately distinguish PDCM subtypes.
CONCLUSIONS PDCM subtypes in our study showed distinct clinical profiles and risks of worse prognosis, and probably have different responses to current standard therapies, which would provide novel directions for precision management and pathological studies of PDCM.
GW35-e0354
Songhao Jia, Wenjian Jiang, Hongjia Zhang
Beijing Anzhen Hospital, Capital Medical
OBJECTIVES The in-hospital mortality rate of patients with acute type A aortic dissection was still as high as 22%, and malperfusion syndrome was considered one of the main causes, with sex differences still lacking research. This study aims to explore sex differences in malperfusion syndrome and outcomes in acute type A aortic dissection repair.
METHODS Between January 2015 and December 2017, 485 patients with acute type A aortic dissection who underwent surgery were included in our study. Patients were divided into a male group (n = 361) and a female group (n = 124) based on sex. Use inverse probability weighting to process two sets of baseline data and compare the impact of sex differences on the prognosis of patients at 30 days and during mid-term follow-up, with death as the primary endpoint.
RESULTS Among patients with acute type A aortic dissection, there were significantly more males than females, with females having older age (52.0% vs. 47.0%, P < 0.001), lower smoking rates (4.8% vs. 44.6%, P < 0.001), lower rates of renal malperfusion (4.8% vs. 19.1%, P < 0.001), lower rates of poor gastrointestinal malperfusion (1.7% vs. 5.6%, P = 0.041), and lower preoperative HB (106.5 vs. 112.0%, P = 0.001). There was no significant difference in early survival rate between female patients and male patients (Log-rank P = 0.730). In the median follow-up time of 6.2 years (IQR, 5.6–6.9 years), there was no significant difference in the mid-term survival rate between female patients and males (Log-rank P = 0.372).
CONCLUSIONS Among patients with acute type A aortic dissection undergoing surgery, female patients had a lower proportion of malperfusion syndrome, and there was no significant difference in postoperative survival rate compared to males.
GW35-e0375
Yasong Wang1,2, Xuan Wu1,3, Tinghao Zhao1,3, Tienan Zhou1, Xiaozeng Wang1
1Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
2Graduate School, Dalian Medical University, Dalian, Liaoning, China
3Graduate School, China Medical University, Liaoning, Liaoning, China
OBJECTIVES This study aims to evaluate the predictive value of the monocyte-to-lymphocyte ratio (MLR) in the prognosis of drug treatment for patients with Type B acute intramural hematoma (IMH) and to construct a predictive model.
METHODS This retrospective observational study collected data from 332 patients diagnosed with Type B IMH via computed tomography angiography (CTA) at the Emergency and Cardiovascular Departments of the General Hospital of Northern Theater Command between May 2018 and May 2024. The primary endpoint was defined as aortic-related adverse events within 30 days, including aortic-related death, progression to penetrating aortic ulcer (PAU), or aortic dissection (AD). Patients were divided into a stable group (n = 225) and a deteriorated group (n = 107) based on the occurrence of these adverse events. Univariate and multivariate logistic regression analyses were performed to identify independent predictors. Two new prognostic models were developed: (1) a clinical model and (2) an inflammatory-clinical model, incorporating inflammatory markers.
RESULTS A total of 32.2% (107/332) of patients experienced aortic-related adverse events within the 30-day follow-up, with 82 cases progressing to PAU, 19 to AD, and 6 resulting in aortic-related death. The ROC curve analysis for the MLR showed an AUC of 0.660 (0.599–0.719, P < 0.001). Comparison of baseline clinical and imaging characteristics indicated that the deteriorated group had a significantly lower proportion of diabetes but higher proportions of anemia, ulcer-like projections, and larger descending aortic diameters (all P < 0.05). Laboratory results showed that the deteriorated group had higher white blood cell counts, absolute neutrophil counts, and monocyte counts, while the stable group had higher absolute lymphocyte counts. The MLR was significantly higher in the deteriorated group (P < 0.05). Multivariate analysis identified diabetes, anemia, ulcer-like projections, descending aortic diameter, and MLR as independent predictors of poor prognosis in Type B IMH patients. The two models included: (1) Clinical Model: diabetes, anemia, ulcer-like projections, and descending aortic diameter; (2) Inflammatory-Clinical Model: diabetes, anemia, ulcer-like projections, descending aortic diameter, and MLR. The inflammatory-clinical model demonstrated superior discriminative ability (AUC: 0.788, 95% CI: 0.737–0.838) compared to the clinical model (AUC: 0.744, 95% CI: 0.690–0.799), with good calibration and significant net benefit according to decision curve analysis.
CONCLUSIONS The inflammatory marker MLR is a novel prognostic indicator for Type B IMH, aiding in optimizing treatment strategies.
GW35-e0388
Xiujuan Wang, Lingling Chen, Fang Liu
Beijing Tsinghua Changgung Hospital, School of Clinical Medicine
OBJECTIVES Pregnant women experience a number of physiologic changes that, if uncompensated, may result in varied degrees of cardiac function impairment. Left ventricular (LV) global longitudinal strain (GLS) and P-wave to A’ duration on tissue Doppler imaging (PA-TDI) are more sensitive and can identify changes in cardiac function early on.
METHODS The study was a prospective cross-sectional study. A total of 165 healthy pregnant women were enrolled in this study, including 48 women in early pregnancy (before 13 weeks’ gestation), 37 in mid-pregnancy (14–27 weeks’ gestation), 80 in late pregnancy (after 28 weeks’ gestation), while 142 age, height, and weight matched healthy nonpregnant women were included. The clinical data and echocardiographic parameters concerning left atrial and left ventricular function were assessed.
RESULTS PA-TDI was prolonged in late pregnancy [121.11 (113.03–129.18)] compared to the first trimester [117.65 (107.27–121.11); P = 0.041] and the second trimester of pregnancy [114.19 (105.54–117.65); P = 0.043]. The inclusion of week of gestation, heart rate, pre-pregnancy body mass index (BMI), and hemoglobin to construct a multifactorial regression equation showed a significant difference in the effect of week of gestation on PA-TDI (b = 0.391, t = 3.960, P < 0.001). The multifactor regression analysis revealed a significant difference in the influence of gestational week on LV-GLS (b = 0.149, t = 5.618, P < 0.001). LV mass (LVM) was higher in late pregnancy. Additionally, mitral valve E peak, E/A, and e′ were lower than in early pregnancy. E/e′ was not statistically different in early, middle and late pregnancy.
CONCLUSIONS Healthy pregnant women showed a trend of reduced left atrial function, left ventricular systolic function and diastolic function, but not to the extent of left heart dysfunction. Moreover, PA-TDI and LV-GLS can be used to evaluate early changes in left cardiac function in pregnant women, and PA-TDI measurements are simple, convenient, accurate and reproducible.
GW35-e0491
Zhankui Du2, Xiaozeng Wang1
1Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110016, China
2Department of Cardiology, Institute of Cardiovascular Research, the Second Hospital Affiliated to Xi’an Medical University, Xi’an, Shaanxi 710038, China
OBJECTIVES To evaluate aortic remodeling of acute type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR) combined with anti-thrombotic (AT) drugs.
METHODS This retrospective observational study enrolled consecutive patients with acute TBAD who underwent TEVAR and had computed tomography angiography (CTA) in preoperative and follow-up from January 2007 to October 2022. The patients were divided into AT and non-anti-thrombotic (NAT) groups according to whether or not to apply AT drugs. Preoperative and follow-up period (6 months) images data were analyzed for the thrombosis status of false lumen (FL), the changes of the maximum diameter of true lumen (TL), FL, transaortic lumen (TAL) in the stented thoracic aorta (STA), unstented thoracic aorta (UTA), and abdominal aorta (AA).
RESULTS One hundred and seventy five patients of acute TBAD were enrolled. For preoperative and follow-up images, there were no significant differences in the FL status (patent, partial thrombosis and complete thrombosis) and the changes of the maximum diameter of TL, FL, and TAL in the STA, UTA, and AA segments between the AT and NAT groups. The FL status of patent and complete thrombosis had significantly favourable in follow-up compared to preoperative image in all segments (all P < 0.001), and compared to preoperative images, the changes of maximum diameter of TL, FL and TAL in the STA, UTA, and AA were significant statistical differences in follow-up, respectively, in the AT and NAT groups (all P < 0.001). For the diameter variation, the expansion of TAL was 4.0%, 14.9% and 53.7%, respectively, in the STA, UTA and AA segment; the stabilization of TAL was 62.3%, 36.6% and 44.6%, respectively, in the STA, UTA and AA segment; the shrinkage of TAL was 33.7%, 48.6% and 1.7%, respectively, in the STA, UTA and AA segment. However, there were no significant statistical differences between the AT and NAT groups in aforementioned segments.
CONCLUSIONS The patients with AT drugs have comparable aortic remodeling prognosis than without AT therapy for acute TBAD underwent TEAVR in midterm. The maximum diameter of the STA and UTA are stable, and the aneurysmal growth of the AA is mainly attributed to FL expansion.
GW35-e0552
Shaomin Chen1,2,3,4
1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
2Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
3Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
4Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
OBJECTIVES An abnormal increase in serum lipid levels during pregnancy has been associated with the development of preeclampsia (PE). However, the relationship between pre-gestational dyslipidemia and PE has not been studied extensively. Women pregnant by in vitro fertilization and embryo transfer (IVF-ET) have more prevalant dyslipidemia and higher risk of PE. The aim of this study was to investigate the relationship between dyslipidemia prior to conception and the risk of PE and to establish a prediction model for the risk of PE in women pregnant by IVF-ET.
METHODS The retrospective cohort study consisted of 2994 women who conceived by IVF-ET and delivered live neonates. The study population was divided into two components: a training set for the prediction model development (2288 women) and a test set for validation (706 women). The total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) performed before IVF-ET were collected. Multivariable logistic regression was used for the development and validation of predictive model for the risk of PE.
RESULTS Among the 2288 women in the training set, 266 women (11.6%) developed PE. Multiple logistic regression analysis identified independent predictors for PE:TG [adjusted odds ratio (aOR) 1.284; 95% confidence interval (CI) 1.113–1.489, P < 0.001]; pre-pregnancy BMI; pre-chronic hypertension; twin pregnancy; protocol of IVF. These independent predictors for PE were used to form a risk prediction model [the area under the receiver-operator characteristic (ROC) curve (AUC) = 0.77, 95% CI 0.73–0.80]. The validation of the prediction model showed that it still had high discriminative ability and calibration (AUC = 0.71, 95% CI 0.65–0.77).
CONCLUSIONS Higher TG levels before pregnancy were independently associated with the risk for PE in women pregnant by IVF-ET. The model encompassing TG, BMI, chronic hypertension, twin pregnancy and protocol of IVF had high accuracy and specificity for the prediction of PE.
GW35-e0632
Wei Xiang, Minghuan Hong, Lingyun Kong, Fang Liu
Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University
OBJECTIVES Corynebacterium striatum (CS) is an uncommon pathogen associated with infective endocarditis (IE). Presently, there is limited information available in the form of comprehensive prospective studies, guidelines, or expert consensus pertaining to Corynebacterium striatum infective endocarditis (CSIE). The objective of this article is to provide insights into the clinical manifestation and management of CSIE by conducting a retrospective review in documented cases of CSIE.
METHODS An electronic search was conducted across various databases including PubMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, and Wanfang database to identify relevant articles in both English and Chinese literature documenting CSIE in adult patients.
RESULTS Systematic search yielded 38 patients from 35 articles. The median patient age was 68 [IQR 54, 73] years and 63.2% of patients were male. 55.3% of cases had a history of heart disease, while 28.9% had a history of cardiovascular electronic device implantation. The mitral valve was the most commonly affected site, accounting for 52.8% of cases. The misdiagnosis and missed diagnosis rate of CSIE was 28.9%. 40.9% of CS isolates were multidrug-resistant, with vancomycin demonstrating the highest sensitivity. Surgical intervention was performed in 55.3% of the patients, and the fatality rate was reported to be as high as 37.8%.
CONCLUSIONS CSIE presents with nonspecific clinical symptoms, making it susceptible to misdiagnosis or under diagnosis, and is often associated with multidrug resistance. The condition is characterized by a high incidence of surgical intervention and fatality, necessitating considerable vigilance and expertise from medical professionals.
GW35-e0690
Ruyue Zhang1, Shuheng Zhou1, Shuo Chen3, Xin Wang2, Xiaobing Liu1, Jimei Chen1
1Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences
2South China University of Technology
3Southern Medical University
OBJECTIVES To explore and summarize the impact of respiratory viral infections on the short-term prognosis of patients undergoing surgery for congenital heart disease.
METHODS A retrospective analysis was conducted on patients who underwent surgery for congenital heart disease and underwent preoperative viral testing at our hospital from February 2019 to April 2023, totaling 835 individuals, Through propensity score matching information was obtained for 300 patients, among whom 60 patients tested positive for respiratory viral infections preoperatively, and 240 patients tested negative preoperatively, with an average surgical age of (11.15+29.62) months, The overall resuits of virus detection and results distributed by month were analyzed, Based on the virus detection results, surgical patients were divided into Group A (60 cases, positive) and Group B (240 cases, negative to analyze postoperative recovery, postoperative complications, and medical expenses for each group. Subsequently, Group A was further subdivided into Group A1 (26 cases not seroconverted) and Group A2 (34 cases, seroconverted) based on whether seroconversion occurred preoperatively, and the postoperative recovery, postoperative complications, and medical expenses for each group were reanalyzed. The impact of preoperative respiratory viral infections on the short-term prognosis of patients with congenita heart disease was explored.
RESULTS Compared with Group B (411,973.34, the average medical expenses of Group A (4,149,283.28) were lower (P < 0.05), with fewer adverse outcomes (P < 0.001) and fewer patients requiring preoperative intubation (P < 0.001. After discussing the subgroups of the positive group it was found that the average medical expenses of the non-seroconverted group (4,157,501.57), seroconverted group (4,130,903.95), and negative group (4,119,713.34) showed a stepwise increase (P < 0.05). The proportion of adverse outcomes in the non-seroconverted group (19.23%) was significantly higher than that in the seroconverted group (5.88%) and the negative group (0.05%). The proportion of preoperative intubation in the positive group (21.67% was significantly higher than that in the negative group (12.5%, while the average postoperative intubation time in the positive group (52.73 hours) was lower than that in the negative group (78.07 hours).
CONCLUSIONS For patients with congenital heart disease complicated by respiratory viral infections, it is necessary to treat respiratory infections before surgery until seroconversion occurs, if the condition allows. Simultaneously, for patients with congenital heart disease who develop respiratory infections preoperatively, we believe that more proactive use of mechanical ventilation before surgery can effectively reduce the duration of postoperative mechanical ventilation for patients with congenital heart disease.
GW35-e0845
Yasong Wang1,2, Xuan Wu1,3, Tinghao Zhao1,3, Tienan Zhou1, Xiaozeng Wang1
1Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
2Graduate School, Dalian Medical University, Dalian, Liaoning, China
3Graduate School, China Medical University, Liaoning, Liaoning, China
OBJECTIVES This study aims to evaluate the predictive value of the monocyte-to-lymphocyte ratio (MLR) in the prognosis of drug treatment for patients with Type B acute intramural hematoma (IMH) and to construct a predictive model.
METHODS This retrospective observational study collected data from 332 patients diagnosed with Type B IMH via computed tomography angiography (CTA) at the Emergency and Cardiovascular Departments of the General Hospital of Northern Theater Command between May 2018 and May 2024. The primary endpoint was defined as aortic-related adverse events within 30 days, including aortic-related death, progression to penetrating aortic ulcer (PAU), or aortic dissection (AD). Patients were divided into a stable group (n = 225) and a deteriorated group (n = 107) based on the occurrence of these adverse events. Univariate and multivariate logistic regression analyses were performed to identify independent predictors. Two new prognostic models were developed: (1) a clinical model and (2) an inflammatory-clinical model, incorporating inflammatory markers.
RESULTS A total of 32.2% (107/332) of patients experienced aortic-related adverse events within the 30-day follow-up, with 82 cases progressing to PAU, 19 to AD, and 6 resulting in aortic-related death. The ROC curve analysis for the MLR showed an AUC of 0.660 (0.599–0.719, P < 0.001). Comparison of baseline clinical and imaging characteristics indicated that the deteriorated group had a significantly lower proportion of diabetes but higher proportions of anemia, ulcer-like projections, and larger descending aortic diameters (all P < 0.05). Laboratory results showed that the deteriorated group had higher white blood cell counts, absolute neutrophil counts, and monocyte counts, while the stable group had higher absolute lymphocyte counts. The MLR was significantly higher in the deteriorated group (P < 0.05). Multivariate analysis identified diabetes, anemia, ulcer-like projections, descending aortic diameter, and MLR as independent predictors of poor prognosis in Type B IMH patients. The two models included: (1) Clinical Model: diabetes, anemia, ulcer-like projections, and descending aortic diameter; (2) Inflammatory-Clinical Model: diabetes, anemia, ulcer-like projections, descending aortic diameter, and MLR. The inflammatory-clinical model demonstrated superior discriminative ability (AUC: 0.788, 95% CI: 0.737–0.838) compared to the clinical model (AUC: 0.744, 95% CI: 0.690–0.799), with good calibration and significant net benefit according to decision curve analysis.
CONCLUSIONS The inflammatory marker MLR is a novel prognostic indicator for Type B IMH, aiding in optimizing treatment strategies.
GW35-e0846
Zhankui Du1, Yasong Wang2, Tienan Zhou2, Xiaozeng Wang2
1Department of Cardiology, Institute of Cardiovascular Research, the Second Hospital Affiliated to Xi’an Medical University, Xi’an, Shaanxi 710038, China
2Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110016, China
OBJECTIVES This study aimed to compare clinical outcomes and aortic remodeling in patients with acute, subacute, and chronic type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR) with anti-thrombotic (AT) drugs in the mid-term.
METHODS Patients who underwent TEVAR for TBAD with AT drugs from January 2007 to May 2023 were included. Demographics, clinical data, and imaging characteristics were retrospectively recorded. All patients (n = 165) were divided into three groups: acute group (n = 112) subacute group (n = 31) and chronic group (n = 22).
RESULTS A total of 159 patients with postoperative computer tomography angiography (CTA) in the follow up. The three groups had comparable baseline characteristics. The mortality and major adverse event rates were similar among the groups both in the early and late terms (P > 0.05). Regarding aortic remodeling, the true lumen (TL) dimension increased in all groups, and a increase more in the acute groups than the other groups at the stented thoracic aorta (STA), uncovered thoracic aorta (UTA), and abdominal aorta (AA) segments, respectively (P all < 0.05). Conversely, the reduction in false lumen (FL) diameter was more pronounced in the acute group than in the subacute and chronic groups at the STA and UTA segments (P all < 0.05). And abdominal expansion showed no significant differences among the three groups. Complete thrombosis of the FL with good remodeling was achieved in 91.2% of cases at STA segment, 71.6% at UTA segment, and 38.4% at AA segment. Acute group showed higher rates of complete FL thrombosis at the STA and UTA segments (P < 0.05) and a lower rate of patent FL at the STA segment compared to the subacute and chronic groups (P < 0.05). Logistic regression analysis indicated that endoleak, multi-tear, non-acute dissected phase, and branches originating from the FL influenced optimal aortic remodeling.
CONCLUSIONS Patients with acute, subacute, and chronic TBAD had similar clinical outcomes after TEAVR combined with AT drugs. Aortic remodeling was more favorable in patients with acute TBAD than subacute and chronic TBAD. TEVAR combined with AT drugs promoted more positive remodeling at the stent graft segment than at the distal aorta.
GW35-e0881
Haochen Xuan1,2,3, Yikming Hung1,3, Kaihang Yiu1,2,3
1The University of Hong Kong
2The University of Hong Kong Shen Zhen Hospital
3Queen Mary Hospital
OBJECTIVES Diabetes mellitus (DM) patients with coronary ischemia face an exceptionally elevated risk, and the achievement of complete revascularization (CR) within this population is significantly arduous. The impact of SGLT2 inhibitors on the prognosis of individuals with DM and residual coronary ischemia remains to be conclusively determined.
METHODS DM Patients and confirmed to have coronary ischemia based on coronary angiography and retrospective coronary angiography-derived fractional flow reserve (caFFR) analysis between January 2014 and December 2016 were included. The successful revascularization of all major coronary artery branches experiencing functional ischemia was defined as complete revascularization (CR). Patients were divided into two groups based on whether they had been prescribed for SGLT2 inhibitors. Subgroup analysis was then performed based on whether CR was achieved. The primary study endpoint was major adverse cardiac events (MACE), with all-cause mortality as the secondary endpoint. Kaplan–Meier analysis and Cox proportional hazards regression modeling assessed the influence of SGLT2 inhibitors on endpoint events occurrence.
RESULTS Among 671 DM patients with coronary ischemia, there were 484 (72.1%) achieved CR, and 206 (30.7%) SGLT2 inhibitors users. During a mean 36 months follow-up, 100 MACE and 89 all-cause mortality occurred. SGLT2 inhibitor users demonstrated lower rates of MACE (8.3% vs. 17.8%; P = 0.002) and all-cause mortality (6.3% vs. 16.3%; P < 0.001) compared to non-users. Subgroup analysis indicated that SGLT2 inhibitors were equally beneficial in both the CR and ICR groups (Pinteraction = 0.804 for MACE and 0.730 for all-cause mortality). After adjusting for confounding factors in multivariable Cox analysis, SGLT2 inhibitors still showed an association with a reduced risk of MACE both in the CR and ICR subgroups (HR, 0.498; 95% CI, 0.246–0.938; P = 0.040 and HR, 0.341; 95% CI, 0.123–0.805; P = 0.023, respectively).
CONCLUSIONS SGLT2 inhibitors were associated with a reduced risk of 3 years MACE and all-cause mortality in DM patients with coronary ischemia, with significant effects observed regardless of whether CR was achieved.
GW35-e0948
Rujie Zheng1,2, Wenjuan Song1,2, Chengzhi Lu1,2
1Tianjin First Central Hospital
2Tianjin Medical University
OBJECTIVES Metabolic dysfunction-associated fatty liver disease (MAFLD), which affects approximately 25% of the worldwide population, not only heightens the risk of liver-related events but also extra-hepatic events, mainly cardiovascular diseases (CVD). Lifestyle changes (weight loss and dietary modification) to delay the occurrence of MAFLD and its related complications seem to be the cornerstone of disease prevention and treatment. However, research on the association between dietary niacin intake and CVD is limited. To address this research gap, we aimed to investigate the correlation between dietary niacin intake and CVD risk in individuals with MAFLD.
METHODS In this cohort study, we analyzed data sourced from the National Health and Nutrition Examination Survey (2003–2018). A total of 5710 participants with MAFLD were included, with MAFLD diagnosed using the United States-Fatty Liver Index ≥30. Dietary niacin intake was measured based on two 24-hour dietary recalls. Weighted regression model, stratified analyses and restricted cubic spline (RCS) analyses with 4 knots were employed to ascertain the link between dietary niacin intake and the risk of CVD. Besides, a series of sensitivity analyses were conducted: (1) participants with only one dietary recall were excluded from the sensitivity analyses; (2) the number of knots of the restricted cubic spline was changed for repeated analyses using 5 knots and 3 knots.
RESULTS Among 5710 enrolled participants, the median age was 50.0 years and 2799 (weighted, 51.05%) of the participants were men. When dietary niacin intake was assessed in quartiles, participants in higher dietary niacin intake quartiles were younger, more often male, had higher family income and education levels, higher HEI-2015 score compared with those in quartile 1 (≤15.17 mg). After fully adjusting for covariates, weighted logistic regression model revealed the most significant reduction in the incidence of total CVD (OR, 95% CI: 0.511, 0.358–0.730), myocardial infarction (OR, 95% CI: 0.590, 0.381–0.915), congestive heart failure (OR, 95% CI: 0.338, 0.182–0.630), and stroke (OR, 95% CI: 0.512, 0.309–0.849) within the quartile 4 (≥29.49 mg), compared to the quartile 1. Consistently in the threshold analysis, for every 1 mg/d increase in dietary niacin, there was a 2.1%, 1.7%, 3.4% and 2.8% decrease in total CVD (OR, 95% CI: 0.979, 0.968–0.991), myocardial infarction (OR, 95% CI: 0.983, 0.969–0.996), congestive heart failure (OR, 95% CI: 0.966, 0.947–0.985) and stroke (OR, 95% CI: 0.972, 0.955–0.989), respectively. We also performed further stratified analyses to assess the association between dietary niacin intake and the risk of CVD risk. There was a significant interaction between dietary niacin and age in relation to congestive heart failure risk (P = 0.03 for interaction). No significant interactions were found between dietary niacin intake and any other strata variables with the risk of CVD. Besides, the RCS did not demonstrate a discernible nonlinear association between dietary niacin intake and CVD risk (P non-linearity > 0.05 for all). In sensitivity analyses, the associations of dietary niacin intake with CVD risk were not materially altered when participants with only 1 dietary recall were excluded. In addition, the results of RCS with 3 knots and 5 knots were consistent with the RCS with 4 knots.
CONCLUSIONS In US adults with MAFLD, dietary niacin intake negatively correlated with CVD risk, suggesting dietary modifications could mitigate the risk of non-fatal cardiovascular disease.
GW35-e1021
Lihui Kang, Jingzhe Liu
The First Hospital of Tsinghua University
OBJECTIVES Cardiovascular diseases are common cause of morbidity and mortality in patients with tumor due to accelerated atherosclerosis which couldn’t be explained solely by traditional risk factors. Coronary artery calcification score is commonly used to predict the risk of cardiovascular events. The H2FPEF score enables robust discrimination of heart failure with preserved ejection fraction (HFpEF) from non-cardiac aetiologies of dyspnea. We aimed to investigate the relationship between H2FPEF and coronary artery calcification score (CACS) in patients with tumor. And explored the value of the H2FPEF score in the cardiovascular risk assessment among these patients.
METHODS This was a single-center, retrospective, and observational study. We recruited 474 consecutive patients with tumor who underwent coronary computed tomographic angiography (CCTA) examination for suspected stable ischemic heart disease from June 2017 through March 2021. Coronary artery calcium score (CACS) was measured by CCTA through Agatston score, and detailed information on cardiovascular risk factors was recorded. The H2FPEF score was calculated for each patient.
RESULTS High CACS (>400) was present in 24% of all tumor patients. After adjustment for cardiovascular risk factors, the odds ratio (OR) of a CACS >400 was 1.6 (95% CI 1.2–3.0, P = 0.009) in patients with H2FPEF score >2 compared to who H2FPEF score ≤2. The mean H2FPEF Score [2.9 (2–3.6) vs. 1 (0.5–1.5), P < 0.001] was higher and LVEF was lower in patients with high CACS compared with low CACS (≤400). H2FPEF score was positively correlated with CACS (r = 0.725, P = 0.003). In ROC curve analysis, an H2FPEF score of ≥3 predicted high CACS with 81.1% sensitivity and 80.2% specificity (AUC: 0.876; 95% CI: 0.835–0.928; P = 0 .007). During a median follow-up of 18 months (interquartile range 9–36), 99 (20.9%) patients died. The H2FPEF score predicted a high risk of all-cause death which remained significant after adjustment for tumor diagnosis, age, N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, and echocardiographic parameters, including LVEF and left ventricular diastolic function (hazard ratio 1.41, 95% confidence interval 1.18–1.86, P = 0.003 for every 1-point increase in H2FPEF score).
CONCLUSIONS High H2FPEF score was associated with coronary artery calcification in patients with tumor. It may be used to estimate the cardiovascular risk for tumor patients.
GW35-e1042
Sulan Huang
The First People’s Hospital of Changde City
OBJECTIVES There are certain limitations to general prediction models, and machine learning has become one of the developing directions in modern medicine to overcome them. Therefore, this study intends to apply machine learning to construct a prediction model for the risk of hypertensive disorders complicating pregnancy in advanced maternal age and adverse pregnancy outcomes.
METHODS A bi-directional cohort study was conducted. Study participants were enrolled in three hospitals in Changde City from 2008 to 2023 and followed up for 3 months after delivery for advanced maternal age patients diagnosed with preeclampsia. In this study, machine learning classification method was used to construct a prediction model of adverse pregnancy outcomes in advanced maternal age patients with hypertensive disorders of pregnancy using six algorithms, including LR, adaptive boosting (AdaBoost), complement naive bayes (CNB), MLP, SVM and K-nearest neighbors (KNN). The performance of the prediction model was re-evaluated, and the optimal adverse pregnancy outcome prediction model based on the data set of this study was obtained. Finally, the model fusion analysis and external validation were carried out.
RESULTS In this part of the study, we enrolled 860 advanced maternal age patients with pre-eclampsia, 322 of whom had adverse pregnancy outcomes. The data were randomly divided into a training set and a validation set, and the size ratio of the training set and the validation set was 8:2, respectively. Respectively using the selected feature index, based on six kinds of algorithms to establish adverse pregnancy outcome prediction model for women, through to the validation set, we have the different classification model validation set AUC and accuracy. Specific as follows: LR classification model of AUC 0.772 (95% CI: 0.692–0.853), and the accuracy of 0.711 (95% CI: 0.670–0.752); AdaBoost classification model of AUC 0.927 (95% CI: 0.884–0.970), the accuracy of 0.847 (95% CI: 0.838–0.857); CNB classification model of AUC 0.770 (95% CI: 0.690–0.850), the accuracy of 0.711 (95% CI: 0.673–0.749); The AUC of MLP classification model was 0.653 (95% CI: 0.561–0.746), and the accuracy was 0.635 (0.601–0.670). The SVM classification model of AUC 0.760 (95% CI: 0.678–0.842), the accuracy of 0.701 (95% CI: 0.662–0.739); The AUC of KNN classification model was 0.861 (95% CI: 0.803–0.919), and the accuracy was 0.766 (95% CI: 0.753–0.779). SHAP algorithm was used to obtain the importance of each predictor variable for the GNB model prediction results, and the results showed that systolic blood pressure, gestational age, urea nitrogen and white blood cell had the greatest predictive value for adverse pregnancy outcomes in advanced maternal age patients with preeclampsia. In the external validation group, the AUC of discrimination was 0.916 (95% CI: 0.865–0.967), and the corresponding accuracy, sensitivity and specificity were 93.0%, 87.0% and 87.6%, respectively.
CONCLUSIONS By comparing the performance of each classification model in the training and validation sets, we conclude that the AdaBoost model performs well and can be used to predict adverse pregnancy outcomes in advanced maternal age patients with preeclampsia.
GW35-e1094
Feng Yang, Chen Jiaqi, Yin Chunmei, Yang Chunjiang
Children’s Hospital of Chongqing Medical University
OBJECTIVES Cardiovascular disease is the leading cause of death in patients with Duchenne muscular dystrophy (DMD) – a fatal X-linked genetic disorder. Three-dimensional speckle tracking technology (3D-STE) and CMR (native T1) were used to assess the structure and function of the left heart in children with DMD, to analyze the potential correlation between myocardial microstructural remodeling and dysfunction, and to explore the value of the left heart parameters for early screening of impaired cardiac function in children with DMD.
METHODS Prospectively enrolled DMD (n = 18, 10.4 ± 3.0 years old) and age-matched healthy boys (n = 10, 10.8 ± 2.7 years old). Left ventricular global longitudinal strain (LVGLS), the Strain of reservoir phase of the left atrium (LASr), the Strain of conduit phase (Scd), and the Strain of contraction phase (Sct) were obtained using three-dimensional strain analysis software. Analyzing the variability of strain indicators and magnetic resonance parameters between the experimental and control groups and to explore their correlation with conventional ultrasound and clinical serological indicators (NT-pro BNP). Receiver Operating Characteristic analysis was used to evaluate native T1 mapping and LV function parameters in the task of distinguishing between healthy controls and boys with DMD.
RESULTS 3D-STE results showed that the absolute values of LVEF, LVGLS, LASr, and LAScd in the experimental group of children with DMD were significantly lower than those in the control group (P < 0.001), and the native T1 of the basal segments were elevated (P < 0.05). LASr and GLS were moderately positively correlated with LVEF (r = 0.525, P < 0.001), while the native T1 of the anteroseptal myocardium of the basal segment was moderately negatively correlated with LVEF (r = 0.539, P < 0.001); However, there was no statistically significant difference in native T1 of normal children compared with children of DMD with decreased ejection fraction. The binary logistic regression analysis showed that GLS and LASr were sensitive predictors for detecting reduced ejection fraction in children with DMD. ROC curve analysis of LASr for diagnosing subclinical cardiac insufficiency had a sensitivity of 82.6%, specificity of 74.3%, and cutoff absolute value of 34.5%.
CONCLUSIONS LASr and Scd change earlier than conventional left ventricular diastolic function parameters, LASr can be used for early monitoring of subclinical left ventricular dysfunction in children. LASr and Scd are expected to become one of the routine test indexes of left ventricular function, whereas the value of the use of native T1 needs to be further studied.
GW35-e1373
Shuwen Zheng1, Haoming He2, Tong Liu3, Xin Du4, Li Li5, Ying Liu6, Yushi Wang7, Ling Bai8, Jiang Wang9, Ye Zhang10, Hang Zhang11, Longyang Zhu12, Wenjing Wu13, Mengwen Yan13, Liu He14, Baoxia Chen15, Yihong Sun14
1Department of Cardiology, Beijing University of Chinese Medicine China-Japan Friendship School of Clinical Medicine, Beijing, China
2Department of Cardiology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
3Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, China
4Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China
5Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
6Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
7Department of Cardiology, The First Hospital of Jilin University, No. 71 of Xinmin Street, Changchun, China
8Department of Cardiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
9Institute of Cardiovascular Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), 183 Xinqiao Street, Chongqing, China
10Department of Cardiology, Daping Hospital, Third Military Medical University; Chongqing Institute of Cardiology, Chongqing, China
11Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
12Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
14Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
13Department of Cardiology, China-Japan Friendship hospital, Beijing, China
15Department of Cardiology, Peking University Third Hospital, 49 Huayuan-Bei Road, Beijing, China
BACKGROUND AND AIMS Takotsubo syndrome (TTS) has not been sufficiently characterized across distinct ethnic population. The present study aimed to describe the clinical features and short/long-term outcomes of Chinese TTS patients.
METHODS Patients diagnosed with TTS were retrospectively enrolled from 2013 to 2023 in 10 tertiary hospitals across China. Baseline patients’ characteristics at admission to each hospital, in-hospital adverse events and long-term outcomes were collected and described. In-hospital adverse events were including cardiogenic shock, mechanical circulatory support, and all-cause death, while long-term outcomes were assessed using all-cause mortality and cardiovascular re-hospitalization.
RESULTS Among the 202 patients analyzed, the average age was 61.7 (SD, 17.6) years and 26.2% were males. Overall, 56.4% appeared as apical type and 57.9% had physical triggers. Overall, 17.8% patients experienced in-hospital death. During a median follow-up of 24 months, the incidence of death or cardiovascular rehospitalization was 10.35 per 100 person-year and the long-term mortality was 8.34 per 100 person-year. Multivariable logistic regression analysis showed that physical triggers, malignancy, and tachycardia were independently associated with increased risk of in-hospital outcomes. The use of renin-angiotensin-aldosterone system (RAAS) inhibitors were negatively related to occurrence of both in-hospital outcomes and long-term outcomes. The area under the curve of the Inter-TAK prognostic score was 0.75 (95% CI: 0.67–0.84) on predicting in-hospital death and 0.72 (95% CI: 0.61–0.83) on long-term death.
CONCLUSIONS Chinese TTS patients were strongly related to physical triggers and at a very high risk of in-hospital and long-term adverse events, particularly those with malignancy. The benefits of RAAS inhibitors should be confirmed in adequately powered randomized controlled trials (Takotsubo syndrome of Chinese patients [TAKOC] Registry; ChiCTR2300075095).
Keywords: Takotsubo syndrome, mortality, risk factor, outcome
OTHERS
GW35-e0099
Zhiqiang Li1, Xinxin Liu1, Xuefeng Wang1, Chen Shen1, Xinran Gong2, Feng Cao2, Xinmiao Guan2, Yin Zhang1, Rongrong Li3, Jianping Liu4
1Centre for Evidence-based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
2School of Public Health, China Medical University, Shenyang 110122, China
3Department of Cardiovascular Medicine, Second Medical Center, Chinese PLA General Hospital, Beijing 100853, China
4The National Research Center in Complementary and Alternative Medicine (NAFKAM), Department of Community Medicine, Faculty of Health Science, UiT The Arctic University of Norway, Tromsø, Norway
OBJECTIVES Hypoproteinemia commonly coexists with CI, and both conditions exhibit a proportional increase with advancing age. Nevertheless, the combined impact of hypoalbuminemia and CI on mortality remains an under-explored area, particularly among Chinese older adults. This study we aimed to investigate the association between plasma albumin, cognitive impairment (CI), and their synergistic effect on mortality in Chinese community-dwelling older adults.
METHODS Data from the Chinese Longitudinal Healthy Longevity Survey (2012) included 1858 participants aged ≥65. Baseline assessments comprised albumin levels and cognitive status. All-cause mortality was confirmed through 2014–2018 surveys. Cox proportional hazards models assessed associations, and restricted cubic splines explored albumin-mortality relationship.
RESULTS During a median follow-up of 48.85 months, 921 deaths occurred. Albumin ≥35 g/L vs. <35 g/L [HR: 1.33 (95% CI, 1.10, 1.62)] and CI vs. normal cognition [HR: 1.69 (95% CI, 1.43, 1.99)] independently predicted mortality. A dose-response relationship with mortality was observed for albumin quartiles (P < 0.001). Each SD increase in MMSE or albumin correlated with 22% and 15% lower mortality risk, respectively. Combined hypoproteinemia and CI increased 55% mortality risk, notably in males and those aged 65–84. Interaction effects of albumin and CI on mortality were observed (P < 0.001). Mortality risk increased by 61% in the hypoproteinemia group with CI, compared to the normal albumin group. Restricted cubic spline revealed a reverse J-shaped association, particularly for participants without CI. For individuals with CI, albumin levels were inversely associated with mortality risk.
CONCLUSIONS Hypoproteinemia and CI, individually and combined, increased all-cause mortality risk in Chinese older adults, with stronger effects in males and younger old adults. These findings emphasize the importance of targeted adjustments and early nutrition programs in health prevention and clinical care for older adults.
GW35-e0163
Yan Li
Center for Clinical and Epidemiologic Research, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
OBJECTIVES The accurate data on global incidence and mortality of cardiovascular disease (CVD) in women are absent. We used data from Global Burden of Disease (GBD) study 2019 to quantify the burden of CVD in women at the global, regional and national levels.
METHODS Annual incident cases, deaths, age-standardized incidence rate (ASIR), and age-standardized mortality rate (ASMR) of CVD in women from 1990 to 2019 were collected from the GBD study 2019. The percentage changes of incident cases and deaths, and the estimated annual percentage change (EAPC) of age-standardized rate were calculated to quantify the temporal trends of CVD in women.
RESULTS Globally, the incident cases of CVD in women increased by 73.86% from 15.90 million in 1990 to 27.64 million in 2019; the number of deaths of CVD in women increased by 47.45% from 6.06 million in 1990 to 8.94 million in 2019. The global ASIR (EAPC = −0.57 [95% CI: −0.61 to −0.53]) and ASMR (EAPC = −1.63 [95% CI: −1.70 to −1.57]) of CVD in women decreased in this period. The ASIR of ischemic heart disease (IHD) in women increased by an average of 0.04% (95% CI: 0.00%, 0.08%) and 0.08% (95% CI: 0.02%, 0.15%) per year in low and middle Socio-demographic Index (SDI) regions, but decreased by an average of 1.09% (95% CI: −1.18%, −1.00%) and 2.24% (95% CI: −2.38%, −2.10%) per year in high-middle and high SDI regions during 1990–2019.
CONCLUSIONS The age-standardized incidence rate of IHD in women remains an increasing trend in low and middle SDI regions.
GW35-e0258
Shimei Yu1, Hailong Wang2
1Wanzhou First People Hospital, Chongqing
2Chongqing University Three Gorges Hospital
OBJECTIVES Celecoxib is a highly selective, non-steroidal anti-inflammatory drug. However, it is not known whether celecoxib has an antiviral effect against coronavirus disease 2019 (COVID-19).
METHODS We retrospectively screened 264 patients who met the inclusion criteria within approximately 2 months (From November 1 to December 26, 2022) and divided patients into a COX-2 celecoxib group and a COX-1 ibuprofen group, with 73 patients in each group based on age and gender. During the diagnosis of COVID-19 patients, COVID-19 virus nucleic acid levels, hospital stay duration, serum C-reactive protein (CRP) levels, serum interleukin-6 (IL-6) levels, and all-cause death rates during hospitalization or follow-up were monitored. We calculated chi-square test values or independent sample t-tests for various indicators to determine whether there is a significant statistical difference between the celecoxib group and the ibuprofen group.
RESULTS Compared with the ibuprofen group, there was a significant difference in the time it took for the nucleic acid negative transformation of the COVID-19 PCR in the celecoxib group (95% confidence interval, CI: 3.48–5.50; P < 0.0001). There was also a significant difference in the hospital stay length (95% confidence interval, CI: 3.15–3.97; P < 0.0001). However, there was no significant difference in serum inflammatory markers, such as IL-6 and C-reactive protein, between the two groups (P > 0.05). There were no deaths in the two groups of patients.
CONCLUSIONS We conclude that celecoxib reduces the length of hospital stay in patients with COVID-19 and shortened the time it took to obtain a negative viral nucleic acid PCR test. However, celecoxib did not decrease serum C-reactive protein and IL-6 levels.
GW35-e0296
Ting Tang, Mingwei Wang
Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou
OBJECTIVES The global epidemic of metabolic disease-associated fatty liver disease (MAFLD) poses a challenge to public health and socio-economic. Traditional auxiliary exams for MAFLD, such as B-ultrasound, are time-consuming. A simple and effective method is needed to screen for MAFLD. Weight-adjusted waist circumference index (WWI) can comprehensively reflect the accumulation of visceral fat and sarcopenia. The aim of this study was to examine whether WWI is associated with MAFLD, and to further examine the influence of different subgroups on this relationship.
METHODS In this single-centered study, we screened 288 participants from the outpatient of the Affiliated Hospital of Hangzhou Normal University (Hangzhou, China). Participants’ hepatic steatosis and hepatic fibrosis were measured by measuring controlled attenuation parameter (CAP) and liver stiffness measurements (E value), using a FibroScan® machine. WWI scores of all participants were computed and subsequently utilized to classify them into four quartile groups. The differences between WWI quartiles were assessed using chi-square tests, single factor ANOVA test, or Kruskal-Wallis tests. Multiple linear regression models were employed to evaluate the association between WWI and hepatic steatosis and hepatic fibrosis. Subgroup analyses were conducted using a stratified multivariate logistic regression model.
RESULTS MAFLD was detected in 185 of 288 patients. Multivariate linear regression analysis showed that WWI was positively correlated with hepatic steatosis and hepatic fibrosis (P < 0.05). After fully adjusting for the relevant covariates (in Model 3), a one-unit increase in WWI score is associated with a corresponding increase of 73.64 dB/m in the CAP (β = 73.64; 95% CI 4.42, 10.78; P < 0.001). In the subgroup analysis, an elevated WWI score were more remarkably associated with hepatic steatosis in both smoking patients and patients aged 18–59 years (P < 0.05). Drinking, female, body mass index (BMI) > 28 and participants with diabetes were observed to have a positive correlation between WWI and liver fibrosis (P < 0.05).
CONCLUSIONS Our study revealed a significant linear positive correlation between WWI and MAFLD. WWI could serve as a valuable and simple indicator for the early screening of MAFLD. These findings have important implications for enhancing the screening and diagnosis of MAFLD.
GW35-e0321
Zaiyong Zheng1, Yanman Li2, Qinlu Jiang2, Fangfang Zang1, Rongchuan Yue2, Houxiang Hu2, Chunxiang Zhang1
1Department of Cardiology, Key Laboratory of Medical Electrophysiology, Ministry of Education; Basic Medicine Research Innovation Center for cardiometabolic diseases, Ministry of Education; The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, China
2Department of Cardiology, Academician Workstation. The Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong 637000, China
OBJECTIVES Air pollution has been a global public concern. According to the World Health Organization (WHO), more than 99% of the global population lives in area with air pollution. In 2021, particulate matter air pollution emerged as the foremost contributor to the global disease burden. Air pollution is responsible for 6.7 million premature deaths worldwide every year. Therefore, this work aims to investigate the acute effects of air pollution on the daily hospitalizations for cardiovascular disease in Nanchong.
METHODS Data of daily hospitalization for cardiovascular disease from June 1, 2015, to December 31, 2023 (9.5 years) were collected from the electronic health record system in Nanchong. The historical air pollutant and meteorological data were obtained from the fixed monitoring stations. We performed over-dispersed Poisson regressions incorporated with distributed lag models to assess associations between short-term exposure to air pollution and the risk of cardiovascular disease hospitalizations.
RESULTS A total of 373,390 of hospitalizations were identified. During the study period, the daily average concentrations of air pollutants were: PM2.5 (42.39 ± 28.68 μg/m3), PM10 (63.70 ± 40.21 μg/m3), SO2 (9.45 ± 6.94 μg/m3), NO2 (24.18 ± 11.09 μg/m3), CO (0.67 ± 0.27 mg/m3), and O3 (68.77 ± 35.97 μg/m3). We found that a 10 μg/m3 increase in 7-day average concentrations of PM2.5 and PM10 was associated with 1.15% (95% CI: 0.55%–1.76%) and 0.51% (95% CI: 0.19%–0.82%) higher cardiovascular disease admissions. NO2 presents the largest adverse effect. The risk of cardiovascular disease admission increased by 6.26% with per 10 μg/m3 increase in NO2. In the sex-specific analysis, the risk of admission for CVD among male increased by 0.48% (95% CI: 0.12%–0.84%) for every 10 μg/m3 increase in PM10. However, we didn’t observe significant associations among female. In age-specific analysis, for CVD patients aged 70–80 years old, the risk of hospitalization increased by 0.81% (95% CI: 0.17%–1.50%) and 0.72% (95% CI: 0.26%–1.18%) for every 10 μg/m3 increase in PM2.5 and PM10, respectively.
CONCLUSIONS High concentrations of air pollution were risk factors for cardiovascular diseases. Short-term cumulative and single exposures to air pollutants increased the risk of hospitalization for cardiovascular disease. Policymakers need to develop policies and strategic plans to combat air pollution.
GW35-e0409
Meiping Zhang
Yanbian University
OBJECTIVES Exposure to chronic psychosocial stress is a risk factor for metabolic disorders. Because dipeptidyl peptidase-4 (DPP4) and cysteinyl cathepsin K (CTSK) play important roles in human pathobiology, we investigated the role(s) of DPP4 in stress-related adipocyte differentiation, with a focus on the glucagon-like peptide-1 (GLP-1)/adiponectin-CTSK axis in vivo and in vitro.
METHODS Plasma and inguinal adipose tissue from non-stress wild-type (DPP4+/+), DPP4-knockout (DPP4−/−) and CTSK-knockout (CTSK−/−) mice, and stressed DPP4+/+, DPP4−/−, CTSK−/−, and DPP4+/+ mice underwent stress exposure plus GLP-1 receptor agonist exenatide loading for 2 weeks and then were analyzed for stress-related biological and/or morphological alterations.
RESULTS On day 14 under chronic stress, stress decreased the weights of adipose tissue and resulted in harmful changes in the plasma levels of DPP4, GLP-1, CTSK, adiponectin, and tumor necrosis factor-α proteins and the adipose tissue levels of CTSK, preadipocyte factor-1, fatty acid binding protein-4, CCAAT/enhancer binding protein-α, GLP-1 receptor, peroxisome proliferator-activated receptor-γ, perilipin2, secreted frizzled-related protein-4, Wnt5α, Wnt11 and β-catenin proteins and/or mRNAs as well as macrophage infiltration in adipose tissue; these changes were rectified by DPP4 deletion. GLP-1 receptor activation and CTSK deletion mimic the adipose benefits of DPP4 deficiency. In vitro, CTSK silencing and overexpression respectively prevented and facilitated stress serum and oxidative stress-induced adipocyte differentiation accompanied with changes in the levels of pref-1, C/EBP-α, and PPAR-γ in 3T3-L1 cells.
CONCLUSIONS These findings indicated that increased DPP4 plays an essential role in stress-related adipocyte differentiation, possibly through a negative regulation of GLP-1/adiponectin-CTSK axis activation in mice under chronic stress conditions.
GW35-e0464
Mei Yang, Menghui Wang, Qing Zhu, Nanfang Li
Xinjiang Hypertension Institute
OBJECTIVES Plasma aldosterone concentrations are suggested to be related to the preeclamptic pathogenesis, but previous literature is scarce and controversial. Our study aims to investigate the association between aldosterone and preeclampsia and its effect on pregnancy outcomes.
METHODS A cross-sectional study was conducted at the obstetric inpatient unit. Ultimately, 170 women were recruited, including 44 with preeclampsia and 126 without hypertensive disorders of pregnancy (HDP). Participants’ clinical data and pregnancy outcomes (neonatal birth weight, gestational weeks at delivery, and the incidence of preterm birth and fetal growth restriction) were collected. Peripheral blood samples were also collected and tested for aldosterone, renin, and angiotensin II, etc. Logistic regression and spearman correlations test were used to describe the association between plasma aldosterone concentrations and admission blood pressure and pregnancy outcomes, Receiver operating characteristic curves were used to assess its predictive value. Sensitivity analyses were performed on study results.
RESULTS Plasma aldosterone concentrations were significantly lower in preeclamptic women than in women without HDP. The results were consistent in the sensitivity analysis. It was negatively associated with the incidence of preeclampsia (β = −0.03, P = 0.001), admission blood pressure (P < 0.001), and the incidence of preterm birth (r = −0.26, P = 0.001) and fetal growth restriction (r = −0.23, P = 0.005). It was positively associated with neonatal birthweight (r = 0.29, P < 0.001) and gestational weeks at delivery (r = 0.33, P < 0.001). Its AUC was 83.8%.
CONCLUSIONS Plasma aldosterone concentrations were negative associated with the prevalence of preeclampsia, preterm birth, and fetal growth restriction. It was positive associated with neonatal weight and gestational weeks. It is useful for preeclamptic diagnosis.
GW35-e0624
Jiaqi Hao
Shandong University of Traditional Chinese Medicine
OBJECTIVES Infective endocarditis (IE) is a highly fatal disease with a severe socioeconomic burden.
METHODS Data on infective endocarditis (IE) due to high systolic blood pressure (HSBP) were extracted from the Global Burden of Disease (GBD) database between 1990 and 2019. The number and age-standardized rate (ASR) of age-standardized death rates (ASDR) and disability-adjusted life years (DALYs) for HSBP-associated infective endocarditis were analyzed by year, age, region, country, and Human Development Index (HDI). Average annual percentage change (AAPC) was analyzed by link-point regression and annual percentage change (APC) modeling.
RESULTS Of all global deaths and disability-adjusted life years (DALYs) from infective endocarditis in 2019, 33.0% and 31.6%, respectively, were attributable to high systolic blood pressure (HSBP). Two thousand and nineteen resulted in 21,863 [95% CI (14,907–29,113)] deaths and 544,405 (95% CI [394,851–6,854,980]) DALYs. There was an increasing trend in the number of deaths and DALYs associated with HSBP. Of the five socio demographic index (SDI) regions, High SDI regions had the highest rates of endocarditis attributable to HSBP for ASDR, and Low SDI regions, the highest rates of age-standardized DALYs. In terms of geographic regions, Southern Latin America and Eastern Europe were at high risk for deaths from IE attributable to HSBP and for DALYs attributable to HSBP, with Kiribati being the country with the highest burden. ASDR and Age-standardized DALYs rate was highest at age 95+ and was higher in females than males. EAPC in ASDR and Age-standardized DALYs rate in 2019 were highly positively correlated with Human Development Index (HDI) with coefficients of 0.317 and 0.255 respectively.
CONCLUSIONS The number of deaths and DALYs from IE associated with HSBP continues to increase globally, and there is substantial heterogeneity across gender, age, and region, reducing HSBP is effective in decreasing the global burden of endocarditis, which may help policymakers and healthcare professionals respond to IE and develop cost-effective interventions.
GW35-e0649
Yu Zhao, Weihua Chen, Rongchong Huang
Capital Medical University Affiliated Beijing Friendship Hospital
OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) has been replaced by the term “metabolic dysfunction–associated steatotic liver disease” (MASLD), which is closely associated with cardiovascular risk factors. Recognizing the heightened mortality risk in MASLD, this study investigates the influence of cardiovascular health (CVH), as measured by Life’s Essential 8 (LE8), on patient outcomes.
METHODS This study included 4231 MASLD participants aged 20 years and older from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. Mortality data was obtained through linkage to the National Death Index, up to December 31, 2019. The LE8 encompasses eight components, each scored from 0 to 100 points, with an unweighted average used to calculate the composite LE8 score, ranging from 0 to 100. Components include diet, physical activity, nicotine exposure, sleep health, body mass index (BMI), blood lipids, blood glucose, and blood pressure. Participants were categorized into low (LE8 < 50) and medium-high CVH (LE8 ≥ 50) groups. A Cox proportional hazards regression model was used to explore the association of LE8 with all-cause mortality.
RESULTS The MASLD cohort’s average LE8 score was 59.6 ± 0.3, with 24% (n = 1014) scoring below 50 and 76% (n = 3217) scoring 50 or above. The three most problematic CVH metrics for MASLD patients, in order of severity, were BMI, diet, and lipids. However, for the LE8<50 group, BMI, diet, and physical activity were the primary concerns. Over a median follow-up of 6.75 years, 483 total deaths occurred. Multivariate Cox regression analysis revealed that MASLD patients with LE8 scores ≥50 exhibited a 26% reduced risk of all-cause mortality compared to those with scores <50 (HR: 0.74, 95% CI: 0.57–0.97, P = 0.030). Each 10-point increase in LE8 score correlated with a 16% reduction in mortality risk (HR: 0.84, 95% CI: 0.75–0.94, P = 0.002). Restricted cubic spline analysis demonstrated a linear decrease in all-cause mortality risk with increasing LE8 score. No significant interactions were found in subgroup analyses by demographic or social characteristics. Sensitivity analyses, excluding patients with existing cardiovascular disease, affirmed the protective effect of higher LE8 scores (HR: 0.66, 95% CI: 0.46–0.94, P = 0.02). Among LE8 components, physical activity, nicotine exposure, sleep health, and blood glucose were negatively correlated with mortality risk (P < 0.05).
CONCLUSIONS This study suggests that adherence to higher LE8 levels is associated with a reduced risk of all-cause mortality in patients with MASLD. Enhancing physical activity, promoting smoking cessation, ensuring healthy sleep, and managing blood glucose may improve long-term prognosis for MASLD patients.
GW35-e0664
Mekhman Mamedov
National Research Center for Therapy and Internal Medicine
OBJECTIVES The aim of this study is to analyze the place of CVD in the structure of mortality and the prevalence of certain risk factors among adults in three countries of the South Caucasus and Turkey.
METHODS Official WHO reports from 2020 were used for the analysis. The populations of Azerbaijan, Armenia, Georgia and Turkey have similar lifestyles and traditions, while the healthcare system and socio-economic system have their own characteristics.
RESULTS The incidence of CHD per 100 thousand population in Azerbaijan was 388.41 cases, and in Turkey this figure is 4 times less – 95.94 cases. Georgia and Armenia occupy intermediate places: 214.9 and 201.5 cases, respectively. An analysis of the contribution of CHD to the structure of adult mortality in 4 countries demonstrates that its share in adult mortality on average is more than 30%. The maximum indicator was found in Azerbaijan – 42.4%, the minimum in Georgia – 31.9%. In Armenia, the contribution of CHD to mortality is 39.6%. In Turkey, every third death among adults is due to complications of CHD. The age-standardized incidence of cerebral stroke per 100 thousand population in Georgia was 159.62 cases, in Azerbaijan 151.52 cases. In Armenia and Turkey, the frequency of cerebral stroke in the mortality structure is 3 times less compared to Georgia and Azerbaijan, and is 48.2 and 49.06 cases per 100 thousand population, respectively. The contribution of cerebral stroke in the structure of mortality in Georgia is ¼ of the case (24%), in Azerbaijan 16%, while in Turkey and Armenia it is 11% and 9%, respectively.
The direct contribution of hypertension to adult mortality in Georgia is 9%, in Turkey 4%, while in Armenia and Azerbaijan its contribution was within 3%. Among adults in 4 countries of the region, men consume the most alcohol in Georgia, with Armenia taking second place. In Turkey and Azerbaijan, men drink several times less alcohol: 1.8 and 1 L, respectively. In 4 countries, every second man smokes. At the same time, in Turkey, every fifth woman smokes; in Georgia, this figure among women is 6.7%. In Armenia and Azerbaijan, tobacco smoking among women was detected in <2% of cases. The highest incidence of obesity was found among women in Turkey, 39.2%. In the countries of the South Caucasus, a high incidence of obesity was found among women and averaged 23.5%. Among men, the highest incidence of obesity was found in Turkey – 24.4%. Among men from the South Caucasus states, the incidence of obesity is in the range of 15.8%–19.2%.
CONCLUSIONS It is obvious that in the countries of the South Caucasus there is a great challenge ahead in reducing the incidence and secondary prevention of CVD among the adult population. The experience of developed countries can serve as an example for these countries in organizing the fight against CVD.
GW35-e0808
Vasily Sukhorukov, Daria Borodko, Andrey Omelchenko, Tatiana Kovyanova, Alexander Orekhov
Institute of General Pathology and Pathophysiology, Moscow, Russia
OBJECTIVES The impairment of human monocytes and macrophages in responding to inflammatory stimulation is a notable aspect of atherosclerosis. In normal circumstances, inflammation should promptly resolve through mechanisms like tolerance developed from repeated stimulation, resulting in lower cytokine secretion during subsequent stimuli. When compromised, this may lead to chronic inflammation. Previous research suggested mitochondrial mutations linked to atherosclerosis contributing to immune response impairment in cytoplasmic hybrids (cybrids) with mutations in mitochondrial DNA (mtDNA). In this study we identified potential master genes that can regulate intolerant immune response.
METHODS Cybrids, with varying mtDNA mutation burdens, underwent 1000 ng/mL LPS stimulation for 4 hours, followed by PBS washing and medium refreshment. A second 20-hour LPS stimulation was applied, and the resulting supernatant was analyzed for TNF, IL-1b, and CCL2 using ELISA. RNA from cybrids, pre- and post-LPS stimulation, was sequenced using Illumina NovaSeq 6000. Transcriptome analysis, using DESeq2 and geneXplain platform, identified DEGs and master regulators with specific parameters (Score > 0.2, FDR < 0.05, Z-score > 1.0) based on assembling interaction networks using GeneWays database.
RESULTS In evaluating the pro-inflammatory response of cybrids, the secretion of four cytokines (CCL2, IL8, IL6, and IL1b) was measured. These specific cytokines were selected due to their distinct roles in the inflammatory response and differing mechanisms in responding to inflammatory stimuli. DESeq2+geneXplain analysis identified DEGs for all 4 cytokines, unveiling dozens of master regulators consistent across them. For intolerant response revealed six up-regulators (ZBTB32, OSM, LBR, IL3, IL16, FANCA) were identified. No common master regulator post-second stimulation was observed.
CONCLUSIONS Six up-regulated master genes (ZBTB32, OSM, LBR, IL3, IL16, FANCA) were identified in intolerant immune responses. These genes may be responsible for chronification of inflammation in atherosclerosis.
This work was supported by Russian Science Foundation Grant # 23-45-00031.
GW35-e0880
Juying Qian1, Mengjun Zhang2, Zhangwei Chen1
1Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
2Hasten Biopharmaceutical Co., Ltd, Shanghai 200124, China
OBJECTIVES Hypertension is a major risk factor and a leading cause of death related to cardiovascular disease (CVD) and stroke. Azilsartan medoxomil has shown superior blood pressure (BP) lowering efficacy with a good tolerability and safety profile. A network meta-analysis was attempted to have an overview on antihypertensive drugs’ efficacy in patients with mild to moderate hypertension.
METHODS A systematic literature search was conducted utilizing the English platforms, from January 2000 until December 2023. A total of 10380 articles were screened. Literature was screened according to the following criteria: 1) Hypertension (mild or moderate); First-line treatment and washout periods; 2) Studies (monotherapy) that included azilsartan medoxomil, angiotensin type II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitor (ARNIs), beta blockers, calcium channel blockers (CCBs), and diuretics, either as intervention or comparator; 3) Antihypertension efficacy and safety as an outcome measure; and 4) Study design was randomized clinical trials. Efficacy variables included absolute systolic and diastolic BP reductions in the office between 4 and 12 weeks of treatment. Following transitivity assessment, a total of 21 of publications provided adequate data for analysis, of which 20 studies reported both SBP and DBP and 1 study reported only the diastolic BP.
RESULTS In 21 studies on office systolic BP, against the common comparator placebo, the differences in systolic BP were significantly in favor of azilsartan medoxomil, amlodipine (5 mg, 10 mg), candesartan (8 mg), irbesartan (150 mg), nebivolol (5 mg, 20 mg), nifedipine (20 mg), olmesartan (20 mg, 40 mg), sacubitril valsartan (100 mg, 200 mg), telmisartan (80 mg), and valsartan (80 mg, 160 mg). The surface under the cumulative ranking curve (SUCRA) ranking shows that azilsartan medoxomil 80 mg had the highest ranking, with a possibility of 93% being the best in all other included treatments. In 20 studies on diastolic BP, against the common comparator placebo, the differences in diastolic BP were significantly in favor of azilsartan medoxomil (40 mg, 80 mg), amlodipine (10 mg), bisoprolol (5 mg), nebivolol (5 mg, 10 mg, 20 mg), olmesartan (40 mg), sacubitril valsartan (100 mg, 200 mg), telmisartan (80 mg), and valsartan (80 mg, 160 mg). Similar to the systolic results, the SUCRA ranking shows that azilsartan medoxomil 80 mg had the highest ranking, with a possibility of 90% being the best in all other included treatments.
CONCLUSIONS Azilsartan medoxomil at 40 mg and 80 mg shows favorable efficacy compared to other anti-hypertensives, and the 80 mg dosage seemed to be most efficacious of all the included treatments in reducing both office measurement of systolic and diastolic BP in patients with mild to moderate hypertension.
GW35-e1044
Miao Yuan1, Hanxue Wu2, Jiawei Wang2, Jiaxi Xu2, Dengfeng Gao1
1The Second Affiliated Hospital of Xi’an Jiaotong University
2School of Basic Medicine Sciences, Xi’an Jiaotong University
OBJECTIVES Cardiovascular disease is one of the leading causes of death worldwide, causing a heavy burden of disease. In recent years, sodium glucose cotransporter 2 inhibitors (SGLT2i) have been mainly used in the treatment of heart failure in cardiovascular diseases and their mechanism for improving cardiac remodeling is not yet clear. This study constructed a model of cardiac remodeling through DOCA+salt to explore the mechanism by which empagliflozin improves cardiac remodeling by inhibiting excitatory output from the sympathetic center.
METHODS Improvement on cardiac remodeling of empagliflozin was comprehensively evaluated through echocardiography, heart weight, HE staining, MASSON staining, WGA staining and the expression level of Collagen III in cardiac tissue. The possible mechanism of empagliflozin improving cardiac remodeling was clarified by detection of blood sodium, plasma osmotic pressure and hematocrit (HCT) levels; sympathetic neural activity and cardiac sympathetic nerve activity were determined by measuring urinary NE levels and cardiac TH staining. Activation of the sympathetic center was determined by c-Fos staining of hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM). The effect of empagliflozin on different types of cells in the sympathetic center and the possible mechanism of its inhibition of excitatory output of the sympathetic center were explored by single cell RNA-sequencing of PVN.
RESULTS Empagliflozin can improve the degree of cardiomyocyte hypertrophy and cardiac fibrosis in mice with the DOCA+ salt model, especially the fibrosis around small blood vessels of the heart. It can also reduce left ventricular mass and increase LVEF, which improves cardiac remodeling and cardiac function. Empagliflozin does not have a significant effect on peripheral blood sodium and plasma osmolality, but it can increase HCT levels. Empagliflozin also reduces levels of sympathetic neural and cardiac sympathetic activation. The c-Fos staining of PVN and RVLM showed that empagliflozin reduced activation of the sympathetic center. Through scRNA-Seq, it was found that empagliflozin can reduce the adhesion of endothelial cells to immune cells and reduce the activation of microglia. This was verified by measuring peripheral lymphocyte counts, detecting inflammatory factors (IFN-γ and MCP-1) and analyzing the number of activated microglia cells in the PVN region. Empagliflozin has the effect of reducing the gene expression level of neuropeptides related to water-sodium balance metabolism in the PVN, which was verified by testing the co-peptin level in peripheral blood.
CONCLUSIONS Empagliflozin can reduce sympathetic neural activity and cardiac sympathetic nerve activity and improve cardiac remodeling. It can also reduce the adhesion of endothelial cells to immune cells in the PVN, inhibit the activation of microglia, and reduce excitatory output in the PVN. Additionally, empagliflozin can participate in water-sodium balance metabolism by regulating neuropeptides in the PVN.
GW35-e1052
Xiaowei Chen1,2, Haiqing Zhang3,4,5, Lijia Liu1,2, Zuoxiang Liu1,2, Houyu Zhao6, Shizhan Ma3,4,5, Meng Zhao3,4,5, Chen Chen7, Yanxin Chen7, Peng Shen8, Yexiang Sun8, Hongbo Lin8, Siyan Zhan1,2, Jiajun Zhao3,4,5, Feng Sun1,2
1Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
2Key Laboratory of Major Disease Epidemiology, Ministry of Education (Peking University), Beijing 100191, China
3Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
4Shandong Clinical Medical Centre of Endocrinology and Metabolism, Jinan, Shandong 250021, China
5Shandong Institute of Endocrine and Metabolic Disease, Jinan, Shandong 250021, China
6School of Medicine, Chongqing University, Chongqing 400044, China
7Merck Serono Co., Ltd., Beijing, China, an affiliate of Merck KGaA
8Yinzhou District Center for Disease Control and Prevention of Ningbo, Ningbo 315100, China
OBJECTIVES Levothyroxine is a common treatment for hypothyroidism and may improve the disease outcomes of patients with comorbid cardiovascular disease (CVD). However, evidence on the protective effects of levothyroxine against adverse. Cardiovascular events in patients with hypothyroidism are inconsistent. This study aimed to assess the effectiveness of levothyroxine, as compared with non-levothyroxine, in preventing adverse cardiovascular events and death in patients with hypothyroidism and CVD.
METHODS This is a non-interventional, retrospective study based on medical record data from the Yinzhou Medical & Health Big Data Platform, a regional longitudinal database in Zhejiang, China. Patients who were newly diagnosed with hypothyroidism between July 2006 and December 2021 and had pre-existing CVD at the time of their first hypothyroidism diagnosis were included in the analysis. Levothyroxine users were defined as patients given at least two prescriptions of levothyroxine with 6 ± 3 months in between. Propensity score matching was performed to match levothyroxine users to non-users on a 1:1 basis. Comparison on the risk of outcomes between users and non-users were assessed using Cox proportional hazards models. Hazard ratios (HRs) with 95% confidence intervals were reported. The primary outcome measure included 3-point major cardiovascular events (3P-MACE, comprised of cardiovascular death, non-fatal myocardial infraction, and stroke). Secondary outcome measures included all-cause death, all-cause hospitalization and cardiovascular related hospitalization.
RESULTS A total of 5845 patients were included (age of 65.2 ± 15.3 years, 60.4% female), of whom 1332 (22.8%) were treated with levothyroxine. In the matched population (n = 1332 in each group), 1285 patients had 3P-MACE during a median follow-up of 3.22 years. Patients treated with levothyroxine displayed significantly decreased risk of 3P-MACE (adjusted HR, 0.75; 95% CI, 0.58~0.95, P = 0.02), all-cause death (adjusted HR, 0.28; 95% CI, 0.17~0.46, P < 0.01), all-cause hospitalization (adjusted HR, 0.27; 95% CI, 0.23~0.31, P < 0.01), and cardiovascular related hospitalization (adjusted HR, 0.74; 95% CI, 0.60~0.92, P < 0.01) when compared with patients not treated with levothyroxine.
CONCLUSIONS Levothyroxine might improve the major adverse cardiovascular outcomes and reduce all-cause hospital admissions in patients with hypothyroidism and cardiovascular disease.
GW35-e1060
Alexandra Aseeva, Daria Nedbaeva, Anastasia Filatova, Galina Kukharchik
Almazov National Medical Research Centre
OBJECTIVES To highlight the diagnostic process, treatment strategies, and follow-up results of a young patient with acute coronary syndrome (ACS) and cardiometabolic syndrome, demonstrating the efficacy of an integrated and multidisciplinary approach.
METHODS A 41-year-old female patient was admitted to the intensive care unit with a history of continuous, recurrent chest pain for a week. The electrocardiogram (ECG) demonstrated a loss of normal R-wave progression from V1 to V5 and T-wave inversion in leads I and aVL. The patient had a history of uncontrolled hypertension and obesity (body mass index of 34.4 kg/m2). Echocardiography revealed eccentric left ventricular hypertrophy with apex akinesia, hypokinesia of the anterior, anterolateral wall, and interventricular septal middle and apical segments, with a left ventricular ejection fraction (LVEF) of 33%. High-sensitive troponin was elevated. Given the clinical presentation and diagnostic findings, myocardial infarction was suspected. An urgent coronary angiography revealed significant stenosis in the left anterior descending artery. A drug-eluting stent was implanted, resulting in complete revascularisation.
The postoperative course was uneventful. Further laboratory tests were conducted, indicating uric acid levels of 489 mmol/L, glucose levels of 6.7 mmol/L, HBA1c levels of 6.2%, total cholesterol (TC) levels of 6.6 mmol/L, triglyceride levels of 3.18 mmol/L, and low-density lipoprotein (LDL) levels of 4.00 mmol/L. The treatment plan included the management of hypertension to achieve target blood pressure, the initiation of high-dose statin therapy, the administration of heart failure therapy and the prescription of medications to reduce uric acid levels. Furthermore, we consulted with the patient regarding smoking cessation and increasing regular physical activity. The patient was also evaluated by a clinical psychologist for increased anxiety, receiving cognitive-behavioral therapy.
RESULTS After discharge, the patient underwent a rehabilitation program, returned to work, and continued outpatient monitoring. Following a three-month period, the patient demonstrated a significant clinical improvement. This included a weight reduction from 103 to 90 kg, a BMI decrease from 34.4 to 30.0 kg/m2, an LVEF increase to 54%, and an improved lipid profile (TC 3.4 mmol/L, LDL 1.9 mmol/L, TG 1.28 mmol/L). Subsequent echocardiographic examination revealed an LVEF of 54%, with no evidence of persistent akinesia or hypokinesia.
CONCLUSIONS This case study illustrates a remarkable response to treatment despite delayed medical attention and extensive myocardial injury. Significant improvements in metabolic health and cardiac function were observed, facilitated by a personalised multidisciplinary approach, proactive lifestyle adjustments, and strong patient compliance. These interventions are expected to result in long-term improvements in prognosis. Consequently, the administration of an appropriate complex treatment, coupled with patient motivation and high compliance, can result in favourable outcomes within a relatively brief timeframe.
GW35-e1069
Ryuya Naruta1, Yasufumi Katanasaka1,2,3, Yuto Kawase1, Yoichi Sunagawa1,2,3, Toshihide Hamabehoriike1,2,3, Koji Hasegawa2, Tatsuya Morimoto1,2,3
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka
2Division of Translational Research, Kyoto Medical Center
3Shizuoka General Hospital
OBJECTIVES The number of patients with chronic kidney disease is increasing with the aging of society. Chronic kidney disease (CKD) is considered to be a pre-stage renal failure, and treatment and prevention of CKD are important clinical issues for overcoming severe renal failure. CKD is caused by a complex combination of various pathologies, and it is known that fibrosis occurs as a common pathology. Fibrosis induced by renal damage is irreversible and leads to renal failure. However, no effective therapeutic agent has been developed. In recent years, research on the preventive effects and functionalities of food ingredients against chronic diseases, such as anti-inflammatory effects, has progressed. Zerumbone, a major active terpene in the endemic wild ginger species, has various physiological activities, including antitumor and anti-inflammatory effects. However, the anti-fibrotic action of Zerumbone is unknown. In this study, we examined the pharmacological effects of Zerumbone on renal fibrosis.
METHODS To examine the effects of Zerumbone on cultured kidney fibrosis, we used the rat renal interstitial fibroblasts cell line NRK-49f. These cells were pretreated with Zerumbone and then stimulated with 5 ng/mL TGF-β for 24 h. The mRNA levels of the genes associated with fibrosis, Col3a1, alpha-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) were measured by qRT-PCR. The protein expressions were assessed by western blotting. Next, 8–10-week-old male C57BL/6j mice were subjected to a unilateral ureteral obstruction (UUO) model, reproducing the pathological characteristics of renal fibrosis, and a sham operation was performed as a control. The UUO mice were orally administered Zer (30, 100 mg/kg/day) or vehicle every day from the day after surgery. Seven days after surgery, the mice were sacrificed, and histological analysis and mRNA expression levels of fibrosis-related genes were examined by qRT-PCR.
RESULTS The mRNA and protein levels of fibrotic markers were significantly increased by TGF-β, but these increases were suppressed by Zer treatment in NRK-49f cells. Picrosirius Red staining showed that the fibrosis was significantly increased in the UUO vehicle group compared to the sham group. This increase was significantly suppressed by the Zer administration. In addition, the qRT-PCR results showed that Zer significantly inhibited the UUO-induced increase in the expression levels of fibrosis-related genes.
CONCLUSIONS These results indicated that Zer suppresses TGF-β-induced fibrotic response and UUO-induced renal fibrosis. Zer may have anti-fibrotic effects and be used to prevent and treat CKD accompanied by fibrosis.
GW35-e1070
Vasily Sukhorukov1, Elizaveta Ponomarchuk2, Mariam Bagheri Ekta3
1Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
2Institute of Physics and Technology, Moscow, Russian Federation
3Petrovsky National Research Centre of Surgery, Moscow, Russian Federation
OBJECTIVES ATF6 is a key regulator in macrophages during the progression of plaques leading to atherosclerosis through its control over endoplasmic reticulum (ER) stress, inflammatory responses, lipid metabolism, and survival. Upon ER stress, ATF6 activation may enable macrophages to survive the harsh plaque microenvironment to maintain cellular function. However, if ER stress is chronic or non-resolving, it can promote apoptosis and perpetuate inflammation, potentially accelerating atherosclerosis. A comprehensive elucidation of the specific mechanisms by which ATF6 exerts these effects may yield therapeutic targets for atherosclerosis. Modulating ATF6 activity could potentially alleviate ER stress, enhance macrophage function, and stabilize atherosclerotic plaques. In our study, we assessed the influence of ATF6 knockout on the cholesterol accumulation ability of macrophages.
METHODS The knockout was confirmed with qPCR. To assess cholesterol accumulation, the PMA-differentiated THP-1 cells with and without ATF6 knockout were incubated with and without atherogenic LDL for 24 hours. Cholesterol accumulation was measured by spectrophotometry and normalized on cellular protein.
RESULTS Two THP-1 cell lines with ATF6 knockout were created. ATF6 knockout in the obtained clone was confirmed by qPCR and Sanger sequencing. Using these cells, we found that the knockout of ER related ATF6 gene prevented cholesterol accumulation in THP-1 cells after incubation with modified LDL.
CONCLUSIONS The endoplasmic reticulum-related ATF6 gene appears to play a role in macrophage cholesterol metabolism. The knockout of this gene can prevent cholesterol accumulation in macrophages.
This work was supported by the Russian Science Foundation #24-45-20004.
GW35-e1082
Masaru Sudo1, Yuto Kawase1, Satoshi Shimizu1, Toshihide Hamabehoriike1,2,3, Yoichi Sunagawa1,2,3, Masafumi Funamoto1,2, Ryuya Naruta1, Yasufumi Katanasaka1,2,3, Koji Hasegawa1,2, Tatsuya Morimoto1,2,3
1Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka
2Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto
3Shizuoka General Hospital, Shizuoka
OBJECTIVES The p300/GATA4 pathway is involved in the development of heart failure. However, the precise regulation mechanism of transcriptional activation by GATA4 is unknown. This study aimed to investigate whether GATA4 multimerization is involved in transcriptional activation during the development of cardiomyocyte hypertrophy.
METHODS A GST pull-down assay was performed to investigate whether GATA4 forms a dimmer. Next, deletion mutants were used to identify GATA4’s binding sites. HEK293T cells were co-transfected with FLAG-GATA4 and HA-GATA4. Nuclear extracts prepared from these cells were immunoprecipitated (IP) with anti-FLAG antibody followed by Western blotting (WB). Since residues 308–326 of GATA4 include lysines that are acetylated by p300, we investigated the relationship between p300 and the multimerization of GATA4. HEK293T cells were transfected with ANF-luc or ET-1-luc in addition to p300 and GATA4, and a reporter assay was performed. To elucidate whether the acetyltransferase activity, scaffold function, and bridge function of p300 play crucial roles in the multimerization of GATA4, HEK293T cells were transfected with the acetyl-deficient GATA4 or HAT-deficient p300, proteins form these cells were extracted, and IP-WB was performed. To determine the effect of the deletion mutant containing GATA4 308–326 (GMP) on GATA4 multimerization, HEK293 cells were transfected with GMP, GATA4, and p300. Proteins were extracted and subjected to the IP-WB, chromatin immunoprecipitation, and DNA pulldown assay. Next, to investigate whether GMP suppresses the hypertrophic response, cultured cardiomyocytes were transfected with GMP, followed by phenylephrine (PE) stimulation. Finally, to investigate whether GATA4 dimerization plays an important role during the development of heart failure in vivo, we generated genetically modified mice in which 3xFLAG or 3xMyc tags were knocked in (KI) at the C-terminus of endogenous GATA4 using the CRISPR/Cas9 system.
RESULTS GST pull-down assay revealed that GATA4 binds itself, amino acids 308–326 are required for this binding, and IP-WB revealed that FLAG-GATA4 binds HA-GATA4. A reporter assay revealed that p300 enhanced the promoter activities of ANF and ET-1. GATA4 self-association was disrupted by both acetyl-deficient GATA4 and HAT-deficient p300. GMP overexpression prevented p300-induced GATA4 self-association. However, chromatin immunoprecipitation and DNA pulldown assays showed that GMP did not inhibit p300-induced DNA binding of GATA4. In cultured cardiomyocytes, the inhibition of GATA4 self-association using GMP suppressed PE-induced hypertrophic transcriptional activity and cardiomyocyte hypertrophy. We confirmed 3xFLAG/3xMyc GATA4 could be detected in the genome.
CONCLUSIONS These results suggest that p300-induced acetylation of GATA4 increased its self-association, transcriptional activity, and cardiomyocyte hypertrophy. Moreover, inhibition of GATA4 multimerization suppressed transcriptional activation of GATA4 and cardiomyocyte hypertrophy. To investigate whether GATA4 multimerization increases during heart failure, we will perform transverse aortic constriction (TAC) surgery on KI mice. Future investigation of compounds that inhibit GATA4 multimerization may lead to the development of novel heart failure therapies.
GW35-e1233
Yang Zhao1,2, Katie Harris1
1The George Institute for Global Health, University of New South Wales, Australia
2The George Institute for Global Health, Beijing, China
OBJECTIVES Multiple chronic diseases could have a lasting impact on cognitive function in later life through biological and socioeconomic pathways. The aim of this study was to determine associations of cardiometabolic multimorbidity (CMM) and dementia.
METHODS The UK Biobank is a large-scale prospective population-based cohort study of 500,000+ women and men aged 40–69 years recruited between 2006 and 2010. CMM was defined at baseline as presence of ≥2 chronic cardiovascular and/or metabolic conditions: hypertension, hyperlipidaemia/dyslipidaemia, diabetes, hyperuricaemia, central obesity, heart disease, and stroke. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) of CMM and incident dementia, adjusting for sociodemographic factors.
RESULTS There were 7129 (47.8% women) with incident dementia (median 12.7 years follow-up) in 480,462 UK Biobank participants without dementia at baseline. There was a 30% higher risk of incident dementia with CMM (vs. no CMM) similarly in women HR (95% CI) 1.31 (1.22, 1.41), and men 1.32 (1.22, 1.42). In subgroup analysis, CMM was associated with a higher risk of dementia in participants who were young (<60 years) and with greater socioeconomic disadvantage, and obesity. Of the seven cardiometabolic conditions, stroke (vs. no stroke) was associated with twice the risk of dementia, similarly in women 1.98 (1.68, 2.08) and men 2.08 (1.84, 2.36).
CONCLUSIONS CMM is associated with a higher risk of dementia, particularly in younger adults and those with low socioeconomic status and obesity. Timely identification of CMM and preventing disease accumulation might improve cognitive function and prevent dementia.
GW35-e1266
Rujie Zheng, Wenjuan Song, Chengzhi Lu
Tianjin First Central Hospital
OBJECTIVES Coronary artery disease (CAD) and atherosclerosis pose significant global health challenges, with intricate molecular changes influencing disease progression. Recent research has shown that monocytes play an important role in the development of atherosclerosis and CAD. In addition, disruptions in mannose metabolism may be closely linked to the onset and progression of CAD. Therefore, we investigate the crucial role of mannose metabolism in the pathogenesis of CAD mediated by monocytes.
METHODS Firstly, we utilized GWAS data on coronary artery disease (CAD), 486 metabolites, and 711 immune cell types to conduct a two-step Mendelian randomization analysis to determine the mediating effects. Next, we downloaded a single-cell RNA sequencing dataset (GSE202625) from the GEO database. After dimensionality reduction and clustering, we selected the HLA-DR+ monocyte subset for further analysis. We scored the monocytes based on their mannose metabolism gene sets, dividing the cells into high mannose metabolism and low mannose metabolism groups. Differential gene enrichment analysis was then performed between these groups. These identified differential genes were underwent GSEA enrichment analysis and then validated across multiple bulk RNA sequencing datasets. We used LASSO regression to screen for significant differential genes and conducted immune infiltration analysis. For the prediction model construction, we employed three machine learning methods: CatBoost, NGBoost, and XGBoost. To interpret the results of the machine learning models, we calculated SHAP values.
RESULTS Mendelian randomization analysis identified 16 SNPs associated with mannose, among which 5 SNPs were related to HLA-DR++ monocytes. These SNPs demonstrated protective effects against coronary artery disease (CAD). Mediation analysis indicated that the protective effect of monocytes on CAD is partially mediated through mannose. By scoring monocyte subsets based on mannose metabolism gene sets, cells were categorized into low metabolism and high metabolism groups. A total of 272 differentially expressed genes were identified between these groups. The two groups exhibited distinct transcription factor expression patterns. Gene set enrichment analysis (GSEA) revealed that the differentially expressed genes were predominantly enriched in pathways such as immunoglobulin production involved in immunoglobulin-mediated immune response, ATP metabolic process, monocyte chemotaxis, and monosaccharide catabolic process. LASSO regression identified 7 key genes: PTPRJ, NAMPT, DDIT4, CD83, CUX1, TREM1, and NOD2. Trajectory analysis showed that as mannose metabolism increased, monocytes gradually transitioned from immature to mature macrophages. Among the three machine learning algorithms (NGBoost, XGBoost, CatBoost), NGBoost exhibited the best predictive performance with an AUC of 0.7. SHAP values were calculated to interpret the results of the machine learning models, highlighting the importance of the identified key genes in predicting CAD outcomes.
CONCLUSIONS In this study, we revealed that mannose metabolism in monocytes influences the development of CAD, suggesting the need to focus on the role of mannose metabolism in monocyte-mediated CAD pathogenesis in future research. Overall, the relationship between monocytes, mannose, and CAD represents a promising area of investigation. Further exploration of these relationships will not only enhance our understanding of CAD pathophysiology but also potentially provide new avenues for the development of novel prevention and treatment strategies.
GW35-e1325
Jie Zhang
General Hospital of Northern Theater Command
OBJECTIVES To investigate the effects of ablation parameters such as base impedance, power, and irrigation rate on lesion dimensions with radiofrequency catheter ablation (RFCA) by different ablation catheters.
METHODS Under the irrigation rate (8, 17, 30 mL/min), RFCAs were performed on ex-vivo porcine left ventricle submerged in 36–37 °C half-normal saline (HNS) by SmartTouch™ SF (ST-SF) catheter and TactiCath™ Quartz (TCQ) catheter. Ablation duration, contact impedance, lesion dimension and other parameters were recorded and analyzed.
RESULTS For 80 ablation lesions were performed. 1) There were no significant differences in the ablation lesion dimensions of the ST-SF catheters with different irrigation rates. For the TCQ catheters, irrigation rates were positively correlated with the ablation duration (r = 0.665, P = 0.008), but negatively correlated with the maximum width and the maximum depth (r = −0.782, P < 0.001. r = −0.789, P < 0.001). 2) For a given target AI/LSI, the maximum widths (ST- II SF: 5.91 ± 0.10 mm vs. 5.68 ± 0.04 mm, P = 0.001. TCQ: 8.27 ± 0.22 mm vs. 7.51 ± 0.40 mm, P = 0.005) and the maximum depth (ST-ST: 3.63 ± 0.07 mm vs. 3.15 ± 0.14 mm, P < 0.001. TCQ: 5.00 ± 0.04 mm vs. 4.25 ± 0.03 mm, P < 0.001) with 0.45% NaCl solution (semi-normal saline) for irrigation and were larger than that of 0.9% NaCl solution (normal saline). 3) AI was 400, the contact angles between the ST-SF catheters and the tissues did not strongly affect the lesion dimensions. LSI was 5, the contact angles of TCQ catheter had negative impact on the maximum width (r = −0.946, P < 0.001) and ablation duration (r = −0.816, P < 0.001) show negative correlation with the maximum depth (r = −0.832, P < 0.001).
CONCLUSIONS Irrigation rate, which has no influences on the ablation lesion dimensions of the ST-SF catheters, is negatively correlated with the TCQ catheters. Compared with 0.9% NaCl solution, the lesion dimensions of the two kinds of catheters with 0.45% NaCl solution for irrigation and were larger. For the TCQ catheters, the greater contact angles, the wider the maximum width of ablation lesions. Whereas, the contact angles have no significant effect on the lesion dimensions for the SF-ST catheters.
GW35-e1326
Jie Zhang
General Hospital of Northern Theater Command
OBJECTIVES War and natural disasters often occur suddenly and are associated with a high incidence of cardiovascular disease and vascular trauma. Interventional and minimally invasive surgical treatments are accepted as effective treatments, but several high-tech medical devices have not yet been applied to pre-hospital emergencies due to factors such as high equipment dependency. This study focuses on the impact and feasibility of using a miniature mobile integrated operating theatre and explores its therapeutic scope, effectiveness and mode.
METHODS The miniature mobile integrated operating theatre were transported to several hospitals in different locations to perform clinical procedures, from April 2012 to March 2024. Surgical outcomes and perioperative complications were observed and the stability, adaptability and mobility of the miniature integrated operating theatre were evaluated.
RESULTS A total of 101 procedures were successfully performed, 98 of which were interventional and 3 of which were minimally invasive. The interventional machine showed good imaging performance and there were no surgical equipment crashes with normal chamber unfolding, no fixed equipment loosening or damaging. One patient had a fever the day after laparoscopy, while other patients had no perioperative complications such as infection, surgical site bleeding/hematoma or reperfusion arrhythmia. The instrument is easily manipulated and can be in line with the needs of clinical surgery and it is perceived by patients to be a comfortable environment in the theatre, with no depressions or other obvious discomfort.
CONCLUSIONS The miniature mobile integrated operating theatre allows interventional or minimally invasive surgical procedures to be performed smoothly, providing on-spot, rapid and efficient treatment of acute and critical illnesses across multiple systems, including cardiovascular, cerebrovascular and gastrointestinal.
GW35-e1374
Zhiyun Yang1, Yingying Ge2, Rui Zuo3, Jingjia Wang1, Wenyao Wang1, Chunli Shao1, Chun Chang2, Yida Tang1
1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China
2Department of Respiratory and Critical Care Medicine, Peking University Third Hospital; Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing 100191, China
3Information Management and Big Data Center, Peking University Third Hospital, Beijing 100191, China
OBJECTIVES Asthma and cardiovascular diseases (CVDs) are intricately linked due to their widespread prevalence and shared pathophysiological processes. Patients who have experienced asthma exacerbation, persistent asthma, or asthma-chronic obstructive pulmonary disease overlap face elevated risks of morbidity and mortality from CVDs. This risk is exacerbated in cases of type 2 asthma, a common phenotype of severe asthma, leading to accelerated progression of CVDs.
BACKGROUNDS AND METHODS Allergic asthma and CVDs may share common and interactional pathogenic mechanisms. Mast cells, eosinophils, inflammatory cytokines, and IgE accumulate in the lung tissue of allergic asthma and cardiovascular diseases. Studies have revealed that exacerbated atherosclerosis in allergic asthma is partly mediated by IL-4 and IL-17. Moreover, the release of IL-4 from activated mononuclear leukocytes exhibits a negative correlation with clinical atherosclerosis. Additionally, IgE contributes to plaque progression through M1 macrophage polarization, foam cell formation, and vascular cell apoptosis. However, IL-5 and IL-13 have been shown to have a protective effect on atherosclerosis. Therefore, it becomes evident that type 2 inflammation plays a dual role, both aggravating and improving CVD complicated with asthma.
RESULTS Type 2 inflammation expedite the progression of CVDs. Type 2 asthma caused by type 2 inflammatory is a prevalent phenotype of severe asthma. According to Korean health check-up data, AR (HR = 1.11 [95% CI: 1.10–1.13]) and AD (HR = 1.14 [95% CI: 1.06–1.24]) are identified as risk factors of myocardial infarction. Moreover, moderate-to-severe AD has been associated with increased vascular inflammation and heart disease. However, it is worth noting that type 2 inflammation exhibits a protective effect on CVDs. Studies on type 2-mediated inflammation have demonstrated that elevated numbers of TH2 cells correlate with decreased common carotid intima-media thickness and a lower risk of acute myocardial infarction. Additionally, the release of the TH2 cytokine interleukin (IL)-4 has been associated with a reduced risk of CVDs. Furthermore, type 2 cytokines such as IL-5 and IL-13 possess protective effects on CVDs. Experimental studies have suggested that IL-5 may play an atheroprotective role by stimulating the expression of immunoglobulin M antibody expression and inhibiting carotid plaque formation. The connection of type 2 inflammation between asthma and CVDs appears to play a dual role, actively and negatively impacting the clinical outcomes of CVDs complicated with asthma.
CONCLUSIONS CVDs with allergic asthma present a notably high incidence and all-cause mortality. Type 2 inflammation emerges as a potential clinical bridge, playing a dual role in CVDs complicated with asthma. Anti-asthmatic drugs targeting type 2 immunity offer therapeutic potential in treating CVDs, yet they also entail safety risks. In the future, It is significant and necessary to unravel the intricate mechanisms underlying the relationship between asthma and CVDs and evaluate the treatment value of anti-inflammatory biological agents on the outcome of CVDs.