BASIC AND TRANSLATIONAL MEDICINE
BASIC RESEARCH OF CARDIOVASCULAR DISEASE
GW34-e0013
Yang Yang
Northwest University
OBJECTIVES Sepsis is a major health threat and often results in heart failure as a major endpoint. Growth arrest-specific gene 6 (GAS6) participates in immune regulation and inflammation through binding to the TAM receptor family. This study was designed to examine the cardioprotective role of GAS6 in sepsis.
METHODS ELISA and single-cell RNA sequencing, immunohistochemical analysis or qPCR were performed to assess GAS6 levels in cardiomyocytes from patients and mice with sepsis. Mice with GAS6 overexpression/knockout and cardiomyocytes with high/low expression of GAS6 were constructed to discern the possible role of GAS6 in septic myocardial injury. Next, the involvement of NLRP3 in GAS6-induced septic myocardial injury responses, if any, was determined. Finally, the cardioprotective effects of vitamin K1 (VK1), a safe and effective GAS6 agonist screened from FDA library, was evaluated in sepsis.
RESULTS Serum GAS6 levels were increased in septic patients and mice while myocardial GAS6 level was decreased in septic mice and patients. Single-cell RNA sequencing further revealed a decline in GAS6 levels in nearly all cell clusters including cardiomyocytes. GAS6 overexpression overtly improved cardiac dysfunction and injury in CLP-challenged mice, along with alleviated mitochondrial injury, endoplasmic reticulum stress, oxidative stress, and apoptosis. However, GAS6-elicited beneficial effects were partially removed by GAS6 knockout. NLRP3 served as a downstream effector for GAS6-initiated myocardial benefits. GAS6 knockout led to elevated levels of NLRP3 and cytokines, the effect of which was reconciled by GAS6 overexpression. Vitamin K1, a safe and effective GAS6 agonist, was identified from the FDA-approved drug library and possessed anti-sepsis myocardial injury through regulation of GAS6/NLRP3 signaling.
CONCLUSIONS These results revealed the therapeutical potential of targeting GAS6/NLRP3 signaling in the management of heart anomalies in sepsis.
GW34-e0020
Liu Yang1, Deng Jing2, Piao Chunmei1
1Beijing Anzhen Hospital Affiliated to Capital Medical University
2Beijing Institute of Heart Lung and Blood Vessel Diseases
OBJECTIVES Pulmonary hypertension (PH) seriously affects the health of patients. We have found in clinical studies that PH has adverse effects on both maternal and offspring.
METHODS Twenty-four SPF C57 mice aged 7–9 weeks, including 12 females and 12 pregnant mice, were selected and further divided into 4 groups with 6 mice in each group according to random number table method: ① Female mice with normal oxygen; ② Female mice with hypoxia/SU5416; ③ Pregnant mice with normal oxygen; ④ Pregnant mice with hypoxia/SU5416. All mice were fed and water freely, two groups of mice were fed in normal oxygen environment, the other two groups of mice with hypoxia/SU5416 were fed in a low oxygen chamber, and nitrogen was continuously injected into the chamber. The controller sensed the oxygen concentration in the chamber through the probe and adjusted the nitrogen intake in real time to maintain the oxygen concentration at 10%. Avoid mice suffocation. SU5416 was injected subcutaneously twice a week, 20 mg/kg. At the same time, water and substrate were replaced, nitrogen was replaced, oxygen content was maintained at 10%, and weight and death of mice were monitored. Considering that the mice delivered at 21 days, 19 days of gestation before delivery was selected as the experimental end point to detect weight, right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI).
RESULTS There was no significant difference in RVSP and RVHI between female and pregnant mice under the same condition. Compared with normal oxygen condition, two groups of mice in hypoxia/SU5416 had poor development, RVSP and RVHI were significantly increased, the number of fetal mice was small, hypoplasia, degeneration and even abortion.
CONCLUSIONS The model of mice PH was successfully established. PH affects the development and health of female and pregnant mice, and seriously affects the fetuses.
GW34-e0025
Xiaodong Jing
The Second Affiliated Hospital of Chongqing Medical University
OBJECTIVES Epicardial cells (EpiCs) are a group of progenitor cells with multi-differentiation potential. But this differentiation potential is quiescent in adulthood. Our objective is to investigate the effects of extracellular matrix (ECM) Agrin on epicardial cells activation and proliferation after myocardial infarction (MI) in mice.
METHODS Mouse myocardial infarction models were constructed and primary mouse embryonic epicardial cells were cultured. The dynamic changes of myocardial Agrin was determined during heart development and after myocardial infarction in mice. Then, we determined the role of myocardial injection of recombinant rat Agrin (rrAgrin) on EpiCs activation and proliferation followed by 1, 3, 5, 7 and 14 days after MI in mouse models.
RESULTS Agrin in myocardium declined from embryonic to adult in mice. Agrin in sub-epicardium decreased significantly in the early stage after MI, but then significantly increased. The myocardial injection of rrAgrin significantly upregulated the epicardial activation marker Tbx18 and Wt1, and the proliferation markers Ki67, PH3, Aurora B and Brd U after MI. Agrin significantly thickened the epicardium by promoting EpiCs proliferation, and the increased EpiCs may migrate into myocardium. In addition, Agrin can also promoted the proliferation and migration of EpiCs by binding to its receptor α-dystroglycan (α-DAG) in vitro.
CONCLUSIONS Myocardial Agrin changes dynamically during heart development and after cardiac injury. Agrin may bind to its receptor α-DAG to promote activation, proliferation, and migration of EpiCs after MI.
GW34-e0043
Dingqian Liu
Zhongshan Hospital, Fudan University
OBJECTIVES Cardiomyocytes autophagy plays a key role in prevention of heart failure (HF), identification of key autophagy-related genes is particularly important to further study the pathological features of HF.
METHODS In this study, autophagy-related genes (ARGs) and HF-related datasets (GSE21610 and GSE57345) were extracted from the human autophagy database and gene expression omnibus (GEO) database, respectively. Firstly, the differentially expressed genes (DEGs) between HF and normal control (HC) samples were screened by “limma”. Secondly, the HF-related genes (module genes) were identified by weighted gene co-expression network analysis (WGCNA). Then, the common genes were obtained by intersecting the DEGs, module genes and ARGs. Besides, the function enrichment analyses of these common genes were conducted by “ClusterProfiler”. Then, the key genes were calculated and identified by both training dataset (GSE21610) and validation dateset (GSE57345). Moreover, the gene set enrichment analysis (GSEA) and immune cell infiltration analysis were performed to reveal the partial molecular mechanisms. Furthermore, the targeted drugs of key genes were predicted in Drug-Gene Interaction database.
RESULTS Five common genes associated with autophagy and catabolic process were obtained by intersecting 447 DEGs, 6370 module genes and 222 ARGs. BNIP3L, CDKN1BI and HIF1A were the key genes of HF, which were associated with endocytosis, lysosome, protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and etc. Besides, HIF1A and BNIP3L were significantly negative associated with the proportion of monocytes. Furthermore, Epoetin alfa and Tretinoin were special drugs synchronously associated with CDKN1B and HIF1A.
CONCLUSIONS This study revealed the potential molecular mechanisms of autophagy-related genes in HF, which could provide novel insights for the clinical diagnosis and treatment of HF.
GW34-e0066
Jiachun Xia1, Yanan Pang1, Chenshan Gao2, Lei Hou1
1Institute of Cardiovascular Diseases, Tongren Hospital, Shanghai Jiao Tong University School of Medicine
2Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University
OBJECTIVES To explore the effects and potential mechanisms of PCSK9 on ventricular remodeling after myocardial infarction.
METHODS Mouse were used to construct a model of acute myocardial infarction. To assess the effect of PCSK9, we used WT mice treated with PCSK9 inhibitor (alirocumab) or PCSK9−/− mice. Regulatory T (Treg) cells in WT mice were depleted by intraperitoneal injection of CD25 antibody. Cardiac function was assessed by cardiac ultrasound on day 1, 14 and 28 after successful construction of the myocardial infarction model; the infarct size was measured by Masson staining of tissue sections, the cross-sectional area of cardiomyocytes was measured by WGA staining and the collagen content was assessed by Sirius Red (PSR) staining 28 days after myocardial infarction. The proportion of Treg cells, proliferative Treg cells, M1 and M2 macrophages in the cardiac tissue was analyzed by flow cytometry on day 7 after myocardial infarction. The induced human iTreg cells were treated with human-derived PCSK9 recombinant protein-treated, and the cellular reactive oxygen species (ROS) level and cell proliferation was analyzed by flow cytometry.
RESULTS Knockdown and inhibition of PCSK9 improved cardiac function, reduced infarct size and cross-sectional area of cardiomyocytes, increased collagen content in the margins of the infarct zone, and increased the proportion of Treg cells and proliferative Treg cells in cardiac tissue. PCSK9 inhibitor promoted M2 polarization of macrophages in cardiac tissue. PCSK9 recombinant protein promoted ROS production and inhibited proliferation of human iTreg cells. After depletion of Treg cells in mice, PCSK9 inhibitor did not improve cardiac function.
CONCLUSIONS Knockdown and inhibition of PCSK9 alleviated ventricular remodeling after myocardial infarction by regulating the proportion of Treg cells in cardiac tissue and promoting proliferation.
GW34-e0068
Liuhua Zhou, Jiateng Sun, Tongtong Yang, Lingfeng Gu, Liansheng Wang
The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES Neonatal mice achieve complete functional and structural repair through endogenous myocardial regeneration after apical resection (AR), but this capacity is rapidly lost 7 days after birth. As one of the DNA chaperone, HMGB2 is widely involved in the regulation of transcription, recombination, repair and genome homeostasis. At present, the role of HMGB2 in cardiac regeneration is unknown. Given that HMGB2 had a significant positive regulation on cell proliferation, targeting cardiomyocytes to promote HMGB2 seems to be a promising attempt at myocardial regeneration therapy. In this research, we investigated whether HMGB2 can promote cardiac regeneration.
METHODS Cardiomyocytes of neonatal and adult mice were detected by proteome TMT mass spectroscopy. And we combined with SnNA-Seq data which was related to dynamic transcriptional responses to regenerative and non-regenerative cardiomyocyte injury to select the target gene HMGB2. Subsequently, the HMGB2 expression was detected by WB, PCR and immunofluorescence staining at the peri myocardial regeneration time. The effect of HMGB2 on the myocardial regeneration potential of cardiomyocytes (CMs) was evaluated using CM-specific HMGB2 overexpression or knockdown adenovirus vector. The models of P1-AR and P7-AR were constructed to verify the effect of HMGB2 on myocardial cell proliferation and myocardial repair. The mechanism of HMGB2 mediated cardiac regeneration was detected by RNA-seq.
RESULTS The results of biogenic analysis showed that HMGB2 was consistent with the spatial and temporal changes of cardiomyocyte regeneration in terms of functional protein and RNA expression. And the expression of HMGB2 was downregulated during postnatal cardiac development. Overexpression of HMGB2 stimulateed the self-proliferating potential of NMCMs, while HMGB2 knockdown had the opposite biological function. In addition, HMGB2 overexpression could prolong the proliferation time window of newborn myocardium. In the real microenvironment in vivo, HMGB2 knockdown inhibited cell cycle activity and cardiac function. However, HMGB2 overexpression promoted cell cycle activity and cardiac function. We transfected NMCMs with Ad5: cTNT-HMGB2 and Ad5: cTNT-Vector and then performed transcriptomic sequencing (RNA-seq) between the two groups. The results of RNA-seq showed that the differential genes were not only enriched in the regulation of cell cycle process, but also in the glycolysis, PI3K/AKT and HIF-1α signaling pathways after HMGB2 overexpression. In terms of mechanism, overexpression of HMGB2 upregulated PI3K/AKT/HIF-1α pathway to activate glycolysis and promote cardiac regeneration after myocardial injury.
CONCLUSIONS In summary, our results suggested that HMGB2 modulated the glucose metabolism via the PI3K/AKT/HIF-1α signaling pathways, which might contribute to the cardiac regeneration after myocardial injury.
GW34-e0072
WeiBin He, Guang Tong, Lin Zeng, WenLong He, XiaoPan Chen, Cien Zhen, PengYuan Chen, Ning Tan, ZhongChan Sun, PengCheng He
Guangdong Cardiovascular Institute
OBJECTIVES Doxorubicin (DOX)-induced cardiotoxicity (DIC) is frequently observed in clinical practice. Autophagy dysregulation is known to be a mechanism of DIC. Mitochondrial-Endoplasmic Reticulum Contact sites (MERCs) is where autophagy initiates and autophagosomes form. However, the role of MERCs in autophagy dysregulation in DIC remains elusive. FUNDC1 is a mitochondria outer membrane protein that serves as a mitophagy receptor as well as a tethering protein of MERCs. The aim of our study was to investigate the effect of DOX on MERCs and explore whether it is involved in the dysregulation of autophagy in DIC.
METHODS We use confocal microscopy and transmission electron microscopy to assess MERCs structure. Overall autophagic flux was analyzed by mCherry-EGFP-LC3B fluorescence assay and western blotting for LC3BII. A total dose of 15 mg/kg of doxorubicin was administrated in mice to construct a DIC model in vivo. Adeno-associated virus (AAV) was used to cardiac-specifically overexpress FUNDC1. Cardiac remodeling was evaluated by Masson’s trichrome staining. Cardiac function (left ventricle ejection fraction, LVEF; left ventricle fraction shortening, LVFS) was measured by echocardiography.
RESULTS DOX treatment led to a significant downregulation of multiple tethering proteins (including FUNDC1) of MERCs and inhibition of MERCs formation, as demonstrated by decreased colocalization coefficients of mitochondria and endoplasmic reticulum in cardiomyocytes. The overexpression of FUNDC1 abolished DOX-induced inhibition on MERCs formation. In addition, DOX treatment blocked the normal autophagic flux, as demonstrated by the decreased autophagosomes synthesis and impaired autophagosomes turnover. Maintaining the MERCs structure by FUNDC1 overexpression was able to restore the blocked autophagic flux mentioned above. Moreover, FUNDC1 overexpression restored the blocked autophagic flux in vivo, as demonstrated by the increased LC3B turnover compared to the DOX treatment group. Importantly, global heart function of FUNDC1 overexpressed mice was significantly improved post DOX treatment compared to the wildtype DOX treatment group, as demonstrated by the increased LVEF and LVFS. In addition, LV fibrosis level was found to be significantly decreased in FUNDC1 overexpressed mice treated with DOX compared to the wildtype DOX treatment group.
CONCLUSIONS We reported for the first time that the impaired MERCs-formation in DOX-treated cardiomyocytes and revealed that restoring the disrupted MERCs structure by FUNDC1 overexpression was able to revert the blocked autophagic flux induced by DOX treatment. Furthermore, cardiac-specific overexpression of FUNDC1 protected DOX-treated mice against adverse cardiac remodeling and improved cardiac function. These findings may shed light on the prevention and treatment of DIC.
GW34-e0092
Chang Cui, Jiuzhou Chen, Huiyuan Qin, Minglong Chen
Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
OBJECTIVES Atrial cardiomyopathy forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. However, generating stable animal models that accurately reflect the whole course of atrial lesions, especially the development of AF is highly challenging. The isoform of CRE-binding protein modulator (CREM-IbΔC-X) has been demonstrated to be involved in the regulation of cardiac development and atrial rhythm. We investigated if cardiac-specific overexpression of CREM-IbΔC-X via CRISPER/Cas9 (CS-CREM) in mice could be a suitable disease model of atrial cardiomyopathy.
METHODS Immunofluorescence staining, immunoblotting, and quantitative real-time PCR were used to verify the expression of CREM-IbΔC-X in patients with AF. CRISPR/Cas9 technology was employed to construct the CS-CREM mice. Subsequently, survival analysis, repeated ECG recordings, echocardiography, histology, proteomics analysis and responses to antiarrhythmic drugs were assessed.
RESULTS CREM-IbΔC-X was highly expressed in atrial biopsies from the patients with AF. The CS-CREM mice well illustrated the development of atrial cardiomyopathy in terms of electrophysiological and structural remodeling over time. Further proteomics analysis of atrial samples identified differentially expressed proteins, which were enriched in extracellular matrix (up-regulated) and metabolic processes (down-regulated) in the CS-CREM mice. Moreover, the correspond responses to anti-arrhythmia drugs, i.e., amiodarone and propafenone, indicated that CS-CREM mice may be an ideal in vivo model for drug testing.
CONCLUSIONS Our study introduced a new model of atrial cardiomyopathy with spontaneous atrial fibrillation by cardiac-specifically overexpressing CREM-IbΔC-X in mice, which would be helpful for investigating the mechanism and therapeutic target of atrial cardiomyopathy.
GW34-e0095
Luxun Tang1, Yu Shi2, Yongjian Yang1, Chunyu Zeng2
1Department of Cardiovascular Medicine, The General Hospital of Western Theater Command PLA
2Department of Cardiology, Daping Hospital, The Third Military Medical University (Army Medical University)
OBJECTIVES The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty regenerating. A metabolic reprogramming from glycolysis to fatty acid oxidation (FAO) occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation.
METHODS Cardiac-specific Cpt1a and Cpt1b knockout mice were used to investigate the effect of reversing metabolic reprogramming by CPT1 inhibition on cardiomyocyte proliferation. The proliferation of cardiomyocytes was evaluated by immunofluorescent staining. The infraction area of heart after myocardial infraction was determined by Masson staining. Etomoxir was also used to inhibit CPT1 activity. An in vitro system with time lapse microscopy can quantify adult cardiomyocyte cytokinesis. We used time-lapse microscopy to verify the cytokinesis rate of adult cardiomyocytes. We used time-lapse microscopy to verify the cytokinesis rate of adult cardiomyocytes. Additionally, we used a lineage-tracing system in which we crossed cardiomyocyte-specific Myh6mERcremER mice with Mosaic Analysis with Double Markers (MADM) mice to examine cardiomyocyte division.
RESULTS Reversing metabolic reprogramming by CPT1 inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction (MI). The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing PARP1 expression, reduced ADP-ribosylation of DUSP1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation.
CONCLUSIONS Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and MI treatment.
GW34-e0100
Jiachun Xia1, Chenshan Gao2, Yanan Pang1, Lei Hou1
1Institute of Cardiovascular Diseases, Tongren Hospital, Shanghai Jiao Tong University School of Medicine
2Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University
OBJECTIVES A series of inflammatory responses triggered by ischemia-reperfusion injury can induce adverse remodeling. In addition to its lipid-lowering effect, proprotein convertase subtilisin/kexin 9 (PCSK9) also plays an important role in atherosclerosis and myocardial infarction inflammation. The protective effect of early PCSK9 inhibitor treatment on myocardial salvage index (MSI) and infarct size remains unclear. This trial aimed to assess the effect of early PCSK9 inhibitor treatment on MSI in patients with anterior ST-segment elevation myocardial infarction (STEMI).
METHODS The PERFECT trial was a prospective, randomized controlled trial. Patients with anterior STEMI who were admitted within 24 h of symptom onset were randomized to receive conventional treatment combined with the PCSK9 inhibitor alirocumab at a dose of 75 mg or conventional treatment alone at a 1:1 ratio. The primary endpoint was MSI, measured by cardiac magnetic resonance imaging (CMR) 5–8 days after PCI. The secondary endpoints were LVEF and the peak time for CK-MB and hs-cTnT.
RESULTS In total, 20 patients met the inclusion criteria and were randomized to the alirocumab group (n=10) and control group (n=10). At 5–8 days, the MSI was comparable between the two groups (56.66±18.3% vs. 48.3±14.34%, P=0.31), albeit the alirocumab group outcome seemed to be better. There were no significant differences in secondary endpoints.
CONCLUSIONS Among patients with anterior STEMI, early application of alirocumab after PCI did not significantly increase the MSI at 5–8 days. Larger trials are required to evaluate the effect of early administration of PCSK9 inhibitors after myocardial infarction.
GW34-e0107
Zhengdong Chen, Naifeng Liu
Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University 87 Dingjiaqiao, Nanjing 210009, PR China
OBJECTIVES Vascular calcification is the most common pathological change in metabolic syndrome. The abnormal metabolism of iron, a crucial trace element, is involved in the occurrence and development of vascular calcification; DNA damage response inextricably linked with iron homeostasis, is a hallmark of vascular calcification. Moreover, vascular smooth muscle cell is essential for keeping the physiological structure and function of blood vessel. The aim of this experiment is to elucidate whether the genomic instability triggered via iron homeostasis abnormality is the underlying pathogenic mechanism of vascular smooth muscle cell osteoblastic differentiation.
METHODS In vivo, the vascular calcification model was developed in mice by vitamin D3. In vitro, the vascular calcification model, was induced in primary vascular smooth muscle cells of mouse thoracic aortas by calcifying medium. The ferrostatin-1 (Fer-1) or deferoxamine (DFO) was used in anti-calcification studies.
RESULTS In vivo, both the elevated expressions of vascular calcification and DNA damage response markers in mouse calcified thoracic aortas were suppressed by Fer-1 or DFO. In vitro, the high levels of vascular calcification and DNA damage response markers in vascular smooth muscle cells were notably ameliorated by Fer-1 or DFO; additionally, the siRNAs knocking down DNA damage response signalling pathway genes partially abolished the protective effects of Fer-1 or DFO.
CONCLUSIONS Taken together, this study indicated that pharmacological iron restriction is a novel strategy for anti-DNA damage response associated vascular smooth muscle cell calcification.
GW34-e0111
Yongshun Wang
Shenzhen People’s Hospital
OBJECTIVES Coronary slow flow phenomenon (CSFP), characterized by slower contrast agent progression throughout the affected coronary artery under angiography, have been linked to chest pain and cardiac diseases, ranging from arrhythmias to myocardial infarction. Furthermore, CSFP patients exhibit similar patterns in cardiovascular biomarker levels as observed for those aforementioned syndromes. In this study, we investigated whether one such biomarker, the phospholipid lysophosphatidic acid (LPA), was associated with CSFP onset, as well as the possible underlying mechanisms involved.
METHODS Thirty randomly-recruited patients, diagnosed with CSFP under angiography, was age- and gender-matched with 30 non-CSFP, atherosclerosis patients, serving as the control group. Computed tomography myocardial perfusion imaging and coronary computed tomography angiography to construct myocardial blood flow maps, followed by collection of coronary and femoral artery blood and high-performance liquid chromatography/electrospray ionization tandem mass spectrometry to measure LPA levels. To examine the effects of LPA on blood vessels, a mouse aorta organ bath was constructed, followed by application of other vasodilative/vasoconstrictive agents. The effects of LPA on nitric oxide and mitochondrial functioning, particularly in terms of reactive oxygen species (ROS) and glucose metabolism, was then examined using human umbilical vein endothelial cells (HUVECs).
RESULTS CSFP patients, compared to control group, had significantly higher plasma LPA levels, particularly for 18:2 and 20:4 isoforms, which were associated with poorer myocardial perfusion. LPA was able to induce vasoconstriction in mouse thoracic aortas, owing to its suppression of NO and increase in ROS production; LPA-treated HUVECs supported these findings, in which it inhibited eNOS, along with increasing expression of ROS-producing enzymes NADPH oxidase 4 and p22phox, in turn contributing to mitochondrial dysfunction.
CONCLUSIONS LPA contributed to CSFP onset by fostering endothelial dysfunction, via inhibiting NO and increasing ROS, thereby serving as a promising therapeutic target for developing future treatment strategies for CSFP.
GW34-e0118
Dong Zhang1, Hui Wu2
1China Three Gorges University
2Yichang Central People’s Hospital
OBJECTIVES Alleviating myocardial ischemia-reperfusion injury (MIRI) plays a crucial role in improving the prognosis and cardiac function after acute myocardial infarction. Pyroptosis, a novel form of cell death, is involved in the regulation of MIRI. This study aims to investigate the impact of the long form of cFLIP (cFLIPL) on pyroptosis in MIRI and the underlying mechanisms.
METHODS H9C2 cells and SD rats were transfected with a recombinant adenovirus vector carrying cFLIPL, and the transfection was allowed to proceed for 3 days. H9C2 cells underwent hypoxia for 4 hours followed by reoxygenation for 12 hours, simulating ischemia-reperfusion (I/R) injury. SD rats experienced 30 minutes of ischemia followed by 2 hours of reperfusion to establish a MIRI model. Model parameters were evaluated by assessing myocardial cell viability, pyroptosis, and the expression of myocardial injury-related proteins.
RESULTS The expression of cFLIPL is significantly reduced during I/R injury and hypoxia/reoxygenation (H/R) injury. Overexpression of cFLIPL can reduce the infarct size in vivo and increase the viability of H9c2 cells in vitro. I/R and H/R upregulate the expression of ASC, cleaved caspase-1, NLRP3, GSDMD-N, interleukin-1β (IL-1β), and interleukin-18 (IL-18) proteins, inducing pyroptosis. Notably, overexpression of cFLIPL can modulate the related proteins to inhibit myocardial cell pyroptosis.
CONCLUSIONS cFLIPL can inhibit pyroptosis by targeting and binding to caspase-1, suppressing the production of inflammatory factors and blocking cell membrane rupture. Therefore, cFLIPL may serve as a potential intervention target for alleviating MIRI by inhibiting the pyroptotic pathway.
GW34-e0138
Wenjie Chen, Yafeng Zhou
Dushu Lake Hospital Affiliated to Soochow University
OBJECTIVES Hypertension is a major risk factor for cerebrovascular disease. During cardiovascular development and disease, epigenetic mechanisms regulate chromatin structure and spectrum-specific gene expression. However, how epigenetics regulate the development and regression of hypertension remains unknown. This review combines histone deacetylase Sirt3 and hypertension with the aim of elucidating recent advances in the development and regression of hypertension and showing the therapeutic potential of Sirt3 expression for targeting vascular dysfunction and hypertension.
METHODS We have collected and analyzed a large amount of researches to explore the role of Sirt3 in various stages of hypertension development, including oxidative stress, vascular inflammation, endothelial damage, vascular remodeling, cardiac fibrosis, and myocardial hypertrophy. We also analyzed the prospective role of Sirt3 as an intermediate molecule for multiple drugs in the reversal and regression of hypertension through different pathways in treated cells or models.
RESULTS Sirt3 targeted drugs can improve the progression of hypertension in animal models and at the cellular level, and may also play a role in reversing elevated blood pressure in human tissue models.
CONCLUSIONS SIRT3 is an important regulator of hypertensive heart dysfunction, hypertrophy, and fibrosis. Future clinical research could develop new Sirt3 agonists and determine the direction of mitochondrial targeting strategies, highlighting the therapeutic potential of targeting Sirt3 in vascular dysfunction, primary hypertension, and end-organ damage in hypertension.
GW34-e0148
Xi Zhang1,2, Meili Wang1,2, Suli Zhang1,2, Huirong Liu1,2
1Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
2Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Diseases, Capital Medical University, Beijing 100069, China
OBJECTIVES Angiotensin II type 1 receptor (AT1R) is a key mediator of the rennin-angiotensin-aldosterone system (RAAS). Autoantibodies against AT1R (AT1-AA), as an activator of AT1R, was found in abdominal aortic aneurysm (AAA) related diseases, such as hypertension and atherosclerosis. However, the role of AT1-AA in AAA is still unclear.
METHODS We used angiotensin II (AngII)–infused male ApoE−/− mice model of AAA. Ultrasonography measurement, histological assessment, western blot, qRT-PCR and RNA sequencing were used to assess the severity of AAA. Nanoluciferase-based bioluminescence resonance energy transfer (NanoBRET) assay, radio assay of receptors, homogeneous time resolved fluorescence (HTRF) and molecular dynamics (MD) studies were used to measure the activation feature of AT1R and the affinity of AT1R with AT1-AA or AngII.
RESULTS AT1-AA increased the incidence of AAA (vehicle vs. AT1-AA: 47 vs. 81%; P<0.05). Furthermore, AT1-AA greatly increased severity of AAA, due to augmenting the diameter of abdominal aorta and the degradation of elastin by enhancing the expression of MMP2/9 (matrix metalloproteinase) and the accumulation of inflammatory cells. Mechanically, AT1-AA enhanced AngII-induced recruitment of Gq, but not β-arrestin1/2. AT1-AA potentiated the AngII-mediated Gq-dependent inositol phosphate and the activation of ERK1/2. The responses were abolished by AT1R antagonist and Gq inhibitor. And AT1-AA significantly potentiated the binding of AngII with AT1R allosterically (mean KD±SEM: 34.11±0.9765 nM at 0 nM AT1-AA vs. 25.63±1.826 nM at 100 nM AT1-AA; P<0.05), without altering the maximum binding. MD studies showed that AT1-AA increased interaction forces of AngII with AT1R, including Lennard-Jones Short Range (LJ-SR) and Coulombic Short Range (Coul-SR).
CONCLUSIONS AT1-AA, as an allosteric activator of AT1R, promotes AAA through increasing the affinity of AngII with AT1R and activating Gq biasedly.
GW34-e0151
Yang Shen1,2, Hang Zhu1,2, Hao Zhou2,3
1Department of Cardiology, School of Medicine, South China University of Technology, Guangzhou 510006, China
2Department of Cardiology, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing 100048, China
3Department of Vascular Medicine, Peking University Shougang Hospital, Beijing 100144, China
OBJECTIVES Dapagliflozin (DAPA) confers significant protection against heart and kidney diseases. However, whether DAPA can alleviate type 4 cardiorenal syndrome (CRS-4)-related cardiomyopathy remains unclear. Cardiomyocyte resistance to chronic damage is enhanced by both aerobic glycolysis stimulated by pyruvate kinase isozyme M2 (PKM2) and FUN14 domain containing 1 (FUNDC1)-dependent mitophagy. Thus, we tested the hypothesis that DAPA attenuates CRS-4-related myocardial damage through PKM2 induction and FUNDC1-related mitophagy.
METHODS Cardiomyocyte-specific PKM2 knockout (PKM2 CKO ) and FUNDC1 knockout (FUNDC1 CKO ) mice were subjected to subtotal (5/6) nephrectomy to establish a CRS-4 model in vivo. To simulate CRS-4 in vitro, HL-1 cardiomyocytes were treated with uremic sera collected from DAPA-treated mice 12 weeks after nephrectomy. Western blots, co-IP, molecular docking, siRNA knockdown technology, immunofluorescence, and ELISA were performed.
RESULTS Our results demonstrated that DAPA treatment enhanced PKM2 expression and improved myocardial function and structure in vivo, and this effect was abrogated by PKM2 knockdown. Moreover, a significant improvement in mitochondrial function was observed in HL-1 cells exposed to sera from DAPA-treated mice, as featured by increased ATP production, decreased mtROS production, improved mitochondrial membrane potential, preserved mitochondrial complex activity, and reduced mitochondrial apoptosis. DAPA restored FUNDC1-dependent mitophagy through post-transcriptional dephosphorylation in a manner dependent on PKM2 whereas ablation of FUNDC1 abolished the defensive actions of DAPA on myocardium and mitochondria under CRS-4. Co-IP and molecular docking assays indicated that PKM2 directly interacted with protein phosphatase 1 (PP1) and FUNDC1, leading to PP1-mediated FUNDC1 dephosphorylation.
CONCLUSIONS These results suggest that DAPA attenuates CRS-4-related cardiomyopathy through activating the PKM2/PP1/FUNDC1-mitophagy pathway.
GW34-e0189
Siting Hong1, Jiaoyan Li2, Dongxue Liu1, Xin Zhang1, Yingchun Luo1, Zeng Wang1, Yue Zhao1, Zengxiang Dong1, Zhaoguang Liang1
1The First Affiliated Hospital of Harbin Medical University
2Xi’an People’s Hospital (Xi’an Fourth Hospital)
OBJECTIVES The current studies demonstrate that gut microbiota and its metabolites, especially Trimethylamine N-oxide (TMAO), play an important role in the onset and progress of cardiovascular diseases (CVDs). (-)-Epicatechin (EPI), the major polyphenolic compound present in green tea, has shown cardioprotective effect. The purpose of this study was to investigate whether EPI could inhibit TMAO-induced cardiac fibrosis.
METHODS We established cardiac fibrosis mice model with TMAO daily intraperitoneal (i.p.) injection for 14 days. Male C57BL/6 mice were randomly separated into 4 groups. Intragastric administration of EPI or vehicle was conducted in mice for 21 days. The cardiac function was performed by the ultrasonic instrument. Histological analysis of mice’s hearts was accessed by H&E and Masson staining. In vitro, cardiac fibroblasts were treated by TMAO with or without EPI. The protein level of fibrosis markers were quantified by western blot.
RESULTS In vivo, cardiac ultrasound results showed that TMAO could damage the cardiac function of mice and lead to cardiac hypertrophy. Pathological staining showed that TMAO induced myocardial hypertrophy and fibrosis in mice. TMAO upregulated the expression of MMP-2, MMP-9 and α-SMA. EPI treatment significantly improved the cardiac function of mice, inhibited the myocardial fibrosis induced by TMAO and reduced the protein levels of MMP-2, MMP-9 and α-SMA. In vitro, EPI blocked TMAO-induced transformation of cardiac fibroblasts into myofibroblasts. TMAO also elevated MMP-2, MMP-9 and α-SMA expression, but decreased after treatment with EPI.
CONCLUSIONS In summary, EPI suppresses TMAO-induced cardiac fibrosis.
GW34-e0200
Xiang Liu1, Yijia Shao2, Jimei Chen1
1Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital
2Department of Geriatrics, The First Affiliated Hospital, Sun Yat-sen University
OBJECTIVES There is increasing evidence that microbiota has an important effect on heart development. Alternative polyadenylation (APA) is a key mechanism for the regulation of gene expression and has shown to be involved in postnatal heart development. However, it remains unclear whether microbiota can affect postnatal heart development by regulating APA.
METHODS Heart tissues from specific pathogen free (SPF) mice within the first 24 hours after birth (P1), 7-day-old SPF mice and 7-day-old germ-free (GF) mice were subjected to APA sequencing to obtain the genome-wide profiling of APA sites. Functional annotations were performed using Metascape and clusterProfiler package. Protein-protein interactions were constructed using STRING and then visualized on Cytoscape. The landscape of immune cells was assessed by CIBERSORT and the correlations between immune cells and key genes were analyzed via Hmisc package. The switching of 3′ untranslated region (3′ UTR) was verified by qPCR.
RESULTS Heart tissues isolated from specific pathogen free (SPF) mice within the first 24 hours after birth (P1), 7-day-old SPF mice and 7-day-old germ-free (GF) mice were subjected to APA sequencing to obtain the genome-wide profiling of APA sites. Here, we found that GF mice harbored evidently longer 3′ untranslated region (3′ UTR) lengths. And the 3′ UTR lengths of mitochondria-related genes, Rala, Timm13 and Uqcc3, were verified to be significantly altered. Furthermore, GF condition led to an obvious reduction in mitochondrial cristae density and a decreased level of Tomm20 in postnatal hearts. Additionally, Rala was found to be connected to Src, and further related to other differentially expressed genes (DEGs). The DEGs were significantly down-regulated in GF mice except for Thbs1 and Egr1. Finally, GF condition appeared to be associated with a lower infiltration of immune cells, and the levels of resting NK cells, Th17 cells, immature dendritic cells and plasma cells in GF mice were comparable to those in P1 mice. Moreover, these immune cells were shown to be significantly correlated with Rala and the related DEGs.
CONCLUSIONS Our findings suggested that microbiota plays a critical role in postnatal heart development by affecting APA switches and immune cell infiltrations.
GW34-e0211
Ziwei Zhu, Xiaowei Zhang
Lanzhou University Second Hospital
OBJECTIVES Ischemic heart failure (HF) is one of the leading causes of global morbidity and mortality, blocking the apoptotic cascade could help improve adverse outcomes of it. RNA-binding motif protein 25 (RBM25) is an RNA-binding protein related to apoptosis, however, its role remains unknown in ischemic HF. The main purpose of this study is to explore the mechanism of RBM25 in ischemic HF.
METHODS Establishing an ischemic HF model and oxygen-glucose deprivation (OGD) model. ELISA was performed to evaluate the BNP level in the ischemic HF model. Echocardiography and histological analysis were performed to assess cardiac function and infarct size. Proteins were quantitatively and locationally analyzed by western blotting and immunofluorescence. The morphological changes of endoplasmic reticulum (ER) were observed with ER-tracker.
RESULTS Cardiac function and myocardial injury were observed in ischemic HF rats. RBM25 was elevated in cardiomyocytes of hypoxia injury hearts and localized in nucleus both in vitro and in vivo. In addition, cell apoptosis was significantly increased when overexpressed RBM25. Moreover, ER stress stimulated upregulation of RBM25 and promoted cell apoptosis through the CHOP related pathway. Finally, inhibiting the expression of RBM25 could ameliorate the apoptosis and improve cardiac function through blocking the activation of CHOP signaling pathway.
CONCLUSIONS RBM25 is significantly up-regulated in ischemic HF rat heart and OGD model, which leads to apoptosis by modulating the ER stress through CHOP pathway. Knockdown of RBM25 could reverse apoptosis-mediated cardiac dysfunction. RBM25 may be a promising target for the treatment of ischemic HF.
GW34-e0216
Yan Xia, Zhangwei Chen, Juying Qian, Junbo Ge
Zhongshan Hospital, Fudan University
OBJECTIVES Mitochondria are highly abundant in the heart and are the “power houses” of the cell. The maintenance of mitochondrial morphology and structure is of critical importance for cardiac function. Mitochondrial dynamics are closely coordinated with cellular biological and metabolic processes. Mitochondria are double membrane-bound organelles, composed of an inner (IMM) and an outer mitochondrial membrane (OMM). The specific role of IMM protein during the progression of mitochondrial fission remains poorly understood. Mitochondrial fission is considered to play a key role in the pathogenesis of dilated cardiomyopathy (DCM) through mitochondrial quality control. However, the specific regulatory mechanism of mitochondrial fission in the development of doxorubicin (DOX)-induced cardiomyopathy remains unclear. The mitochondrial aspartate-glutamate carrier isoform 1 (AGC1, or aralar) is located in IMM. We report that AGC1 interacts with the fission protein dynamin-related protein 1 (Drp1) and the underlying the functional and molecular mechanism in DOX-induced cardiomyopathy.
METHODS This study examined the role of AGC1 in mitochondrial fission in doxorubicin-induced cardiomyopathy. Left ventricle (LV) samples were obtained from six end-stage DCM patients after heart transplantation in Zhongshan Hospital, Fudan University. We generated DOX-induced mice and Cardiac-specific Drp1 conditional knockout (CKO-Drp1) mice. Stable cell lines were prepared to conduct mechanistic studies.
RESULTS Results of co-immunoprecipitation mass spectrometry (CO-IP MS) anaylsis by based on heart tissue of DCM patients indicated that AGC1 expression was significantly upregulated DCM-induced injury and AGC1 level was closely correlated with mitochondrial morphogenesis and function. We showed that knockdown of AGC1 protected mice from DOX-induced cardiomyopathy by preventing mitochondrial fission, while overexpression of AGC1 in the mouse heart led to impairment of cardiac function. Mechanistically, AGC1 overexpression could upregulate Drp1 expression and contributed to subsequent excessive mitochondrial fission. Specifically, knockdown of AGC1 or use of Drp1-specific inhibitor Mdivi-1 alleviated cardiomyocyte apoptosis and inhibited impairment of mitochondrial function induced by DOX exposure.
CONCLUSIONS In summary, our data illustrate that AGC1, as a novel contributor to DCM, regulates cardiac function via Drp1-mediated mitochondrial fission. Our study indicates that inhibiting AGC1 or mitochondrial fission could be a potential therapeutic strategy and may provide cardioprotection.
GW34-e0232
Fengzhou Liu1,2, Xide Shi3, Chao Liu3, Jiangwei Chen4, Shiqiang Zhou3, Yajuan Li2, Junhui Xue1,2, Fei Li3
1Department of Aviation Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, China
2Aerospace Clinical Medical Center, School of Aerospace Medicine, Fourth Military Medical University, Xi’an, China
3Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
4State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Department of Medical Rehabilitation, School of Stomatology, Fourth Military Medical University, Xi’an, China
OBJECTIVES Myocardial microvascular injury is the key event in early diabetic heart disease. The injury of myocardial microvascular endothelial cells (CMECs) is the main cause and trigger of myocardial microvascular disease. Mitochondrial calcium homeostasis plays an important role in maintaining the normal function, survival and death of endothelial cells. Considering that mitochondrial calcium uptake 1 (MICU1) is a key molecule in mitochondrial calcium regulation, this study aimed to investigate the role of MICU1 in CMECs and explore its underlying mechanisms.
METHODS To examine the role of endothelial MICU1 in DCM, we used endothelial-specific MICU1ecKO mice to establish a diabetic mouse model and evaluate the cardiac function. In addition, MICU1 overexpression was conducted by injecting adeno-associated virus 9 carrying MICU1 (AAV9-MICU1). Transcriptome sequencing technology was used to explore underlying molecular mechanisms.
RESULTS Here, we found that MICU1 expression is decreased in CMECs of diabetic mice. Moreover, we demonstrated that endothelial cell MICU1 knockout aggravated the levels of cardiac hypertrophy and interstitial myocardial fibrosis and led to a further reduction in left ventricular function in diabetic mice. Notably, we found that AAV9-MICU1 specifically upregulated the expression of MICU1 in CMECs of diabetic mice, which inhibited nitrification stress, inflammatory reaction, and apoptosis of the CMECs, ameliorated myocardial hypertrophy and fibrosis, and promoted cardiac function. Further mechanistic analysis suggested that MICU1 deficiency result in excessive mitochondrial calcium uptake and homeostasis imbalance which caused nitrification stress-induced endothelial damage and inflammation that disrupted myocardial microvascular endothelial barrier function and ultimately promoted DCM progression.
CONCLUSIONS Our findings demonstrate that MICU1 expression was downregulated in the CMECs of diabetic mice. Overexpression of endothelial MICU1 reduced nitrification stress induced apoptosis and inflammation by inhibiting mitochondrial calcium uptake, which improved myocardial microvascular function and inhibited DCM progression. Our findings suggest that endothelial MICU1 is a molecular intervention target for the potential treatment of DCM.
GW34-e0235
Qi Pan, Cheng Chen, Yuejin Yang, Guihao Chen
State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College
OBJECTIVES The increasing burden of heart failure with preserved ejection (HFpEF) has become a global health problem. HFpEF is characterized by systematic inflammation, cardiac metabolic remodeling and fibrosis. Eosinophils act as an essential, but generally overlooked subgroup of white blood cells, which participant in cardiac fibrosis, as reported in several recent studies. Herein, we explored the role of eosinophils in a “two-hit” preclinical HFpEF model.
METHODS A novel preclinical model of HFpEF induced by normal diet 12-week treatment of high-fat diet (HFD) plus N[w]-nitro-L-arginine methyl ester (L-NAME, 0.5 g/L) and ΔdblGATA1 knock-out (Gata1 KO) C57BL/6N mice, which have complete ablation of the eosinophil lineage, were applied in this study. Blood eosinophil counts were conducted. Mice were divided into 4 groups (n=13–14 per group): wild type (WT) and normal diet (Group I), Gata1 KO and normal diet (Group II), WT and HFpEF model (Group III), and Gata1 KO and HFpEF model (Group IV). Evaluation of heart failure and hypertrophy were performed to examine the association of eosinophils and HFpEF.
RESULTS The level of circulating eosinophil didn’t alter between normal diet and HFpEF mice (normal diet v.s. HFpEF, 11.83±7.02 v.s. 10.87±4.60, P=0.81). Body weight (Group III v.s. IV, 33.46±1.50 v.s. 32.79±1.17 [g], P=0.72), systolic blood pressure (129.3±4.36 v.s. 132.6±4.15 [mmHg], P=0.27), exercise tolerance (running distance, 59.71±21.52 v.s. 63.30±25.35 [m], P=0.98), the ratio of E to e’ (E/e’, 42.34±4.10 v.s. 41.06±5.78, P=0.98), heart weight to tibial length (HW/TL, 6.82±0.18 v.s. 6.77±0.19 [mg/mm], P=0.86) and wet lung weight to dry lung weight (4.48±0.10 v.s. 4.43±0.11, P=0.76) were comparable between Group III and IV. Additionally, no alternation was observed in the levels of B-type natriuretic peptide (3.24±1.05 v.s. 3.57±1.80 [fold change], P=0.99) and transforming growth factor-β (20,691±2949 v.s. 19,049±3660 [pg/g tissue], P=0.81) between Group III and IV.
CONCLUSIONS Deficiency of eosinophils failed to alter the phenotype of HFpEF. The development of HFpEF is independent of eosinophils in terms of the functional, biochemical and histological results.
GW34-e0249
Lang Hu1, Feng Fu2, Yan Li1
1Department of Cardiology, Tangdu Hospital, Airforce Medical University
2Department of Physiology and Pathophysiology, Airforce Medical University
OBJECTIVES The heart derives its energy primarily from fatty acid oxidation, while excessive lipid supply may result in intra-myocardial lipotoxic damage and cardiac dysfunction. Nevertheless, the endogenous mechanism that determines the transition from adaptive lipid utilization to maladaptive lipotoxicity is still not well understood. The present study investigated the role of mitochondria-lipid droplet (LD) membrane contacts (MLC) and its underlying mechanisms in the transition.
METHODS Mice were fed continuous high-fat diet (HFD). Cardiac function and intra-myocardial lipid accumulation were examined. Multiple approaches including fluorescent imaging, lipidomics, fatty acids pulse-chase assay, proximity ligation assay, co-immunoprecipitation, mutagenesis and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis were used to elucidate the underlying mechanisms.
RESULTS Tight MLC was observed in the hearts of mice fed HFD for 5 weeks, accompanied by adaptive lipid usage. As lipid-overload was prolonged, reduced MLC and increased LD number were detected in the hearts of mice fed HFD for 20 weeks and patients with obesity (BMI≥30 kg/m2), and were associated with maladaptive lipotoxicity. Mechanistically, mitochondria-localized Mitofusin2 (Mfn2) directly binds to LD-localized heat shock cognate protein 70 (Hsc70) via its 649–692 aa domain, tethering mitochondria to LDs and facilitating fatty acids (FAs) transfer from LDs to mitochondria for β-oxidation. Excessive lipid-induced Mfn2 reduction inhibits MLC and impedes FAs transfer, leading to lipid accumulation and cardiac damage. Restoration of Mfn2 reconstituted MLC and relieved myocardial lipotoxicity under lipid overload in-vivo and in-vitro. Hsc70 knockdown largely blocked the above effects of Mfn2. Moreover, Mfn2 inhibition was induced in the ubiquitin-proteasome pathway following Mfn2 acetylation at the K243 site that was triggered by lipid overload.
CONCLUSIONS Mfn2/Hsc70 complex-mediated MLC is a novel regulator of cardiac lipid metabolism. Lipid overload induces Mfn2/Hsc70 complex disassociation, leading to intra-myocardial lipid accumulation and maladaptive lipotoxicity. Therefore, targeting MLC may help in therapeutic interventions in cardiac lipotoxicity.
GW34-e0263
Jing Geng, Xiaoliang Zhang, Dong Guo, Ying Wang, Lang Hu, Yan Li
Department of Cardiology, Tangdu Hospital, Airforce Medical University
OBJECTIVES A high-calories diet (HCD) combined with lack of physical exercise is the major cause of obesity, leading to lipid metabolic disorder and cardiac lipotoxicity. Physical exercise has long been recognized as an effective strategy for preventing diet-induced obesity and improving cardiovascular health. However, it is still unclear whether exercise training would protect against cardiac lipotoxicity in a large number of individuals with HCD.
METHODS Wild-type female C57BL/6J mice were fed ad libitum either a normal diet (ND, 10% calories from fat) or a high-fat, high calories diet (HFCD, 60% calories from fat). Meanwhile, ND and HFCD-fed mice were subjected to sedentary or three different-intensity exercise. Body weight, lipid accumulation, metabolic-related indicators and cardiac function were determined. Lipidomics, proteomics, mitochondrial function analysis was also performed to evaluate cardiac lipid metabolism.
RESULTS HFCD-feeding led to a significant elevation of body weight, blood glucose and serum lipid level. Also, continues HFCD-feeding induced both systolic and diastolic function impairment. As expected, all of the three different-intensity exercise prevented the development of obesity and whole-body metabolic disorders, as indicated by decreased blood glucose, serum lipid, body weight and lipid content in liver and white-adipose tissue. Low-intensity exercise (LIE) showed cardiac protective effect on HFCD-fed mice, as evidenced by improved cardiac diastolic function. However, moderate- or high-intensity exercise (MIE or HIE) failed to protect against HFCD-induced cardiac dysfunction but in contrast deteriorated the development of cardiac dysfunction and pathological hypertrophy. Mechanistically, MIE promoted the activation of lipid intake-related genes (mainly CD36) in HFCD-fed mice, leading to more severe intra-myocardium lipid accumulation. As a result, accumulated toxic lipid further impaired mitochondrial respiratory function and impeded lipid metabolism in heart of HFCD-fed mice.
CONCLUSIONS Our work firstly reported that moderate-intensity exercise, which was previously considered to be beneficial to cardiovascular system, exacerbated HCD-induced cardiac lipotoxicity and dysfunction. The underlying mechanism was associated with excessive cardiac lipid uptake and toxic lipid-induced mitochondrial damage. Our results deepen current insights into the cardiovascular effect of physical exercise on a specified population. Considering the large population with high-calories diet around the world, this study also provided guidance for individuals with HCD to establish rational exercise strategies to avoid the potential negative effects.
GW34-e0268
Weili Li, Yawen Zhang, Guanjing Ling, Nannan Tan, Yan Wei, Jinchi Jiang, Wei Li, Xiaoping Wang, Jing Cao
Beijing University of Chinese Medicine
OBJECTIVES Doxorubicin (DOX), a broad-spectrum chemotherapy drug, has life-threatening cardiotoxicity. Therefore, searching cardioprotective drugs for DOX-induced cardiotoxicity (DIC) is urgently needed. The results of previous high-throughput screening showed that aucubin (AUC) had significant protection on DOX-treated zebrafish. This study aimed to investigate the cardioprotective effects of AUC and the specific mechanism by which AUC alleviates DIC, and to provide an alternative for the treatment of DIC.
METHODS A DIC mice model via tail vein injection with DOX (5 mg⋅kg−1) once weekly for 4 weeks and a DOX-induced H9C2 cell injury model with DOX (1 μmol/L) were established. In vivo, the mice were divided into saline-injected group, DOX-injected group, DOX+low and high dose of AUC-treated group, and DOX+enalapril (ENA)-treated group (Positive control). Echocardiography, histological examination and CK-MB and LDH detection were applied for assessment of protective effects of AUC on cardiac structure and function. TUNEL, DHE, 8-OHdG staining and serum MDA were used to detect myocardial apoptosis and oxidative stress levels. Whereafter, western blot and transmission electron microscope were utilized to evaluate the regulation of autophagy proteins (Beclin-1, LC3 and p62) and autophagy flow by AUC. In vitro, after siRNA of Hipk2 and Nrf2 were combined with AUC, a variety of methods were used, including GFP-mRFP-LC3 double-labeled adenovirus monitoring autophagy flow, DCFH-DA staining to detect ROS, 8-OHdG immunofluorescence staining to quantify DNA damage, Hoechst staining to detect apoptosis rate, and western blot detected autophagy and apoptosis-related proteins, which jointly verified AUC regulating autophagy, oxidative stress and apoptosis through Hipk2 or Nrf2. Finally, siRNA and plasmid overexpression were performed on Hipk2 and Nrf2 respectively, and the protein expression and luciferase intensity of Nrf2 and Hipk2 were detected accordingly, so as to further interpret the cross-talk between Hipk2 and Nrf2.
RESULTS AUC exerted cardioprotection manifested as enhanced cardiac function, and reduced structural damage and myocardial injury markers CK-MB and LDH. In addition, AUC significantly alleviated ROS and MDA production, DNA damage and apoptosis in DIC mice. Mechanically, AUC promoted the expression of Beclin1 and the formation of autophagosomes, and reduced the accumulation of p62 and LC3 proteins in DIC mice. In vitro, AUC increased Beclin-1 expression and reduced DOX-induced accumulation of LC3 and P62 proteins, thus promoting the formation of autophagosomes and reducing the accumulation of autophagolysosomes. In addition, AUC reduced DOX-induced ROS production, DNA oxidative damage, and apoptosis. Interestingly, knockdown of Nrf2 or Hipk2 reversed the above effects on autophagy, oxidative stress and apoptosis. More importantly, there is a cross-talk mechanism between Hipk2 and Nrf2. When Hipk2 was inhibited or overexpressed, the protein expression and luciferase intensity of Nrf2 decreased or increased correspondingly; When Nrf2 was inhibited or overexpressed, the protein expression and luciferase intensity of Hipk2 also decreased or increased correspondingly.
CONCLUSIONS The results partially revealed that AUC exerts cardioprotective effects against DIC through Nrf2-Hipk2 signal crosstalk to activate autophagy and thus alleviate oxidative stress damage and apoptosis induced by DOX.
GW34-e0279
Chengcheng Zhao1,2, Xiangrui Jiang3, Liyuan Peng1,2, Yan Zhang3, Huihui Li1,2, Qiumeng Zhang3, Yinhui Wang1,2, Feipu Yang3, Junfang Wu1,2, Zheng Wen1,2, Jingshan Shen3, Chen Chen1,2, Dao Wen Wang1,2
1Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
3Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China
OBJECTIVES Epoxyeicosatrienoic acids (EETs), which exert multiple endogenous protective effects, are easily hydrolyzed into less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). However, relative commercial drugs are not in clinic use yet.
METHODS Firstly, the plasma concentration of EETs and DHETs of 316 patients with heart failure (HF) were detected by liquid chromatography-tandem mass spectrometry. Then, transverse aortic constriction (TAC)-induced HF was introduced in cardiomyocyte-specific Ephx2−/− mice. Moreover, Western blot, real-time PCR, luciferase reporter, ChIP assays were employed to explore the underlying mechanism of the reason why sEH was upregulated. Finally, multiple sEH inhibitors were designed, synthesized, and validated in vitro and in vivo.
RESULTS The ratios of DHETs and EETs were increased in the plasma from patients with HF. Meanwhile, the expression of sEH was upregulated in the heart of patients and mice with HF, especially in cardiomyocytes. Cardiomyocyte-specific Ephx2−/− mice ameliorated cardiac dysfunction induced by TAC. Consistently, Ephx2 knockdown protected AngII-treated cardiomyocytes against injury and hypertrophy via increasing EETs in vitro. Mechanistically, AngII could enhance the expression of transcript factor Krüppel-like factor 15 (KLF15), which in turn upregulated sEH. Importantly, glimepiride was identified as a novel sEH inhibitor, which benefited from the elevated EETs during HF.
CONCLUSIONS Glimepiride, as a sEH inhibitor, could attenuate heart failure by increasing EETs concentration.
GW34-e0305
Haizhe Ji, Yinong Jiang
The First Affiliated Hospital of Dalian Medical University
OBJECTIVES Dual specificity phosphatase 1 (DUSP1) is regarded as an anti-inflammatory factor in cardiovascular disorders. Mitophagy removes damaged mitochondria and thus promotes mitochondrial regeneration. We investigated whether DUSP1 could attenuate inflammation-induced cardiomyopathy by improving mitophagy.
METHODS Lipopolysaccharide was used to induce septic cardiomyopathy in wild-type (WT) and DUSP1 transgenic (DUSP1 TG ) mice.
RESULTS Echocardiography revealed that lipopolysaccharide impaired heart function by reducing the cardiac systolic and diastolic capacities of WT mice. Freshly isolated single cardiomyocytes from lipopolysaccharide-treated WT mice also exhibited reduced contractile/relaxation parameters. However, DUSP1 overexpression not only maintained the mechanical properties of cardiomyocytes, but also improved heart performance. Lipopolysaccharide upregulated myocardial inflammatory gene transcription and adhesive factor expression, which increased myocardial neutrophil accumulation and cardiomyocyte apoptosis in WT mice. DUSP1 overexpression inhibited the inflammatory response and therefore promoted cardiomyocyte survival. Lipopolysaccharide disrupted mitochondrial respiration and metabolism in WT cardiomyocytes, but DUSP1 overexpression restored mitochondrial metabolism, maintained the mitochondrial membrane potential and inhibited mitochondrial reactive oxygen species production, possibly by increasing FUN14 domain-containing 1 (FUNDC1)-dependent mitophagy. Silencing of FUNDC1 abolished the protective effects of DUSP1 overexpression on cardiomyocytes and their mitochondria following lipopolysaccharide treatment.
CONCLUSIONS These results demonstrated that DUSP1 is a novel anti-inflammatory factor that protects against septic cardiomyopathy by improving FUNDC1-induced mitophagy.
GW34-e0306
Haizhe Ji, Yinong Jiang
The First Affiliated Hospital of Dalian Medical University
OBJECTIVES Cardiorenal syndrome type-3 (CRS-3) is an abrupt worsening of cardiac function secondary to acute kidney injury. Mitochondrial dysfunction is a key pathological mechanism of CRS-3, and empagliflozin can improve mitochondrial biology by promoting mitophagy. Here, we assessed the effects of empagliflozin on mitochondrial quality surveillance in a mouse model of CRS-3.
METHODS Cardiomyocyte-specific FUNDC1-knockout (FUNDC1 CKO ) mice were subjected to CRS-3 prior to assessment of mitochondrial homeostasis in the presence or absence of empagliflozin.
RESULTS CRS-3 model mice exhibited lower heart function, increased inflammatory responses and exacerbated myocardial oxidative stress than sham-operated controls; however, empagliflozin attenuated these alterations. Empagliflozin stabilized the mitochondrial membrane potential, suppressed mitochondrial reactive oxygen species production, increased mitochondrial respiratory complex activity and restored the oxygen consumption rate in cardiomyocytes from CRS-3 model mice. Empagliflozin also normalized the mitochondrial morphology, mitochondrial dynamics and mitochondrial permeability transition pore opening rate in cardiomyocytes. Cardiomyocyte-specific ablation of FUN14 domain-containing protein 1 (FUNDC1) in mice abolished the protective effects of empagliflozin on mitochondrial homeostasis and myocardial performance. Empagliflozin activated β-catenin and promoted its nuclear retention, thus increasing FUNDC1-induced mitophagy in heart tissues; however, a β-catenin inhibitor reversed these effects.
CONCLUSIONS In summary, empagliflozin activated Wnt/β-catenin to stimulate FUNDC1-dependent mitochondrial quality surveillance, ultimately improving mitochondrial function and cardiac performance during CRS-3. Thus, empagliflozin could be considered for the clinical management of heart function following acute kidney injury.
GW34-e0314
Naixin Wang, Zhonghua Tong, Xiaoqi Wang, Jian Wu, Maomao Zhang
Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University
OBJECTIVES The early activation of reparative signals in monocyte-macrophages is essential for the timely restoration of immune homeostasis and the initiation of the repair process post-MI. However, it remains unknown whether bone marrow (BM) and circulating monocytes are pre-educated to initiate the reparative transcriptional response in the early stage of MI. Furthermore, the mechanisms and molecular cues involved in the initiation of reparative gene activation in peripheral monocytes before cardiac recruitment remain to be fully elucidated. A newly identified epigenetic modification, histone lactylation, induces reparative gene transcription during M1 macrophage polarization to promote immune homeostasis. However, the pattern and involvement of histone lactylation in the early remote activation of reparative response post-MI remain unclear.
METHODS Single-cell RNA sequencing (scRNA-seq) was performed on BM and circulating monocytes to detect the early and remote transcriptional response prior to cardiac recruitment post MI. Western blot and immunofluorescence staining were used to explored the dynamic patterns of histone lactylation levels in monocyte-macrophages post MI. Cleavage under targets and tagmentation (CUT&Tag) and paired RNA sequencing (RNA-seq) were performed to identify potential downstream targets of histone lactylation. CHIP-qPCR and qRT-PCR verified modification and expression level of the target genes. Flow cytometry, EdU labeling, transwell, scratch/wound migration, and tube formation assays assessed the reparative activity of macrophages regulated by histone lactylation. Murine MI models induced by LAD ligation were treated with sodium lactate or a lactate dehydrogenase inhibitor, FX-11, thus manipulate the level of histone lactylation to assess the effects of histone lactylation on the ischemic cardiac immune environment.
RESULTS ScRNA-seq data confirmed the early remote activation of reparative signals in peripheral monocytes post-MI. Meanwhile, we observed increases of histone lactylation levels in peripheral monocytes and cardiac macrophages, including the previously identified histone H3K18 lactylation (H3K18la) early post MI. Reparative genes Lrg1, Vegf-a, and IL-10 were identified as target genes of histone lactylation post-MI. Then we demonstrated that histone lactylation regulates the anti-inflammatory and pro-angiogenic dual activities of monocyte-macrophages by facilitating reparative gene transcription in vitro, confirmed that increased histone lactylation favors a reparative environment and improves cardiac function post-MI in vivo. We also explored the positive role of monocyte histone lactylation in reperfused MI. Mechanistically, we revealed that endogenous glycolysis re-programming in circulating monocytes post-MI and MCT1-mediated extracellular lactate transportation contributed to histone lactylation. Finally, we revealed that GCN5 served as a writer for lactylation, and then confirmed the catalytic effect of IL-1β-dependent GCN5 recruitment on H3K18la and elucidated its potential role as an upstream regulatory element in the regulation of monocyte histone lactylation and downstream reparative gene expression post-MI.
CONCLUSIONS In summary, we demonstrated that histone lactylation favors a reparative environment by promoting reparative gene activation in monocytes early and remotly post-MI, and highlighted that the metabolome-epigenome cascade may provide clues to the endogenous protective effect and underlying mechanism of histone lactylation in MI.
GW34-e0316
Yinhui Wang, Jia Cheng, Ling Zhou, Chunxia Zhao
Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
OBJECTIVES Aberrant amino acid metabolism is implicated in cardiac hypertrophy, whereas the involvement of tryptophan metabolism in pathological cardiac hypertrophy remains elusive. Herein, we aimed to investigate the effect and potential mechanism of indoleamine 2,3-dioxygenase (IDO1) and its metabolite kynurenine on pathological cardiac hypertrophy.
METHODS Transverse aortic constriction (TAC) was performed to induce cardiac hypertrophy in IDO1-KO mice and AAV9-cTNT-shIDO1 mice. Liquid chromatography-mass spectrometry (LC-MS) was used to detect the metabolites of tryptophan–kynurenine pathway. Subcutaneous injection was used for delivery of exogenous Kyn and INCB. Chromatin Immunoprecipitation (ChIP) assay and dual luciferase assay were employed to validate the binding of protein and DNA.
RESULTS IDO1 expression was upregulated in both human and murine hypertrophic myocardium, alongside with increased cardiac IDO1 activity and kynurenine (Kyn) content in TAC-induced mice determined by liquid chromatography-mass spectrometry (LC-MS) analysis. Myocardial remodeling and heart function were significantly improved in IDO1-deficient TAC-induced mice, but were greatly exacerbated with subcutaneous kynurenine administration. IDO1 inhibition or kynurenine addition confirmed the alleviation or aggravation of hypertrophy in vitro, respectively, in cardiomyocyte treated with isoprenaline (ISO). Mechanistically, IDO1 and metabolite kynurenine contributed to pathological hypertrophy via the aryl hydrocarbon receptor (AhR)-GATA4 axis.
CONCLUSIONS These findings suggested that IDO1 deficiency and consequent kynurenine insufficiency can protect against pathological cardiac hypertrophy by decreasing GATA4 expression in an aryl hydrocarbon receptor (AhR)-dependent manner, and IDO1 has the potential to be a therapeutic target for pathological cardiac hypertrophy.
GW34-e0318
Shiyu Gong, Ming Zhai, Jiayun Shi, Guanye Yu, Zhijun Lei, Wenhui Peng
Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai, China
OBJECTIVES Efferocytosis and metabolic reprogramming of macrophages are necessary for myocardial infarction (MI) reparation. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is a transmembrane immune receptor that improves macrophage efferocytosis. However, the potential function of TREM2 and its molecular mechanisms remain unknown in MI. Therefore, we aim to uncover the effect of TREM2+ macrophage and explore the link between efferocytosis and metabolism in MI.
METHODS LysMcre, TREM2flox/flox; LysMcre, B6-G/R; CCR2cre-EGFP, TREM2flox/flox transgenic mice and cardiac macrophages overexpressing TREM2 by adenovirus were used to determine the function of TREM2 in MI. Efferocytosis and metabolic functions were examined using flow cytometry, immunofluorescence, and quantitative polymerase chain reaction. Targeted Metabolomics (LC-MS) was used to detect concentrations of metabolites. RNA-seq was used to screen the potential downstream pathways of TREM2. Protein and molecular docking were predicted with AutoDock Vina software.
RESULTS Macrophage-specific TREM2 knockout mice (Mac-TREM2KO) showed worsened cardiac function and impaired post-MI repair. Deletion of TREM2 induced macrophages to transform into a pro-inflammatory phenotype of CCR2+MHCIIhigh. On the contrary, macrophages expressing TREM2 had decreased SLC25A53 transcription through the SYK-SMAD4 signaling pathway, which impaired NAD+ transport into mitochondria, thereby restricting the tricarboxylic acid cycle and increasing itaconate production in anoxia condition. In vitro, itaconate secreted by TREM2+ macrophage inhibited cardiomyocyte apoptosis and increased fibroblast proliferation.
CONCLUSIONS Our data described a novel role of myeloid-derived macrophage-specific TREM2 in MI, linking efferocytosis to immune metabolism during cardiac repair by transporting NAD+ into mitochondria, mainly through mitochondria protein SLC25A53. Moreover, the metabolism by-product itaconate could alleviate MI injury.
GW34-e0332
Toshihide Hamabe-Horiike1,2,3, Kana Shimizu1,2, Yoichi Sunagawa1,2,3, Yuto Kawase1, Yasufumi Katanasaka1,2,3, Satoshi Shimizu1, Koji Hasegawa1,2, Tatsuya Morimoto1,2,3
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka
2Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization
3Shizuoka General Hospital, Shizuoka
OBJECTIVES Heart failure is a serious public health problem. As the number of people suffering from the disease is expected to continue increasing over the coming decades, heart failure is one of the most significant health problems worldwide. Neurohormonal antagonists, including β blockers and renin-angiotensin system inhibitors, are the established standards for heart failure therapy based on clinical studies demonstrating that these drugs suppress cardiac remodeling and improve prognosis. However, as the prognosis remains poor even with the use of these drugs, new heart failure therapies are urgently needed. Drug repositioning has recently emerged as a strategy for developing new treatments at low cost. In this study, we focused on a drug repositioning strategy for heart failure therapy using a library of approved drugs to screen for compounds that suppress phenylephrine (PE)-induced hypertrophy in primary cultured cardiomyocytes. The antiplatelet drug sarpogrelate, a selective serotonin-2A (5-HT2A) receptor antagonist, was identified as capable of suppressing PE-induced cardiomyocyte hypertrophy. However, it was unclear whether sarpogrelate suppresses cardiac dysfunction in the pressure overload-induced mice model.
METHODS To investigate the effects of sarpogrelate on cardiomyocyte hypertrophy, primary cultured cardiomyocytes prepared from neonatal rats were pretreated with 1 μM sarpogrelate and then stimulated with PE, angiotensin II (Ang II), or endothelin1 (ET-1) for 48 h. Immunofluorescence staining and qPCR analysis were performed. To identify the phosphorylation of ERK and GATA4, Western blot analysis was performed. Next, to investigate the effects of sarpogrelate on systolic function, eight-week-old mice were subjected to transaortic constriction (TAC) surgery. One day after the surgery, mice were randomly assigned to the oral treatment with sarpogrelate (5 mg/kg/day) or vehicle for 8 weeks. Echocardiography, qPCR, and histological qPCR analyses were performed. To evaluate the phosphorylation of ERK and GATA4, Western blot analysis was performed.
RESULTS Immunofluorescence staining showed that sarpogrelate suppressed the cardiomyocyte hypertrophy induced by each of the stimuli. PE-induced increase in hypertrophic-related genes mRNA levels was inhibited by sarpogrelate. Western blotting analysis revealed that sarpogrelate suppressed PE-induced phosphorylation of ERK1/2 and GATA4. Echocardiography showed that 5 mg/kg of sarpogrelate suppressed TAC-induced cardiac hypertrophy and systolic dysfunction. qPCR analysis showed that TAC-induced increase in hypertrophic-related genes mRNA levels was inhibited by sarpogrelate treatment. Wheat germ agglutinin staining showed that sarpogrelate suppressed a TAC-induced increase in the cross-sectional area of the left ventricle, and Masson trichrome staining showed that sarpogrelate also suppressed TAC-induced perivascular fibrosis. Western blotting revealed that sarpogrelate suppressed TAC-induced phosphorylation of ERK1/2 and GATA4.
CONCLUSIONS These results indicate that sarpogrelate suppresses the development of heart failure at least, in part, by inhibiting the ERK1/2–GATA4 signaling pathway. Further study is needed to determine whether the inhibition of ERK1/2, including the inhibition caused by sarpogrelate, may be effective for heart failure therapy.
GW34-e0336
Minghui Li, Zhiwei Chen, Hui Shi, Ruizhen Chen
Department of Cardiology, Zhongshan Hospital, Fudan University
OBJECTIVES The mechanism of bradycardia arrhythmia in viral myocarditis is still unclear. This study aims to investigate this issue.
METHODS Balb/c mice were intraperitoneally injected with CoxsackievirusB3 to establish viral myocarditis model. Survival curves of mice were plotted. Electrocardiograms were recorded to observe changes in heart rhythm. Ten days after infection, the hearts of mice were collected, and some tissues were fixed for histology observation. Some were frozen and stored at −80°C for Western blot analysis of calpain1, MCU, TBX18, and HCN4 protein. In vitro models were established by directly infecting neonate rat cardiomyocytes with CVB3 and observing changes in MCU expression with calpain inhibitor PD150606 treatment.
RESULTS Survival rate of infected mice decreased significantly (P<0.05). Histological examination showed inflammatory cell infiltration in the myocardial tissue of surviving mice at the end of the observation period, while no obvious inflammatory cell infiltration was observed in the myocardium of dead mice during the observation period, suggesting a potential death cause of malignant arrhythmia. Electrocardiogram recordings showed that the heart rate of infected mice decreased significantly (P<0.05). Molecular biology analysis showed that calpain1 expression was upregulated and TBX18 and HCN4 expression were downregulated in infected myocardial tissue (Ps<0.05). In vitro calpain1 inhibition downregulated MCU expression (P<0.05), indicating that calpain1 mediated the MCU upregulation in viral infection and the sinus node autonomic regulation genes alterations.
CONCLUSIONS Calpain1 is activated in infected myocardial tissue, mediating the upregulation of MCU, leading to bradycardia arrhythmia by affecting TBX18 and HCN4 expression.
GW34-e0345
Ayaka Ishima1, Yoichi Sunagawa1,2,3, Masafumi Funamoto1,2, Ayumi Katayama1, Toshihide Hamabe1,2, Yasufumi Katanasaka1,2,3, Ryota Hosomi4, Koji Hasegawa1,2, Tatsuya Morimoto1,2,3
1Division of Molecular Medicine/School of Pharmaceutical Sciences/University of Shizuoka
2Division of Translational Research/Clinical Research Institute/Kyoto Medical Center/National Hospital Organization
3Shizuoka General Hospital
4Laboratory of Food and Nutritional Sciences/Faculty of Chemistry/Materials and Bioengineering/Kansai University
OBJECTIVES Hypertrophic stimuli activate cardiac transcription factors such as SRF, MEF-2, and a zinc finger protein GATA4 and modulate gene expression in cardiac myocytes. These changes finally lead to the development of heart failure in vivo. Acetylation is one of the critical mechanisms that activate these transcriptional factors and is mediated, in part, by intrinsic histone acetyltransferase (HAT) such as a transcriptional coactivator p300. Although many studies have shown a cardioprotective effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 unsaturated fatty acids, little is known about the effects of the EPA and DHA on cardiomyocyte hypertrophy and systolic dysfunction. In this study, we investigated the effects of the EPA and DHA on hypertrophic responses in cardiomyocytes and the development of heart failure in rats with myocardial infarction (MI).
METHODS First, Neonatal rat cultured cardiomyocytes were treated with EPA, or DHA. Palmitic acid (PA) or stearic acid (STA) were used as control. These cells were stimulated with saline or 30 μM phenylephrine (PE). After 48 hours, we measured cardiomyocyte surface area, hypertrophic responses gene transcriptions, and the ratio of acetylated histone H3. Next, we performed in vitro HAT assay using recombinant p300-HAT domain to determine the directly effect of EPA and DHA on p300-HAT activity. Finally, Rats with moderate MI (FS<40%) were randomly assigned to 3 groups; vehicle (saline), EPA, and DHA (1 g/kg). Oral administrations were repeated for six weeks from one week after the operation.
RESULTS Treatment with either DHA or EPA significantly inhibited the PE-induced hypertrophic responses such as myofibrillar organization, increase in cell size and mRNA expression of ANF and BNP. Moreover, DHA and EPA repressed the PE-induced acetylation of histone-3 in cardiomyocytes as much. The result of in vitro HAT assay revealed that 100 μM EPA and 100 μM DHA significantly inhibited p300-HAT activity. The echocardiographic analysis demonstrated that both EPA and DHA treatments prevented MI-induced systolic dysfunction and cardiac hypertrophy. Furthermore, EPA and DHA significantly suppressed the MI-induced increase in myocardial cell diameter, perivascular fibrosis, mRNA levels of hypertrophic and fibrotic markers, and acetylation of histone H3K9.
CONCLUSIONS These results suggested that both EPA and DHA suppressed MI-induced development of heart failure by inhibiting p300-HAT activity to the same extent. Thus, omega-3 unsaturated fatty acids EPA and DHA may exert as therapeutic agents to prevent the development of heart failure after MI.
GW34-e0357
Zhen Yao1, Yueli Liu2, Yong Zhang1, Yan Zhang1, Yuanchuan Chen1
1Cardiovascular Center, The Geriatric Hospital Of Hainan Province, Haikou 570000, China
2Pharmacy Institute of Hainan Medical College
OBJECTIVES To study frequency distribution of polymorphism in exon 13 of LDL-R gene in health people of Li and Han nationality in Hainan province and relationship between genotype and blood lipid, in order to understand the abnormal condition of lipid metabolism among Li people.
METHODS Five hundred and eighteen Li people and 592 Han people were recruited during this study. Fasting blood was drawn to evaluate levels of triglyceride (TG), cholesterol (TC), high density lipoprotein (HDL-C), low density of lipoprotein (LDL-C). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine AvaII Polymorphism of low density lipoprotein receptor gene.
RESULTS The results showed that A−A−, A+A− and A+A+ genotype frequency of low density lipoprotein receptor gene between Li and Han groups are [70.7 (366/518) vs 70.3% (416/592); 24.7 (128/518) vs 27% (160/592); 4.6 (24/518) vs 2.7% (16/592); x2=0.785, P=0.579] respectively, there is no significant difference between them. Comparisons of blood lipid levels in Li and Han group of TG, TC, HDL, and LDL are [(1.32±0.05) mmol/L vs (1.49±0.08) mmol/L, P=0.08]; [(5.03±0.07) mmol/L vs (5.16±0.06) mmol/L, P=0.21]; [(1.57±0.02) mmol/L vs (1.33±0.02) mmol/L, P<0.001]; [(2.72±0.06) mmol/L vs (3.13±0.05) mmol/L, P<0.001] respectively.
CONCLUSIONS In conclusion, Ava II polymorphism of LDL-R gene between Li and Han group is basically identical, and LDL-R gene polymorphism of the healthy of Li and Han group is not associated with blood lipid level. Level of HDL in Li group is significantly higher than that in Han group, and level of LDL in Li group is significantly lower than that in Han group.
GW34-e0361
Liming Chen, Shijun Wang, Junbo Ge, Yunzeng Zou
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Sciences, Fudan University
OBJECTIVES EphrinB2 (erythropoietin-producing hepatoma interactor B2) is a key member of the Eph/ephrin family, promoting angiogenesis, vasculogenesis, and lymphangiogenesis during embryonic development. However, the role of EphrinB2 in cardiac lymphangiogenesis following myocardial infarction (MI) and the potential molecular mechanism remains to be demonstrated. We sought to investigate whether and how EphrinB2 regulates cardiac lymphangiogenesis in the pathological remodeling process after MI.
METHODS Since homozygous Efnb2 knockout results in embryonic lethality, we utilized heterozygous Efnb2 knockout and adeno-associated virus of serotype 9 (AAV9)-mediated Efnb2 overexpression as loss- and gain-of-function approaches, respectively. We then investigated the effects of Efnb2 and its downstream mediators using RNA-sequencing analysis and in vitro experiments.
RESULTS We found that the expression of EphrinB2, which was rich in endothelium, was downregulated in the ischemic area of the heart two weeks after experimental MI. we subjected global Efnb2+/- mice and lymphatic-specific Efnb2 knockdown mice to either MI or sham operation. After two weeks, we observed that Efnb2 deficiency impaired cardiac lymphangiogenesis and led to adverse cardiac remodeling and ventricular dysfunction. Conversely, AAV9-mediated overexpression of EphrinB2 significantly improved cardiac function after MI. Intriguingly, overexpression of EphrinB2 also accelerated the resolution of inflammation, both macrophages and proinflammatory mediators. Moreover, the beneficial effects of EphrinB2 on inflammation and cardiac function were dependent on Lyve1. Additionally, EphrinB2 overexpression promoted the proliferation and migration of human lymphatic endothelial cells (hLECs) challenged by hypoxia. Our RNA-seq data showed that ISL1 appears to be a key factor in EphrinB2-driven lymphangiogenesis. Knockdown of ISL1 in hLECs greatly reduced the contributions of EphrinB2 in promoting cell proliferation and migration. Eventually, we confirmed the effects of ISL1 on lymphangiogenesis in vivo.
CONCLUSIONS Our findings uncovered a novel mechanism whereby EphrinB2 promotes cardiac lymphangiogenesis to improve myocardial remodeling and function following acute MI.
GW34-e0362
Shijun Wang, Liming Chen
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Sciences, Fudan University
OBJECTIVES Cardiac dysfunction and pathological remodeling are serious complications of sepsis, which is a leading cause of death in sepsis. RCAN1 is a feedback regulator of cardiac hypertrophy. Here, we aim to investigate the role of RCAN1 in septic cardiomyopathy.
METHODS Mice were randomly divided into control-WT, control-RCAN1−/−, LPS-induced WT, and LPS-induced RCAN1−/− groups, some with Midiv-1 or KN93 treatment. The protein levels of RCAN1, p-ERK1/2, NFAT3, Drp1, p-Drp1, and p-CaMKII in mouse hearts or cultured cardiomyocytes were detected by Western blotting. Cardiac function was assessed by echocardiography. Cardiac hypertrophy and fibrosis were detected by H&E and Masson’s trichrome staining. Mitochondrial morphology was examined by transmission electron microscope. Serum level of LDH was detected by ELISA.
RESULTS RCAN1 was downregulated in septic mouse hearts and LPS-treated cardiomyocytes. RCAN1−/− mice presented severe impairment of cardiac function and elevated myocardial hypertrophy and fibrosis. The protein levels of NFAT3 and p-ERK1/2 were significantly increased in the heart tissues of RCAN1−/− mice. Further, RCAN1 deficiency aggravated sepsis-induced cardiac mitochondrial injury as indicated by increased ROS production, pathological fission, and the loss of mitochondrial membrane potential. Inhibition of fission with Mdivi-1 reversed LPS-induced cardiac hypertrophy, fibrosis, and dysfunction in RCAN1−/− mice. Moreover, RCAN1 depletion promoted mitochondrial translocation of CaMKII, which enhanced fission and septic hypertrophy, while inhibition of CaMKII with KN93 reduced excessive fission, and improved LPS-mediated cardiac remodeling and dysfunction in RCAN1−/− mice.
CONCLUSIONS Our findings demonstrated that RCAN1 deficiency aggravated the mitochondrial injury and septic dysfunction by activating CaMKII. RCAN1 serves as a novel therapeutic target for the treatment of sepsis-related cardiac cardiomyopathy.
GW34-e0374
Sonoka Iwashimizu1, Ono Masaya1, Sunagawa Yoichi1,2,3, Mochizuki Saho1, Inai Kyoko1, Funamoto Masafumi1,2, Shimizu Kana1,2, Katanasaka Yasufumi1,2,3, Hamabe Toshihide1,2,3, Hawke Philip4, Hasegawa Koji1,2, Morimoto Tatsuya1,2,3
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka
2Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization
3Shizuoka General Hospital
4Laboratory of Scientific English, School of Pharmaceutical Sciences, University of Shizuoka
OBJECTIVES The prognosis of patients with malignant neoplasms has been improving due to advances in surgical treatment, radiation therapy, and chemotherapy with anticancer drugs. However, it has recently become clear that this longer period of patient survival has also resulted in increased exposure to the cardiotoxicity of anticancer drugs. The anthracycline anticancer drug doxorubicin (DOX) induces dose-dependent cardiotoxicity, ranging from occult changes in myocardial structure and function to severe cardiomyopathy and congestive heart failure. Since this cardiotoxicity affects the QOL and survival of cancer patients, a solution to this problem is urgently required. Anti-inflammatory activity. However, its effect on DOX-induced cardiotoxicity is still unknown. It has recently been reported that Chrysanthemum morifolium extract (CME) has antioxidant and anti-inflammatory activity. However, its effect on DOX-induced cardiotoxicity is still unknown.
METHODS To investigate whether CME suppressed DOX-induced cytotoxicity, an MTT assay was performed using H9C2 cells and primary cultured cardiomyocytes. Additionally, to examine the effect of CME on the anti-tumor activity of DOX, an MTT assay was performed using various cancer cells. Next, apoptosis was evaluated by TUNEL assay. The expression levels of p53, phosphorylated p53, cleaved-caspase3, and cleaved-caspase9 were also examined by western blotting. Eight-week-old C57BL/6J male mice were randomly assigned to treatment with either vehicle or 400 mg/kg CME orally for 15 days, beginning 2 days before intraperitoneal injection of 20 mg/kg DOX. After this treatment, survival assessments, echocardiography, and a TUNEL assay were performed.
RESULTS An MTT assay revealed that CME reduced DOX-induced cytotoxicity in H9C2 cells and primary cultured cardiomyocytes, but not in the cancer cell lines for which DOX is clinically indicated. A TUNEL assay showed that CME treatment improved DOX-induced apoptosis in H9C2 cells. Moreover, DOX-induced increases in the expression levels of p53, phosphorylated p53, and cleaved caspase-3 and -9 were significantly suppressed by CME treatment. Next, an experiment using a mouse model of acute heart failure showed that CME treatment substantially inhibited the DOX-induced decrease in survival rate. Echocardiographic analysis indicated that CME treatment reduced DOX-induced left ventricular systolic dysfunction. A TUNEL assay showed that CME treatment suppressed DOX-induced apoptosis in the mouse heart.
CONCLUSIONS These results suggest that CME treatment ameliorates DOX-induced cardiotoxicity by suppressing apoptosis. Therefore, CME may have the therapeutic potency to reduce DOX-induced cardiotoxicity in cancer patients. Further clinical study is needed to clarify this effect in humans.
GW34-e0376
Yingwen Lin1,2,3, Dongtu Hu1,2,3, Xiangjie Lin1,2,3, Juncong Li1,2,3, Shuwen Su1,2,3, Dingli Xu1,2,3, Qingchun Zeng1,2,3
1State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University
2Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University
3Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)
OBJECTIVES Galectin-1, a beta-glycoside binding protein, has been reported to involve a variety of cell functions including proliferation, cell migration and focal adhesion. The role of cell-matrix interaction in calcific aortic valve disease (CAVD) is not fully investigated and whether galectin-1 is involved in this process remains unclear. We hypothesized that galectin-1 mitigates the fibrocalcific response and mechanosensitivity of valve interstitial cells (AVICs) by modulating integrin-mediated cytoskeletal reorganization and focal adhesion.
METHODS We enrolled patients with CAVD and age- and sex-matched controls to detect serum galectin-1.
RESULTS We enrolled patients with CAVD and age- and sex-matched controls to detect serum galectin-1 and found that circulating galectin-1 was lower in CAVD. The expression of galectin-1 decreased in fibrocalcific valves and AVICs cultured in osteogenic medium (OM), as shown by western blot, qPCR, immunohistochemistry (IHC) and immunofluorescence. AVICs cultured in OM also presented enhanced integrin signaling, cytoskeletal reorganization and focal adhesion. Silencing galectin-1 by short-interfering RNA exacerbated the fibrocalcific change of AVICs in vitro while recombinant galectin-1 (rGal-1) prevented these effects. Anti-integrin blocking experiments and co-immunoprecipitation assays demonstrated that the galectin-1 directly interacted with integrin αvβ1 to regulate AVICs adhesion to a fibronectin matrix. Western blot, qPCR and Immunofluorescence assays confirmed that actin cytoskeletal reorganization was induced by αvβ1 activation through Rac1-WRC-Arp2/3 signaling axis. Western blot, alkaline phosphatase (ALP) as well as Alizarin red staining demonstrated that silencing galectin-1 enhanced AVICs sensitivity to piezo1 activation, which is dependent on αvβ1 binding and actin polymerization. In vivo, aortic valve disease was constructed by direct wire injury (DWI), and we showed that overexpression of galectin-1 by adeno-associated virus significantly accelerated the progression of aortic valve lesion induced by DWI in mice.
CONCLUSIONS Galectin-1 interacts with integrin αvβ1 to modulate cytoskeletal reorganization and AVICs adhesion to fibronectin, thus mitigating the fibrocalcific response of AVICs and aortic valve calcification.
GW34-e0391
Dmitry Kashirskikh1, Raisa Surkova1, Igor Sobenin1, Alexander Yakovlev2, Alexander Orekhov1
1Institute of General Pathology and Pathophysiology, Moscow, Russia
2Institute of Higher Nervous Activity and Neurophysiology, Moscow, Russia
OBJECTIVES Previously we found sialidase activity circulating in the blood of atherosclerotic patients. This sialidase is responsible for atherogenic modification of low-density lipoprotein. We have shown that desialylation is an atherogenic modification of LDL that makes the lipoprotein capable of inducing lipid accumulation in arterial wall cells, turning them into foam cells. The aim of this study was to isolate and identify proteins possessing sialidase activity.
METHODS The blood serum of atherosclerotic patients was screened for the presence of significant sialidase activity using commercial kits. Isolation of proteins with sialidase activity was performed using affinity chromatography followed by polyacrylamide gel electrophoresis. In order to identify the isolated proteins, the MALDI-TOF mass spectrometry method was used.
RESULTS About 700 blood serum samples were tested and 84 samples with sialidase activity were selected. Proteins of 65 kDa and 116 kDa were isolated from the eluate after affinity chromatography using polyacrylamide gel electrophoresis. Mass spectrometry revealed a wide range of proteins, but no known human neuraminidase was found among them. During chromatography, exosomes are isolated together with an affinity-binding protein, which explains the wide range of proteins identified by mass spectroscopy and masking the real result of affinity isolation.
CONCLUSIONS The data obtained suggest that an unidentified protein with sialidase activity circulates in the blood, both in free form and non-covalently bound to the extracellular vesicles membrane (exosomes).
This work was supported by the Russian Science Foundation (Grant # 22-65-00005).
GW34-e0392
Dmitry Kashirskikh, Alexandra Melnichenko, Alexander Orekhov
Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia
OBJECTIVES Electronegative LDL, small dense LDL, and desialylated LDL circulating in the blood of patients were obtained by different methods. Naturally, the question arises what are the similarities and differences between these forms of LDL modification. We believe that multiple modified LDL particle (small, dense, electronegative, desialylated, etc.) occurs in blood. Ex vivo experiments have revealed mechanisms of multiple modification of LDL in the blood.
METHODS Fraction of native LDL was isolated from blood plasma of healthy subjects. Blood serum of patients with assessed atherosclerosis was also obtained. LDL and serum were mixed and incubated for various periods at 37°C.
RESULTS After 1 hour incubation of native LDL with atherosclerotic serum desialylated LDL appears. After 3 hours, LDL becomes able to cause accumulation of cholesterol in cultured cells. After 6 hours, LDL demonstrates reduction of neutral lipids and phospholipids as well as reduction in its size. After 36 hours, an increase in the electronegativity of the lipoprotein particle is detected. After 48–72 hours, loss of α-tocopherol, increase of susceptibility to oxidation, and accumulation of lipid peroxidation products in LDL are observed. Thus, multiple modification of LDL is a cascade of sequential changes in lipoprotein particle, namely: desialylation, loss of lipids, size reduction, increase of electronegative charge, lipid peroxidation in LDL. Desialylation of LDL particle is one of the first or primary events of atherogenic modification. We have established that the reason of LDL desialylation is trans-sialidase. We found trans-sialidase activity in the blood of patients with atherosclerosis and other cardiovascular diseases. We have shown that human neuraminidases 2 and 4 possess trans-sialidase activity. On the other hand, selective inhibitors of viral sialidases suppress trans-sialidase activity in the blood of atherosclerotic patients.
CONCLUSIONS Thus, trans-sialidase causing atherogenic desialylation of LDL may be of both endogenous and exogenous origin.
This work was supported by the Russian Science Foundation (Grant # 23-65-10014).
GW34-e0393
Vasily Sukhorukov, Alexander Orekhov
Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia
OBJECTIVES Accumulation of lipid-laden (foam) cells in the arterial wall is known to be the earliest step in the pathogenesis of atherosclerosis. There is almost no doubt that atherogenic modified low-density lipoproteins (LDL) are the main sources of accumulating lipids in foam cells. Atherogenic modified LDL are taken up by arterial cells, such as macrophages, pericytes, and smooth muscle cells in an unregulated manner bypassing the LDL receptor. The present study was conducted to reveal possible common mechanisms in the interaction of macrophages with associates of modified LDL and non-lipid latex particles of a similar size.
METHODS To determine regulatory pathways that are potentially responsible for cholesterol accumulation in human macrophages after the exposure to naturally occurring atherogenic or artificially modified LDL, we used transcriptome analysis.
RESULTS Previous studies of our group demonstrated that any type of LDL modification facilitates the self-association of lipoprotein particles. The size of such self-associates hinders their interaction with a specific LDL receptor. As a result, self-associates are taken up by nonspecific phagocytosis bypassing the LDL receptor. That is why we used latex beads as a stimulator of macrophage phagocytotic activity. We revealed at least signaling pathways that were regulated by the interaction of macrophages with the multiple-modified atherogenic naturally occurring LDL and with latex beads in a similar manner. Therefore, modified LDL was shown to stimulate phagocytosis through the upregulation of certain genes. We have identified at least three genes (F2RL1, EIF2AK3, and IL15) encoding inflammatory molecules and associated with signaling pathways that were upregulated in response to the interaction of modified LDL with macrophages. Knockdown of two of these genes, EIF2AK3 and IL15, completely suppressed cholesterol accumulation in macrophages. Correspondingly, the upregulation of EIF2AK3 and IL15 promoted cholesterol accumulation.
CONCLUSIONS These data confirmed our hypothesis of the following chain of events in atherosclerosis: LDL particles undergo atherogenic modification; this is accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. This chain of events may explain the relationship between cholesterol accumulation and inflammation. The primary sequence of events in this chain is related to inflammatory response rather than cholesterol accumulation.
This work was supported by the Russian Science Foundation (Grant # 23-45-00031).
GW34-e0396
Vasily Sukhorukov, Alexander Orekhov
Institute for Atherosclerosis Research, Osennyaya Street 4-1-207, Moscow 121609, Russia
OBJECTIVES Mitochondrial dysfunction is thought to be one of the causative factors of impaired innate immunity during atherosclerosis development. The presence of heteroplasmic mutations in mitochondrial DNA (mtDNA) can result in the appearance of dysfunctional mitochondria in intimal cells. The aim of this study was to evaluate the effect of the m.15059G>A mitochondrial nonsense mutation on cellular functions related to atherosclerosis, such as lipoidosis, pro-inflammatory response, and mitophagy. It was suggested that heteroplasmic mutations could be responsible for mitochondrial dysfunction, which could lead to a disturbance of the innate immunity response and, ultimately, the chronic inflammation associated with atherosclerosis.
METHODS The human monocytic cell line THP-1 and cytoplasmic hybrid cell line TC-HSMAM1 were used. An original approach based on the CRISPR/Cas9 system was developed and used for the elimination of mtDNA copies carrying the m.15059G>A mutation in the MT-CYB gene. The gene expression levels of genes encoding enzymes related to cholesterol metabolism were analyzed by quantitative RT-PCR. The evaluation of pro-inflammatory cytokine secretion was assessed using ELISA. Mitophagy in cells was detected using confocal microscopy.
RESULTS In contrast to intact TC-HSMAM1 cybrids, in Cas9-TC-HSMAM1 cells, incubation with atherogenic LDL led to a decrease in the expression of the gene encoding fatty acid synthase (FASN). It was found that TC-HSMAM1 cybrids are characterized by defective mitophagy and are also unable to reduce the production of pro-inflammatory cytokines (to form immune tolerance) in response to repeated LPS stimulation. Elimination of mtDNA carrying the m.15059G>A mutation led to the restoration of immune tolerance and activation of mitophagy in the studied cells.
CONCLUSIONS The m.15059G>A mutation was found to be associated with defective mitophagy, immune tolerance, and impaired metabolism of intracellular lipids due to upregulation of the FASN in monocytes and macrophages.
This study was supported by Russian Science Foundation, Grant # 22-15-00064.
GW34-e0397
Victoria Khotina, Alexander Zhuravlev, Vasily Sukhorukov
Institute of General Pathology and Pathophysiology
OBJECTIVES Recent studies have identified mutations in mitochondrial DNA (mtDNA) that are linked with the development of atherosclerosis. Such mutations can cause mitochondrial dysfunction, ultimately leading to the activation of signaling pathways that promote the secretion of pro-inflammatory cytokines. It is possible to facilitate the study of this association using cytoplasmic hybrid cell lines, that can be created by fusion of mitochondria-depleted THP-1 monocytes with enucleated thrombocytes derived from atherosclerotic patients with mtDNA mutations. This study aimed to evaluate the correlation between the m.15059G>A mutation in the mitochondrial MT-CYB gene and pro-inflammatory cytokine secretion, as well as the ability of monocytes to form immune tolerance.
METHODS Human monocyte-like cell line THP-1, cybrid line TC-HSMAM1 with m.15059G>A mutation (MT-CYB), and cybrid cells TC-HSMAM1 with eliminated m.15059G>A mutation (Cas9-TC-HSMAM1) by CRISPR/Cas9 editing were used. The pro-inflammatory response was induced by bacterial lipopolysaccharide (LPS). The secretion of cytokines was assessed by ELISA. To assess immune tolerance, cells were incubated for 16 hours with LPS followed by additional incubation with LPS for 4 h.
RESULTS The study revealed that both TC-HSMAM1 and Cas9-TC-HSMAM1 cybrids showed an increased basal level of IL-1β, IL-6, IL-8, and MCP-1 (CCL2) compared to the control THP-1 cells (P<0.05). Nevertheless, while the basal secretion level of TNFα had no difference between Cas9-TC-HSMAM1 cells and control THP-1 cells, the secretion of this cytokine by TC-HSMAM1 cybrids was significantly increased (P<0.01). Following stimulation of the pro-inflammatory cell phenotype with LPS, there was a significant increase in the secretion of all cytokines in all studied cells. Notably, the secretion of IL-8 and MCP-1 in both TC-HSMAM1 and Cas9-TC-HSMAM1 cybrids did not have any statistically significant differences from control THP-1 cells. Furthermore, the secretion of IL-1β and TNFα by TC-HSMAM1 cybrids was observed to decrease compared to control THP-1 cells after LPS stimulation (P<0.05). On the other hand, the secretion of these cytokines by Cas9-TC-HSMAM1 cells did not differ from the control THP-1 cells. However, IL-6 secretion was significantly increased in TC-HSMAM1 cybrids compared to THP-1 cells (P<0.05), whereas the secretion of this cytokine in Cas9-TC-HSMAM1 exceeded that of both cell lines. The evaluation of the ability to form immune tolerance by cells showed that Cas9-TC-HSMAM1 and THP-1 cells were able to form immune tolerance, which consisted of an increase in TNFα secretion after the first LPS stimulation and a decrease in the secretion of pro-inflammatory cytokines after repeated LPS stimulation. However, TC-HSMAM1 cybrids showed elevated TNFα secretion in response to repeated LPS stimulation demonstrating the inability to form immune tolerance.
CONCLUSIONS The study findings suggest that monocytes with the m.15059G>A mutation in MT-CYB exhibit increased basal secretion and decreased LPS-stimulated secretion of TNFα compared to Cas9-TC-HSMAM1 and THP-1. Additionally, TC-HSMAM1 cells were found to be unable to form immune tolerance in response to repeated stimulation of cells with LPS.
This work was supported by Russian Science Foundation Grant #22-25-00393.
GW34-e0398
Victoria Khotina, Vasily Sukhorukov
Institute of General Pathology and Pathophysiology
OBJECTIVES Recent researches have shown an association between mutations in mtDNA and the development of atherosclerosis. In particular, the m.15059G>A mutation in the mitochondrial MT-CYB gene has been found in lipofibrous plaque cells from patients with atherosclerosis. However, it is still unclear how these mutations affect key processes such as apoptosis regulation, synthetic activity, and proliferation of macrophages, that play a crucial role in atherosclerotic plaque development. To investigate this association, cytoplasmic hybrid cell lines with mutations in mtDNA, created from THP-1 monocyte cells, can be utilized. In this study, we aim to investigate the association between the m.15059G>A mutation in the MT-CYB and the expression of genes related to apoptosis, cell cycle regulation, and protein synthesis in monocytes and macrophages.
METHODS Human monocyte-like cell line THP-1, cybrid line TC-HSMAM1 with m.15059G>A mutation (MT-CYB), and cybrid line TC-HSMAM1 with eliminated m.15059G>A mutation (Cas9-TC-HSMAM1) by CRISPR/Cas9 editing were used. The qPCR was used to assess the expression of apoptotic pathway related genes (BCL2, BAX, CASP3, CASP9, APAF1), the expression of cell cycle regulation related genes (PCNA, CCNB1, CCND1), and the expression of protein synthesis related genes (POLR1A, POLR3A, COL6A1).
RESULTS It was found that TC-HSMAM1 cybrids had an increased expression of BCL2, CASP3 and APAF1, and a decreased expression of BAX and CASP9 compared to THP-1 cells (P<0.001). Elimination of mutated mtDNA from cybrids led to an increase of BAX and CASP9 expression and a decrease of CASP3 expression (P<0.01). However, there were no differences in expression of BCL2 and APAF1 between TC-HSMAM1 and Cas9-TC-HSMAM1 cells (P>0.05). Moreover, BAX/BCL2 ratio in TC-HSMAM1 cells was reduced compared to control THP-1 cells (P<0.001). In contrast, BAX/BCL2 ratio in Cas9-TC-HSMAM1 cells was increased compared to TC-HSMAM1 (P<0.05). It was shown that the expression of PCNA, CCNB1 and CCND1 in TC-HSMAM1 cells was increased compared to THP-1 cells (P<0.001). Increased expression of PCNA and CCND1 was observed in Cas9-TC-HSMAM1 cells compared to the control THP-1 cells (P<0.01), while the expression of the CCNB1 had no difference. No statistically significant difference was found in the expression of the PCNA and CCND1 in cybrid cells before and after the elimination of the m.15059G>A mutation. However, decreased CCNB1 expression was observed in Cas9-TC-HSMAM1 cells compared to TC-HSMAM1 (P<0.01). It was found that the expression of the POLR1A and COL6A1 in the TC-HSMAM1 cybrids was increased compared with THP-1 cells (P<0.001), while the expression of POLR3A was decreased. Increased expression of the POLR3A and COL6A1 was found in Cas9-TC-HSMAM1 cells compared with the control THP cells (P<0.001), while POLR1A expression was significantly decreased (P<0.001). However, POLR1A and COL6A1 expression was decreased in Cas9-TC-HSMAM1 compared with the TC-HSMAM1 cells (P<0.01), while POLR3A expression was increased.
CONCLUSIONS Our findings suggest that the m.15059G>A mutation may be associated with decreased expression of BAX, CASP9 and POLR3A, and the increased expression of CASP3, CCNB1, POLR1A and COL6A1, indicating a possible role of this mutation in regulation of macrophage apoptosis, cell cycle (proliferation activity) and protein synthesis. Furthermore, the presence of this mutation was accompanied by a reduced BAX/BCL2 ratio.
This work was supported by Russian Science Foundation Grant #22-25-00393.
GW34-e0399
Victoria Khotina1, Alexander Zhuravlev1, Vasily Sukhorukov1,2
1Institute of General Pathology and Pathophysiology
2Petrovsky National Research Centre of Surgery
OBJECTIVES A growing body of research demonstrates the role of mutations in mitochondrial DNA (mtDNA) in the development of inflammatory diseases, such as atherosclerosis. These mutations may cause mitochondrial dysfunction, promoting the activation of pro-inflammatory cell response, including the formation of NLRP3 inflammasomes. In turn, NLRP3 inflammasomes produce pro-inflammatory cytokines such as IL-1β. Interestingly, recent findings have discovered the presence of mtDNA mutations in atherosclerotic plaque cells, but little information exists on how these mutations impact the pro-inflammatory response of macrophages. Improved knowledge of the association between mtDNA mutations and the expression of pro-inflammatory cytokines could pave the way for the development of new therapeutic approaches for atherosclerosis treatment. This study aimed to investigate the association between the m.15059G>A mutation in the MT-CYB gene and the expression of NLRP3 inflammasome-related genes.
METHODS Human monocyte-like cell line THP-1, TC-HSMAM1 cybrids with m.15059G>A mutation (MT-CYB), and TC-HSMAM1 cells with eliminated m.15059G>A mutation (Cas9-TC-HSMAM1) by CRISPR/Cas9 editing were used. NLRP3 inflammasome (NLRP3), caspase 1 (CASP1) and interleukin 1β (IL1B) gene expression was measured by qPCR. Pro-inflammatory response was induced by bacterial lipopolysaccharide (LPS). IL-1β secretion was assessed by ELISA.
RESULTS It was shown, that the basal expression of NLRP3 and IL1B genes was increased in TC-HSMAM1 cybrids compared to control THP-1 cells, while the CASP1 expression had no changes. However, elimination of the m.15059G>A mutation resulted in decreased basal expression of all studied genes. Under stimulation with LPS, an increased CASP1 expression was observed in TC-HSMAM1 cells compared to unstimulated cells, while the expression of IL1B and NLRP3 remained unaltered. Nevertheless, IL1B expression was increased, and CASP1 expression was reduced in LPS-stimulated TC-HSMAM1 cells when compared to LPS-stimulated control THP-1 cells. Stimulation of Cas9-TC-HSMAM1 cells with LPS resulted in increased expression of all studied genes compared to unstimulated cells. In addition, NLRP3 expression was found to be elevated in Cas9-TC-HSMAM1 cybrids compared to the TC-HSMAM1 cells. Nevertheless, CASP1 and IL1B expression was shown to have no significant differences from the TC-HSMAM1 cells, as confirmed by IL-1β cell secretion.
CONCLUSIONS Our results suggest that the presence of the m.15059G>A mutation in the MT-CYB gene may increase the formation of NLRP3 inflammasomes in macrophages due to an increased expression of NLRP3 and IL1B genes in normal physiological conditions.
This work was supported by Russian Science Foundation Grant #22-25-00274.
GW34-e0400
Victoria Khotina, Vasily Sinyov, Vasily Sukhorukov
Institute of General Pathology and Pathophysiology
OBJECTIVES Mitochondrial dysfunction can arise from a range of factors, including mutations in mtDNA. Among these mutations, the m.15059G>A mutation in the MT-CYB gene is of particular interest due to its impact on the cytochrome b protein, which plays a critical role in the electron transport chain of mitochondria. The m.15059G>A mutation leads to the formation of a truncated variant of cytochrome b, which can impair its functional activity and consequently perturb the mitochondrial bioenergetic profile of monocytes and macrophages. Monocytes and macrophages have high bioenergetic demands and rely on the proper functioning of mitochondria to carry out their diverse functions including phagocytosis and cytokine production. The bioenergetic profile of these cells is regulated by the balance between mitochondrial respiration and glycolysis. Any perturbations to this balance, such as those resulting from the m.15059G>A mutation, can have profound impacts on the function and behavior of these cells. While the exact mechanisms underlying this association remain unclear, we aimed to investigate the association between the m.15059G>A mutation in the MT-CYB with impaired mitochondrial respiration and bioenergetic profile in monocytes.
METHODS Human monocyte-like cell line THP-1, TC-HSMAM1 cybrids with m.15059G>A mutation (MT-CYB), and TC-HSMAM1 cells with eliminated m.15059G>A mutation (Cas9-TC-HSMAM1) by CRISPR/Cas9 editing were used. The Oxygraph+ System with S1 Clark-type polarographic oxygen electrode was used to measure oxygen consumption rate (OCR) of cells. Parameters of the cellular mitochondrial function was assessed using respiratory chain inhibitors (oligomycin A, FCCP, antimycin A).
RESULTS It was shown that the OCR traces of all studied lines displayed a similar profile. However, basal OCR was found to be significantly reduced in Cas9-TC-HSMAM1 cells compared to the control THP-1 cells and TC-HSMAM1 cybrids (P<0.05). Conversely, under treatment with oligomycin A and antimycin A, TC-HSMAM1 cybrids demonstrated an increase in OCR compared to control THP-1 cells and Cas9-TC-HSMAM1 cybrids. Analysis of mitochondrial bioenergetic profiles revealed that TC-HSMAM1 cybrids exhibited significantly increased parameters such as non-mitochondrial OCR and proton leak OCR in comparison to control THP-1 cells (P<0.001). However, these parameters did not differ significantly between Cas9-TC-HSMAM1 and THP-1 cells. Furthermore, parameters including ATP-linked OCR, maximal OCR, and reserve capacity OCR did not demonstrate statistically significant differences between THP-1 and TC-HSMAM1 cells. Nevertheless, there was a decrease in maximal OCR observed in Cas9-TC-HSMAM1 cells as compared to control THP-1 cells and TC-HSMAM1 cybrids (P<0.05). Evaluation of the cellular Bioenergetic Health Index (BHI), calculated using a logarithmic dependence of reserve capacity OCR, ATP-linked OCR, non-mitochondrial OCR, and proton leak OCR, revealed that BHI was reduced in TC-HSMAM1 cybrids compared to the control. Conversely, BHI was found to be significantly increased in Cas9-TC-HSMAM1 cybrids when compared to TC-HSMAM1.
CONCLUSIONS The m.15059G>A mutation in the MT-CYB gene has been shown to impact various parameters related to the bioenergetic functions of mitochondria, including non-mitochondrial OCR, proton leakage, and BHI.
This work was supported by Russian Science Foundation Grant #22-65-00005.
GW34-e0401
Victoria Khotina1, Mariam Bagheri-Ekta2, Arthur Lee1,2, Vasily Sukhorukov1,2
1Institute of General Pathology and Pathophysiology
2Petrovsky National Research Centre of Surgery
OBJECTIVES PERK is a transmembrane protein located in the endoplasmic reticulum (ER) of cells, and it plays an essential role in the regulation of ER-stress response. Recent studies have shown that ER stress and unfolded protein response induction alter the expression of genes related to lipid metabolism. Moreover, it has been shown that an increase of cellular cholesterol in vascular smooth muscle cells from atherosclerotic plaques triggers ER-stress and activates PERK signaling. However, it is not fully understood how PERK is involved in altering lipid metabolism in macrophages and in the formation of foam cells, a hallmark of atherosclerosis. The main aim of this study was to evaluate the impact of PERK on macrophage cholesterol accumulation and the regulation of expression of genes related to lipid metabolism.
METHODS Human monocyte-like cell line THP-1 was used as control. CRISPR/Cas9 editing was used to generate THP-1 cell line with PERK gene knockout (THP-1 PERK −/−). Macrophage-like phenotype differentiation was induced by phorbol 12-myristate 13-acetate (PMA). Foam cell formation was induced by cell incubation with low-density lipoproteins (LDL). LDL was isolated from plasma from atherosclerotic patients using preparative ultracentrifugation technique. Cholesterol accumulation was measured by spectrophotometry. The expression of ATP binding cassette subfamily A member 1 (ABCA1), acetyl-CoA acetyltransferase 1 (ACAT1), fatty acid synthase (FASN), neutral cholesterol ester hydrolase 1 (NCEH1) and cluster of differentiation 36 (CD36) genes was assessed by qPCR.
RESULTS To induce PERK knockout, THP-1 cells were transfected using two sgRNAs and a plasmid containing an expression cassette with the sequence of the puromycin resistance gene. A stable clone of cells with the most effective PERK knockout was obtained after 4 weeks of puromycin selection. PERK gene knockout in the obtained clone was confirmed by qPCR and Sanger sequencing. Incubation of THP-1 macrophages with atherogenic LDL induced an increase in intracellular cholesterol level compared to untreated control (P<0.001). In turn, incubation of THP-1 PERK −/− cells with atherogenic LDL had no impact on intracellular cholesterol accumulation. It was found that the basal expression of ABCA1, FASN, NCEH1 and CD36 was decreased in THP-1 PERK −/− macrophages compared to control cells (P<0.001). Incubation of THP-1 macrophages with atherogenic LDL led to an increased expression of the ACAT1 and NCEH1, as well as a decreased expression of ABCA1, FASN and CD36 compared to the untreated cells (P<0.001). At the same time, decreased expression of FASN, NCEH1 and CD36 in response to cholesterol accumulation was observed in THP-1 PERK −/− macrophages compared to the untreated cells (P<0.05), while the expression of ACAT1 and ABCA1 had no changes. Moreover, the expression level of ACAT1 had no difference between THP-1 and THP-1 PERK −/− cells under cell incubation with atherogenic LDL.
CONCLUSIONS Thus, it was found that PERK may be involved in the regulation of signaling pathways of ABCA1, FASN, NCEH1 and CD36. The obtained results may indicate a possible involvement of PERK in the intracellular lipid metabolism of macrophages, contributing in foam cell formation process.
This work was supported by Russian Science Foundation Grant #22-25-00393.
GW34-e0407
Jingyi Zhang1,2, Ziyang Xue1,2, Mingke Chang1,2, Xinxin Feng1,2, Yifan Cai1,2, Liang Bai1,3, Weirong Wang1,3, Sihai Zhao3, Enqi Liu1,3, Rong Wang1,2
1Institute of Cardiovascular Science, Translational Medicine Institute, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
2Department of Laboratory Animal Science, School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
3Laboratory Animal Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
OBJECTIVES Phenotypic switching of vascular smooth muscle cells (VSMCs) plays an essential role in the development of atherosclerosis. Protein inhibitor of activated STAT (Pias) regulates VSMCs phenotype via acting as sumo E3 ligase to promote protein sumoylation. Our previous study indicates that Pias3 expression decreased in atherosclerotic lesions. Therefore, this study was aimed to explore the role of Pias3 on VSMCs phenotype switching during atherosclerosis.
METHODS ApoE −/− and ApoE −/− Pias3 −/− double-deficient mice were fed with high-fat/high-cholesterol diet to induce atherosclerosis. Aorta tissues and primary VSMCs were collected for assessing plaque formation and VSMCs phenotype. In vitro, Pias3 was overexpressed in A7r5, a VSMCs cell line, by transfecting with Pias3 plasmid. Quantitative PCR, immunoblotting, immunoprecipitation, etc. were used to analyze the effect of Pias3 on VSMCs phenotypic switching.
RESULTS Pias3 deficiency significantly exacerbated atherosclerotic plaque formation and promoted VSMCs phenotypic switching to synthetic state. In vitro, overexpressing Pias3 in VSMCs increased the expression of contractile markers (myosin heavy chain 11, calponin 1), whereas decreased the level of synthetic marker (vimentin). Additionally, Pias3 overexpression impeded PDGF-BB-induced VSMCs proliferation and migration. Immunoprecipitation and mass spectrometry results showed that Pias3 enhanced the sumoylation and ubiquitination of vimentin, as well as shortened its half-life. Moreover, the ubiquitination level of vimentin could be impaired by 2-D08, a sumoylation inhibitor. It suggests that Pias3 might accelerate the ubiquitination-degradation of vimentin by promoting its sumoylation.
CONCLUSIONS These results indicated that Pias3 might ameliorate atherosclerosis progression by suppressing VSMCs phenotypic switching and reducing vimentin protein stability.
GW34-e0415
Linqiang Xi
Cardiac Pacing and Electrophysiology/Department of Cardiac Electrophysiology and Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China
OBJECTIVES Energy metabolism in atrial remodeling has been implicated in the development of atrial fibrillation. Renault oxazine inhibits fatty acid oxidation and increases glucose oxidation, without causing an increase in glycolysis or lactic acid release. It improves the coupling between glycolysis and glucose oxidation, and can improve the REDOX balance and mitochondrial function, thereby suppressing the occurrence of atrial fibrillation. This study is aimed at understanding the specific mechanism by which Renault oxazine reshapes energy metabolism in atrial fibrillation.
METHODS Male SD rats were randomly divided into 3 groups (n=12): control group, ANgII group, and ANgII+Renault oxazine group. Blood samples were taken weekly and electrocardiogram, ultrasound, and electrophysiological examinations were carried out before sacrificing the rats for analysis. HL-1 cells were divided into five groups: control group, ANgII treatment group, deferoxamine treatment group, ANgII plus Renault oxazine group, and ANgII and Renault lamictal and deferoxamine combination treatment group. Western blotting was used to analyze the expression of key enzymes related to glucose and lipid metabolism.
RESULTS ANgII-induced atrial remodeling was associated with a significant increase in left atrial diameter and a high rate of atrial fibrillation. However, treatment with Renault oxazine significantly improved these parameters. Western blotting confirmed the existence of molecular expression disorders related to glucolipid metabolism in the ANgII treatment group HL-1 cells. HIF-1α and PPAR-gamma expression were significantly lower in this group, while Renault oxazine did not show any statistically significant differences from the control group. Treatment with Renault oxazine resulted in no significant differences in the expression of key enzymes related to glucose and fatty acid intake, when compared to the control group.
CONCLUSIONS Renault oxazine improves the energy metabolism of rat atrial fibrillation induced by ANgII remodeling by inhibiting the HIF-1α-PPAR-gamma pathway.
GW34-e0422
Jishou Zhang, Menglong Wang, Jun Wan
Renmin Hospital of Wuhan University
OBJECTIVES Inflammation plays a critical role in the development of hypertension and vascular remodeling. Resolvin E1 (RvE1), as one of the specialized proresolving lipid mediators, promotes inflammation resolution by binding with a G protein-coupled receptor, ChemR23. However, whether RvE1/ChemR23 regulates hypertension and vascular remodeling is unknown.
METHODS Hypertension in mice was induced by Angiotensin II (AngII) infusion (750 ng/kg/min) and RvE1 (2 μg/kg/day) was administrated through intraperitoneal injection. We knocked down ChemR23 expression in mice by intravenously injecting adeno-associated virus-9 (AAV9) encoding shRNA against ChemR23 (AAV9-ChemR23).
RESULTS We found that RvE1 lowered blood pressure, reduced aortic media thickness, attenuated aortic fibrosis, mitigated vascular smooth muscle cell (VSMC) phenotypic transformation and proliferation, which were all reversed by the knockdown of ChemR23 that was mainly expressed on VSMCs. Moreover, RvE1 reduced the aortic infiltration of macrophages and T cells, which was also reversed by ChemR23 knockdown. RvE1 inhibited Ccl5 expression in VSMCs via an AMPKα/Nrf2/canonical NF-κB pathway, thereby reducing the infiltration of macrophages and T cells. The AMPKα/Nrf2 pathway also mediated the effects of RvE1 on VSMC phenotypic transformation and proliferation. In hypertensive patients, the serum levels of RvE1 and other eicosapentaenoic acid (EPA)-derived metabolites were significantly decreased.
CONCLUSIONS RvE1/ChemR23 ameliorated hypertension and vascular remodeling by activating AMPKα/Nrf2 signaling, which mediated immune cell infiltration through inhibiting canonical NF-κB/Ccl5 pathway and regulated VSMC proliferation and phenotypic transformation in VSMCs. RvE1/ChemR23 may be a potential therapeutic target for hypertension.
GW34-e0423
Yijia Shao1, Xiang Liu2, Fang Wu1, Long Chen3
1Department of Geriatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou
2Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou
3The International Medical Department of Shenzhen Hospital, Southern Medical University, Shenzhen
OBJECTIVES Trimethylamine-N-Oxide (TMAO) is recognized as a novel marker and mediator of atherosclerotic cardiovascular disease (ASCVD). Endothelial progenitor cells (EPCs) are crucial for maintaining vascular homeostasis. Impaired EPC numbers and function correlate with increased adverse cardiovascular events. The aim of this study was to determine the effect of TMAO on late EPCs (LEPCs) and its underlying molecular mechanism.
METHODS In vitro migration and tubulogenic capacities of LEPCs were attenuated by TMAO in a dose-dependent manner, accompanied with inhibition of manganese superoxide dismutase (MnSOD) and mitochondrial damage. TMAO induced mitochondrial damage provoked the proinflammatory responses (increased levels of IL-6, IL-1b, ICAM-1, E-sel and TNF-α) and autophagic cell death (confirmed by Western blot immunofluorescent staining and transmission electron microscopy) in LEPCs.
RESULTS Overexpression of MnSOD through adenovirus transfection reversed TMAO-related LEPCs dysfunction. To study the effect of TMAO on LEPCs-mediated vascular repair in vivo, hind limb ischemia model was established in nude mice and LEPCs were injected in the ischemic hind limb. Laser Doppler imaging of mouse ischemic hindlimbs at 21 days indicated that TMAO treatment inhibited LEPCs-mediated blood flow recovery, which was restored by MnSOD overexpression. Tissue analyses further revealed consistent alterations in capillary density determined by CD31 staining.
CONCLUSIONS TMAO induces mitochondrial damage in LEPCs via MnSOD suppression, which leads to cell dysfunction, proinflammatory activation and autophagic cell death in vitro and impaired LEPCs-mediated revascularization in vivo. Overexpression of MnSOD restores TMAO-induced LEPCs dysfunction and further enhances LEPCs-mediated revascularization in the ischemic hind limbs in nude mice.
GW34-e0432
Zikun Duan1, Jing Gan1, Yulin Li2, Fan Wu1, Zhuofeng Lin1
1The First Affiliated Hospital, School of Pharmaceutical Sciences, Wenzhou Medical University
2Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Anzhen Hospital of Capital Medical University
OBJECTIVES Bone morphogenetic protein 9 (BMP9) is a member of the TGF-β family of cytokines with pleiotropic effects on glucose metabolism, pro-fibrosis, and lymphatic development. However, the role of BMP9 in myocardial infarction (MI) remains elusive.
METHODS The expressional profiles of BMP9 in cardiac tissues and plasma samples of subjects with MI were determined by immunoassay or immunoblot. The roles of BMP9 in MI were determined by evaluating the impact of BMP9 deficiency and replenishment with adeno-associated virus-mediated BMP9 (AAV-BMP9) expression in mice with MI.
RESULTS Circulating BMP9 levels and its cardiac contents are markedly increased in humans and mice with MI and are negatively associated with cardiac functions. BMP9 deficiency causes a marked exacerbation of left ventricle dysfunction, increases infarct size, and cardiac fibrosis in mice with MI. In contrast, replenishment of BMP9 strikingly attenuates these adverse effects via two independent mechanisms, improving lymphatic drainage function, thereby leading to decrease cardiac edema, and triggering the mitochondrial production of 2,4-Dienoyl-CoA reductase (DECR1), a rate-limiting enzyme involved in β-oxidation of unsaturated fatty acids in mitochondria, which in turn promotes cardiac mitochondrial bioenergetics, then mitigating MI-induced cardiomyocyte injuries. Furthermore, DECR1 deficiency exacerbated MI-induced cardiac injury in mice, whereas this adverse effect was restored when treated with AAV-DECR1. In addition, DECR1 deletion strikingly abrogates the beneficial impact of BMP9 against MI-induced cardiac dysfunction and damage in mice.
CONCLUSIONS These results indicated that BMP9 protects against MI via fine-tuning the multiorgan crosstalk among the liver, lymph, and heart.
GW34-e0434
Zhongming Li1,2, Kai Wang1, Yinzhang Ding3, Yansong Li1, Di Xu1
1Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, Jiangsu 210029, China
2Department of Echocardiography, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, Jiangsu 210004, China
3Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, Jiangsu 210029, China
OBJECTIVES Myocardial fibrosis is an essential pathological feature of ventricular remodeling in post-myocardial infarction (MI). Dapagliflozin (DAPA), the sodium-glucose cotransporter 2 inhibitor (SGLT2i), is a new type of anti-glycemic agent, whose cardiovascular protective mechanisms have been the focus of recent research. However, the effects of dapagliflozin on myocardial fibrosis post-myocardial infarction are still unclear. It is objected to investigating the effects of dapagliflozin on myocardial fibrosis in post-myocardial infarction mice and the regulation of the Nrf2/HO-1 signaling pathway.
METHODS MI or sham-operated models were established in C57BL/6 mice, individually treated with saline (10 mL/kg) or 1 mg/kg DAPA by gavage once a day for 28 days since the operation day. In vitro, cardiac fibroblasts were isolated and cultured from 1 to 3 days C57BL/6J mice, and the cell model was constructed by oxygen-glucose deprivation (OGD). The in vitro models were treated with or without 1 μM DAPA. The Nrf2 inhibitor ML385 was applied to investigate whether it reverses the effect of dapagliflozin on the OGD cell model and to explore the potential mechanism of dapagliflozin to improve myocardial fibrosis. Cardiac structure and function, cardiac fibrosis, and oxidative stress were measured.
RESULTS Our results revealed that DAPA significantly improved cardiac function and remodeling, reduced cardiac fibrosis, and ameliorated oxidative stress in the post-MI model. The Nrf2/HO-1 signaling pathway was suppressed in the MI group compared to the Sham and Sham+DAPA groups and activated in the post-infarction mice treated with DAPA. Similar observations were made in the OGD model after treatment with DAPA. Moreover, the Nrf2 inhibitor ML385 reverses the effect of dapagliflozin on the OGD-induced cardiac fibroblasts.
CONCLUSIONS Dapagliflozin ameliorated cardiac function, myocardial fibrosis, and oxidative stress in mice post-myocardial infarction by a mechanism that may be related to the activation of the Nrf2/HO-1 signaling pathway. In an OGD-induced cardiac fibroblast model, dapagliflozin ameliorated myocardial fibrosis by activating the Nrf2/HO-1 signaling pathway.
GW34-e0440
Dmitry Kashirskikh1,2,3, Nelya Chicherina1,4, Vadim Cherednichenko3, Igor Sobenin2,5, Alexander Orekhov1,2,3
1Institute for Atherosclerosis Research
2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology
3Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Avtsyn Research Institute of Human Morphology of FSBI “Petrovsky National Research Centre of Surgery”
4Sirius University of Science and Technology
5Laboratory of Medical Genetics, National Medical Research Center of Cardiology
OBJECTIVES Pathological processes in the human body lead to various modifications of native low-density lipoproteins (LDL), and desialylation is a well-known atherogenic modification. Desialylated LDL (desLDL) are highly susceptible to oxidation, aggregation, and self-association, which can contribute to the development of atherosclerosis. Moreover, desLDL particles are actively phagocytosed by macrophages and smooth muscle cells in the aorta. Although atherosclerosis has been extensively studied in mouse models, there is currently no appropriate model to study LDL desialylation in mice. Present study aims to establish a mouse model that accurately simulates the desialylation of LDL.
METHODS Control group of C57Bl/6J wild-type mice (n=70 in each group) was injected with saline, while the experimental group was subjected to a single injection of immobilized Vibrio cholerae neuraminidase with an enzymatic activity of 0.2 U/mL. At each time point (1–7 days after a single injection), 10 mice from both groups were randomly selected for sacrifice. The control group (n=30 in each group) received saline injections for 6 weeks, while the experimental group underwent a series of injections of immobilized Vibrio cholerae neuraminidase for 6 weeks. At 2, 4, and 6 weeks, 10 mice were randomly selected from both the control and experimental groups. The sialic acid content in LDL samples was determined using the Warren method. Blood lipids were measured using commercial kits. Atherosclerotic burden in the mouse aorta was quantified by staining with Oil Red O and hematoxylin-eosin.
RESULTS A single injection of 100 μL of immobilized Vibrio cholerae neuraminidase solution at a concentration of 0.2 U/mL reduced LDL sialic acid levels by an average of 25±7.2% for 5 days. On days 1 to 5 after a single injection of immobilized neuraminidase, there was a significant decrease in LDL sialic acid content compared to the control group (P<0.05). The reductions were 34.3±4.2%, 27.4±4.3%, 18.2±2.8%, 28.0±1.8%, and 17.0±6.2% on days 1 to 5, respectively. Additionally, the sialic acid content in LDL was restored to initial values in the experimental group on days 6–7. Decreased sialic acid LDL levels were observed at 2, 4, and 6 weeks after the start of the series of injections of immobilized neuraminidase (14.3±1.4%, 38.26±5.8%, and 29±3.7% reductions, respectively) compared to the control group. No atherosclerotic lesions were observed in the aortic cross-sections stained with hematoxylin-eosin or in aortas stained with Oil Red O in C57Bl/6J wild-type mice after subchronic administration of immobilized Vibrio cholerae neuraminidase at a concentration of 0.2 U/mL for 6 weeks. Furthermore, LDL desialylation did not lead to significant changes in the levels of blood lipids in the experimental group compared to the control group of C57Bl/6J wild-type mice.
CONCLUSIONS Our findings demonstrate that LDL desialylation, a characteristic previously found in patients with atherosclerosis, can be successfully modeled in wild-type mice Notably, the administration of immobilized neuraminidase did not result in the development of atherosclerotic lesions in the aortic intima or alterations in blood lipid levels in wild-type mice. This work was supported by the Russian Science Foundation (Grant No. 22-25-00391).
GW34-e0441
Dmitry Kashirskikh1,2,3, Nelya Chicherina1,4, Vadim Cherednichenko3, Igor Sobenin2,5, Alexander Orekhov1,2,3
1Institute for Atherosclerosis research
2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology
3Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Avtsyn Research Institute of Human Morphology of FSBI “Petrovsky National Research Centre of Surgery”
4Sirius University of Science and Technology
5Laboratory of Medical Genetics, National Medical Research Center of Cardiology
OBJECTIVES Atherosclerosis is a multifactorial disease characterized by the formation of atherosclerotic plaques in arterial walls. Desialylation of low-density lipoproteins (LDL), a modification of LDL particles, is known to be a key contributor to the initiation and progression of atherosclerosis. However, the lack of suitable animal models has impeded the study of this phenomenon. The present study sought to investigate the impact of LDL desialylation on the development of atherosclerotic lesions in ApoE−/− mice, with the aim of establishing a reliable animal model for exploring this modification.
METHODS The control group of ApoE−/− mice received a series of saline injections, while the experimental group of ApoE−/− mice (n=10 in each group) received a series of injections of 20 mU of neuraminidase for 6 weeks. Another experimental group of ApoE−/− mice received a series of saline injections and a high-fat diet (HFD) for 6 weeks. Animals were sacrificed 6 weeks after the start of the experiment. Atherosclerotic lesions were identified by Oil Red O staining.
RESULTS It was shown that in the experimental group of ApoE−/− mice, the area of atherosclerotic lesions was increased by 29.6±8.9% after a series of injections of neuraminidase compared to the control group of mice on a chow diet (P<0.01). Furthermore, LDL desialylation in ApoE−/− mice resulted in a 48.5±5.95% increase in the area of atherosclerotic lesions compared to the control group of mice on a chow diet (P<0.001). Atherosclerotic lesions were predominantly observed in the aortic arch and surrounding areas of large artery branching points, including the brachiocephalic, left carotid, and left subclavian arteries. In addition, atherosclerotic lesions were also present spontaneously throughout the aorta.
CONCLUSIONS The findings of this study suggest that LDL desialylation in ApoE−/− mice significantly increases the development of atherosclerosis. Our results demonstrate that LDL desialylation in vivo in ApoE−/− mice results in an increase in the area of atherosclerotic lesions, similar to that observed in ApoE−/− mice fed an atherogenic diet. This work was supported by the Russian Science Foundation (Grant No. 22-25-00391).
GW34-e0442
Dmitry Kashirskikh1,2,3, Igor Sobenin2,4, Alexander Orekhov1,2,3
1Institute for Atherosclerosis Research
2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology
3Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Avtsyn Research Institute of Human Morphology of FSBI “Petrovsky National Research Centre of Surgery”
4Laboratory of Medical Genetics, National Medical Research Center of Cardiology
OBJECTIVES Numerous studies have established a clear association between desialylation of low-density lipoproteins (LDL) and atherosclerosis. The subchronic administration of immobilized neuraminidase may mimic the pathological reduction in LDL sialic acid levels previously observed in individuals with atherosclerosis, and enable the examination of its deleterious effects. The combination of ApoE−/− mice and neuraminidase injections presents an opportunity to investigate whether sustained LDL desialylation promotes the development of atherosclerosis. The aim of this study was to investigate the effect of LDL desialylation on blood lipid levels in ApoE−/− mice.
METHODS The experimental group of ApoE−/− mice (n=10) received a series of injections of 20 mU of neuraminidase for 6 weeks, while the control group of ApoE−/− mice (n=10) received a series of saline injections. In addition, there was another experimental group of ApoE−/− mice fed a high-fat diet (HFD) and received saline injections for a duration of 6 weeks. At the end of the 6-week experiment, the animals were sacrificed. The levels of blood lipids, including total cholesterol, LDL cholesterol (LDL-C), high-density lipoprotein (HDL) cholesterol (HDL-C) and triglycerides (TG), were assessed at the endpoint of a 6-week experiment in mice.
RESULTS It was revealed that plasma levels of total cholesterol and LDL-C in ApoE−/− mice significantly increased by 22.4±4.6% (P<0.001) and 28±1.1% (P<0.01), respectively, after the 6-week series of neuraminidase injections compared to the lipid levels in the control ApoE−/− mice. Furthermore, there were no significant differences in the levels of TG and HDL-C between the experimental group of ApoE−/− mice receiving neuraminidase injections and the control group of ApoE−/− mice on a chow diet. The ApoE−/− mice on the HFD, which consisted of mice on an atherogenic diet, exhibited elevated plasma levels of total cholesterol and LDL-C by 40.8±3.6% and 46±10.5% (P<0.001), respectively, compared to the control group of ApoE−/− mice on a chow diet. Moreover, TG levels did not change significantly, while HDL-C was significantly reduced by 54.3±8.6% (P<0.001) in the ApoE−/− mice on the HFD group compared to the values of the control ApoE−/− mice on a chow diet.
CONCLUSIONS The development of atherosclerosis in ApoE−/− mice subjected to a series of neuraminidase injections was characterized by notable elevations in the levels of total cholesterol and LDL-C in the plasma. These alterations closely resembled the changes observed in the group of mice maintained on an atherogenic diet. Our findings highlight the potential influence of neuraminidase on cholesterol metabolism and suggest a potential role in the pathogenesis of atherosclerosis. This work was supported by the Russian Science Foundation (Grant No. 23-45-00031).
GW34-e0443
Dmitry Kashirskikh1,2,3, Igor Sobenin2,4, Alexander Orekhov1,2,3
1Institute for Atherosclerosis Research
2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology
3Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Avtsyn Research Institute of Human Morphology of FSBI “Petrovsky National Research Centre of Surgery”
4Laboratory of Medical Genetics, National Medical Research Center of Cardiology
OBJECTIVES Modifications of native low-density lipoproteins (LDL) play a critical role in the development of atherogenesis. Desialylated LDL is one of the modifications found in individuals with atherosclerosis. Notably, desialylated LDL has been identified as being more prone to self-association and accumulation within the intima. The enzymatic process responsible for LDL desialylation is primarily mediated by neuraminidases. Therefore, studying the alterations in the expression patterns of endogenous neuraminidases within different types of atherosclerotic lesions and healthy areas can significantly contribute to our understanding of the underlying mechanisms involved in atherosclerosis. The objective of this study was to evaluate the expression of endogenous neuraminidases in atherosclerotic lesions of patients with atherosclerosis.
METHODS The expression levels of lysosomal (NEU1), cytosolic (NEU2), plasma (NEU3), and mitochondrial (NEU4) neuraminidase genes were assessed using Real-time qPCR. Autopsy aorta samples were collected, including fatty streaks, lipofibrous plaques, and fibrous plaques. Unaffected human aortic intima samples served as the control. RNA isolation from the samples was performed using TRIzol, followed by DNase I treatment for DNA elimination. RNA was converted into cDNA using a two-step RT-PCR procedure.
RESULTS It was found that NEU1 gene transcripts were elevated in fatty streaks by 2-fold (P=0.05) when compared to healthy tissues. However, NEU1 mRNA levels were observed to be lower in fibrous and lipofibrous plaques. Lipofibrous plaques exhibited a 5-fold decrease in NEU2 and NEU3 gene expression (P=0.01) compared to healthy tissue. Additionally, lipofibrous plaques displayed increased NEU4 mRNA expression by 2-fold (P=0.005) compared to the control.
CONCLUSIONS Our study revealed distinct alterations in the expression levels of neuraminidase genes (NEU1–NEU4) in different stages of atherosclerotic plaque development. Fatty streaks exhibited an upregulation of NEU1 gene transcripts, suggesting increased neuraminidase activity in these early lesions. However, NEU1 mRNA was found to be less expressed in fibrous and lipofibrous plaques, suggesting a downregulation of NEU1 gene expression during plaque progression. Notably, lipofibrous plaques showed a significant decrease in NEU2 and NEU3 gene expression, indicating a potential role for these neuraminidases in the advanced stages of plaque formation. Interestingly, NEU4 mRNA levels were elevated in lipofibrous plaques, indicating a potential involvement of mitochondrial neuraminidase in the pathogenesis of these plaques. These findings provide valuable insights into the dynamic regulation of neuraminidase genes during atherosclerotic plaque development and highlight their potential significance in plaque pathophysiology. Further investigations are warranted to elucidate the specific functional implications of these neuraminidase alterations in the context of atherosclerosis. This work was supported by the Russian Science Foundation (Grant No. 23-45-00031).
GW34-e0446
Jinyao Liu1, Yumiko Oba1, Yaowei Chang1, Seiko Yamano2
1Graduate School of Medicine, Yamaguchi University
2Science Research Center, Institute of Life Science and Medicine, Yamaguchi University
OBJECTIVES Fatty liver disease has increased rapidly, and the risk of developing cardiovascular events in metabolic disorder-associated fatty liver disease (MAFLD) is higher than in non-alcoholic fatty liver disease. On the other hand, about 70% of adults are experienced drinker (nonheavy alcohol consumption), and the factors related to metabolic disorders, such as nutritionally unbalanced diet and non-excessive alcohol consumption, account for a considerable proportion of the population which may have a synergistic effect on the progression of liver disease. In the present study, the risk of sudden cardiac death in advanced MAFLD caused by an atherosclerosis-inducing diet (low-carbohydrate, high-protein, high-fat diet: AD) in parallel with non-excessive drinking are confirmed. Sympathetic nerve activation in the heart, myocardial fibril formation, and gap junction protein-related gene variations are assessed at the same time.
METHODS Thirteen-week-old hyperlipidemic spontaneous transgenic mice (apolipoprotein E/low-density lipoprotein receptor double-knockout mice: AL) were divided into four groups and maintained for 16 weeks i.e., AL mice on a standard chow diet (SCD) with or without ethanol (Et) treatment and AL mice on an AD with or without Et treatment. Age-matched male C57BL/6J mice on SCD without Et treatment served as controls. Blood is used to evaluated liver function and hyperlipidemia. Arrhythmia provocation test (acute restraint and intraperitoneal epinephrine injection) is used to confirm the risk of sudden cardiac death in advanced MAFLD. Liver and left ventricular (LV) tissues are used to evaluated liver and LV sympathetic nerve activation, fatty liver, hepatic inflammatory response and fibrogenesis (formation of fibrous bridges indicating progressive MAFLD), myocardial fibrogenesis and gap junction protein synthesis-related mRNA expression with pathology tests and RT-PCR.
RESULTS A combination of nonheavy alcohol consumption and AD for 16 weeks caused obesity, hyperlipidemia, hepatomegaly and liver dysfunction, and cardiac hypertrophy. It caused increased intrahepatic fat deposition, ballooning of hepatocytes, hepatic lobular inflammation, increased Kupffer cells and formation of hepatic fibrous bridges accompanying with high arrhythmia induction rate with two of 8 mice died. Regarding the onset mechanism, we focused on sympathetic nerve activation. In liver, hepatic Kupffer cells and stellate cells exhibited sympathetic activation with increased inflammatory response and fibrogenesis, which may be one of the pathogenesis mechanisms of progressive MAFLD. In LV, myocardium showed cardiac sympathetic nerve activity with myocardial interstitial fibril formation, up-regulated gap junction protein synthesis-related genes, which may be one of the mechanisms for the high risk of fatal arrhythmias.
CONCLUSIONS MAFLD caused by a combination of nonheavy alcohol consumption with a nutritionally imbalanced diet may be associated with the high risk of sudden cardiac death.
GW34-e0450
Zheng Jia, Zheng-jiang Xing, Hong-lin Zou, Jie Wei, Fan-di Meng, Ying Xie
Kunming Medical University Affiliated to Yan’an Hospital
OBJECTIVES Coronary atherosclerotic heart disease (CAD), as a major cardiovascular disease, is the leading cause of death worldwide. The Klotho/FGF23 axis is involved in the occurrence and development of cardiovascular diseases, but the role and underlying mechanism of the Klotho/FGF23 axis in CAD are still unclear.
METHODS Blood samples from 67 CAD patients undergoing coronary artery bypass grafting were collected, and the levels of Klotho and FGF23 were detected by ELISA. Cardiomyocytes from SD rats aged 0–3 days were isolated and cultured. Klotho, FGF23 and cardiomyocyte markers α-actin (α-SA), myosin heavy chain (MHC) and cardiac troponin I (cTnI) were detected by immunofluorescent staining. The expression of Klotho and FGF23 mRNA was detected by qRT-PCR. Cell apoptosis and cell cycle were detected by flow cytometry. Cell viability was detected by CCK-8. Western blotting was used to detect the expression of ERK/MAPK pathway-related proteins and the production of cytokines.
RESULTS The level of Klotho increased after CABG in patients with coronary heart disease, while the level of FGF23 decreased. The cardiomyocytes were integral in shape and structure, stable in beating after 15 days of culture, and positive for α-SA, MHC and cTnI. After lti-Klotho and lti-FGF23 were transfected into cardiomyocytes, fluorescent staining showed that the transfection was successful. The mRNA expression levels of Klotho and FGF23 were significantly higher than those in the NEG (empty vector) group showed to qRT-PCR results. Compared with the NEG group, the Klotho overexpression (Klotho) group had a higher Klotho positive rate and a lower FGF23 positive rate, while the FGF23 overexpression (FGF23) group had a higher Klotho positive rate and a lower Klotho positive rate displayed in the results of immunofluorescence staining. However, the expressions of p-ERK1/2 and p-P38 decreased in the Klotho group, but increased in the FGF23 group. In addition, overexpression of Klotho can inhibit cardiomyocyte apoptosis, increase the proportion of S phase, promote cell proliferation, increase transforming growth factor β1 (TGF-β1), nuclear factor κB (NF-κB), angiotensin-II (AT-II) and activator protein-1 (AP-1), overexpression of FGF23 had opposite effects, while ERK agonist (TPA) and inhibitor (U0126) reversed the effects of Klotho and FGF23.
CONCLUSIONS Klotho was negatively correlated with the expression of FGF23. The Klotho/FGF23 axis can regulate cardiomyocytes through the ERK/MAPK pathway and play an important role in the progression of CAD.
GW34-e0458
Yuto Kawase1, Kana Shimizu1,2, Masafumi Funamoto1,2, Yoichi Sunagawa1,2,3, Yasufumi Katanasaka1,2,3, Toshihide Hamabe-Horiike1,2,3, Satoshi Shimizu1,2,3, Philip Hawke4, Maki Komiyama2, 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, Japan
3Shizuoka General Hospital, Shizuoka, Japan
4Laboratory of Scientific English, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
OBJECTIVES Cardiac remodeling induced by hypertrophic stresses such as hypertension or myocardial infarction is a compensatory mechanism associated with cardiomyocyte hypertrophy and cardiac fibrosis. Continuation of these responses eventually result in heart failure (HF). The histone acetyltransferase p300 plays an important role in the development of HF and may be a target for HF therapy. The phenolic phytochemical 6-shogaol, a pungent component of raw ginger, has various bioactive effects. However, its effect on HF has not been investigated. This study examined the effect of 6-shogaol on cardiomyocyte hypertrophy and fibrosis phenotype in vitro and on the development of heart failure in vivo.
METHODS To investigate the inhibitory effect of 6-shogaol against p300-HAT activity, an in vitro HAT assay was performed using a recombinant p300-HAT domain and core histones. Next, primary cultured cardiomyocytes and cardiac fibroblasts were treated with 1 μM 6-shogaol and then stimulated with phenylephrine (PE) or transforming growth factor-beta (TGF-β), respectively. Immunofluores staining, quantitative PCR (qPCR) analysis, and western blotting (WB) were performed on the cardiomyocytes. Measurement of L-proline incorporation, qPCR analysis, and WB were carried out on the cardiac fibroblasts. C57BL/6J mice were subjected to transverse aortic constriction (TAC) surgery, and then given a daily oral administration of 1 mg/kg 6-shogaol for 8 weeks. Echocardiographic analysis, histological staining, and WB were performed.
RESULTS An in vitro p300-HAT assay revealed that 6-shogaol significantly suppressed histone acetylation. In cardiomyocytes, immunofluores staining revealed that 6-shogaol significantly suppressed PE-induced increase in cell surface area. qPCR analysis demonstrated that 6-shogaol significantly suppressed PE-induced increases in the mRNA levels of hypertrophic response genes such as ANF and BNP. 6-shogaol also suppressed PE-induced increase in histone acetylation. Next, in primary cultured cardiac fibroblasts, 6-shogaol suppressed TGF-β-induced increases in L-proline incorporation, the mRNA and protein expression levels of α-smooth muscle actin, and histone H3K9 acetylation. Finally, echocardiography showed that 6-shogaol prevented the TAC-induced increase in the posterior wall thickness and decrease in the systolic function. Histological staining revealed that 6-shogaol suppressed the increases in the cardiomyocyte cross-sectional area and the area of perivascular fibrosis induced by TAC surgery. 6-shogaol also suppressed TAC-induced increase in histone H3K9 acetylation.
CONCLUSIONS These results indicate that 6-shogaol, a ginger extract, suppressed both PE-induced cardiomyocyte hypertrophy in cardiomyocytes and TGF-β-induced differentiation into myofibroblasts in cardiac fibroblasts. 6-shogaol also suppressed pressure overload-induced HF by inhibiting p300-HAT activity. Clinical studies are required to assess the potential of 6-shogaol as a heart failure treatment.
GW34-e0460
Yaowei Chang1, Jinyao Liu1, Yumiko Oba1, Seiko Yamano2
1Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
2Science Research Center, Institute of Life Science and Medicine, Yamaguchi University, Ube, Japan
OBJECTIVES Atherosclerosis is a chronic arterial disease and a major cause of vascular death. Dysfunction of endothelial progenitor cells (EPCs), with their ability to replace old and injured cells and differentiate into healthy and functional mature endothelial cells, contributes to the development of atherosclerosis. Using apolipoprotein E/low-density lipoprotein receptor double-knockout (AL) mice, the influences of a combination of alcohol consumption with an atherosclerosis-inducing diet (AD, a low-carbohydrate–high-protein-high-fat atherogenic diet) on EPCs and their regulatory factors were assessed.
METHODS We maintained 13-week-old male AL mice on an AD with or without ethanol (Et) treatment for 16 weeks. Age-matched male C57BL/6J (WT) mice on a standard chow diet (SCD) without ethanol treatment served as controls. The aorta (from the aortic root to the iliac bifurcation) were harvested after systemic perfusion with Hanks’ balanced salt solution via the left ventricle. Flow cytometry was performed to analyze aortic EPCs accumulation identified as CD34+/CD45- cells in the whole of the aortic cell suspension. The EPCs regulatory factors (CD133, FLK-1, and NRP-1) were evaluated with RT-PCR.
RESULTS AD without Et treatment induced the increased EPCs in the whole of the aortic cell suspension, however, the combination of AD and Et suppressed this increase accompanying with CD133, FLK-1 and NRP-1 mRNA expression down-regulations which up-regulated by AD.
CONCLUSIONS This study indicated that the synergistic effect of alcohol consumption and an atherosclerosis-inducing diet inhibited the increases in EPCs and its regulatory factors mRNA expressions, resulted in the dysfunction of EPCs recruitment and differentiation, which may be responsible for the progression of atherosclerosis.
GW34-e0474
Yanru Duan1, Yunhui Du2
1Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China
2Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, P. R. China
OBJECTIVES APN, adiponectin, is a vascular protective molecule secreted by adipocytes. APPL1, adiponectin receptor-binding protein-like 1, functions as an adaptor and is also involved in vascular protection. APN exerts its vascular protective effects by interacting with APPL1. However, the downstream target genes that mediate the protective effects of this signaling axis on vascular endothelium in the context of diabetes remain unclear.
METHODS High-fat-diet (HFD)-induced diabetic vascular injury and hindlimb ischemia models were used for in vivo function demonstration. Diabetic medium-cultured human umbilical vein endothelial cells (HUVECs) and 293 T cells were utilized for in vitro molecular/cellular investigation. Transcription factor expression detection kits, transcription factor activity assay kits, and mass spectrometry techniques were employed to mechanism exploration.
RESULTS APPL1 knock-out mice were fed normal or HFD for 10 weeks. Eight weeks after HFD, mice were randomized to receive vehicle or APN treatment for another two weeks. Aortic vessels were prepared for transcriptome analysis. Bioinformatics analysis indicates that the Tight Junction (TJ) pathway exhibited the most prominent changes. Using a global signaling transduction network showed that TJ-related genes had the highest degree values. Among these genes, PCR results indicated that Occludin was the sole gene inhibited in endothelial cells treated by HG/HL and promoted by APN treatment in an APPL1-dependent manner. The protein level of Occludin was reduced in diabetic condition, and APN treatment upregulated the expression of Occludin in APPL1-mediated manner in vivo and vitro. Endothelial specific OCLN knockdown blunted APN-mediated blood flow recovery after femoral artery ligation in vivo, and abolished APN’s effects upon HG/HL-induced permeability, and apoptosis in vitro. Mechanically, we discovered MYB, HDAC1, and FOXO1 play a role in the regulation of Occludin. This finding was validated by CHIP-QPCR. Western blot analysis revealed that the APN-induced increase in Occludin protein level was abolished after knockdown of MYB and FOXO1. However, knockdown of HDAC1 in endothelial cells did not alter the expression of Occludin mediated by APN. Finally, CHIP-qPCR showed that both MYB and FOXO1 were involved in the enrichment of Occludin promoters mediated by APN.
CONCLUSIONS Our findings provide the first evidence that the APN/APPL1 signaling axis promotes the expression of Occludin through the transcription factors MYB and FOXO1, ultimately exerting a protective effect on vascular endothelium. This suggests that Occludin may serve as a novel therapeutic target for treating diabetic vascular endothelial injury.
GW34-e0485
Mengqiu Dang, Junyan Jin
Department of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
OBJECTIVES Cardiac hypertrophy is a key remodeling during diabetic cardiomyopathy, leading to heart dysfunction. Recent studies have demonstrated that mDia1 regulated the filamentous/globular (F/G)-actin ratio in response to pressure overload in mice. However, the mechanisms of mDia1 remain not fully understood in the progression of diabetic cardiomyopathy.
METHODS High-fat diet (HFD) for 16 weeks was used to induced diabetic cardiomyopathy. Male wild-type (WT) and mDia1-knockout (mDia1KO) mice were subjected to HFD and normal diet (ND). Echocardiography was used to accessed cardiac function. Pathological staining and mRNA expression of ANP, BNP as well as β-MHC were performed to access cardiac remodeling. Proteomic profiling and Glycometabolomics used to evaluate molecular changes.
RESULTS Blood glucose increased after HFD for 8 weeks. The expression of mDia1 was significant increased in HFD mice. mDia1 knockout decreased cell area, IVRT and E/A ratio meanwhile increased left ventricular diastolic volum. Whereas, LVEF was not changed after disruption of mDia1 as well as FS. A quantitative proteomics analysis revealed significant increases of mitochondrial pyruvate carrier 2 (MPC2) after mDia1 knockout in mice which was the unique entry point for the glycolytic end-product pyruvate to the mitochondria. Furthermore, results of glycometabolomics indicated that mDia1 knockout increased the products of glucose metabolism and tricarboxylic acid cycle including D-glucose-6-phosphate, alpha-ketoglutaric acid, fumaric acid malic acid and Adenosine monophosphate as well as adenosine diphosphate.
CONCLUSIONS Our results suggested that mDia1 deteriorates diabetic cardiomyopathy via decreasing of MPC2 expression, which is resulted to reducing glucose metabolism.
GW34-e0489
Changjin Li
Department of Cardiovascular Medicine, Changhai Hospital, Naval Medical University, Shanghai 200433, China
OBJECTIVES To explore the identification of clotting and fibrinolysis-related genes (CFRG) in atherosclerosis (AS) and analyze immune infiltration using bioinformatics techniques, aiming to determine the impact of CFRG in AS.
METHODS We performed differential expression analysis (AS samples vs normal samples) to obtain differentially expressed genes (DEGs) in GSE100927 dataset. Coagulation and fibrinolysis related differentially expressed genes (CFR-DEGs) were obtained by overlapping DEGs and CFRGs. Further, generalized linear model (GLM), grandient boosting machine (GBM) and randomForest (RF) algorithm were implemented to build a diagnostic model. We further performed immune infiltration and gene set enrichment analysis (GSEA) based on diagnostic genes.
RESULTS We identified 2211 DEGs associated with AS. Then, 13 CFR-DEGs were obtained via venn diagram. Subsequently, 5 feature genes (TNF, SERPINA3, F12, PLAU and CSF3) were identified via machine learning. Moreover, 4 diagnostic biomarkers associated with coagulation and fibrinolysis, including F12, PLAU, SERPINA3 and TNF, were screened via receiver operating characteristic (ROC) analysis. The immune infiltration and Gene Set Enrichment Analysis (GSEA) analysis suggested that these diagnostic biomarkers were related to the function of cytokine interaction pathway and some differential immune cells. Finally, we found significant lower expression of CSF3 and SERPINA3 in AS group compared to the normal group by RT-qPCR.
CONCLUSIONS This study identified four CFRG in AS: IF12, PLAU, SERPINA3, and TNF. Analyses of drug networks and immune cell infiltration shed light on the molecular mechanisms of CFRG in AS, providing potential directions for AS treatment.
GW34-e0495
Mizuho Yamamoto1, Masafumi Funamoto1,2, Yoichi Sunagawa1,2,3, Sho Uehara1, Yasufumi Katanasaka1,2,3, Toshihide Hamabe-Horiike1,2,3, Kana Shimizu1,2, Satoshi Shimizu1, Koji Hasegawa1,2, Tatsuya Morimoto1,2,3
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka
2Division of Translational Research, National Hospital Organization Kyoto Medical Center
3Shizuoka General Hospital
OBJECTIVES Epigenetic regulatory mechanisms such as histone post-translational modifications are involved in the development of heart failure (HF). The histone acetyltransferase p300 accelerates gene transcription via epigenetic mechanisms, including chromatin remodeling, in which chromatin changes structurally from heterochromatin to euchromatin. Acetylation of the histone tail domain has been intensively studied, including the domains H3 lysine 9 (H3K9) and 14 (H3K14). Recently, H3 lysine 122 (H3K122) has been reported to be a novel p300 histone acetylation site. H3K122 is located at a globular domain on the surface of the histone. H3K122 acetylation attenuates histone-DNA binding and dramatically activates gene transcription. However, nothing is known about the acetylation of the histone tail and globular domains in left ventricular hypertrophy (LVH) or HF. Therefore, the present study aims to examine how the acetylation of the histone tail and globular domains changes during the transition from the LVH to HF stages in Dahl rats, a model of hypertension-induced HF.
METHODS To analyze the acetylation levels of H3K9 and H3K122 during the transition from LVH to HF in salt-sensitive Dahl rats, Western blotting (WB) was performed. Next, a chromatin-immunoprecipitation (ChIP) assay was performed to examine the acetylation levels of H3K9 and H3K122 on the promoters of cardiac hypertrophic response genes, ANF and BNP. In addition, we analyzed the recruitment of p300 onto the promoters of the cardiac hypertrophy response genes using a ChIP assay. Finally, we investigated the expression levels of BRG1, a chromatin remodeling factor, and the binding of BRG1 to p300 during the transition from LVH to HF. To examine the recruitment of BRG1 on the promoter of hypertrophic response genes, a ChIP assay was performed.
RESULTS WB revealed that acetylation of H3K9 was increased in LVH, and that of H3K122 was increased in HF. ChIP assay showed that acetylation of H3K9 was increased in LVH and acetylation of H3K122 was increased in HF on the cardiac hypertrophic response gene promoter and that recruitment of p300 to the hypertrophic response factor promoters was comparable in LVH and HF. IP-WB results showed that the binding of BRG1 to p300 was significantly increased in HF. Furthermore, in vivo ChIP assay showed that the recruitment of BRG1 to the hypertrophic response factor promoters was increased considerably in HF compared to LVH.
CONCLUSIONS These data suggest that the acetylation of the histone globular domain H3K122 is enhanced during the transition from LVH to HF and that the formation of the p300/BRG1 complex is involved in the acetylation of H3K122. These findings may contribute to the discovery of a novel epigenetic regulation mechanism for HF, which may, in turn, lead to a much-needed new treatment for the disease.
GW34-e0535
Yan-Yun Pan
The First Affiliated Hospital of Zhejiang Chinese Medical University
OBJECTIVES During the pathogenesis of early pulmonary arterial hypertension (PAH), pulmonary arterial adventitial fibroblast act as an initiator and mediator of inflammatory processes that predispose vessel walls to excessive vasoconstriction and pathogenic vascular remodeling. Emerging studies report that Yin Yang-1 (YY-1) plays important roles in inflammatory response and vascular injury. Our recent study finds that activation of CD40L-CD40 signaling promotes pro-inflammatory phenotype of pulmonary adventitial fibroblasts. However, whether YY-1 is involved in CD40L-CD40 signaling-triggered inflammatory response in pulmonary adventitial fibroblasts and its underlying mechanism is still unclear.
METHODS Here, we show that soluble CD40L (sCD40L) stimulation promotes YY-1 protein expression and suppresses anti-inflammatory cytokine, IL-10 expression in pulmonary adventitial fibroblasts, while YY-1 knockdown prevents sCD40L-mediated reduction of IL-10 expression via enhancing IL-10 gene transactivation. Further, we find that sCD40L stimulation significantly increases H3K27me3 modification on IL-10 promoter in pulmonary adventitial fibroblasts, and YY-1 knockdown prevents the effect of sCD40L on IL-10 promoter through reducing recruitment of EZH2, a histone methyltransferase, binding to IL-10 promoter.
RESULTS Moreover, we find that sCD40L stimulation promotes YY-1 protein, but not mRNA expression, via decreasing m6A methylation on YY-1 mRNA to suppress YTHDF2-medicated mRNA decay. Overall, this in-depth study shows that activation of CD40L-CD40 signaling upregulates YY-1 protein expression in pulmonary adventitial fibroblasts, which results in increasing YY-1 and EZH2 binding to the IL-10 promoter region to enhance H3K27me3 modification, eventually leading to suppress IL-10 transactivation.
CONCLUSIONS This study firstly uncovers the roles of YY-1 on CD40L-CD40 signaling-triggered inflammatory response in pulmonary adventitial fibroblasts.
GW34-e0536
Xianjun Wu
First Affiliated Hospital of Zhejiang Chinese Medical University
OBJECTIVES Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect in the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on Cardiovascular disease.
METHODS In present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti-cardiovascular disease mechanism of quercetin.
RESULTS The outcomes showed that quercetin possess favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, PI3K-Akt signaling pathway.
CONCLUSIONS The outcomes showed that quercetin possess favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, PI3K-Akt signaling pathwa
GW34-e0540
Tan Nannan, Li Weili, Zhang Yawen, Ling Guanjing, Wei Yan, Wang Xiaoping
Beijing University of Chinese Medicine
OBJECTIVES Doxorubicin (DOX) is the cornerstone of clinical cancer therapy, but the clinical application is restricted due to the doxorubicin-induced cardiotoxicity (DIC). Restoring or enhancing autophagy flux is one of the most promising therapeutic strategies for DIC patients. Recent studies have found that abnormal mitochondrial-lysosomal contact could affect lysosomal function, and then lead to autophagy disorder. TBC1D15 plays a key role in this process. The role of TBC1D15 in myocardial infarction and cardiac ischemia-reperfusion models has been confirmed. Qishen granule (QSG) has a strong cardioprotective effect, but the pharmacological mechanism in DIC has not been elucidated. This study aimed to investigate whether QSG could protect against DIC from heart injury through activating autophagy via TBC1D15-mediated mitochondria-lysosome contact.
METHODS A DIC model was established via tail vein injection with DOX (5 mg·kg−1) weekly for 4 weeks and a DOX-induced H9C2 cell injury model was induced by 1 μmol/L DOX. In vivo, the mice were divided into five groups, control group, model group, QSG-low group, QSG-high group, and Pravastatin (positive drug) group. Echocardiographic assessment, histological examination, mRFP-GFP-LC3 double-labeled adenovirus and western blot analysis of TBC1D15 were collectively implemented to evaluate the cardioprotective effects of QSG. In vitro, the effects of over expressed TBC1D15 and QSG were evaluated by analyzing cell viability with a microplate reader using cell counting kit-8 (CCK-8). siRNA TBC1D15 was transfected to H9C2 with QSG, and then western blot was used for detecting the level of LC3 and P62, lysosome-sensor probe was used to detect the acidification of lysosome, which further verified whether QSG exerted its effect through TBC1D15.
RESULTS Overexpression of TBC1D15 could reverse cell viability, mitochondrial membrane potential and lysosomal acidification, and restore autophagy. QSG improved cardiac function and decreased serum levels of myocardial injury markers in vivo. Moreover, QSG could improve myocardial pathological damage, reduce the level of reactive oxygen species in myocardial tissue, reduce myocardial cell apoptosis, and repair mitochondrial cristae rupture. The TBC1D15 level in the DOX group was decreased and was increased after administration of QSG. The results of mRFP-GFP-LC3 double labeled adenovirus showed that the accumulation of autolysosomes in the QSG group was reduced. When TBC1D15 was knocked down by siRNA, the beneficial effect of QSG on mitochondria, autophagy and lysosomal acidification was disappeared.
CONCLUSIONS Qishen granule can improve Doxorubicin-induced cardiac dysfunction in mice by improving lysosomal acidification and restoring autophagy, and the mechanism is related to increasing the level of TBC1D15.
GW34-e0545
Bing Yan, Zhu Mei, Haixu Song, Dan Liu, Xiaolin Zhang, Chenghui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES CREG (Cellular repressor of E1A-stimulated genes) is a glycoprotein, which first described as a transcription repressor that represses the transcription and cellular transformation induced by the E1A oncoprotein. Recently, CREG is identified as a vascular protective molecule, and it is significantly downregulated in atherosclerotic vessels. Macrophages transform into foam cells upon taking-in lipids is crucial for atherogenesis, but no role for CREG in foam cell formation has previously been reported.
METHODS CREG expression was examined in western diet-fed atherosclerosis-prone ApoE−/− mice. CREG expression was examined after exposure of macrophages (Raw264.7 cells and bone marrow–derived macrophages) to OxLDL (oxidized low-density lipoprotein) in vitro. Foam cell formation, lysosomal maturation, and expression of scavenger receptor A (SRA) was examined in CREG deficiency (using CREG siRNA) macrophages (Raw264.7 cells and bone marrow–derived macrophages) in vitro. Further we generated macrophage-specific CREG-deficient mice in ApoE−/− background. Atherosclerotic lesion in whole aorta and aortic root were examined after ApoE−/− CREGfl/fl and ApoE−/− CREGfl/flLyz2cre mice fed with western diet for 16 weeks. SRA expression in aortic root lesions was also examined by immunostaining.
RESULTS CREG expression was markedly reduced in mice atherosclerotic plaques when compared with nonatherosclerotic vessels (Target protein levels fold, normal vs atherosclerotic vessel 1.000.06 vs 0.420.06, n=3, P<0.05; Relative transcript levels fold, normal vs atherosclerotic vessel 1.000.08 vs 0.670.09, n=3, P<0.05). Exposure of macrophages to OxLDL downregulated CREG in vitro (Target protein levels fold, control vs OxLDL 1.000.07 vs 0.530.05, n=3, P<0.05; Relative transcript levels fold, control vs OxLDL 1.000.09 vs 0.700.07, n=3, P<0.05). Furthermore, CREG deficiency in macrophages increased the expression of SRA (Target protein levels fold, siNC vs siCREG 1.000.21 vs 1.450.07, n=3, P<0.05). But CREG deficiency did not markedly change SRA mRNA levels (Relative transcript levels fold, siNC vs siCREG 1.000.01 vs 1.370.18, n=3, P=0.10). CREG deficiency also increased modified low-density lipoprotein uptake (Dii-Ac-LDL staining fold, siNC vs siCREG 0.990.23 vs 2.420.46, n=3, P<0.05) and foam cell formation (Oil red O staining fold, siNC vs siCREG 1.000.39 vs 2.810.39, n=3, P<0.05). Further we found CREG deficiency decrease lysosome staining and lysosomal marker protein LAMP-2 (Target protein levels fold, siNC vs siCREG 1.000.14 vs 0.540.08, P<0.05). Compared with ApoE−/− CREGfl/fl wild type control ApoE−/− CREGfl/fl Lyz2cre mice developed more atherosclerotic lesions in whole aorta (Lesion area % of total area, ApoE−/− CREGfl/fl vs ApoE−/− CREGfl/flLyz2cre 37.769.05 vs 49.786.235, n=7, P<0.05) and aortic root area (Lesion area % of total area, ApoE−/− CREGfl/fl vs ApoE−/− CREGfl/flLyz2cre 28.576.58 vs 48.7710.89, n=7, P<0.05), with increased SRA expression in aortic root lesions.
CONCLUSIONS Our study demonstrated that macrophage CREG reduction caused by OxLDL decreases SRA degradation and lysosomal maturation, which promotes foam cell formation and the progression of atherosclerosis. These results suggest CREG might be a novel therapeutic target for inhibition of atherosclerosis.
GW34-e0547
Yaohan Tang, Chenhui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Acute myocardial infarction (AMI) refers to myocardial ischemia and hypoxia caused by coronary artery obstruction. Myocardial mitochondrial function is impaired during ischemia-hypoxia, which leads to insufficient mitochondrial function and ATP production, and then affects the function of myocardial cells. Voltage-dependent anion-selective channel 3 (VDAC3), a major mitochondrial outer membrane protein, is known to be essential for mitochondrial function. However, the role of VDAC3 in acute myocardial infarction has not been reported. The aim of this study is to clarify the role and mechanism of VDAC3 in AMI.
METHODS AMI was induced by permanent ligation of the left anterior descending coronary artery. The autophagy of myocardium was observed by transmission electron microscope. Overexpression or knockdown of VDAC3 was performed in vivo using adeno-associated viruses. Plasmid and siRNA were used to over-express and knock down VDC3 in HL-1 cells, respectively. Western Blot and RT-PCR were used to detect the expression of VDAC3, LC3, P62, BNP, IL-6 and IL-1β. CCK-8 kit was used to detect cell viability.
RESULTS The protein and mRNA levels of VDAC3 were significantly decreased at 3 d, 7 d, 14 d and 28 d after AMI (P<0.05), and the decrease was most obvious at 28 d. AAV-VDAC3 overexpression significantly reduced mortality (16.7 vs 46.1%, P<0.05), improved cardiac function, and reduced infarct size and fibrosis area in AMI mice. After VDAC3 knockdown by adeno-associated virus, sh-VDAC3 significantly increased the mortality (27.3 vs 77.3%, P<0.05) and cardiac function, as well as the area of myocardial infarction and fibrosis in AMI mice. Transmission electron microscopy results showed that autophagy was significantly reduced in AAV-VDAC3 group after MI. Western Blot results also showed that LC3 expression was significantly decreased, while autophagy was significantly increased in sh-VDAC3 group after MI. Consistent with the animal results, LC3 expression in HL-1 cells was significantly decreased in VDAC3 overexpression group after CoCl2 stimulation, while VDAC3 knockdown had opposite results. When HL-1 cells were exposed to CoCl2-induced hypoxia, 3-MA, an autophagy inhibitor, significantly rescued siVDAC3-induced cell death, indicating that VDAC3 reduced cardiomyocyte death by inhibiting autophagic cell death.
CONCLUSIONS VDAC3 can improve cardiac function and reduce mortality in mice with AMI by inhibiting autophagic cell death. VDAC3 has the potential to be a therapeutic target for AMI.
GW34-e0549
Qingbin Hou, Chenhui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, 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.
GW34-e0550
Qingbin Hou, Yisi Liu, Chenhui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Abdominal aortic aneurysm (AAA) is a serious and fatal disease, but until now there has not been an effective drug to treat AAA. MicroRNAs are small noncoding RNAs that modulate gene expression by negatively regulating translation of target genes. Although the role of several miRNAs in vascular smooth muscle cells (VSMCs) has been extensively characterized, the function of miRNA-3154 is still unknown.
METHODS Ang II-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, immunoblotting, protein interactome analysis, immunofluorescence, immunohistochemistry, Flourescence in situ hybridization, luciferase Assay were performed to clarify the phenotype and elucidate the molecular mechanisms.
RESULTS We screened for miRNAs whose expression is modulated in VSMCs by AngII-induced murine AAA model, and among the hits, we selected miR-3154. We found that miR-3154 was expressed in various tissues, primary murine cells, and pathological murine and human vascular specimens. Through gain- and loss-of-function approaches, we determined that miR-3154 affects VSMC proliferation, migration, differentiation, and contractility. The alterations of those properties were dependent upon epigenetic regulation of key VSMC differentiation genes. Notably, Pax7 was found to be a direct target of miR-3154 and able to modulate the Myocd, a potent cardiac and smooth muscle tissue-specific transcriptional coactivator of serum response factor (SRF), plays a vital role in inducing smooth muscle differentiation. Finally, in vivo tail intravenous injection antagomir miR-3154 and AAV-cmv-pax7 prevented the formation of abdominal aortic aneurysms in an AngII-induced model.
CONCLUSIONS miR3154 maintains the contractile phenotype of VSMCs through Pax7-Myocd signaling in vitro and in vivo. Its modulation in the context of disease could be exploited for therapeutic purposes.
GW34-e0552
Qingbin Hou, Jinping Jiang, Kun Na, Xiaolin Zhang, Dan Liu, Quanmin Jing, Chenghui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Both primary Sjogren’s syndrome (pSS) and acute myocardial infection (AMI) are intricately linked to one another. However, their common mechanism is not fully understood. Herein, we examined the underlying network of molecular action associated with the development of this complication.
METHODS pSS (GSE40611) and AMI (GSE66360 discover cohort, DC) datasets were retrieved from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were assessed via the R-based ‘limma’ packages. Subsequently, we explored the physiological roles of DEGs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein–protein interaction (PPI) axis was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database, followed by visualization via Cytoscape. Hub gene selection employed the cytoHubba plugin, and validation was performed using GSE7451 for pSS and GSE66360 for AMI. Hub gene set enrichment (GSEA) and immune invasion analyses were carried out, and transcription factor (TF)- and TF-miRNA modulator axes for hub genes were constructed accordingly.
RESULTS Overall, we observed 453 highly- and 45 scarcely-expressed genes between the AMI patients and controls in the GSE66360 DC. In addition, we noted 796 highly- and 876 scarcely-expressed genes between pSS patients and controls in the GSE40611 dataset. The intersection of DEGs from both datasets identified 49 common highly expressed and 2 identical scarcely expressed genes. Moreover, the following pathways were markedly enriched among pSS and AMI patients: inflammatory response axis (P=1.3E-06), direct modulation of interleukin-1 beta synthesis (P=1.9E-06), fungus detection (P=9.8E-06), direct modulation of NF-kappaB transcription factor activity (P=1.2E-05), direct modulation of interleukin-6 synthesis (P=1.9E-05), MyD88-based toll-like receptor axis (P=4.4E-05), direct modulation of T cell proliferation (P=5.3E-05), direct modulation of apoptosis (P=8.1E-05). Following verification, S100A8, IGSF6, MNDA, NCF2, and MMP9 were recognized as hub genes, and the area under the curve (AUCs) of all genes were >0.7 for both pSS and AMI. Based on our GSEA analysis, the adaptive immune response network was strongly associated with enhanced IGSF6, MMP9, S100A8, MNDA, and NCF2 contents in the GSE66360 DC and GSE40611 datasets. Functional enrichment of these five hub genes is adaptive immune response. The Type 1 T helper cell showed the most association among all cell types related to AMI and pSS. Lastly, using TF-gene interaction and TF-miRNA co-modulatory network analyses, we identified 27 common TFs and 20 identical TF-miRNAs.
CONCLUSIONS Herein, we revealed common networks involving pSS and AMI etiologies. Knowledge of these networks and hub genes can enhance research into their associated mechanism and development of future robust therapy.
GW34-e0553
Zheming Yang1,2, Chenghui Yan1, Yaling Han1,2
1College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China
2National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Sorafenib (sor) is a widely used chemotherapeutic drug to treat hepatocellular carcinoma. However, it often results in significant cardiac dysfunction, which limits its use. Recent research has suggested that this side effect may be a result of necroptosis, a unique type of programmed cell death. Previous studies have shown that the cardiac homeostasis regulatory protein cellular repressor of E1A stimulated genes (CREG) is crucial in maintaining the heart’s physiological and pathological processes, this study explores CREG’s potential use in reducing sor-induced cardiac dysfunction by investigating its effect on necroptosis.
METHODS Mice with CREG knockout, CREG overexpression and mice pretreated with infusion of recombinant 0.3 mg/kg·d CREG protein were treated with sor, cardiac function was detected by animal ultrasound technology. Sor-induced myocardial injury were investigated by histological analyses, quantitative RT-PCR, western blotting. HepG2 cell lines and prepared primary mouse cardiomyocytes were treated with sor and various other treatments. Cardiomyocyte necroptosis was detected by flow cytometry, western blotting, and transmission electron microscopy (TEM). Immunofluorescence staining, JC-1 staining and western blotting were used to detect mitophagy. Mitochondrial Ca2+ uptake was detected by Rhod-2 probes using confocal imaging. Morphological changes in lysosome, mitochondria and mitochondria-associated endoplasmic reticulum membranes were imaged using TEM and confocal microscopy.
RESULTS The study found that the expression of CREG in the heart of mice treated with sor was reduced, further in vitro studies indicated that sor caused the degradation of CREG via the lysosomal pathway. Loss of function research showed that CREG deficiency aggravated the sor-induced cardiac dysfuntion, while function acquisition research suggested that CREG overexpression had the opposite effect. In vitro experiments have also found that overexpression of CREG reduced sor-induced necroptosis, while silencing CREG aggravated sor-induced necroptosis. More importantly, our results showed that treatment of mice with CREG recombinant protein effectively reduced the sor-induced cardiac dysfuntion. Mechanically, CREG increased the expression of mitofusin-2 (MFN2) by reduced excessive mitophagy induced by sor, which in turn inhibits sor-induced myocardial necroptosis. Moreover, we found that CREG did not impact sor-induced death of liver cancer cells.
CONCLUSIONS The overexpression of CREG could rescue sor-induced cardiomyocyte necroptosis without disturbing the anti-tumor effects. CREG protein may have clinical applications in the prevention of sor-induced cardiac dysfuntion.
GW34-e0559
Jinping Jiang, Xiaolin Zhang, Chenhui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, 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 RAW264.7 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.
GW34-e0560
Hanlin Wu, Jing Wang, Yuxin Bu, Jia Li, Yiming Li, Quanmin Jing, Chenghui Yan, Dan Liu, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Cardiology and Cardiovascular Research Institute of PLA, General Hospital of Northern Theater Command, Shenyang, Liaoning Province 110016, China
OBJECTIVES Pentamethylquercetin (PMQ) is a natural polymethyl flavonoid that possesses anti-apoptotic and other biological properties. Abdominal aortic aneurysm (AAA), a fatal vascular disease with a high risk of rupture, is associated with phenotypic switching and apoptosis of medial vascular smooth muscle cells (VSMCs). This study aimed to investigate the protective effects of PMQ on the development of AAA and the underlying mechanism.
METHODS ApoE−/− mice were continuously infused with angiotensin II (Ang II) for 4 weeks to develop the AAA model. Intragastric administration of PMQ was initiated 5 days before Ang II infusion and continued for 4 weeks. VSMCs of mice from each group were analyzed to understand the effects of PMQ on apoptosis.
RESULTS PMQ dose-dependently reduced the incidence of Ang II-induced AAA, aneurysm diameter enlargement, elastin degradation, VSMC phenotypic switching and apoptosis. Furthermore, PMQ also inhibited phenotypic switching and apoptosis in Ang II-stimulated VSMCs. PMQ exerted protective effects by regulating GSK-3β phosphorylation via the C/EBPβ/PTEN/AKT axis. AAV-mediated overexpression of PTEN reduced the therapeutic effects of PMQ in the AAA model mice, suggesting that the effects of PMQ on Ang II-mediated AAA formation are related to the C/EBPβ/PTEN/AKT/GSK-3β axis.
CONCLUSIONS PMQ inhibits VSMCs phenotypic switching and apoptosis by bounding to C/EBPβ at Lys253 with hydrogen bond to regulate C/EBPβ nuclear translocation and PTEN/AKT/GSK-3β axis, thereby inhibiting Ang II-induced AAA formation. Thus, PMQ might be a potential therapeutic agent for the treatment of AAA.
GW34-e0561
Hanlin Wu, Ting Zhou, Jing Wang, Yuxin Bu, Zheming Yang, Chenghui Yan, Dan Liu, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Cardiology and Cardiovascular Research Institute of PLA, General Hospital of Northern Theater Command, Shenyang, Liaoning Province 110016, China
OBJECTIVES Type 2 diabetes is prevalent worldwide. Cardiovascular complications in patients with diabetes include diabetic cardiomyopathy (DCM). Ubiquitin-conjugating enzyme E2 I (UBC9) is the only SUMO-E2 enzyme that plays a key role in cardiomyocytes. The present study aimed to elucidate the role and mechanism of action of UBC9 in the development of DCM.
METHODS We established myocardial-specific UBC9 knockout (UBC9-CKO) and adeno-associated virus-overexpressing mouse models. Additionally, a mouse model of DCM was established using high-fat diet feeding and low-dose streptozotocin injection. This mechanism was explained by the stimulation of cultured cardiomyocytes with palmitic acid.
RESULTS The transcript and protein levels of UBC9 were significantly decreased in the myocardium of patients with DCM. Myocardial-specific UBC9 knockout aggravated cardiac dysfunction, alleviated myocardial fibrosis and hypertrophy, and promoted mitophagy and mitochondrial damage. Meanwhile, UBC9 overexpression exhibited the opposite effects. UBC9 exerted mitochondrial protective effects independent of SUMOylation. UBC9 regulated RUNX2 degradation by directly binding to NEDD4, thus regulating PSEN2 to exert protective effects against mitophagy. Moreover, the effect of UBC9 on mitochondrial function was reversed upon PSEN2 knockdown.
CONCLUSIONS UBC9 regulates mitophagy through the NEDD4/RUNX2/PSEN2 pathway and alleviates DCM development by improving myocardial mitochondrial dysfunction. These findings offer novel perspectives on the application of UBC9 as a therapeutic target for DCM
GW34-e0562
Yuxin Bu, Chenhui Yan, Dan Liu, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Trim55 (Tripartitemotif-containing55), is a member of the Trims family, is mainly expressed in myocardium and skeletal muscle. Trim55 plays an important role in promoting the development of mouse heart embryo. However, the role of Trim55 in myocardial infarction (MI) and its related molecular mechanism has not been reported.
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 The transcription and protein levels of Trim55 in the border zone of myocardium post-MI were significantly increased. Trim55 gene knockout could significantly improve the cardiac systolic function, decrease cardiomyocytes apoptosis and infarct size after MI. However, Trim55 overexpression could led to the opposite effect. In vitro, overexpression of Trim55 promoted cardiomyocytes apoptosis by inhibiting HO-1 protein expression. On the contrary, Trim55 knockdown caused the opposite effect. In addition, Trim55 was proved to be the direct target of forkhead box transcription factor 3 (Foxo3) in cardiomyocytes.
CONCLUSIONS Trim55 promoted cardiomyocytes apoptosis by regulating the expression of HO-1, thereby aggravating myocardial injury after MI.
GW34-e0563
Jing Wang, Dan Liu, Xiaoxiang Tian, Chenhui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Vascular calcification (VC) is a common pathological feature of atherosclerosis, chronic kidney disease, vascular injury and aging. VC is characterized by different mineral deposits accumulating in blood vessels and valves. Cellular repressor of E1A-stimulated genes (CREG) is a small molecule secreted glycoprotein and is consisted by 220 amino acids. Studies have shown that CREG is involved in regulating cell growth and differentiation. The aim of this study is to clarify the role of CREG participates in the development of VC.
METHODS Male C57BL/6J, CREG transgenic (CREGTG), and CREG smooth muscle cell-specific knockout (CREGSMKO) mice were used to establish a VC model induced by VitD3 injection. Alizarin red staining, Von Kossa staining, and western blotting 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, real-time PCR, western blotting, Alizarin red staining were used to assess the severity of VSMCs calcification.
RESULTS In vivo, the mRNA and protein levels of CREG were significantly decreased in VitD3-induced VC. CREGSMKO mice aggravated VC by increasing the expressions of the osteogenic markers runt-related transcription factor 2 (Runx2) and osteopontin (OPN), and inhibiting SMA expression. In contrast, CREGTG mice inhibit VC by inhibiting the expressions of Runx2 and OPN, and increasing SMA expression. In vitro, CREG expression was significantly decreased in Pi-induced VSMCs. CREG knockdown exacerbated Pi-induced VSMCs differentiation and calcification, CREG overexpression inhibited VSMCs differentiation and calcification induced by Pi stimulation. Mass spectrum and western blotting revealed that FHL2 was a downstream molecular of CREG, and was involved in the regulation of CREG in VC. Moreover, CREG could regulate FHL2 protein expression in lysosome-dependent pathway.
CONCLUSIONS Our study identified that CREG was a novel endogenous inhibitor of VC by regulating FHL2 protein expression. This study could provide a promising target for VC therapy.
GW34-e0564
Ting Zhou1,2, Hanlin Wu2, Chunying Liu2, Xiaodong Jia2, Dan Liu2, Chenghui Yan2, Haixu Song2, Chenhui Yan1, Yaling Han2
1National 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
2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430022, 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).
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.
GW34-e0568
Zhu Mei1,2, Ziping Song1, Chenghui Yan1, Yaling Han1,2
1National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110016, China
2College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China
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.
GW34-e0571
Zhen Zhang1,2, Yanqiu Xing1,2
1Department of Geriatric Medicine, Qilu Hospital of Shandong University
2Key Laboratory of Cardiovascular Proteomics of Shandong Province
OBJECTIVES Aging is widely accepted as an independent risk factor for cardiovascular disease, which contribute to the increasing morbidity and mortality in the elderly population. Lysine β-hydroxybutyrylation (Kbhb) was discovered as a novel post-translational protein modifications (PTM) in which β-hydroxybutyrate (BHB) is covalently attached to lysine ε-amino groups. Recent studies have revealed that histone Kbhb may contribute to tumor progression, diabetic cardiomyopathy progression, and postnatal heart development. However, to date, there have been no studies reporting a global analysis of Kbhb proteins in aging hearts or elucidating the underlying mechanisms of this modification in the aging process. Herein, we conducted quantitative proteomics and Kbhb PTM omics to comprehensively elucidate the alterations of global proteome and Kbhb modification in the hearts of aged mice.
METHODS In this study, twenty C57BL/6J mice at 3- and 22-months of age were adopted as young controls (WTY, n=10) and aged models (WT-A, n=10), respectively. Various measurements and analyses were conducted during the experiment, including body weight, heart weight, grip strength, echocardiography, serum parameters, and myocardial morphology. In the end, three hearts from each group were used as biological replicates for high-throughput and quantitative data-dependent acquisition (DDA) proteomics analysis. Kbhb modification omics analyse was conducted using affinity enrichment followed by high-resolution high-throughput mass spectrometry (LC-MS/MS) analysis.
RESULTS Our results revealed a decline in grip strength and cardiac diastolic function in 24-month-old aged mice compared to 3-month-old young mice. Through LC-MS/MS we identified a total of 1710 β-hydroxybutyrylated lysine sites in 641 proteins in the cardiac tissue of young and aged mice. Additionally, we observed 183 Kbhb sites were identified in 134 proteins, which exhibited significant differential modification in aged hearts (fold change >1.5 or <1/1.5, P<0.05). Notably, the Kbhb-modified proteins were primarily found in energy metabolism pathways, such as fatty acid elongation, glyoxylate and dicarboxylate metabolism, citrate cycle (TCA cycle), and oxidative phosphorylation. Furthermore, these Kbhb-modified proteins were predominantly localized in mitochondria.
CONCLUSIONS For the first time, our study provides a global proteomic profile and Kbhb modification landscape of cardiomyocytes in aged hearts. These findings open up new possibilities for treating cardiac aging and aging-related cardiovascular diseases by reversing abnormal Kbhb modifications.
GW34-e0589
Jiaxin Xu, Haixu Song, Chenhui Yan, Yaling Ha
National 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 belonging to the S100 subfamily of myeloid-related proteins that acts as an alarmin to induce a pro-inflammatory innate immune response. Cardiac hypertrophy is a key biological response to injurious stresses such as pressure overload and when excessive can lead to heart failure. Previous studies revealed that S100A12 markedly expressed in the serum from HF patients, which suggested that S100A12 is a prognostic marker for several adverse events in HF patients. Although it has been linked to several chronic inflammatory diseases, however, its role in myocardial interstitial fibrosis remains unknown. In order to study this issue, we generated the transgenic (TG) mice which specific expressed the human S100A12 in myeloid cells and further explored that the level of S100A12 was markedly upregulated in the blood and heart from HF patients. Furthermore, we explored that S100A12 highly expression in macrophages is involved in Ang II-induced adverse cardiac fibrosis and dysfunction in vivo and in vitro.
METHODS Angiotensin II (1000 ng kg−1 min−1, Ang II) was administered to wild-type (WT) and transgenic (Tg) mice expressing human S100A12 in myeloid cells for 28 d. Humanized S100A12 markedly aggravated Ang II-induced myocardial fibrosis compared with that in WT mice. Furthermore, thereceptor for advanced glycation end products (RAGE) blocker (Tranilast, 5 mg kg−1 d−1) administration significantly attenuated Ang II-induced myocardial fibrosis and dysfunction in the Tg mice. Previous studies indicated that S100A12 is associated with cystic fibrosis, idiopathic pulmonary fibrosis, and renal fibrosis. In addition, the findings in our study showed that S100A12 also promoted cardiac fibrosis and dysfunction. In vivo and in vitro study, S100A12 increased expression of GSK-3β and Smad3 phosphorylation which associated with cardiac fibrosis. Using immunoprecipitation experiments, we show that GSK-3β is able to bind to RAGE. Primary Mouse Embryonic Fibroblasts (MEFs) isolation and culture. Mechanistically, S100A12 (200 pg/mL) significantly promoted proliferation, migration, collagen production, and phenotypic transdifferentiation of primary mouse embryonic fibroblasts (MEFs).
RESULTS S100A12 expressed in macrophages exaggerated Ang II-induced cardiac fibrosis in mice. Silencing RAGE (RAGE-siRNA, 20 μmol/L) ameliorated the potent fibrotic role of S100A12 by phosphorylation of glycogen synthase kinase-3β (GSK-3β), indicating the involvement of the RAGE/GSK-3β/Smad3 cascade in S100A12-mediated cardiac fibrosis. Notably, circulating and cardiac S100A12 levels were higher in patients with heart failure than in normotensive individuals.
CONCLUSIONS S100A12, in the presence of Ang II, promotes cardiac fibrosis and dysfunction; Using RAGE blocker develop less cardiac fibrosis and dysfunction; In CHF patients, high levels of S100A12 were detected in serum and heart. These findings indicate that S100A12 could be a key regulator of cardiac fibrosis and dysfunction in CHF patients. Ang II-induced myocardial fibrosis and dysfunction are largely mediated by the S100A12-RAGE-GSK-3β axis. The inhibition of S100A12 may represent a new therapeutic target for the treatment of myocardial fibrosis.
GW34-e0591
Yiming Li, Yuying Li, Chenhui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
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.
RESULTS 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 Creg1 tg mice was improved compared to that of Creg1 wt/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. 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.
GW34-e0592
Yiming Li, Chenghui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
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 found out treated target.
METHODS The protein, RNA and transcription factor chip were used between humanic dissected and normal aorta to screen target differentially expressed genes. Pathological and serological verification of the local and systemic expression of target genes in AD patients. Construction of S100A12tg/tg AD mouse model using BAPN drinking+AngII micropump method. Ultrasound, micro-CT, and PET-CT were used to evaluate aortic remodeling status in vivo. Western blotting, immunofluorescence, flow cytometry, and qPCR were used to study the expression level of neutrophil and vascular smooth muscle cell (VSMC) in vitro.
RESULTS Neutrophil Elastase (NE), one of the key components of NETs, 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 modulation happened. There was a significant overexpression of S100A12 and NE in the mass spectrometry detection of human AD and adjacent 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+AngII to establish AD mice model, myeloid overexpression S100A12 mice showed higher negative vascular remodeling rate and rupture rate compared to C57 mice. WB and PCR showed high expression of TLR4 in the aorta of S100A12 transgenic AD mice, which is consistent with the results of human AD aorta. S100A12 can promote the expression and degranulation of NE through TLR4-PAD4 axis, while siTLR4 and siPAD4 can partially reduce the expression level of NE. However, when co-culturing neutrophils and VSMCs, only specific inhibition of NE activity can better save the migration, apoptosis and Phenotypic Modulation of VSMCs induced by NETosis, rather than other links of NETosis. After intraperitoneal injection of Sivelestat, a specific inhibitor of NE activity, at different stages of the AD mice model, PET-CT showed that Sivelestat 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 and degranulation through TLR4-PAD4 axis. Released activated NE can promote VSMC migration, apoptosis and phenotype transformation, while specific inhibition of NE activity can save this effect.
GW34-e0593
HaiXu Song, Jiayin Li, Zhu Mei, Xiaoxiang Tian, Dan Liu, Chenhui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Megakaryocytes are the precursors of platelets, abnormal megakaryocyte maturation and platelet production will lead to platelet-related diseases, and destroy the dynamic balance of hemostasis and bleeding. Cellular repressor of E1A-stimulated genes 1 (CREG1), is a small molecular weight secreted glycoprotein widely expressed in mature tissue cells, and has ability to maintain tissue and cell maturity, and promotes tissue differentiation, however, the role of CREG1 in megakaryocytes differentiation and platelet production is not clear.
METHODS In this study, we generated a megakaryocyte/platelet-specific creg1 knockout mouse (Creg1pf4-cre ). Creg1-floxed mice (Creg1fl/fl ) were crossed with a transgenic line expressing Cre recombinase under the megakaryocyte/platelet-specific pf4 promoter. To investigated the role of CREG1 in the regulation of megakaryocyte maturation and platelet production by using the megakaryocyte/platelet-specific knockout mice. The results showed that Creg1fl/fl mice had normal platelet lifespans by detecting the proportions of biotin-labeled platelets at different time points. We also found that CREG1 deficiency significantly impaired thrombopoiesis by used anti-CD42b monoclonal antibodies to deplete platelets.
RESULTS The platelets from peripheral blood were detected by annexin V staining and western blot, the results indicated that there was no difference in apoptosis between Creg1fl/fl mice and Creg1pf4-cre mice. Fetal livers were isolated from Creg1fl/fl and Creg1pf4-cre embryos and incubated with IL-3 and TPO for 5 days. The results showed that Creg1pf4-cre megakaryocytes produced fewer proplatelets and morphologically less differentiated than Creg1fl/fl megakaryocytes by using immunofluorescence confocal microscopy. Mechanistic studies showed that the MEK-ERK1/2 pathway plays a critical role in the megakaryocyte differentiation and proplatelets production, Creg1-deficient megakaryocytes resulted in inactivation of MEK-ERK1/2 pathways. We further demonstrated that CREG1 interacted with MEK-ERK1/2 pathway directly. Immunoprecipitation analysis and immunofluorescent staining revealed that CREG1 directly interacted with MEK1. PAK/LIMK1/Cofilin pathway is required for the regulation of megakaryocyte cytoskeleton protein recombination, polyploidy, and DMS polarization. Western blot analysis revealed that phosphorylation of PAK1 and LIMK1 was impaired in Creg1pf4-cre megakaryocytes cultured from bone marrow, further leading to a significantly decreased in Cofilin phosphorylated protein. Further, we determined the core promoter of CREG1 gene in 293T cells, and used the dual-luciferase report assay to discover that C/EBPβ (CCAAT enhancer binding protein beta) combined with the core promoter of CREG1. C/EBPβ is an important transcriptional regulator involved in the proliferation, differentiation and maturation of blood cells, adipocytes and mammary cells, especially in hematopoietic differentiation. Luciferase assay demonstrated that C/EBPβ significantly up-regulated the activity of the core promoter of CREG1, and promoted the differentiation of megakaryocyte.
CONCLUSIONS This study uncovers the role of CREG1 in regulation of megakaryocyte mature and thrombopoiesis, and provides a possible theoretical basis for the prevention and treatment of thrombocytopenia.
GW34-e0594
Dan Liu, Xiaoli Cheng, Haixu Song, Chenhui Yan, Yaling Han
National 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). The effect of CREG1 overexpression on ferroptosis of cardiomyocytes 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.
GW34-e0595
Xiaolin Zhang, Minghui Cheng, Xiaoxiang Tian, Dan Liu, Chenhui Yan, Yaling Han
National 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.
GW34-e0597
Xiaodong Jia, Kun Na, Zhu Mei, Chenhui Yan, Yalin Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES In recent years a large number of clinical studies have found that serum APN levels in patients with HF increased, positively correlated with severity of the disease, then put forward “adiponectin paradox” point of view. So, as a cardioprotective factor, APN significantly increases the pathological mechanism and What is the biological function? Is it to combat or aggravate heart function impairment? The correlation between the increase of APN serological level and the severity of HF can make it a biomarker for predicting poor prognosis of HF? These issues have not been clarified so far.
METHODS APN expression in plasma and adipose tissue of mice at different time points was detected by ELISA and Western blot to evaluate the relationship between APN expression and cardiac function. Western blot was used to detect the expression of AMPKα2 and pAMPK protein in the adipose tissue of HF mice, and to evaluate the correlation between the expression and activity of AMPKα2 in the adipose tissue of HF mice before and after HFD feeding and the expression of APN. The 3T3L1 fat progenitor cell lines were used to Compound C and Si-AMPK Compound 2, respectively, for low expression of AMPK and AMPK Compound 2. Established of C57BL6J male mouse and adipoq-ko mouse model of HF by isoprenaline and fed normal diet for 8 weeks.
RESULTS After 20 weeks of feeding with HFD, the body weight of mice showed an obvious decreasing trend. Cardiac ultrasonography showed that LVEF decreased from 53.03±2.80% before feeding to 38.08±1.92% at the end of 28 weeks (P<0.01). FS decreased from 26.98±1.81% to 18.44±1.07% (P<0.01). At 14 weeks of modeling, the plasma APN concentration of the model mice was 2928±129 ng/mL, lower than that of the control mice (P<0.05). The plasma APN concentration of the control mice was 4134±455 ng/mL. The expression of APN in adipose tissue was significantly increased 7 days after Compound C injection compared with the control group. The plasma APN concentration of mice in the Compound C injection group (9963±736 pg/mL) was significantly higher than that in the control group (4377±319 pg/mL), with statistical significance (P<0.05). At the same time, mRNA level detection showed that Compound C intervention did not increase the expression of APN mRNA in the adipose tissue of mice.
CONCLUSIONS Animal and cytological studies confirmed that there was a two-way regulatory relationship between APN and AMPK, and inhibition of AMPK, especially AMPKα2, could up-regulate the expression of APN protein. In mice with HF, adipoq-ko group heart function is worse than C57+ISO group. Experiments have shown that APN has a protective effect on the heart. But, when the heart failure is severe, the APN index is also significantly higher. Then the “adiponectin paradox” point of view needs further study.
GW34-e0600
Cheng Yu, Weihong Lin, Lianglong Chen
Department of Cardiology, Fujian Heart Center, Provincial Institute of Coronary Disease, Affiliated Union Hospital of Fujian Medical University
OBJECTIVES Cell proliferation of vascular smooth muscle cells (VSMCs) accounts for the pathogenesis of vascular neointima formation. Recent studies have reported that RNA modification plays a crucial role in the progression of neointima formation. Acetylated nucleobase ac4C, catalyzed by N-acetyltransferase 10 (NAT10), is well conserved in the enzymatic modification of RNA and is widely distributed in mRNA. However, the biological functions and underlying regulatory mechanisms of mRNA ac4C modifications in CVDs, including vascular remodeling, remain unknown.
METHODS The atherosclerotic segments of the left anterior descending coronary arteries (LAD) and control internal mammary coronary arteries (IMA) were collected. Immunohistochemical staining (IHC), western blotting (WB), HPLC-MS/MS, and Dot blot were performed to detect the level of NAT10 and ac4C modification in LAD and IMA. The rat carotid artery balloon injury model and mouse carotid wire injury were used to study postinjury neointima formation in vivo. Cell proliferation assay, cell migration assay, cell apoptosis assay, HPLC-MS/MS, dot blot, and immunofluorescent staining were conducted to probe the biological functions of NAT10. The potential mechanisms of NAT10 in vascular neointima formation were clarified by RNA-seq, RNA binding protein immunoprecipitation (RIP), acetylated mRNA immunoprecipitation (acRIP), proteomics, etc.
RESULTS IHC and WB showed that NAT10 was highly expressed in LAD compared with IMA. NAT10 protein expression, assessed at days 7, 14, and 28 post balloon injury, was gradually increased in injured carotid arteries compared with sham arteries. Knockdown of rat carotid vascular NAT10 expression suppressed the vascular neointima formation, reduced cell proliferation, and promoted cell apoptosis. Consistently, local overexpression of NAT10 by adenovirus infection significantly exacerbated the balloon injury-induced neointima formation in rats. VSMC-specific deletion of NAT10 dramatically inhibited neointima formation in the vascular wire injury model. Loss- and gain-of-function NAT10 assays also showed that NAT10 promotes the proliferation, migration, and cell apoptosis of VSMCs. HPLC-MS/MS and Dot blot assay results showed that the abundance of ac4C modifications was significantly increased in the sample from human atherosclerotic arteries, rat-injured carotid arteries. RNA-seq, NAT10 RIP, acRIP, and proteomics analysis revealed that NAT10, through an acetylate-modified domain, mediated the stability of Itgb1 mRNA by binding to its mRNA 3′ UTR region and up-regulating its mRNA ac4C modification. CCK-8 and Ki67 staining showed that Itgb1 knockdown significantly abolished the promotion effect of NAT10 ectopic expression. The wound healing and transwell assay demonstrated that the enhancing effect of NAT10 on the invasive potential of VSMC was abrogated by Itgb1 silencing. Besides, the inhibitor of NAT10, remodelin, was applied in vivo which showed an inhibitory effect on vascular neointima formation.
CONCLUSIONS Our results suggested that NAT10 maintained Itgb1 mRNA stability through mRNA ac4C modification resulting in increased IGTB1 expression, and aggravated postinjury neointima formation in vivo.
GW34-e0606
Guanxing Pan1,2, Zhiyong Qi3, Xiaowen Wu4, Lin Chang2, Wei Zhang2, Jianjun Zhang2,5, Haoxuan Zhong3, Si Zhang2, She Chen2, Zhongren Ding2,4
1Department of Pharmacy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
2Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
3Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
4School of Pharmacy, Tianjin Medical University, Tianjin, China
5Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
OBJECTIVES Atherosclerosis, the main pathological basis of cardiovascular diseases including coronary artery disease (CAD) and stroke, has been proved to be a chronic inflammatory disease. The role of nucleotide-binding oligomerization domain 2 (NOD2) in atherosclerosis remains undetermined despite its pivotal role in immunity and inflammation.
METHODS NOD2 in platelets, peripheral blood mononuclear cells (PBMCs), and exosomes isolated from blood samples of patients with CAD and atherosclerotic mice was analyzed by qPCR and Western blot (WB). Washed platelets were activated by agonists and NOD2 in supernatant exosomes was analyzed by WB. The uptake of platelet-derived exosomes by human monocytic THP-1 cells was visualized by immunofluorescent staining. The effects of NOD2 on THP-1 cell migration, adhesion, differentiation, and inflammatory response were investigated using a NOD2-overexpressing lentiviral vector or NOD2 antagonist GSK669, followed by WB analysis of the underlying mechanism. GSK669 was intravenously administrated to ApoE−/− mice fed on a high-fat diet (HFD) to seek the therapeutic effects of GSK669 on atherosclerosis.
RESULTS Unexpectedly, we found that platelets from patients with CAD and atherosclerotic mice express less NOD2 at the protein level; interestingly, the PBMCs from the same patients and mice show higher NOD2 expression. The NOD2 change is not caused by transcriptional regulation. We also observed the higher NOD2 protein contents in the plasma exosomes of patients. In line, activated platelets release NOD2-containing exosomes, which increase NOD2 expression in THP-1 monocytes. NOD2 overexpression in THP-1 monocytes enhances cell migration and inflammatory response without changing cell adhesion and differentiation. Consistently, NOD2 antagonist GSK669 attenuates the migration and inflammatory response of THP-1 monocytes. Mechanically, NOD2 triggers the phosphorylation of receptor-interacting protein 2 (RIP2), further enhancing the JNK/p38 axis during THP-1 differentiation. Intravenous administration of GSK669 significantly reduces atherosclerotic lesions and macrophage infiltration in hyperlipidemic ApoE−/− mice.
CONCLUSIONS Platelet NOD2 exacerbates atherosclerosis. Mechanistically, activated platelets secret exosomes that transfer NOD2 protein to monocytes and enhance monocyte migration and inflammatory response through the RIP2/JNK/p38 signaling cascade. GSK669, the NOD2 receptor antagonist, shows the potential as a therapeutic agent for atherosclerosis.
GW34-e0630
Kaifan Niu, Zhixiang Wang, Tianbao Ye, Liang Liu, Xia Lu, Xian Jin
Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
OBJECTIVES Accumulation of senescent cells and production of senescence-associated secretory phenotype (SASP) are associated with many cardiac pathologies. The precise function and mediation of senescent cells, especially senescent cardiomyocytes, under myocardial ischemia remains poorly understood. Nuclear receptor subfamily 4 group A member 1 (NR4A1), an important regulator of biological processes such as oxidative stress and inflammatory response, may serve as a potential target in mediating cellular senescence.
METHODS Myocardial ischemia/reperfusion (I/R) injury was constructed in mice by left anterior descending coronary artery ligation for 45 minutes, followed by reperfusion for 24 hours. Hypoxia/reoxygenation injury were conducted with neonatal rat cardiomyocytes (NRCMs) with hypoxia for 6 hours, followed by reoxygenation for 18 hours. NR4A1 knockout mice were utilized to determine the function of NR4A1, while adeno-associated virus 9 (AAV9) and adenovirus (Adv) were employed to manipulate the expression of NR4A1 in mice hearts and cultured NRCMs, respectively. Senescence-associated ß-galactosidase (SA-ß-gal) staining was used to detect senescent cells. Senescent markers p16 and p21 were examined through immunofluorescence (IF) and western blot (WB), and SASP was measured by real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Morphological alterations of cardiomyocytes were observed by wheat germ agglutinin (WGA) staining in vivo and IF staining of cardiac troponin T (cTnT) in vitro. Live cell imaging of NRCMs were taken to evaluate cardiomyocyte contractility function, while cardiac systolic and diastolic function in mice were assessed by transthoracic echocardiography. Coimmunoprecipitation (Co-ip) and nucleoplasmic separation were performed to explore the underlying mechanism of NR4A1 on cardiomyocyte senescence.
RESULTS Cellular senescence was evident in injured myocardial tissues after I/R, as shown by SA-ß-gal staining. In vitro experiments proved cardiomyocyte senescence was markedly increased in NRCMs after H/R, as significant elevation of senescent markers p16 and p21 were observed. Transcriptome analyses discovered cellular senescence in strong correlation with inflammatory response, and NR4A1, reduced after I/R, may be a potential regulator of these biological processes. Remarkably elevated senescent markers were observed in NR4A1 knockout I/R mice, while NR4A1 overexpression attenuated I/R induced myocardial senescence. With addition of D-galactose as positive control, it is affirmed NR4A1 overexpression protected against cardiomyocyte senescence. Live cell imaging and cytoskeletal staining demonstrated that senescent cardiomyocytes exhibited impaired contractility with hypertrophic morphology, while cardiomyocytes overexpressing NR4A1 showed a less severe decline in contractile function, along with milder morphological alterations. Overall, NR4A1 knockout led to exacerbated cardiac function, and myocardial specific NR4A1 overexpression exerted protective effects after I/R. To explore the precise function and possible mechanism of NR4A1 in regulating cardiomyocyte senescence, markers of SASP were evaluated to reveal significantly increased levels of pro-inflammatory SASP factors in NR4A1 knockout I/R mice, including IL-1β, CXCL1, CCL2, while noticeably lower levels in NR4A1 overexpressing I/R mice, suggesting NR4A1 may contribute to weakened inflammatory response. As a prominent reduction in the elevation of NF-κB p65 phosphorylation was observed in NR4A1 overexpressing I/R mice compared to wildtype I/R mice, IF and nucleoplasmic separation were further employed to reveal NR4A1 overexpression inhibited p65 nuclear translocation. Furthermore, co-ip confirmed interaction between NR4A1 and NF-κB as well as significantly stronger interaction after NR4A1 overexpression after both I/R and H/R.
CONCLUSIONS Cardiomyocyte senescence exacerbated in response to I/R injury can be attenuated by NR4A1, at least partly through inhibition of NF-κB signaling. Anti-senescence treatment of cardiomyocytes can be a novel therapeutic strategy for myocardial ischemia and infarction.
GW34-e0636
Xi Zhang, Dan Liu, Ziqi Liu, Haixu Song, Xiaolin Zhang, Quanmin Jing, Chenhui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Members of the S100 protein family have been reported to function as endogenous danger signals (alarmins) playing an active role in tissue inflammation and repair when released from myeloid cells. S100A12 represents a novel biomarker and therapeutic target that regulates cardiovascular disease after its release. However, the role of S100A12 in the etiology of acute myocardial infarction (AMI) is not well understood. Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of AMI and in the externalization of some S100 family members. Here, we investigated the effect of S100A12 on neutrophils’ function and myocardial injury after AMI.
METHODS Since S100A12 is a human specific molecule and not expressed in mice, we constructed transgenic (TG) mice expressing S100A12 in myeloid cells. Myocardial infarction was induced by ligating the left anterior descending coronary artery (LAD). Cardiac function was assessed by echocardiography. Neutrophils from TG and WT mice bone marrow were isolated and cultured. In vitro experiments we used the overexpressing plasmid to increase the expression of S100A12 and small interfering RNA (siRNA) to inhibit the expression of S100A12. We used Western blotting, quantitative RT-PCR, immunofluorescence, immune-histochemistry and Masson’s trichrome staining to explore the function of S100A12. The levels of S100A12 and NETs related markers (Such as MPO) were detected in the blood by ELISA. The levels of NETosis- and apoptosis-associated proteins were analysed by western blot. The formation of NETs was visualized using differential interference contrast (DIC) method.
RESULTS We found significant increase of S100A12 level after AMI in vitro and in vivo. Moreover, S100A12 markedly increased neutrophil infiltration and exacerbated the damage of myocardial injury in TG mice compared to WT mice. Within the infarct zone, more markers of NETs were observed in TG mice, whereas intraperitoneal injection of DNase I decreased the damage effect of NETs. By ChIP and dual-luciferase reporter assay we found that Hypoxia-inducible factor-1α (HIF1α) directly bound to the promoter of the S100A12 gene and regulated S100A12 expression. We used the overexpressing plasmid of S100A12 and observed that S100A12 enhanced the level of NETosis. Whereas, siRNA-mediated S100A12 silencing reduced the production of NETs. Mechanistically, S100A12 binds with the receptor for advanced glycation end products (RAGE) and increases NETs formation and siRNA-mediated gene of RAGE ameliorated the effect of S100A12. We next used tandem mass tag (TMT) labeling quantitative proteomic technology and discovered that annexin a5 (ANXA5) was a receptor with significantly different expression level in TG compared with WT mice. In vitro experiments demonstrated that there existed a direct interaction between ANXA5 and RAGE. Importantly, S100A12-ANXA5-RAGE pathway was confirmed to be involved in the formation of NETs in neutrophils. We found and verified that GATA1 and STAT3 are transcription factors that play an important role among them.
CONCLUSIONS Our findings reveal a critical role of S100A12 in regulating neutrophil activation and NETs formation, resulting in aggravated myocardial injury after AMI. In such a process, S100A12 regulates NETosis via the Hif1α-S100A12-ANXA5/RAGE pathway. S100A12 is a useful molecular marker and possible target for treatment for AMI.
GW34-e0651
Yujie Zhang
National Key Laboratory of Frigid Zone Cardiovascular Disease and Department of Cardiology, The General Hospital of Northern Theatre Command
OBJECTIVES Qiliqiangxin Capsules (QLQX), a traditional Chinese patent medicine, has been approved for clinical treatment of heart failure. However, protective effects and molecular mechanism of QLQX on Ang II-induced chronic heart failure remains little known.
METHODS Chemical constituents and potential targets of QLQX were obtained via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). The DisGeNET, and GeneCards databases were used to collect chronic heart failure-related target genes. Based on common targets related to both QLQX and chronic heart failure, a protein interaction network was generated using the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Network diagrams of the active component–target and protein–protein interactions (PPI) were constructed using Cytoscape. Finally, the most important signaling pathway was validated experimentally in C57 mice administrated by Angiotensin II (1000 ng kg−1 min−1) for 28 days.
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, which have different high expression in different cells in the heart: Immunocytes (52), endothelial cells (51), cardiomyocytes (34), smooth muscle cells (33) and fibroblasts (31). A protein-protein interaction network with 99 nodes and 1747 edges was obtained by topological screening. The average node degree value was 38, in which the node represented the target, the edge represented the association between two targets, and the degree value represented the intensity of the association. The top ten targets of correlation strength were Interleukin-6 (IL-6), Albumin (ALB), Threonine kinase 1 (AKT1), Vascular endothelial growth factor (VEGFA), Tumor necrosis factor (TNF), Nitric oxide synthase 3 (NOS3), Epidermal growth factor (EGF), Mitogen activated protein kinase 8 (MAPK8), Chemokine-8 (CXCL8) and Endothelin1 (EDN1). 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 10 signaling pathways related to CHF were AGE-RAGE, IL-17, blood flow shear stress and atherosclerosis, HIF-1, TNF, NF-kappa B, cGMP-PKG, JAK-STAT, MAPK, and AMPK signaling pathways. It is suggested that QLQX may play a role in the treatment of CHF through the above pathways. Among these signaling pathways, AGE-RAGE was selected for validation in C57 mice. The results indicated that QLQX may inhibit inflammatory processes in chronic heart failure via the AGE-RAGE signaling pathway.
CONCLUSIONS This study provides a strategy for understanding the mechanism of QLQX against chronic heart failure by combining network pharmacology and experimental validation.
GW34-e0652
Yujie Zhang
National Key Laboratory of Frigid Zone Cardiovascular Disease and Department of Cardiology, The General Hospital of Northern Theatre Command
OBJECTIVES Cardioembolic stroke (CS) contributes significantly to a growing proportion of ischemic strokes (IS). Furthermore, the incidence of CS is anticipated to increase manifold in the upcoming decade. Recent studies suggest that inflammatory immune response and fibrosis in the atrial substrate lead to atrial fibrillation (AF)/CSs. Nonetheless, the regulatory mechanisms related to immune infiltration and fibrosis in CS have received insufficient attention in academic research.
METHODS Initially, the GEO database was accessed to obtain gene expression profiles of control and CS samples. The identification of immune- and fibrosis-associated genes was conducted separately through the ImmPort and DisGeNet databases, respectively. Twenty-seven hub genes associated with CS were acquired through differential analysis as well as WGCNA; the analyses were conducted on whole blood samples obtained from GSE58294. Moreover, in order to obtain the key gene MMP9, a core subnetwork comprising twenty-seven hub genes was identified and subsequently intersected with immune- and fibrosis-related differential expression genes (DEGs) (ImmDEGs and FibDEGs).
RESULTS Twenty-two herbal ingredients were predicted based on MMP9. Eventually, the results revealed that MMP9 docks well with isoliquiritigenin (ISL), shikonin, and 1,4-naphthoquinone. Furthermore, herbs rich in ISL, shikonin, and 1,4-naphthoquinone, suppress immune infiltration and alleviate myocardial fibrosis, ultimately leading to an improvement in CS by regulating MMP9.
CONCLUSIONS The proposed strategy offers a systematic approach to elucidate phenotype-target-herb compound associations based on CS, thereby providing novel perspectives for identifying lead compounds from Chinese herbs.
GW34-e0677
Zihui Zhang1, Heng Ma1,2
1Xi’an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi’an, Shaanxi 710072, China
2Department of Physiology and Pathophysiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
OBJECTIVES Myocardial ischemia/reperfusion (I/R) injury is characterized by cell death via various cellular mechanisms upon reperfusion. As a new type of cell death, ferroptosis provides new opportunities to reduce myocardial cell death. Ferroptosis is known to be more active during reperfusion than ischemia. However, the mechanisms regulating ferroptosis during ischemia and reperfusion remain largely unknown.
METHODS The contribution of ferroptosis in ischemic and reperfused myocardium were detected by administered of Fer-1, a ferroptosis inhibitor to C57BL/6 mice, followed by left anterior descending (LAD) ligation surgery. Ferroptosis was evaluated by measurement of cell viability, ptgs2 mRNA level, iron production, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels. H9C2 cells were exposed to hypoxia/reoxygenation to mimic in vivo I/R. We used LC-MS/MS to identify potential E3 ligases that interacted with frataxin in heart tissue. Cardiac-specific overexpression of frataxin in whole heart was achieved by intracardiac injection of frataxin, carried by adeno-associated virus serotype 9 (AAV9) containing cardiac troponin T (cTnT) promoter, then cardiac function as well as ferroptosis were measured.
RESULTS We showed that regulators of iron metabolism, especially iron regulatory protein, were increased in the ischemic myocardium or hypoxia cardiomyocytes. In addition, we found that frataxin, which is involved in iron metabolism, is differentially expressed in the ischemic and reperfused myocardium and involved in the regulation of cardiomyocytes ferroptosis. Furthermore, we identified an E3 ligase, NHL repeat-containing 1 (NHLRC1), that mediates frataxin ubiquitination degradation. Cardiac-specific overexpression of frataxin ameliorated myocardial I/R injury through ferroptosis inhibition.
CONCLUSIONS Through a multi-level study from molecule to animal model, these findings uncover the key role of frataxin in inhibiting cardiomyocyte ferroptosis and provide new strategies and perspectives for the treatment of myocardial I/R injury.
GW34-e0678
Wang Xiaoqi1,2, Yan Xiangyu1,2, Chen Yujia1,2, Mang Ge1,2, Zhang Maomao1,2
1Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University
2The Key Laboratory of Myocardial Ischemia
OBJECTIVES Neutrophils have been implicated as intense responders of Myocardial ischemia reperfusion (MI/R) injury for immunometabolic rewiring locally. Metabolic stress derived protein lactylation plays an important role in immune response. However, the functions of lactylation in neutrophils post MI/R remain unknown. We aimed to investigate the mechanism of lactylation involving in remote immunometabolic reprogramming in neutrophils post-MI/R.
METHODS We utilized single-cell transcriptome of bone marrow and circulating neutrophils exposed to various MI/R periods to explore immunometabolic pattern. We combined with proteomic and lactyl proteomics analysis to identify the S100a9K26 as a major lactylated target. Mouse models including Padi4-knockout, Tlr4-knockout, and S100a9K26R mutant mice, followed by multiple molecular biological methodologies, were used to demonstrate the role of S100a9K26 lactylation (S100a9K26la) in MI/R. Serum S100a9K26la levels were measured in acute myocardial infarction (AMI) patients after percutaneous coronary intervention (PCI) to evaluate the clinical relevance.
RESULTS We demonstrated that inflammatory and glycolytic process in neutrophils were activated in the distant bone marrow, far from the injury heart. We provided the first evidence that S100a9k26la driven by glycolysis elevated in neutrophiles along their trajectory post MI/R. Mechanistically, lactylation of S100a9 amplified the inflammation through the inhibition of S100a9 degradation, promotion of neutrophil extracellular traps (NETs) dependent S100a9 release and boost of neutrophils hyperactivition via toll like receptor 4 (TLR4). Blockade of S100a9K26la inhibits inflammation and improves cardiac function post MI/R. Finally, we demonstrated that K26-Lactylated s100a9 is associated with cardiac death in AMI patients.
CONCLUSIONS Our results show that innate immune signaling of neutrophils begins in the bone marrow, implicate glycolysis-derived S100a9K26 lactylation in governing S100a9 degradation and release. We provide evidence that S100a9K26la may serve as a novel therapeutic target and clinical prognostic biomarker for MI/R.
GW34-e0682
Yihui Wang1,2,3, Tang Gao1,2,3, Wenyuan Wang1,2,3, Lingling Xu1,2,3, Yishu Song1,2,3, Lufang Wang1,2,3, Li Zhang1,2,3, Mingxing Xie1,2,3
1Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
2Clinical Research Center for Medical Imaging in Hubei Province
3Hubei Province Key Laboratory of Molecular Imaging
OBJECTIVES Heart transplant rejection (HTR) significantly affects the survival time and living quality of postoperative patients. How to effectively control it has always been an important scientific problem. Inducing immune tolerance and noninvasive monitoring it through ultrasound imaging is an extremely promising method for HTR treatment. However, there is still no mature strategy.
METHODS This study proposed the induction of immune tolerance by transfusion of engineered macrophages and the implementation of ultrasound molecular imaging to monitor graft rejection. Secondly, a mouse heart transplantation model was established, and the engineered macrophages were transfused back to induce tolerance and explore the mechanism of induction of immune tolerance. Finally, in vivo bio-orthogonal reactions were used to achieve ultrasound molecular imaging of the engineered macrophages and monitor the rejection reaction.
RESULTS In vitro experiments, RAW264.7 cells were induced to express PD-L1 at 48 h using interferon IFN-γ, and the immunofluorescence results showed that the PD-L1 level was significantly higher in the treated group compared with the control group. In addition, macrophages were incubated with rapamycin nanoparticles for 8 h. Under the stimulation of an inflammatory environment simulated by lipopolysaccharide, macrophages showed a significant increase in drug release at 36 h, while the non-inflammatory group showed a stable drug release level. In vivo experiments, azide-labelled macrophages were infused back into the tail vein of transplanted mice and DBCO-CY5 was injected 24 h later. The fluorescence intensity of the transplanted target site was observed to increase in a time-dependent manner, with a dense fluorescence signal at 5 h. The statistical results were highly significant when compared to the other time points.
CONCLUSIONS Bio-orthogonal glycolytic markers successfully enable non-invasive monitoring of graft rejection sites, and engineered macrophages are biologically active and can respond to the inflammatory microenvironment at the rejection site to target the release of rapamycin in order to induce immune tolerance with PD-L1.
GW34-e0687
Yuan Song1,2,3, Yihui Wang1,2,3, Lingling Xu1,2,3, Wuqi Zhou1,2,3, Wenyuan Wang1,2,3, Tang Gao1,2,3, Li Zhang1,2,3, Mingxing Xie1,2,3
1Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
2Clinical Research Center for Medical Imaging in Hubei Province
3Hubei Province Key Laboratory of Molecular Imaging
OBJECTIVES Myocardial ischemia-reperfusion injury (MIRI) has been shown to be closely associated with ferroptosis. Ferroptosis, as a way of cell death caused by iron ion overload, often leads to lipid peroxidation, and then causes rapid stress of lipid droplets (LDs). AIE-based multimodal probes have not been reported to monitor the dynamic changes of LDs in ferroptosis. Therefore, this study intends to use AIE probe to guide lipid drop multimodal imaging in ferroptosis to warn the risk of MIRI, in order to provide a new strategy for the early diagnosis of MIRI.
METHODS In vitro, three different cell lines, Hela, RAW264.7 and H9c2, were cultured with an ferroptosis induction agent (Erastin). The lipid imaging performance of AIE was evaluated by comparing the AIE probe with the commercial lipid trap BODIPY. Secondly, the dynamic relationship between LDs content and lipid peroxidation level in continuous time points after ferroptosis was analyzed and established. In addition, hypoxia and reoxygenation of cardiomyocytes were simulated to further evaluate the correlation between LDs and ferroptosis. Finally, a mouse model of myocardial ischemia-reperfusion injury was constructed. Combined with multimodal imaging such as fluorescence and ultrasound, AIE probe monitoring LDs metabolism was explored at the organismal level to verify the early diagnosis ability of AIE probe on MIRI.
RESULTS The probe is highly sensitive to LDs and can reflect lipid distribution more accurately than BODIPY. The probe study showed that Erastin induced LDs content increased gradually within 9 h and the intracellular lipid peroxidation level was lower. However, the LDs content tended to decrease after 12 h and reached the peak of ferroptosis within 24 h. In addition, the continuous frozen sections and staining of the ischemic myocardium in mice showed that the distribution of LDs could not only accurately indicate the target site of myocardial injury, but also reflect the degree of myocardial injury in mice. In particular, the echocardiography was used to evaluate the myocardial function of mice. it could accurately reflect the pathological status of the myocardium in early MIRI by ultrasonic measurement and quantification.
CONCLUSIONS AIE probe successfully realized early multimodal noninvasive monitoring of MIRI, and for the first time reflected its correlation with ferroptosis through guided LDs imaging, which could further clarify the pathological course of MIRI, especially the metabolic level of ferroptosis, and provide a promising new idea for the early diagnosis of MIRI.
GW34-e0688
Xiaoqiang Tang1,2,3
1Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, No.17 People’s South Road, Chengdu, Sichuan 610041, China
2Health Commission Key Laboratory of Chronobiology, Sichuan University, No.17 People’s South Road, Chengdu, Sichuan 610041, China
3Development and Related Diseases of Women and Children, Key Laboratory of Sichuan Province, West China Second University Hospital, Sichuan University, No.17 People’s South Road, Chengdu, Sichuan 610041, China
OBJECTIVES Cardiovascular aging and remodelling have become the key risk factors for cardiovascular diseases and contribute to increased mortality globally. Metabolic dysregulation is the fundamental mechanism underlying cardiovascular aging and diseases. Metabolic dysregulation reprogrammes epigenetic modifications by regulating the metabolite pool to remodel the cardiovascular tissues. However, the epigenetic mechanisms underlying cardiovascular aging and diseases remain largely unknown.
METHODS Our previous studies used clinical samples, animal models, and multiple-omics strategies to elucidate the epigenetic mechanisms underlying cardiovascular aging and diseases. We mainly focused on crotonylation and acetylation to understand the epigenetic mechanisms underlying cardiovascular aging.
RESULTS Our findings have elucidated that: 1) The mitochondrial metabolic enzyme ECHS1 regulated histone crotonylation to drive the reprogramming of cardiomyocyte transcriptome and aging-related cardiac hypertrophy, 2) The deacetylases SIRT2-4 regulated the balance between the anti-oxidative and prooxidative system within the mitochondria to regulate cardiovascular aging and diseases, 3) The deacetylase SIRT2 and metabolic sensor AMPK formed a positive feedback loop to maintain metabolic homeostasis and repressed cardiovascular aging and remodelling.
CONCLUSIONS Our studies have decoded some key epigenetic mechanisms underlying cardiovascular aging and diseases. These findings were published in journals such as Circulation (2017, 2021), Eur Heart J (2017, 2023), J Exp Med (2022), and Signal Transduct Target Ther (2022, 2023). Two of these papers were selected as the Top 10 Basic Research on Cardiovascular Diseases in China, three were highlighted in EHJ/F1000/JACC, and these papers were cited over 2600 times.
GW34-e0708
Jiawen Chen, Tiankai Shan, Tianwen Wei, Liansheng Wang
The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES Cancer therapies inhibiting CHK1-dependent pathways have been shown to be effective in wide variety of tumors, especially combined with gemcitabine. However, the incidence of related cardiac complications limits the further clinical application. This study aimed to elucidate the mechanism of CHK1 inhibition with gemcitabine clinical treatment induced cardiotoxicity.
METHODS Pharmacological CHK1 inhibition and cardiomyocyte-conditional knock out of CHK1 was characterized in conjunction with gemcitabine treatment in murine models. Proteomics analysis was performed to clarify the mechanisms of the combination therapy-induced cardiotoxicity. Changes in cardiac morphology, function and molecule were examined. CHK1 subcellular location was observed on mitochondria by tissue mitochondria isolation assay and immunofluorescent. Overexpression of CHK1 in mitochondria was achieved by mitochondria-targeting sequence directed AAV9 viruses in vivo. Further protein docking analysis and CO-IP was conducted to verify the interaction of SIRT3 and CHK1 in mitochondria. NMCM and adult mice were used for confirming the role of SIRT3-dependent michondrial redox homeostatsis in the combination therapy-induced cardiotoxicity.
RESULTS Both CHK1 pharmacological inhibition and knock out with gemcitabine induced weight loss, heart atrophy and cardiac dysfunction in mice, with the enrichment of dysregulated inflammatory genes identified by proteomics. Further experiments revealed that the united therapy resulted in respiratory chain dysfunction, mitochondrial redox imbalance and cardiomyocyte pyroptosis. We primarily found that CHK1 was localized in mitochondria. Restoration of mitochondrial CHK1 in cKO mice regained mitochondrial redox homeostatsis, inhibited cardiomyocyte pyroptosis and mitigated united therapy induced cardiotoxicity. Mechanically, mitochondrial CHK1 directly binded SIRT3 while CHK1 inhibition or knock out and gemcitabine treatment decreased SIRT3 expression. Overexpression SIRT3 in mice with united therapy maintained mitochondrial function, alleviated pyroptosis and improved cardiac function.
CONCLUSIONS We concluded that mitochondrial CHK1 plays a critical role for mitochondrial redox homeostatsis through SIRT3. Targeting SIRT3 may be a new therapeutic approach for the prevention and clinical treatment of CHK1 pathway inhibition with gemcitabine induced cardiotoxicity.
GW34-e0728
Jianghui Chen, Rongfeng Huang, Haoran Xin, Meiyu Zhou, Lihua Li, Zhihui Zhang, Min-Dian Li
Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University
OBJECTIVES Irregular eating patterns are recently discovered new risk factors for dyslipidemia and hepatic lipid metabolism disorders, which are positively correlated with the risk of cardiovascular diseases. Time-restricted feeding (TRF) that controls the eating time window can improve blood pressure and blood lipids in patients with metabolic syndrome. Meal timing resets circadian clocks in peripheral tissues, particularly in the liver. However, it remains largely uncharacterized whether and how meal timing organizes circadian rhythms beyond the transcriptome. Therefore, in-depth exploration of the mechanism of the peripheral circadian clock system adapting to feeding rhythms will provide new strategies and targets for the prevention and treatment of the risk of cardiovascular diseases related to circadian clock disorders.
METHODS We systematically profiled the proteomes of non modified proteins and those containing the four major PTMs in livers from TRF female mice. Samples were derived from the same cohort of mice and collected every 4 hours for two complete diurnal cycles. We obtained profiles of the rhythmic proteins or modified proteins from each time-restricted feeding regimen and compared the phase regulatory pattern between day/sleep time-restricted feeding (DRF) and night/wake time-restricted feeding (NRF) mice. Trans-omics integrative analyses were performed to reveal essential circadian protein features related to meal timing.
RESULTS We detected robust daily rhythms in 43% of phospho-proteins, 31.9% of lipids, 26.1% of non-modified proteins, 24.6% of ubiquitylated proteins, 17.1% of glycosylated proteins and 2.2% of succinylated proteins. Integrative analyses revealed that clock regulation of fatty acid metabolism represents a key circadian feature that is reset by meal timing.
CONCLUSIONS Together, this dataset represents a comprehensive resource detailing the proteomic and lipidomic responses by the liver to alterations in meal timing, which can provide some references for the prevention and treatment of the risk of cardiovascular diseases related to circadian clock disorders.
GW34-e0734
Jianxin Zhang, Rongfeng Huang, Haoran Xin, Lihua Li, Zhihui Zhang, Min-Dian Li
Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University
OBJECTIVES Circadian desynchrony results in adipose dysfunctions, which further leads to metabolic syndrome such as obesity, hypertension and dyslipidemia. High-fat diet (HFD) feeding rewires circadian rhythms of feeding behavior and peripheral organs. While the liver has been extensively studied, it remains largely unknown how adipose tissue adapt their circadian rhythms upon diet-induced obesity and the flexibility towards weight loss after dietary intervention.
METHODS Eight-week old of wild type male mice on HFD for 13 weeks and achieved an average body weight of 50 grams. Then these diet-induced obese (DIO) mice were randomly assigned to two groups, one group was fed HFD for 7 days and the other was fed matched low-fat diet (LFD). The heart tissue was dissected from mice at Zeitgeber time 0 h (9:00 am, ZT0) and ZT12 (21:00 pm).
RESULTS We detected about 200 and 2500 diurnal genes in HFD and LFD, respectively. Pathway analysis revealed that rhythmic pathways in HFD are represented by circadian rhythm, ribosome biogenesis, nucleosome organization, whereas those in LFD are represented by myeloid cell function. Remarkably, the majority of the circadian clock genes except Clock exhibit robust diurnal rhythm in the adipose tissue of HFD-fed mice. Analysis of mRNAs and proteins in another cohort of HFD-fed mice confirmed that Clock lost rhythmicity at the transcript level but not in proteins. Diet reversal to LFD specifically restores diurnal difference in Clock transcripts in adipose tissue. We matched transcriptomics data with global profiling of neutral lipids, and found that lipid metabolism catalyzed by triglycerol hydrolase Ces1d is a key circadian feature that is activated by diet reversal.
CONCLUSIONS Our work defines the circadian signatures in the adipose tissue of diet-induced obese mice, and their flexibility upon dietary intervention, thereby shedding light on potential clock-modulated tissue-specific pathways during obesity.
GW34-e0735
Cheng-Lin Zhang1, Lei Zhao2, Lei He3, Yu Huang3
1Department of Pathophysiology, Shenzhen University
2School of Biomedical Sciences, Chinese University of Hong Kong
3Department of Biomedical Sciences, City University of Hong Kong
OBJECTIVES Endothelial nitric oxide synthase (eNOS) monomerization/dimerization plays crucial role in regulating endothelium-dependent relaxations (EDR). Growing evidence has revealed that autophagic dysregulation is involved in the pathogenesis of diabetic endothelial dysfunction. However, whether autophagy regulates eNOS activity through controlling eNOS monomerization/dimerization remains elusive.
METHODS Autophagy and autophagic flux was evaluated through WB or through the mCherry-GFP-LC3 system. eNOS dimer and monomer were evaluated through low temperature WB. Autophagy and autophagic flux were induced by torin, rapamycin, as well as calorie restriction. Vascular tone was measured by the wired myograph system.
RESULTS The present study shows that autophagic flux was impaired in the endothelium of diabetic db/db mice as well as in human endothelial cells exposed to advanced glycation end products or oxidized low-density lipoprotein. Inhibition of autophagic flux by chloroquine or bafilomycin A1 reduces eNOS dimerization and lowers nitric oxide bioavailability through raising mitochondrial reactive oxygen species (mtROS). Overexpressing transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis, restored autophagic flux, lowered endothelial cell ROS level, increased eNOS dimerization, and improved vascular function in db/db mouse aortas. Inhibition of mammalian target of rapamycin kinase (mTOR) increased TFEB nuclear localization, reduced mtROS accumulation, facilitated eNOS dimerization, and improved EDR in db/db mice. Moreover, calorie restriction also increased aortic TFEB expression, improved autophagic flux, and restored EDR in db/db mice.
CONCLUSIONS Taken together, the present study reveals that autophagy deficiency-mtROS-eNOS monomerization axis is involved in the endothelial dysfunction of db/db mice. Restoration of autophagy by targeting TFEB represents a novel approach for the treatment of diabetic endothelial dysfunction.
GW34-e0752
Wenwu Zhu, Wei Du, Bing Han
Division of Cardiology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Institute of Cardiovascular Disease
OBJECTIVES The ideal treatment for myocardial infarction should be able to effectively improve the oxygen supply in the infarct area and reduce the death of myocardial cells. In this study, we designed a nano-delivery system of MnO2@INN@Alb (IHM) used as an effective hypoxia mitigation and pyroptosis control strategy for improving cardiac activity in patients with myocardial infarction, and ultimately reducing mortality in patients with myocardial infarction.
METHODS INN@Alb nanoparticles were first prepared to improve the solubility of INN order to reach the effective concentration for pyroptosis inhibition. Then we verified the encapsulation of each element after modifying INN@Alb with KMnO4 and PEG.
RESULTS We have demonstrated that the synthesized IHM can efficiently produce O2 in the presence of acid (pH<6.5) and H2O2. IHM actively reverses hypoxia, scavenges reactive oxygen species (ROS) and stimulate angiogenesis in the ischemic myocardium of AMI rat. Also, IHM can significantly reverse the occurrence of cardiomyocyte pyroptosis and repress pyroptotic signaling pathway. Moreover, IHM significantly attenuated apoptosis of cardiomyocytes and reduced the infarct size and fibrosis area in ischemic myocardium. Subsequently, the remodeling of the left ventricle was significant alleviated, and heart function of AMI rat was markedly improved and reduced the infarct size and fibrosis area in ischemic myocardium.
CONCLUSIONS This IHM nanoparticle provides a new way to improve the existing treatment and is a potential new venue to treat patients with acute myocardial infarction in the near future.
GW34-e0762
Chaoqun Ma1, Qiang Xu2
1National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
2Department of Cardiology, Navy 905 Hospital, Naval Medical University
OBJECTIVES Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which may cause right heart failure and even death. Accumulated evidence has confirmed that microRNA-26 family members play critical roles in cardiovascular disease; however, their function in PAH remains largely unknown. Our study aims to elucidate the role and underlying mechanism of the miR-26a-5p in the development of PAH.
METHODS The expression levels of miR-26 family members were investigated through quantitative reverse transcription polymerase chain reaction (qRT-PCR). Chromatin immunoprecipitation (ChIP) analysis and luciferase reporter assays were used to explore the upstream regulator of miR-26a-5p expression in pulmonary arterial smooth muscle cells (PASMCs). Furthermore, the regulatory role of miR-26a-5p in PASMC autophagy was detected through tandem mRFP-GFP-LC3B fluorescence microscopy and western blots. Gain and loss of function assays were performed to explore the effect of miR-26a-5p on PASMC proliferation and migration, as determined by cell counting kit-8, 5-Ethynyl-2′-deoxyuridine (EdU) staining, wound-healing and transwell assays. Mechanistically, dual-luciferase reporter gene assays and western blots were used to identify the direct downstream targets of miR-26a-5p. Moreover, hypoxia-induced PAH rat models were established. Right ventricular hypertrophy and pulmonary vascular remodeling were evaluated using hemodynamic measurements and histological analysis followed by intraperitoneal injection administration of adeno-miR-26a-5p in vivo.
RESULTS Among the miR-26 family, miR-26a-5p was identified as the most downregulated member in plasma from PAH patients. Meanwhile, the expression of miR-26a-5p was decreased in the hypoxia-induced PASMC autophagy models, as well as lung tissues of PAH patients. Furthermore, ChIP analysis and luciferase reporter assays revealed that hypoxia inducible factor 1α (HIF-1α) specifically interacted with the promoter of miR-26a-5p and inhibited its expression in PASMCs. Tandem mRFP-GFP-LC3B fluorescence microscopy demonstrated that miR-26a-5p inhibited hypoxia-induced PAMSC autophagy, characterized by reduced formation of autophagosomes and autolysosomes. Consistently, miR-26a-5p obviously inhibited the conversion of LC3B-I to LC3B-II and p62 degradation in hypoxia-induced PASMCs. In addition, miR-26a-5p overexpression potently inhibited PASMC proliferation. Mechanistically, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), unc-51 like autophagy activating kinase 1 (ULK1) and ULK2 were identified as direct targets of miR-26a-5p, involving in hypoxia-induced PASMC dysfunction. Meanwhile, PFKFB3 could further enhance the phosphorylation level of ULK1 and promote autophagy in PASMCs. Moreover, intratracheal administration of adeno-miR-26a-5p markedly alleviated right ventricular hypertrophy and pulmonary vascular remodeling in hypoxia-induced PAH rat models in vivo.
CONCLUSIONS These results indicate that the HIF-1α/miR-26a-5p/PFKFB3/ULK1/2 axis plays critical roles in the regulation of hypoxia-induced PASMC autophagy and proliferation. MiR-26a-5p may represent as an attractive biomarker for the diagnosis and treatment of PAH.
GW34-e0763
Chaoqun Ma1, Dingyuan Tu2, Qiang Xu3
1National 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
2Department of Cardiology, The 961st Hospital of Joint Logistic Support Force of PLA, Qiqihaer, Heilongjiang 161000, China
3Department of Cardiology, Navy 905 Hospital, Naval Medical University, Shanghai 200052, P.R. China
OBJECTIVES Heart failure (HF) is the end stage of various cardiovascular diseases with high mortality rate. Novel diagnostic and therapeutic biomarkers for HF are urgently warranted. This study aims to identify potential hub genes and immunological characteristics of HF by the combination of bioinformatics analysis and machine learning.
METHODS The gene expression profiles of 124 HF patients and 135 nonfailing donors (NFDs) were obtained from six datasets in the Gene Expression Omnibus (GEO) public database. We applied robust rank aggregation (RRA) with weighted gene co-expression network analysis (WGCNA) method to identify critical hub genes in HF development. Furthermore, three machine learning methods were employed to discover novel diagnostic markers in HF, including best subset regression, regularization technique, and support vector machine-recursive feature elimination (SVM-RFE). Besides, immune infiltration was investigated in HF by single-sample gene set enrichment analysis (ssGSEA).
RESULTS Through the combination of RRA with WGCNA method, 39 shared genes were recognized to be associated with HF. Through integrating the three machine learning methods, FCN3 and SMOC2 were identified as novel diagnostic markers for HF. In addition, differences in immune infiltration signature were also found between HF patients and NFDs. Immune cell infiltration analysis found that aDCs, B cells, Macrophages, Mast cells, Th2 cells, and Treg may be involved in the HF development. Similarly, there was a different infiltration of immune-related functions in APC co inhibition, cytolytic activity, HLA, inflammation promoting, T cell co inhibition, T cell co stimulation, Type I IFN response between HF and NFDs. Moreover, we explored the potential associations between the expression of two diagnostic markers and immune response in the pathogenesis of HF.
CONCLUSIONS In summary, FCN3 and SMOC2 can be used as diagnostic markers of HF, and immune infiltration plays an important role in the initiation and progression of HF.
GW34-e0764
Chaoqun Ma1, Dingyuan Tu2, Qiang Xu2
1National 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
2Department of Cardiology, Changhai Hospital, Naval Medical University, Shanghai 200433, P.R. China
OBJECTIVES Cuprotosis is a newly discovered programmed cell death which acts by modulating tricarboxylic acid cycle. Emerging evidence has showed that cuprotosis-related genes (CRGs) play critical roles in the development of multiple diseases. However, the mechanism of cuprotosis involved in the occurrence and progression of heart failure (HF) has not been investigated yet.
METHODS Six HF microarray datasets (GSE16499, GSE26887, GSE42955, GSE57338, GSE76701, and GSE79962) were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed CRGs between HF patients and nonfailing donors (NFDs) using R package “limma”. Furthermore, three regularised linear methods-least absolute shrinkage and selection operator (LASSO) regression, RIDGE regression, and elastic net (EN) regression were applied to identify key diagnostic CRGs features by the “glmnet” package, and model performance was assessed by root mean squared error (RMSE). In addition, the potential biological functions of diagnostic CRGs were investigated by utilizing Gene Ontology (GO) function enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, together with immune infiltration analysis.
RESULTS Nine CRGs were differentially expressed in heart tissues from HF patients and NFDs. In addition, a three-CRG diagnostic signature, DLAT, SLC31A1, and DLST, which can easily distinguish HF patients and NFDs, was established by cross-combination of three machine learning algorithms, including LASSO, RIDGE and EN regression. Moreover, function enrichment and immune infiltration analysis demonstrated that the three diagnostic CRGs expression was strongly correlated to alterations of energy metabolism and immune microenvironment in HF.
CONCLUSIONS Our study discovered for the first time that cuprotosis was strongly related to the pathogenesis of HF. A three-CRG diagnostic signature for HF (DLAT, SLC31A1, and DLST) associated with energy metabolism and immune signaling pathways was identified, providing new insights into the underlying mechanisms and effective treatments of HF.
GW34-e0769
Bofang Zhang1,2,3, Hong Jiang1,2,3, Jing Chen1,2,3
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
2Cardiovascular Research Institute of Wuhan University, Wuhan, China
3Hubei Key Laboratory of Cardiology, Wuhan, China
OBJECTIVES Maladaptive ventricular remodelling greatly impacts the life quality and long-term prognosis of acute myocardial infarction (AMI) patients. The activation and differentiation of cardiac fibroblast is the core of ventricular remodelling after infarction and initiate the heart’s pathological remodelling process. LncRNAs have been confirmed to be critical in regulating AMI, besides, recently published studies disclosed that several LncRNAs play key roles in regulating the activation of fibroblast. Our present study is to investigate LncRNA that regulates fibroblast activation in AMI and uncover the potential mechanisms.
METHODS RNA-sequencing and bioinformatical analyses were conducted to identify the candidate LncRNAs for AMI. Adenovirus for LncRNA knockout and overexpression were constructed to alter the PVT1 expression of cardiac fibroblast in vitro. Fibroblast-specific knockout and overexpression mice were also constructed to alter PVT1 expression in vivo. Cardiac fibroblast characteristics measurement, including proliferation, migration, secretion, and differentiation, were performed to verify the ability of PVT1 to regulate the activation of fibroblasts. Cardiac morphological, structural, functional, and hemodynamic changes as well as the degree of fibrosis were also measured to assess the effect of PVT1 on AMI. RNA-pulldown+Mass spectrometry and RNA immunoprecipitation were performed to identify the specific binding factors of PVT1.
RESULTS RNA-sequencing results revealed the expression of PVT1 was significantly and persistently elevated from 1 to 7 days after AMI. Besides, RNA-FISH and q-PCR analysis uncovered PVT1 was mainly enriched in the nucleus of the cardiac fibroblast. Thereafter, gain- and loss-of-function experiments were performed both in vitro and in vivo. Functionally, PVT1 knockout dramatically inhibited the proliferation, migration, secretion, and differentiation capability of fibroblast, as well as reduced infarct size, improved cardiac performance and alleviated cardiac fibrosis by mitigating fibroblast activation. However, enforced PVT1 expression resulted in the opposite effects. Mechanistically, RNA-pulldown+Mass spectrometry indicated histone methylase Suv39h1 was a direct target of PVT1, which was also confirmed by RIP assays. In addition, Chip-PCR analysis also demonstrated that Suv39h1 could directly bind to the promoter region of the NF-κB/p65, thus altering the level of H3K9me3 and inhibiting its transcription. Moreover, subsequent rescue experiments further verified that PVT1 regulated the expression of NF-κB/p65 to exaggerate AMI-induced fibrosis in a Suv39h1-dependent manner.
CONCLUSIONS This study demonstrates that PVT1-Suv39h1-NF-κB/p65 pathway is a promising therapeutic target for the treatment of AMI and the subsequent maladaptive ventricular remodelling by ameliorating the activation of cardiac fibroblast.
GW34-e0770
Chenhuiyu Qian1, Zijian Huang1, Yuhan Cao2, Cong Fu1
1Department of Cardiology, The First Affiliated Hospital of Wannan Medical College
2Department of Nephrology, The First Affiliated Hospital of Wannan Medical College
OBJECTIVES The mechanism of myocardium regeneration after myocardial infarction (MI) is still unknown. Exosome-based therapy is a promising cell-free approach for repairing the ischemic myocardium. This study investigated the protective effect of cardiomyocyte derived exosomes carrying myeloid triggering receptor 2 (TREM-2) on myocardium regeneration after MI.
METHODS First, Plasma samples from healthy controls and patients with myocardial infarction were collected to measure plasma exosomes TREM-2 levels. TREM2 expression in hypoxic myocardium derived exosomes was detected in vitro. Myocardial infarction models were established in wild type (WT) mouse and TREM2 gene knockout (TREM-2−/−) mouse by ligating the left anterior descending branch (LAD). Plasma exosomes from WT MI mouse (WT-P-exo) and TREM-2−/− MI mouse (KO-P-exo) were collected. Before ligation of anterior descending branch, exosomes were injected into the myocardium (TREM2−/− mice injected with WT-P-exo, WT mice injected with KO-P-exo). Exosomes inhibitor GW4869 was injected to inhibiting exosomes secretion. The AKT signal pathway inhibitor LY294002 intraperitoneal injected in myocardium 2 hours before surgery. The expression levels of TREM2, Cyclin A2, AKT, and p-AKT were detected in the infarcted and peri-infarcted areas. In addition, the therapeutic efficacy of intramyocardially injected exosomes for MI treatment was evaluated through functional and histological analyses. Macrophage scavengers was used to eliminate the impact of macrophage TREM-2.
RESULTS First, Expression of TREM-2 and Cyclin A2 mRNA in the peri-infarct area of WT mice increased after MI. The expression of TREM-2 derived from hypoxic cardiomyocytes exosomes was elevated compared to normal cardiomyocytes. The TREM-2 expression in plasma exosomes was also increased in MI patients. Injection of GW4869 resulted in a significant decrease in the expression of TREM-2, Cyclin A2 and p-AKT proteins in the peri-infarct area in WT MI mice. Immunofluorescence, HE and Masson staining demonstrated that injection of GW4869 reduced the average fluorescence intensity of CyclinA2 in the infarct margin area, promoted myocardial damage and increased fibrosis area of WT MI mice. The ultrasound results showed that injection of GW4869 aggravated heart damage in WT MI mice. In TREM-2 knock out (TREM-2−/−) mice, the expression of cyclin A2 and p-AKT was no elevated. Injection of WT-P-exo resulted in a significant increase in the expression of TREM-2, Cyclin A2 and p-AKT proteins in the peri-infarct area in TREM-2−/− MI mice, while injection of KO-P-exo did not affected the expression of TREM-2, Cyclin A2 and p-AKT proteins in the peri-infarct area in WT MI mouse. Injection of WT-P-exo into the TREM2−/− MI mice added the average fluorescence intensity of CyclinA2 in the infarct margin area and alleviated myocardial damage and decreased fibrosis area and improved cardiac function. In addition, intraperitoneal injection of LY294002 decreased the levels of TREM-2, Cyclin A2 and p-AKT proteins in the peri-infarct area in WT MI mice and WT-P-exo injected TREM2−/− mice. Further, LY294002 reduced the average fluorescence intensity of CyclinA2 in the infarct margin area, promoted myocardial damage, increased fibrosis area and decreased cardiac function in WT MI mice and WT-P-exo injected TREM2−/− mice.
CONCLUSIONS Exosomes carrying TREM-2 were released from cardiomyocytes to promote the regeneration of cardiomyocytes in infarction margin. The expression of CyclinA2 was increased in infarction margin which makes cardiomyocytes re-enter the cell cycle. It suggested a potential target to intervene myocardial regeneration after MI.
GW34-e0774
Yi Zhong1,2,3, Xueke Li1,2,3, Luyang Yi1,2,3, Yishu Song1,2,3, Wuqi Zhou1,2,3, Wenqu Li1,2,3, Qiaofeng Jin1,2,3, Tang Gao1,2,3, Li Zhang1,2,3, Mingxing Xie1,2,3
1Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2Clinical Research Center for Medical Imaging in Hubei Province, Wuhan 430022, China
3Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
OBJECTIVES Ischemia-reperfusion injury (IRI) after heart transplantation is a clinically significant sterile inflammation. It can induce primary graft dysfunction within 24 hours after heart transplantation and is the main pathogenic mechanism of post-transplant cardiac dysfunction and failure, leading to death and disability. Alleviating IRI is of great significance for improving graft survival. Recent studies have shown that ferroptosis plays a key role in the initiation of IRI after heart transplantation. Ferroptosis-induced release of damage-associated molecular patterns (DAMPs) promotes the adhesion of neutrophils to coronary endothelial cells through toll-like receptor 4-dependent signaling pathways, thereby triggering harmful inflammatory reactions in the transplanted heart. Therefore, inhibiting ferroptosis can reduce the release of DAMPs and alleviate IRI. As a promising cell-free therapy, extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) can effectively attenuate IRI. However, whether BMSC-EVs can alleviate transplant heart IRI by inhibiting ferroptosis remains unknown, and the underlying mechanisms need to be elucidated. The aim of this study is to reveal the molecular mechanisms by which BMSC-EVs alleviate cardiac allograft IRI by inhibiting ferroptosis.
METHODS In this study, a heterotopic heart transplantation model was established using BALB/c mice as donors and C57BL/6 mice as recipients. Allografts were collected at 2 h, 5 h, 8 h, 24 h, 48 h, and 72 h after reperfusion to investigate the timing of ferroptosis occurrence. After heart transplantation, mice were intravenously injected with BMSC-EVs, and the control group received an equal volume of saline to evaluate the therapeutic effect of EVs. MicroRNA databases, EV databases, and dual luciferase reporter gene experiments were used to identify miRNAs targeting ferroptosis-related genes in BMSC-EVs. The molecular mechanisms by which BMSC-EVs inhibit ferroptosis in transplanted hearts and cardiac cells through their miRNAs were further explored using gene overexpression/knockdown, qRT-PCR, western blotting, flow cytometry, and biochemical analysis. Additionally, histological analysis was performed to assess the efficacy of BMSC-EVs in attenuating cardiac allograft IRI.
RESULTS Biochemical analysis and qRT-PCR showed that compared to the control group, the levels of ACSL4, BECN1, Hmox1, iron, and malondialdehyde were significantly elevated in the cardiac allografts at 24 h after reperfusion, indicating that 24 h after reperfusion is the optimal timepoint to observe ferroptosis in cardiac transplant mice. BMSC-EVs significantly inhibited ferroptosis in cardiac allografts, as demonstrated by the significant reduction in ACSL4, BECN1, Hmox1, iron, and malondialdehyde. Histological analysis also indicated that BMSC-EVs significantly alleviated cardiomyocyte apoptosis and tissue damage, and reduced the levels of inflammatory factors in myocardial tissue. Based on TargetScan and ENCORI database analysis, miR-144-3p, which is rich in BMSC-EVs, was found to inhibit the expression of ACSL4. The direct binding of miR-144-3p to ACSL4 was validated through dual luciferase reporter gene experiments. Gene overexpression and knockdown experiments confirmed that ACSL4 promotes ferroptosis in cardiomyocytes during the process of hypoxia-reoxygenation. Moreover, cell co-incubation experiments with BMSC-EVs demonstrated that BMSC-EVs inhibited ACSL4 and upregulated GPX4. This effect was weakened when BMSC-EVs containing miR-144-3p inhibitor were used, indicating that BMSC-EVs can inhibit ferroptosis in cardiomyocytes during the process of hypoxia-reoxygenation by suppressing ACSL4 through miR-144-3p.
CONCLUSIONS This study revealed that BMSC-EVs can inhibit ferroptosis and alleviate cardiac allografts IRI by delivering miR-144-3p to suppress ACSL4. This novel mechanism by which BMSC-EVs exert their therapeutic effects will provide new strategies for developing more potent engineered BMSC-EVs.
GW34-e0779
Hanwen Zhang, Qi Chen
Department of Pathophysiology, Nanjing Medical University, Nanjing 211166, China
OBJECTIVES Macrophage-elicited inflammation is an essential player in obesity-associated heart disease. However, the underlying mechanism remains obscure. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response.
METHODS We conducted an epidemiological study of 8567 patients with cardiovascular diseases (CVDs) to identify etiological factors involved in obesity-induced cardiac dysfunction. We used lineage tracing to evaluate the contribution of resident and monocyte-derived macrophages in diet-induced obesity mice. Single-cell RNA-sequencing analysis of CD45+CD11b+F4/80+ cardiac macrophages from normal and obese mice were performed to explore the heterogeneity of macrophages. We then used a dual recombinase system (Cre and Dre) to specifically ablate CCR2+ macrophages. We further investigated the role of CCR2 in modulating obesity-induced cardiac inflammation and dysfunction by macrophage specific CCR2 deletion or CCR2 antagonist treatment. The molecular mechanism underlying the pro-inflammatory effect of CCR2+ macrophages was finally assessed at in vivo and in vitro by CUT&TAG, ChIP-PCR, luciferase assay, and macrophage-specific lentivirus transfection.
RESULTS Our population study and mouse model experiments reveal that inflammation, particularly monocyte-derived macrophage infiltration, exacerbates obesity-associated cardiac dysfunction in humans and mice. We identify 17 macrophage clusters in normal and obese hearts. We further show that the Ccr2 cluster undergoes functional transition from homeostatic maintenance to pro-inflammation. Consistently, inducible ablation of CCR2+ macrophages or selective deletion or inhibition of macrophage CCR2 prevents cardiac dysfunction. At the mechanistic level, we demonstrate that obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/ATF3/Lysozyme C/NF-κB signaling. We uncover a noncanonical role for lysozyme C as a transcription activator, binding to the RelA promoter and driving NF-κB signaling, and strongly promotes inflammation and cardiac dysfunction in obesity.
CONCLUSIONS We present here a revelation of macrophages in cardiac dysfunction under metabolic challenge. In addition, we elucidate the contribution of CCR2+ macrophages to cardiac inflammation and dysfunction through the regulation of ATF3/Lysozyme C/NF-κB signaling. Our findings suggest that lysozyme C may represent a potential target for diagnosis of obesity-induced inflammation and treatment of obesity-induced heart disease.
GW34-e0827
Victoria Khotina1, Mariam Bagheri-Ekta2, Arthur Lee1,2, Vasily Sukhorukov1,2
1Institute of General Pathology and Pathophysiology
2Petrovsky National Research Centre of Surgery
OBJECTIVES PERK is an endoplasmic reticulum-resident transmembrane protein that plays a crucial role in the unfolded protein response (UPR), which is activated in response to ER stress. While PERK’s primary function is to regulate protein folding and maintain ER homeostasis, emerging evidence suggests that PERK may be also involved in the regulation of inflammatory pathways in macrophages. However, there is a lack of data on PERK-mediated regulation of the inflammatory response in macrophages during atherosclerosis. The main aim of this study was to evaluate the impact of PERK on the regulation and activation of the inflammatory pathways in macrophages.
METHODS Human monocyte-like cell line THP-1 was used as control. CRISPR/Cas9 editing was used to generate THP-1 cell line with PERK gene knockout (THP-1 PERK −/−). Macrophage-like phenotype differentiation was induced by phorbol 12-myristate 13-acetate (PMA). Pro-inflammatory response was induced by cell incubation with lipopolysaccharides (LPS). The expression of C-Jun N-Terminal Kinase 1 (JNK1A2), nuclear factor kappa B subunit 1 (NFKB1), peroxisome proliferator activated receptor gamma (PPARG), tumor necrosis factor alpha (TNFA), interleukin 1 beta (IL1B) and interleukin 6 (IL6) genes were assessed by qPCR.
RESULTS To induce PERK knockout, THP-1 cells were transfected using two sgRNAs and a plasmid containing an expression cassette with the sequence of the puromycin resistance gene. A stable clone of cells with the most effective PERK knockout was obtained after 4 weeks of puromycin selection. PERK gene knockout in the obtained clone was confirmed by qPCR and Sanger sequencing. It was observed that there was no difference in the basal expression of JNK1A2, NFKB1, TNFA, IL1B and IL6 between THP-1 and THP-1 PERK −/− macrophages. However, the basal expression of PPARG in THP-1 PERK −/− was significantly increased compared to the control cells (P<0.001). Upon pro-inflammatory stimulation of THP-1 macrophages with LPS, there was an upregulation in the expression of JNK1A2, NFKB1, TNFA, IL1B and IL6, accompanied by a downregulation of PPARG compared to the untreated cells (P<0.01). On the other hand, the expression levels of JNK1A2, NFKB1, PPARG showed no significant differences in THP-1 PERK −/− macrophages compared to the untreated cells following LPS stimulation. However, LPS stimulation of THP-1 PERK −/− macrophages resulted in a decreased expression of TNFA and an increased expression of IL1B and IL6 compared to the untreated cells (P<0.01). Interestingly, the expression level of IL6 was decreased in THP-1 PERK −/− cells compared to the control cells upon LPS stimulation (P<0.01), while the expression of IL1B showed no significant differences.
CONCLUSIONS Our findings suggest that PERK may play a role in regulating the expression of pro-inflammatory genes, particularly JNK1A2, NFKB1, PPARG, TNFA and IL6, in macrophages during inflammatory responses. This indicates that PERK-mediated signaling in macrophages may have a significant impact on modulating inflammation, which is a crucial factor in the development and progression of atherosclerotic plaques.
This work was supported by Russian Science Foundation Grant #22-25-00393.
GW34-e0845
Yilin Zhou, Xiaomin Wei, Yuan Han, Enge Shao, Zhiwen Xiao, Yanbing Wang, Xiaoran Shi, Xinzhong Li
Department of Cardiology, Nanfang Hospital, Southern Medical University
OBJECTIVES Myocardial infarction (MI) leads to reactive oxygen species (ROS) production, which triggers DNA damage response (DDR) and cell cycle arrest in the cardiomyocytes (CMs) of infarcted area, thereby limiting the efficiency of endogenous myocardial regeneration and interfering with cardiac repair. Telomeric DNA, located at the ends of chromosomes, is particularly vulnerable to ROS-induced damage, while effective repair methods for the damage are currently lacking. This study aims to investigate whether telomerase reverse transcriptase (Tert), which has a protective effect on telomeric DNA, can effectively repair telomeric DNA damage caused by ROS, inhibit DDR-induced cell cycle arrest, and promote myocardial regeneration after MI.
METHODS The telomere length and telomerase activity were assessed using TEL-CY3 immunofluorescence staining and ELISA. Primary CMs were isolated and various interventions such as siRNA knockdown, adenoviral overexpression, and specific inhibitors were used to modulate the expression and function of Tert. Additionally, CM-specific Tert knockout mice generated using the Cre-loxP system or mice with adenovirus-mediated Tert overexpression were used for in vivo experiments. WB, qPCR, immunofluorescence and other techniques were employed to validate the impact of Tert on telomeric DNA damage repair and CM cell cycle re-entry. Echocardiography and histological staining were performed to evaluate heart function and cardiac remodeling. Subsequently, DNA pulldown and immunoblotting experiments were conducted to explore the upstream and downstream mechanisms of Tert regulation.
RESULTS The telomere length and telomerase activity in mouse CMs were found to be negatively correlated with age. Overexpression of Tert enhances telomerase activity and lengthens telomeres, thereby repairing DNA damage induced by ROS and promoting CM proliferation in vitro. In vivo experimental results demonstrate that enhancing Tert significantly improves cardiac function and prognosis by alleviating CM DNA damage post-MI. In terms of mechanism, DNA pulldown experiments identified hnRNPA2B1 as a potential upstream regulator of Tert in CMs. Further immunoblotting analysis revealed that Tert protects DNA from ROS-induced damage by inhibiting ATM phosphorylation and blocking activation of the Chk1/p53/p21 pathway.
CONCLUSIONS HnRNPA2B1-activated Tert could repair telomeric DNA via extending the length of telomeres and enhancing telomerase activity, thus blocking the ATM/Chk1/p53/p21signaling pathway, inducing the cell cycle re-entry to achieve the cardiac regenerative repair after MI.
GW34-e0852
Hao Zhang1,2,3, Zhuqing Li2, Wei Cai4, Yanxin Wang2, Jiaxin Feng2, Ning Yang1, Chengzhi Lu2, Yuming Li1
1Clinical School of Cardiovascular Disease, Tianjin Medical University, Tianjin, China
2The First Central Clinical School, Tianjin Medical University, Tianjin, China
3Center for Disease Control in Hanzhong, Hanzhong, Shaanxi, China
4Characteristic Medical Center of People’s Armed Police Force, Tianjin, China
OBJECTIVES Researchers have suggested the hypotensive effect of Sodium-dependent glucose transporters-2 inhibitor (SI), which may be a new target to improve hypotensive effect of renal denervation (RDN). We used spontaneously hypertensive rats (SHRs) to confirm this conjecture and explore relevant possible pathways.
METHODS 7 Wistar-Kyoto (WKY) rats and 35 SHRs were randomly divided into 6 groups. The blank control group (WKY Control, W group) was 7 WKY rats, while hypertension group (SHR control group, S group), the hypertensive sham operation group (Sham group), the RDN group (RDN group, R group), the SGLT-2 inhibitor control group (SI group) and RDN combined with sodium-dependent glucose transporters-2 inhibitor group (SIR group) was 7 SHR rats. Before RDN of R and SIR group, the SIR group was gavaged with dapagliflozin (DAPA), and the SI group was gavaged at the same time. Sham group was treated with sham operation. One week after the operation, the rat tail manometry and echocardiography were performed, and the peripheral blood inflammatory cells were detected by flow cytometry before sample collection. After sample collection, the serum was tested by enzyme linked immunosorbent assay (ELISA), Including interleukin-6(IL-6), Angiotensin-II (Ang-II), renin and norepinephrine (NE). Pathological testing included HE staining, Masson staining of myocardial tissue, tyrosine hydroxylase (TH) immunohistochemistry and C-Fos immunofluorescence staining of hypothalamus tissue.
RESULTS We found that RDN operation after intragastric administration of DAPA could significantly reduce systolic blood pressure in SHRs, better than RDN alone (mean systolic blood pressure: 133.5±9.093 mmHg versus 162.8±5.355 mmHg), which was independent of its hypoglycemic effect (Pearson correlation coefficient<0.2). At the same time, in pathological results of SIR group, it was found that compared with R group, there was a more significant improvement in the intensity of TH staining in hypothalamus tissue, closer to the normal level of cross-sectional area in myocardial cells (SIR versus W group: 262.2±21.58 versus 182.7±21.67 μm2), a stronger sympathetic inhibition in the brain (C-Fos mean fluorescence intensity SIR versus R group: 0.4880±0.03613 versus 0.3153±0.06217) and a lower fibrotic area in myocardial cells (SIR versus R group: 6.186±0.7125% versus 12.67±1.394%), and the proportion of inflammatory mononuclear cell subsets and the level of inflammatory factors were improved as well. While DAPA reduced inflammation and sympathetic nerve overexcitation alone, it could not completely reverse blood pressure and cardiac function. Similarly, the amelioration of inflammatory status and blood pressure reduction of rats treated with RDN alone was not better than that of rats treated with RDN combined with DAPA.
CONCLUSIONS The addition of DAPA before RDN operation can reduce the blood pressure of SHRs, and the effect was far better than RDN alone, and the level of related inflammatory factors also decreased correspondingly. At the same time, it was considered that the enhancement of hypotensive effect of DAPA in RDN was caused by inhibiting sympathetic activity and reducing inflammatory reactions. The possible common pathway of RDN and DAPA involves multiple inflammatory and blood pressure related signaling pathways, we still need further experimental verification, our study may have important clinical implications for RDN treatment in the future.
GW34-e0875
Yang Li, Yu Xue, Haixu Song, Chenghui Yan, Yaling Han
Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Guanxin Shutong (GXST) capsule is a Chinese medicinal formula that has been used clinically for the treatment of coronary heart disease in China. However, the molecular mechanisms of the cardioprotective effect are still unclear.
METHODS This study explores the cardioprotective effect and mechanism of GXST using the hypoxia reoxygenation (H/R)-induced myocardial injury model. In the in vivo study, an animal model of myocardial ischemia-reperfusion (MI/R) was induced by coronary occlusion. Fourteen male C57BL/6 mice were randomized into two groups: MI/R group (n=7), MI/R group treated with GXST (n=7). MI/R was induced by ligation of the left anterior descending coronary artery for 30 minutes, followed by ligature removed to restore coronary blood flow. GXST capsule (1.5 g/(kg·d)) or saline were administered via direct gastric gavage for 56 day after surgery. Mice were sacrificed and the hearts were harvested for histopathology and western blot analysis. In the in vitro experiments, H9c2 cells were incubated with GXST (200 μg/mL) capsule to explore the direct effects of CXST following exposure to CoCl2. Apoptosis and autophagy were measured to assess the protective effect of GXST. Proteins related to autophagy, apoptosis and AMPK/mTOR signalling pathways were detected using Western blotting.
RESULTS In vivo, GXST capsule significantly decreased levels of autophogy, apoptosis index, infarct size and myocardial fibrosis. In vitro, apoptosis and autophagy induced by H/R were significantly reduced after treating the H9C2 cells with GXST capsule. Moreover, GXST capsule also suppressed the AMPK/mTOR signalling pathway. Furthermore, the AMPK inhibitor Compound C (at 0.5 mmol/L), and GXST significantly inhibited CoCl2-induced autophagy and apoptosis, while AICAR (an AMPK activator, at 0.5 mmol/L) increased cardiomyocyte apoptosis and autophagy and abolished the anti-apoptotic effect of GXST capsule. Similar phenomena were also observed on the expressions of apoptotic and autophagic proteins, demonstrating that GXST reduced the apoptosis and autophagy in the CoCl2-induced injury model via inhibiting the AMPK/mTOR pathway.
CONCLUSIONS GXST capsule plays a cardioprotective role by alleviating apoptotic and autophagic cell death through inhibition of the AMPK/mTOR signaling pathway.
GW34-e0903
Wenjiao Gu
Second Hospital of Lanzhou University
OBJECTIVES The purpose of the present study was to study the effects of adenosine disodium triphosphate (ADTP) and alendronate sodium (AL), two extragenous PPi sources, on Atherosclerotic calcification (AC) in ApoE KO mice and to explore the potential its mechanism by examination of PPi content, lipid profiles and inflammation status.
METHODS We established AC models on ApoE KO mice, ADTP and AL were intraperitoneally injected for 2 months respectively. After the experiment, the cross-sectional samples of the aortic root were stained with von kossa staining kit to investigate the effects of ADTP and AL on AC in ApoE KO mice. Based on the work of previous section, serum lipid profiles, contents of pyrophosphate and inflammatory factors were examined in the blank, model and experimental groups of mice to explore the possible mechanisms of ADTP and AL on the inhibition of AC.
RESULTS We found that ApoE KO mice developed severe AC accompanied with hyperlipidemia, inflammation and with low level of PPi in serum. Compared with that in ApoE KO group, ADTP and AL dose-dependently reduced the aortic calcification lesions, and ADTP and AL had no effect on the contents of the serum TC, TG, LDL-C and HDL suggesting that the inhibitory effects of ADTP and AL on AC may not be related to the contents of lipid profiles. In addition, mice in ApoE KO group had low PPi content, meanwhile ADTP and AL increased the PPi content, the results suggested that deficiency of PPi in serum of ApoE KO mice might contribute to the AC and that complementation of PPi with ADTP and AL might be the important mechanism underlying their inhibition of AC. Finally, we found that ADTP and AL decreased the content of TNF-α and IL-6 in the serum of ApoE KO mice in dose-dependently manner suggesting that inhibition of inflammation by ADTP and AL might be another critical mechanism underlying their attenuation of AC.
CONCLUSIONS ADTP and AL, two exogenous PPi sources, reduced AC in ApoE KO mice by increasing the PPi level and inhibiting the inflammation.
GW34-e0915
Yi Yang1,2, Xinquan Wang1,2, Dan Wang1,2, Tao Luo1,2, Peijian Wang1,2
1Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College
2Key Laboratory of Aging and Vascular Homeostasis of Sichuan Higher Education Institutes, The First Affiliated Hospital, Chengdu Medical College
OBJECTIVES Diabetic cardiomyopathy is a major cause of mortality in patients with diabetes mellitus, but specific strategies for the prevention and therapy of cardiomyopathy in diabetic population still remains elusive. G protein-coupled receptor 35 (GPR35), a novel member of GPRs, plays important roles in cardiac physiology and pathology. To date, however, the role of GPR35 in diabetic hearts has not been identified yet.
METHODS A leptin receptor-deficient (db/db) C57BLKS mouse, a mouse model of type 2 diabetes, was used in our study. Neonatal murine ventricular myocytes (NMVMs) were isolated from wild-type (WT) and GPR35 knockout (GPR35−/−) mice and cultured separately in normal-glucose medium, high-glucose medium (HG), high fatty acid (HF), and HG plus HF medium (HG-HF).
RESULTS Here, we found that GPR35 was increased in diabetic NMVMs and hearts in a time-dependent manner, respectively. The impaired cardiac function, aggravated cardiac hypertrophy, and deteriorated myocardial fibrosis in diabetic hearts were significantly attenuated by GPR35−/−. Moreover, in vitro results showed that GPR35 silencing inhibited the apoptosis of cardiomyocytes and the generation of ROS induced by HG-HF, through increasing mitochondrial morphology and function and subsequently activating the antioxidant system. Finally, our results indicated that HG-HF induced the upregulation of GPR35 by inhibiting optic atrophy 1 (OPA1) expression in diabetic cardiomyocytes.
CONCLUSIONS Collectively, our findings provide the evidence that GPR35−/− improves cardiac function and fibrosis in diabetic mice, suggesting that ablation of GPR35 may be pharmacological approach to alleviate diabetic cardiomyopathy.
GW34-e0941
Zijian Huang1, Chenhuiyu Qian1, Yuhan Cao2, Cong Fu1
1Department of Cardiology, Yi Ji Shan Hospital Affiliated to Wan Nan Medical College
2Department of Nephrology, Yi Ji Shan Hospital Affiliated to Wan Nan Medical College
OBJECTIVES Recent studies have identified MDSCs as an important player after acute myocardial infarction. However, the mechanism remains unclear. Our study indicated that ticagrelor can exert anti-inflammatory effects after acute myocardial infarction by altering the phenotype of MDSCs.
METHODS Phenotypic changes of MDSCs were analyzed by Flow Cytometry with or without ticagrelor treatment in vitro. The expression of P2y12 on MDSCs was detected by qRT-PCR and Western Blot. A mouse AMI model was established by left anterior descending coronary artery (LADCA) ligation. Phenotype of MDSCs were analysed by Flow Cytometry with or without ticagrelor gavage in vivo. The expression of TNF-α and IL-10 were detected by qRT-PCR and Western Blot. Myocardial injury degree was detected by HE staining. Cardiac systolic function was evaluated by transthoracic echocardiography.
RESULTS No statistical difference in mRNA and protein expression of P2y12 receptor in MDSCs in vitro compared to macrophages. In AMI model mice, the percentage of MDSCs was increased in the circulation and infarcted heart and decreased in the spleen. The ratio of PMN-MDSC in the circulation and infarcted heart was significantly increased while M-MDSC was not changed compared with the control and sham groups. Meanwhile, PMN-MDSC but not M-MDSC decreased significantly in the spleen of AMI mice. Ticagrelor significantly reduced the proportion of PMN-MDSC in the infarcted heart and circulation. The proportion of M-MDSC increased in a dose-dependent manner. The proportion of PMN-MDSC and M-MDSC in the spleen increased. In addition, ticagrelor treatment increased IL-10 expression and decreased TNF-α expression in infarcted hearts. Ticagrelor treatment also improved cardiac function after MI. Splenectomy in AMI mice reduced the proportion of PMN-MDSC and increased the proportion of M-MDSC in circulation and infarcted hearts, reduced cardiac inflammation level and improved cardiac function. AMI mice circulating-derived MDSC injection increased the PMN-MDSC ratio and decreased the M-MDSC ratio in infarcted hearts and circulation in Splenectomy AMI mice and increased TNF-α expression and cardiac injury and decreased IL-10 expression in infarcted hearts. In contrast, ticagrelor-treated AMI mice circulating-derived MDSCs injection significantly increased the M-MDSC ratio and decreased the PMN-MDSC ratio in the infarcted heart and circulation in Splenectomy AMI mice compared with non-ticagrelor-treatment-MDSC injection. The cardiac inflammation level was also decreased and cardiac function improved.
CONCLUSIONS Ticagrelor treatment promotes the spleen-derived MDSC differentiate to M-MDSC after AMI and the mobilization of M-MDSC to heart, which reduces cardiac inflammation and improves cardiac function.
GW34-e0948
Yunpeng Zhang1, Yang Zhao2, 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
2Department of Radiology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin
OBJECTIVES Doxorubicin (DOX) is the first-line standard treatment of numerous cancers. However, DOX may lead to irreversible degenerative cardiomyopathy, congestive heart failure, and various arrhythmias, known as doxorubicin-induced cardiotoxicity (DIC), which limits the clinical applications. Studies reported that ferroptosis plays an important role on the development of DIC. Targeted intervention of ferroptosis with the specific inhibitors, such as ferrostatin-1 (Fer-1), could effectively prevent DIC. In recent years, catalytic nanozymes, such as cerium oxide (CeO2), have received much attention due to their strong antioxidant properties. Our previous research found that the transferrin receptor (TFR1) protein expression was significantly upregulated in DIC mice. In this study, we synthesized a biomimetic CeO2-based nanozyme by biomineralization with transferrin (Tf) proteins as the template, and then we assessed its targeted therapy for DIC via Tf-TFR1 mediated endocytosis.
METHODS The physicochemical and biological properties of NPs were characterized. Cellular uptake, cytotoxicity test, intracellular mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial ferrous ions and lipid peroxidation toxicity were verified with rat cardiomyocytes line H9c2 cells. Afterward, the male C57BL/6N mice were randomly divided into control, DOX, DOX+Fer-1, and DOX+NPs groups. Heart structure and function were measured by echocardiographic, electrocardiography and epicardial electrical labelling. Hematoxylin and eosin to observe the morphological changes. Western blot determines mitochondrial homeostasis regulation-related proteins and ferroptosis signalling pathway. Finally, the biodistribution and biocompatibility of CeO2@Tf was assessed.
RESULTS Transmission electron microscopy images revealed the encapsulated CeO2@Tf was ≈4 nm in diameter and remain stable in deionized water. The X-ray photoelectron spectroscopy revealed the ratio of Ce (III) to Ce (IV) ions was roughly 1:2.5. Meanwhile CeO2@Tf NPs showed good catalase (CAT) mimetics and superoxide dismutase (SOD) mimetics enzyme activity. The viability of H9c2 cells were not influenced by NPs even at high doses of Ce up to 200 μM. The nanozyme significantly reversed cardiac structural and electrical remodelling and reduced myocardial necrosis. Meanwhile, RNA sequencing of ventricular tissue revealed increased cardiac Hmox1 mRNA levels in DIC mice. Further, it demonstrated that nanozyme intervention not only significantly suppressed the oxidative stress, mitochondrial lipid peroxidation and mitochondrial membrane potential damage, but also inhibited activation of Nrf2/Hmox1 signalling pathway to restore mitochondria-dependent ferroptosis. Furthermore, the nanozyme could be cleared by the hepatobiliary systems, and showed a good biocompatibility.
CONCLUSIONS The current study showed that biomimetic mineralization of hybrid CeO2-based nanozyme against DIC were mediated by effect of antioxidant stress and the inhibition of Nrf2/Hmox1 signalling pathway, thereby maintaining mitochondrial homeostasis and function, and re-storing mitochondria-dependent ferroptosis. This provides some insights into the role of ferroptosis in DIC. Furthermore, the nanozyme could be a promising prevention and treatment candidate for clinical translation as a novel cardiomyocyte ferroptosis protector to mitigate DIC and improve the prognosis and quality of life of cancer patients.
GW34-e0982
Dong Guo, Mingming Zhang, Lang Hu, Yan Li
Department of Cardiology, Tangdu Hospital, Airforce Medical University
OBJECTIVES Lipid droplet (LD) accumulation is a notable feature of obesity-induced cardiomyopathy. Multiple studies have revealed the presence of excess LDs in the hearts of obese patients, and the extent of LD accumulation is directly related to cardiac function impairment. However, molecular details of LD biogenesis and pathological processes governing cardiac LD content remains poorly understood. Reticulon 3 (RTN3), an endoplasmic reticulum (ER)-localized protein, was recently identified as a key modulator of lipid metabolism in adipocytes. Therefore, we investigated the role of RTN3 in cardiac lipid metabolism and its regulatory mechanism in the development of obesity-induced cardiomyopathy.
METHODS Mice were fed high-fat diet (HFD; 60 kcal% fat) to induce obesity. Cardiac-specific RTN3 knockout/overexpression mice were developed using Cre/loxp system or adeno-associated virus 9 intramyocardial injection. Multiple analyses, including serial echocardiography, lipidomics, transmission electron microscopy, and oil red O staining were performed in vivo. Primary neonatal rat ventricular cardiomyocytes (NRVCs) were isolated and treated with palmitate in vitro. Adenovirus was used to upregulate or downregulate RTN3 in NRVCs. Long-term live-cell monitoring, fluorescent imaging, co-immunoprecipitation (Co-IP), chromatin immunoprecipitation, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were employed to elucidate the mechanism by which RTN3 affected cardiac lipid metabolism.
RESULTS HFD-fed mice exhibited significantly elevated cardiac LD amount and RTN3 expression. Cardiac-specific RTN3 overexpression induced obvious cardiac LD accumulation and functional impairment in normal diet-fed mice, phenotyping the detrimental effects of HFD. In contrast, RTN3 ablation ameliorated HFD-induced cardiac dysfunction and intramyocardial lipid accumulation, suggesting the important role of RTN3 in cardiac lipid metabolism. Then we investigated the linkage between RTN3 and myocardial lipid accumulation in vitro in NRVCs. Live cell imaging revealed that RTN3 overexpression significantly accelerated LD biogenesis in cardiomyocytes. Co-IP coupled with LC-MS/MS analysis identified fatty acid binding protein 5 (FABP5), a famous intracellular carrier for long-chain fatty acid (FA), as an interaction partner of RTN3. Silencing FABP5 blunted LD boosting induced by RTN3 overexpression. Moreover, the channeling of FA into LDs induced by RTN3 overexpression were also attenuated by FABP5 knockdown. Further investigations discovered that the 1st–65th amino acids of RTN3 were indispensable for the interaction between RTN3 and FABP5 and could induce a parallel effect on LD content and FAs channeling compared with full length RTN3. Finally, the mechanism underlying the upregulation of RTN3 was explored. We found that lipid overload-induced RTN3 upregulation was due to the increased expression of CCAAT/enhancer binding protein α (C/EBPα), which positively regulates RTN3 transcription by binding to its promoter region.
CONCLUSIONS Our study reveals a novel mechanism contributing to LD biogenesis in cardiomyocytes. ER-localized RTN3 directly interacts with FABP5 and facilitates FABP5-mediated FA directional transport to the ER, thereby promoting LD biogenesis. Under lipid overload conditions, C/EBPα was upregulated and then positively regulates RTN3 transcription, which ultimately led to the overactivated LD biogenesis and cardiac lipid accumulation. These findings advance our current understanding of the pathophysiology of obesity-induced myocardial lipid accumulation and cardiac dysfunction and lay the groundwork for novel strategies to treat cardiac dysfunction in obese patients.
GW34-e0984
Ya Qi Huang, Kuang Peng, Jie Wu
The First Affiliated Hospital of University of South China
OBJECTIVES This study aimed to observe whether ferroptosis is involved in cardiac and renal fibrosis in Dahl salt-sensitive hypertensive rats under long-term high-salt load.
METHODS Ten 7-week-old male Dahl salt-sensitive rats were adaptively fed for 1 week and then randomly divided into two groups: the normal-salt group fed with regular chow containing 0.3% NaCl and the high-salt group fed with high-salt chow containing 8% NaCl. After 8 weeks of feeding, non-invasive blood pressure measurements were performed using a rat tail artery blood pressure measurement device, and data were observed and recorded weekly to assess the success of the model. After the modeling period, histological changes in the heart and kidney tissues were observed using HE staining, and collagen fiber changes in the heart and kidney tissues were evaluated using Masson staining. The morphological features of mitochondrial Ferroptosis in cardiomyocytes and podocytes were observed under electron microscopy. Prussian blue staining was used to observe iron deposition in the tissues. Immunofluorescence analysis was conducted to observe the expression of GPX4 and xCT in the tissues. Iron content and MDA levels in the tissues were measured using colorimetric assays, and the expression levels of GPX4 and xCT in the tissues were detected using Western blot analysis.
RESULTS The systolic and diastolic blood pressures of the high-salt group rats were significantly higher than those of the normal-salt group (P<0.01). Histological staining with HE and Masson’s trichrome revealed that the myocardial tissues of the high-salt group rats exhibited cellular hypertrophy, disorganized arrangement, inflammatory cell infiltration in the interstitium, and increased collagen fiber proliferation around the interstitium and blood vessels (P<0.05). In the kidney tissues, partial glomeruli showed increased volume, sclerosis, disorganized arrangement, and atrophy of some renal tubules. Inflammatory cell infiltration and abundant collagen fiber proliferation were observed in the glomeruli, interstitium, and around blood vessels of the high-salt group rats (P<0.05), while the heart and kidney tissue structures of the normal-salt group rats appeared normal. Electron microscopy examination revealed that the heart and kidney tissues of the high-salt group rats exhibited mitochondrial shrinkage, decreased or absent cristae, and increased density of the mitochondrial double membrane, whereas no such changes were observed in the normal-salt group rats. Prussian blue staining of the heart and kidney tissues of the high-salt group rats showed deposition of blue particles, indicating iron deposition in the tissues, whereas little blue staining was observed in the heart and kidney tissues of the normal-salt group rats. The high-salt group exhibited elevated tissue iron content and MDA levels compared to the normal-salt group (P<0.05). Immunofluorescence analysis revealed reduced expression of xCT and GPX4 in the myocardium and kidneys of the high-salt group compared to the normal-salt group (P<0.05), and Western blot analysis similarly showed decreased expression of xCT and GPX4 in the myocardium and kidneys of the high-salt group compared to the normal-salt group (P<0.05).
CONCLUSIONS Ferroptosis, characterized by mitochondrial changes, is observed in the damaged heart and kidney tissues of Dahl salt-sensitive hypertensive rats. The downregulation of xCT/GPX4, proteins associated with Ferroptosis, suggests the involvement of Ferroptosis in the organ damage of salt-sensitive hypertension.
GW34-e1043
Feng Wang
Department of Cardiology, First Affiliated Hospital of Bengbu Medical College
OBJECTIVES The clinical application of doxorubicin (Dox) in tumor chemotherapy is limited by time-dependent and dose-dependent cardiotoxicity. Hence, there is an urgent need to elucidate doxorubicin cardiotoxicity and to solve the difficult problem in clinical application. It has been verified that serum and glucocorticoid-regulated kinase 1 (SGK1) possess cardioprotective effects.
METHODS H9c2 cells were treated with 1 μM doxorubicin for 24 h to establish doxorubicin cardiotoxicity, so as to determine the biological role of SGK1 in doxorubicin cardiomyopathy and to elucidate the underlying molecular mechanism. SGK1 level in doxorubicin-treated H9c2 cells was assessed by performing Western blot assay and RT-qPCR. CCK-8 assay and TUNEL staining were employed to evaluate the cell viability and cell apoptosis. Besides, apoptosis-related proteins were measured by Western blot assay to analyze cell apoptosis. Additionally, the release of TNF-α, IL-1β, IL-6, and IL-10 and the levels of ROS, MDA, and SOD were detected to reflect inflammation and oxidative stress. Moreover, Western blot assay was adopted for determination of ERS-associated proteins.
RESULTS Upregulation of SGK1 alleviated doxorubicin-induced cardiotoxic injury, cell apoptosis, inflammation and oxidative stress in H9c2 cells. Moreover, SGK1 overexpression mitigated doxorubicin-induced ERS in H9c2 cells. The suppressing effects of SGK1 on doxorubicin-induced cardiotoxic injury, apoptosis, inflammation, oxidative stress and ERS in H9c2 cells were partially abolished upon GRP78 overexpression.
CONCLUSIONS To conclude, upregulation of SGK1 may alleviate doxorubicin cardiotoxicity by repressing GRP78-mediated ERS.
GW34-e1058
Nikita Nikiforov1,2,3, Tatiana Kirichenko1,2, Marina Kubekina3, Yegor Chegodaev1,2, Alexander Zhuravlev1,2, Leonid Ilchuk3, Alexander Orekhov1,2,4
1Laboratory of Angiopathology, The Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow 125315, Russia
2P. Avtsyn Research Institute of Human Morphology, Federal State Budgetary Scientific Institution “Petrovsky National Research Centre of Surgery”, 3 Tsyurupa Street, Moscow 117418, Russia
3Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilova str., Moscow 119334, Russia
4Institute for Atherosclerosis Research, Osennyaya Street 4-1-207, Moscow 121609, Russia
OBJECTIVES The pro-inflammatory reaction of human monocytes and macrophages in response to a pathogen is characterized by a subsequent attenuation and the tolerance formation. We decided to study the pro-inflammatory response of monocytes from patients with preclinical atherosclerosis and the subsequent decrease in the pro-inflammatory activity of cells during differentiation into macrophages.
METHODS The study included 46 healthy patients with normal intima-media thickness (IMT) of the carotid arteries and 26 patients with atherosclerotic plaque and thickened IMT. CD14+ monocytes were isolated from blood, stimulated with 1 μg/mL LPS for 1 day and cultured for 7 more days without LPS. Secretion of IL-1β, IFN-α2, IFN-γ, TNF-α, CCL2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23 and IL-33 were measured in supernatants at each stage by ELISA.
RESULTS We found no differences in the generation of cytokines by monocytes in response to LPS. However, further in the course of cell differentiation into macrophages, we found that the cells of patients with atherosclerosis are characterized by increased secretion of the cytokines CCL2 and IL-6 on days 1–6 in culture. Moreover, after changing the medium, 7-day-old macrophages from atherosclerotic patients retained increased secretory activity compared to macrophages from healthy donors. This was manifested in increased basal secretion of the cytokines CCL2, IL-6, and IL-8. The degree of secretion of these cytokines significantly (P<0.01) correlated directly with IMT.
CONCLUSIONS Macrophages derived from LPS-stimulated monocytes from patients with asymptomatic atherosclerosis are characterized by prolonged and increased pro-inflammatory activity. The causes of chronification of inflammation in the vascular wall may lie at the level of circulating monocytes.
Supported by RSF (Grant No. 22-15-00273).
GW34-e1073
Zheng Yin1,2,3, Jun Wan1,2,3
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
2Cardiovascular Research Institute, Wuhan University, Wuhan, China
3Hubei Key Laboratory of Cardiology, Wuhan, China
OBJECTIVES Hypertension is one of the most notorious chronic diseases, which leads to approximately 30% of all deaths worldwide. Hypertensive vascular remodeling is defined as the changes in vascular function and structure induced by persistent hypertension. Maresin-1 (MaR1), one of metabolites from Omega-3 fatty acids, has been reported to promote inflammation resolution in several inflammatory diseases. This study aims to investigate the effects of MaR1 on hypertensive vascular remodeling.
METHODS We constructed an Angiotensin II (Ang II)-infused mouse model of hypertension, and evaluated the effects of MaR1 on blood pressure and hypertensive vascular remodeling. In addition, rat-derived vascular smooth cells (VSMCs) were used to construct vascular inflammation model in vitro. The biobehavior of VSMCs in response to Ang II was evaluated through CCK-8, EdU and wound healing assay.
RESULTS In vivo, MaR1 administration significantly decreased the systolic and diastolic blood pressure, decreased the medial thickness of aorta, attenuated aorta fibrosis, suppressed phenotype transition of VSMCs. In vitro, MaR1 treatment significantly modulated VSMC phenotype, and inhibited VSMC proliferation and migration. Moreover, MaR1 could attenuate NLRP3 inflammasome activation and GSDMD-related pyroptosis both in vivo and in vitro. Mechanically, the blocking of Nrf2/HO-1 pathway could reverse the protective effects of MaR1 on VSMC phenotype switching, proliferation, migration through the suppression of pyroptotic cell death.
CONCLUSIONS MaR1 may attenuate hypertensive vascular remodeling by inhibiting VSMC pyroptosis through the Nrf2/HO-1 signaling pathway. Overall, MaR1 may be a novel therapeutic strategy for the treatment of hypertension in the future.
GW34-e1075
Ya Liu, Xiaokang Chen, Dongdong Sun, Chao Zhang, Wujian Liu, Wei Eric Wang
Department of Geriatrics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
OBJECTIVES The metabolic phenotype of proliferative cardiomyocytes differs significantly from non-proliferative cardiomyocytes. Several studies indicated that the metabolic features include the augment of intermediate metabolite NAD+ in proliferative cardiomyocytes. However, whether and how NAD+ regulates adult cardiomyocyte proliferation is unknown.
METHODS The pro-proliferative effect of NAD+ was detected with Ki67 and PH3 immunostaining in both cultured cardiomyocytes and heart tissues. NAD+ was manipulated by supplementation of NAD+ precursor NMN or inhibition of NAD+ synthesis by FK866. The therapeutic effect of NAD+ against myocardial infarction (MI) was examined by echocardiograph.
RESULTS The NAD+ level in cardiomyocytes reduced during the first postnatal week, coinciding with the timeframe when cardiomyocytes transit from a proliferative state to a quiescent state. Supplementation of NAD+ promoted the proliferation of cultured postnatal 1 (P1) and P7 cardiomyocytes in-vitro, while inhibition of NAD+ synthesis inhibited the proliferation. Supplementation of NAD+ prolonged the proliferative window period of cardiomyocytes in neonatal mouse. It also promoted cardiomyocyte proliferation in adult post-MI heart, and enhanced cardiac function and improved long-term survival of the post-MI mice. Mechanistically, NAD+ regulated cardiomyocyte proliferation through a SIRT1-dependent manner. Inhibition of SIRT1 blocked the pro-proliferative effect of NAD+. Among the histone proteins related to SIRT1, the expression of H3K9ac profoundly decreased under the supplementation of NAD+, which could be partially rescued by SIRT1 inhibitor. Decreased H3K9ac lead to a downregulation of the cell cycle inhibitor p27.
CONCLUSIONS The ratio of cytoplasmic NAD+/NADH influences cardiomyocyte proliferation both in-vitro and in-vivo, through regulating SIRT1 deacetylase which suppresses cell cycle inhibitory gene p27 by modifying H3K9ac. Supplementation of NAD+ might be a potential therapeutic strategy for treating MI.
GW34-e1081
Qian Chen1, Xixiang Tang2, Suhua Li1
1Department of Cardiovascular Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
2VIP Medical Service Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
OBJECTIVES Lipotoxicity is a well-established contributor to cardiomyocyte death and heart damage, with ferroptosis being identified as a crucial death mode in cardiomyocyte disease. However, the role and underlying mechanisms of lipotoxicity in cardiomyocyte ferroptosis remain poorly understood. Therefore, this study aims to explore the potential role and mechanism of lipotoxicity in cardiomyocyte ferroptosis.
METHODS To establish an in vitro lipotoxic cell model, Rat H9c2 cardiomyocytes were treated with palmitic acid (PA). Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) were added to the cell model to inhibit ferroptosis. To explore the role of STING in H9c2 cardiomyocytes, siRNA transfection was employed to knockdown STING expression. In addition, an in vivo lipotoxic SD rat model was established using a high-fat diet (HFD), and ferroptosis was intervened by intraperitoneal injection of ferroptosis inhibitor Fer-1. STING expression in rats was knocked down by tail vein injection of myocardial-specific interference adeno-associated virus (AAV), or systemically inhibited by intraperitoneal injection of STING inhibitor H151. Doppler ultrasound technology was used to monitor changes in rat cardiac structure and function. HE and MASSON staining were employed to observe myocardial pathology and fibrosis changes in rats. Cell viability and death were measured using the CCK-8 assay kit and the Calcein-AM/PI assay kit, respectively. BODIPY™ 581/591 C11 was used to observe the level of lipid peroxidation in cells. The end-products of lipid peroxidation, malondialdehyde (MDA), and glutathione (GSH) levels in H9c2 cells/myocardium were detected by the thiobarbituric acid reactive substances (TBARS) kit and GSH assay, respectively. The levels of ferroptosis related proteins (ACSL4, SCL7A11, TFRC and GPX4) and STING pathway related proteins (STING, TBK/p-TBK, p65/p-65 and IRF3/p-IRF3) in cell and heat tissue were detected by Western blot analysis.
RESULTS In vivo experiments revealed that ferroptosis inhibitors significantly reduced the level of death and lipid peroxidation of PA-induced lipotoxic cardiomyocytes. Additionally, they increased the level of GSH and GPX4 in cardiomyocytes. The time-dependent activation of the STING pathway following PA stimulation was also observed. Knockdown the expression of STING could reduce PA-induced cell death and lipid peroxidation levels while restoring the expression of GPX4. Furthermore, the hearts of HFD rats showed worse structure and function compared to normal control rats. Specifically, HFD rats exhibited more disordered myocardial structure and arrangement, significantly increased fibrosis level, and reduced GSH levels. In addition, the protein levels of SCL7A11 and GPX4 were decreased, while STING protein level was increased in the hearts of HFD rats. In HFD rats with myocardial specific knockdown of STING, GPX4-GSH antioxidant capacity was restored, and the level of lipid peroxidation was reduced, improving the structure and function of the heart, disorder of myocardial structure arrangement and significantly reducing the level of myocardial fibrosis.
CONCLUSIONS The findings suggests that lipotoxicity can induce ferroptosis in cardiomyocytes through the activation of the STING pathway, providing new targets, and strategies for the treatment of lipotoxicity cardiomyopathy.
GW34-e1091
Ziyu Guo1, Ao Wang2, Yanxiang Gao3, Jingang Zheng3
1Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
2Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University
3Department of Cardiology, China-Japan Friendship Hospital
OBJECTIVES After cardiac ischaemia, an insufficient myocardial perfusion often occurs despite flow is successfully and completely restored in an upstream artery. This “no-reflow phenomenon” is caused by coronary microvascular dysfunction and is linked to a poor clinical outcome. This study aimed to assess the dynamic change of the CFR before and after ischemia reperfusion by pulsed-wave Doppler measurements.
METHODS Use a modified parasternal long-axis (PLAX) view to examine the left anterior descending coronary artery. CFR is defined as the ratio of the maximal flow velocity induced by a metabolic or pharmacologic stimulus to the resting left coronary artery (LCA) flow velocity. Measure the coronary flow velocity and CFR again in 1 hour, 3 hours, 5 hours, 8 hours and 24 hours, 48 hours after reperfusion, respectively. Compare the measurements to before IR measurements.
RESULTS Before the IR surgery, the baseline CFR and the mice had a normal CFR value near 2.14±0.43. After the IR surgery, CFR was significantly decreased in reperfusion 1 hour compared to the before IR surgery (1.18±0.14 vs 2.14±0.43), indicating that microcirculation was still not immediately restored even after opening the criminal vessels. As the reperfusion time was prolonged, the CFR values improved, but remained lower than before the procedure. What’s more, there was no significant difference between the CFR of reperfusion for 24 h and the CFR of reperfusion for 1 h. And there were no significant changes in cardiac function of the left ventricle when the CFR was significantly reduced in the mice.
CONCLUSIONS After ischemia reperfusion, the 1-hour CFR was significantly decreased than pre-operation. The CFR has gradually recovered over time, but remains below normal. The systolic function was preserved. Therefore, it is important to establish a practical guide to help doctors detect early microvascular dysfunction and study the progression of cardiovascular disease over time.
GW34-e1097
Xiaoming Xu
Department of Cardiology, Xijing Hospital, Fourth Military Medical University
OBJECTIVES Fibronectin type III domain containing 4 (FNDC4) displays a high homology with FNDC5 which has a wide range of cardiac metabolic protection. Recent findings indicated that FNDC4 was highly expressed in liver, and was involved in fatty metabolism and inflammation. In this study, we investigated the effects of FNDC4 on a mouse model of myocardial infarction and reperfusion (MI/R) injury.
METHODS MI/R models were established by ligation of the anterior descending branch followed by removal of the knot at 30 min, to investigate the change of FNDC4 expression. FNDC4-knockout (FNDC4−/−) and overexpression of myocardial FNDC4 were induced to clarify the effects of FNDC4 by determining myocardial infarct size, cardiomyocyte apoptosis and cardiac function. Cardiomyocytes apoptosis induced by hypoxia/reoxygenation treatment in vitro was further detected to access the effect of FNDC4. A nonbiased approach via the RNA sequencing (RNA-seq) analysis was performed to identify the underlying mechanism.
RESULTS Downregulation of myocardial FNDC4 expression was observed in MI/R mice in contrast to sham mice. FNDC4 deficiency further exacerbated cardiac function, augmented cardiac infarct size and increased cardiomyocyte apoptosis, compared with wide type (WT) mouse. While FNDC4 overexpression by intramyocardially injected with recombinant adeno-associated virus 9 encoding FNDC4 (rAAV9-Fndc4-3Flag) significantly improved cardiac function, reduced infarct size and cardiomyocyte apoptosis compared to mice injected with control virus. Results from in vitro studies demonstrated FNDC4 overexpression in NRVMs markedly decreased cardiomyocyte apoptosis induced by hypoxia/reoxygenation injury evidenced by expression of cleaved caspase 3, proportion of TUNEL-positive nuclei and annexin V+/PI+/- cells, as well as cell viability. By performing RNA-sequence analysis, a ERK1/2/Nrf2/HO-1&NQO1 axis was identified and was responsible for the beneficial effects of FNDC4 on cardiomyocytes.
CONCLUSIONS We discover and confirm for the first time that FNDC4 mediates cardioprotection in a MI/R injury model through ERK1/2/Nrf2/HO-1&NQO1 pathway. These findings show that FNDC4 is a potential therapeutic target for MI/R injury.
GW34-e1107
Fan Pan
West China Hospital of Sichuan University
OBJECTIVES Commercial biological Artificial heart valves (BHVs), which are made by cross-linking Glutaraldehyde with pig pericardium (PP), bovine pericardium (BP) and other animal tissues, have been widely used in interventional valve replacement. However, Glutaraldehyde cross-linked biological valve has many problems that limit its service life, the most important of which is thrombosis and calcification. We use sulfonated Betaine Zwitterion hydrogel to modify the Glutaraldehyde crosslinked biological valve, and evaluated the antithrombotic and anti-calcification properties of the valve leaf modified by this method.
METHODS
1. In vitro antithrombogenicity assay: To evaluate the antithrombogenic properties of the valve leaflets with the copolymer, an arteriovenous shunt model in rabbits was used to conduct an ex vivo perfusion experiment. After 2 hours of circulation, the samples were gently removed from the catheter and photographed. The samples with thrombus were also collected for quantitative analysis.
2. Subcutaneous implantation assay: The male Sprague Dawley rats (approximately 50 g) were anesthetized with pentobarbital sodium solution. Surgical incisions (10 mm) were made at the rat’s back, and then the samples were implanted subcutaneously. After 90 days, the samples were harvested and used to evaluate the degree of calcification.
RESULTS
1. The weight of the thrombus in the control group was 3.52±0.64 mg, while the weight of the thrombus in the experimental group was 0.95±0.12 mg. The experimental group was superior to the control group in terms of antithrombotic activity.
2. The calcium content in the control group is 202.75±3.16 μg/mg, while the calcium content in the experimental group is 65.78±2.12 μg/mg, indicating that the experimental group has better anti calcification capacity.
CONCLUSIONS Sulfonated betaine zwitterion hydrogel can improve the antithrombotic and anti-calcification ability of artificial biological valve.
GW34-e1112
Peinan Ju, Qing Yu, E Guangxi, Yawei Xu, Jianhui Zhuang, Wenhui Peng
Department of Cardiology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
OBJECTIVES Sleep is vital to health. Sleep arousal is associated with the increased mortality of cardiovascular disease in the elderly. Our study is to determine the role of sleep in myocardial infarction (MI) and to dissect the underlying mechanisms.
METHODS Sleep fragmentation (SF) model were used to simulate long-term sleep disorders. Left anterior descending coronary artery ligation mouse model were used to cause myocardial infarction in mice. Echocardiography was used to evaluate cardiac function after MI. Several morphological staining experiments were conducted to observe infarct area and fibrosis in heart. Flow cytometry was used to evaluate the infiltration of leukocytes after MI in the heart, as well as emergency hematopoiesis in bone marrow. Dihydrorhodamine 123 was used to detect oxidative stress levels in cardiac neutrophils. Bone marrow transplantation (BMT), Ly6G neutralizing antibodies, and SiglecF neutralizing antibodies were used to explore whether SF exacerbate MI through hematopoiesis and neutrophils. Adoptive cell transfer and competitive BMT were conducted to clarify the effect of SF on proliferation and differentiation of Granulocyte-Macrophage Progenitor (GMP) into neutrophils. High-throughput sequencing was used to explore the impact of sleep disorders on GMP during acute MI, search for related signaling pathways and differential expressed genes. Myeloid-specific Cebpe deletion mice and GMP adoptive transfer were conducted to clarify the specific mechanism by which Cebpe in GMP regulates sleep disorders and exacerbates MI. Chromatin immunoprecipitation-Sequencing (Chip-Seq) of transcription factor Cebpe was conducted to find related genes regulated by GMP through Cebpe.
RESULTS Mice with SF had higher mortality after MI. The cardiac function was decreased, infarct area was increased in sleep fragmented mice. SF also significantly aggravated MI-induced pathological cardiac fibrosis and collagen I synthesis. In addition, SF resulted in a significant increase in the number of neutrophils in infarcted heart, mainly due to an increase in SiglecFhigh neutrophils. Neutrophils in the infarcted heart of SF mice produce more reactive oxygen species (ROS). Neutralization of neutrophils or SiglecFhigh subsets of neutrophil can significantly alleviate the MI progression in SF mice. Infiltrated neutrophils in the heart of SF mice are mainly derived from GMP in bone marrow. The amount of GMP increases in the bone marrow of SF mice, which is more significant after MI. Transcription factor Cebpe was increased in GMP after long term SF. GMP-specific Cebpe deletion alleviated the progression of MI in SF mice.
CONCLUSIONS Our findings suggest that long term sleep disorder promotes the increase of bone marrow GMP Cebpe expression in the acute phase of MI, accelerates the proliferation and differentiation of GMP into neutrophils, leads to more neutrophil released to the infarcted area and transformed into SiglecFhigh subtype, and finally aggravates MI through the synthesis of ROS and collagen I.
GW34-e1113
Bolin Li1,2, Yue Wu1
1Department of Cardiovascular Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
2Department of Cardiovascular Medicine, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
OBJECTIVES Deep vein thrombosis (DVT) is a common vascular disease of which pulmonary embolism is the most serious complication. In obese humans, impaired fibrinolysis plays an important role during thrombus formation. Plasminogen activator inhibitor 1 (PAI1) functioning primarily as a negative regulator of fibrinolysis has increased significantly in obesity. And liver that sense obesity-induced metabolic stress was identified as a major determinant of circulating PAI1 in obese individuals. But the mechanism of increased PAI1 during obesity is not clear. Here we explored the upstream regulator of the PAI1 and how it functions in fibrinolysis and DVT.
METHODS Mice were fed with normal diet or high fat diet for 4 months. Then, each group of mice were randomly selected for inferior vena cava stenosis model for evaluating DVT burden, and the remaining mice for blood sampling for evaluating plasm fibrinolytic capacities by fibrin formation and lysis test. To explore the upstream regulator of PAI1, Bioinformatic analysis on transcriptomics and targeted bile acid metabolomics in human, baboon and mice liver samples were performed. Then, the expression of PAI1 was assessed in mice and MPH treated by FXR agonist as well as in MPH derived from FXR knock out (KO) mice. FXR KO mice were randomly selected for DVT modeling and blood sampling to measure plasm fibrinolytic capacities and DVT burden. Ultimately, Obese mice treated with Tropifexor were used to assess plasm fibrinolytic capacities and DVT burden.
RESULTS Obese mice had significantly reduced fibrinolysis and increased DVT burden compared to lean mice. And the levels of plasma PAI1 were also higher in obese participants and mice, due largely to their increased hepatocyte expression. Transcriptomics and targeted bile acid metabolomics analysis of human, baboon and mice liver samples suggest that increased PAI1 expression may be related to decreased FXR transcription activity in obesity; and similar results were obtained in MPH treated by palmitic acid. We focused on the FXR-PAI1 pathway, which may mitigate the reduction in fibrinolysis in obesity. FXR activation could inhibit mRNA and protein expression of PAI1 in both mice and MPH, and FXR KO could block the decline of PAI1 in MPH induced by FXR agonist. The fluorescent enzyme activity was significantly reduced after FXR activation in both AML12 and HEK293 cells transfected with plasmids containing PAI1-1 promoter area. FXR KO mice present significantly increased plasma PAI1 as well as further impaired fibrinolysis and increased DVT burden. Tropifexor activating FXR in obese mice lowered plasma PAI1 as well as further alleviated fibrinolysis and DVT burden.
CONCLUSIONS We identify FXR acting as a novel regulator of PAI1 and playing a new role in fibrinolysis and DVT. Clinical trial drugs targeting FXR in hepatocytes may suggest therapeutic strategies for improving fibrinolysis and lowering the risk of DVT in obesity.
GW34-e1120
Jianshu Chen
Lanzhou University Second Hospital
OBJECTIVES Endoplasmic reticulum stress (ERS) and mitochondrial autophagy are closely associated with myocardial damage in heart failure with preserved ejection fraction (HFpEF). The endoplasmic reticulum is involved in regulating mitochondrial function through the mitochondria-associated membrane (MAM). Here, we identified the role of leucine-rich repeat kinase 2 (LRRK2) in ER–mitochondrial tethering, which is essential for the treatment of myocardial damage caused by HFpEF.
METHODS With WKY as the control group, female SHR constructed HFpEF model, and rat tail blood pressure measurement, hemodynamics, echocardiography and exercise fatigue test to explore the successful establishment of HFpEF model. The protein expression of ATF6, LRRK2 and Parkin was changed by using different doses of LRRK2 inhibitor GNE-7915 in HFpEF rat model, and the changes of ERS and mitochondria were observed by electron microscopy.
RESULTS ERS transcription factor 6 (ATF6) had specific sequence pairing with the LRRK2 promoter region. Compared with WKY and SHR rats, HFpEF rats showed decreased lung dry weight/wet weight ratio and a large number of red blood cells clustered in the HE-stained alveolar cavity of the lung tissue. The ratio of type I/III collagen in myocardial tissue of HFpEF rats increased, and the ratio of type I/III collagen in myocardial tissue decreased after the intervention of GNE7915. The cross-sectional area of cardiomyocytes in HFpEF rats was larger than that in the other three groups. Compared with WKY and SHR rats, transmission electron microscopy showed that the mitochondrial arrangement of myocardial tissue in HFpEF rats was disordered, the shape was irregular, the original structure was lost, the mitochondrial ridge was blurred, some mitochondria vacuolated, and the endoplasmic reticulum was swollen. Western blot results showed that the expression of LRRK2 after the intervention of GNE-7915 was lower than that in the non-intervention group of HFpEF.
CONCLUSIONS MAM and the expression of LRRK2 were increased in HFpEF rats. ERS ATF6 may play a regulatory role in mitochondrial autophagy through the MAM complex LRRK2 pathway and participate in myocardial damage by HFpEF.
GW34-e1135
Zhuqing Li, Chengzhi Lu
Tianjin First Center Hospital
OBJECTIVES Heart Failure with Preserved Ejection Fraction (HFpEF) is a multifaceted disease, intricately linked with sympathetic nervous system activation. Despite advancements, therapeutic options for HFpEF remain constrained, largely due to a dearth of fitting preclinical models. Renal denervation (RDN), an emerging intervention, holds potential in attenuating sympathetic activity and ameliorating HFpEF high-risk factors such as hypertension and insulin resistance. Our study is designed to establish a multifactorial HFpEF mouse model and assess the therapeutic implications of RDN.
METHODS Aged 12-month-old male C57BL/6N mice were exposed to a high-fat diet (60% calories from lard) and L-NAME (0.5 g/L in drinking water) over a 5-week period to generate a multi-hit HFpEF model. The efficacy of the model was assessed through a range of methods, encompassing echocardiography, histology, exercise exhaustion tests, serum NT-proBNP measurements, and intraperitoneal glucose tolerance tests. Upon successful model establishment, mice were randomized to receive either bilateral renal denervation or a sham operation. The subsequent impact of RDN on the aforementioned parameters was then evaluated.
RESULTS In C57BL/6N mice, a cardiometabolic HFpEF phenotype was effectively induced through a multi-hit approach encompassing a high-fat diet, L-NAME administration, and aging. This potent combination triggered obesity and glucose intolerance, culminating in the emergence of characteristic HFpEF features such as cardiac hypertrophy, fibrosis, preserved fractional shortening with impaired deformation, atrial enlargement, lung congestion, hypertension and decreased exercise endurance. Intervention with RDN mitigated this cardiometabolic dysregulation and enhanced cardiac function, as demonstrated by reductions in cardiac hypertrophy, myocardial fibrosis, atrial weight, NT-proBNP levels (sham-RDN vs. RDN: 687±18 vs. 473±27, P<0.05), lung congestion, and improved exercise endurance (sham-RDN vs. RDN: 320±23% vs. 411±19%, P<0.05).
CONCLUSIONS Our study suggests that RDN effectively mitigates cardiac function and structure in a multi-hit HFpEF mouse model, indicating its potential as a promising therapeutic strategy for HFpEF.
GW34-e1136
Qingbo Lv1,2, Min Shang1, Wenbin Zhang1,2, Guosheng Fu1,2
1Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
2Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
OBJECTIVES Metabolic modulation is a promising target in preventing adverse remodeling of pressure overload induced cardiac hypertrophy. Previous studies have well documented the metabolic remodeling during the cardiac hypertrophy, mainly focusing on the glycolysis, FA oxidation, and BBCA metabolism. Little is known about the role of proline in regulating cardiac metabolism. In this study, we mainly demonstrated the importance of proline metabolism in pressure-overloaded induced cardiac remodeling.
METHODS In this study, we initially established the TAC model and the PE-induced neonatal rat ventricular myocytes (NRVM) hypertrophy model as in vivo and in vitro experimental models, respectively. We examined proteins, mRNA, and other factors in cardiac tissues to ascertain the changes in relevant metabolic enzymes. Subsequently, the construction of small interfering knockdown system and over-expression viruses allowed us to regulate the expression of the target gene, PRODH, in in vitro cell experiments and to explore its function in the development of cardiomyocytes hypertrophy. Following this, we employed the CRISPR-CAS9 technology to construct cardiac conditional PRODH knockout mice (PRODH-cKO) and cardiac-specific overexpression viruses mediated by AAV9, thus achieving in vivo regulation of PRODH expression. Mechanistically, we utilized unbiased transcriptome profiling, metabolic flux analysis, and non-targeted LC-MS, among other techniques, to systemically analyze the transcriptomics and metabolomics of cardiac tissue or cardiomyocytes. This thorough investigation revealed changes in metabolic enzymes and substrates in cardiac remodeling.
RESULTS In this study, we initially established the TAC model and the PE-induced neonatal rat ventricular myocytes (NRVM) hypertrophy model as in vivo and in vitro experimental models, respectively. We examined proteins, mRNA, and other factors in cardiac tissues to ascertain the changes in relevant metabolic enzymes. Subsequently, the construction of small interfering knockdown system and over-expression viruses allowed us to regulate the expression of the target gene, PRODH, in in vitro cell experiments and to explore its function in the development of cardiomyocytes hypertrophy. Following this, we employed the CRISPR-CAS9 technology to construct cardiac conditional PRODH knockout mice (PRODH-cKO) and cardiac-specific overexpression viruses mediated by AAV9, thus achieving in vivo regulation of PRODH expression. Mechanistically, we utilized unbiased transcriptome profiling, metabolic flux analysis, and non-targeted LC-MS, among other techniques, to systemically analyze the transcriptomics and metabolomics of cardiac tissue or cardiomyocytes. This thorough investigation revealed changes in metabolic enzymes and substrates in cardiac remodeling.
CONCLUSIONS Our research rigorously investigated the role of PRODH expression in pathological cardiac remodeling through in vivo and in vitro experiments. The absence of PRODH led to a deterioration of cardiac function, whereas the overexpression of PRODH could improve the TCA cycle’s energy supply by promoting the utilization of proline by cardiomyocytes, and stimulate glutathione synthesis by synthesizing glutamate. In summary, our study is the first to systematically demonstrate the role of proline metabolic cycling in pathological cardiac remodeling. This not only reveals the metabolic remodeling changes in pathological cardiac remodeling but also provides new therapeutic targets for the treatment of cardiac remodeling and heart failure.
GW34-e1139
Bingjun Lu
Army Medical University Southwest Hospital
OBJECTIVES The aim of this study was to compare the molecular characteristics of myocardial cell populations with different proliferative abilities in order to reveal the molecular mechanisms underlying changes in myocardial cell proliferation, and to identify potential targets for promoting cardiomyocyte cytokinesis.
METHODS In this study, weighted gene co-expression network analysis was employed to classify genes into 9 expression modules based on their expression patterns during cardiac development. Gene functional enrichment analysis and Pearson correlation analysis were then combined to screen and identify genes associated with cell cycle regulation during heart development.
RESULTS Gene functional enrichment analysis revealed that genes in the blue and turquoise modules may be involved in cell cycle regulation during heart development. Further analysis using Pearson correlation identified 3807 genes significantly correlated with the expression patterns of Ki67 and Ccnb1 genes. By analyzing myocardial cell populations with different regenerative capacities after cardiac tissue injury, proliferative cardiomyocyte populations were identified, and 825 genes were found to be significantly upregulated. In addition, a comparison between nuclei division and cytokinesis myocardial cell subpopulations led to the identification of 207 genes that may promote cardiomyocyte cytokinesis.
CONCLUSIONS In conclusion, this study compared and analyzed the molecular characteristics of myocardial cell populations with differing proliferative abilities from multiple perspectives. Thirty novel genes that potentially promote cardiomyocyte cytokinesis were identified. These findings provide new insights and therapeutic targets for the treatment and prevention of future heart diseases. By analyzing gene expression modules and cell cycle regulation during cardiac development, we can better understand the mechanisms of cardiac cell proliferation and division, which can contribute to the development of innovative treatment methods and drugs.
GW34-e1140
Xiaoyan Zhu, Lin Yuan, Hu Liang
Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
OBJECTIVES Oroxylin A (OrA) is a flavonoid obtained from the traditional Chinese medicine Scutellaria baicalensis. Overwhelming pieces of evidence expound on the anti-inflammatory, anti-bacterial, anti-viral, and anti-cancer potentials of this flavonoid, which makes it an engrossing compound for research. However, its effect on platelet activation remains unclear. The present study investigated the effects of OrA on platelet activation and thrombus formation in vitro and in vivo.
METHODS We detected the effects of OrA on platelet aggregation and ATP release induced by various agonists using aggregometer in vitro. Clot retraction and spreading were imaged by digital camera and fluorescence microscope. PAC-1 and CD62P was measured by Flow cytometry. Platelet adhesion on collagen-coated surface under flow conditions was performed using the BioFlux 200 setup. We also evaluated the antithrombotic effect of OrA using mouse mesenterial arteriole thrombosis model induced by FeCl3.
RESULTS OrA concentration-dependently suppressed platelet aggregation at the concentration range of 25–200 μM induced by ADP, thrombin and collagen. OrA presented the superior antiplatelet activity on ADP-induced platelet aggregation, and the IC50 value of OrA for ADP-induced platelet aggregation was 25±5.0 μM. OrA also inhibited ATP release, platelet spreading and clot retraction. We examined PAC-1 and CD62P, two platelet activation markers, via flow cytometry and found that OrA decreased expression of PAC-1 and CD62P in platelets. Finally, administration of OrA also suppressed platelet adhesion on collagen in flow condition and decreased thrombus formation in mouse mesenteric arterioles.
CONCLUSIONS In conclusion, we for the first time demonstrated that OrA suppressed platelet activation and thrombus formation, highlighting its therapeutic potential in cardiovascular diseases.
GW34-e1145
Ryosuke Tsukabe1, Satoshi Shimizu1,2, Yoichi Sunagawa1,2,3, Yasufumi Katanasaka1,2,3, Toshihide Hamabe1,2,3, Masafumi Funamoto1,2, Kana Shimizu1,2, Koji Hasegawa1,2, Tatsuya Morimoto1,2,3
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
2Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto 612-8555, Japan
3Shizuoka General Hospital, Shizuoka 420-8527, Japan
OBJECTIVES Hypertrophic stimuli activate cardiac transcription factors such as the zinc finger protein GATA4 and modulate gene expression in cardiomyocytes. Acetylation is a critical GATA4 activation mechanism mediated partly by intrinsic histone acetyltransferases (HAT) such as transcriptional coactivator p300. However, the details of the regulatory mechanism of GATA4 transcriptional activity remain unclear. In this study, we investigated whether GATA4 self-association is involved in transcriptional activation during the development of cardiomyocyte hypertrophy.
METHODS To investigate whether GATA4 undergoes homodimerization in vitro, a GST pull-down assay was performed with a 35S-labelled GATA4 protein using GST-GATA4. To identify the dimerization region necessary for the homodimerization of GATA4, we performed a series of GST pull-down assays. Moreover, we investigate whether GATA4 forms a multimer, full-length GATA4 produced by E. coli was subjected to size exclusion column chromatography, followed by Western blotting using an anti-GATA4 antibody. To determine how many GATA4 units formed a multimer, HEK293T cells were co-transfected with FLAG-GATA4, HA-GATA4, and 3xMyc-GATA4. Nuclear extracts prepared from these cells were immunoprecipitated with an anti-FLAG antibody followed by an anti-HA antibody, and Western blotting was performed using an anti-Myc antibody. HEK293 cells were transfected with ANF-luc or ET-1-luc, GATA4 or acetyl-deficient GATA4, and p300 or HAT-deficient p300, and then reporter gene assay was performed. Finally, HEK293 cells were transfected with FLAG-GATA4 and HA-GATA4, and the deletion mutant containing GATA4 multimerization region peptide (GMP). Nuclear extracts prepared from these cells were immunoprecipitated with anti-FLAG antibody followed by Western blotting. Cultured cardiomyocytes were transfected with GMP and then treated with PE. These cells were immunostaining with anti-MHC.
RESULTS A GST pull-down assay showed that GATA4 is bound to itself in vitro and that amino acids 308–326 are required for this binding. Size exclusion column chromatography showed that GATA4 formed multimers. Immunoprecipitation-Western blotting revealed that GATA4 formed, at least, a trimer. A reporter assay showed that p300 enhanced the promoter activities of ANF and ET-1. The self-association of GATA4 was disrupted by both acetyl-deficient GATA4 and HAT-deficient p300. Overexpression of GMP prevented p300-induced GATA4 self-association but not binding with p300 nor acetylation of GATA4. Chromatin immunoprecipitation and DNA pull-down assays showed that GMP did not inhibit p300-induced DNA binding of GATA4. The inhibition of GATA4 self-association using GMP suppressed phenylephrine-induced hypertrophic transcriptional activity and cardiomyocyte hypertrophy in cultured cardiomyocytes.
CONCLUSIONS These results suggest that GATA4 multimerization plays an essential role in hypertrophic gene transcription and that inhibiting this multimerization suppresses hypertrophic responses in cardiomyocytes. Future investigation of compounds that inhibit GATA4 multimerization may lead to the development of novel heart failure therapies.
GW34-e1181
Chaowei Hu1, Zhiyong Du1, Lijie Han1, Jing Li2, Huahui Yu1, Yu Wang1, Yanwen Qin1,3
1Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China
2Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
3Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China
OBJECTIVES Homozygote familial hypercholesterolemia (HoFH) is a rare metabolic disorder attributed to the expression and functional defects of low-density lipoprotein receptor (LDLR), which result in extremely high level of LDL-c and ultimately metabolic dysfunction in patients. Intestinal flora have been uncovered to be implicated in various metabolic disorders. However, whether gut microbiota participates in the development of HoFH remains largely unknown.
METHODS To investigate this issue, we performed comprehensive metagenomic and metabolomic analyses of LDLR knockout hamsters, and fecal microbiota transplantation from LDLR−/− to germ-restriction hamsters.
RESULTS The global gut microbial characteristics including richness and diversity in LDLR−/− group were similar to those in controls. It was identified that Staphylococcus hominis, Kushneriaavicenniae and Bacillus dielmoensis were significantly enriched in LDLR knockout hamsters, whereas Bacillus halotolerans and Bacillus drentensis were reduced. In addition, LDLR−/− hamsters showed profound alterations in metabolomic phenotypes as compared to the control group. LDLR−/− hamsters exhibited enhanced abundance of Glycerolipids, Hormones and Organic Acid, as well as its derivatives such as Mag (18:1), 7-Ketocholesterol and Palmitoylethanolamide (PEA). Moreover, by fecal transplantation from LDLR−/− hamsters to germ-restriction recipients, elevated cholesterol level was observed to be transferrable through gut microbiota, and the direct causal impact of gut microbiota on serum metabolomics shifts of the host was also demonstrated. Here it was further confirmed that, the circulating level of circulating PEA, which was enriched in LDLR−/− donors, was significantly augmented in serum of recipients following fecal microbiota transplantation. In vitro, PEA administration elicited markedly elevated expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) in Human Hepatocellular Carcinoma (Huh7) cell line.
CONCLUSIONS The present results demonstrate that gut microbiota in LDLR−/− hamsters lead to enhanced cholesterol levels through modulating metabolites. Meanwhile, it provides insights into a potential role of LDLR−/− specific intestinal microbiota-associated PEA as a key factor in regulating cholesterol synthesis. These findings describe a novel causal role of aberrant gut microbiota and metabolomics in contributing to the pathogenesis of HoFH.
GW34-e1200
Runmin Sun, Qiongying Wang, Jing Yu
Lanzhou University Second Hospital
OBJECTIVES The present study was designed to investigate whether mitochondrial dysfunction and oxidative stress in HTN-injured cardiomyocytes are associated with SIRT3 SUMOylation and whether SIRT3 deSUMOylation can ameliorate the related cardiomyocyte injury.
METHODS The human cardiomyocyte AC16 cell line was selected as the study target. The SIRT3-K288R cell line construction was verified by immunoprecipitation and the effect of Ang-II on SIRT3 SUMOylation was explored; the expression of SOD2, Acetyl-SOD2 (MnSOD), protein acetylation level, inflammatory vesicles NLRP3, etc. in different subgroups were determined by Western Blot to explore the SUMOylation modifications and SIRT3 deacetylation in HTN-related cell injury.
RESULTS
(1) Immunoprecipitation results showed that the level of SIRT3 SUMOylation was reduced after SIRT3-K288R transfection; compared to the control group, the level of SIRT3 SUMOylation was increased in the presence of AngII;
(2) Western Blot results showed that compared to the HTN cell injury model, the cardiomyocytes in the SIRT3-K288R intervention group had increased Acetyl-SOD2/SOD2 levels were increased (P<0.05) and protein acetylation levels were decreased in the SIRT3-K288R intervention group compared with the HTN cell injury model, indicating that SIRT3 increased the deacetylation effect on mitochondria and increased cellular antioxidant stress enzyme activity.
CONCLUSIONS In the HTN-associated cell injury model, the level of SIRT3 class ubiquitination was significantly increased, and the removal of SUMOylation modification by viral transfection could improve oxidative stress, protein acetylation levels and associated inflammatory responses in HTN-injured cardiomyocytes, indicating that SIRT3 SUMOylation may play an important mechanism in HTN-associated cell injury, and reducing SIRT3 SUMOylation modification may be a possible direction for future research.
GW34-e1217
Liangpeng Li, Qiao Liao, Chunyu Zeng
Department of Cardiology, Amy Medical Center (Daping Hospital), Army Medical University
OBJECTIVES Stimulating adult cardiomyocyte proliferation is a promising strategy for treating heart failure post myocardial infarction (MI). The cardiac metabolic pattern switching from glucose utilization to fatty acids oxidation are key factors contributing to the decreased proliferation potential of cardiomyocyte after birth. However, the underlying mechanisms are unclear, the potential targets for therapeutic purpose are still lacking.
METHODS We used Trimetazidine (TMZ), a metabolic modulator which inhibits fatty acids oxidation, to treat neonatal C57/BL6J mice, adult mouse and Bama minipig MI. The glucose utilization and fatty acids oxidation of cardiomyocytes were measured by XF24e Seahorse analyzer. Cardiomyocyte proliferation was evaluated by Ki67/Ph3, time lapse live cell imaging, and Myh6-MerCreMer/Mosaic analysis with double markers (MADM) transgenic mice. The cardiac function, scar size were also assessed. RNA-sequencing are performed on neonatal mouse heart to elucidate the transcriptional profile.
RESULTS
1. TMZ repressed fatty acid oxidation. As revealed by Seahorse analyzer, TMZ treatment inhibited fatty acids oxidation and enhanced glucose utilization in both neonatal and adult rodent cardiomyocyte.
2. TMZ promotes cardiomyocyte proliferation in postnatal mice. In neonatal mice, TMZ increased the heart weight and gross volume while decreased the cross-section area of cardiomyocyte, Ki67 and Ph3 positive cardiomyocytes were significantly elevated by TMZ treatment.
3. TMZ stimulate cardiomyocyte proliferation in adult mice and pigs. In adult mice and Bama minipig MI, TMZ improved the cardiac function, limited the scar size, and increased the number of Ki67 and Ph3 positive cardiomyocytes 4 week post MI. In Myh6-MerCreMer/MADM mice MI, the cardiomyocytes with single-color fluorescence, which represent authentic proliferated cardiomyocyte, were increased by TMZ. Time-lapse live cell video also showed that the cytokinesis was elevated in TMZ treated group compared with control.
4. ECM/SMAD4/BMP10 are potential mechanism underlying TMZ’s effect. RNA-seq revealed that in postnatal mouse heart treated with or without TMZ, “ECM” and “integrin binding” were most enriched GO terms. Immunostaining also confirmed that Collagen I is decreased by TMZ treatment. RNA-seq revealed that Bone Morphogenetic Protein 10 (BMP-10) is the top one in foldchange among up-regulated genes, administration of recombinant BMP10 mimic the stimulation effect of TMZ on cardiac proliferation. Transactor predicting tool ChEA3 suggested that SMAD4 is potential regulators of BMP10. The nuclear localization of SMAD4 is indeed increased by TMZ compared with control in postnatal mouse cardiomyocyte.
The nuclear translocation of SMAD4 is regulated by its phosphorylation. As integrin signaling are known molecular sensing ECM mechanical stress and transduced into intra-cellular signaling, we speculate that the effector down-stream of integrin signaling may regulate SMAD nuclear localization. We also found that the inhibition of ROCK1, the kinase which is activated while ECM component bind to integrin, reduced SMAD4 nuclear localization and the subsequent BMP10 production.
CONCLUSIONS We firstly showed that in both mouse and swine model, metabolic alteration by TMZ ameliorated cardiac remodeling post MI by promoting cardiomyocyte proliferation. This effect is potentially associated with ECM remodeling/SMAD4/BMP10 signaling. These findings revealed the mechanism by which metabolism regulate cardiac regeneration and provide potential targets for therapeutic purpose.
GW34-e1218
Jia Li
Changhai Hospital
OBJECTIVES Heart failure is the ultimate stage in the development of various cardiovascular diseases, and morbidity and mortality have increased rapidly in recent years. Splicing factors control alternative splicing events, forming a complex regulatory network to regulate biological process which is associated with heart failure. Our research aimed to comprehensively analyze and identify variable splicing factors and alternative splicing regulatory networks in heart failure utilizing RNA-seq data and machine learning algorithms.
METHODS Three RNA-seq raw sequencing datasets contain heart failure and non-heart failure donors were retrieved and downloaded from the GEO database, and the gene expression matrices of the three datasets were obtained by bioinformatics analysis. The batch effects were removed by the SVA method and combined into one expression matrix. The SpliceAid 2 database was used to obtain the expression of splicing factors from the expression matrix. The differentially expression alternative splicing events in heart failure patients compared with non-heart failure donors was identified by calculating the percent spliced-in (PSI) value to quantify, and the regulatory network of splicing factors and variable splicing events was constructed. Functional enrichment analysis was performed for differential alternative splicing genes. Furthermore, heart failure samples were clustered unsupervised according to differential variable splicing events. Finally, characteristic splicing factor genes were selected through integrating LASSO and SVM-RFE algorithms, and validated in a microarray dataset.
RESULTS A total of 4055 differential alternative splicing events and 3142 DEAS related genes were identified. A total of 30 alternative splicing factors were identified from expression matrix according to the SpliceAid 2 database, of which 12 splicing factors showing higher expression levels in heart failure samples compared to non-heart failure samples. In addition, we identified the splicing regulation network of which contain 203 significant SF-ASE pairs in heart failure. The functional enrichment analysis result revealed that the differentially alternative splicing genes showed high enrichment in PPAR signaling pathway, regulation of actin cytoskeleton, muscle contraction and Z-disc. Furthermore, heart failure patients were divided to two distinct DASE-based clusters by unsupervised clustering method. Finally, four splicing factor genes were selected as characteristic genes using two machine learning algorithms in heart failure.
CONCLUSIONS Our study provided a systematic portrait analysis of alternative splicing regulatory network and splicing factors in heart failure, and uncovered splicing networks that are valuable in deciphering the underlying mechanisms of AS in heart failure. Heart failure characteristic SF genes were determined, which were remarkably linked to RNA metabolism process.
GW34-e1223
Huahui Yu1,2, Yunhui Du1,2, Xiaolu Jiao1,2, Qianwen Lv1,2, Fan Li1,2, Yu Wang1,2, Yanwen Qin1,2
1Beijing Anzhen Hospital, Capital Medical University
2Beijing Institute of Heart Lung and Blood Vessel Disease
OBJECTIVES Myocardial infarction (MI) contributes substantially to CVD-associated mortality. Despite the success of current therapies for MI, many patients still develop adverse cardiac remodeling and heart failure. ANGPTL8 is a secretory protein, which plays a critical role in cardiovascular diseases, including atherosclerosis. However, the direct role of ANGPTL8 in the progression of myocardial remodeling after MI is still unknown. Thus, we explored the contribution of ANGPTL8 to myocardial remodeling after MI and its underlying mechanisms.
METHODS The MI model was induced by the ligation of LAD coronary artery, and the cardiac function of mice was determined 28 days later by echocardiography. By using ANGPTL8 knockout mice, we determined the role of ANGPTL8 on post-MI in vivo. Cardiac fibrosis was measured by Masson staining. and the molecular markers of remodeling were evaluated by Western blot and immunohistochemistry. The mice primary cardiac fibroblasts with ANGPTL8 overexpression were used to detect the mechanism of ANGPTL8 promoted the progression of myocardial remodeling after MI.
RESULTS ANGPTL8 mRNA and protein levels were increased in mice hearts after 28-day MI. Genetic deletion of ANGPTL8 reduced pathological cardiac remodeling and increased survival rate. ANGPTL8 knockout significantly attenuated fibroblast activation, collagen production and fibrosis, cardiomyocyte hypertrophy and improved impaired heart function, at infarcted border zone after MI. Mechanistically, ANGPTL8 was shown to induce cardiac fibroblast-myofibroblast transformation via the transforming growth factor (TGF)-β level.
CONCLUSIONS In conclusion, MI upregulates cardiac ANGPTL8 expression. ANGPTL8 knockout could attenuate cardiac fibrosis at infarcted border zone and improve impaired heart function, suggesting that ANGPTL8 may be a novel therapeutic target against pathologic remodeling in MI patients.
GW34-e1243
Jie Wang, Yanmin Zhang
National Regional Children’s Medical Centre (Northwest); Key Laboratory of Precision Medicine to Pediatric Diseases of Shaanxi Province; Xi’an Key Laboratory of Children’s Health and Diseases, Shaanxi Institute for Pediatric Diseases; Xi’an Children’s Hospital, Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710003, China
OBJECTIVES Complement C1q binding protein (C1QBP) is primarily localized in mitochondrial matrix and associated with mitochondrial oxidative phosphorylative function. C1QBP deficiency presents as a mitochondrial disorder involving multiple organ systems. Recently, disease associated C1QBP mutations have been identified in patients with a combined oxidative phosphorylation deficiency (COXPD) taking an autosomal recessive inherited pattern. The clinical spectrum ranges from intrauterine growth restriction to childhood (cardio) myopathy and late-onset progressive external ophthalmoplegia. We previously identified a homozygous C1QBP-L275F mutation in two COXPD brothers with cardiac hypertrophy.
METHODS The patient and his mother specific induced pluripotent stem cells (iPSC) carrying a homozygosis and heterozygous C1QBP-L275F mutation respectively were generated from PBMCs. Thus PBMCs were reprogrammed using non-integrative sendai viral vectors containing reprogramming factors OCT4, SOX2, KLF4 and C-MYC. Cardiomyocytes were derived from iPSCs named as Proband-Homo-iPSC-CMs and Mother-Hetero-iPSC-CMs respectively. Then the hypertrophic phenotypes of cardiomyocytes were investigates using confocal microscope, Image J and Real-time-PCR. And mitochondrial function studies using transmission electron microscopy and XFe 24 Extracellular Flux Analyzer. Finally, C1qbp-L272F gene knockin mice are generated to investigate the potential mechanism at the whole, organ and molecular levels at 4 months old.
RESULTS Generated iPSCs expressed pluripotent markers, trilineage differentiation potential, carrying C1QBP-L275F mutation, and have a normal karyotype. iPSC-CMs derived from iPSC expressed cardiomyocyte marker CTNT and α-actine. Successfully differentiated iPSC-CMs were using for further investigations. Thus firstly Proband-Homo-iPSC-CMs showed cardiomyocyte area larger and the cardiac hypertrophic marker genes ANP, BNP, and MYH6 was significantly up-regulated compared with Mother-Hetero-iPSC-CMs. Secondly mitochondrial structures were vacuole-impaired, the number and area of mitochondria decreased significantly in Proband-Homo-iPSC-CMs. Furthermore, mitochondrial fusion/fission dynamics disturbance and a decrease in complex I and complex IV subunits was present in Proband-Homo-iPSC-CMs. High-resolution respirometry respiration results showed reduced basal and maximal respiration, proton leakage, and ATP production were found in Proband-Homo-iPSC-CMs. Finally, echocardiographic measurements was performed, and thickness of interventricular septum and posterior left ventricular wall were present in homozygosis C1qbp-L272F mice. Similarly, cardiac hypertrophy markers of Anp and Bnp present an up-regulation trend in homozygosis C1qbp-L272F mice. The results of cardiac electron microscopy showed that the cardiac fiber arrangement of homozygous C1qbp mutant mice was disordered, mitochondrial swelling and partial mitochondrial ridge disappeared, and the expression of mitochondrial dynamic was significantly abnormal compared with that of wild type group.
CONCLUSIONS We successfully established the C1QBP-L275F iPSC-CMs and C1qbp-L272F gene knockin mice. The cardiac hypertrophy was recurrented in this two models. Moreover mitochondrial structure, function, energy metabolism changes was exhibited and potential mechanism was explored. C1QBP/C1qbp mutation-specific iPSC-CMs and mouse models can provide a tool for future research on the mechanism of mitochondrial cardiomyopathy.
GW34-e1246
Yingchao Gong1, Chenyang Jiang1, Guosheng Fu1, Peng Zhang2, Dongwu Lai1
1Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
2Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
OBJECTIVES Cardiac pathological remodeling following myocardial infarction (MI) can result in heart failure and sudden cardiac death. Mtus1A (Mitochondrial tumor suppressor 1A) is located in mitochondrion and its deficiency is associated with mitochondrial disorder. However, the precise involvement of Mtus1A in MI remains unclear. In this study, we aimed to reveal the critical role of Mtus1A in post-MI cardiac remodeling.
METHODS We performed single-cell sequencing analysis to clarify the expression of Mtus1 in cardiomyocytes subjected to ischemic stress. The impact of Mtus1 on cardiac functions and the integrity of MAMs (mitochondria-associated endoplasmic reticulum membranes) was investigated in cardiomyocyte-specific Mtus1 gene knockout mice and in neonatal rat ventricular myocytes through siRNA transfection. Additionally, immunoprecipitation-mass spectrometry was employed to identify the interactive proteins of Mtus1A. In order to investigate their roles in MI, adeno-associated virus serotype 9 (AAV9) carrying Mtus1A or shRNA targeting Fbxo7 (F-box protein 7) was employed.
RESULTS Our study revealed a significant downregulation of Mtus1 expression in the hearts of both patients and mice with MI. Additionally, we identified the localization of Mtus1A to the MAMs both in vitro and in vivo settings. Furthermore, loss of Mtus1A disrupted the association between endoplasmic reticulum and mitochondria, resulted in impairment of heart function and mitochondrial structure under basal conditions. At the mechanistic level, our study demonstrated that Mtus1A acted as a scaffold protein to maintain the stability of the IP3R1-Grp75-VDAC1 complex in MAMs. Additionally, we observed that Mtus1A can be stabilized through K6-linked ubiquitination by Fbxo7. At the functional level, our finding indicated that overexpression of Mtus1A mitigates cardiac function induced by left anterior descending ligation by preserving the connection between the ER and mitochondria.
CONCLUSIONS Taken together, our findings suggest that Mtus1A is essential for the maintaining the structural soundness of the IP3R1-Grp75-VDAC1 complex and facilitating the interaction between the ER and mitochondria. Disruption of this pathway leads to mitochondrial dysfunction and exacerbates MI-induced cardiac dysfunction.
GW34-e1261
Yao Zhang, Wei Zhao, Rongjie Tang, Yingxin Huo, Feng Sun, Qiufang Lian
Xianyang Hospital of Yan’an University
OBJECTIVES To observe the effect of allicin (ALL) on renal fibrosis in salt-sensitive hypertensive rats and explore the mechanism of ALL based on Klotho/TGF-β1 signaling pathway.
METHODS Twenty-four male Dahl salt-sensitive rats, 8 weeks old, were randomly divided into normal-salt (NS), high-salt (HS) and high-salt plus ALL (HS+ALL) groups after 1 week of acclimatization feeding. They were given 0.3% NaCl, 8% NaCl and 8% NaCl with ALL (16 mg/kg, p.o), respectively, once a day for 4 weeks. Systolic blood pressure (SBP) was measured using a non-invasive blood pressure monitor, 24-hour urine was collected, the kidney weight coefficient (kidney weight/rat weight) was calculated, renal tissue was collected. The collagen volume of kidney (CVF) was calculated. The contents of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in kidney tissue were determined by ELISA, the mRNA and protein levels of Collagen I, Fibronectin, Klotho and TGF-β1 in kidney tissue were detected by qRT-PCR and Western Blot.
RESULTS
1. Compared with the NS group, SBP was increased (P<0.05), urine creatinine and protein levels were increased (P<0.05), and renal weight coefficient was increased in the HS group rats (P<0.05). These were reversed in part in HS+ALL group (P<0.05).
2. Compared with the NS group, H&E staining showed severe renal injury, compensatory hypertrophy of some glomeruli, widening of peritubular space, and significant inflammatory cell infiltration, Masson staining showed significant renal fibrosis and increased CVF (P<0.05), levels of IL-6 and TNF-α in renal tissue were increased (P<0.05), Collagen I and Fibronectin mRNA and protein content in kidney tissue were increased (P<0.05) in the HS group. The above indicators were reversed in part in HS+ALL group (P<0.05).
3. Compared with the NS group, the mRNA and protein expression levels of Klotho in kidney tissue decreased in the HS group (P<0.05), the mRNA and protein expression levels of TGF-β1 in kidney tissue increased (P<0.05). The above indicators were reversed in part in HS+ALL group (P<0.05).
CONCLUSIONS ALL can improve renal dysfunction and renal fibrosis caused by salt-sensitive hypertension, which is related to its regulation of Klotho/TGF-β1 signaling pathway.
GW34-e1265
Yingxin Huo, Wei Zhao, Rongjie Tang, Yao Zhang, Feng Sun, Qiufang Lian
Xianyang Hospital of Yan’an University
OBJECTIVES To observe the effect of allicin (ALL) on cardiac fibrosis in salt-sensitive hypertension and explore the mechanism of ALL based on the TGF-β1/Smad2/3 signaling pathway.
METHODS Twenty-four male Dahl salt-sensitive rats, 8 weeks old, were randomly divided into normal-salt group (NS), high-salt group (HS) and high-salt group plus ALL group (HS+ALL) after 1 week of adaptive feeding, and were given sodium chloride containing 0.3% NaCl, 8% NaCl and 8% NaCl and ALL (16 mg/kg, p.o) once a day for 4 weeks, respectively. Systolic blood pressure (SBP) was measured by non-invasive blood pressure monitor, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) were measured by small animal ultrasound, rat hearts were taken, heart mass index (HMI) and left ventricular mass index (LVMI) were calculated, ELISA was performed to determine the contents of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in kidney tissue, qRT-PCR and Western Blot were performed to detect the mRNA and protein levels of Collagen I, TGF-β1, p-Smad2 and p-Smad3 in kidney tissue.
RESULTS
1. Compared with the NS group, SBP was increased (P<0.05), LVEF was decreased, LVESV and LVEDV were increased, HMI and LVMI were increased in the HS group rats. These were reversed in part in HS+ALL group (P<0.05).
2. Compared with the NS group, HE staining in the HS group showed disturbed arrangement of LV myocytes and significant inflammatory cell infiltration, increased interstitial collagen deposition in LV cells and increased CVF (P<0.05), increased IL-6 and TNF-α content in kidney tissue, increased mRNA and protein content of Collagen I in kidney tissue (P<0.05). The above indicators were reversed in part in HS+ALL group (P<0.05).
3. TGF-β1 mRNA and protein expression levels were increased in renal tissue of the HS group compared with the NS group (P<0.05), in addition, the protein levels of p-Smad2 and p-Smad3 were also increased in renal tissue (P<0.05). The above indicators were reversed in part in HS+ALL group (P<0.05).
CONCLUSIONS ALL can improve cardiac hypofunction and cardiac fibrosis caused by salt-sensitive hypertension, which is related to its inhibition of TGF-β1/Smad2/3 signaling pathway.
GW34-e1268
Ming Bai1,2,3,4, Jingjing Zhang5,6, Shuwen Hu4, WenJun Zhang1,2,3,4, Fei Zhao7, Xiaowei Niu1,2,3,4
1Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou 730000, China
2Gansu Key Laboratory of Cardiovascular Diseases, Lanzhou 730000, China
3Gansu Clinical Medical Research Center for Cardiovascular Diseases, Lanzhou 730000, China
4The First School of Clinical Medicine of, Lanzhou University, Lanzhou 730000, China
5Gansu Provincial Maternity and Child-care Hospital/Gansu Provincial Central Hospital, Medical Genetics Center, Lanzhou 730000, China
6Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou 730000, China
7TEDA International Cardiovascular Hospital, Department of Electrophysiology, Tianjin 300000, China
OBJECTIVES Myocardial ischemia reperfusion (MI/R) injury often leads to adverse cardiovascular outcomes in patients with acute myocardial infarction. Effective strategies for preventing and treating myocardial ischemia-reperfusion (MI/R) injury are still lacking in clinical practice. Our previous research has conducted the network pharmacology analysis, which identified Angelica sinensis polysaccharide (ASP), a major water-soluble component of Angelica sinensis, with potential cardioprotective effects. In this study, we aim to elucidate the mechanism of action of ASP by integrating bioinformatics analysis with both in vivo and in vitro experiments.
METHODS In the in vitro experiments, we established a hypoxia/reoxygenation (H/R) model using H9c2 rat cardiomyocyte cell line. In the in vivo experiments, we induced myocardial ischemia-reperfusion (MI/R) injury by ligating the left anterior coronary artery in rats. Myocardial samples were collected for transcriptome sequencing and subsequent bioinformatics analysis.
RESULTS
ASP decreases H/R-induced cell pyroptosis: Compared to the H/R model group, pre-treatment with ASP significantly mitigated the inhibitory effects of H/R on H9c2 cell viability. ASP treatment markedly reduced the release of lactate dehydrogenase (LDH) and the percentage of TUNEL-positive cells induced by H/R. ELISA analyses demonstrated that ASP intervention decreased the levels of inflammatory cytokines (IL-1β, IL-18, and TNF-α) induced by H/R. Western blot analysis revealed that ASP treatment significantly downregulated the expression levels of NLRP3 and N-GSDMD compared to the H/R group. Additionally, ASP intervention inhibited the activity of Caspase-1.
ASP alleviates inflammatory injury following MI/R: In the rat MI/R model, pre-treatment with ASP significantly reduced the infarct size, levels of myocardial enzymes (LDH and cTNT), and ST-segment elevation on the electrocardiogram. HE staining showed that ASP treatment significantly reduced inflammatory cell infiltration and improved the morphology of myocardial tissue. Echocardiographic analysis demonstrated that ASP therapy significantly ameliorated heart dysfunction with increased ejection fraction and fractional shortening. Consistent with the in vitro results, ASP treatment markedly decreased the percentage of TUNEL-positive cells induced by MI/R, as well as the release of inflammatory cytokines (IL-1, IL-18, and TNF-α). ASP intervention also reduced the activity of Caspase-1 and downregulated the expression levels of NLRP3 and N-GSDMD.
Bioinformatics analysis: Differential expression analysis, gene set enrichment analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis revealed that the FN1/NF-κB/NLRP3 signaling pathway could be a potential molecular mechanism.
Investigation of the molecular mechanism: The Western blot analysis and rescue experiments showed that ASP significantly downregulated the FN1/NF-κB/NLRP3 signaling pathway. Additionally, the administration of the NLRP3 agonist nigericin significantly reversed the protective effects of ASP against MI/R injury.
CONCLUSIONS Our findings suggest that ASP protects the myocardium against ischemia/reperfusion injury by inhibiting cardiomyocyte pyroptosis. The FN1/NF-κB/NLRP3 inflammasome pathway mediates the cardioprotective effects of ASP. These results offer new insights into the development of ASP-related drugs, and provide a theoretical basis for exploring novel strategies for treating MI/R injury.
GW34-e1273
Dong Han1, Tingwen Zhou2, Yongjun Wang2, Feng Cao1
1National Clinical Research Center for Geriatric Diseases, 2nd Medical Center, Chinese PLA General Hospital, Beijing 100853, China
2Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
OBJECTIVES Calcification of the aortic valve leads to increased leaflet stiffness and consequently results in the development of calcific aortic valve disease (CAVD). However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified a novel aortic valve calcification-associated PIWI-interacting RNA (piRNA) (AVCAPIR) that increases valvular calcification and promotes CAVD progression.
METHODS Using piRNA sequencing, we identified piRNAs contributing to the pathogenesis of CAVD that we termed AVCAPIRs. High-cholesterol diet (HCD)-fed ApoE−/− mice with AVCAPIR knockout were used to examine the role of AVCAPIR in aortic valve calcification (AVC). Gain- and loss-of-function assays were conducted to determine the role of AVCAPIR in the induced osteogenic differentiation of human primary valvular interstitial cells (hVICs). To dissect the mechanisms underlying the AVCAPIR-elicited procalcific effects, we performed various analyses, including an RNA pulldown assay followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), methylated RNA immunoprecipitation sequencing (MeRIP-seq), quantitative reverse transcription polymerase chain reaction, Western blotting, and RNA sequencing (RNA-seq). RNA pulldown and RNA immunoprecipitation (RIP) assays were used to study piRNA interactions with proteins.
RESULTS We found that AVCAPIR was significantly upregulated during AVC and exhibited potential diagnostic value for CAVD. AVCAPIR deletion markedly ameliorated AVC in HCD-fed ApoE−/− mice, as shown by reduced thickness and calcium deposition in the aortic valve leaflets, improved echocardiographic parameters (decreased peak transvalvular jet velocity and mean transvalvular pressure gradient, as well as increased aortic valve area), and diminished levels of osteogenic markers (Runx2 and Osterix) in the aortic valves. These results were confirmed in osteogenic medium-induced hVICs. Using unbiased protein-RNA screening and molecular validation, we found that AVCAPIR directly interacts with FTO, subsequently blocking its N6-methyladenosine (m6A) demethylase activity. Further transcriptomic and m6A modification epitranscriptomic screening and molecular validation confirmed that AVCAPIR hindered FTO-mediated demethylation of CD36 mRNA transcripts, thus enhancing CD36 mRNA stability through the m6A reader IGF2BP1. The AVCAPIR-dependent increase in CD36 in turn stabilizes CD36’s binding partner PCSK9, a procalcific gene, at the protein level, which accelerates the progression of AVC.
CONCLUSIONS We identified a potentially novel piRNA that induced AVC via an RNA epigenetic mechanism and provide novel insights into piRNA-directed theranostics in CAVD.
GW34-e1281
Lei Wang
Capital Medial University
OBJECTIVES Pathological cardiac hypertrophy leads to heart failure and is the leading causes of death from cardiovascular disease. Understanding the molecular mechanism of pathological cardiac hypertrophy will contribute to the prevention and treatment of heart failure. β-catenin is an important regulator of cardiac development and remodeling. The high β-catenin activity leads to cardiac hypertrophy and heart failure. Ubiquitination modification is essential to maintain the normal activity, localization, and degradation of β-catenin. However, which deubiquitinating enzymes participated in the regulating of β-catenin activity remain largely unknown.
METHODS Immuno-coprecipitation-mass spectrometry (IP-MS) was used to identify the BRISC deubiquitinating enzyme scaffolding protein ABRO1 was the interacting protein of β-catenin in cardiomyocytes. To confirm the direct interaction of ABRO1 and β-catenin, we performed co-immunoprecipitation and GST-pull down. The truncated text of ABRO1 and β-catenin were designed to recognize the interaction location of ABRO1 and β-catenin. To identify the β-catenin-ubiquitination modification site by BRISC complex, we performed ubiquitinating proteome. Then ubiquitination-modification-sites mutation of β-catenin were generated to confirm the ubiquitination modification sites induced by ABRO1. The role of ABRO1 in cardiac hypertrophy and heart failure was further evaluated in MYH6creABRO1flox/flox mice and cardiomyocyte-specific overexpression of ABRO1 mice in response to angiotensin II (Ang II). Immunofluorescent staining and qPCR were used to verify β-catenin nuclear trans-location and transcriptional activity in ABRO1 knockout and overexpression cardiomyocytes and heart. Moreover, we performed the rescue study in MYH6creABRO1flox/flox mice either by intravenous injection of AAV9-encoding ABRO1 under the cTnT promoter or using the β-catenin inhibitor ICG-001 to validate the biological function of ABRO1 and β-catenin interaction.
RESULTS We revealed that the BRISC deubiquitinating enzyme scaffolding protein ABRO1 was the interacting protein of β-catenin in cardiomyocytes. ABRO1 bound to β-catenin directly via the lysine at position 508 and exerted de-ubiquitination to decrease the activity of β-catenin by removing the K63 ubiquitin chain, therefore inhibiting β-catenin nuclear translocation and transcriptional activity. The protein level of ABRO1 in murine cardiomyocytes subject to Ang II and transverse aortic constriction stimulation and in hypertrophic myocardium tissues of patients with heart failure was significantly increased. Cardiac ABRO1 deficiency aggravated cardiac hypertrophy and heart failure under Ang II treatment by increasing β-catenin activity. Inversely, cardiac specific ABRO1 overexpressing attenuated Ang II induced cardiac hypertrophy and dysfunction. Restoration of ABRO1 expression via AAV9 vectors or inhibiting β-catenin activity in MYH6creABRO1flox/flox mice could attenuate Ang II-induced heart failure.
CONCLUSIONS We confirmed that ABRO1 inhibited cardiac hypertrophy by deubiquitinating and inhibiting β-catenin activation.
GW34-e1295
Tianxin Ye1, Jinxiu Yang1, Bo Yang2, Xingxiang Wang1
1Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University
2Department of Cardiology, Renmin Hospital of Wuhan University
OBJECTIVES Post-operative atrial fibrillation (POAF) is a common complication in patients undergoing cardiac surgery. The purinergic receptor P2X7 (P2X7R) is involved in ventricular arrhythmia after myocardial infarction (MI), whereas its effects on atrial fibrillation (AF) are unclear. This study was to assess the effect of P2X7R on atrial arrhythmogenic remodeling in the experimental sterile pericarditis (SP)-induced POAF model.
METHODS MI and POAF rat models were induced. Electrocardiogram, atrial electrophysiological protocol, histology, mRNA sequencing, real-time quantitative PCR, western blot, and Elisa assay were performed.
RESULTS The P2X7R was significantly up-regulated in the atrium both in the MI and SP rats. SP significantly increased AF susceptibility; reduced the protein expression of ion channels including Nav1.5, Cav1.2, Kv4.2, Kv4.3, and Kv1.5; caused atrial fibrosis; increased norepinephrine level in plasma; promoted the production of inflammatory cytokines and accumulation of immune cells; and activated NLRP3 inflammasome signaling pathway. P2X7R antagonist Brilliant Blue G (BBG) suppressed SP-induced alterations. The mRNA sequencing demonstrated that BBG prevented POAF mainly by regulation of the immune system. In addition, IL-1R antagonist anakinra also reduced AF incidence in SP-induced POAF.
CONCLUSIONS P2X7R inhibition prevents SP-induced atrial proarrhythmic remodeling, which is closely associated with the improvement of inflammatory changes, ion channel expression, atrial fibrosis, and sympathetic activation. The findings point to P2X7R inhibition as a promising target for POAF and perhaps other conditions.
GW34-e1298
Dong Han1, 2, Yongjun Wang2, Feng Cao1, 2
1National Clinical Research Center for Geriatric Diseases, 2nd Medical Center, Chinese PLA General Hospital, Beijing 100853, China
2Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
OBJECTIVES Anthracycline cardiotoxicity remains a major challenge to the survival and life quality of cancer patients receiving anthracycline-based chemotherapy. Previous studies have indicated that heart and tumor could interact and influence the course of each other’s pathologies in patients with these two disease entities. Small extracellular vesicles (sEVs) critically orchestrate proximal and distant organ-organ communications and may play essential roles in heart-tumor interaction. However, whether cancer-secreted sEVs affect the progression of anthracycline cardiotoxicity via regulating the tumor cell-cardiomyocyte crosstalk has not yet been explored.
METHODS To decipher the potential interaction of breast cancer cells (BCCs) with cardiomyocytes in DOX-induced cardiotoxicity (DOXIC), a transwell based coculture system was employed. To determine whether BCC-sEVs were able to aggravate DOX-induced myocardial injury in vivo, sEVs derived from DOX-treated syngeneic E0771 breast cancer cells or normal control E0771 cells were intramyocardially injected into the myocardium of DOX-treated mice. To identify the specific functional miRNA in D-BCC-sEVs, differentially expressed miRNAs in D-BCC-sEVs and N-BCC-sEVS were revealed by miRNA sequencing. To investigate the mechanisms of exsomal miRNA’s function, we performed various analyses including quantitative reverse transcription polymerase chain reaction, Western blot, histology, cardiac function (by echocardiography), functional rescue experiments, RNA pulldown, RNA immunoprecipitation, luciferase reporter assay.
RESULTS Here, we demonstrate that doxorubicin (DOX)-treated breast cancer cells (D-BCCs) secreted sEVs that can exacerbate DOX-induced ferroptosis in cardiomyocytes and in an orthotopic mice model of breast cancer. The expression of miR-338-3p in D-BCCs and plasma-sEVs of DOX-treated tumor bearing mice was significantly upregulated. Incubation of cardiomyocytes with sEVs isolated from D-BCCs (D-BCC-sEVs) or overexpression of miR-338-3p alone intensified DOX-induced ferroptotic cell death in vitro. N6-methyladenosine was revealed to mediate the upregulation of miR-338-3p in D-BCCs through enhanced maturation. D-BCCs-enriched miR-338-3p was packaged in sEVs and transferred into cardiomyocytes in a RBMX-dependent manner. Anti-ferroptotic genes CP, SLC7A11, and GPX4 were experimentally established as targets of miR-338-3p in cardiomyocytes. Blockage of BCC-D-EXOs release with Rab27a silence or systematic anti-miR-338-3p antagomir treatment assuaged BCC-D-EXOs-induced myocardial ferroptosis and injury. Plasma sEVs isolated from DOX-induced cardiomyopathy patients potently enhanced DOX-induced ferroptosis in hiPSC-CMs, which was rescued by miR-338-3p inhibitor.
CONCLUSIONS Our findings uncovered for the first time that DOX-treated BCCs exacerbated DOXIC through releasing miR-338-3p-enriched sEVs. Therefore, targeting sEV-mediated tumor/cardiomyocyte pathological communication may offer a novel approach for the management of DOXIC.
GW34-e1305
Tianxin Ye1, Jinxiu Yang1, Bo Yang2, Xingxiang Wang1
1Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University
2Department of Cardiology, Renmin Hospital of Wuhan University
OBJECTIVES Depression, the most prevalent psychiatric disorder characterized by a depletion of pleasure, is closely associated with the occurrence and development of atrial fibrillation (AF), whereas the underlying mechanisms remain unclear. Activation of the P2X purinoceptor 7 (P2X7R) is involved in some cardiovascular diseases and participates in the development of depression, but little attention has been given to its role in AF. This study was to investigate the effects of P2X7R on depression-related AF.
METHODS Chronic unpredictable stress (CUS) or lipopolysaccharide (LPS) was carried out to induce rodent models of depression. Behavioral assessments, atrial electrophysiological parameters, Electrocardiogram (ECG) parameters, western blot, and histology were performed.
RESULTS Shortened effective response period (ERP), prolonged activation latency (AL), and increased inducibility of AF were observed in both LPS- and CUS-induced depression, along with the up-regulation of P2X7R in atria. CUS facilitated atrial fibrosis. CUS reduced HRV and increased the expression of TH and GAP43, representing autonomic dysfunction. Downregulation of Nav1.5, Cav1.2, Kv4.3, Kv1.5, Cx40, and Cx43 in CUS indicated the abnormalities in ion channels. In addition, the expression levels of TLR4, P65, P-P65, NLRP3, ASC, caspase-1, and IL-1β were remarkably elevated in depression. The pharmacological inhibitor (Brilliant Blue G, BBG) or genetic deficiency of P2X7R significantly mitigated depressive-like behaviors, and ameliorated electrophysiological deterioration and autonomic dysfunction in CUS-induced rats or mice. Moreover, BBG improved ion channel expression, atrial fibrosis, and attenuated atrial inflammation in the pathophysiological process of depression-related AF.
CONCLUSIONS Depression induces AF and promotes P2X7R-dependent activation of NLRP3 inflammasome, while pharmacological P2X7R inhibition or P2X7R genetic deficiency prevents atrial remodeling without interrupting normal atrial physiological functions. Our results point to P2X7R as an important factor in the pathology of depression-related AF.
GW34-e1349
Ruirui Chen, Yan Li
Department of Cardiology, Second Affiliated Hospital, Military Medical University of the Air Force
OBJECTIVES The amount of blood immune cells and the risk of heart failure (HF) are known to be positively associated. However, the causal impact of peripheral blood immune cells on HF has not been fully elucidated. We performed a Mendelian randomization (MR) study to examine the possible etiologic role of peripheral blood immune cells in HF.
METHODS A Mendelian randomization (MR) analysis was performed using genetic variants closely associated with circulating leukocyte, granulocyte, lymphocyte, and monocyte counts and monocyte subpopulations as instrumental variables (IV). A genome-wide association study (GWAS) dataset of 977,323 participants of European ancestry, including 47,309 HF cases and 930,014 controls, was collected to identify genetic variants in HF. A two-sample Mendelian randomization framework was implemented to examine the causal relationship between peripheral blood immune cells and HF. And then to find more effective ways to treat heart failure.
RESULTS Our findings indicated that higher monocyte count [odds ratio (OR), 0.914; 95% confidence interval (CI), 0.846–0.988; P=0.023] was causally associated with HF susceptibility. In addition, the absolute amount of CD14- CD16+ monocyte and CD14+ CD16- monocyte were negatively associated with the increased susceptibility to HF.
CONCLUSIONS Our findings show that the genetic predisposition to lower peripheral monocyte cell counts, especially CD14- CD16+ monocyte and CD14+ CD16- monocyte subtypes, can exert a causal effect on HF risk. This may play a guiding role in finding more effective drug treatment for heart failure.
GW34-e1357
Jian Zhang1, Ping Ren2, Poli Lin2, Boya Cao2, Jiali Chen3, Ping He1, Wei Wang4, Linghui Lu3, Junling Cao2,5
1School of Life Sciences, Beijing University of Chinese Medicine
2School of Chinese Materia Medica, Beijing University of Chinese Medicine
3School of Chinese Medicine, Beijing University of Chinee Medicine, Beijing
4School of Basic Medical Sciences, Guangzhou University of Chinese Medicine
5Dongfang Hospital, Beijing University of Chinese Medicine
OBJECTIVES Lonicerae Japonicae Flos (LJ), one of the genuine medicinal materials in China, is mainly used to treat inflammation related diseases clinically for hundreds of years. Inflammation plays an important role in the occurrence and development of myocardial infarction (MI) and clinical studies have shown that anti-inflammatory treatment can improve myocardial ischemia post MI. This study was undertaken to explore the anti-inflammation mechanism of Lonicerae Japonicae Flos extract (LJE) against myocardial injury post MI targeting lipoxygenases pathway.
METHODS LJE was extracted from the herb of LJ. Left anterior descending ligation was applied to induce an MI mice model. LJE was orally administered 24 h after MI for 7 days, and then cardiac function, myocardial pathology, serum cardiac markers CKMB and cTnI, and inflammatory factors TNF-α and IL-6 in myocardium were evaluated, respectively. In vitro, the injury model of H9C2 cardiomyocytes was induced by oxygen-glucose deprivation/reperfusion (OGD/R). Cell viability, LDH, TNF-α and IL-6 in cell supernatant were detected. The expression levels of lipoxygenases pathway related proteins ALOX5, ALOX12 and ALOX15 was detected by western blotting both in vivo and in vitro.
RESULTS The results of echocardiography and serum cardiac markers showed that LJE improved cardiac function and relieved the impairment of myocardial tissue after MI. Additionally, LJE treatment could reduce inflammation levels in myocardial tissue. Moreover, lipoxygenases pathway was activated after MI and it was inhibited by the treatment of LJE with the significant decrease of ALOX5. In vitro, LJE treatment improved the cell viability and reduced the release of LDH, TNF-α and IL-6. Moreover, the protein expression levels of ALOX5, ALOX12 and ALOX15 were significantly decreased with LJE treatment.
CONCLUSIONS LJE improves cardiac function and ameliorates myocardial injury post MI by inhibiting inflammation via regulating lipoxygenases pathway.
GW34-e1370
Hailin Zhang, Lishan Zeng, Dajun Chai
The First Affiliated Hospital, Fujian Medical University
OBJECTIVES Ischemic cardiomyopathy (ICM) is the leading cause of cardiovascular disease. Recent studies have shown that ketone bodies not only act as a “super fuel” for the heart, but also inhibit adverse cardiac remodeling by improving vascular endothelial function, reducing oxidative stress, and regulating inflammation. Autophagy is an important means of self-repair after injury, and cardiomyocyte autophagy levels are reduced after myocardial infarction. It is unclear whether ketone bodies can improve the structure and function of the ICM rat heart by increasing cardiomyocyte autophagy levels.
METHODS 1,3-Butanediol (1,3-Butanediol, 1,3-BD) is a precursor for ketone body metabolism and can be converted to β-hydroxybutyric acid (β-hydroxybutyric acid, β-HD) in the liver. β-HD is not only an energy substrate but also an important molecule for cell signaling. In this study, an ICM rat model was established by continuously ligating the left anterior descending coronary artery branch of standard SD rats for 5 weeks, and the non-infarcted rats were randomly divided into control, ICM, and 1,3-BD intervention groups, with 15 rats in each group. In the 1,3-BD group, 1,3-BD (1 mL/100 g) was administered by gavage daily for 4 weeks. The effects of 1,3-BD on cardiac structure and function and myocardial pathological damage in ICM rats were evaluated by cardiac ultrasound, hemodynamics, hematology, and histopathology at week 5 after left anterior descending ligation. Changes in mitochondrial ultrastructure and autophagy levels in myocardial tissue at the infarct border were observed by transmission electron microscopy and laser confocal microscopy, and possible regulatory mechanisms were investigated in combination with transcriptomic and metabolomic analyses and validated by immunoblotting.
RESULTS After 5 weeks of continuous ligation of the left anterior descending branch of the coronary artery, both cardiac ultrasound and invasive hemodynamic monitoring showed significantly enlarged left ventricular chambers and significantly reduced systolic and diastolic functions in the rats in the ICM group. 1,3-BD intervention significantly improved cardiac structure and function. Left ventricular ejection fraction: 50.39±5.94% vs 71.92±6.08% (both P<0.05). Compared with the rats in the ICM group, HE staining of the rats in the 1,3-BD group showed a reduction in the left ventricular chambers, wall thickening, and inflammatory cell aggregation, and Masson staining showed reduced collagen fiber deposition in myocardial tissue. Mitochondrial transmission electron microscopy confirmed that 1,3-BD significantly improved the structure and number of myocardial mitochondria in the marginal zone, and autophagic vesicles were significantly increased. Extracted proteins from myocardial cells in the marginal zone were analyzed by immunoblotting, and compared with the Ctr group, the levels of ATG7, ATG13, beclin1, SQSTM1/p62, ULK1 and LC3II/LC3I proteins were significantly decreased in the ICM group, and autophagy-related protein expression was significantly upregulated after 1,3-BD intervention; meanwhile, PI3K, AKT and FOXO3 proteins were significantly downregulated in the ICM group compared with the Ctr group, and 1,3-BD intervention significantly reversed the expression of PI3K, AKT and FOXO3 proteins, suggesting that 1,3-BD may enhance autophagy in injured cardiomyocytes through upregulation of PI3K/AKT/FOXO3 pathway.
CONCLUSIONS 1,3-BD significantly improved cardiac structural function, attenuated myocardial pathological injury and mitochondrial damage in ICM rats, and could upregulate myocardial autophagy levels in the limbic zone through activation of PI3K/AKT/FOXO3 signaling pathway. Exogenous supplementation of 1,3-BD not only provides richer energy support to the ischemic heart, but also improves the poor prognosis of ICM by enhancing autophagy of injured cardiomyocytes through ketone body β-Hb. Appropriate ketone body supplementation may be a potentially effective means of treating ICM.
GW34-e1372
Bingyu Zheng
The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES Tyrosine kinase inhibitors (TKIs), a type of targeted therapy for non-small cell lung cancer, were reported to cause QT prolongation. In our clinical practice, we found that crizotinib administration increases the risk of QT prolongation. The aim of this study was to characterize the mechanism behind.
METHODS By using intracellular calcium indicator and voltage sensitive dye, we tested the effect of crizotinib treatment on electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The effect of crizotinib administration In vivo was investigated in adult zebrafish. qRT-PCR and Western Blot were applied for detection of ion channels expression. With mass spectrometry-based proteome and phosphoproteome analysis, molecular mechanism of crizotinib induced QT prolongation was revealed.
RESULTS Up to 1 μM crizotinib treatment did not show toxicity to hiPSC-CMs viability 24 hours of crizotinib treatment led to prolonged action potential duration (APD90) compared with control in 1 Hz paced hiPSC-CMs. However, the calcium transients between two groups were of no significant difference. Adult zebrafish treated with 10 μM crizotinib presented prolongated QT intervals compared with control. qRT-PCR of ion channels involved in repolarization revealed that KCNH2 expression level was reduced in crizotinib exposure group. In addition, Cell membrane hERG expression were significantly decreased in crizotinib-treated group. Phosphorylated protein quantification combined with total protein quantification analysis suggested reduced histone acetyltransferases p300 phosphorylation. To study the relation between p300 and hERG expression, we used p300 overexpression plasmid, p300 siRNA and p300 inhibitor A-485 in human cardiomyocytes AC-16. Western blot showed that overexpression of p300 increased the cytomembrane hERG, while siRNA and A-485 reduced it. Further co-Immunoprecipitation demonstrated the interaction between p300 and hERG. Moreover, overexpression of p300 increased the hERG acetylation, decreased the hERG ubiquitination, thus reversed the crizotinib induced hERG degradation, while siRNA and inhibitor A-485 had the opposite effect.
CONCLUSIONS Previous studies have showed that crizotinib led to blockage of hERG. Our study provided a new prospective to explain crizotinib induced cytomembrane hERG down-regulation.
GW34-e1384
Xiuxiang Liu, Jie Liu
Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai Heart Failure Research Center, Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
OBJECTIVES Diabetes mellitus (DM) is currently a main public health problem, one of its complications is diabetic cardiomyopathy (DC), which is recognized as a microvascular disorder that leads to morbidity and mortality in diabetic patients. Endothelial cells play an important role in the maintenance of cardiac homeostasis and function, Transcription factor Klf11 highly expressed in endothelial cell and plays a protective role in many cardiovascular diseases, but the detailed effects of endothelial KLF11 in DC has not been reported. This study aimed to explore the role of endothelial cell KLF11 in the pathogenesis of DC and the underlying mechanisms.
METHODS Analysis of GEO profiles in hearts tissues from both Streptozotocin (STZ) induced diabetes and db/db background diabetes mouse models. Mouse model of DC was generated using a high-fat diet combined with a low-dose STZ injection (110 mg/kg) in vivo. mCMVECs cells with siRNA-KLF11 or siRNA-NOX2 were used to study endothelial cell KLF11 function in vitro. DHE staining was used to evaluate oxidative stress levels, NO Elisa kit was used to measure cultured medium Nitric Oxide concentration, qRT-PCR and western blot to further explore the mechanisms of KLF11 regulating oxidative stress through the NOX2/eNOS/NO pathway to protect diabetic cardiomyocyte injury. Coculture siRNA-KLF11 or siRNA-NOX2 cultured medium with MCM cell line were exposed in high glucose (HG) 25 mM to study cardiomyocyte hypertrophy in vitro. NOX2 knockout mice was generated by CDH5-specific nanoparticles loaded NOX2 gRNA Cas9 plasmids to rescue the phenotype of diabetic cardiomyopathy.
RESULTS Analysis of GEO profiles revealed that Klf11 is downregulated in hearts tissues from both Streptozotocin (STZ) induced diabetes and db/db background diabetes mouse models. Mouse model of DC was generated using a high-fat diet combined with a low-dose STZ injection (110 mg/kg) in vivo, we found significantly downregulated Klf11 expression in cardiac ECs accompanied by increased expression of oxidate stress genes (Cybb) in cardiac tissues and cardiac hypertrophy in T2DM mouse compared with sham operated mice. Moreover, we found significantly elevated Klf11 expression in mouse cardiac microvascular endothelial cells (mCMVECs) when exposed to high glucose (25 mM). Knockdown of Klf11 by siRNA in mCMVECs showed a significantly increased oxidative stress by DHE staining accompanied by decreased nitric oxide (NO) concentration in the medium upon high glucose exposure compared with scramble-siRNA transfected mCMVECs. Mechanistic study revealed a significantly upregulated NADPH oxidases 2 (Nox2) expression in mCMVECs upon Klf11 siRNA-knockdown. NOX2 converts oxygen into the superoxide anion which further reacts with NO to form perxynitrite (ONOO-). Perxynitrite is the main cause of eNOS uncoupling in ECs which leads to produces superoxide instead of NO and causing oxidate stress in ECs. Further study showed that Nox2 knockdown by siRNA significantly reversed increased oxidative stress and downregulated NO secretion upon Klf11 knockdown in mCMVECs with high glucose exposure as well as reduced the conditioned medium stimulated mouse cardiomyocytes (MCMs) hypertrophy. Finally, we generated a nanoparticle combined with cdh5 promoter driven Nox2 gRNA Cas9 plasmid to achieve ECs targeted Nox2 deletion in vivo. The results showed that EC-specific Nox2 knockdown protected against STZ induced ECs oxidative stress and CMs hypertrophy.
CONCLUSIONS These data demonstrate that KLF11 is a novel transcriptional suppressor of Nox2 in endothelial cells, constituting a potential molecular target for treatment of DC.
GW34-e1388
Lishan Zeng
The First Hospital, Fujian Medical University
OBJECTIVES This study investigates the mechanism by which the nuclear receptor LXR agonist T0901317 improves the development of calcific aortic valve disease (CAVD) through in vitro and in vivo experiments in mice, and proposes to demonstrate that T0901317 inhibits the osteogenic phenotype of aortic valve mesenchymal cells by regulating endoplasmic reticulum stress (ERS), thereby delaying the development of CAVD, and provides a new theoretical basis for further understanding of CAVD, as well as a new auxiliary assessment index and intervention target for the prevention and treatment of the disease.
METHODS Primary human aortic valve interstitial cells (hAVICs) were used to induce osteogenesis by giving calcification medium (OM), with comparison of T0901317. Immunofluorescence staining was used to detect the expression of the osteogenic markers Runx2 and OPN as well as the ERS marker PERK. Immunoblotting was used to detect the expression of proteins of the PERK-eIF2α-ATF4-Runx2 pathway. Alizarin staining was used to observe calcium salt deposition and calcium nodule formation. ApoE−/− mice were used to establish a CAVD model by high-fat diet (HFD) feeding for 24 weeks, with comparison of T0901317 oral administration. Ultrasound imaging system was used to assess the functional changes of aortic valve and heart structure. HE staining, Masson staining and Von Kossa staining were used to observe the thickness of aortic valve leaflets, degree of valve fibrosis, calcium salt deposition and calcium nodule formation. Immunofluorescence staining was used to detect the expression of Runx2, OPN and PERK.
RESULTS Immunofluorescence staining results showed that the expression of the OM component bone markers Runx2 and OPN as well as the ERS marker PERK was upregulated compared to the CTL group, while T0901317 intervention induced downregulation of Runx2, OPN and PERK expression. Immunoblotting results showed that the expression of PERK-eIF2α-ATF4-Runx2 pathway protein was increased in the OM group compared with the CTL group, while T0901317 intervention led to a decrease in the expression of this pathway protein. Alizarin staining showed that a large amount of calcium salt deposition and calcium nodule formation were seen in the OM group compared to the CTL group, while T0901317 intervention significantly improved these conditions. Echocardiographic results showed a significant increase in aortic orifice flow velocity and transvalvular pressure difference in the HFD-induced CAVD mice compared with the normal, drug control and model control groups, which was largely reversed in the T0901317 intervention group. After T0901317 treatment, increased valve fibrosis, calcium salt deposition and calcium nodule formation were improved, meanwhile the expression of Runx2, OPN and PERK was significantly reduced by immunofluorescence staining.
CONCLUSIONS LXR agonist T0901317 inhibits the transformation of human aortic valve interstitial cells to an osteogenic phenotype. T0901317 improves the ERS response in human aortic valve interstitial cells and slows the osteogenic response in human aortic valve interstitial cells via the PERK-eIF2α-ATF4-Runx2 pathway. T0901317 protects aortic valve structure and function in CAVD mice by a mechanism that may be related to the inhibition of osteogenic transition and ERS.
GW34-e1389
Poli Lin1, Ping Ren1, Boya Cao1, Jiali Chen2, Ping He3, Junling Cao4, Jian Zhang3
1School of Chinese Materia Medica, Beijing University of Chinese Medicine
2School of Chinese Medicine, Beijing University of Chinese Medicine
3School of Life Sciences, Beijing University of Chinese Medicine
4Dongfang Hospital, Beijing University of Chinese Medicine
OBJECTIVES Scrophulariae Radix (known as xuanshen, XS), is a traditional Chinese medicine which has strong anti-inflammatory effects and is widely used in the formulation of cardiovascular diseases. Toll-like receptor 4 (TLR4) pathway is an important inflammatory response pathway and a key regulator of the initiation and spread of inflammation after acute myocardial ischemia (AMI). This study aims to explore and verify the pharmacological function and the mechanism of XS and its effect component in regulating TLR4 pathway on AMI.
METHODS First, the components that may act on TLR4 target in XS were screened by network pharmacology, and further identified by molecular docking technology. Then, the efficacy of XS and the screened component on AMI was evaluated based on AMI mouse model which was established by 7 days left coronary artery ligation and hypoxia-inflammation compound induced H9C2 cardiomyocyte model which was treated by 1 μg/mL lipopolysaccharide and incubated with oxygen deprivation for 8 h. XS and Asn were given orally by gavage. Carvedilol and TAK-242, the TLR4 inhibitor, were given as positive control. Then, the regulation of XS and the screened component on proteins of TLR4 pathway was determined by western blot assay, including TLR4, nuclear factor kappa B (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), gasdermin D (GSDMD) and interleukin-1β (IL-1β).
RESULTS By network pharmacology, L-Asparagine (Asn) was predicted as the potential effect component of XS in regulating TLR4 pathway. The result of molecular docking showed that Asn could bind to TLR4 and its co-receptor protein respectively by hydrogen bonds. XS and Asn inhibited the dilatation of the left ventricle and alleviated acute ischemic injury, including a significant increase of ejection fraction and fractional shortening, a significant decrease of creatine kinase MB and cardiac Troponin I in serum, and collagen volume fraction. Meanwhile, XS and Asn protected cardiomyocytes against inflammation damage through reducing inflammatory cell infiltration and the expression levels of tumor necrosis factor-α and interleukin-6. Furthermore, XS could significantly decrease the protein levels of TLR4, NLRP3, GSDMD and IL-1β in AMI mice. Asn could significantly decrease the protein levels of TLR4, NF-κB, NLRP3 and IL-1β in AMI mice. In vitro, XS and Asn significantly protected H9C2 cardiomyocyte against hypoxia and inflammatory injury. Moreover, XS could significantly decrease the protein levels of TLR4 and NF-κB in hypoxia-inflammation induced cell model. Asn could significantly decrease the protein levels of TLR4, NF-κB and NLRP3 in hypoxia-inflammation induced cell model.
CONCLUSIONS XS is effective in alleviating myocardial ischemic injury, improving cardiac function and inhibiting the excessive inflammation, possibly by regulating TLR4 pathway. Asn is the potential effect compound of XS and also could alleviate myocardial ischemic injury and inhibit the activation of TLR4 and its downstream proteins to inhibit the inflammation.
GW34-e1393
Yuangengshuo Wang, Wenyao Wang, Chunli Shao, Chen Li, Yitian Zheng, Yida Tang
Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital
OBJECTIVES Calcific aortic valve disease (CAVD) is a structural heart disease with a high incidence and mortality rate but limited pharmacological treatment. Clinical studies have found that patients with CAVD exhibit a significant reduction of local thyroid hormone concentration, suggesting that thyroid dysfunction may play an essential role as an inducement factor in the occurrence and progression of CAVD. The purpose of this study is to explore the relationship and underlying mechanisms between thyroid function and CAVD.
METHODS In this study, we use both in vivo and in vitro models to investigate the role of thyroid hormone in CAVD development. C57BL/6J mice aged 10–12 weeks were randomly divided into four groups (n=6). The aortic valves in the surgical group were directly injured by a spring wire under the guidance of echocardiography. The T3 group was treated with triiodothyronine (5 μg/g·d) after surgery for 8 weeks. The PTU group was treated with 0.025% propylthiouracil (PTU) after surgery for 8 weeks. Sham surgery was performed similarly but without wire insertion into the left ventricle. Additionally, different concentration gradients of thyroid hormone were employed as interventions to investigate their impact on the osteogenic differentiation process in valvular interstitial cells. The EF, FS, aortic valve peak velocity, and effective orifice area (EOA) were recorded before and every 4 weeks after the operation. Von Kossa staining and Alizarin red staining were used to estimate the degree of calcification. qRT-PCR, Western blot, and Opal multiplex immunofluorescence were used to measure the RNA and protein expression levels.
RESULTS Compared to the sham-operated group, mice with wire-induced injury to the aortic valve demonstrated a significant increase in aortic valve peak velocity and a decrease in EOA. Among them, the T3 group had a larger EOA than the sham-operated group, more significantly than the PTU group. Results from Von Kossa staining, Sirius Red staining, and alkaline phosphatase staining indicated that the extent of valve calcification was more severe in the PTU group than in the sham-operated group and greater in the sham-operated group than in the T3 group. These results suggested that decreased thyroid hormone levels accelerated valve calcification and remodeling. Mechanistically, low thyroid hormone level decreased the expression of Med1 in vitro. Thyroid hormone deficiency can impair BMP/TGF-β signaling pathway transduction by affecting Med1 expression, which is associated with calcific aortic valve disease (CAVD) progression.
CONCLUSIONS Low thyroid hormone concentration is a significant inducement factor for CAVD. It can impede valvular interstitial cells’ repair function and promotes valve calcification and structural remodeling. This process may be achieved by affecting Med1 expression levels and thus impairing BMP/TGF-β signaling pathway transduction. Supplementation of thyroid hormones helps maintain normal valvular interstitial cell function and inhibits osteogenic differentiation.
GW34-e1398
Ruimin Liu
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Obesity related cardiomyopathy is a worldwide health problem caused by lipid accumulation in the heart. Chemerin, an adipocyte-secreted protein, has been recently suggested to be linked to metabolic syndrome and cardiac function in obese and diabetes mellitus. This study aimed to investigate the potential roles of adipokine chemerin on high fat-induced cardiac dysfunction.
METHODS Six to eight-week-old male Rarres2 −/− mice and WT littermates were studied. Mice were fed with normal diet or high fat diet for 20 weeks in a 12-hour cycle environment. For calorimetric analyses, mice were acclimated to metabolic cages 1 week after fed with 16 weeks of HFD. Heart function was measured by echocardiography, HE staining and Masson trichrome staining were used for observing cardiac morphology and collagen deposition.
RESULTS Firstly we found that an increase of serum chemerin in HFD mice, which is mainly released in adipose tissues, induced CMKLR1 to express its primary receptor. This early occurrence may protect against cardiomyopathy brought on by obesity. Next, chemerin knockout mice were created to confirm this notion. When they were fed a high-fat diet, it was shown that the Rarres2 knock further generated lipotoxicity, which caused inflammation, glucose/insulin resistance, and cardiac dysfunction. Nevertheless, these abnormalities above were not observed in Rarres2 −/− mice under normal-diet feeding. Thirdly, using lipid-overloaded cardiomyocytes, we observed that chemerin supplementation lowered lipid accumulation, insulin resistance, and inflammation. Furthermore, knocking down the CMKLR1 gene could abolish these protective effects of chemerin in lipid-overloaded cardiomyocytes. Herein, our data demonstrate that adipocyte-derived chemerin functions as a critical protective regulator of cardiac function in the obese/or pre-diabetic heart.
CONCLUSIONS Together, these data obtained demonstrate that adipocyte-derived chemerin functions as an endogenous cardioprotective factor in the presence of obesity, alleviates lipid overload-induced lipotoxicity, insulin resistance, inflammation and improves cardiac dysfunction, it therefore indicates that chemerin and as a novel potential treatment approach for the obese related cardiomyopathy.
GW34-e1404
Chao Yang1,2, Yuxing Chen1,2, Xinyang Hu1,2, Wei Zhu1,2, Jian’an Wang1,2,3
1Department of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
2Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, China
3Binjiang Institute of Zhejiang University (Research Center for Life Science and Human Health), Hangzhou 310053, China
OBJECTIVES The therapy of left ventricular mechanical unloading, such as transcatheter aortic valve replacement (TAVR) and left ventricular assist devices (LVAD) has significantly improved the prognosis for patients with heart failure. However, the detailed cellular and/or molecular mechanisms of recovery of cardiac function remain largely unknown. We aimed to build a cellular atlas of the heart that experienced stress and de-stress, focusing on myofibroblasts, precisely its cell fate of differentiation and function.
METHODS We conducted single-cell sequencing, ATAC sequencing on non-myocardial cells from mouse heart samples of pressure overload-induced heart failure and recovery, using TAC (transverse aortic arch constriction)/deTAC (with suture for the constriction removed 2 weeks after TAC) mouse model to identify the dynamic changes. The lineage tracing technique was also used to gain further insight into cell fate and reciprocal interactions. During this process, the macrophage subgroup was cleared using various approaches to investigate the cross-talk between myofibroblast and macrophage.
RESULTS We successfully generated a TAC/deTAC mouse model, which can faithfully simulate a reversal process of functioning for the heart that underwent a pressure overload stress (a hypertrophy process). Mouse multi-omics sequencing reveals the genetic changes, spatial distribution, and transcriptional regulation of cell populations at different stages. Among the different cell types, significant changes in the gene expression pattern were observed in fibroblasts. Aided by myofibroblast lineage tracing, flow cytometry examinations suggested that remaining in a quiescent state rather than showing a decrease in its number appeared as the central fate of myofibroblasts that accompanied the reversal of cardiac function when the over-loading was relieved. Surprisingly, however, simultaneous pressure unloading and macrophage clearance significantly reduced the number of myofibroblasts.
CONCLUSIONS With a reliable TAC/deTAC mouse model, our multi-omics data revealed dynamic changes in cell populations of the heart that underwent pressure overload stress followed by unloading; our data demonstrated a quiescent state rather than a reduction in number was the significant fate for the activated myofibroblasts for which macrophages were involved. These findings unveiled some novel mechanisms that had never been described before.
GW34-e1405
Xianbao Liu, Jinyong Chen, Jian’an Wang
The Second Affiliated Hospital, Zhejiang University School of Medicine
OBJECTIVES Calcific aortic valve disease (CAVD) poses a serious threat to the health of older adults, yet no available drugs have proven effective against its progression. A proper drug delivery system can be a potential solution to CAVD drug therapy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, targeted drug delivery for CAVD are hard to achieve.
METHODS The expression of protease-activated-receptor-2 (PAR2) was analyzed, and a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide and loaded with XCT790 for dual-active targeting therapy was developed. A parallel-plate flow chamber was designed and a mouse CAVD model was established to evaluated the targeting curative ability of the nanoplatform in vitro and in vivo.
RESULTS PAR2 expression in human CAVD samples and osteogenically differentiated valvular interstitial cells (VICs) was increased. Intravenous injection of our nanocarriers led to significantly higher enrichment within the calcified valves under magnetic-field guidance compared to those without PAR2-targeting peptides. Loaded with XCT790, an anti-calcification drug, our nanocarrier effectively inhibited osteogenic differentiation of VICs, and alleviated aortic valve calcification and stenosis in mouse model. Mechanical study revealed the pyruvate dehydrogenase kinase 4 (PDK4)-mediated metabolic reprograming is partly involved in the therapeutic effect of targeted nanoparticles on CAVD.
CONCLUSIONS This work presents the first effective targeted drug delivery system for the prevention and treatment of CAVD in induced animal model to the best of our knowledge. The composite drug delivery platform combining PAR2- and magnetic-targeting features may represent a promising therapeutic strategy for CAVD.
GW34-e1406
Ying Lin, Qifan Yang, Xiaoping Lin, Xianbao Liu, Wei Zhu, Jian’an Wang
The Second Affiliated Hospital, School of Medicine, Zhejiang University
OBJECTIVES Extracellular matrix (ECM) is closely involved in aortic valve development and interrupted ECM maturation contributes to aortic valve anomaly. Several ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) gene family members have been reported to be related to or cause aortic valve diseases. Therefore, we aimed to test whether the other ADAMTS gene family members also involved in the aortic valve diseases.
METHODS Morpholino based approach was applied for targeted gene phenotype-screening the outflow tract anomaly in zebrafish and the 19 ADAMTS family genes exon Sanger sequencing was carried out for a cohort BAV registry study (with 304 BAV patients and 301 controls with normal cardiac valve structure). Adamts gene specific genetic tracing mouse models were generated to evaluate the spatiotemporal expression pattern in the aortic valve, and different gene modified mouse models (including mutant gene knock-in and conditional gene knock-out) were generated using the CRISPR/Cas9 method to evaluate their roles in aortic valve development and valvular pathogenesis. Movat’s pentachrome staining was used to describe the altered ECM maturation process in cardiac valves. Bulk RNA-seq was also performed based on both genetic mouse heart tissue and iPSC induced endothelial cells generated from BAV patient peripheral blood cells to explore the potential molecular pathways, which was further confirmed in ex vivo embryonic outflow tract tissue culture study.
RESULTS We identified some novel ADAMTS genes that can be involved in cardiac outflow valve development, exon sequencing identify ADAMTS16 p.H357Q variant in an inherited BAV family. Therefore, the Adamts16-Cre; Rosa26-tdTomato mouse model was generated which showed Adamts16-expressing cells were primarily restricted to valvular endothelial cells (VECs) at E12.5 and then started to be expressed in valvular mesenchymal cells (VICs) at E13.5. The CRISPR/Cas9 based Adamts16 +/ - and Adamts16+/H355Q mice both exhibited an R-NC-type BAV phenotype, with progressive aortic valve thickening, whereas conditional Adamts16 knockout mouse models demonstrated that Adamts16 deficiency mainly in endothelial lineage cell recapitulated the BAV phenotype. ADAMTS16 deficiency demonstrated worse ECM deposition and loss of the ECM trilaminar structure. Bulk RNA sequencing using iPSC-induced endothelial cells (iPSC-ECs) and genetic mouse embryonic tissue unveiled enhanced focal adhesion signaling, which was accompanied by elevated fibronectin levels. Both in vitro iPSC-ECs culture and ex vivo embryonic tissue explant studies validated the altered focal adhesion signaling.
CONCLUSIONS Our present study identified a novel BAV-causing ADAMTS16 p. H357Q variant. ADAMTS16 deficiency led to BAV formation.
GW34-e1411
Pengqi Lin1, Quanwei Pei1, Bin Li1, Jiemei Yang2, Lina Zou1, Dezhan Su1, Junpei Zhang1, Hongpeng Yin1, Mbabazi Nadine1, Junjie Yang1, Zhenwei Pan3, Jingjie Li1, Dechun Yin1
1Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
2Department of Echocardiography, The First Affiliated Hospital of Harbin Medical University, Harbin, China
3Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China
OBJECTIVES Current stress cardiomyopathy (SCM) theories revolve mostly around “catecholamine myocardial toxicity” and “sympathetic hyperactivation”. However, the role of the central nervous system (CNS) in the pathogenesis of stress cardiomyopathy remains unknown. Microglia can secrete glial transmitters in the central nervous system to support and trophic neurons and participate in the regulation of neural activities. The paraventricular nucleus of the hypothalamus is the central sympathetic outflow tract. In this study, we investigated the role of microglial activation in the paraventricular hypothalamic nucleus (PVN) in the development of SCM.
METHODS To create a SCM model, male Sprague-Dawley (SD) rats were immobilized under stress for 6 hours every day for 7 days. RNA sequencing, ventricular electrical stability, left ventricular morphology, and sympathetic nerve activity were measured. In addition, brain tissues were extracted to detect microglial activation and inflammatory cytokine expression.
RESULTS (1) RNA sequencing analysis showed that functions of differentially expressed genes were significantly enriched in neuroinflammatory pathway. (2) Microglial were significantly activated in PVN, as evidenced by an increase in their number as well as axon process length and branching. (3) In SCM, microglial in the PVN increased central sympathetic outflow by increasing the expression of inflammatory factors. (4) It is possible that inhibiting microglial activation could suppress central inflammation and increase the electrical stability of the heart in SD rats with SCM.
CONCLUSIONS Inhibiting activated microglial in the PVN possibly reduce ventricular fibrillation vulnerability in SCM rats by central neuroinflammatory pathway. These findings suggest that microglial are a potential target for sudden cardiac death prevention in SCM.
GW34-e1415
Lihong Yao, Mengkang Fan, Hongzhuan Sheng
Affiliated Hospital of Nantong University
OBJECTIVES Betaine, as a non-hazardous natural plant compound found in beetroot and seafood, acts as an osmolyte and a methyl donor. Betaine has been shown to have a variety of benefits in a variety of human diseases. However, its role in cardiac hypertrophy is unclear. Our aim is to investigate the role and regulatory mechanism of betaine in occurrence of pressure overload-induced cardiac hypertrophy.
METHODS C57 BL/6 mice were used for preparing pressure overloaded-induced cardiac hypertrophy model in vivo by TAC (transverse aortic constriction) surgery, and neonatal rat cardiomyocytes (NRCMs) were used for preparing cardiac hypertrophy model in vitro by phenylephrine (PE) stimulation. Adenovirus containing shRNA-HCAR1 (ADV-shHCAR1) were constructed to knockdown HCAR1 in NRCMs. The surface area of cardiomyocytes was detected by HE staining, WGA staining and actin-tracker staining, and the level of cardiac fibrosis was detected by masson staining. ELISA kit was used to determine the level of cAMP, real-time quantitative PCR was used to detect the level of cardiac hypertrophy related markers (ANP, BNP, MHC), and western blot was used to detect the changes of MHC and Hippo signaling pathway related molecules. Binding interaction between HCAR1 and betaine was predicted by AutoDock 4 and further validated with RNA-seq analysis.
RESULTS In vivo experiments revealed that betaine administration of male C57BL/6 mice for 4 weeks after transverse aortic constriction preserved ejection fraction and decreased the left ventricular posterior wall thickness, heart weight/tibia length, cross-sectional area and cardiac fibrosis area. Computer molecule docking screening analysis identified betaine as a potential ligand of HCAR1. Treatment with betaine significantly attenuated PE-induced hypertrophy in NRCMs, which was alleviated by transfection of ADV-shHCAR1. Transcriptome sequencing analysis and probative experiment proved that betaine took effects via regulating HCAR1/Hippo signaling pathway.
CONCLUSIONS 1. Betaine attenuated pressure overload-induced cardiac hypertrophy by inhibiting HCAR1 activation and activated Hippo signaling pathway. 2. Betaine was a candidate for the treatment of cardiac hypertrophy.
TRANSLATIONAL RESEARCH OF CARDIOVASCULAR DISEASE
GW34-e0093
Yusi Chen
The Second Xiangya Hospital of Central South University
OBJECTIVES Idiopathic pulmonary arterial hypertension (IPAH) is a potentially fatal pulmonary vascular disease with an extremely poor natural course of IPAH. The limitations of current treatment and the unclear etiology and pathogenesis of IPAH require new targets and avenues of exploration involved in the pathogenesis of IPAH. tRNA-derived small RNAs (tsRNAs), a new type of small noncoding RNAs, have a significant part in the progress of diverse diseases. However, the potential role of tsRNAs in IPAH remains unknown.
METHODS Small RNA microarray was implemented on three pairs of plasma of IPAH patients and healthy controls to investigate and compare tsRNAs expression profiles. Validation samples were used for real-time polymerase chain reaction (Real-time PCR) to verify several dysregulated tsRNAs. miRanda and TargetScan were adopted to determine the potential target genes and mechanisms of the validated tsRNAs in IPAH by bioinformatic analysis.
RESULTS Microarray detected 816 statistically differentially expressed tsRNAs, of which 243 tsRNAs were upregulated and 573 were downregulated in IPAH. Eight validated tsRNAs in the results of Real-time PCR were concordant with the small RNA microarray: four upregulated (tRF3a-AspGTC-9, 5′tiRNA-31-GluCTC-16, i-tRF-31:54-Val-CAC-1 and tRF3b-TyrGTA-4) and four downregulated (5′tiRNA-33-LysTTT-4, i-tRF-8:32-Val-AAC-2, i-tRF-2:30-His-GTG-1, and i-tRF-15:31-Lys-CTT-1). The Gene Ontology analysis has shown that the dysregulated tsRNAs are related to cellular macromolecule metabolic process, regulation of cellular process, regulation of cellular metabolic process. It is disclosed that potential target genes of dysregulated tsRNAs are involved in PPAR signaling, BMPR2 signaling, and HIF-1 signaling significant to the pathogenesis of IPAH by Kyoto Encyclopedia of Genes and Genomes.
CONCLUSIONS This study investigated tsRNA profiles in IPAH and found that the expression of eight dysregulated tsRNAs may become a novel type of bio-diagnostic indicators and possible targets for IPAH.
GW34-e0212
Ziwei Zhu, Xiaowei Zhang
Lanzhou University Second Hospital
OBJECTIVES Myocardial infarction (MI) causes a significant contributor to morbidity and mortality worldwide. However, the molecular mechanism remains unclear. Cold-inducible RNA-binding protein (CIRP) acts as a damage-associated molecular pattern, raising critical implications for the pathobiology of inflammatory diseases. We explored the underlying mechanism of CIRP as MI therapeutic target that may help patients reduce the mortality rate.
METHODS CIRP and cTnI were highly expressed in patients with acute MI, and this elevation was confirmed in rats with acute MI compared with the Sham group. Rats were randomly assigned into 4 groups: sham group, sham-Cirbp−/− group, WT group, and Cirbp−/− group, and the last two groups underwent left anterior descending (LAD) ligation.
RESULTS Cardiac function and myocardial injury were significantly better in the Cirbp−/− group than in the WT group after acute MI. The degree of neutrophil infiltration and the expression levels of C5a, ICAM-1, MMP-9, IL-1β, IL-6, and TNF-α was lower in the Cirp−/− group than the WT group. Consistent results were obtained in evaluating the expression of inflammatory-related proteins in tissue samples and cell cultures.30 minutes after LAD ligation, C23, a competitive inhibitor of CIRP, was administered intravenously to evaluate the effect of C23 on MI and found that C23 can improve cardiac function and have an anti-inflammatory effect after MI.
CONCLUSIONS CIRP is one of damage-associated molecular patterns that aggravates the myocardial injury of acute coronary syndrome, and that the use of CIRP specific antagonist C23 can alleviate the myocardial injury and ventricular remodeling.
GW34-e0239
Zhen Wang
Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
OBJECTIVES Cardiac dysfunction is a well-recognized complication of sepsis and is associated with the outcome and prognosis of septic patients. Evidence suggests that IL-12A participates in the regulation of various cardiovascular diseases, including heart failure, hypertension and acute myocardial infarction. However, the effects of IL-12A in sepsis-induced cardiac dysfunction remain unknown. Hence, this study aimed to determine the role of IL-12A in sepsis-induced cardiac dysfunction and explore its underlying mechanisms.
METHODS In our study, lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) model were used to mimic sepsis, and cardiac IL-12A expression was assessed. In addition, IL-12A knockout mice were used to detect the role of IL-12A in sepsis-related cardiac dysfunction.
RESULTS We observed for the first time that IL-12A expression is upregulated in mice after LPS treatment and macrophages were the main sources of IL-12A. In addition, our findings demonstrated that IL-12A deletion aggravates LPS-induced cardiac dysfunction and injury, as evidenced by the increased serum and cardiac levels of lactate dehydrogenase (LDH) and cardiac creatine kinase-myocardial band (CK-MB). Moreover, IL-12A deletion enhances LPS-induced macrophage accumulation and drives macrophages toward the M1 phenotype in LPS-treated mice. IL-12A deletion also downregulated the activity of AMP-activated protein kinase (AMPK) but increased the phosphorylation levels of p65 (p-p65) and NF-κB inhibitor alpha (p-IκBα). In addition, IL-12A deletion aggravates CLP-induced cardiac dysfunction and injury. Treatment with the AMPK activator AICAR abolishes the deterioration effect of IL-12A deletion on LPS-induced cardiac dysfunction.
CONCLUSIONS IL-12A deletion aggravated LPS-induced cardiac dysfunction and injury by exacerbating the imbalance of M1 and M2 macrophages. Our data provide evidence that IL-12A may represent an attractive target for sepsis-induced cardiac dysfunction.
GW34-e0303
Yan Zhao, Hangtian Yu, Angwei Gong, Shuaidan Zhang, Bing Xiao
Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China
OBJECTIVES The causal relationship between heart rate variability and cardiovascular diseases and the associated events is still unclear, and the conclusions of current studies are inconsistent. We aimed to explore the relationship between heart rate variability and cardiovascular diseases and the associated events with the Mendelian randomization study.
METHODS We selected normal-to-normal inter-beat intervals (SDNN), root mean square of the successive differences of inter-beat intervals (RMSSD), and peak-valley respiratory sinus arrhythmia or high-frequency power (pvRSA/HF) as the three sets of instrumental variables for heart rate variability. The outcome for cardiovascular diseases included essential hypertension, heart failure, angina pectoris, myocardial infarction, non-ischemic cardiomyopathy, and arrhythmia. Cardiac arrest, cardiac death and major coronary heart disease event were defined as the related events of cardiovascular diseases. The data for exposures and outcomes were derived from publicly available genome-wide association studies. Inverse variance weighted was used for the main causal estimation. Analyses of heterogeneity and pleiotropy were conducted using the Cochran Q test of Inverse variance weighted and MR-Egger, leave-one-out analysis, and MR-Pleiotropy Residual Sum and Outlier methods.
RESULTS The Inverse variance weighted method indicated that genetically predicted pvRSA/HF was associated with the increased risk of cardiac arrest (odds ratio 2.02, 95% confidence interval 1.25–3.28, P=0.004). The results were free of heterogeneity and pleiotropy. There were no outliers and the leave-one-out analysis proved that the results were reliable.
CONCLUSIONS This study provides genetic evidence that pvRSA/HF is causally related to cardiac arrest.
GW34-e0353
Yang Zhang1,2, Xiaoman Wang1, Xunkai Li1, Shuangjie Lv1, Bo Yan3, Houzao Chen1, Xiaoqiang Tang4
1State Key Laboratory of Medical Molecular Biology, Department of Biochemistry & Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
2Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai 200032, China
3Institute of Precision Medicine, Jining Medical University, Jining, Shandong 272067, China
4Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu 610041, China
OBJECTIVES The mechanisms underlying ageing-induced vascular remodelling remain unclear. This study investigates the role and underlying mechanisms of the cytoplasmic deacetylase sirtuin 2 (SIRT2) in ageing-induced vascular remodelling.
METHODS The expression of Sirtuins was analyzed by bulk RNA-seq, quantitative real-time PCR, western blot, and immunofluorescence staining. Male C57BL/6 WT and Sirt2-KO mice were used to analyze the effects of SIRT2 on ageing- and stress-induced vascular dysfunction. Vascular function was evaluated by pulse-wave velocity and constriction-relaxation of aortas. Vascular remodeling was analyzed by hematoxylin-eosin staining and vascular transcriptome was analyzed by bulk RNA-seq. Mechanism study was performed with western blot, immunoprecipitation, dihydroethidium and MitoSOX stainings. Finally, the SIRT2 coexpression module in aortas was analyzed for predicting the age-related aortic diseases in humans.
RESULTS SIRT2 level was the highest among the Sirtuins in human and mouse aortas. In aged mouse aortas, SIRT2 enzymatic activity and protein level were decreased. Functional and histological experiments demonstrated that knockout of Sirt2 aggravated dysfunction (increased stiffness and reduced constriction-relaxation function) of the aorta in aged mice, which was coupled with the remodeling of the vascular medial layer. Further transcriptome and immunofluorescence staining analyses revealed the potential contribution of mitochondrial reactive oxygen species (mROS) to SIRT2 roles in ageing-related vascular dysfunction. Mechanism studies showed that Sirt2 knockout led to hyperacetylation and hyperphosphorylation (activation) of the ageing-controlling protein p66Shc, which is one of the ringleaders of mROS. Scavenging mROS with MnTBAP repressed Sirt2-knockout-induced aggravation of vascular remodeling and dysfunction in aged or angiotensin II (Ang II)-infused mice. Finally, we found that the SIRT2 coexpression module in aortas was reduced with ageing across species and was a significant predictor of age-related aortic diseases in humans.
CONCLUSIONS The deacetylase SIRT2 is a response to ageing that delays vascular ageing, and the cytoplasm–mitochondria axis (SIRT2–p66Shc–mROS) is important for vascular ageing. Therefore, SIRT2 may serve as a potential therapeutic target for vascular rejuvenation.
GW34-e0370
Ru Ying, Cheng-Long Wu, Ran Yin, Jia-Ling Yin
Department of Cardiology, The First Affiliated Hospital of Nanchang University
OBJECTIVES Atrial fibrosis is important as an atrial fibrillation (AF) substrate. The purpose of our study was to evaluate the effect of Chemokine C-X-C motif ligand-1 (CXCL1) on atrial fibrosis and atrial fibrillation and the role of endoplasmic reticulum stress (ERS) and TXNDC5 plays in the process.
METHODS CXCL1 levels in peripheral blood, left atrial blood and right atrial blood of 16 control patients and 29 AF patients were evaluated. We evaluated the effect of CXCL1 on rat atrial fibrosis by Masson staining and expressions of Collagen 1, collagen 3, TGF-β, GRP78, ATF6 and TXNDC5 using an organo-culture system. CXCL1 effects on rat cardiac fibroblasts were also investigated, and the role of ERS and TXNDC5 was investigated by ERS inhibitors and TXNDC5 shRNA.
RESULTS Serum CXCL1 levels were increased in peripheral blood, left atrial blood and right atrial blood in AF group compared with the control group. In Exvivo, CXCL1 promoted fibrosis in rat atrial muscle, as well as upregulated GRP78, ATF 6, TXNDC5 expression and increased collagen 1, collagen 3 and TGF-β1 secretion. Both ERS inhibitor 4-phenylbutyrate (4-PBA) and TXNDC5 shRNA could reverse the pro-fibrotic effect of CXCL1 in rat cardiac fibroblasts.
CONCLUSIONS CXCL1 promote atrial fibrosis by activing ERS and TXNDC5, which may further contribute to the progression of atrial fibrillation.
GW34-e0483
Kun Li, Ping Zhang
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.
GW34-e0546
Yaohan Tang, Chenghui Yan, Yaling Han
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES The cellular repressor of E1A stimulated genes 1 (CREG1) has been previously found to have anti-inflammatory and cardiac effects in our laboratory, but the active region of CREG1 is still unclear. This has become an obstacle to the translation of CREG1 into small molecule peptide drugs. The aim of this study is to identify the active region of CREG1 that plays an anti-inflammatory and cardioprotective role in AMI, and to obtain an effective fragment with a smaller molecular weight.
METHODS In this study, four peptides containing different domains of CREG1 were synthesized. These peptides or human CREG1 recombinant protein were added to the macrophage cell line RAW264.7 and stimulated by lipopolysaccharide (LPS) to induce inflammation model. The effect of the active fragment on macrophage migration was examined by a scratch assay. AMI mice were treated with the four peptides or the full-length CREG1 protein by subcutaneous implantation of an implantable osmotic sustaine-release pump. Cardiac function was assessed by small animal ultrasound 28 days later.
RESULTS A peptide containing the N-terminal 30–80 amino acids (NC51) of CREG1 protein inhibited the expression of IL-1β and IL-6 in a concentration-dependent manner and had no effect on the viability of macrophages. Treatment with NC51 peptide significantly reduced LPS-induced macrophage migration; NC51 could down-regulate iNOS expression and up-regulate CD206 expression. Compared with the MI group, the EF and FS% of the hearts in NC51 group and CREG1 group were significantly increased, and the heart weight to body weight ratio and heart weight to tibia length ratio were significantly decreased, and the area of myocardial infarction and fibrosis were also significantly reduced. NC51 group and CREG1 group also reduced the content of CKMB in the serum of mice, but had no significant effect on AST and ALT. In addition, NC51 and CREG1 reduced the infiltration of CD68-positive macrophages and the expression of IL-1β and IL-6 in the myocardial tissue of the infarct border zone, and also inhibited the expression of iNOS, but increased the expression of CD206. Compared with the CREG1 group, the NC51 group and the CREG1 group had no significant differences in the above indicators. Mechanically, NC51 plays an inhibitory role in the inflammatory response of macrophages through ANXA1-mediated entry and depends on Sirt1/NF-κB pathway.
CONCLUSIONS NC51 (N30-80aa), a small active polypeptide fragment of CREG1 recombinant protein, can protect against macrophage inflammatory response and cardiac function injury in mice after AMI. Mechanistic studies suggested that NC51 entered macrophages through ANXA1 and exerted anti-inflammatory effects dependent on Sirt1/NF-κB. NC51 peptide may be a potential therapeutic peptide drug for inhibiting inflammation and fibrosis after myocardial infarction and alleviating heart failure.
GW34-e0709
Tianwen Wei, Tiankai Shan, Jiawen Chen, Liansheng Wang
The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES The regenerative capacity of adult mammalian hearts is limited. While numerous studies have explored mechanisms of cardiomyocyte cell-cycle withdraw, the regulative network is still complex. This study aimed to explore whether CHK1 could promote cardiac regeneration and repair in pigs after myocardial infarction and the specific mechanisms.
METHODS I/R injury was induced in pigs, recombinant human checkpoint kinase 1 (rhCHK1) protein (1 mg/kg) encapsulated in hydrogel or equivalent hydrogel was injected into the infarct border zone. The therapeutic efficacy of rhCHK1 was evaluated by echocardiography, cardiac magnetic resonance imaging (MRI), hematological indices and immunofluorescence. Multi-omics analysis were performed to explore the potential mechanisms of rhCHK1. Further, protein interaction prediction and CO-IP experiments were conducted to verify the specific interaction pattern and domains between CHK1 and PKM2. Hipsc-CMs and porcine models were used for confirming whether rhCHK1 promotes cardiac regeneration through combining with the PKM2 C-domain.
RESULTS RhCHK1 protein stimulated cardiomyocytes (CMs) proliferation and reduced cardiac inflammation response at 3 days post operation, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after I/R injury. Mechanistically, multiomics sequencing analysis showed that glycolysis and mTOR pathways were significantly enriched in this process. Further CO-IP experiments and protein docking prediction showed that CHK1 directly bound to and activated the S37 and Y105 sites of PKM2 to promote metabolic reprogramming. We further constructed plasmids that knock out different CHK1 and PKM2 domains, and transfected them into H293T cells for CO-IP experiments. It was found that the 391–476 domain of CHK1 directly binds to the 157–400 amino acids of PKM2. Further hipsc-CMs in vitro and pig in vivo experiments both demonstrated that CHK1 stimulates CMs renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming and mTORC1 pathway.
CONCLUSIONS This study demonstrates that rhCHK1 could combine with PKM2 391–476 amino acid domain to mediate metabolic reprogramming and mTORC1 pathways to promote cardiomyocytes proliferation and myocardial repair. This study is the first to clarify the specific functional mechanism of CHK1 in adult Bama pigs. Our results underscore the potential of the local applied CHK1 protein kinase as a safe and simple feasible treatment option for repairing heart.
GW34-e0758
Zhongyin Zuo1,2, Sainan Li3, Fengqi Xuan3, Jie Zhang3, Zichen Liu3, Shibei Zhang4, Ming Liang4,5, Zulu Wang4,5
1Department of Cardiology, General Hospital of Northern Theater Command of Jinzhou Medical University, Shenyang 110016, China
2Department of Cardiology, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai 200080, China
3Department of Cardiology, General Hospital of Northern Theater Command of China Medical University, Shenyang 110016, China
4Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
5National Key Laboratory of Frigid Zone Cardiovascular Diseases, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Catheter ablation (CA) of idiopathic ventricular arrhythmias (IVAs) originating from the left ventricular summit (LVS) and the interventricular septum pose a serious challenge due to anatomical constraints. However, a novel ablation technique with guidewire has emerged as a promising approach for mapping and ablation of these arrhythmias.
METHODS Ablation models were established to simulate blood vessels of different diameters (1.17 mm, 2.24 mm) in isolated swine myocardial tissue, and guidewire ablation (GA) was performed with different power of 10 W, 15 W, 20 W, and 25 W during 60 sec to determine the maximum safe power without steam pop occurring for each diameter group. Then with the maximum safe power, GA was performed on each group for different duration of 10, 20, 30, 40, 50, and 60 sec, and generator impedance (GI) changes, steam pop events as well as lesion diameters were recorded to elucidate the correlation between ablation duration and lesion size. Finally, GA was performed on in vivo swine heart and the animals was dissected at 48 hours and 8 weeks later to verify the feasibility of the maximum safe power and the lesion formation.
RESULTS Occurrence of steam pop increased along with the raise of ablation power in both two groups, and the maximum safe power was 10 W for the 1.17 mm group and 15 W for the 2.24 mm group. Under the specific maximum safe power, as the ablation duration prolonged, the increase in lesion diameter and decrease in GI were seen in both groups. There was a stronger correlation between GI drop and lesion diameter in group with smaller vessel diameter (1.17 mm-10 W group: maximum lesion diameter & GI drop, R = 0.965, minimum lesion diameter & GI drop, R=0.951; 2.24 mm-15 W group: maximum lesion diameter & GI drop, R=0.872, minimum lesion diameter & GI drop, R=0.888). In vivo experiment, besides VF happened once, no other adverse events were seen, and lesions were found at both 48-hour and 8-week groups.
CONCLUSIONS The vessel diameter, power and duration of ablation have effects on lesion formation. As the vessel diameter decreases, the safe power decreases as well. Additionally, there is a stronger correlation between GI drop and lesion diameter in smaller vessels.
GW34-e0759
Zhongyin Zuo1,2, Sainan Li3, Fengqi Xuan3, Jie Zhang3, Zichen Liu3, Shibei Zhang4, Ming Liang4,5, Zulu Wang4,5
1Department of Cardiology, General Hospital of Northern Theater Command of Jinzhou Medical University, Shenyang 110016, China
2Department of Cardiology, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai 200080, China
3Department of Cardiology, General Hospital of Northern Theater Command of China Medical University, Shenyang 110016, China
4Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
5National Key Laboratory of Frigid Zone Cardiovascular Diseases, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Guidewire ablation (GA) is a novel alternative ablation method for the patients who had previous ablation failure. Howerer as a novel technology, the energy transmission process of GA is unknown.
METHODS (1) 2 groups of 1.17 mm (4F) and 2.24 mm (8F) tissues were divided, and then each group was further divided into four sub-groups of 10 W, 15 W, 20 W and 25 W on the basis of the ablation power. During the ablation process, the baseline impedance, generator impedance (GI) changes, steam pop events and their occurrence time were recorded, and the lesion diameters were measured after operation. (2) In accordance with the power, each group was divided into four sub-groups of 10 W, 15 W, 20 W and 25 W, and the same parameter changes were recorded, and the lesion diameters were measured as the study (1). (3) As the secure power obtained in the study (2), the myocardial tissues were segmented into 10 mm group and 20 mm group for the exposed length of the guidewire, and then segmented into 7 sub-groups base on ablation durations (10 s, 20 s, 30 s, 40 s, 50 s, 60 s and 90 s). (4) The influence of the infusion velocity of normal saline on the diameter of the lesion. Using the secure power and duration of GA obtained from the previous studies, GA was performed according to the normal saline infusion speed of 0, 1, 2, 3 and 4 mL/min, and the relationship between the lesion diameter and the saline infusion speed was analyzed.
RESULTS In the 1.17 mm (n=32) and 2.24 mm (n=32) simulating vessel diameter groups, we observed that steam pop rate raised with the increase of ablation power. The steam pop rates of 10 W (n=8), 15 W (n=8), 20 W (n=8) and 25 W (n=8) were 0% (0/8), 50% (4/8), 87.5% (7/8) and 100% (8/8) respectively, and the secure power of 1.17 mm group is 10 W possibly (1.17 mm group; 10 W, 0%; 15 W, 50%, P<0.01). In the 2.24 mm group, the steam pop rates were 0% (0/8), 0% (0/8), 0%, 50% (4/8) at 10 W, 15 W, 20 W and 25 W, therefore, we deem the safe power was 20 W (2.24 mm; 20 W, 0%; 25 W, 50%, P<0.01). (2) The steam pop rates raised with the increase of ablation power in the 10 mm (n=32) and 20 mm (n=32) groups. As the power of 10 W (n=8), 15 W (n=8), 20 W (n=8), and 25 W (n=8), the steam pop rates of 10 mm group were 0% (0/8), 12.5% (1/8) 62.5% (5/8) and 100% (8/8), the secure power was identified as 15 W (10 mm group; 15 W, 12.5%; 20 W, 62.5%, P<0.01). In the 20 mm group, the steam pop rates were 0% (0/8), 0% (0/8), 25% (2/8) and 75% (6/8) at 10 W, 15 W, 20 W and 25 W respectively, and the secure power might be 20 W (20 mm group: 20 W, 25%; 25 W, 75%, P<0.01). (3) The lesion diameter of 10 mm group (n=42) and 20 mm group (n=42) increased significantly within 10–40 seconds, (4) We recognized that 2 mL/min may be the best infusion speed.
CONCLUSIONS If the guidewire exposed was shorter and the target vessel diameter was smaller, high power and long duration ablation should be more cautious to decrease steam pop rate, and saline infusion should be provided to balance the effectiveness and safety of GA.
GW34-e0789
Tingting Lv, Ying Yang, Ping Zhang
Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University
OBJECTIVES It was reported that mexiletine benefited for type 2 long QT syndrome (LQT 2) patient carrying a G604C hERG (G604C) mutation while propranolol did not in our clinical practice. However, the possible mechanism of mexiletine on hERG—G604C mutant potassium channels current (IKr ) remains unclear.
METHODS Here hERG—WT (WT), G604 and heterozygous (WT/M) monoclonal stable cells were constructed in HEK293 cells. Western Blot assay and Real Time PCR assay were used to detect the levels of hERG protein and mRNA, western blot of membrane protein and immunofluorescence to evaluate protein trafficking, and whole-cell patch-clamp to detect IKr current.
RESULTS As a result, the expression of hERG mRNA and protein were both identical in WT and G604C group. HERG trafficking deficiency was presented in G604C group. IKr current decreased over 50% in WT/M group compared to WT group, and presented the loss of function in the G604C group. Incubation of increased concentration of propranolol didn’t change hERG mRNA and protein, but inhibited IKr current with a concentration-dependent manner. Mexiletine rescued hERG protein trafficking deficiency in WT/M group but not in G604C group, representing the transient effect of mexiletine on IKr current as a concentration-dependent inhibition while the chronic effect of mexiletine as promotion on G604C mutant hERG channel.
CONCLUSIONS Consequently, hERG—G604C mutation presented hERG trafficking deficiency and damaged IKr current, which can be improved by mexiletine in heterozygous (WT/M) HEK 293 cells.
GW34-e0812
Luyang Yi1,2,3, Xueke Li1,2,3, Wuqi Zhou1,2,3, Rui Wang1,2,3, Yishu Song1,2,3, Mengdan Ding1,2,3, Li Zhang1,2,3, Mingxing Xie1,2,3
1Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
2Hubei Province Clinical Research Center for Medical Imaging
3Hubei Province Key Laboratory of Molecular Imaging
OBJECTIVES Cardiac allograft vasculopathy (CAV) is a significant complication that arises from the phenotypic conversion of vascular smooth muscle cells (VSMCs) and has a severe impact on the prognosis of patients following heart transplantation. In this study, a novel ultrasound-triggered delivery system was developed, which involved a dextran nanoparticle microbubble complex encapsulating miR-145. The aim was to prevent CAV by modulating the expression of Krüppel-like factor 4 (KLF4) in VSMCs.
METHODS To prepare Spermine-dextran encapsulating miR-145 (SpeDex-miR-145), the reductive amine method was employed. Subsequently, SpeDex-miR-145 was conjugated to microbubbles (MB) through thiol bonding. A mouse model of cardiac allograft vasculopathy was established. On day 3 after successful surgery, SpeDex-miR-145@MB was administered via injection into the tail vein. Ultrasound irradiation was then conducted above the allograft through the abdominal wall. On postoperative day 28, graft vessels were subjected to quantitative RT-PCR analysis, HE staining, EVG staining, and immunofluorescence (IF). These techniques were used to assess graft vessel characteristics, miR-145 expression levels, and to identify the phenotype of vascular smooth muscle cells (VSMCs). This comprehensive analysis allowed for the evaluation of the therapeutic effects of SpeDex-miR-145@MB on graft vessels and the modulation of VSMC phenotype.
RESULTS The expression miR-145 was upregulated after ultrasound triggered SpeDex-miR-145@MB delivery. The expression levels of KLF-4 and KLF5, the upstream target genes of miR-145, were downregulated after ultrasound triggered SpeDex-miR-145@MB delivery. The VSMCs contractile marker SM22 was significantly upregulated after ultrasound triggered SpeDex-miR-145@MB delivery; while the expression of OPN, a synthetic marker of VSMCs, was downregulated significantly. The intima-media ratio was smaller after ultrasound triggered SpeDex-miR-145@MB delivery.
CONCLUSIONS The utilization of this nano-delivery system demonstrated effective delivery of miR-145 into VSMCs through ultrasound triggering. This targeted delivery successfully prevented the progression of CAV by reversing the phenotypic conversion of VSMCs. These findings indicate that the ultrasound nano-delivery system holds promise as a novel approach for preventing CAV.
GW34-e0977
Ke Gao1,2, Lei Yang1, Yanbo Xue1, Xiaorui Huang1, Yajie Gao1, Ruijuan Shi1, Qian Yin1,2, Hongyan Tian1,2, Xiaohui Zheng3, Xiaopu Zheng1
1Department of Cardiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
2Department of Peripheral Vascular Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
3Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, China
OBJECTIVES While accelerated arterial stiffening may represent a critical mechanistic factor driving cardiovascular risk in diabetes mellitus (DM), specific therapies to contain the underlying diabetic arterial remodeling have been elusive. The typical pathological changes of vascular remodeling include vascular fibrosis, the destruction of elastic fibers, and the proliferation and migration of vascular smooth muscle cells (VSMC), all of which are the important pathological basis for the occurrence and progression of arteriosclerosis and diabetic macrovascular complications. At present, there is a lack of effective therapeutic drugs to improve diabetic vascular remodeling. Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is one of the main bioactive metabolites of the Chinese medicinal herb Danshen, which can be absorbed into blood compounds by oral administration of Compound Danshen dripping pills. The purpose of this study was to investigate whether IDHP can prevent and treat diabetic vascular remodeling, and to explore the possible effects and mechanisms of IDHP on aortic medial fibrosis, elastic fibers destruction, VSMC proliferation and migration during vascular remodeling.
METHODS In vivo, the animal model of diabetic vascular remodeling was established after 8 weeks of diabetes, and IDHP preventive intervention and therapeutic intervention were given respectively. HE, Masson, PAS and Verhoeff’s Van Gieson staining were used to observe the histological morphology of thoracic aorta, the degree of vascular fibrosis, and the destruction of elastic fibers in vascular media. In vitro, VSMCs were pretreated with normal glucose (NG), 25 mM high glucose (HG), IDHP+HG and IDHP for 48 h, respectively. The expressions of Collagen I, p-p38 MAPK, p38 MAPK, Runx2, PCNA, MMP 2, MMP 9, NOX1, NOX4 and ROS levels in VSMC were detected by western blotting, DHE fluorescence probe and flow cytometry. Moreover, VSMCs were pretreated with Runx2 agonist Muramyl dipeptide, p38 MAPK agonist Anisomycin, p38 MAPK inhibitor SB203580, ROS scavenger NAC, the non-specific NOX inhibitor Diphenyleneiodonium chloride, and Mito-TEMPO, a mitochondria-targeted superoxide dismutase mimetic, respectively. Next, VSMCs proliferation was analyzed using CCK-8 method. Cell migration was examined using wound-healing and transwell assay. MitoSOX fluorescent probe was used to detect superoxide levels generated from VSMC mitochondria.
RESULTS Vascular media thickening, VSMC hyperplasia and vascular medial fibrosis were observed in the thoracic aorta of DM rats, and the elastic fibers in the media of thoracic aorta were degraded and fractured obviously. All these changes indicated that there was obvious vascular remodeling in the thoracic aorta of DM rats, but pretreatment with IDHP could prevent DM-induced vascular remodeling. More importantly, post-treatment with IDHP can effectively attenuate vascular remodeling under diabetic conditions. We also demonstrated that IDHP decreased the expression of VSMC Collagen I by inhibiting HG-induced activation of the ROS/p38 MAPK/Runx2 signaling pathway, and thereby improving vascular medial fibrosis. In addition, HG promotes the proliferation and migration of VSMC and enhances the expression of MMP 2 and MMP 9 by inducing the mitochondrial, NOX1 and NOX4-derived ROS-activated p38 MAPK signaling pathway. However, IDHP inhibits VSMC proliferation, migration and MMPs expression by weakening the p38 MAPK signaling pathway mediated by ROS generated from mitochondria, NOX1 and NOX4 in VSMCs.
CONCLUSIONS IDHP can prevent and treat diabetic vascular remodeling, and it attenuates vascular remodeling through ROS/p38 MAPK signaling pathway. These novel findings suggest that IDHP is a potential pharmacologic candidate for treating diabetic vascular remodeling.
GW34-e0996
Dong Guo, Xue Yang, Lang Hu, Yan Li
Department of Cardiology, Tangdu Hospital, Airforce Medical University
OBJECTIVES Iron overload has been cited as an important detrimental factor contributing to the poor prognosis of myocardial infarction (MI). Iron chelating therapy was reported to ameliorate MI-induced cardiac injury. However, the existing iron chelators has many side effects, thereby hindering their application in the treatment of post-MI injury. The current study aimed to explore a biological process-based strategy for iron chelating in MI-induced cardiac injury.
METHODS MI model were constructed by ligation of left anterior descending coronary artery. Cardiomyocytes were subjected to hypoxia treatment to mimic MI in vitro. Extracellular vesicles (EVs) were collected from the culture medium of macrophage by ultracentrifugation and then co-incubated with cardiomyocytes or intramyocardially injected into mice hearts. The iron content, oxidative stress, ferroptosis level, cell survival, infarcted area, and cardiac function were determined to investigate the effect of macrophages-derived EVs on iron overload and cardiac injury in hypoxia cardiomyocytes or post-MI hearts. To further explore the mechanism, multiple approaches including mass spectrometry, immunoelectron microscopy, nano-flow cytometry, and enzyme-linked immunosorbent assay were conducted. Besides, in vivo imaging and fluorescent labeling were employed to elucidate the distribution of macrophages-derived EVs.
RESULTS Cardiac iron level, serum iron level, and cardiac expression of iron-binding proteins, including transferrin and ferritin heavy chain 1 (FTH1), were significantly elevated in MI mice. Moreover, the hearts of MI mice showed obviously increased oxidative stress and ferroptosis level, as evidenced by increased malondialdehyde (MDA) content, elevated 4-hydroxynonenal (4-HNE) expression, decreased glutathione (GSH) expression, and reduced glutathione peroxidase 4 (GPX4) level. EVs were successfully isolated from culture medium of macrophages and showed remarkable iron-chelating capacity in bioactive sample including myocardium lysate, cardiomyocytes lysate, serum and culture medium of cardiomyocytes. Intramyocardially injection of macrophages-derived EVs effectively decreased the iron level of serum and myocardium in post-MI mice. Also, co-incubation with macrophages-derived EVs reduced the iron level of hypoxia-treated cardiomyocytes and their culture medium. Further in vitro and in vivo experiments revealed that iron overload-induced oxidative stress and ferroptosis were also remarkedly alleviated by macrophages-derived EVs. Mechanistically, we found that macrophages-derived EVs inherited TfR from their parent cells and could bind with transferrin. Ablation of TfR on EVs abrogated their capacity in preventing iron overload, oxidative stress, ferroptosis, and cardiac dysfunction in post-MI mice. In addition, we discovered that macrophages-derived EVs were ultimately captured and processed by liver-resident macrophages.
CONCLUSIONS In this study, we identified macrophages-derived EVs as a novel endogenous biological chelator for excess iron in MI hearts. Macrophages-derived EVs inherited TfR from parent cells, based on which macrophages-derived EVs could bind with transferrin, remove excess protein-bound iron, and thus treat iron overload. Our work demonstrated that macrophages-derived EVs were a powerful endogenous tool for iron chelating, which provides a novel and promising therapeutic approach for treating iron overload-induced injury in the pathogenesis of MI and other cardiovascular diseases.
GW34-e0998
Wang Yu, Qin Yanwen
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Hypercholesterolemia is an independent risk factor for cardiovascular disease. Studies have shown that effectively lowering circulating levels of low-density lipoprotein cholesterol (LDL-C) can prevent and reduce cardiovascular events. MicroRNA-181d (miR-181d) is a potent inhibitor of liver fat droplets, reducing liver fat droplets by about 60%. Can reduce cell triglycerides and cholesterol esters. The expression of miR-181d was decreased in plasma and adipose tissue of obese people. However, no relationship between miR-181d and LDL-C has been reported.
METHODS Two hyperglycemia animal models were used to analyze the potential relationship between miR-181d-5p and LDL-C. AAV-mediated liver-directed miRNA which over expressed in high cholesterol diet (HCD)-fed mouse model was used to examine the effect of miR-181d-5p on LDL-C and WB/RT-PCR/ELISA/luciferase assays were used to investigate the underlying mechanism.
RESULTS The expressions of miR-181d-5p were obviously lower in hyperglycemia mouse model, decreased 44.2% and had a negative correlation with serum LDL-C level (P<0.001 r=-0.8575); in hyperglycemia hamster model, miR-181d-5p expression was reduced by 48.7% and had a negative correlation with serum LDL-C level (<0.001 r=-0.8811). After AAV-mediated liver-directed miR-181d-5p over expressed, the serum cholesterol was obviously decreased about 15.2%, serum LDL-C decreased about 21.1%. After miR-181d-5p was over expressed, the liver cholesterol was obviously decreased about 25.2%, liver triglyceride decreased about 34.1% than that of control mouse. After confirming the effect of miR-181d-5p on the improvement of serum lipid in vivo, through Target Scan 8.0, we discovered PCSK9 was the possible target genes regulated by miR-181d-5p, which was further proved by in vitro experiments. MiR-181d-5p could directly interact with both the PCSK9 3′-UTR and promoter to inhibit PCSK9 translation and transcription. Furthermore, the result from Dil-LDL uptake assay under the knockdown of PCSK9 demonstrated that miR-181d-5p promoting the absorption of LDL-C in Huh7 cells was dependent on PCSK9. And the result from LDLR−/− mouse model indicated that miR-181d-5p regulating LDL-C was dependent on PCSK9/LDLR pathway.
CONCLUSIONS We discovered miR-181d-5p targets PCSK9 3′-UTR and regulated PCSK9 expression and serum Lipid, suggesting miR-181d-5p might be a new therapeutic target for reducing hypercholesterolemia.
GW34-e1055
Xingdong Ye, Yumei Xue
Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences
OBJECTIVES Atrial fibrillation (AF) is a common arrhythmia, which is closely related to aging and is a “senile disease”. However, its current treatment effect is not good enough and there is a certain recurrence rate. It is urgent to further explore the specific molecular mechanism of its pathogenesis in order to obtain better treatment. AF is associated with the aging of atrial fibroblasts, but its pathological mechanism is still unclear. The purpose of this study is to observe whether Piezo1/β-catenin pathway participated in the aging of atrial fibroblasts.
METHODS Primary atrial fibroblasts were isolated from male C57BL/6 mice (1 month) by enzyme digestion, and 100 μM tert-butyl hydroperoxide (TBHP) was used to induce the aging of mouse atrial fibroblasts (MAFs). Expression levels of Piezo1, β-catenin and aging-associated proteins p53/p21 in the cells treated with TBHP were detected by Western blot. The aging MAFs were treated with Piezo1 inhibitor GsMTx4 (3 or 10 μM) or Piezo1 siRNA, or β-catenin inhibitor XAV939 (3 or 10 μM) respectively. Changes in expression levels of β-catenin and aging-associated proteins p53/p21 in the MAFs were observed by Western blot.
RESULTS Expression levels of Piezo1, β-catenin and aging-associated proteins p53/p21 in the cells treated with TBHP increased significantly (P<0.05). GsMTx4, Piezo1 siRNA or XAV939 could ameliorate the increased expression levels of β-catenin and aging-associated proteins p53/p21 in the MAFs induced by TBHP (P<0.05).
CONCLUSIONS Piezo1/β-catenin pathway participates in the aging of atrial fibroblasts.
GW34-e1150
Yajun Xue
Beijing Tsinghua Changgung Hospital
OBJECTIVES This study aimed to review the research status and to demonstrate the hotspots and frontiers of chronotherapy.
METHODS Literatures regarding chronotherapy from inception to 2022 were retrieved from the Web of Science Core Collection database. CiteSpace 5.6.R3 was used to generate network maps about the distributions of authors, countries, institutions, references, journals and reveal hot spots and frontiers of chronotherapy.
RESULTS A total of 1059 studies related to chronotherapy were included. The number of literatures regarding chronotherapy was generally increased with some fluctuations. The field of vascular calcification research involves many disciplines, such as pharmacology pharmacy, biology, and physiology. High-yielding countries include the United States and European countries, with China also having a place. Major research institutes include the Hôpital Paul Brousse, Universidade de Vigo, and so on. High-yielding and most cited authors include Levi FA and Hermida RC. Chronobiol Int published the most of research regarding chronotherapy. The first co-cited reference reported the MAPEC trial which analyzed the effect of circadian rhythm time of hypertension treatment on cardiovascular risk. Hot topics focused on the circadian rhythm, hypertension, sleep deprivation, cancer and rheumatoid arthritis. It can be predicted that future correlative studies of chronotherapy will revolve around hypertension, cancers, immune system disorders, and psychiatric disorders.
CONCLUSIONS This study suggested the prosperous research trends and close cooperation. Major ongoing research trends include the timing of antihypertensive medication dosing, sleep deprivation, cancer and rheumatoid arthritis.
GW34-e1170
Ying Wang, Liming Chen, Jinyi Lin, Chancing Huang, Kejia Jin, Hao Wang, Jianguo Jia, Zhiwen Ding, Junbo Ge, Hui Gong, Yunzeng Zou
Zhongshan Hospital of Fudan University
OBJECTIVES Ischemia/reperfusion (I/R) injury causes cardiomyocytes death, including apoptosis and ferroptosis, which remains a significant challenge for reperfusion treatment. This study aimed to investigate the potential protective role of Wnt2 against cardiomyocytes death after I/R injury.
METHODS Serum Wnt2 levels in patients with acute myocardial infarction (AMI) before and after percutaneous coronary intervention (PCI) and in mice subjected to I/R were measured by ELISA. Cardiac function was assessed by echocardiography of M-mode Strain analysis and MRI. Cardiomyocyte death, including apoptosis and ferroptosis, which were examined by TUNEL and thiobarbituric acid reactive substances (TBARs) assay, respectively. TMT6-based proteomics analysis was used to identify critical molecules mediating the effects of Wnt2.
RESULTS Serum Wnt2 levels significantly decreased after 1, 2, 3, and 4 days of PCI in comparison to AMI patients before PCI, and the levels had negative correlation with cTnT and CKMB levels, the cardiac injury biomarkers, respectively, within the first 48 h following PCI. Serum or cardiac Wnt2 also decreased in I/R mice in compared with sham group. Supplement of rbWnt2 significantly improved cardiac function and reduced infarct area and improved the reduced ATP levels in I/R hearts as well. RbWnt2 treatment also significantly inhibits cardiomyocytes apoptosis and ferroptosis by suppressing lipid peroxidation via decreased reactive oxygen species (ROS) production in response to I/R injury. Proteomics analysis revealed that Wnt2 significantly decreased Nap1L1 expression following I/R injury, which was validated by Western Blot. Cardiac specific overexpression of Nap1L1 partly abolished inhibitory effect of rbWnt2 on apoptosis and ferroptosis in vivo and in vitro, and then, attenuated protection effect of rbWnt2 against I/R injury, whereas cardiac specific knockdown of Nap1L1 improved the cardiac function, alleviate infarct area, inhibited apoptosis and ferroptosis and increased ATP levels via suppressing ROS during I/R injury as rbWnt2 treatment. Mechanically, Wnt2 promoted Nap1L1 degradation and subsequently attenuated ROS production and cardiomyocyte death to improve cardiac function following I/R. UbiBrowser database analysis revealed that putative E3 ligases Trim11 and Rapsn interacted with Nap1L1. Western blot analysis indicated rbWnt2 treatment reversed the reduced expression of Trim11 but did not alter the increased expression of Rapsn mediated by H/N. Co-immunoprecipitation (co-IP) analysis demonstrated that the interaction of Trim11 and Nap1L1 was decreased in cardiomyocytes after H/N injury, which was restored by rbWnt2 treatment. Trim11 silence blocked the increased Nap1L1 ubiquitination mediated by Wnt2 in H/N-cardiomyocytes. Further analysis indicated that Wnt2 acted on Lrp6 to enhance Trim11 expression for ubiquitination of Nap1L1 in ischemic cardiomyocytes.
CONCLUSIONS The present study showed that I/R mediated the decreased Wnt2 level in heart and serum, supplement of Wnt2 acts on Lrp6 to attenuate apoptosis and ferroptosis by degradation of Nap1L1 through Trim11 following I/R. Supplement of Wnt2 maybe a novel therapeutic strategy for the clinical treatment of ischemia/reperfusion injury and the present findings also suggest new insights into the regulation of Nap1L1 as a target in the treatment of cardiac ischemia/reperfusion injury.
GW34-e1228
Yishu Song1,2,3, Qiaofeng Jin1,2,3, Cheng Deng1,2,3, Luyang Yi1,2,3, Li Zhang1,2,3, Mingxing Xie1,2,3
1Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2Clinical Research Center for Medical Imaging in Hubei Province, Wuhan 430022, China
3Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
OBJECTIVES Cardiac patch based therapy has emerged as a promising strategy for the treatment of heart disease, such as severe myocardial infarction. We aimed to develop a novel hydrogel patch for heart disease treatment which can sustained release drugs on the heart surface.
METHODS PLGA microspheres were prepared using a standard water-oil-water double emulsion procedure. Lyophilized PLGA microspheres were doped in GelMA solution containing photoinitiator LAP. To form microspheres hybrid GelMA hydrogel, the precursor solution was illuminated with a 405 nm light source. We used RITC-Dextran as model drug to study the drug release. In vivo, hydrogel precursor solution was spread on the heart surface immediately followed by light crosslinking to prepare the hydrogel cardiac patch.
RESULTS The lyophilized microspheres were white powder with an average particle size of 25.56±0.37 μm. SEM images indicate that the microspheres had a smooth surface and a interconnected porous structure inner it. The PLGA microspheres hybrid GelMA hydrogel was white colloid. SEM images showed that hybrid hydrogel exhibited 3D network structures with an average pore size of 67.96±30.62 μm. Microspheres were encapsulated in the pore wall or distributed in the pore. In vitro drug release study showed that GelMA hydrogel had significant burst release during 0–2 h, with a cumulative release of 96.73±5.38%. The incorporation of microspheres improved the sustained release ability, we demonstrated that RITC-Dextran are released over 28 d from this formulation, with a cumulative release of 30.47±1.57% on 28 d. In vivo experiments demonstrated that the hydrogel precursor solution irradiated by 405 nm light source could be cross-linked in situ to form a hydrogel cardiac patch on the heart surface. The patch also showed wet adhesion behavior and could be attached to the surface of beating heart.
CONCLUSIONS In summary, microspheres hybrid GelMA hydrogel performed a stable sustained drug release behavior and in situ photocuring on the heart surface was also achieved, which suggested a promising approach to the treatment of heart disease such as heart transplantation rejection and myocardial infarction.
GW34-e1290
Guangzhi Cong, Ru Yan, Shaobin Jia
General Hosptital of Ningxia Medical University
OBJECTIVES Promoting angiogenesis in the infarcted area is the key to the treatment of sequelae of AMI. The latest research suggests that monocyte-derived macrophages were recruited to the border zone after MI and secrete vascular endothelial growth factor (VEGFA), promoting angiogenesis. An attractive therapeutic strategy is to stimulate angiogenesis after myocardial infarction.
METHODS We reanalyzed large-scale, publicly available bulk (GSE151834) and single-cell RNA sequencing datasets (GSE163129) from the myocardial infarction mice model. Myeloid-specific TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) knockout mice (TREM2-/-MF) and wild-type mice (TREMflox/flox) underwent MI induced by ligation of the left anterior descending coronary artery. Cardiac functionality was assessed by longitudinal echocardiographic measurements. Histological, fluorescence-activated cell sorting, and in vitro/ex vivo studies were used to assess the myocardial neovascularization, macrophage pro-angiogenesis ability, and activity in response to TREM2.
RESULTS Bioinformatic trajectory analysis indicates TREM2 positive macrophages are the majority monocyte-derived macrophages during the late phase post myocardial infarction and governing VEGFA expression. TREM2-/-MF mice showed a reduced cardiac systolic function with a lower ejection fraction and fractional shortening in a time-dependent manner. Furthermore, the angiogenesis maker CD31 expression decreased in the myocardial infarction border zone. In vitro, when challenged with hypoxia, peritoneal macrophages from TREM2 mice (TREM2-/-MF) have a lower ability to produce VEGFA and NRF2 (Nuclear Factor erythroid 2-related factor 2). When cocultured with HUVEC, angiogenesis was worsened in the peritoneal macrophages from TREM2 mice (TREM2-/-MF) detected by matrigel assay with fewer angiogenesis meshes and junctions. NRF2 inhibitor treatment (MF385) can improve VEGFA production and the pro-angiogenesis ability of TREM2-deficient peritoneal macrophages.
CONCLUSIONS Our findings indicate that cardiac macrophages maintain healing through promoting myocardial angiogenesis by TREM2-NFR2 signaling.
GW34-e1333
You Jieyun1, Li Xuan2, Dai Fangjie2, Liu Jun1, Zhang Qi1, Guo Wei1
1Department of Cardiovascular Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
2Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
OBJECTIVES Gasdermin D (GSDMD) forms membrane pores to execute pyroptosis. But the mechanism of how cardiomyocyte pyroptosis induces cardiac remodeling in pressure overload remains unclear. We investigated the role of GSDMD-mediated pyroptosis in the pathogenesis of cardiac remodeling in pressure overload.
METHODS Wild-type (WT) and cardiomyocyte-specific GSDMD-deficient (GSDMD-CKO) mice were subjected to transverse aortic constriction (TAC) to induce pressure overload. Four weeks after surgery, left ventricular structure and function were evaluated by echocardiographic, invasive hemodynamic and histological analysis. Pertinent signaling pathways related to pyroptosis, hypertrophy and fibrosis were investigated by histochemistry, RT-PCR and western blotting. The serum levels of GSDMD and IL-18 collected from healthy volunteers or hypertensive patients were measured by ELISA.
RESULTS We found TAC induced cardiomyocyte pyroptosis and release of pro-inflammatory cytokines IL-18. The serum GSDMD level was significantly higher in hypertensive patients than in healthy volunteers, and induced more dramatic release of mature IL-18. GSDMD deletion remarkably mitigated TAC-induced cardiomyocyte pyroptosis. Furthermore, GSDMD deficiency in cardiomyocytes significantly reduced myocardial hypertrophy and fibrosis. The deterioration of cardiac remodeling by GSDMD-mediated pyroptosis was associated with activating JNK and p38 signaling pathways, but not ERK or Akt signaling pathway.
CONCLUSIONS In conclusion, our results demonstrate that GSDMD serves as a key executioner of pyroptosis in cardiac remodeling induced by pressure overload. GSDMD-mediated pyroptosis activates JNK and p38 signaling pathways, and this may provide a new therapeutic target for cardiac remodeling induced by pressure overload.
GW34-e1361
Qingbo Lv1,2, Yu Xiao1, Guosheng Fu1,2
1Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
2Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
OBJECTIVES Myocardial infarction (MI) is one of the leading cause of global mortality. Ferroptosis, a newly recognized iron-dependent form of cell death, plays a crucial role in progression of MI. The excessive deposition of free irons within cardiomyocytes is a vital cause of severe oxidative stress and lipid peroxidation, directly leading to the occurrence of ferroptosis. Therefore, therapeutic strategies targeting ferroptosis could potentially serve as a novel approach to treat myocardial infarction. In this study, we employed deferoxamine (DFO), a proven effective ferroptosis inhibitor, as our chosen therapeutic agent. However, DFO has an extremely short circulation half-life, making it unfeasible for sustained drug delivery in vivo. In response, we utilized chitosan (CS), a substance with excellent biocompatibility, to self-assemble nanoparticles as carriers. Through nanoscale self-assembly and chemical bonding, DFO was encapsulated within these nanoparticles, forming chitosan-deferoxamine nanosponges (CDNS) capable of adsorbing free iron.
METHODS To construct CDNS, deferoxamine was first dissolved in Dulbecco’s Modified Eagle Medium (DMEM), followed by the addition of CS. The pH was adjusted to 7.4 using 0.1 M Tris solution, and the complex was incubated for 2 hours to form CDNS. After obtaining CDNS, we performed standard material testing. High-performance liquid chromatography (HPLC) experiments were conducted to detect its release curve under different pH solutions and to examine its iron-binding capabilities. Subsequently, we tested the protective effect of CDNS on oxidative stress damage induced by hydrogen peroxide and ferroptosis induced by erastin. We then established a mouse MI model, and delivered CDNS to the margin of the infarcted myocardium via intramyocardial injection. Initially, using the water-soluble fluorescent dye indocyanine green (ICG), we confirmed the CDNS system’s ability for sustained drug release within the heart. Subsequently, with cardiac ultrasound, tissue section staining, and other methods, we focused on whether administration of CDNS improved heart function and reduced infarct size in post-MI mice, and ameliorated adverse myocardial remodeling post-infarction. Furthermore, we closely monitored the indicators of ferroptosis and angiogenesis in the hearts of mice post-MI surgery.
RESULTS First, we observed that CDNS were well-dispersed nanoparticles with diameters ranging from 50 to 200 nm through TEM. HPLC tests confirmed that CDNS were stable in a neutral solution environment, with minimal drug release. In acidic conditions, CDNS could sustainably release DFO and exhibited excellent iron-chelating capabilities. In the in vitro study, we found that CDNS could significantly alleviate oxidative stress damage in cardiomyocytes and inhibit myocardial ferroptosis. In animal experiments, we found that CDNS could achieve in-situ long-term drug release. From echocardiograms, we observed a significant improvement in heart function post-MI in mice treated with CDNS. CDNS significantly reduced apoptosis of myocardial cells and attenuated cardiac inflammation within the acute stage of MI. Meanwhile, CDNS significantly inhibited myocardial fibrosis and promoted angiogenesis in the infarcted area of the heart in the long-term.
CONCLUSIONS Our results suggest that CDNS are the powerful therapeutic approach for the prevention and treatment of MI by inhibiting ferroptosis and promoting angiogensis. Given their high efficacy and good biosafety, CDNS hold great promise for future clinical applications in the management of MI.
CARDIOVASCULAR DISCIPLINARY RESEARCH
PULMONARY VASCULAR DISEASE
GW34-e0131
Xin Li, Zhang Yi, Zhao Zhihui, Liu Zhihong
Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES The occurrence of complications associated with balloon pulmonary angioplasty (BPA) is frequent and may potentially lead to perioperative mortality. Nevertheless, the current academic literature lacks a predictive model pertaining to the complications related to BPA.
METHODS A retrospective analysis was performed on data obtained from a consecutive series of patients diagnosed with chronic thromboembolic pulmonary hypertension who underwent BPA. The main objective of the study was to investigate complications associated with BPA. The secondary endpoints of the study were mortality rates and hemodynamic changes observed following BPA.
RESULTS The study comprised 207 patients with chronic thromboembolic pulmonary hypertension who underwent a total of 614 sessions of BPA. During the study, complications were observed in 63 BPA sessions (10.26%) among 49 patients. The study findings revealed that hemoptysis or hemosputum (6.51%) was the most frequently encountered complication, whereas the incidence of pulmonary reperfusion edema was relatively low (0.49%). The results of multivariable logistic regression analysis indicated a significant correlation between BPA-related complications and disease duration, mean pulmonary arterial pressure, and the proportion of occlusion lesions. Subsequently, a nomogram was constructed and demonstrated superior predictive accuracy compared to previously reported predictors, as indicated by the area under the curve value of 0.703. Validation and calibration revealed a favorable level of accuracy, as evidenced by a slope of 0.978 and a Brier score of 0.163. Multivariable linear regression analysis that adjusted for the number of BPA sessions revealed that there was no significant correlation detected between the occurrence of complications and alterations in hemodynamics subsequent to BPA. Furthermore, patients who experienced complications exhibited a comparable 3-year survival rate to those who did not encounter such complications (98.0 vs. 94.8%, log-rank P=0.503).
CONCLUSIONS The nomogram, which incorporates multiple parameters such as mean pulmonary artery pressure, occlusion lesions, and disease duration, exhibits superior predictive capabilities for complications associated with BPA compared to individual parameters that have been previously reported. Notably, despite the occurrence of complications, the favorable effects of BPA on hemodynamics and survival were maintained. Thus, the presence of complications should not dissuade patients from pursuing ongoing BPA sessions.
GW34-e0195
Sun Na1,2, Fan Youli1,2, Chen Yansheng1,2, Gao Xuan1,2, Wang Yongbing1, Wu Bingxiang1,2
1Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
2Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, China
OBJECTIVES The aim of the present study was to evaluate the correlation of plasma DCA levels with clinical and hemodynamic parameters in patients with acute pulmonary embolism patients (APE).
METHODS We prospectively recruited 149 adult patients with APE. Plasma DCA levels were measured by rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry. Baseline clinical and hemodynamic parameters were evaluated according to different plasma DCA levels.
RESULTS Compared with controls, the plasma DCA levels are significantly lower (0.15 (0.10, 0.31) μg/mL versus 0.08 (0.04, 0.16) μg/mL, P<0.001) in APE patients. Recruited APE patients were divided into two groups according to the media plasma DCA levels (0.08 μg/mL), high DCA group and low DCA group. Compared with high DCA group, low DCA group patients present more adverse cardiac function with higher NT-proBNP levels (2629.0 (752.5, 6225.5) pg/mL versus 1262.0 (158.0, 4444.0) pg/mL, P=0.010), higher WHO functional class levels (P=0.023). Low DCA group also possess serious hemodynamic status, with higher PVR levels (4.3 (1.9, 6.4) Wood units versus 2.5 (1.6, 4.6), P=0.027) and lower CI levels (2.5±0.8 versus 2.8±0.8, P=0.024). For the correlation analysis between DCA and cardiac function and hemodynamic parameters, PVR was negatively correlated with plasma DCA levels (R=-0.198, P=0.027). CI was positively correlated with DCA level (R=0.205, P=0.024). For the cardiac functional parameters, NT-proBNP (R=-0.215, P=0.010) and WHO functional class (R=-0.187, P=0.022) were negatively correlated with plasma DCA levels. Kaplan–Meier survival analysis demonstrated that APE patients with lower plasma DCA levels had significantly higher event rate (P=0.009). In the univariate and multivariate Cox regression analysis, plasma DCA level was an independent predictor to clinical worsening event after adjusted by age, sex, WHO functional class, NT-proBNP, PVR and CI (HR 0.370, 95% CI 0.161, 0.852; P=0.019).
CONCLUSIONS Low plasma DCA levels predict adverse cardiac function and hemodynamic collapse. Low DCA level correlates with higher clinical worsening event rate and could be an independent predictor of clinical outcome in multivariate analysis.
GW34-e0199
Jingxian You1,2,3,4,5, Guili Lian1,2
1Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
2Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
3Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 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, People’s Republic of China
5Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China
OBJECTIVES Pulmonary arterial hypertension (PAH) is a pathophysiological syndrome, characterized by pulmonary vascular remodeling. Immunity and inflammation are progressively recognized properties of PAH, which are crucial for the initiation and maintenance of pulmonary vascular remodeling. This study explored immune cell infiltration characteristics and potential biomarkers of PAH using comprehensive bioinformatics analysis.
METHODS Microarray data of GSE117261, GSE113439 and GSE53408 datasets were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified in GSE117261 dataset. The proportions of infiltrated immune cells were evaluated by CIBERSORT algorithm. Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to identify feature genes of PAH, and fivefold cross-validation was performed using random forest and logistic regression. The GSE113439 and GSE53408 datasets were used as validation sets and logistic regression and receiver operating characteristic (ROC) curve analysis were performed to evaluate the prediction value of PAH. Weighted gene association network analysis (WGCNA) was used to identify modules associated with PAH. Intersection of genes in the modules screened and DEGs was used to construct protein-protein interaction (PPI) network and identify the core genes. After intersection of feature genes and core genes, the hub genes were identified. Pearson correlation analysis was performed to analyze the correlation between hub genes and immune cell infiltration. Western blotting and immunohistochemistry (IHC) were used to validate the expression of LTBP1 in the lungs and pulmonary arteries in monocrotaline-induced PH rats.
RESULTS A total of 419 DEGs were identified, including 223 upregulated genes and 196 downregulated genes. Functional enrichment analysis revealed that a significantly enrichment in inflammation, immune response, and transformed growth factor β (TGFβ) signaling pathway. CIBERSORT analysis showed that ten significantly different types of immune cells between PAH and control were identified. Seventeen feature genes were identified by LASSO regression for PAH prediction. WGCNA identified 15 co-expression modules. PPI network was constructed and 100 core genes were obtained. Complement C3b/C4b receptor 1 (CR1), thioredoxin reductase 1 (TXNRD1), latent TGFβ binding protein 1 (LTBP1) and toll like receptor 1 (TLR1) were identified as hub genes and LTBP1 has the highest diagnostic efficacy for PAH (AUC=0.968). Pearson correlation analysis showed that LTBP1 was positively correlated with resting memory CD4+ T cells, but negatively correlated with monocytes and neutrophils. We also comfirmed the expression of LTBP1 by Western blotting and immunohistochemistry and the results showed that protein levels of LTBP1 was increased in lungs and pulmonary arteries in PAH rats as compared to control.
CONCLUSIONS LTBP1 is upregulated and correlated to immune infiltration in PAH, identified as a new critical biomarker for PAH. Our study suggests that LTBP1 is involved in the development of PAH and serves as a potential diagnostic and therapeutic target for PAH.
GW34-e0208
Jingyuan Chen, Wenjie Chen, Zilu Li, Jun Luo, Li Li
The Second Xiangya Hospital of Central South University
OBJECTIVES Endoplasmic reticulum (ER) stress is involved in the development of pulmonary arterial hypertension (PAH), and glucose-regulated protein-78 (GRP78) is an important marker of ER stress in PAH. Most studies have shown that its expression is increased at the tissue and cellular levels during ER stress. Current studies have shown that its circulating GRP78 levels are also significantly increased in a subset of diseases and can be used as a disease biomarker.
METHODS For in vitro studies, cardiomyocytes and pulmonary arterial smooth muscle cells (PASMCs) were treated by hypoxia and platelet derived growth factor-BB. For in vivo studies, 18 rats were divided equally into three groups: 1) control group received saline injection, 2) MCT group received 60 mg/kg MCT intraperitoneally injection for once, 3) SuHx group received 20 mg/kg Sugeon 5416 once per week and were placed in hypoxia chamber for 3 weeks. Sixty-six PAH participants were recruited from Second Xiangya Hospital from July 2018 to July 2020. A detailed disease history and demographic data, disease related information were collected. Another 40 healthy control participants were recruited from physical examination center at the same period and verified with no cardiopulmonary disease by transthoracic echocardiography. For all plasma or culture medium samples, GRP78 levels are measured by ELISA.
RESULTS Extracellular GRP78 levels were significantly elevated in hypoxia-treated PASMCs and cardiomyocytes compared to the normoxic group (P<0.05 and P<0.001, respectively). Circulating levels of GRP78 were significantly elevated in the MCT and SuHx groups compared to the control group (P<0.05 and P<0.01, respectively). Circulating GRP78 levels were higher in PAH compared to healthy controls (3.20±2.03 vs 2.54±0.66 μg/mL, P<0.001). In subgroup analysis, GRP78 was higher in the IPAH, CHD-PAH, WHO-FC III/IV and medium-high risk groups. The primary endpoint event occurred in 30 patients over a median follow-up time of 20 (15–37) months. Univariate Cox regression analysis showed that GRP78 was a prognostic risk factor HR=1.422 (95% CI: 1.188–1.703) (P<0.001).
CONCLUSIONS In PAH, circulating GRP78 has significant increase and could be a prognostic risk biomarker for disease-free survival.
GW34-e0843
Wanying Xia1, Yuling Qian1, Qing Gu1, Changming Xiong1, Huijun Han2, Jianguo He1
1Department of Pulmonary Vascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Disease, Beijing, China
2Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China
OBJECTIVES Off-label targeted drugs are commonly prescribed for non-operated chronic thromboembolic pulmonary hypertension (CTEPH) in developed and developing countries, but their effect on the long-term prognosis of CTEPH remains unknown. This study aimed to investigate the effect of off-label targeted drugs on the long-term survival of CTEPH patients receiving pharmacotherapies.
METHODS The prospective national registry recruited patients diagnosed with CTEPH between 2009 and 2018 at 18 centers (ClinicalTrials.gov Identifier NCT01417338). Those from the CTEPH registry treated with pharmacotherapies were analyzed. Five-year survival was compared between patients using off-label targeted drugs and patients receiving conventional drugs in the original and propensity score-matched samples.
RESULTS Of 347 enrolled patients, 135 were treated with conventional therapy and 212 with off-label targeted therapy at baseline (173, initial targeted therapy) or during follow-up (39, subsequent targeted therapy). The 1-, 2-, 3-, and 5-year survival of patients with off-label targeted therapy was significantly higher than that of patients with conventional therapy (97.1 vs. 89.4%, 92.3 vs. 82.1%, 83.2 vs. 75.1%, and 71.1 vs. 55.3%, respectively, log-rank test, P=0.005). Initial targeted therapy was correlated with better 5-year survival after excluding patients with subsequent targeted therapy to reduce the immortal time bias (hazard ratio: 0.611; 95% confidence interval: 0.397–0.940; P=0.025). In propensity score-matched samples, patients given initial targeted therapy showed significantly better 5-year survival than those given conventional therapy (68.9 vs. 49.3%, log-rank test, P=0.008).
CONCLUSIONS Off-label targeted drugs contributed to improved long-term survival in CTEPH patients treated with pharmacotherapies.
GW34-e0851
Zhongchao Wang
General Hospital of Northern Theater Command
OBJECTIVES Hemoptysis is a rare but severe complication of advanced pulmonary arterial hypertension (PAH). Yet, no management consensus has been made till present. Importantly, the effect of targeted drug therapy (TDT) still remains unclear concerning its vasodilative effect on the pulmonary circulation, which may aggravate hemoptysis in the context of vascular rupture. Thus, the present study was designed to investigate short-term effects of continued use of TDT on outcomes of advanced PAH complicated by hemoptysis.
METHODS PAH patients associated with congenital heart disease (PAH-CHD) and complicated by hemoptysis from General Hospital of Northern Theater Command since Mar 2011 to Aug 2022 were retrospectively screened and grouped according to in-hospital targeted medication. 1:1 propensity score matching (PSM) analysis was conducted to adjust confounding factors.
RESULTS Seventy-four patients were included and allocated to TDT (n=39) or non-TDT (n=35) group. General comparison showed continued use of TDT was associated with significantly more days of in-hospital stay (P=0.045). No significant difference was found in mortality or other clinical outcomes, including time for hemoptysis termination and other symptom relief, WHO functional class and NT-proBNP at discharge. PSM analysis further selected 21 pairs of cases and showed no significant difference in mortality or other clinical outcomes between groups.
CONCLUSIONS These results have demonstrated no association between continued use of TDT and worse clinical outcomes of PAH-CHD patients complicated by occurrent hemoptysis, supporting continued use of TDT for patients with advanced PAH even when they are complicated by hemoptysis.
GW34-e1005
Gufeng Gao1,2,3,4,5, Ai Chen1,2,3,4,5, Guili Lian1,2,3,4,5, Li Luo1,2,3,4,5
1Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, People’s Republic of China
2Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, People’s Republic of China
3Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, People’s Republic of China
4Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
5Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, People’s Republic of China
OBJECTIVES This study aims to examine the changes in the PKC/IRS-1/ERK in the lung tissue of pulmonary arterial hypertension (PAH) rats induced by monocrotaline (MCT) and to investigate its role in the excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs).
METHODS
(1) 8-week-old male SD rats were injected intraperitoneally with 20 mg/kg MCT twice at a one-week interval to establish the PAH model. We measured mean pulmonary arterial pressure (mPAP) and right ventricular hypertrophy index (RVHI) four weeks after the first treatment. The percentage of wall area (WA%) and the percentage of wall thickness (WT%) are also calculated. The protein levels of protein kinase C (PKC), p-PKC, insulin receptor substrate 1(IRS-1), p-IRS-1, ERK and p-ERK in lung tissue were detected by Western blot.
(2) After starvation for 24 h, platelet-derived growth factor-BB (PDGF-BB), PKC inhibitor Gö 6983 and IRS-1-expressing adenovirus (AdIRS-1) were added for intervention. The expression of PKC, p-PKC, IRS-1, p-IRS-1, ERK, and p-ERK were detected by Western blot. EdU method was used to detect cell proliferation, while the scratch method was performed to observe cell migration.
RESULTS
(1) mPAP, RVHI, WA% and WT% of MCT-PAH rats were significantly increased four weeks after the first MCT administration,
(2) The expression levels of p-PKC, p-IRS-1 and p-ERK in the lung tissue of MCT-PAH rats were significantly elevated compared with control group. IRS-1 was decreased in the lung tissue of PAH rats; however, the difference in the expressions of PKC and ERK between those two groups was insignificant.
(3) The expression levels of p-PKC, p-IRS-1 and p-ERK were significantly increased after PDGF-BB stimulated PASMCs for 15 min; however, there was no statistically significant difference in expression levels of PKC, IRS-1 and ERK between the two groups.
(4) The expression of IRS-1 in PASMCs treated with PDGF-BB for 48 hours was significantly lower than that in the control group; while there was no statistically significant difference in expression levels of p-PKC, p-IRS-1, p-ERK, PKC and ERK between these two groups.
(5) After PKC inhibitor Gö 6983 treatment for 48 h, the expression of IRS-1 in PDGF-BB-PASMCs was significantly increased. The expression levels of p-PKC, p-IRS-1 and p-ERK were significantly lower than those in the control group and the PDGF-BB-PASMCs, while the differences in the expression levels of PKC and ERK among the three groups were not significant.
(6) After being infected with AdIRS-1, the expression of IRS-1 was increased while the level of p-ERK was downregulated compared with AdNull-PASMCs treated by PDGF-BB for 48 h.
(7) The PKC inhibitor Gö6983 and overexpression of IRS-1 inhibited the proliferation and migration levels of PASMCs 48 h after PDGF-BB induction.
CONCLUSIONS
1. Decreased expression of IRS-1 and its enhanced serine phosphorylation were observed in the lung tissue of PAH rats;
2. PDGF-BB promotes the excessive proliferation and migration of PASMCs through abnormal activation of PKC/IRS-1/ERK pathway.
3. Overexpression of IRS-1 can attenuate the proliferation and migration of PASMCs induced by PDGF-BB.
GW34-e1087
Zeying Zhang1, Yunbin Xiao2, Qiming Liu1
1The Second Xiangya Hospital of Central South University
2Hunan Children’s Hospital
OBJECTIVES Congenital malformations are an important cause of death in children whose important component is congenital heart disease (CHD). Mutations in a variety of genes can lead to CHD, including transcription factors, heart and vascular development, and other genes not related to transcription or translation. Pulmonary artery stenosis as a congenital heart disease is attracting increasing attention because of its association with pulmonary hypertension in children.
METHODS Whole exome sequencing (WES) was used to identify clinically relevant gene variants of proband associated with pulmonary artery stenosis. Sanger sequencing is used to identify candidate variants in all individuals of this Chinese family that can be used for familial co-isolation analysis. Bioinformatics tools were used to predict possible pathogenic mutations and multiple sequence alignments were performed. The pathogenicity of this variant was further evaluated by population-based screening of variant frequencies and American Society for Medical Genetics and Genomics (ACMG) scores.
RESULTS We identified a novel heterozygous deletion variant (c.69delC) on the first exon of the elastin gene ELN by WES. This variant resulted in frameshift mutation just before the protein hydrophobic region (p.Ser24Leufs). The deletion variant was present in the proband and his mother and uncle, but not in his father. Bioinformatic analysis predicted that this mutation would cause nonsense-mediated mRNA degradation (NMD) and be pathogenic.
CONCLUSIONS We shown a novel ELN frameshift mutation c.69delC (p.Ser24Leufs*98) in a family, which expands the understanding of the phenotypic characteristics of mutations in the ELN gene. Patients with pulmonary artery stenosis carrying the ELN variant should be given more attention.
GW34-e1090
Sicheng Zhang, Luyang Gao, Zhihua Huang, Zhihui Zhao, Qin Luo, Qing Zhao, Zhihong Liu
Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
OBJECTIVES Emerging evidence has showed that outdoor artificial light at night (ALAN) is closely associated with healthy sleep and cardiovascular health. However, few studies have investigated the association between ALAN and sleep disorders. The unique pathophysiologic contributions of obstructive sleep apnea (OSA) toward pulmonary hypertension still represent an understudied area. This study aims to investigate the association of ALAN with OSA and pulmonary hemodynamics.
METHODS From January 1, 2020 to December 31, 2021, a total of 1005 participants were recruited from Fuwai Hospital. Apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were measured by polysomnography or home sleep test. Participants’ daytime sleepiness scores were evaluated using the Epworth Sleeping Scale (ESS). Right cardiac catheterization was performed in OSA patients with high suspicion of pulmonary hypertension. Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 1000 m of each participant’s residential address obtained from the satellite imagery data. Generalized linear regression models were used to assess the associations of exposure to outdoor ALAN with OSA indexes and right heart catheterization metrics after adjusting for multiple covariates.
RESULTS Of 859 OSA patients (38.7% male), 453 had pulmonary hypertension. In adjusted models, an inter-quartile range (IQR) increase in outdoor ALAN exposure was significantly associated with 11.3% (95% confidence interval [95% CI]: 4.2%, 18.8%) and 10.0% (95% CI: 2.7%, 17.6%) increases in AHI and ODI, respectively. Furthermore, an IQR increase in outdoor ALAN exposure was significantly associated with 4.7% (95% CI: 0.4%, 9.2%) and 7.0% (95% CI: 2.6%, 11.5%) increases in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR), respectively. Mediation analyses suggested that the effect of outdoor ALAN exposure on mPAP could be partly mediated by ODI.
CONCLUSIONS Our study indicates that higher exposure to outdoor ALAN was significantly associated with higher AHI, ODI, mPAP and PVR in patients with OSA in North China. The effect of outdoor ALAN exposure on pulmonary hemodynamics is mediated partly by OSA indexes.
GW34-e1092
Sicheng Zhang, Luyang Gao, Qin Luo, Zhihui Zhao, Qing Zhao, Zhihong Liu
Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
OBJECTIVES Emerging evidence has showed that Blood urea nitrogen to serum albumin ratio (BAR) is associated with the severity and prognosis of heart failure. However, its role in pulmonary arterial hypertension (PAH) remains unclear. The aim of this study was to investigate the associations between BAR and functional status, echocardiography, hemodynamics as well as long-term outcomes among patients with PAH.
METHODS Consecutive patients who underwent right heart catheterization and diagnosed with idiopathic or heritable PAH between January, 2014 and December, 2021 in Fuwai hospital were enrolled. The primary outcome was clinical worsening. Spearman correlation coefficients were used to evaluate the association between BAR and established markers of PAH severity. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff and predictive performance of BAR. Kaplan–Meier analysis and Cox proportional hazard models were used to assess the relationship between BAR and clinical worsening.
RESULTS A total of 472 patients with idiopathic or heritable PAH were included in the study. BAR was correlated with well-validated variables that reflected severity of PAH, such as World Health Organization functional class, 6-min walk distance, N-terminal pro-brain natriuretic peptide (NT-proBNP), mixed venous oxygen saturation and cardiac index. Kaplan–Meier curves indicated that patients with BAR>3.28 had a significantly higher clinical worsening rate (log-rank test, P<0.001) than those with BAR=3.28. Multivariable Cox analysis showed that BAR could independently predict clinical worsening [Hazard ratio (HR): 1.265, 95% confidence interval (CI) 1.072–1.494, P=0.005]. Further, ROC curve analysis showed that BAR provided additional predictive value in addition to the established PAH biomarker NT-proBNP.
CONCLUSIONS BAR could reflect disease severity and was independently associated with prognosis in patients with PAH.
GW34-e1094
Sicheng Zhang, Luyang Gao, Zhihui Zhao, Qing Zhao, Qin Luo, Zhihong Liu
Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
OBJECTIVES Greenness has been associated with cardiovascular health, whereas higher air pollution exposure is linked with increased risks of chronic diseases. To date, limited studies have explored the interaction between residential greenness and air pollution on the clinical outcome in patients with pulmonary arterial hypertension (PAH).
METHODS This study analyzed 457 patients with idiopathic or heritable PAH recruited from Fuwai hospital. The normalized difference vegetation index (NDVI) around each participant’s residence was used to characterize greenness exposure. The air pollution data were derived from the China High Air Pollutants (CHAP) dataset, which was used to analyze individual long-term exposure to air pollution, including particulate matter with aerodynamic diameters =2.5 μm (PM2.5) and =10 μm (PM10). Cox proportional hazard models were used to describe the association of residential greenness and air pollutants with the long-term outcome of patients with PAH. Associations of residential greenness and air pollutants with PAH risk stratification and hemodynamic severity at baseline were assessed.
RESULTS Higher estimated exposure to greenness was associated with lower risk of death (hazard ratio (HR)=0.875, 95% confidence interval (CI): 0.773, 0.981 per 0.1-unit increment in NDVI) after adjusted for potential confounding variables. However, long-term exposures to air pollution were associated with higher mortality (HR=1.422, 95% CI: 1.194, 1.692 per 10 μg·m-3 for PM2.5; HR=1.318, 95% CI: 1.160, 1.497 per 10 μg·m-3 for PM10). Mediation analyses suggested that the beneficial effect of residential greenness on long-term outcomes of PAH could be partly mediated by reducing the exposure to PM2.5. In addition, an increase in residential greenness exposure was associated with lower PAH risk score at baseline, reducing the likelihood of being diagnosed within the European Society of Cardiology (ESC)/European Respiratory Society (ERS) intermediate-high risk clinical stratification. Residential greenness correlated with pulmonary hemodynamics at baseline. This association was strongest for cardiac index.
CONCLUSIONS In idiopathic or heritable PAH, higher residential greenness exposure was associated with lower mortality and higher probability of ESC/ERS low-risk categories when diagnosed, while air pollutants were positively associated with long-term mortality. Meanwhile, residential greenness may improve the outcomes of PAH by reducing exposure to PM2.5.
GW34-e1152
Luying Sun1, Xuegang Xie2, Zhenwen Yang3, Bin Jia4, Lan Wang5, Qiguang Wang6, Jiang Li7, Hong Gu8, Weiping Xie9, Nuofu Zhang10, Fenling Fan11
1Johnson and Johnson (China) Investment Ltd, Shanghai, China
2First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi, China
3Tianjin Medical University General Hospital, Tianjing, China
4Johnson and Johnson (China) Investment Ltd, Shanghai, China
5Shanghai Pulmonary Hospital, Shanghai, China
6General Hospital of Northern Theater Command, Shenyang, Liaoning, China
7The Second Xiangya Hospital of Central South University, Changsha, Hunan
8Beijing Anzhen Hospital, Capital Medical University, Beijing, China
9Jiangsu Province Hospital, Nanjing, Jiangsu, China
10The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
11First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi, China
OBJECTIVES Current ESC/ERS Guidelines for the management of pulmonary arterial hypertension (PAH) recommend initial combination therapy with an endothelin receptor antagonist (ERA, e.g. macitentan) and a phosphodiesterase type 5 inhibitor (PDE5i, e.g. tadalafil). For patients without comorbidities and a low/intermediate risk status at diagnosis. A single-tablet fixed dose combination of macitentan 10 mg and tadalafil 40 mg (M/T FDC) would add convenience, increase adherence and ultimately improve clinical outcomes. A DUE evaluated the efficacy and safety of M/T FDC vs monotherapies in PAH. This subgroup analysis aims to explore whether the efficacy and safety of the M/T FDC in Chinese participants are consistent with the overall population.
METHODS A DUE was a multicenter, double-blind Phase 3 adaptive study (NCT03904693) and randomized WHO FC II-III PAH patients: 2:1:1 to M/T FDC, macitentan, or tadalafil, if treatment-naïve; 2:1 to M/T FDC or macitentan, if on prior ERA; and 2:1 to M/T FDC or tadalafil, if on prior PDE5i. The primary endpoint was change in pulmonary vascular resistance (PVR), expressed as the Week 16: baseline ratio of geometric means. Safety/tolerability was also assessed.
RESULTS In the A DUE study, 187 participants were randomized (108 to M/T FDC, 35 to macitentan, and 44 to tadalafil) across 16 countries/territories, including 23 participants in China (13 to M/T FDC, 5 to macitentan, and 5 to tadalafil). Demographics and baseline disease characteristics of Chinese participants were generally consistent with the overall population. As for the overall population, a higher proportion of WHO FC II patients was observed in the M/T FDC arm. In the overall population, PVR reduction with M/T FDC was significantly greater vs macitentan (29%) and vs tadalafil (28%) (Week 16 to baseline PVR ratio 0.71 [95% adjusted repeated confidence limits (RCL): 0.61, 0.82, P<0.0001] for M/T FDC vs macitentan and 0.72 [95% adjusted RCL: 0.64, 0.80, P<0.0001] for M/T FDC vs tadalafil). Consistent results were observed for the primary endpoints in Chinese participants compared with the overall population, with PVR reductions of 50% for M/T FDC vs macitentan (50%) and of 41% for M/T FDC vs tadalafil (41%) (adjusted geometric mean ratios vs. monotherapy were 0.5 [95% CL: 0.35, 0.72, P=0.0017] for M/T FDC vs macitentan and 0.59 [95% CL: 0.43, 0.80, P=0.0040] for M/T FDC vs tadalafil in Chinese participants.) No clinically important differences were observed between the overall population and Chinese participants in the incidence of AEs, SAEs, and AEs leading to premature discontinuation. In overall population, there were 3 deaths (reported as drug-unrelated) in the M/T FDC arm, no deaths were reported in Chinese participants. Adverse events (AE) leading to discontinuation, serious AE and those of special interests (anemia, hypotension, edema) were more frequent in the M/T FDC arm.
CONCLUSIONS M/T FDC significantly improved PVR vs monotherapies in PAH pts, with a safety and tolerability profile consistent with the known profile of the individual components. The observed efficacy results and safety profile for M/T FDC in the Chinese participates were generally consistent with the overall population.
GW34-e1236
Rui Wang1, Jie Wang2, Yun Wu1
1Department of General Medicine, First Affiliated Hospital of Xinjiang Medical University
2Department of Pharmacy, First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES The exact mechanism by which Mfn2 participates in the interaction between the endoplasmic reticulum (ER) and mitochondria remains unclear. Based on our previous studies, we propose that Mfn2 may facilitate the transport of Ca2+ from the ER to the mitochondria by interacting with the calcium channel receptor IP3R in the mitochondria-associated endoplasmic reticulum membranes (MAMs) pathway. This process is crucial for maintaining Ca2+ homeostasis in the cytoplasm, thereby inhibiting the proliferation of pulmonary arterial smooth muscle cells (PASMCs), reducing pulmonary artery stenosis, and lowering pulmonary artery hypertension (PAH).
METHODS (1) The rat model of PAH was established using monocrotaline, and intervention with 4-PBA was conducted. Hemodynamic parameters, including mean pulmonary artery pressure and mean right ventricular pressure, were measured using a biological information acquisition system. Pulmonary vascular remodeling changes were observed through hematoxylin-eosin staining, and relevant indicators of pulmonary vascular remodeling were quantified using ImageJ pathological analysis software. Mitochondrial status in PASMCs was examined under electron microscopy. The mRNA and protein expression levels of key factors involved in the endoplasmic reticulum stress (ERS) pathway were measured using qPCR and Western blotting techniques. (2) In the inflammation-induced injury model of PASMCs stimulated by TNF-α, adenoviral transduction was employed to overexpress or silence Mfn2. Furthermore, intervention with the IP3R3 inhibitor Xestospongin C was performed. Under electron microscopy, the fusion and fission status of mitochondria were observed. Apoptosis and proliferation were assessed using flow cytometry and the CCK-8 assay. The concentrations of Ca2+ in the endoplasmic reticulum, cytoplasm, and mitochondria were measured using fluorescent probes. The mRNA and protein expression levels of key factors involved in the endoplasmic reticulum-mitochondria pathway for Ca2+ transport were determined using qPCR and Western blotting.
RESULTS (1) Following 4-PBA intervention in monocrotaline-induced rat models for PAH, there was a significant decrease in mPAP (53.89±4.69 vs 22.34±1.21) and mRVP (29.61±1.94 vs 17.24±1.59). Additionally, there was a notable improvement in pulmonary arteriole remodeling. The extent of normal mitochondrial structural damage was reduced, and mitochondrial autophagy was decreased. The expression levels of key factors involved in the ERS pathway (Perk/elF2α/Atf4/CHOP) were suppressed, while the expression levels of Mfn2 and IP3R3 were upregulated. (2) In the TNF-α-induced inflammatory injury model of PASMCs, compared to the TNF-α group, overexpression of Mfn2 resulted in an increased number of mitochondria with normal structure and intact mitochondrial cristae. The concentration of Ca2+ within the mitochondria significantly increased, while the cytoplasmic Ca2+ concentration decreased significantly. The expression of key factors involved in ERS pathway, including Perk/elF2α/Atf4/CHOP, was downregulated. Additionally, the expression levels of Drp1, OPA1, and IP3R3 were also decreased. Following the addition of the IP3R3 inhibitor Xestospongin C to the TNF-α group, cell proliferation was suppressed, and apoptosis was increased. The concentration of Ca2+ within the mitochondria increased, while the cytoplasmic Ca2+concentration decreased. The expression of eIF2a, CHOP, and VDAC1 were inhibited, while the mRNA and protein expression of Mfn2 and SEACA were upregulated.
CONCLUSIONS Targeted intervention of Mfn2 can influence intracellular Ca2+ transport by interacting with the key calcium transporter protein IP3R3 on MAMs, thereby reducing calcium overload in PASMCs during PAH and maintaining intracellular Ca2+ homeostasis. This mechanism inhibits excessive proliferation of PASMCs and provides a new perspective for targeted therapy in PAH.
GW34-e1258
Lu Yan, Zhihui Zhang
Department of Cardiovascular Medicine, and the Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Army Medical University
OBJECTIVES Pulmonary arterial hypertension (PAH) is a life-threatening condition with poor prognosis. Due to its high fatality rate and limited therapies, the pathogenesis of PAH needs to be explored urgently.
METHODS Transcriptome data of patients including PAH from the GSE113439, GSE117261 and GSE15197 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified. Hub genes were identified by constructing a protein-protein interaction (PPI) network with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and analyzing in Cytoscape. Further, gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation were performed. CIBERSORT was used to compare immune cells composition in PAH and control groups. Correlations between immune cells and hub genes was analyzed in GSE113439 and validated in GSE117261.
RESULTS Four hundred and fifty-six integrated DEGs with 205 up-regulated and 251 down-regulated were identified, which are mainly enriched in inflammation and immune response GO terms and KEGG pathways, including cell chemotaxis, myeloid leukocyte migration and IL-17 signaling pathway. Forty-four hub genes were selected in top PPI modules. The percentages of resting memory CD4+ T cells and activated dendritic cells were significantly higher in PAH tissues; resting NK cells, monocytes and neutrophils were significantly lower.
CONCLUSIONS Resting memory CD4+ T cells, activated dendritic cells, resting NK cells, monocytes and neutrophils may play important roles in immune responses in the development of PAH. CCL5, ITGAM, FGR, CCL7, S100A8, CCR1, HMOX1 contributing to the pathogenesis of PAH via diverse mechanisms.
GW34-e1282
Jiang Yu, Yongzheng Guo, Suxin Luo
Division of Cardiology, The First Affiliated Hospital of Chongqing Medical University
OBJECTIVES Pulmonary vascular leakage is a prevalent outcome of sepsis, resulting in acute lung injury. We have reported a positive correlation between S100 calcium-binding protein (S100) A8/S100A9 and inflammation-associated damage before. However, limited knowledge exists concerning the biological role of S100A8/A9 in pulmonary vascular endothelial barrier dysfunction, as well as the diagnostic and prognostic value of S100A8/A9 in sepsis.
METHODS Sepsis was induced in C57BL/6J mice and S100A9-knockout (KO) mice lacking the S100A8/A9 heterodimer through the cecal ligation and puncture (CLP) technique. Disease severity was evaluated using the rectal temperature, carotid pressure, and survival rate. Pulmonary vascular leakage was determined by measuring extravasated Evans blue (EB). Reverse transcription polymerase chain reaction and the histological score were used to evaluate inflammation and lung injury, respectively. Immunofluorescence staining and Western blotting were used to evaluate occludin and vascular endothelial (VE)-cadherin expressions in the lungs. Recombinant S100A8/A9 (rhS100A8/A9) was used to identify the effects of S100A8/A9 on endothelial barrier dysfunction in human umbilical vein endothelial cells (HUVECs). Additionally, the diagnostic and prognostic value of S100A8/A9 in sepsis was assessed using receiver operating characteristic and Kaplan–Meier curves.
RESULTS S100A8/A9 expression was up-regulated in the lungs of CLP-operated mice. S100A9 KO in mice significantly reversed CLP-induced hypothermia and hypotension, resulting in an improved survival rate compared with wild-type mice. S100A9 KO also decreased the inflammatory response, EB leakage, and histological scores in the lungs of CLP-operated mice. Occludin and VE-cadherin expressions were decreased in the lungs of CLP-operated mice; however, S100A9 KO attenuated this decrease. Moreover, CLP-induced signal transducer and activator of transcription 3 (STAT3) and p38/extracellular signal-regulated kinase (ERK) signalling activation and apoptosis were mitigated by S100A9 KO in lungs. In addition, rhS100A8/A9 administration significantly decreased occludin and VE-cadherin expressions, increased the phosphorylated (p)-ERK/ERK, p-p38/p38, and B-cell leukaemia/lymphoma 2 protein (Bcl-2)-associated X protein/Bcl-2 ratios in HUVECs. Finally, our findings further support the potential of S100A8/A9 as a diagnostic and prognostic biomarker for human sepsis.
CONCLUSIONS The present study demonstrated a novel role of S100A8/A9 in the progression of sepsis-induced pulmonary inflammation, vascular permeability, and lung injury. This was achieved, at least partially, by activating the P38/STAT3/ERK signalling pathways. Therefore, these findings provide valuable insights into a potential therapeutic target for preventing and treating sepsis-induced pulmonary vascular leakage and lung injury.
DIABETES, CEREBROVASCULAR DISEASES, KIDNEY-DISEASES, CARDIO-ONCOLOGY
GW34-e0053
Houyong Zhu1, Xiaoqun Xu2
1Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University
2Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine
OBJECTIVES The purpose of this study was to evaluate the predictive value of the inflammation based Glasgow Outcome Scale (GPS) for cardiovascular death in patients with diabetes.
METHODS This study included 4956 patients (=18 years old) with diabetes in the National Health and Nutrition Survey from 1999 to 2010. The death result is determined by the correlation with the national death index on December 31, 2019. GPS is composed of serum C-reactive protein and albumin. The primary outcome was cardiovascular death and the secondary outcome was all-cause death. The Cox proportional risk model adjusted for demographic factors and traditional cardiovascular risk factors was used to analyze the cumulative risk of outcomes.
RESULTS Among 4956 diabetes patients with a median follow-up of 10.9 years, 601 cardiovascular deaths and 2187 all-cause deaths were recorded. After adequate model adjustment, compared with the low GPS group, the high GPS group [HR, 1.257 (1.007–1.570), P=0.043] had a higher cardiovascular mortality. Compared with the low GPS group, the all-cause mortality of the high GPS group [HR, 1.394 (1.245–1.560), P<0.001] was higher. The trend of subgroup analysis was consistent with that of the overall cohort.
CONCLUSIONS The high level of baseline GPS is closely related to the increased risk of cardiovascular and all-cause death in patients with diabetes. GPS may be a convenient and efficient clinical practical risk assessment tool for diabetes patients.
GW34-e0064
Chan Li1, Zhaoya Liu2
1Xiangya Hospital, Central South University
2Third Xiangya Hospital, Central South University
OBJECTIVES Patients with diabetes mellitus (DM) has a higher mortality and morbidity of ischemic heart disease (IHD). This study aimed to analyze the quantitative analyze the trends and topics of publications related to DM-related IHD in the past three decades.
METHODS Publications indexed under the Medical Subject Headings (MeSH) term “Diabetes Mellitus” and “Myocardial Ischemia” from 1992 to 2021 were obtained from PubMed. Metadata were extracted by R package for bibliometric analyses. MeSH analyses and Latent Dirichlet allocation (LDA) were conducted to speculate research hot spots and establish a topic network to illustrate their relationships.
RESULTS A total of 17,850 publications were included in this study, the quantity of publications constantially increased and reached the peak in 2004. Most of the studies were clinical studies. In MeSH analyses, coronary angiography, body mass index, and biomarkers were recognized as the leading terms of diagnosis. Hypoglycemic agents, coronary balloon angioplasty, and coronary artery bypass were the top terms of treatment. Stroke, life style and recurrence were the top terms of prognosis. Three clusters, including diagnosis and manifestation, epidemiology and mechanism, and treatment and prognosis, were identified by LDA analyses. Most studies focused on the treatment and prognosis of DM-related IHD. Risk factors and biomarkers were the most studied topics.
CONCLUSIONS The annual publication on DM-related IHD scarcely changed during the past two decades. Risk factors and biomarkers attracted most attentions in the field of DM-related IHD. More basic studies should be performed to figure out the associations and specific mechanisms between DM and IHD.
GW34-e0123
Rui Wang1,2,3, Ya-Rong Zhang1,2,3, Yong-Fen Qi1,2,3
1State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China
2Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, Beijing, China
3Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
OBJECTIVES Vascular calcification is an independent risk factor for cardiovascular events and an important cause of death and disability in patients with type 2 diabetes mellitus (T2DMs). Vascular calcification is common in diabetic patients and multiple factors promote the occurrence and development of diabetic vascular calcification. However, there is still no effective treatment for diabetic vascular calcification. As a new cardiovascular bioactive peptide, intermedin (IMD)/adrenomedullin 2 (ADM2) plays a protective role in cardiovascular disease. Our previous work showed that IMD could inhibit chronic kidney disease- and age-related vascular calcification. However, the role and mechanism of IMD in diabetic vascular calcification remain unknown.
METHODS Plasma of T2DM patients and healthy controls were used for detecting IMD contents. In vivo, male Sprague-Dawley (SD) rats and Adm2 knockout/transgenic mice were used in the experiment to induce diabetic vascular calcification, IMD was administered with subcutaneous Alzert mini-osmotic pumps in the last 4 weeks of the experiment. In vitro, rat and mouse vascular smooth muscle cells (VSMC) were treated to induce VSMC calcification. Histochemical staining was used to observe vascular morphology and calcium deposition in blood vessels. Enzyme-linked immunosorbent assay, colorimetric method and Western blot were performed to detect the levels of diabetes and vascular calcification-related molecules.
RESULTS IMD level was decreased in the plasma of diabetic patients and rats and calcified rat aortas. Meanwhile, Adm2 mRNA expression was significantly down-regulated in calcified aortas of diabetic rats, and its receptor calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1) were increased, RAMP3 was decreased. Exogenous IMD reduced fructose-induced calcium deposition, calcium contents and expression levels of VSMC osteogenic markers in diabetic rat aortas. Endogenous Adm2 deficiency aggravated and Adm2 overexpression attenuated vascular calcium deposition and alkaline phosphatase (ALP) activity in diabetic mice induced by high-fat diet. In addition, IMD significantly inhibited the high glucose induced rat vascular smooth muscle cell (VSMC) calcium deposition, calcium contents, ALP activity and expression levels of osteogenic markers. Adm2 deficiency exacerbated mouse VSMC calcium deposition and further decreased the expression levels of contractile markers induced by high glucose. Further studies showed that IMD diminished ROS production in diabetic rat calcified aortas and high glucose-treated VSMC. IMD reduced diabetic vascular calcification by inhibiting the rat plasma advanced glycation end products (AGEs) concentration and reducing the receptor for AGEs (RAGE) expression level in calcified aortas and VSMCs.
CONCLUSIONS IMD alleviated diabetic vascular calcification by inhibiting AGEs/RAGE and subsequent oxidative stress.
GW34-e0128
Zidun Wang, Huiyuan Qin, Minglong Chen
Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
OBJECTIVES Previous clinical studies have shown that ibrutinib increases the risk of atrial fibrillation (AF) in chronic lymphocytic leukemia (CLL) patients. However, the mechanism underlying ibrutinib-related AF is not fully understood. Herein, we investigated the proportion of patients with new-onset AF in a CLL cohort treated with ibrutinib.
METHODS Optical mapping was conducted to reveal the proarrhythmic effect of ibrutinib on HL-1 cells. The expression levels of connexins 43 and 40 (Cx43 and Cx40) were further compared between cells that were treated with ibrutinib or the blank control using fluorescence staining and western blotting. Moreover, autophagy-related protein expression was investigated, and an inhibitor of autophagy was administered to reverse the detrimental effect of ibrutinib.
RESULTS As a result, 5% of patients developed atrial arrhythmias after ibrutinib administration. HL-1 cells that were treated with ibrutinib had significantly lower conduction velocity and higher incidence of reentry-like arrhythmia than control cells. In parallel, the expression of Cx43 and Cx40 was significantly decreased and the levels of autophagy markers were increased in HL-1 cells that were treated with ibrutinib. Inhibition of autophagy increased the expression of Cx43 and Cx40. Hence, ibrutinib could induce connexin degradation, thus contributing to atrial arrhythmia, by inducing autophagy via its off-target effect on the PI3K-AKT-mTOR signaling pathway.
CONCLUSIONS Our study provided a new perspective on the mechanisms by which ibrutinib causes atrial arrhythmias and potential intervention targets for treatment.
GW34-e0231
Zhiyue Liu, He Huang
West China hospital, Sichuan University
OBJECTIVES Cancer therapy-related cardiovascular toxicity (CTR-CVT) is a major contributor to poor prognosis in breast cancer (BC) patients undergoing chemotherapy. Left ventricular global longitudinal strain (LV GLS) has predictive value for CTR-CVT, while few researchers take into account late-onset CTR-CVT. This study sought to provide a guide for the prediction of late-onset CTR-CVT in primary BC over the 2 years follow-up via strain and contrast-enhanced echocardiography.
METHODS Anthracycline and anthracycline + targeted medication groups were created from 111 patients with stage I–III primary BC who were prospectively included. The left ventricular diastolic function, LV global long-axis strain (GLS); left ventricular ejection fraction by contrast-enhanced echocardiography (c-LVEF), and electrocardiograms were collected at baseline, 3, 6, 12 and 24 months after the start of cancer treatment. The high-sensitivity troponin-T and NT-pro BNP at baseline and 3 months after chemotherapy were measured.
RESULTS 1) LV GLS decreased in BC patients over time. 2) After 12 months’ follow-up, the LV GLS in the anthracycline+ targeted group was lower than in the anthracycline group. After 24 months’ follow-up, the GLS and c-LVEF in the anthracycline + targeted group declined while the E/e’ increased. 3) Decreased LVEF (56%) and arrhythmia (38%) are the common causes of CTR-CVT. Lower LVEF was a major factor in late-onset CTR-CVT. 4) Combination of LV GLS and c-LVEF at 3 months were used as predictors for CTR-CVT exhibited a higher AUC than either one alone (AUC=0.929, 95% CI: 0.863–0.970). LV GLS at 3 months can predict the late-onset CTR-CVT (AUC=0.745, P<0.001) and the cut-off is 20.32%.
CONCLUSIONS As time went on, the systolic and diastolic dysfunction of BC patients get worsened. The combination of LV GLS and c-LVEF is better in the prediction of CTR-CVT. Only the LV GLS at 3 months can predict the late-onset CTR-CVT.
GW34-e0317
Zhihui Zhu1,2, Chenyu Li1
1Medizinische Klinik und Poliklinik IV, Klinikum der Universität München
2Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Dual inhibition of the renin-angiotensin system (RAS) and sodium-glucose transporter (SGLT)-2 as well as dual RAS and mineralocorticoid receptor (MR) antagonism have demonstrated renoprotective effects in large clinical trials but whether a triple combination is even more potent is unclear. We hypothesized that triple RAS/SGLT2/MR blockade would be superior to dual RAS/SGLT2 blockade in prolonging kidney lifespan.
METHODS We performed a preclinical randomized controlled trial in Col4a3-deficient mice with spontaneous and progressive CKD (registry ID: PCTE0000266). At 6 weeks of age 50% male and 50% female mice were randomized in a 1:1:1:1 manner to 8 weeks of nil or food admixes of ramipril (exposure dose 10 mg/kg), ramipril plus empagliflozin (30 mg/kg) or ramipril, empagliflozin plus finerenone (10 mg/kg). The prespecified primary endpoint was total lifespan to uremic death. Ancillary studies examined empagliflozin and finerenone monotherapy, baseline histology, and mechanisms.
RESULTS At the time of randomization, Col4a3 −/− mice had albuminuria, elevated serum creatinine, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Total lifespan was 63.7±10.0 days (vehicle), 77.3±5.3 days (ramipril), 80.3±11.0 days (ramipril+empagliflozin), and 103.1±20.3 days (triple therapy), respectively. Total lifespan was 70.4±9.2 for empagliflozin and 71.1±7.1 for finerenone monotherapy, respectively. Histopathology and RNA sequencing analysis documented a potent anti-sclerotic, anti-inflammatory, and fibrotic effect of the triple combination.
CONCLUSIONS Adding finereone to dual RAS/SGLT2 blockade significantly prolongs uremia-free lifespan even when started at an advanced stage of Alport nephropathy. Triple RAS/SGLT2/MR blockade could be a potent treatment strategy to prolong uremia-free lifespan in patients with CKD related to Alport syndrome and possibly other progressive kidney disorders.
GW34-e0321
Kaiyi Chi1, Tianwang Guan2
1Department of Clinical Medicine, The Second Clinical College of Guangzhou Medical University
2Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University
OBJECTIVES Cardiovascular disease (CVD) is the leading cause of death worldwide. Of concern, older survivors with female-specific cancer (including breast and gynecologic cancers) may have an increased risk of CVD death, owing to estrogen deficiency, anticancer-therapy cardio-toxicities and common risk factors of cancer and CVD. Thus, more attention should be focused on the CVD death risk of older survivors with female-specific cancer. However, there are relatively few studies concerning CVD death risk of older patients with female-specific cancer. Therefore, we performed a comprehensive analysis to evaluate the risk of CVD death in 3 highly prevalent cancers among older female patients with the following two objectives: 1) to quantify the risk of CVD death in the older female-specific cancer compared to the general older population; 2) to identify and characterize age subgroups with a higher CVD death risk. These findings will provide a scientific evidence for CVD death risk management strategies for older survivors with female-specific cancer.
METHODS Older patients (over 65 years) of female-specific cancer diagnosed between 1975 and 2018 were included. The common of cancer in older female, including breast, endometrium and vulva, was defined as female-specific cancer. The proportion of deaths, competing-risk regressions models, standardized mortality ratios (SMRs), and absolute excess risks (AERs) were used to assess the risk of CVD deaths among older patients with female-specific cancer.
RESULTS This study included 230,742 older female patients (195,106 breast cancers, 30,862 endometrium cancers and 4774 vulva cancers). The risk of CVD death exceeded primary neoplasm death in older patients with cancers of the breast, endometrium and vulva over time. Compared to the general older population, increased SMR and AER of CVD death were observed in older patients with breast cancer (SMR 1.24–4.20; AER 36.45–487.77), endometrium cancer (SMR 1.17–3.56; AER 26.03–390.28) and vulva cancer (SMR 2.41–5.76; AER 215.27–725.50). Older patients with female-specific cancer diagnosed after more than 15 years had higher risk of CVD death than those diagnosed after less than 15 years. Compared to the general older population, older breast cancer had increased SMR and AER of CVD death in those diagnosed at 65–74 years (SMR 2.19–14.09; AER 45.80–505.43), those diagnosed at 75–84 years (SMR 1.61–8.85; AER 81.29–1050.73) and those diagnosed at 85+ years (SMR 1.36–3.99; AER 196.11–1634.60). Compared to the general older population, older endometrium cancer had increased SMR and AER of CVD death in those diagnosed at 65–74 years (SMR 1.71–12.01; AER 27.56–424.94), those diagnosed at 75–84 years (SMR 1.46–7.10; AER 61.40–816.55) and those diagnosed at 85+ years (SMR 1.34–4.54; AER 184.91–1934.47). Compared to the general older population, older vulva cancer had increased SMR and AER of CVD death in those diagnosed at 65–74 years (SMR 3.68–18.40; AER 103.65–671.81), those diagnosed at 75–84 years (SMR 2.47–10.63; AER 196.20–1289.73) and those diagnosed at 85+ years (SMR 1.56–5.10; AER 307.24–2243.97).
CONCLUSIONS For older cancers patients, common female-specific cancers including breast, endometrium and vulva were at high risk of CVD death. With the extension of follow-up years after diagnosis, the risk of CVD death may increase correspondingly. Strategies for long-term cardiovascular care in older patients with female-specific cancer are needed.
GW34-e0346
Haowei Li1, Shige Qi2, Zhihui Wang2, Miao Liu3, Yao He1,4
1Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, Second Medical Center of Chinese PLA General Hospital, Beijing 100853, China
2National Center for Chronic and Non-Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China
3Department of Statistics and Epidemiology, Graduate School of PLA General Hospital, Beijing 100853, China
4State Key Laboratory of Kidney Diseases, Beijing 100853, China
OBJECTIVES Cardiometabolic diseases (CMDs), including diabetes, coronary heart diseases, stroke and hypertension, increases the risk of cognitive decline, but the extent to which this can be offset by adherence to an active integrated lifestyle is unknown. We aimed to associations of CMDs with early cognitive decline and explore the role of integrated lifestyle in this association.
METHODS The participants were from PINDEC Project. A total of 2537 dementia-free older adults≥60 years old who completed the 2015 baseline survey and the 2017 follow-up survey with a cognitive function status assessment were included. Lifestyle factors (including physical exercise, social interaction, leisure activities, sleep quality, smoking status, and alcohol consumption) were collected through questionnaires and the integrated score was calculated. Participants were divided into three groups based on integrated score tertiles (inactive, =3 score; intermediate, 3 score; and active,≥5). Logistic regression was used in data analysis.
RESULTS 35.2% participants had 5–6 healthy components, while only 5.4% of all the participants had all 6 healthy lifestyles. The multiadjusted odds ratios (ORs, 95% confidence interval) of early cognitive decline was 1.223 (0.799–1.871) and 1.832 (1.140–2.943) for participants who had only one CMD and any two or more CMDs, respectively. For integrated lifestyle scores, an inverse dose-response relationship was found between lifestyle scores and early cognitive decline (Ptrend=0.017). In participants with active lifestyle, the OR for early cognitive decline comparing the CMDs status of any two or more CMDs vs. CMDs-free was 0.778 (95% CI: 0.302–2.007). Participants with inactive lifestyle and any two or more CMDs had a near 3.4-fold increased risk of early cognitive decline than those without CMDs who had intermediate to active lifestyle (OR=3.435, 95% CI: 1.772–6.660).
CONCLUSIONS A dose–response relationship exists between CMDs status and risk of early cognitive decline. However, adherence to an active integrated lifestyle may mitigate this risk.
GW34-e0435
Lihua Liao1, Xingmo Dong2, Yani Wang1, Xueqin Lin1, Ying Liao2, Huaijing Luo2, Yu Yi2
1The Third Clinical Medical College, Fujian Medical University
2Longyan First Affiliated Hospital of Fujian Medical University
OBJECTIVES The incidence of kidney stone disease has increased worldwide over the past decades, resulting in high medical costs and social burden. Kidney stone disease shares some common features with the risk factors of cardiovascular diseases (CVDs). Here, we investigated the association between cardiovascular health (CVH) based on the Life’s Essential 8 (LE8) score developed by the American Heart Association and the incidence of kidney stone disease in US adults.
METHODS We analyzed the data of 29,469 US adults aged 20 years or above from the National Health and Nutrition Examination Survey, 2007–2018. The components of LE8 included diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. According to the LE8 score, CVH was divided into three categories: poor, intermediate, and ideal. Logistic regression was used to determine the association between CVH and the incidence of kidney stone disease by estimating odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS The average age of the participants was 48.6 years, and 50% of the participants were women. The numbers of participants with poor, intermediate, and ideal CVH were 4149, 19,782, and 5538, respectively. After adjusting for related confounding factors, ideal CVH was associated with a reduction in the odds of kidney stone occurrence as compared to poor CVH (adjusted OR [aOR]: 0.45, 95% CI: 0.35–0.57, P<0.001). Moreover, if the ideal CVH score was≥6, the odds of kidney stone occurrence decreased by up to 61% (aOR: 0.39, 95% CI: 0.30–0.51).
CONCLUSIONS In the present study, ideal CVH, a factor indicative of a healthy lifestyle, was associated with lower odds of kidney stone occurrence. These findings suggest that interventions to prevent CVDs are also expected to prevent kidney stone occurrence.
GW34-e0579
Hongzhao You, Heng Zhang, Xiaojue Li, Xinxing Feng, Rong Guo, Hansong Sun, Wei Feng, Guangwei Li, Zhe Zheng, Yanyan Chen
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Uncontrolled blood glucose level is a risk factor for postoperative complications after coronary artery bypass grafting (CABG). However, the association between postoperative blood glucose fluctuation and in-hospital adverse events in patients with diabetes remains unknown. The Largest Amplitude of Glycemic Excursions (LAGE), which serves as a reliable indicator of short-term blood glucose fluctuation, is acknowledged as a potent risk factor for diabetes-related complications. We aimed to determine the effect of post-operative blood glucose variability on in-hospital adverse events in diabetic patients undergoing CABG.
METHODS We reviewed medical records for diabetic patients who received CABG at Fuwai Hospital from January 2011 to December 2014. The variability of postoperative glucose during the initial 5 days was gauged by LAGE. Subgroups were divided based on whether the LAGE was equal to or above 4.4 mmol/L. The primary endpoint encompassed a composite endpoint incorporating in-hospital all-cause mortality and major cardiovascular complications. The secondary endpoint encompassed major cardiovascular complications such as acute myocardial infarction, stroke, and acute kidney injury.
RESULTS The study enrolled 3387 eligible patients, among which 241 (7.1%) patients met the composite endpoint. When compared to patients with LAGE below 4.4 mmol/L, the ones with LAGE equal to or above 4.4 mmol/L exhibited a higher rate of both the composite endpoint (6.2 vs 10.2%, P<0.001) and major vascular complications (6.1 vs 10.2%, P<0.001). Moreover, LAGE equal to or above 4.4 mmol/L is an independent risk factor for the composite endpoint (OR=1.69, 95% CI 1.26–2.25, P<0.001) and major vascular complications (OR=1.74, 95% CI 1.30–2.32, P<0.001) after adjusting for the established risk factors (age, sex, BMI, smoking, low density lipoprotein cholesterol, chronic renal failure, congestive heart failure, stroke, previous myocardial infarction and peripheral vascular diseases).
CONCLUSIONS Patients who exhibit a LAGE equal to or above 4.4 mmol/L are subject to an elevated risk of in-hospital adverse events. Relatively large blood glucose fluctuations (LAGE equal to or above 4.4 mmol/L) after CABG is significantly associated with in-hospital adverse events in patients with diabetes who underwent CABG.
GW34-e0640
Cong Liu, Xiaozeng Wang
General Hospital of Northern Theater Command
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 1week, 3weeks, 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.
GW34-e0657
Yilan Li, Yao Zhang
Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University,
OBJECTIVES Sorafenib is a standard first-line treatment for advanced hepatocellular carcinoma. However, the serious cardiotoxic effect restricted its clinical application. We previously have illuminated the protective role of canonical Slc7a11/GPX4 signaling in sorafenib-induced cardiotoxicity. Meanwhile, ferroptosis suppressor protein 1 (FSP1) is recently identified as a seminal breakthrough owing to its property of versus ferroptosis. In this study, we investigated the protective effect of FSP1 in sorafenib-induced cardiotoxicity in vitro and in vivo.
METHODS The expression of FSP1 was significantly decreased in rat cardiomyocyte (H9c2), mouse cardiomyocyte (HL-1) (5 μM) cell lines and mice heart (30 mg/kg/injection for 14 days i.p.), which can be partially prevented by treatment with ferroptosis inhibitor Ferrostatin-1(Fer-1).
RESULTS Sorafenib reduced levels of ferroptotic markers involving glutathione peroxidase 4 (GPX4), increased PTGS2, reactive oxygen species (ROS), malonaldehyde (MDA), apart from causing obvious mitochondria damage, which were alleviated by Fer-1. Overexpression of FSP1 protected cells from ferroptosis, while knock-down of FSP1 made cardiomyocytes sensitive to ferroptosis caused by sorafenib. Meanwhile, we found that knockdown for FSP1 showed similar results to GPX4 knockdown, and FSP1 overexpression can largely abrogate GPX4 inhibition-induced ferroptosis. iFSP1, a potent FSP1 inhibitor, was used to induce ferroptosis in GPX4 knockout cells. We found iFSP1 selectively induced ferroptosis in GPX4-knockout cells that overexpressed FSP1.
CONCLUSIONS Based on these findings, we concluded that FSP1-mediated ferroptosis is one of the key mechanisms leading to sorafenib-induced cardiotoxicity. Targeting ferroptosis may be a novel therapeutic approach for preventing sorafenib-induced cardiotoxicity in the future.
GW34-e0800
Yemin Li1,2, Tianwang Guan3,4, Caiyun Ou5
1Department of Clinical Medicine, The First Clinical College of Guangzhou Medical University, Guangzhou 510182, China
2Cardiovascular Medicine and Cardio-Oncology Group, Medical Exploration and Translation Team, Guangzhou 510000, China
3Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
4Dongguan Hospital of Southern Medical University (Dongguan People’s Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Guangzhou 510280, China
5The 10th Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Guangzhou 510280, China
OBJECTIVES Penile cancer is a rare malignancy, with almost 35,000 new cases worldwide every year. The incidence peak is around 60 years of age and increases with increasing age. Recently, Cardiovascular disease (CVD) has become the leading cause of death for cancer patients, which should receive more attention in older patient with penile cancer. Neoadjuvant chemotherapy as the strategy of treatment before surgical consolidation may exposes patients to cardiac toxicity, such as paclitaxel, ifosfamide and cisplatin. In addition, shared risk factors between penile cancer and CVD suggest CVD as a frequent co-morbidity of penile cancer, including chronic inflammation and smoking. Therefore, reinforcing our understanding and management of CVD may help improve survival in older patients with penile cancer. However, due to the rarity of this disease, there is still a lack of research to explore the risk of CVD death in older patients with penile cancer. Our study aimed to assess the risk of CVD death in older patients with penile cancer.
METHODS Older patients with penile cancers aged over 65 years were included in the study. The proportions of deaths, competing-risk regressions models, standardized mortality ratios (SMRs), and absolute excess risks (AERs) were utilized to evaluate the risk of CVD death.
RESULTS This study included 1283 older patients with a median follow-up of 13.5 years. Older patients with penile cancer were at a higher risk of CVD death. The proportions of CVD death increased witha peak in 5 to 10 years following diagnosis (except subgroup age 85+) and the proportions of primary neoplasms death tended to decrease. The cumulative mortality from CVD death exceeded primary neoplasm death 5–10 years after the cancer diagnosis. Compared with the general older population, older patients with penile cancer had higher risk of CVD death with increased SMR and AER (SMR 1.70–9.13; AER 133.01–1145.74).
CONCLUSIONS For older patients, penile cancer was at a higher risk of CVD death which exceeded primary neoplasm death over the survival time and became the major cause of death. Long-term strategies for cardiovascular care and a multidisciplinary approach in older patients with penile cancer are imperative.
GW34-e0964
Yan Wei, Xiaoping Wang, Guanjing Ling, Yong Wang
Beijing University of Chinese Medicine
OBJECTIVES Doxorubicin (DOX), as a first-line chemotherapy agent, plays an irreplaceable role in anti-tumor therapy. However, cumulative doses of DOX can cause severe cardiotoxicity even put cancer patients at risk for developing dilated cardiomyopathy. Up to now, the precise molecular mechanisms underlying the progression of DOX-induced cardiac remodeling (DICR) remain puzzling. Mitochondrial bioenergy is critical for maintaining healthy cardiac function. Previously, we have demonstrated that Traditional Chinese medicine compound of Qishen granule (QSG), which is composed of Radix Astragali mongolici, Radix Salvia miltiorrhizabunge, Flos Lonicerae, Radix Scrophulariae, Radix Aconiti Lateralis Preparata, and Radix Glycyrrhizae, possesses beneficial effects on mitochondrial ecosystem. Here, we aim to evaluate whether QSG exerts protective effects on DICR and identify the deep regulatory mechanism.
METHODS C57BL/6 mice were injected with DOX (5 mg/kg) through the tail vein once every 7 days for 4 weeks to establish the DIC model. In vivo, the mice were divided into four groups, control group, model group, QSG group and Enalapril (positive drug) group. The protective effect of QSG on the heart was evaluated by echocardiographic assessment, histological examination, myocardial hypertrophy and energy metabolism gene (qPCR) and pathway protein (Western blots) analysis. Mechanistically, H9c2 cells were induced with 1 μmol/L DOX, combined with Rev-erbα siRNA, Cpt1b siRNA model, exerted Seahorse analysis and Mito-SOX immunofluorescence for mitochondrial function, and Phalloidin immunofluorescence for evaluate cell hypertrophy to further investigate pharmacodynamic mechanism of QSG.
RESULTS In vivo, QSG effectively improved the cardiac structure and function of DICR mice. Further, QSG promoted mitochondrial structural and functional integrity, reduced ROS production and enhanced oxidative metabolism, of which reversed DICR. Moreover, the protein levels of Rev-erbα and Cpt1b were up-regulated, and E4bp4 was down-regulated in the hearts of DICR mice treated with QSG. Mechanistically, the protective effects conferred by QSG against mitochondrial oxidative stress, cardiomyocyte hypertrophy and apoptosis were counteracted by Rev-erbα gene silencing in vitro. Meanwhile, the expression of E4bp4 was increased and Cpt1b was decreased. Of note, after interfering with Cpt1b, the protective effect of QSG was also weakened, but the expression of Rev-erbα and E4bp4 were not affected.
CONCLUSIONS In summary, the results demonstrated QSG could prevent from DICR by regulating the Rev-erbα-E4bp4-Cpt1b axis, which plays an indispensable role in cardiac energy metabolism This study will provide a potential approach for the treatment of DOX induced clinical cardiotoxicity.
GW34-e1012
Mekhman Mamedov, Azamat Karimov, Ksenia Badeynikova, Bahodir Mardanov
National Research Center for Therapy and Preventive Medicine
OBJECTIVES The chronic noncommunicable diseases remain the leading cause of disability and death among adults in the developed world. Their total share in mortality is about 77%. Cancers, along with cardiovascular diseases (CVD) associated with atherosclerosis, are among the top three causes of death in the adult population. According to the forecast of WHO experts, in the next 5–10 years, CVD will account for 26.5% in the structure of mortality, and 8.5% for cancers of various localization. Determination of the comorbidity of somatic diseases in patients with coronary artery disease and cancer of various localization plays an important role in the development of treatment tactics in order to improve the prognosis and quality of life.
METHODS The cross-sectional clinical study included 220 men and women aged 40–65 years. Depending on the presence of coronary artery disease and cancer of various localization, patients were divided into two group. The first group with ischemic heart disease and lung cancer (n=110), the second group with ischemic heart disease and colon cancer (n=110). In stationary conditions, with the help of clinical and instrumental studies, other somatic diseases were recorded in patients.
RESULTS According to results among patients with lung cancer and colon cancer, the most common disease was AH. In patients with cancer of both localizations, its frequency was comparable, 76 and 75%, respectively. The comorbidity of somatic diseases is also associated with the cancer’s localization. Type 2 diabetes in the group with lung cancer was diagnosed in 13.6% of cases, while in the group with bowel cancer it occurred twice as often, in 26% of cases. In the group with lung cancer, stomach diseases were detected in almost every second patient (44.5%), among people with bowel cancer this figure reached 70% of cases (P=0.034). Concomitant chronic obstructive pulmonary disease in patients with lung cancer was diagnosed in 62% of cases, and in the group of patients with bowel cancer it was 3.5 times less and amounted to 18% (P<0.001).
CONCLUSIONS Thus, in patients with coronary artery disease and cancer, additional somatic diseases are identified that are associated with cancer localization. When developing secondary prevention, it is necessary to take into account the presence of additional diseases that play an important role in the prognosis and quality of life of patients.
GW34-e1034
Fei Liu, Peiling Mi, Chenglin Li, Xiaolei Yang, Yunlong Xia
First Affiliated Hospital of Dalian Medical University
OBJECTIVES The aim of this study is to analyze and compare the distribution of cardiovascular (CV) comorbidities, risk factors and Electrocardiograph (ECG) parameters and other baseline characteristics in patients with primary Lung cancer (LC) and Thyroid cancer (TC), with the aim of providing a reference for the monitoring, early prevention and treatment of CV toxicity in these patients.
METHODS This study retrospectively included 15,145 patients who were hospitalized at the First Hospital of Dalian Medical University with a primary diagnosis of LC and TC between January 1, 2011 and May 31, 2022. Patients were finally included. General information, cardiovascular comorbidities, risk factors and electrocardiographic parameters were collected and statistically analyzed for both groups.
RESULTS 1. LC and TC patients carry a high burden of CV comorbidities at the time of initial diagnosis. The most common comorbidity in both groups was hypertension (20.2%), and the occurrence rate of hypertension was significantly higher in the LC group than in the TC group (21.8 vs. 16.6%, P<0.001), followed by coronary heart disease (8.1%), myocardial infarction (2.0%), atrial fibrillation (1.0%), atrial premature beats (0.7%), atrial tachycardia (0.4%), ventricular tachycardia (0.4%), and atrial flutter (0.3%), which were all significantly higher in the LC group than in the TC group (P<0.001); 2. The most common abnormal ECG parameter was prolonged QTc interval (15.4%), followed by increased P-wave duration (5.4%) and increased Sokolow-Lyon index (4.1%). The occurrence rates of prolonged QTc interval (16.8 vs. 12.3%, P<0.001), prolonged P-wave duration (5.5 vs. 4.1%, P<0.001), and increased Sokolow-Lyon index (4.9 vs. 2.7%, P<0.001) were significantly higher in the LC group. 3. After adjusting for age and sex, binary logistic regression analysis revealed that LC patients with concomitant low hemoglobin had a significantly increased risk of prolonged QTc interval (OR=1.01, 95% CI: 1.0–1.01, P<0.001), while TC patients with concomitant high systolic blood pressure (OR=3.3, 95% CI: 2.02–5.36, P<0.001), low hemoglobin (OR=0.98, 95% CI: 0.96–1, P=0.037), and low potassium (OR=0.38, 95% CI: 0.17–0.8, P=0.012) had a significantly increased risk of prolonged QTc interval. 4. In this study, a total of 142 patients (6.2%) with prolonged QTc interval and concomitant low potassium were identified. Among these patients, 25 (44%) in the LC group and 38 (45%) in the TC group did not undergo dynamic monitoring of potassium levels, and 28 (49%) in the LC group and 45 (53%) in the TC group did not receive potassium supplementation.
CONCLUSIONS Patients with initial diagnosis of LC and TC often have comorbid CV diseases or multiple CV risk factors even before initiating anti-tumor treatment. A considerable proportion of patients have abnormal ECG parameters, with prolonged QTc interval being the most common. Patients with prolonged QTc interval and concomitant hypokalemia account for a certain proportion in both the LC and TC groups, but the rate of close monitoring and potassium supplementation for these patients during hospitalization is relatively low, indicating inadequate management of CV risk factors in cancer patients in current clinical practice.
GW34-e1047
Zeya Li1, Shanshan Wu2, Dan Li3, Gang Wang1, Na Zhang1, Feng Zhao3, Jing Hao3, Chunlei Yang3, Jiashu Song3, 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 unclear. In this study, the effects of UA levels on kidney function (KF) in patients with normal versus impaired 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) and impaired KF group (60=eGFR<90 mL/min/1.73 m2). The primary endpoint was the composite of a decrease in eGFR of≥30% from baseline or new onset of CKD diagnosed during the annual checkups. Multivariate logistic and restricted cubic splines models were employed to evaluate potential associations.
RESULTS A total of 284 participants reached the primary endpoint during the 5-year follow-up period. There was a significant association 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 impaired 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.
CONCLUSIONS Baseline KF is predictive of the association of increased UA levels and decreased KF. Patients with 60=eGFR<90 mL/min/1.73 m2 could benefit from UA-lowering therapy.
GW34-e1128
Junzhen Li
Zhongnan Hospital of Wuhan University
OBJECTIVES The objective of this study was to examine the correlation between fluctuations in metabolic syndrome (MetS) status and the occurrence of cardiovascular diseases (CVD), stroke, and all-cause mortality.
METHODS This prospective cohort study consisted of 4840 individuals who participated in the China Longitudinal Study of Health and Retirement (CHARLS) form 2011 to 2018. Participants were classified according to the change in their MetS status as follows: MetS-free at both time point (n=2169), MetS-recovery (n=744), MetS-developed (n=534), and MetS-chronic (n=1393). CVD and stroke were defined as the presence of physician-diagnosed heart disease and stroke. Logistic regression models were done to calculate the odd ratio (ORs) and confidence intervals (95% CIs).
RESULTS These participants were followed up in 2018. During follow-up period, 346 (7.1%) participants developed CVD, 246 (5.1%) participants developed stroke in 4840 participants in the longitudinal cohort. Compared with the MetS-free group, MetS-chronic increased the risk of CVD (adjusted OR, 1.40 [CI, 1.07 to 1.83]) and stroke (adjusted OR, 2.56 [CI, 1.83 to 3.58]). However, the increased risk in all MetS status were not significant for all-cause mortality. When stratified by age of MetS status changes, compared with the MetS-free group, MetS-chronic (<65 years) had higher risks of CVD (adjusted OR, 1.45 [CI, 1.03 to 2.05]), MetS-chronic (=65 years) had higher risks of stroke (adjusted OR, 2.81 [CI, 1.66 to 4.75]). In both genders, the MetS-chronic group had the highest risk of stroke, respectively, in women (adjusted OR, 3.32 [CI, 1.90 to 5.75]) and men (adjusted OR, 2.28 [CI, 1.46 to 3.58]), compared with the MetS-free group.
CONCLUSIONS Dynamic changes of MetS altered the risks of CVD and stroke, MetS-chronic increased the risk of CVD and stroke.
GW34-e1202
Xinhai Cui1, Yuanlong Hu2, Mengkai Lu3, Zhiyuan Zhang3, Yunlun Li3, Chao Li3
1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine
2First Clinical Medical College, Shandong University of Traditional Chinese Medicine
3Innovation Research Institute of traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine
OBJECTIVES Carotid femoral pulse wave velocity has been found to be an independent predictor of both cardiovascular mortality and kidney injury, which can be estimated non-invasively using estimated pulse wave velocity (ePWV). The objective of this study was to investigate the association between ePWV and in-hospital mortality of critically ill patients diagnosed with acute kidney injury (AKI).
METHODS This study included 5960 AKI patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The low and high ePWV groups were compared using a Kaplan–Meier survival curve to evaluate differences in survival status. Cox proportional hazards models were utilized to explore the association between ePWV and in-hospital mortality among critically ill patients with AKI. To examine the dose-response relationship further, we used a restricted cubic splines (RCS) model. Additionally, stratification analyses were conducted to investigate the effect of ePWV on hospital mortality across various subgroups.
RESULTS Survival analysis results indicated that high ePWV had lower survival rate compared with low ePWV. Following adjustment, high ePWV demonstrated a statistically significant association with increased risk of in-hospital mortality among AMI patients (HR=1.84, 95% CI=1.62–2.08, P<0.001). Analysis using RCS model confirmed a linear increase in the risk of hospital mortality as ePWV values increased (P for nonlinearity=0.602).
CONCLUSIONS High ePWV was significantly associated with increased risk of in-hospital mortality among AKI patients. Furthermore, ePWV proved to be an independent predictor of hospital mortality in critically ill individuals with AKI.
GW34-e1214
Xixiang Tang1, Jiafu Wang2, Yesheng Ling2, Xiaolan Ouyang2, Qian Chen2, Long Peng2, 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 Risk of contrast-induced nephropathy (CIN) is markedly increased in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship between the adipose tissue thickness and the CIN in T2DM patients following coronary catheterization.
METHODS A total of 603 T2DM patients undergoing percutaneous coronary angiography or angioplasty were enrolled in this study. The thicknesses of perirenal fat (PRF), subcutaneous fat (SAT), intraperitoneal fat (IPT) and epicardial fat (ECF) were measured by Color Doppler Ultrasound respectively. The association of various adipose tissues with CIN were analyzed.
RESULTS Out of the 603 patients, 77 (12.8%) developed CIN. Patients who developed CIN had significantly thicker PRF (13.7±4.0 mm vs. 8.9±3.6 mm, P<0.001), slightly thicker IPT (P=0.046), and similar thicknesses of SAT (P=0.782) and ECT (P=0.749) compared to those who did not develop CIN. Correlation analysis showed that only PRF was positively associated with maximal sCr postoperatively (r=0.18, P=0.012), maximal absolute change (r=0.33, P<0.001) and maximal percentage of change in sCr (r=0.36, P<0.001). In ROC analysis, the area under the curve of PRF (0.809) for CIN was significantly higher than those of SAT (0.490), IPT (0.594) and ECT (0.512). Multivariate logistic regression analysis further confirmed that the thickness of PRF, rather than other adipose tissues, was independently associated with the development of CIN after adjusted for confounding factors (OR=1.53, 95% CI: 1.38–1.71, P<0.001).
CONCLUSIONS PRF is independently associated with the development of CIN in T2DM patients undergoing coronary catheterization.
GW34-e1260
Yan Ma, Dong Han, Shasha Sun, Feng Cao
Second Medical Centre & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
OBJECTIVES Despite the irreversible cardiotoxicity, anthracyclines, represented by doxorubicin, are still widely used to treat various tumors, which necessitates more effective strategies to lessen their cardiotoxicity. The role of cancer-heart crosstalk in DOX-induced cardiotoxicity (DOXIC) remains unidentified.
METHODS A co-culture system was used to observe the effects of DOX-injured BCCs on DOXIC in cardiomyocytes. EXOs derived from DOX-treated BCCs (4T1 cell, D-BCC-EXOs) were extracted and purified to examine their effects on adult murine ventricular cardiomyocytes (AMVC) injury and pyroptosis. An orthotopic breast cancer mouse model was used to explore whether EXOs could aggravate DOXIC in vivo. Exosomal miRNA sequencing and mechanistic studies were used to identify the functional miRNAs encapsulated in D-BCC-EXOs. Bioinformatics analysis combined with experimental validations were used to explore the upregulation and selective packaging mechanism of the functional miRNAs in D-BCC-EXOs as well as the downstream targets of the identified miRNAs.
RESULTS DOX-induced AMVCs injury and pyroptosis can be worsened by co-culturing with 4T1 BCCs as well as D-BCC-EXOs treatment in vivo and in vitro. Depletion of BCCs’ miRNA cargo by Dicer knockout blocked the effect of D-BCC-EXOs to aggravate DOXIC. Exosomal miRNA sequencing and mechanistic investigations identified that miR-216a-5p was highly expressed in DOX-induced EXOs from both DOX-treated tumor-bearing mouse serum and 4T1 BCCs and functioned as a cardiomyocytes pyroptosis aggravator both in vivo and in vitro. Mechanistically, DOX-induced ATF3 promotes miR-216a-5p transcription in BCCs, and ATF3 knockdown attenuated the pro-pyroptotic effects of D-BCC-EXOs. RNA binding protein-associated assays showed that SF3B4 bound to miR-216a-5p and facilitated the selective packaging and delivery of miR-216a-5p to BCC-D-EXOs. ITCH was identified as a bona fide target mRNA of miR-216a-5p, and miR-216a-5p-mediated ITCH decay reduced TXNIP ubiquitination and degradation to activate the TXNIP/NLRP3 inflammasome pathway to incite pyroptosis in cardiomyocytes, thereby aggravating DOXIC.
CONCLUSIONS Taken together, our study found that EXO-mediated pathological communication between BCCs and cardiomyocytes caused additional cardiac injury in the setting of DOXIC. This effect is achieved through the exosomal transfer of miR-216a-5p from DOX-induced BCCs to cardiomyocytes and activation of the ITCH/TXNIP/NLRP3 inflammasome pathway to predispose cardiomyocytes to DOX-induced pyroptosis. Targeting the pathological EXOs releasing or blocking miR-216a-5p may be an effective strategy to mitigate additional cardiac injury in DOXIC.
GW34-e1287
Lichuan Chen, Jilang Zeng, Kaiyang Lin, Yansong Guo
Shengli Clinical Medical College of Fujian Medical University, Department of Cardiology, Fuzhou, China
OBJECTIVES Contrast-associated acute kidney injury (CA-AKI), a common cause of hospital-acquired AKI, is related to poor outcome. Recent studies suggested that a novel biomarker described as the derived neutrophil-to-lymphocyte ratio (dNLR) can reflect systemic inflammation and is related to the adverse outcome of coronary heart disease, chronic inflammatory diseases, and cancers. However, it is unclear whether dNLR has the capacity to predict CA-AKI and long-term mortality in patients receiving elective percutaneous coronary intervention (PCI). The aim of the current study was to assess the predictive value of dNLR for the occurrence of CA-AKI and long-term mortality in patients undergoing elective percutaneous coronary intervention.
METHODS This was a retrospective analysis of 5807 consenting patients from January 2012 to December 2018. The dNLR is calculated by the following formula: neutrophil count/(leukocyte count - neutrophil count). CA-AKI was defined as an increase in serum creatinine≥50% or 0.3 mg/dL within 48 hours after contrast medium exposure.
RESULTS Overall, the incidence of CA-AKI after PCI was 6.1% (n=352). Based on receiver operating characteristic (ROC) curves, a baseline dNLR value of 1.77 was used as the best cut-off for predicting CA-AKI. The patients were divided into low dNLR group (dNLR<1.77) and high dNLR group (dNLR=1.77) according to the cut-off value. The dNLR showed an area under the curve (AUC) of 0.618 [95% confidence interval (CI): 0.589–0.649] in predicting CA-AKI. Multivariate logistic analysis revealed that the dNLR=1.77 was independently associated with the incidence of CA-AKI (odds ratio=1.45, 95% CI: 1.12–1.88, P=0.004). There were 499 (8.6%) deaths during the median follow-up of 2.85 years. Kaplan–Meier survival analysis suggested dNLR=1.77 was significantly associated with worse outcomes (P<0.001). Furthermore, the patients in the high dNLR group had a significantly higher risk of all-cause death than those in the low dNLR group (hazard ratio=1.35, 95% CI: 1.11–1.65, P=0.003) in the fully adjusted Cox proportional hazards model.
CONCLUSIONS In patients treated with elective PCI, dNLR is an independent predictor of CA-AKI and long-term mortality.
GW34-e1289
Qiaorui Wen1,2, Shengfeng Wang1,2
1Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China
2Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China
OBJECTIVES To investigate whether Life’s Essential 8 (LE8) could attenuate the association between cancer and incident cardiovascular diseases (CVD).
METHODS The baseline survey of UK Biobank study (ethics approval No. 16/NW/0274) was conducted in 2006–2010, and followed up till 2021. Exposure and covariates information were collected through baseline questionnaires. Cardiovascular health (CVH) was divided into low (<50), moderate (50–79), and high (=80) according to LE8 score, which included diet, physical activity, smoke, sleep, BMI, non-HDL cholesterol, blood glucose, and blood pressure. CVD (I20–I25, I60–I69) diagnosis were ascertained through electronic linkage. Hazard ratios (HR) and 95% confidence intervals (CI) for the associations of cancer diagnosis and chemotherapy with incident CVD were estimated by Cox regression, with adjustment for sociodemographic characteristics, lifestyles and family history. Joint analysis was conducted to investigate the effect of cancer diagnosis and CVH on CVD risk.
RESULTS Among 270,807 participants free of CVD at baseline and with complete data on LE8, 10.91% were cancer survivors. The mean±SD age was 55.9±8.1 years. Over a median 12.5-year follow-up, 25,353 CVD cases were recorded. Compared with the general population, cancer survivors had a 21% (95% CI 1.17–1.25) higher risk of incident CVD. While considering the CVD subtypes, cancer survivors had higher risks of incident coronary heart disease and stroke, with HR (95% CI) of 1.18 (1.13, 1.23) and 1.26 (1.19, 1.34). Compared with non-cancer patient (despite of their CVH), cancer survivors with low or moderate CVH had 100% (1.75–2.29) and 23% (1.18–1.28) higher CVD risks respectively, while those with high CVH had no increased risk (0.95, 0.86–1.05). Compared with those free of cancer but with low CVH, cancer survivors with low CVH had were associated 19% (1.03–1.37) higher risk of CVD, while those with moderate or high CVH were associated with lower risks of CVD, with HR (95% CI) of 0.72 (0.68, 0.77) and 0.56 (0.50, 0.62), respectively.
CONCLUSIONS Achieving higher CVH could attenuate or even counteract the increased CVD risk in cancer survivors.
GW34-e1359
Meizhen WU1,2, Jiayi Huang1,2, Qingwen Ren1,2, Kai-Hang Yiu1,2
1The University of Hong Kong, Queen Mary Hospital
2The University of Hong Kong-Shenzhen Hospital
OBJECTIVES Sodium-glucose cotransporter-2 (SGLT2) inhibitors are increasingly prescribed due to its potential cardiorenal protective effect, while it was demonstrated to be associated with increased risk of urinary tract infection (UTI). Whether to continue or stop SGLT2 inhibitors after experiencing a UTI remains unclear. The aim of present study is to explore the association of incident UTI with subsequent cardiovascular and renal events. Additionally, the impact of continuing versus stopping SGLT2 inhibitors after UTI on subsequent cardiovascular and renal events.
METHODS We recruited patients with T2DM prescribed SGLT2 inhibitors from 2015 to 2022 from Clinical Data Analysis and Reporting System in Hong Kong. The primary outcomes were major adverse cardiovascular events (MACE), a composite of renal outcome, all-cause mortality, and recurrent UTI. UTI was modelled as time-varying covariates. A Fine-Gary model was applied to adjust for competing risk. Multivariable Cox proportional hazards model was used to estimate the risk of UTI versus non-UTI and continuing versus stopping SGLT2 inhibitors after UTI on subsequent adverse events.
RESULTS Among 63,799 SGLT2 inhibitors users, 4769 (7.48%) patients developed incident UTI during a median follow-up of 1.80 years. After UTI, 1836 (38.50%) patients stopped using SGLT2 inhibitors. UTI was associated with higher risk of MACE [hard ratio (HR) 2.02, 95% confidence interval (CI) 1.83–2.23], a composite of renal outcome (HR 2.01, 95% CI 1.83–2.19), and all-cause mortality (HR 3.90, 95% CI 3.58–4.25). Stopping SGLT2 inhibitors after incident UTI was associated with lower risk of recurrent UTI (HR 0.70, 95% CI 0.61–0.85), but higher risk of a composite of renal outcome (HR 1.61, 95% CI 1.35–1.91), MACE (HR 1.25, 95% CI 1.04–1.51) and all-cause mortality (HR 2.54, 95% CI 2.21–2.92).
CONCLUSIONS UTI has been linked to increased risk of cardiovascular and renal outcomes in patients with T2DM compared to no incident UTI. Moreover, stopping SGLT2 inhibitors was associated with reduced risk of recurrent UTI, but increased risk of adverse cardiovascular and renal events.
PERIPHERAL VASCULAR DISEASE
GW34-e0164
Peibiao Mai1, Junping Li2, Chunhong Wang2, Shuwan Xu1, Xiaofang Wang3, Kun Zhang2,4
1Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat-sen University
2Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
3Department of Dermatology and Venerology, University of Chinese Academy of Sciences Shenzhen Hospital
4Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Cardiology, RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
OBJECTIVES Peripheral arterial calcification is a prevalent condition in patients with type 2 diabetes mellitus (T2DM), resulting in lower-limb amputation and reduced life quality. Nonalcoholic fatty liver disease (NAFLD) which can be simply evaluated by fatty liver index (FLI) is closely associated with T2DM development. In this study, we aimed to explore the relationship between FLI and lower limb arterial calcification (LLAC) in T2DM patients.
METHODS This was a retrospective, observational, single-center study between January 2018 and January 2019. Seventy-seven T2DM patients with suspiciously symptomatic lower limb PAD were enrolled in this study. Clinical and laboratory data were collected. FLI was calculated by body mass index, waist circumference, triglycerides, and γ-glutamyltransferase. LLAC was evaluated by computed tomography with Agatston scoring algorithm.
RESULTS T2DM patients were divided based on the FLI values: low risk (FLI<30, n=29), intermediate risk (30=FLI<60, n=32) and high risk (FLI=60, n=16) groups. Compared with low risk group, T2DM patients in high risk group had significantly lower LLAC scores [270.0 (3.3, 1020.3) vs. 2024.0 (481.5–7317.5); P=0.018], accompanied with higher triglyceride and glucose (TyG) index [(9.89±0.70) vs. (8.86±0.57) vs. (8.34±0.61); P<0.001]. The correlation analysis showed FLI was negatively associated with LLAC scores (r=-0.311, P=0.006).
CONCLUSIONS Major finding of the present study shows that FLI, an indicator used to diagnose NAFLD, is negatively associated with LLAC in T2DM patients, which implies that NAFLD may not be a risk factor for LLAC in T2DM patients.
GW34-e0609
Jiaxin Cheng1,2
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, Liaoning, China
OBJECTIVES This study aims to investigate the effects of statin therapy on patients with acute Stanford type B aortic dissection after undergoing TEVAR procedure.
METHODS This retrospective analysis reviewed the medical records of 742 patients who had acute type B aortic dissection and received TEVAR treatment at Department of Cardiology of General Hospital of Northern Theater Command from April 2002 to March 2022. The patients were categorized into two groups: the statin group (S-group, n=366), and non-statin group (NS-group, n=376) based on wheater they accepted postoperative statin therapy or not. The main observation outcomes were all-cause mortality and aortic-related adverse events. Kaplan–Meier survival curves analyzed survival between the two groups, and COX regression analysis corrected for confounding factors.
RESULTS There were significant differences between the S-group and NS-group in terms of coronary heart disease history (S-group 20.77%, NS-group 9.57%), postoperative Calcium channel blockers (S-group 87.43%, NS-group 77.66%), and postoperative β-blockers (S-group 86.25%, NS-group 79.79%) (P<0.05). There were no significant differences between the two groups in other baseline data (P>0.05). Significant differences between the S-group and NS-group were observed for all-cause mortality (S-group n=26, NS-group n=46, P=0.018), stent graft-induced distal redissection (S-group n=6, NS-group n=23, P=0.001), and re-intervention (S-group n=4, NS-group n=17, P=0.005). While Kaplan–Meier survival analysis showed that statin therapy had differences for stent graft-induced distal redissection (P=0.01), re-intervention (P=0.03), it had no significant impact on all-cause mortality over time. COX regression analysis showed that statin therapy was an independent protective factor, reducing stent graft-induced distal redissection [HR (95% CI): 0.241 (0.081, 0.723), P=0.011] and re-intervention [HR (95% CI): 0.210 (0.052, 0.840), P=0.027].
CONCLUSIONS Statin therapy after TEVAR treatment for patients with acute Stanford type B aortic dissection can help reduce aortic adverse events and the risk of both stent graft-induced distal redissection and re-intervention. Nevertheless, larger samples and multi-center studies are needed to validate these findings.
GW34-e0715
Jiaxin Cheng1,2, Zhiqiang Zhang2, Yasong Wang2, Xiaozeng Wang2
1College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning, China
2The Department of Cardiology of General Hospital of Northern Theater Command of Chinese People’s Liberation Army, Shenyang, China
OBJECTIVES This study aims to investigate the effects of statin therapy on patients with acute Stanford type B aortic dissection after undergoing TEVAR procedure.
METHODS This retrospective analysis reviewed the medical records of 742 patients who had acute type B aortic dissection and received TEVAR treatment at Department of Cardiology of General Hospital of Northern Theater Command from April 2002 to March 2022. The patients were categorized into two groups: the statin group (S-group, n=366), and non-statin group (NS-group, n=376) based on wheater they accepted postoperative statin therapy or not. The main observation outcomes were all-cause mortality and aortic-related adverse events. Kaplan–Meier survival curves analyzed survival between the two groups, and COX regression analysis corrected for confounding factors.
RESULTS There were significant differences between the S-group and NS-group in terms of coronary heart disease history (S-group 20.77%, NS-group 9.57%), postoperative Calcium channel blockers (S-group 87.43%, NS-group 77.66%), and postoperative β-blockers (S-group 86.25%, NS-group 79.79%) (P<0.05). There were no significant differences between the two groups in other baseline data (P>0.05). Significant differences between the S-group and NS-group were observed for all-cause mortality (S-group n=26, NS-group n=46, P=0.018), stent graft-induced distal redissection (S-group n=6, NS-group n=23, P=0.001), and re-intervention (S-group n=4, NS-group n=17, P=0.005). While Kaplan–Meier survival analysis showed that statin therapy had differences for stent graft-induced distal redissection (P=0.01), re-intervention (P=0.03), it had no significant impact on all-cause mortality over time. COX regression analysis showed that statin therapy was an independent protective factor, reducing stent graft-induced distal redissection [HR (95% CI): 0.241 (0.081, 0.723), P=0.011] and re-intervention [HR (95% CI):0.210 (0.052, 0.840), P=0.027].
CONCLUSIONS Statin therapy after TEVAR treatment for patients with acute Stanford type B aortic dissection can help reduce aortic adverse events and the risk of both stent graft-induced distal redissection and re-intervention. Nevertheless, larger samples and multi-center studies are needed to validate these findings.
GW34-e0795
Liyuan Chen1, Xue Wang2, Lina Pan1, Lingling Yang2, Xutao Zhang1, Chang Liu3, Houyuan Hu1
1Department of Cardiology, Southwest Hospital, Third Military Medical University
2Department of Occupational Health (Key Laboratory of Electromagnetic Radiation Protection, Ministry of Education), Third Military Medical University
3Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University
OBJECTIVES Even if endovascular treatment (EVT) getting to be the first-line therapeutic modality for large vessel occlusion in the anterior circulation (ALVO), nearly one in three of these patients obtained poor outcome. With the facts that valvular diseases were widely detected in these patients, present study aimed to evaluate the roles of valvular diseases in determining outcomes of these individuals to explore novel risk factors for poor clinical consequences among these individuals.
METHODS Among 798 LVO patients receiving EVT across 32 medical centers in China who underwent transthoracic echocardiography (TTE) were included in analysis. After grading the regurgitation and stenosis of the mitral, aortic, and tricuspid valves, logistics regression analysis was engaged in evaluating their relationship with outcomes. Outcomes includes acute heart failure after EVT, modified Rankin Scale score (mRS) of 0–2 and mortality at 3 months. Causal mediation analyses were used to estimate the effects of valvular diseases and the potential mediators.
RESULTS The presence of MR was found in 27.2% of patients. Compared to non-significant MR (nMR), patients with significant mitral regurgitation (sMR) were older (P=0.005), and they also had more comorbidities, such as diabetes mellitus (30.61 vs. 19.85%; P<0.080) and long-standing atrial fibrillation (29.39 vs. 6.12%; P<0.001). sMR was independently associated with functional independence after 3 months [adjusted odds ratio: 0.41, 95% confidence interval: 0.21 to 0.77; P=0.006] and mortality [adjusted odds ratio: 1.92, 95% confidence interval: 1.21 to 2.47; P=0.012]. Mediation analysis showed sMR-increased acute heart failure explained 20.0% (95% CI 4.1–76.0%) of the effect of sMR on functional independence. In addition to MR, we did not detect significant relationship between outcomes and the other valvular diseases among enrolled patients.
CONCLUSIONS sMR constitutes an underrated high-risk group in LVO stroke patients who received EVT, with an increase in the overall high mortality and significant reduced functional independence. Our study also stressed the importance of echocardiography monitoring of the leaflet of MR in high-risk stroke patients.
PSYCHO-CARDIOLOGY
GW34-e0757
Li Feng, Li Hui
The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
OBJECTIVES Accumulated studies have indicated that depression was significantly associated with the atrial fibrillation (AF) risk. However, the causal effect of major depressive disorder (MDD) on the risk of AF was elusive.
METHODS We performed a two-sample Mendelian randomization (MR) analysis using two genetic instrument tools for MDD to assess the potential causal effect of MDD on the AF risk, including a training dataset (37 single-nucleotide polymorphisms (SNPs) significantly associated with MDD) and a validation dataset (11 SNPs robustly associated with MDD). Inverse-variance weighted method (IVW), weighted median method, MR-Egger, MR-Pleiotropy REsidual Sum and Outlier (MR-PRESSO) test, pleiotropy test, and leave-one-out sensitivity analysis were performed for MR analyses.
RESULTS We first performed MR analysis for a training data using multiple data processing steps, including removing SNPs related with AF risk factors, removing one outlier with MR-PRESSO, and tighten instrument P value threshold. The final MR estimates suggested that MDD had no causality on AF incidence (IVW method, OR=1.04, 95% CI=0.79–1.36, P value=0.785; weighted median, OR=1.15, 95% CI=0.90–1.46, P value=0.268; MR-Egger, OR=1.00, 95% CI=0.35–2.85, P value=0.999). Moreover, a consistent result was displayed in MR estimates using a validation data. Pleiotropy test and leave-one-out sensitivity analysis revealed that our results were robust.
CONCLUSIONS Our MR analysis suggested that MDD may have no causality on the AF risk.
GW34-e0999
Shenghui Zhang, Siqi Hu, Yao You, Jiake Tang, Chen Chen, Mingwei Wang
Department of Cardiology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Institute of Cardiovascular Diseases, Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou Normal University, Hangzhou 310015, China
OBJECTIVES Previous studies have found that amygdala activity independently and robustly predicts cardiovascular disease events. The purpose of this study was to calculate functional connectivity (FC) using resting-state functional MRI (rs-fMRI). To explore the characteristics of brain functional network in patients with coronary heart disease (CHD), and to better understand the relationship between the changes of amygdala-based FC and the clinical characteristics and cognition of patients with CHD.
METHODS A total of 14 CHD patients and 10 healthy controls were enrolled in this study. All subjects underwent resting-state fMRI scan in the Affiliated Hospital of Hangzhou Normal University, and administered the biochemical testing of blood. Neuropsychological assessment was performed by 2 trained physicians: the assessment scale includes Mini-Mental State Scale (MMSE), Hamilton Rating Scale for Depression (HAMD-17).
RESULTS Compared with healthy controls, patients with CHD had increased functional connectivity between the amygdala and the medial superior frontal gyrus (BA11, P<0.05, FDR corrected, Q<0.05). The FC between amygdala and medial superior frontal gyrus was significantly associated with HDL-C (r=−0.53, P<0.05), HAMD score (r=0.66, P<0.05) and MMSE scores (r=−0.60, P<0.05).
CONCLUSIONS This study found that the whole brain functional connectivity based on amygdalae in CHD patients is different from that in healthy controls, and this functional connectivity pattern is correlated with laboratory indicators and cognitive scales, which may help us to further understand the relationship between brain function and diseases.
GW34-e1165
Xing Liang, Qiaoling Ye, Yisong Pei, Guozhu Chen
The Second Affiliated Hospital of Chongqing Medical University
OBJECTIVES Anxiety, often accompanied by somatic symptoms and sleep disorder, is commonly observed in populations infected with COVID-19. Patients with pre-existing cardiac conditions are considered a high-risk demographic for fatality following COVID-19 infection. This study aims to evaluate the psychological conditions, including the severity of anxiety, somatic symptoms, and sleep quality in patients with ACS (acute coronary syndrome) during the COVID-19 pandemic.
METHODS The subjects of the study were 336 patients diagnosed with ACS who sought medical consultation between February 2022 and February 2023 at the Second Affiliated Hospital of Chongqing Medical University and the Wushan County People’s Hospital of Chongqing. Among these, nine patients were not infected with COVID-19. All patients underwent assessment using the following scales: Short Health Anxiety Inventory (SHAI), Patient Health Questionnaire-15 (PHQ-15), and the Pittsburgh Sleep Quality Index (PSQI). Assessments were conducted through online questionnaires.
RESULTS In the SHAI scale, 44.3% of the patients with ACS displayed symptoms of anxiety, with an average score of 21.56±7.377. The ACS onset time showed a significant correlation with the state of anxiety (P<0.05), the earlier the onset of ACS, the longer the time from COVID-19 infection, and the lower rates of anxiety. In the PHQ-15 scale, 24.71% of the patients had somatic symptoms. Patients with mild somatic symptoms were 9 times more likely to moderate ones, no severe cases. The earlier the ACS onset, the longer the time from COVID-19 infection, the longer follow-up interval, and the lower incidence of somatic symptoms (P<0.05). STEMI and NSTEACS differed markedly in terms of somatic symptoms measured by PHQ-15, the incidence in STEMI group is notable higher than the NSTEACS. A significant positive correlation was found between SHAI and PHQ-15 scores (P<0.001). The PSQI scale indicated a sleep disorder incidence of 22.9%, somatic symptoms had a obvious impact on sleep quality (P<0.05), and the more severe the somatic symptoms, the more likely to have sleep disorders. In the subgroup analysis, remarkable differences were observed in PHQ-15 scores between patients with stents [3.0 (2.0–5.0)] and those without stents [5.0 (2.0–6.0)] (P<0.05). The analysis indicated that they were independent of factors such as age, gender, ischemic time, severity of COVID-19 infection, and the presence of residual symptoms (P>0.05).
CONCLUSIONS After the recent COVID-19 pandemic, psychological problems such as anxiety, somatic symptoms and sleep disorders were common in ACS patients. It was found that the incidence of anxiety and somatic symptoms is related to the time from ACS onset to COVID-19 infection, the longer the time, the lower the proportion of patients with psychological condition. The somatic symptoms are related to the severity of ACS, meanwhile they may decrease sleep quality. These demonstrated that more severe ACS and shorter interval between ACS onset and COVID-19 infection may increase psychological problems of patients. Those patients require more active psychological attention and intervention.
CARDIOVASCULAR IMAGING
GW34-e0037
Yao Lu, Xiaoli Zhang
Beijing Anzhen Hospital Affiliated Capital Medical University
OBJECTIVES To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with 18F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET).
METHODS Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with 18F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and 18F-FDG gated PET at different stages (3∼12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR−). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and 18F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3∼12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified.
RESULTS A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR-group ((51.8±17.9%) vs. (35.7±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR [Odds ratio=1.073, 95% Confidence interval: 1.005–1.145, P=0.035]. ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82, 60 and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD=38.3% group (n=64) (all P<0.05).
CONCLUSIONS Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD=38.3% can accurately predict RR and the improvement of cardiac function after CABG.
GW34-e0039
Yankai Mao1, Yuan Yang1, Jürgen Duchenne2, Christophe Garweg2, Xia Sheng3, Jiefang Zhang3, Yang Ye3, Min Wang3, Ying Yang3, Gabor Vöros2, Yaxun Sun3, Mingming Ma1, Guosheng Fu3, Jens-Uwe Voigt2
1Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw hospital, Zhejiang University
2Department of Cardiovascular Sciences, Catholic University Leuven, Belgium
3Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
OBJECTIVES Left bundle branch pacing (LBBP) has emerged as a novel pacing modality. Although it has been proved to maintain electrical synchrony better than right ventricular pacing (RVP), little is known about the impact on mechanical synchrony. This study investigates if LBBP preserves mechanical synchrony and cardiac function better compared to conventional (CRVP) and leadless (LRVP) RVP.
METHODS Sixty-eight patients with pacing indication for bradycardia were prospectively enrolled: Twenty-five were treated with LBBP, 23 with CRVP and 20 with LRVP. 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. Regional septal (SW) and lateral wall work (LW) was calculated as the average from the respective basal and mid-ventricular segments in the apical four-chamber and three-chamber view. The lateral-septal (LW-SW) work difference was used as a measure of mechanical dyssynchrony.
RESULTS At baseline, LW-SW work difference were similar in all three groups. SW was markedly decreased in CRVP and LRVP while LW work remained unchanged, resulting in a larger LW-SW work difference compared to LBBP (1308.4±732.9 mmHg*% and 1451.3±606.1 mmHg*% vs. 286.0±479.9 mmHg*%, both P<0.001). During one year follow-up, LVEF and LV GLS decreased more in CRVP compared to LBBP (both P<0.05).
CONCLUSIONS LBBP causes less LV dyssynchrony than CRVP and LRVP as it preserves a more physiologic conduction pattern. With this, LBBP appears to preserve LV function better than CRVP. CRVP and LRVP did not differ in mechanical dyssynchrony or LV remodelling.
GW34-e0044
Yankai Mao1, Yuan Yang1, Chan Yu1, Yunhe Wang2, Chenyang Jiang2
1Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
2Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
OBJECTIVES Atrial fibrillation (AF) is associated with left atrial (LA) mechanical dysfunction, which predispose to stasis of blood within the LA and thus increase the risk of stroke. However, limited is known about the mechanical functional alterations of left atrial appendage (LAA) in relation to stages of AF. Here, we sought to analyse LA and LAA mechanics during different stages of AF in detail.
METHODS A total of 92 patients with AF referring for radiofrequency ablation were consecutively enrolled. Patients were categorized according to rhythm and stages of AF: sustained AF (SAF) (n=31), paroxysmal AF with sinus rhythm (PAF-SR) (n=30) and AF rhythm (PAF-AF) (n=31) at the time of echocardiography. Twenty-seven patients without a history of AF were included as controls. Using speckle-tracking echocardiography, LA reservoir strain (LASr), LAA 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 PAF-AF and SAF displayed prominently impaired LA and LAA mechanics (all P<0.01 vs. PAF-SR and no AF). In the presence of SR, only LAA mechanical function were lower in PAF patients than patients without AF (LAA GLS 20.5±5.7% (no AF) vs 15.9±5.4% (PAF-SR); LAA MD 6.9±3.8% (no AF) vs 9.4±3.9 (PAF-SR), both P<0.01). AF stages were independent determinants of LA and LAA mechanics after adjusting for age and comorbidities.
CONCLUSIONS AF affected mechanical function of LA and LAA on their own, and more so if stage of AF has advanced to more persistent forms. In addition, LAA mechanical dysfunction occurred earlier than that of LA.
GW34-e0203
Yining Wang1, Xuejing Duan2, Leyi Zhu1, Jian He1, Baiyan Zhuang1, Jing Xu1, Di Zhou1, Wenjing Yang1, Arlene Sirajuddin3, Andrew E. Arai3, Hongyue Wang2, Shihua Zhao1, Minjie Lu1
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
2Department of Pathology, 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
3Department of Health and Human Services, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, USA
OBJECTIVES The diagnostic performance of cardiovascular magnetic resonance (CMR) compared with endomyocardial biopsy (EMB) in patients with suspected acute myocarditis (AMC) has not been extensively evaluated, and characteristics of patients with false-negative EMB results are not well understood. This study aimed to evaluate the diagnostic performance of CMR compared with EMB in patients with suspected AMC and identify characteristics of patients with false-negative EMB results.
METHODS A total of 311 patients with clinically suspected AMC who underwent CMR with 3.0 T. The CMR protocol consisted of cine-SSFP, T2-weighted STIR, late gadolinium enhancement (LGE), T1 and T2 mapping. Patients were considered to have confirmed myocarditis when both ESC statement and 2018 Lake Louise criteria (LLC) supported the diagnosis.
RESULTS The 2018 LLC yielded a sensitivity of 96.3% and a specificity of 84.6%, while the sensitivity of EMB was 62.8% and the specificity was 85.7%. Of the patients who underwent EMB, 55 (59.1%) were diagnosed with myocarditis, three (3.2%) were diagnosed with dilated cardiomyopathy and no specific myocardial injury was found in the remaining 35 (37.6%). Based on predetermined classification criteria, 27 patients (29.0%) were classified in the false-negative group, 53 (57.0%) in the true-positive group, and 11 (11.8%) in the true-negative group. Patients prone to have false-negative EMB results may have clinical symptoms present as infarct-like or arrhythmias and normal cardiac function, with CMR performance including preserved left ventricular ejection fraction, atypical LGE patterns and elevated T1 or T2 relaxation times.
CONCLUSIONS CMR shows superior diagnostic performance compared with EMB in the diagnosis of AMC. False-negative EMB results may occur more frequently in patients with specific clinical and CMR characteristics. Our findings suggest that all patients with clinically suspected myocarditis should undergo CMR to optimize diagnosis and clinical management.
GW34-e0215
Jinwei Tian1, Chao Li2, Zhifeng Qin1, Taishi Yonetsu3, Rocco Vergallo4, Bo Zhang5, Zhao Wang2, Bo Yu1
1Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China
2School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China
3Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
4Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy
5Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, China
OBJECTIVES Coronary artery calcification (CAC) is a surrogate of atherosclerotic disease burden and has been associated with worse stent expansion and clinical outcomes. However, evidence from large-scale high-resolution imaging studies is lacking, and the 3D morphological significance of CAC is yet to be elucidated.
METHODS We proposed a novel deep learning method that can automatically identify and quantify CAC in massive intravascular OCT data. 1,106,347 OCT images from 1048 patients with ischaemic heart disease were collected and utilized to train and evaluate the method. All possible CACs were segmented from OCT pullbacks using the proposed method (Ca-Net) trained with sparsely annotated data, which were then screened and classified by a 3D CNN network. After validating the performance of the AI-model by external evaluation, we applied the method to 1259 patients with ST-segment elevation myocardial infarction (STEMI) and evaluated the predictive value and clinical significance of CAC.
RESULTS The Dice similarity coefficient for CAC segmentation and the accuracy for CAC classification in internal evaluation were 0.693 and 0.932 respectively, reaching human-level performance. We found that patients with greater extent of calcification in the culprit vessels were significantly more likely to have major adverse cardiovascular and cerebrovascular events (MACCE), and calcification is more severe in culprit vessels than in non-culprit vessels.
CONCLUSIONS The proposed AI method trained with massive clinical data has achieved human-level performance in CAC segmentation and quantification. Severe CACs in culprit vessels of STEMI patients identified by the AI algorithm were associated with MACCE.
GW34-e0240
Nuo Xu, Yingjie Zhao, Haiyan Chen, Xianhong Shu
Zhongshan Hospital, Fudan University
OBJECTIVES Transjugular intrahepatic portosystemic stent shunt (TIPS) is a non-surgical treatment for portal hypertension. Right heart overloading is one of the main complications of the procedure, leading to heart failure. However, research on right heart function after TIPS is limited. This study aims to assess the efficiency of speckle tracking echocardiography for evaluating cardiac function before and after TIPS and to examine the short-term impact of TIPS on right heart function.
METHODS This prospective study included 51 patients (32 males, 19 females; 56±9 yrs) with a clinical history of intractable esophageal varices or refractory ascites. Transthoracic echocardiograph data were collected at baseline and 7 days, 90 days after TIPS. Conventional and advanced echocardiographic parameters were analyzed, including right atrium (RA) and right ventricle (RV) structure, function and 2D strain. The Model for End-stage Liver Disease (MELD) score was also calculated.
RESULTS
• RASr showed a significant increase at day 7, and although it decreased after day 7, it was still remarkably higher at day 90 than before therapy. (PRE vs Day7: 42.35±6.90% vs 47.45±5.56%, P<0.01; PRE vs Day90: 42.35±6.90% vs 46.12±4.26%, P<0.05). RAScd and RASct showed the same trends.
• RVFWSL decreased significantly at day 7 but increased significantly at day 90. (PRE vs Day7: −33.61±4.70% vs −30.35±3.35%, P<0.01; Day7 vs Day90: −30.35±3.35% vs −34.78±3.18%, P<0.01).
• ΔRASr was remarkably linearly correlated with ΔRAA (PRE vs Day7: P=0.014, r=0.484; PRE vs Day90: P=0.016, r=0.529).
• ΔRVFWSL was linearly related to ΔFAC (PRE vs Day7: P=0.042, r=-0.414).
• The MELD score correlated with RVFWSL, indicating that RV strain is somewhat predictive of liver cirrhosis outcome. (PRE: P=0.039, r=-0.378, Day90: P=0.030, r=-0.424).
CONCLUSIONS
• Speckle tracking echocardiography is more sensitive than conventional echocardiography in detecting changes in right heart function.
• TIPS may cause RA overload and RV function decrease shortly after the procedure, but right heart strains and function ultimately increase 90 days after therapy.
• The MELD score correlates with RV longitudinal strain, indicating its potential as a predictor of liver cirrhosis outcome.
GW34-e0287
Ran Xin1,2, Guanhua Dou3, Yundai Chen1, Junjie Yang1
1Senior Department of Cardiology, The Sixth Medical Center, Chinese PLA General Hospital
2School of Medicine, Nankai University
3Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital
OBJECTIVES To explore the value of CCTA-based radiomics technology in improving the identification efficiency of left atrial appendage (LAA) thrombus in patients with nonvalvular atrial fibrillation (NVAF).
METHODS Six hundred and seventy patients with NVAF who underwent CCTA and transesophageal echocardiography (TEE) from May 2015 to May 2020 were retrospectively enrolled and classified as thrombus group and non-thrombus group by TEE, dividing the training dataset (N=404) and the validation dataset (N=266) by a ratio of 6:4. Clinical baseline data and CCTA parameters were collected and the ratio of minimum Hounsfield units (HU) in the thrombus (LAAmin) to those in the ascending aorta (AAmin) was also calculated (LAAmin/AAmin). Mean value interpolation was used to interpolate the missing values. Radiomics features were automatically extracted from the region of interest (ROI) of LAA. Random Forest (RF) were used for feature selection, and multivariate logistic regression was used for modeling. Receiver operator characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were plotted and the performance parameters, the net reclassification index (NRI) and C-index were calculated to evaluate the efficacy in terms of discrimination, calibration and clinical net benefit. The radiomics nomogram was plotted to describe the fraction of components in the predictive model. Optimal radiomics was compared between different groups.
RESULTS The AF type, CHA2DS2-VAS score, HAS-BLED score, LAA length (LAA-L), LAA diameter (LAA-D) and LAAmin/AAmin were significantly different between two groups (P<0.05). 1232 radiomics features were extracted and 20 features were finally selected for modeling. The composite model had a higher area under curve (AUC) than the other three models (Training dataset: 0.949 vs. 0.757, 0.829, 0.913; Validation dataset: 0.900 vs. 0.832, 0.825, 0.822, respectively). The accuracy (ACC), specificity (SPE), positive likelihood ratio (PLR), Positive predictive value (PPV), Negative percent Agreement (NPA) and Kappa value of composite model were significantly higher (Training dataset: 0.874, 0.870, 7.296, 0.275, 0.997, 0.874; Validation dataset: 0.917, 0.924, 10.38, 0.367, 0.917, 0.461, respectively). The composite model had a positive NRI compared to the other three models (0.421, 0.059, 0.113, respectively), and a C-index greater than 0.5 (0.802, 0.662, 0.648, respectively). The calibration curve and decision curve suggested that the composite model had better calibration and clinical net benefits. The radiomics nomogram showed that the efficiency ratio of radiomics features in the composite model. The value of optimal radiomics feature in thrombus group was significantly higher than that in non-thrombus group (P<0.05), which had no significant difference in the subgroups divided by LAA morphology and CHA2DS2-VAS score (P>0.05).
CONCLUSIONS CCTA-based radiomics can improve the predictive efficiency of traditional predictive models for LAA thrombosis in NVAF patients, and it can also assess factors associated with thrombosis in multiple dimensions.
GW34-e0288
Ran Xin1,2, Yipu Ding1,2, Xi Wang1, Zinuan Liu1,3, Yundai Chen1, Junjie Yang1, Dongkai Shan1
1Senior Department of Cardiology, The Sixth Medical Center, Chinese PLA General Hospital
2School of Medicine, Nankai University
3Medical School of Chinese PLA
OBJECTIVES The study aims to investigate the association of Perivascular adipose tissue (PVAT) volume and attenuation with the risk of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).
METHODS T2DM patients with suspected CAD were retrospectively included in this study, and non-diabetic patients were selected as the control group according to the 1:1 propensity matching score. Demographic data and clinical risk factors were collected, and the PVAT volume and attenuation measured by CCTA were calculated. The PVAT volume and attenuation differences between T2DM patients and non-diabetic patients were compared. And the correlation between RCA, LAD, and LCX volume and metabolic syndrome-related factors, univariate and multivariate regression analysis of RCA-PVAT volume and attenuation, metabolic syndrome-related factors, and diabetes status. Continuous normal data were represented by mean±standard deviation (mean±SD), while non-normal data were represented by quartile and median. The student’s T-test was used for the comparison of normal distribution and the Mann-Whitney U test was used for that of non-normal distribution. The categorical data were expressed as percentages and compared using the Chi-square test or Fisher’s exact test. Pearson or Spearman r correlation method was used for correlation analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.
RESULTS One hundred and thirty patients with T2DM complicated with CAD were enrolled in this study, and a total of 260 subjects were enrolled after 1:1 propensity score matching (PSM). A comparison of baseline data found that waist circumference, BMI, total serum cholesterol, triglycerides, LDL-C, and HbA1C were significantly higher in T2DM patients compared with those without diabetes. Compared with the non-diabetic population, the PVAT volume in T2DM patients increased significantly, while the attenuation did not change statistically. Multivariate regression analysis indicated that RCA-PVAT volume, waist circumference, and HbA1C were independent correlation factors of T2DM.
CONCLUSIONS PVAT volume, rather than attenuation, was associated with an increased risk of CAD in T2DM patients.
GW34-e0291
Wang Yi
Sichuan Provincial People’s Hospital
OBJECTIVES Heart failure remains the main cause for cardiac death. Lots of heart failure with reduced ejection fraction (HFrEF) patients often have concomitant significant mitral regurgitation. It’s not quite clear who would benefit from transcatheter edge-to-edge repair (TEER). Some evidence showed that right ventricular function was an important predictor for heart failure. We therefore try to refine the evaluation of the association between right ventricular function evaluated by pressure-strain loops (PSL) and the clinical improvement after TEER. We sought to (1) analyze the change of different right ventricular myocardial work (RVMW) parameters by PSL in HFrEF patients undergoing TEER; (2) evaluate the association between immediately change of RVMW parameters and clinical improvement among HFrEF patients who underwent TEER treatment for secondary mitral regurgitation (SMR).
METHODS Eligible patients had ischemic or nonischemic cardiomyopathy with a left ventricular ejection fraction of 20 to 50%, had moderate-to-severe (grade 3+) or severe (grade 4+) SMR that was confirmed at the echocardiographic laboratory before enrollment, and remained symptomatic (NYHA functional class II, III, or IVa [ambulatory]) despite the use of optimal doses of guideline-directed medical therapy and cardiac resynchronization therapy (if appropriate), which were administered in accordance with guidelines of professional societies. If the interventional cardiologist confirmed that the patient was anatomically eligible for device implantation, and the cardiothoracic surgeon determined that mitral valve surgery was not appropriate, patients would undergo TEER procedure. From May, 2021 to January, 2023, a total of 48 HFrEF patients (median age 68 (57–84) years) with moderate-to-severe or severe SMR were enrolled. Patients were followed up for 6 months. One patient died during follow up. Non-invasive analysis of LVMW and RVMW was performed before and immediately after MitraClip treatment.
RESULTS There’s no significant change in RVEDV (128.5±20.7 mL vs 136.7±28.5 mL), RVESV (82.9±17.6 mL vs 73.5±20.6 mL) after TEER. While RVSV (44.5±9.8 mL vs 58.8±14.5 mL) and RVEF (36.6±3.6% vs 45.4±3.9%) increased. TAPSE, RV GLS, RV S’and RV FAC were not significantly changed immediately after MitraClip treatment (16.5±5.1 mm, −9.7±3.8%, 6.7±2.2 m/s and 37±14% before vs 17.1±2.1 mm, −10.5±3.5%, 6.9±1.8 m/s and 39±12% after MitraClip treatment). While RVGWI, RVGCW, RVGWE were significantly increased after MitraClip treatment (452.4±112.5 mmHg%, 596.3±127.5 mmHg% before and 85.7±15.6 mmHg% vs 589.4±119.6 mmHg%, 778.8±135.3 mmHg% and 80.9±22.4% after MitraClip treatment). And RVGWW was significantly decreased after MitraClip treatment (113.8±19.7 mmHg% vs 91.2±22.4 mmHg%). Mean KCCQ-OS and 6MWD were increase after MitraClip treatment (23.7±9.8 points and 103 (79–121) m). On multivariable linear regression analysis, RVGWI and RVGCW immediate change was independently associated with KCCQ-OS (ΔRVGWI: β=0.40, P<0.001; ΔRVGCW: β=0.39, P=0.003), RVGWI, RVGCW and RVGLS immediate change were independently associated with 6MWD improvement (ΔRVGWI: β=0.31, P=0.029; ΔRVGCW: β=0.30, P=0.039; ΔRVGLS: β=0.35, P=0.041).
CONCLUSIONS RVMW was significantly increased after MitraClip treatment. And RVGWI and RVGCW increase were independently associated with clinical improvement among HFrEF patients who underwent MitraClip treatment for SMR. The application of the proposed RVMW analysis is easy to perform and RV reserve function is an important predictor of clinical improvement in HFrEF patients with TEER.
GW34-e0302
Fei Yu1, Yan Huang2, Han Zhang1, Xuepin Hu1, Shanshan Qin1
1Shanghai Tenth People’s Hospital
2Anhui University of Science and Technology
OBJECTIVES Gate myocardial perfusion single-photon emission computer tomography (GSPECT) overestimated left ventricle (LV) ejection fraction (EF) in patients with small LV volumes, the SH reconstructed algorithm dedicated for small LV volumes provides an enhanced reconstructed spatial resolution. This study aimed to explore the clinical application value of SH.
METHODS We retrospectively analyzed patients who had both underwent GSPECT and Echocardiography (Echo) within one week. Small LV volume was defined as rest end-systolic volume (rESV)=25 mL which was reconstructed using the Standard (SD) algorithm. The LVEF difference >5% between the two algorithms was considered successfully corrected, and the ROC curve was used to calculate the optimal cut-off value of the SH algorithm. Echo being the gold standard for LV function parameters, the differences between the three methods were evaluated in comparison.
RESULTS The final study included 209 patients (73.21% female, age 67.34±7.85 years). In the overall population, SH significantly decreased LVEF (67.43±7.38% vs 71.30±7.61%, P<0.001) compared with SD, but still had statistical difference compared with Echo in the overall patients (67.43±7.38% vs 63.15±2.65%, P<0.001). The optimal cut-off value for using SH was rESV>17 mL (AUC=0.651, sensitivity=78.43%, specificity=45.57%, P=0.001). In the subgroup of rESV>17 mL, there was no statistical difference of LVEF (61.84±4.67% vs 62.83±2.85%, P=0.481) between SH and Echo.
CONCLUSIONS The pilot study demonstrated the SH algorithm could effectively correct the overestimation of LVEF in patients with small LV volumes, which yield more clinical value in the subgroup of rESV>17 mL.
GW34-e0337
Zinuan Liu1,2, Yipu Ding2,3, Guanhua Dou4, Xi Wang2, Dongkai Shan2, Bai He2, Jing Jing2, Tao Li5, Junjie Yang2, Yundai Chen2
1Medical School of Chinese PLA, Beijing, China
2Senior Department of Cardiology, The Sixth Medical Center, Chinese PLA General Hospital, Beijing, China
3School of Medicine, Nankai University, Tianjin, China
4Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
5Department of Radiology, The First Medical Center of PLA General Hospital, Beijing, China
OBJECTIVES Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (CT-FFR) enables physiological assessment and risk stratification, which is of significance in diabetic patients with nonobstructive coronary artery disease (CAD). We aim to evaluate prognostic value of the global trans-lesional CT-FFR gradient (GΔCT-FFR), a novel metric, in patients with diabetes without flow-limiting stenosis.
METHODS Patients with diabetes suspected of having CAD were prospectively enrolled. GΔCT-FFR was calculated as the sum of trans-lesional CT-FFR gradient in all epicardial vessels greater than 2 mm. Patients were stratified into low-gradient without flow-limiting group (CT-FFR >0.75 and GΔCT-FFR <0.20), high-gradient without flow-limiting group (CT-FFR >0.75 and GΔCT-FFR≥0.20), and flow-limiting group (CT-FFR =0.75). Discriminant ability for major adverse cardiovascular events (MACE) prediction was compared among 4 models [model 1: Framingham risk score; model 2: model 1+Leiden score; model 3: model 2+ high-risk plaques (HRP); model 4: model 3+Global ΔCT-FFR] to determine incremental prognostic value of GΔCT-FFR.
RESULTS Of 1215 patients (60.1±10.3 years, 53.7% male), 11.3% suffered from MACE after a median follow-up of 57.3 months. GΔCT-FFR (HR: 2.88, 95% CI: 1.76–4.70, P<0.001) remained independent risk factors of MACE in multivariable analysis. Compared with the low-gradient without flow-limiting group, the high-gradient without flow-limiting group (HR: 2.86, 95% CI: 1.75–4.68, P<0.001) was associated with higher risk of MACE. Among the 4 risk models, model 4, which included GΔCT-FFR, showed the highest C-statistics (C-statistics: 0.75, P=0.002) as well as a significant net reclassification improvement (NRI) beyond model 3 (NRI: 0.605, P<0.001).
CONCLUSIONS In diabetic patients with non-obstructive CAD, GΔCT-FFR was associated with clinical outcomes at 5-year follow-up, which illuminates a novel and feasible approach to improved risk stratification for a global hemodynamic assessment of coronary artery in diabetic patients.
(Approval S2020-255-01).
GW34-e0558
Shuang Li, Baiyan Zhuang, Yue Ren, Hui Wang, Lei Xu
Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
OBJECTIVES Myocardial fibrosis is a significant pathological characteristic observed in various cardiovascular diseases and is closely associated with prognosis. The noninvasive assessment of myocardial fibrosis using cardiac magnetic resonance (CMR) has emerged as a promising method to improve risk stratification in patients. However, limited knowledge exists regarding the myocardial fibrosis in individuals with alcoholic cardiomyopathy (ACM). The study aims to investigate the prognostic importance of myocardial fibrosis detected through CMR in patients diagnosed with ACM.
METHODS In this retrospective study, we included a consecutive series of patients with ACM who underwent enhanced CMR with T1 mapping between September 2015 and January 2023. Myocardial fibrosis was assessed by late gadolinium enhancement (LGE), as well as native T1 and extracellular volume (ECV) fraction. The primary endpoint was a composite of cardiac-related death, heart transplantation, hospitalization for heart failure, life-threatening arrhythmias, and implantable cardioverter-defibrillator or cardiac resynchronization therapy implantation. Cox proportional hazards models were used to identify independent predictors of these endpoints.
RESULTS A total of 127 patients with ACM (127 men, 51±10 years) were enrolled. Over a median follow-up period of 23.0 months (interquartile range (IQR) of 10.8–34.3), 35 patients experienced the primary endpoints. Multivariate analyses revealed that the LGE presence (hazard ratio [HR]: 1.86; 95% confidence interval [CI]: 1.08, 4.25; P=0.01), native T1 (per 10 ms increase, HR: 1.06; 95% CI: 1.02, 1.11; P=0.002), and ECV (per 3% increase, HR: 1.74; 95% CI: 1.31, 2.31; P<0.001) were identified as independent predictors of the primary endpoints. In a series of prognostic models, the addition of myocardial fibrosis (LGE, native T1 and ECV) improved the predictive capability compared to models comprising only clinical and functional variables. We found a nonlinear correlation between the total lifetime ethanol dosage and myocardial fibrosis, with a slightly increased or relatively stable fibrosis level at lower total lifetime doses but a more pronounced increase at higher doses of ethanol exposure.
CONCLUSIONS CMR-detected myocardial fibrosis in patients with ACM demonstrated predictive and incremental value beyond clinical and functional variables for major adverse events, suggesting its potential as a tool for risk stratification in this population.
GW34-e0627
Yan-qiu Wang, Wei-wei Zhou
General Hospital of Northern Theater Command
OBJECTIVES To investigate the clinical application value of instant bedside echocardiography in etiology differential diagnosis of patients with acute chest pain.
METHODS A total of 114 patients with acute chest pain admitted to the General Hospital of Northern Theater Command from November 2022 to February 2023 were selected as the study subjects. All patients were admitted to the chest pain center and underwent bedside echocardiography within 30 minutes. The results of bedside echocardiography and misdiagnosed cases were recorded. Bedside echocardiography was recorded and compared with clinical diagnosis.
RESULTS A total of 114 patients with acute chest pain admitted to the General Hospital of Northern Theater Command from November 2022 to February 2023 were selected as the study subjects. All patients were admitted to the chest pain center and underwent bedside echocardiography within 30 minutes. The results of bedside echocardiography and misdiagnosed cases were recorded. Bedside echocardiography was recorded and compared with clinical diagnosis.
CONCLUSIONS Instant bedside echocardiography can quickly and effectively assist clinical diagnosis of common acute chest pain causes, and can effectively differentiate the diagnosis of common acute chest pain diseases such as acute myocardial infarction, aortic dissection, acute pulmonary embolism, etc.
KEY WORDS: Bedside echocardiography; Acute chest pain; Chest pain center; Cause of disease; Differential diagnosis.
GW34-e0644
Wenwen Yang1,2,3, Yueqi Wang3, Changgeng Fu1,2, Changjian Li4, Feng Feng5, Hongzheng Li1,2,6, Ling Tan1,2, Hua Qu1,2, Hui Hui3, Jingjing Wang3,7, Jie Tian3, Linzi Long1,2,8
1Department of Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, People’s Republic of China
2National Clinical Research Center for Cardiovascular Diseases of Traditional Chinese Medicine, Beijing 100091, People’s Republic of China
3CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China
4School of Engineering Medicine, Beihang University, Beijing 100191, People’s Republic of China
5College of energy engineering, Zhejiang University, Zhejiang 310058, People’s Republic of China
6Beijing University of Traditional Chinese Medicine Graduate School, Beijing University of Chinese Medicine, Beijing 100105, People’s Republic of China
7Department of Cardiovascular Medicine, First Medical Center, General Hospital of the People’s Liberation Army of China, Beijing 100853, People’s Republic of China
8Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, People’s Republic of China
OBJECTIVES The most effective therapy for limiting infarct size and improving clinical outcomes following acute myocardial infarction (MI) is the rapid restoration of blood flow through the occluded coronary artery via primary percutaneous coronary intervention. Compared with thrombolytic therapy, primary percutaneous coronary intervention exhibits reduced morbidity and mortality; however, MI/R lesion, a complication of vascular reperfusion therapy for acute myocardial infarction, is estimated to occur in≥60% of patients. Specifically, reperfusion injury may be independently associated with adverse left ventricular (LV) remodeling, an increased risk of fatal arrhythmias, and hospitalization for heart failure. Ferroptosis, an iron-dependent form of regulated cell death, has been increasingly recognized as an important process that mediates the pathogenesis and progression of numerous cardiovascular diseases, including MI/R injury, sepsis-induced cardiomyopathy, arrhythmia, etc. The absorption of iron by cells is mediated by iron-binding transferrin (Tf) and its receptor 1 (TfR1), which together can induce the endocytosis of reticulin-dependent complexes. The changes in TfR1 expression and alterations in iron transport from cytosol to mitochondria result in the increased mitochondrial iron associated with ferroptosis during heart injury. To this end, TfR1 represents a promising biomarker for specifically detecting MI/R-induced ferroptosis, as it corresponds to MI/R changes injury. The early stages of MI/R lesions are associated with ferroptosis, however, in vivo, noninvasive visualization of ferroptosis in MI/R using molecular imaging methods remains difficult.
METHODS Seven-week-old C57BL/6N mice were purchased from Beijing Charles River Experimental Animal Technology Company, China. In the MI/R mouse model, using 2% isoflurane to anesthetize 60 mouse. Following this, the skin was cut between the third and fourth ribs on the left side of the mouse, and the muscles were passively separated layer-by-layer, quickly extruding the myocardium and ligating the anterior descending branch of the coronary artery of the heart ∼2 mm below the junction of the left atrial appendage and conus arteriosus. The heart was quickly placed back into the heart cavity and the skin was sutured. After 30 min of ligation, the ligature thread was removed to restore cardiac perfusion. When the electrocardiogram showed obvious ischemia, the MI/R mice were randomly divided into two groups, as follows: (1) CON NPs and (2) CCI NPs. Each group was injected with 100 μL of nanoparticles at a concentration of 1 mg·mL−1 for 120 h of multimodal imaging, including ex vivo NIR and MPI imaging for 48 h.
RESULTS The feMPI, based on the TfR1-targeting and cell-penetrating peptides (CPPs) dual-targeted probe, detects cardiac injury ∼48 h in advance and quantitatively determines damage degree during post-MI/R, as compared to existing clinical imaging detection methods.
CONCLUSIONS This new imaging strategy compensated for the difficulty in detecting I/R damage during cardiac remodeling. These findings are notably consistent with the commonly used clinical biochemical indicators in the early stage of MI/R. In addition, optical and MI/R imaging was integrated as a multimodal to precisely monitor the occurrence and development of MI/R-induced cardiac injury. This study proposes a powerful imaging-effect-based feMPI strategy for the precise assessment of MI/R-induced cardiac injury, which may help elucidate diagnostic methods for ferroptosis-related heart diseases.
GW34-e0661
Yu-Ting Tan1,2,3, Yu-Man Li1,2,3, Li Zhang1,2,3, Ming-Xing Xie1,2,3, Jing Wang1,2,3
1Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
2Clinical Research Center for Medical Imaging in Hubei Province, Wuhan, Hubei Province, China
3Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei Province, China
OBJECTIVES Left atrial reservoir strain (LARS) is a sensitive imaging biomarker of left ventricular (LV) diastolic dysfunction. However, the prognostic implications of LARS in aortic regurgitation (AR) remains unknown. The purpose of this study was to examine the prognostic value of LARS in bicuspid aortic valve (BAV) patients with significant (=moderate) AR.
METHODS Two hundred and twenty BAV patients with significant AR were enrolled in our study. LARS and left ventricular global longitudinal strain (LVGLS) were derived from speckle-tracking echocardiography. The endpoint was a composite of all-cause mortality, heart failure hospitalization, and aortic valve repair or replacement. The Cox regression was used to evaluate the independent association between LARS and the endpoint.
RESULTS During a median follow-up of 364 days, 46 (20.9%) patients reached the composite endpoint. On multivariable Cox analysis, LARS (adjusted hazard ratio [aHR]: 0.85, 95% confidence interval [CI]: 0.80–0.90, P<0.001) was independently associated with adverse outcomes after adjustment for other clinical and echocardiographic indices. As dichotomized variables, patients with LARS<24% showed increased adverse outcomes risk (aHR: 2.22, 95% CI: 1.01–4.47, P=0.025). Furthermore, Model 2 incorporating LARS exhibited the best performance in model discrimination and reclassification for predicting adverse outcomes (Net reclassification index [NRI]=0.78, Integrated discrimination improvement [IDI]=0.17, all P<0.001 compared with Model 1 [i.e. Basic model plus LVGLS (%)]; NRI=0.62, IDI=0.10, all P<0.001 compared with Basic model [i.e. age, New York Heart Association≥ III, and LV end-systolic dimension]).
CONCLUSIONS In BAV patients with significant AR, LARS is an independent predictor of adverse outcomes and confers incremental prognostic utility for adverse outcomes. These findings suggest that LARS could be considered in clinical decision-making processes for such populations.
GW34-e0662
Yuting Tan1,2,3, Yuman Li1,2,3, Zhang Li1,2,3, Mingxing Xie1,2,3, Jing Wang1,2,3
1Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
2Clinical Research Center for Medical Imaging in Hubei Province, Wuhan, Hubei Province, China
3Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei Province, China
OBJECTIVES Noninvasive left ventricular (LV) pressure-strain myocardial work (MW) is a novel method for evaluating LV function by integrating myocardial deformation and afterload, with advantages over global longitudinal strain (GLS). The study aims to analyze MW in patients with well-functioning bicuspid aortic valve (BAV) and explore the influences of aortic dilation and arterial stiffness on LV function.
METHODS A total of 104 patients with well-functioning BAV and 50 controls were enrolled in our study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), global longitudinal strain (GLS), and aortic stiffness index were measured. Based on the ascending aorta diameters, BAV patients were divided into three subgroups (nondilated, mild dilated, and moderate dilated).
RESULTS GWI, GCW, GWW, and aortic stiffness index were increased (all P<0.05), while GWE and GLS were significantly reduced (all P<0.001) in total BAV patients compared with controls. BAV patients with mild dilated aorta and moderate dilated aorta had increased GWW and aortic stiffness index, and a decreased GWE compared with BAV patients with nondilated aorta (all P<0.05), whereas GCW and GLS did not differ among BAV subgroups (all P>0.05). GWI was elevated in BAV patients with moderate dilated aorta compared with BAV patients with nondilated aorta (P<0.05).
CONCLUSIONS Myocardial work could assess myocardial impairment early in patients with well-functioning BAV. MW may help to differentiate the detrimental effect of aortic dilation on LV function, whereas GLS may not.
GW34-e0663
Yu-Ting Tan1,2,3, Ming-Xing Xie1,2,3, Jing Wang1,2,3
1Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
2Clinical Research Center for Medical Imaging in Hubei Province, Wuhan, Hubei Province, China
3Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei Province, China
OBJECTIVES Chronic aortic regurgitation (AR) is a cardiac lesion combining left ventricular (LV) pressure and volume overload characteristics, eventually detrimental to the myocardium. Noninvasive myocardial work offers a promising method to evaluate LV myocardial performance as it integrates myocardial deformation and afterload. The study aimed to investigate the value of noninvasive LV myocardial work in LV dysfunction in patients with chronic AR after aortic valve surgery.
METHODS Pre-operative LV ejection fraction (LVEF), global longitudinal strain (GLS), and noninvasive LV myocardial work parameters (work index [GWI], constructive [GCW] and wasted [GWW] work, and work efficiency [GWE]) were measured. Post-operative LV impairment defined as LVEF<50% at 6 to 12 months after surgery. The logistic regression model was used to determine the independent association between noninvasive LV myocardial work indices and post-operative LV dysfunction.
RESULTS The study included one hundred and twenty-five (50.02±10.16 years; 83.2% men) with severe chronic AR and preserved LVEF who underwent aortic valve surgery. Seventeen percent developed LV impairment after aortic valve surgery. Patients with post-operative LV dysfunction displayed significantly higher E/e′ ratio, lower LVEF and LV GLS. Compared with patients without post-operative LV dysfunction, patients with post-operative LV dysfunction showed lower GWI (1932.85±136.55 mmHg% vs 1795.43±143.83 mmHg%, P<0.001), GCW (2223.96±164.53 mmHg% vs 2120.57±162.57 mmHg%, P=0.010) and GWE (92.68±1.39% vs 90.38±2.13%, P<0.001), higher GWW (165.88±37.83 mmHg% vs 207.48±57.74 mmHg%, P<0.001). Moreover, a multivariate logistic regression model with GWE (Odd ratio [OR]: 0.47; 95% confidence interval [CI]: 0.34 to 0.67; P<0.001; Akaike information criterion [AIC]=86.234, C-index=0.836) showed the best capability in predicting post-operative LV dysfunction.
CONCLUSIONS Noninvasive LV myocardial work may be paramount in predicting post-operative LV impairment with advantages over afterload-dependent echocardiographic parameters in patients with chronic AR.
GW34-e0666
Su Yuxin
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Using transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) to investigate the occurrence and related causes of iatrogenic atrial septal defect (iASD) after catheter ablation combined with left atrial appendage closure (LAAC) for atrial fibrillation (AF).
METHODS We retrospectively analyzed 330 patients that underwent combined procedure of catheter ablation for AF and LAAC at General Hospital of Northern Theater Command from January 2018 to March 2022. There were 179 males and 151 females, with an average age of 65.81±4.35 years. These patients underwent TEE at 3 month and TTE at 3, 6 and 12 months after operation and were divided into persistent iASD group and spontaneous closure group according to whether there was persistent iASD at 3-months follow-up. CHA2DS2-VASc score, HAS-BLED score, atrial fibrillation type, preoperative anticoagulation, type/size of device, type/size of sheath, number/position of TSP, procedure time of left atrium. TTE was used to measure the left atrial diameter (LAd), left atrial ejection fraction (LAEF), mitral and tricuspid valve regurgitation area and regurgitation velocity. TEE was used to assess the LAA. The data from TTE and TEE before and after surgery were collected to evaluate the relevant causes of iASD after combined operation of catheter ablation and LAAC.
RESULTS
1. Comparison of baseline information and operative data between the two groups:
Preoperative left atrial volume was larger in the persistent iASD group (76.5±35.2 mL vs 61.1±21.9 mL, P=0.036).
The persistent iASD group has longer procedure time within left atrium (92.1±36.3 vs 69.1±17.8 min, P=0.003) and larger size of sheath (4.1±1.2 mm vs 3.3±1.2 mm, P=0.022). We found that the use of ICE was associated with iASD (P=0.048). In addition, we also observed that the puncture site was relatively low, about 1.85±2.23 cm above the ostium of the inferior vena cava.
2. Comparison on Echocardiographic parameters 3 months after operation between the two groups:
The persistent iASD group had higher occurrence of postoperative MR (32.3 vs 12.8%, P=0.018) and postoperative TR (27.1 vs 7.3%, P=0.002).
Results of Logistic regression analysis:
The risk factors for the closure of iASD were larger left atrium before operation, higher pressure of left atrium, longer operation time within left atrium, larger size of sheath and the use of ICE during operation (P<0.05). The risk of non-closure of iASD increased by 20.8% for every 1 mm increase in the size of left atrium before operation. The more severe the MR, the more difficult the closure of iASD (OR 3.936).
CONCLUSIONS
1. The occurrence of iASD 3 months after combined atrial fibrillation ablation and LAAC was high.
2. The size of left atrium, the pressure of left atrium, the manipulation time within left atrium, the size of sheath, and the use of ICE during operation was related to the closure of iASD.
GW34-e0674
Yu Xie1,2, Li Zhang1,2, Mingxing Xie1,2
1Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
2Hubei Province Key Laboratory of Molecular Imaging
OBJECTIVES Acute cardiac allograft rejection (ACAR) is one of the main reasons for mortality after heart transplantation. Its precise diagnosis has always to be a big obstacle in the clinic. Lymphocyte infiltration is essential in ACAR, and CD4+ lymphocytes were crucial. We hypothesized that ultrasound molecular imaging with nanobubbles targeted to CD4+ lymphocytes (NBCD4) could achieve the precise diagnosis of ACAR.
METHODS NBCD4 were fabricated by conjugating anti-CD4 antibodies onto nanobubbles, and isotype-conjugated nanobubbles (NBIso) were the isotype control. The characteristics and target abilities were assayed. Rat heart transplantation models were established. Ultrasound molecular imaging was performed in the syngeneic group, the allogeneic groups on post-operative day (POD) 1 and 3, and cyclosporin A (CsA)-treated allogeneic group. Histology was further analyzed for ACAR grading and infiltrating CD4+ cell quantification.
RESULTS NBCD4 adhered to CD4+ lymphocytes more efficiently than NBIso did. In the allogeneic POD3 group and CsA-treated group, the ultrasound molecular imaging signals of NBCD4 were significantly higher than those of NBIso. In the syngeneic group and allogeneic POD1 group, the signals of NBCD4 and NBIso were comparable. Furthermore, the signal of NBCD4 on POD3 allografts was significantly higher than that on CsA-treated allografts, which was still significantly higher than that on POD1 allografts. The signals of NBIso were not conspicuously different in different groups. Histology confirmed no rejection in isografts, 1R rejection in POD1 allografts, 2R rejection in CsA-treated allografts, and 3R rejection in the untreated POD3 allografts. Moreover, the signals of NBCD4 were strongly correlated with the rejection grades, as well as the number of infiltrated CD4+ lymphocytes.
CONCLUSIONS Ultrasound molecular imaging with NBCD4 might be a new approach to achieve the precise diagnosis of ACAR.
GW34-e0802
Zhuxin Wei1, Hongchuang Xu2, Xing Yang2, Shihua Zhao1
1Department of MRI, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
2Department of Nuclear MedicinePeking, University First Hospital
OBJECTIVES Ischemic myocardial tissue often causes an unsuitable local inflammatory response resulting in structural and biochemical changes that cause adverse cardiac remodeling and the subsequent heart failure after MI. Thus, accurate evaluation of harmful inflammation and apoptosis after MI can help guide preventive treatment in the clinic. The role of inflammation mediated by monocyte-macrophage cell system and molecular imaging targeted these have been the subject of experimental research in the field of myocardial injury remodeling for decades, whereas T lymphocytes cells have only recently come into focus. Recently, the role of cytotoxic CD8+ T lymphocytes has been revealed that the CD8+ T lymphocytes are recruited in the ischemic heart and release of Granzyme B (GzmB) leading to enhanced apoptosis and myocardial inflammation. Studies on GzmB indicated that it contributes to tissue remodeling and fibrosis by augmenting inflammation and promoting fibroblast activation. Therefore, we investigated for the first time (to our knowledge) the effects of GzmB on inflammation, repair and functional outcomes in myocardial infarction rats model using 68Ga-grazytracer PET/CT imaging.
METHODS Forty-six male Sprague-Dawley rats underwent permanent ligation and a 30-min transient occlusion of left coronary artery. The rats underwent 68Ga-grazytracer PET/CT on days 1, 3, 6, 14 and 28 after myocardial infarction. The percentage injected tracer dose per gram of within the infarct and remote tissue were assessed. Autoradiography was used to verify the effect of in vitro imaging. The Masson stain and immunohistochemical of GzmB and CD8+ were tested to assess CD8+ T cells recruited, GzmB released and fibrous repairment in infarct and remote tissues. Hearts were harvested on days 1, 3, 6, 14 and 28 after myocardial infarction for ex vivo analyses (enzyme-linked immunosorbent assay) of inflammation and repair related markers. The ischemia reperfusion model rats were tested PET/CT to analyze the relationship between infarct size and GzmB signal. The treatment group received GzmB inhibitor carbobenzoxy-IETD-fluoromethylketone (Z-IETD-FMK) early and late induce CD8+ T cells functional depletion and then underwent 68Ga-grazytracer PET/CT to test inhibitory effect. Cardiac functional tests were performed by echocardiograph to assess cardiac function 6 weeks after myocardial infarction.
RESULTS There were significantly increased 68Ga-grazytracer uptake within the infarct on days 1, 3, 6, 14 after myocardial infarction (P<0.01). Immunohistochemical showed significantly higher expression of GzmB and CD8, in line with PET/CT imaging result. And small amount of GzmB release was also present in the remote myocardial tissue. Autoradiography showed that 68Ga-grazytracer accumulation was observed in the infarcted myocardium defined by histology. The 68Ga-grazytracer uptake of ischemia reperfusion rats and GzmB inhibitor treated rats were significantly reduced compared with myocardial infarction groups (P=0.015 and P=0.013). Echocardiographic cardiac function showed that left ventricular end-diastolic volume (EDV) and end-systolic volume (ESV) were larger and left ventricular ejection fraction (LVEF) was lower in myocardial infarction than in ischemia reperfusion group. Late GzmB inhibitor treatment was shown to be effective in improving cardiac function without significant shortening of infarct size.
CONCLUSIONS This study highlighted the potential of 68Ga-grazytracer imaging to delineate adverse inflammatory response and pathological cardiac remodeling, predict heart function. PET/CT imaging-guided therapy can limit myocardial injury and improve heart function after short-term GzmB inhibition in myocardial infarction.
GW34-e1116
Yifan Chen1, Leilei Cheng2, Junbo Ge1
1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China
2Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging
OBJECTIVES Transcatheter duct closure (TCDC) of patent ductus arteriosus (PDA) can be guided by aortoangiography (AAG) or transthoracic echocardiography (TTE), but feasibility of TTE-guided TCDC for all duct types and sizes remains uncertain. This study sought to investigate the comparative outcomes of TTE-guided versus AGG-guided TCDC for all duct types with various sizes.
METHODS AAG and TTE was used as a major procedural guidance of AGG-guided and TTE-guided TCDC, respectively. Clinical and echocardiographic follow-up were conducted. The primary endpoints were the intraprocedural device occluding success (DOS) defined as successfully delivering, positioning, fixing and releasing ADO without ADO-dislodgement/embolism; and one-year clinical occluding success (COS) as no residual shunting or procedure-associated complications (PACs). The secondary endpoint was PACs and its component of ADO-migration/embolism, ADO-caused obstruction, hemolysis, any cardiac surgery due to PACs or death.
RESULTS Of 842 included patients, 308 were treated by AAG-guided TCDC and 534 by TTE-guided TCDC. There was insignificant difference in baseline characteristics between the treatments. Compared AAG-guided versus TTE-guided TCDC, the final DOS was similar (100.0 vs. 99.8%, P>0.05) with more ADO replacing-reoccluding per DOS (0.12 vs. 0.06, P<0.05) in AAG-guided TCDC; COS was also similar (95.3 vs. 97.1%, P>0.05) with comparable PACs (2.5 vs. 1.2%, P>0.05) at one-year. There were 2 intraprocedural ADO-dislodgement/embolization (1 in each treatment), and 1 acute hemolysis (leading to surgical ADO extraction and duct ligation) in TTE-guide TCDC. No death occurred in one-year follow-up.
CONCLUSIONS For closure of all duct types with various sizes, TTE-guided and AAG-guided TCDC are associated similarly with high intraprocedural device success, one-year clinical success and few procedure-associated complications.
GW34-e1118
Xiaorui Xiang, Shihua Zhao
Fuwai Hospital
OBJECTIVES Trabecular complexity is a unique biometric marker like fingerprint, but its prognostic impact in patients with dilated cardiomyopathy (DCM) remains unclear. This study aimed to explore the prognostic value of trabecular complexity by using fractal analysis in patients with DCM.
METHODS A total of 276 consecutive patients with DCM from January 2011 to December 2012 were enrolled in this study. Comprehensive clinical evaluation and cardiovascular magnetic resonance (CMR) imaging investigation were obtained. Trabecular complexity was quantified with fractal analysis of cine images to estimate the global, basal, and apical fractal dimensions (FD). All patients were followed up for major adverse cardiac events (MACE) of all-cause mortality, aborted sudden cardiac death, and heart transplantation. Univariable and multivariable Cox regression analyses were applied to identify the predictors. Patients’ survival was illustrated by Kaplan-Meier curves and differences were evaluated by log-rank test. The reproducibility of FD assessment was evaluated by intraclass correlation coefficients.
RESULTS Over a 5.37-year median follow-up, 103 (37.32%) patients experienced MACE. All left ventricular FD parameters were higher in patients with events than those without events (all P<0.05). Max Basal FD emerged as the strongest MACE prognosticator among FD parameters (area under the curve [AUC], 0.84 [95% CI, 0.78–0.88]), and the optimal cutoff value was 1.27. Furthermore, Cox proportional hazards analysis revealed that Max Basal FD was independently associated with MACE (hazard ratio [HR]:1.07 per %, P=0.002) after adjustment for clinical and imaging risk factors including NT-proBNP, left ventricular ejection fraction (LVEF), and late gadolinium enhancement (LGE) presence. By Kaplan-Meier analysis, the risk of MACE increased significantly with increased Global FD, Mean Basal FD, and Max Basal FD (all log-rank P<0.001).
CONCLUSIONS Left ventricular max basal FD was an independent predictor of adverse outcomes, and fractal analysis may contribute to improving the risk stratification for patients with DCM.
GW34-e1158
Ruohan Zhao1,2, Jing Zhang1,2, Yuting Tan1,2, Siyi Zhang1,2, Li Zhang1,2, Mingxing Xie1,2, Qing Lv1,2
1Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2Hubei Province Key Laboratory of Molecular Imaging
OBJECTIVES Coronary artery disease (CAD) without wall motion abnormality is difficult to diagnose clinically before coronary angiography. The object of this study is to investigate the diagnostic value of echocardiographic non-invasive pressure/volume loop (P/V loop) for CAD without wall motion abnormality and to establish a novel diagnostic model.
METHODS A total of 204 patients with suspected CAD without wall motion abnormality were enrolled. According to random allocation at the ratio of 7:3, they were divided into the training set (144 cases) and the validation set (60 cases). All patients underwent coronary angiography to confirm diagnosis. Conventional echocardiographic parameters such as left atrial diameter, left ventricular diastolic volume index, etc. were obtained. The noninvasive P/V loop was obtained by left ventricular diastolic volume, left ventricular systolic volume, systolic blood pressure, diastolic blood pressure, early diastolic mitral flow velocity E, late diastolic mitral flow velocity A, and early diastolic mitral lateral annulus velocity e′. Stroke work (SW), filling energy (FE), total energy (TE), end systolic energy (ESE) and energy efficiency (EE) were inferred from the P/V loop. Logistic regression was used to develop a multi-parameter model including gender, diabetes, and EE for the diagnosis of CAD without wall motion abnormality. The diagnostic performance of the model was tested in the validation set.
RESULTS There were 101 (70.1%) patients with CAD in the training set. TE (10186.77±2888.34J vs. 9017.12±2531.66J, P<0.05) and ESE (4942.10± 1623.74J vs. 4126.67±1250.82J, P<0.05) were significantly higher in CHD patients than in non-CHD patients. EE (51.31±4.68% vs. 53.80±5.57%, P<0.05) was significantly lower than that in patients without CAD (P<0.05). SW, TE, FE, ESE were weakly correlated with Gensini score, and the correlation coefficients were r=0.18 (P<0.05), r=0.22 (P<0.05), r=0.20 (P<0.05), r=0.25 (P<0.05), respectively. Multivariate stepwise Logistic regression analysis showed that gender (OR, 9.83; 95% CI, 3.66–26.39; P<0.001), diabetes (OR, 9.00; 95% CI, 1.85–43.74; P<0.05), A (OR, 30.52; 95% CI, 2.10–443.41; P<0.05), EE (OR, 0.91; 95% CI, 0.83–0.99; P<0.05) had greater diagnostic value (AUC in training set: 0.84; AUC in validation set: 0.76).
CONCLUSIONS The non-invasive P/V loop based on echocardiography has an independent diagnostic value for coronary artery disease without wall motion abnormality. The diagnostic model in this study included gender, diabetes, A and EE, which could provide a noninvasive and simple pretest probability estimation for CAD without wall motion abnormality before coronary angiography.
GW34-e1175
Tian Xu1, Jia-Cong Nong1, Yi Xu1, Wei You1, Yan-Qing Wang2, De-Feng Pan3, Hai-Bo Jia1, Fei Ye1
1Nanjing First Hospital, Nanjing Medical University
2Jinling Hospital, Clinical Medicine School of Nanjing University
3The Affiliated Hospital of Xuzhou Medical University
OBJECTIVES Negative remodelling (NR) often contributes to stenosis of side branch ostium (SBO), which cannot be recognized by only angiography in bifurcation lesions. Whether NR affects the efficacy of percutaneous coronary intervention (PCI) for SBO in bifurcation lesions remains unclear. To investigate the influence of severe NR (sNR) of SBO for in-stent neointimal hyperplasia (NIH) and clinical outcome for patients who underwent PCI with a 2-stent strategy for distal left main bifurcation (LMb) lesions.
METHODS A total of 328 patients from four Chinese heart centres with true LMb lesions treated with a 2-stent strategy guided by intravascular ultrasound (IVUS) were enrolled into analysis retrospectively. Among them, 48 patients with completed IVUS data pre-, post-PCI and at the 1-year follow-up were considered in phase I analysis with the endpoint of in-stent NIH, then the cut-off value of remodelling index (RI) predicting percent NIH≥50% was used as the grouping basis for sNR and its correlation with target lesion failure (TLF) within 5 years was analyzed in all populations by Kaplan-Meier analysis (in phase II).
RESULTS In phase I analysis, only NR of the left circumflex ostium (LCxO) showed correlation with in-stent NIH (P=0.044), but not for the left anterior descending ostium (LADO). The predictive cut-off values of the RI of the LCxO for percent NIH≥50% was 0.854 by receiver operating characteristic curve analysis (P=0.002). In phase II analysis, the incidence of TLF related to LMb at 5-year follow-up was higher in the sNR (defined as RI =0.85) group than the non-sNR group (32.0 vs 8.1%, P<0.001).
CONCLUSIONS NR of LCxO is associated with more in-stent NIH for distal LMb lesions with a 2-stent strategy, and sNR is linked to percent NIH≥50% at the 1-year follow-up and more TLF at the 5-year follow-up.
GW34-e1199
Ying Han, Wei Tong, Yundai Chen
Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, Beijing, China
OBJECTIVES Inflammation contributes to progression of atherosclerotic plaques, and reflects the disease activity and severity of atherosclerosis. However, detecting and evaluating inflammatory reaction of the unstable plaque by 18F-FDG-PET imaging may put human body in danger due to its radioactivity. Magnetic particle imaging (MPI) is an emerging, highly sensitive, radiation-free, and no-tissue-background tomographic technique that uses superparamagnetic iron oxide nanoparticles (SPIONs) as its contrast agent. Theoretically, SPIONs can be taken up by accumulated macrophages via surface scavenger at sites of inflammation. Therefore, We aimed to investigate: 1) whether SPIONs-enhanced MPI could assess inflammation in unstable plaques by imaging macrophages; 2) compare the efficacy of four types of commercially available SPIONs in atherosclerotic inflammation imaging using MPI.
METHODS We fed six-week-old male ApoE−/− mice a high-fat diet and induced unstable plaques by cast placement over the left carotid artery. After twenty weeks, mice were divided in four groups (N=3–4) and intravenously administered with four types of SPIONs (Fe concentration, 8 mg/kg), including Nanoeast (Nanjing Nanoeast Biotech Co., China), Vivotrax (Magnetic Insight Inc., USA), Synomag (Micromod Partikeltechnologie GmbH, Germany) and Ferumoxytol (AMAG pharmaceuticals, USA). MPI scanning was performed at Pre, 4 h, 12 h, 24 h, 48 h, and 72 h post-injection. Signal-to-noise ratio (SNR) value of unstable plaques on MPI images was calculated. Plaque specimens were analyzed histologically.
RESULTS For the ApoE−/− mice injected with Nanoeast, the MPI SNR values of unstable plaques at multiple time points were 1.20±0.12 (Pre), 7.11±0.79 (4 h), 9.86±1.94 (12 h), 12.20±1.23 (24 h), 6.70±1.15 (48 h), 6.01±1.57 (72 h). These revealed that MPI SNR values reached the peak at 24 h after intravenous injection of Nanoeast. While the MPI SNR values reached the peak at 12 h after intravenous injection of Synomag and Vivotrax, and were both significantly lower than the peak SNR values of the Nanoeast group (Synomag 6.91±0.52 vs. Nanoeast 12.20±1.23, P<0.05; Vivotrax 3.14±0.36 vs. Nanoeast 12.20±1.23, P<0.05). Of interest, the ferumoxytol group showed no significant differences in MPI SNR values between different time points. Histological analysis confirmed that more SPIONs accumulated in the ustable plaques of Nanoeast group than in those of the three other groups.
CONCLUSIONS The radiation-free MPI enabled macrophage detection in atherosclerotic plaques via imaging of SPIONs, which allows in vivo visualization of inflammation in atherosclerosis. Among the commercial MPI contrast agents, Nanoeast shows the highest MPI SNR values and may represent the most promising contrast agent in MPI imaging of atherosclerotic inflammation.
GW34-e1356
Shukun He1,2,3, Qiaofeng Jin1,2,3, Tianshu Liu1,2,3, Mingxing Xie1,2,3, Jing Wang1,2,3
1Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2Clinical Research Center for Medical Imaging in Hubei Province, Wuhan 430022, China
3Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
OBJECTIVES Pressure overload leads to myocardial fibrosis formation and reduction of myocardial compliance, further leads to left ventricular dysfunction, and eventually heart failure (HF). Early assessment of left ventricular remodeling and dysfunction in HF will have implications for the clinical management of HF patients. First-phase ejection fraction (EF1) has been proved to be a sensitive parameter for detection early left ventricular systolic dysfunction. Here we aimed to investigate the diagnostic value of EF1 in the assessment of left ventricular remodeling and dysfunction in HF.
METHODS Six-week-old SD rats were randomly divided into blank control group (n=6), sham-operated group (n=6) and modeling group (n=7). Pressure overload-induced HF model was established by minimally invasive transverse aortic constriction. Serial echocardiography was performed weekly to evaluate EF1, myocardial strain and conventional parameters in baseline and 4 consecutive weeks after operation. Rat hearts were examined weekly for haematoxylin and eosin staining and Masson’s trichrome staining analysis. The correlation between EF1 and left ventricular fibrosis and hypertrophy were analyzed.
RESULTS EF1 was decreased at 2 weeks after operation, and further reduced with the progress of observation time (P<0.05). Left ventricular global longitudinal strain (GLS) and ejection fraction (EF) impaired at 3 weeks after operation (P<0.05). Left ventricular fibrosis and hypertrophy presented at 2 weeks after operation, and continued to show an upward trend (P<0.05). Correlation analysis showed that EF1 was strongly correlated with myocardial fibrosis and hypertrophy (r=-0.80, P<0.001 and r=-0.75, P<0.001, respectively).
CONCLUSIONS EF1, the early left ventricular systolic dysfunction predictor, is a sensitive and dynamically accessible biomarker for detecting primitive left ventricular remodeling and dysfunction of HF induced by pressure overload.
CARDIOVASCULAR DISEASE NURSING
GW34-e0016
HuiMin Zhang
Second Hospital of the Army Medical University
OBJECTIVES Growing evidence indicates that nurse staffing affects the hospital mortality. but little is known about whether the educational composition of registered nurses (RNs) in hospitals is related to patient outcomes. To examine whether the proportion of hospital RNs educated at the baccalaureate level or higher is associated with risk-adjusted mortality and failure to rescue (deaths in cardiac patients with serious complications).
METHODS Cross-sectional analyses of outcomes data for 1825 cardiovascular medical, Cardiovascular surgery and CCU patients discharged from our hospitals between March 1, 2022, and December 31, 2022, linked to administrative and hospital data providing information on educational composition, staffing, and other characteristics. Risk-adjusted patient mortality and failure to rescue within 30 days of admission associated with nurse educational level.
RESULTS The proportion of RNs holding a bachelor’s degree or higher ranged from 77 to 97% across the hospital. After adjusting for patient characteristics and wards structural characteristics (size, teaching status, level of technology), as well as for nurse staffing, nurse experience, a 10% increase in the proportion of nurses holding a bachelor’s degree was associated with a 5.6% decrease in both the likelihood of patients dying within 30 days of admission and the odds of failure to rescue (odds ratio, 0.95; 95% confidence interval, 0.91–0.99 in both cases).
CONCLUSIONS In wards with higher proportions of nurses educated at the baccalaureate level or higher, CCU patients experienced lower mortality and failure-to-rescue rates.
GW34-e0220
Zhipeng Bao, Ying He
The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES Radiofrequency catheter ablation (RFCA) for patients with atrial fibrillation (AF) can generate considerable physical and psychological discomfort under conscious sedation. App-based mindfulness meditation combined with an electroencephalography (EEG)-based brain-computer interface (BCI) shows promise as effective and accessible adjuncts in medical practice.
METHODS This single-center pilot randomized controlled trial involved 84 eligible patients with AF scheduled for RFCA, who were randomized 1:1 to the intervention and control groups. Both groups received a standardized RFCA procedure and a conscious sedative regimen. Patients in the control group were administered conventional care, while those in the intervention group received BCI-based app–delivered mindfulness meditation from a research nurse. The primary outcomes were the changes in the numeric rating scale, State Anxiety Inventory, and Brief Fatigue Inventory scores. Secondary outcomes were the differences in hemodynamic parameters (heart rate, blood pressure, and peripheral oxygen saturation), adverse events, patient-reported pain, and the doses of sedative drugs used in ablation.
RESULTS BCI-based app–delivered mindfulness meditation, compared to conventional care, resulted in a significantly lower mean numeric rating scale (mean 4.6, SD 1.7 [app-based mindfulness meditation] vs mean 5.7, SD 2.1 [conventional care]; P=0.008), State Anxiety Inventory (mean 36.7, SD 5.5 vs mean 42.3, SD 7.2; P<0.001), and Brief Fatigue Inventory (mean 3.4, SD 2.3 vs mean 4.7, SD 2.2; P=0.01) scores. No significant differences were observed in hemodynamic parameters or the amounts of parecoxib and dexmedetomidine used in RFCA between the 2 groups. The intervention group exhibited a significant decrease in fentanyl use compared to the control group, with a mean dose of 3.96 (SD 1.37) mcg/kg versus 4.85 (SD 1.25) mcg/kg in the control group (P=0.003). The incidence of adverse events was lower in the intervention group (5/40) than in the control group (10/40), though this difference was not significant (P=0.15).
CONCLUSIONS BCI-based app–delivered mindfulness meditation effectively relieved physical and psychological discomfort and may reduce the doses of sedative medication used in RFCA for patients with AF.
GW34-e0223
Tianxi Yu, Guozhen Sun
School of Nursing, Nanjing Medical University
OBJECTIVES Chronic Heart Failure (CHF) still affects millions of people worldwide despite great advances in therapeutic approaches in the cardiovascular field. Cardiac rehabilitation (CR) is known to improve disease-related symptoms, quality of life and clinical outcomes, yet implementation was suboptimal, a frequently low engagement in rehabilitation programs has been found globally. To quantify diverse CR-engaged processes and elucidate predictors of the various levels of CR engagement in CHF patients.
METHODS CHF patients admitted or discharged from cardiology departments between May 1 2022 to November 1 2022 were enrolled. Individuals who met the inclusion criteria filled the questionnaires, including the generalized anxiety disorders scale, patient health questionnaire, cardiac rehabilitation inventory, patient activation measure, Tampa scale for kinesiophobia heart, social frailty, Patient Health Engagement Scale (PHE-s®) We obtained sociodemographic characteristics and clinical data from medical records. The survey was distributed via mobile phone text messaging or face-to-face completed. Chi-square tests and multivariable logistic regression analyses were performed to examine the factors associated with CR engagement phases.
RESULTS A total of 684 patients were included in the study. Univariate analysis showed that only kinesiophobia had no correlation with engagement phases besides socio-demographic and clinical variables. Multivariate logistic regression analysis revealed that compared with the blackout phase process anxiety (Arousal: OR 0.829, 95% CI: 0.73∼0.94; Adhesion: OR 0.725, 95% CI: 0.64∼0.82; Eudaimonic Project: OR 0.674, 95% CI: 0.59∼0.77), monthly income (RMB yuan) equal to or more than 5000 (Arousal: OR 6.342, 95% CI: 1.30∼31.01; Adhesion: OR 5.226, 95% CI: 1.09∼24.96; Eudaimonic Project: OR 6.658, 95% CI 1.26∼34.76) were the most important factor impacting CHF patients CR engagement. In the Arousal phase, versus the Blackout phase, regular exercise or not (OR 3.29, 95% CI: 1.19∼9.10), severe depression (OR 0.019, 95% CI: 0.00∼0.813), previous cardiac-related hospitalizations 1 or 2 times (OR 3.75, 95% CI: 1.19∼11.86), Age (OR 0.958, 95% CI: 0.92∼0.998) influenced patient CR engagement. Besides, compared to the Blackout phase, outcome anxiety (OR 1.269, 95% CI: 1.11∼1.46) and activation level (level 2: OR 9.357, 95% CI: 1.44∼60.68; level 3: OR 29.96, 95% CI: 3.67∼244.92; level 4: OR 29.71, 95% CI: 3.62∼243.61) were independent factors predicting the Eudaimonic Project phase.
CONCLUSIONS This study characterized CR engagement, and explored demographic, medical, and psychological factors-with the most important being process anxiety, monthly income, patient activation, severe depression, and previous cardiac-related hospitalizations. The predictor factors of CR engagement were not identical among different phases which strongly indicates a significant role in quantifying CR engagement. Our findings suggested that factors could potentially be targeted in clinical practice to identify low CR engagement patients, and strategies implemented to strengthen or overcome these associations to address low CR engagement in CHF patients.
GW34-e0264
Zhijie Tang, Guozhen Sun
Nanjing Medical University School of Nursing
OBJECTIVES The sleep quality following radiofrequency ablation in patients with atrial fibrillation is subject to variation due to numerous factors. However, the specific trajectories of sleep quality remain unmapped, and the predictors of such trajectories remain unclear. The objective of this study is to identify the trajectories of sleep quality within six months post-radiofrequency ablation in patients with atrial fibrillation and to determine the multivariate predictors thereof.
METHODS Three hundred patients with atrial fibrillation undergoing radiofrequency ablation were followed up four times over a six-month period. We used patient self-report questionnaire and clinical information system to collect patient related information. The latent class growth analysis (LCGA) was used to identify trajectories of sleep quality. Multinomial Logical Regression was used to identify the influence of socio-demographic, psychological, and clinical factors on trajectories of symptom burden for patients.
RESULTS The study’s findings indicate that patients with atrial fibrillation who underwent ablation experienced a gradual improvement in sleep quality across four assessments, with four distinct trajectories observed: Mild-Gradual Improvement 25.0%, Mild-Stability 32.7%, High-Stability 32.0%, and High-Deterioration 10.3%. Predictive factors for poor trajectories included hypertension, Type D personality, history of atrial fibrillation>3 years, frailty, female, monthly income <3000¥.
CONCLUSIONS There are different trajectory subgroups of sleep quality in patients after atrial fibrillation ablation. Clinical and community health care workers can give patients targeted sleep support measures based on the characteristics of patients after radiofrequency ablation, in order to improve sleep quality.
GW34-e0413
Shuyi Sun1, Min Gao2, Guozhen Sun1,2, Tianxi Yu1, Shenxinyu Liu1, Zhijie Tang1
1The Nursing School, Nanjing Medical University, Nanjing, China
2Department of Cardiology Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
OBJECTIVES Patients with heart failure require multiple self-control to handle physical, psychological, and social challenges, which may result in ego-depletion. However, there is a lack of evidence about ego-depletion in patients with heart failure in China. Hence, this study aimed to explore the level of ego-depletion in patients with heart failure and the associated factors.
METHODS In this cross-sectional study, we screened patients with heart failure treated in the Department of Cardiology Medicine, People’s Hospital of Jiangsu Province between February 2022 and October 2022. T-test, analysis of variance, Pearson correlation analysis, and multiple regression analysis were applied to explore the factors associated with ego-depletion in patients with heart failure.
RESULTS A total of 327 patients with HF were included in the study. The mean and SD of ego-depletion was 44.50±8.18. Univariate analysis showed that education level, household per capita monthly income, exercise habits, sleep status, food intake status, Cardiac function grade of NYHA, age, the number of comorbidities, LAD, BNP, self-care ability, anxiety, depression, and psychological distress were associated with ego-depletion (P<0.05). The multiple linear regression analysis showed that psychological distress, depression and exercise habits were found to be independently associated with the ego-depletion in patients with HF (P<0.01).
CONCLUSIONS Patients with HF experience high level of ego-depletion. Depression, psychological distress, and lack of exercise were considered as independent risk factors of ego-depletion. Health workers should pay enough attention to ego-depletion, improve the understanding of ego-depletion, and apply targeted interventions to alleviate ego-depletion in patients with heart failure.
GW34-e0980
Sisi Wu, Daqiong Wei, Chunhua Long, Xuemei Tu, Shasha Li
Department of Cardiovascular Medicine, Chongqing University Three Gorges Hospital
OBJECTIVES Low physical activity has long been identified as a risk factor for coronary heart disease. Risk factors for physical activity after percutaneous coronary intervention need to be determined. To investigate the level of physical activity in patients after percutaneous coronary intervention at 3 months after discharge, and to explore the influencing factors of physical activity in patients after percutaneous coronary intervention.
METHODS A longitudinal research design was adopted. From April 2021 to December 2021, the patients with acute myocardial infarction in the cardiovascular medicine ward of a tertiary hospital in China were selected by convenience sampling. A general information questionnaire, anxiety screening scale (GAD-7), depression screening scale (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and the Mini-Nutrition Assessment (MNA) were used to investigate influencing factors of physical activity in patients after percutaneous coronary intervention before discharge. Two hundred and forty-one patients were investigated with the International Physical Activity Questionnaire at 3 months after discharge.
RESULTS 72.2% of patients with acute myocardial infarction reported low levels of physical activity 3 months after discharge. Logistic regression analysis showed age (OR=2.060, P<0.001) and sleep quality (OR=21.732, P=0.044) were risk factors for physical activity.
CONCLUSIONS The level of physical activity of patients with acute myocardial infarction 3 months after PCI is low, and age and sleep quality are important predictors of physical activity in patients with acute myocardial infarction. It is recommended to develop a physical activity strategy suitable for the rehabilitation of patients with acute myocardial infarction and to carry out continuous health promotion behaviors as soon as possible.
GW34-e1209
Mengqi Liu1, Pingping He2
1School of Nursing, University of South China
2Medical College, Hunan Normal University
OBJECTIVES This study aimed to describe social isolation in elderly patients with coronary heart disease and examine the relationship between Type D personality, chronic disease resources, experiential avoidance, and social isolation.
METHODS A total of 322 elderly patients with coronary heart disease were recruited at 3 general hospitals from Hengyang, China using convenience sampling method. The Chinese version of the General Alienation Scale (GAS), the Chronic Illness Resource survey (CIRS), the type D personality scale (DS-14) and the Acceptance and Action Questionnaire-II (AAQ-II) were used to collect data from September 2022 to April 2023. The structural equation modelling was used to analyze the serial mediation model.
RESULTS Results from 322 study subjects indicated that social isolation in elderly patients with coronary heart disease is at a moderate or severe levels. Multiple mediation analysis showed that Type D personality had a direct positive effect on social isolation, and the relationship between them can be mediated by chronic disease resources and experiential avoidance, respectively. Moreover, there are serial mediating effect between chronic disease resources and experiential avoidance in this relationship.
CONCLUSIONS Social isolation in elderly patients with coronary heart disease needs attention., especially in patients with type D personality. Improving chronic disease resource and reducing experiential avoidance may be effective strategies to mitigate the adverse impact of type D personality and social isolation. This study extends our understanding of the relationships between Type D personality, chronic illness resources, experiential avoidance, and social isolation among older patients with coronary heart disease. Effective interventions by well-trained healthcare providers are needed to alleviate patients’ social isolation.
CARDIOVASCULAR LAB MED
GW34-e0245
Umida Kamilova, Gulnosa Zakirova, Dylafruz Masharipova, Nuriddin Nuritdinov, Bobur Utemuradov
Republican Specialized Scientific and Practical Medical Center of Therapy and Medical Rehabilitation
OBJECTIVES Assessment of hemostasis parametrs and endothelial dysfunction in COVID-19 convalescents.
METHODS One hundred and five COVID-19 convalescents were examined. Patients were included in the study 4–6 months after infection with COVID-19. The average age of the participants was 51.8±6.7 years. The following laboratory studies were performed: general blood analysis, coagulogram, detection of D-dimer by immunoenzyme method (Vector-Best, Russia), high-sensitivity C reactive protein (CRP) (Demeditec Diagnostics, Germany), endothelin-1, von Willebrand factor (VWF), thrombomodulin was determined by immunoenzymatic method on the Humareader HS (“HUMAN”, Germany) analyzer with the use of Elabscience (USA) reagents.
RESULTS The main markers of endothelial dysfunction - endothelin-1, VWF and thrombomodulin were analyzed depending on hemostasis indicators. In patients with a normal level of fibrinogen (less than 400 mg/dL), endothelin-1 was 82.81±3.12 pg/mL, VWF - 122.69±4.8%, thrombomodulin - 1384±19.2 pg/mL did, and in the group of patients with elevated fibrinogen level (more than 400 mg/dL) compared to patients with normal fibrinogen level, these indicators were 28.5% (r<0.01), 23.5% (r<0.05) and 15.7% (r<0.05) was correspondingly high. In patients with a normal level of D-dimer (less than 0.6 mg/L), the endothelin-1 index was 85.44±2.82 pg/mL, VWF - 116.78±5.95% and thrombomodulin 1215.9±24, 7 pg/mL, and compared to patients with normal D-dimer levels, in patients with high D-dimer levels (more than 0.6 mg/L), these values were 30.8% for endothelin-1 (r<0.01), 28.7% (r<0.01) for VWF and 18.6% (r<0.05) for thrombomodulin were convincingly higher, respectively. Studies have shown that D-dimer levels in patients with COVID-19 persisted long into the post-COVID period and were associated with impaired endothelial function.
CONCLUSIONS In COVID-19 convalescents, coagulation hemostasis indicators - fibrinogen and D-dimer levels were significantly increased, which were associated with signs of endothelial dysfunction. The combined use of three humoral markers characterizing endothelial dysfunction - endothelin-1, VWF and thrombomodulin - opens new perspectives for monitoring in the post-Covid period.
GW34-e0985
Ryuya Naruta1, Sari Nurmali1, Yasufumi Katanasaka1,2,3, Yoichi Sunagawa1,2,3, Toshihide Hamabe-Horiike1,2,3, Masafumi Funamoto1,2, Satoshi Shimizu1, Kana Shimizu1, Akira Murakami4, 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
4Department of Food Science and Nutrition, School of Human Science and Environment, University of Hyogo
OBJECTIVES Heart failure (HF) is one of the leading causes of death in developed countries. Cardiac hypertrophy and fibrosis are known to be essential factors in cardiac remodeling and the progression of HF, but highly effective therapeutic agents targeting these processes have not yet been developed. We have previously shown that natural compounds such as Curcumin inhibit HF by suppressing cardiac hypertrophy and fibrosis in vivo, suggesting that these compounds are possible candidates for HF therapy and prevention. Zerumbone (Zer) is a major active terpene found in the endemic wild ginger species of Southeast Asia. This wild ginger is usually used not only as a spice and fragrance but also as a medicine, mainly in Indonesia and Malaysia. The purpose of this study is to investigate whether the natural compound Zer inhibits cardiomyocyte hypertrophy, fibrosis, and the development of HF.
METHODS To investigate the effect of Zer on cardiac hypertrophy and cardiac fibrotic responses, primary cultured cardiomyocytes and cardiac fibrosis prepared from neonatal rats were pretreated with Zer and then stimulated with phenylephrine (PE) or transforming growth factor beta (TGF-β), respectively. Immunofluorescent staining, quantitative PCR (qPCR) analysis, and western blotting (WB) were performed. To determine whether Zer prevents the development of pressure overload-induced HF in vivo, a transverse aortic constriction (TAC) mouse model was utilized. Cardiac function was evaluated by echocardiography. The cardiomyocyte surface area was observed using histological analysis (HE and WGA staining). Fibrosis formation was measured by picrosirius staining. The total mRNA levels of genes associated with hypertrophy (ANF and BNP) and fibrosis (Postn and α-SMA) were examined by qRT-PCR. The protein expressions (Akt and α-SMA) were assessed by western blotting.
RESULTS To investigate the effect of Zer on cardiac hypertrophy and cardiac fibrotic responses, primary cultured cardiomyocytes and cardiac fibrosis prepared from neonatal rats were pretreated with Zer and then stimulated with phenylephrine (PE) or transforming growth factor beta (TGF-β), respectively. Immunofluorescent staining, quantitative PCR (qPCR) analysis, and western blotting (WB) were performed. To determine whether Zer prevents the development of pressure overload-induced HF in vivo, a transverse aortic constriction (TAC) mouse model was utilized. Cardiac function was evaluated by echocardiography. The cardiomyocyte surface area was observed using histological analysis (HE and WGA staining). Fibrosis formation was measured by picrosirius staining. The total mRNA levels of genes associated with hypertrophy (ANF and BNP) and fibrosis (Postn and α-SMA) were examined by qRT-PCR. The protein expressions (Akt and α-SMA) were assessed by western blotting.
CONCLUSIONS The present study has shown for the first time the protective effect of Zer against PE-induced hypertrophy in cultured cardiomyocytes and TGF-β-induced fibrotic phenotypes in cardiac fibroblasts. Moreover, Zer ameliorates TAC-induced cardiac dysfunction. These suggest that Zer may be a prospective drug candidate for HF prevention in humans.
TRADITIONAL CHINESE MEDICINE
GW34-e0427
Yuxuan Liu1,2, Ping Li2
1Third Clinical Medical College, Beijing University of Traditional Chinese Medicine
2Department of Cardiology, Beijing University of Chinese Medicine Third Affiliated Hospital
OBJECTIVES Visually analyze the scientific achievements of Curcumin in the field of cardiovascular disease, and clarify its research status, hot spots and frontiers.
METHODS The data comes from the Web of Science (WoS) core collection database. The search strategies was TS=(curcumin or “Turmeric Yellow” or “Yellow Turmeric” or “Curcumin Phytosome” or “Phytosome Curcumin” or Diferuloylmethane or Mervia) AND TS=(Cardiovascular or Cardiology or circulation or heart). The language is English. The search scope is from January 1, 2004 to June 13, 2023. The selected literature types are research papers and reviews. All records (including title, author, source code, keywords, abstract, doi) and references in search results are exported in plain text format and download– * * Name in txt format. The search was completed within 1 day (June 13, 2023) to avoid changes caused by daily database updates. Use visual analysis software Cite Space 5.8.R3 for country, institutional, and keyword analysis.
RESULTS A total of 1235 articles related to Curcumin and cardiovascular diseases were included, including 843 research papers and 392 reviews. The global research of Curcumin in the field of cardiovascular disease is on the rise. A total of 82 countries participated in the study, with China being the most productive country and publishing a total of 345 papers. Germany is the country with the highest between centrality (BC). Mashhad University Medical Science not only has the highest BC (0.2), but also has the highest publication volume (66 articles). Sahebkar Amirhossein devoted himself to the research of Curcumin, and published 47 articles in total. Keywords that occur more than 100 times include oxidative stress, curvature, nf kappa b, in vivo, and expression. The top 5 keywords with BC include cancer, activation, disease, apoptosis, and advertisement issue. Lipid peroxidation is the keyword with the strongest explosive intensity.
CONCLUSIONS The research on Curcumin and cardiovascular disease is on the rise as a whole, and the antioxidant mechanism of Curcumin is the focus of researchers.
GW34-e0963
Guanjing Ling, Xiaoping Wang, Yan Wei, Yong Wang
Beijing University of Chinese Medicine
OBJECTIVES Although the development of therapies for heart failure (HF) continues apace, clinical outcomes are often far from ideal. Current studies suggest that mitophagy defects and accumulation of damaged mitochondria are linked to the progression of HF. Developing molecularly targeted agents to enhance mitophagy and characterizing more in-depth mechanisms are of great research value and clinical development prospects for curing HF. Of note, Unc51-like-kinase 1 (ULK1)-mediated mitophagy prevents pathological cardiac remodeling and HF. However, molecularly ULK1-targeted agent to enhance mitophagy is scanty. Ginsenoside Rg3 (Rg3), a major active ingredient of the root of Panax ginseng or Panax notoginseng, exerts a wide range of pharmacological protective effects on cardiovascular diseases. However, whether Rg3 could regulate mitophagy in the heart has never been reported up to now. This study aimed to investigate whether Ginsenoside Rg3 (Rg3) can activate ULK1 to trigger FUNDC1-mediated mitophagy for protecting HF.
METHODS An established HF rat model and transcriptome sequencing were used to evaluate the therapeutic effect and regulatory mechanism of Rg3. Surface plasmon resonance was used to detect the ULK1 binding behavior of Rg3. Loss-of-function approaches in vivo and in vitro were performed to determine the intrinsic mechanism of ULK1 in Rg3-elicited myocardial protection against HF. Adenovirus expressing the pH-sensitive fluorescent protein mt-Keima was used to visualize and quantify mitophagy. Fundc1 siRNA, Fundc1-S17A mutant and Fundc1-S17A mutant of plasmid were applied for mechanistic research.
RESULTS In vivo, Rg3 improved cardiac dysfunction, adverse remodeling, and mitochondrial damage in HF rats. Transcriptomics profiling revealed that Rg3 promoted Ulk1-Fundc1 axis-mediated mitophagy in the heart tissues of HF rats. Consistent with this observation, Rg3 treatment increased the phosphorylation level of Ulk1, which in turn induced the colocalization of Fundc1 and Lc3 to trigger mitophagy both in vitro and in vivo. Structurally, a good binding mode was unveiled between ULK1 and Rg3. Of note, the protective effects conferred by Rg3 against mitophagy defects, the collapse of mitochondrial potential, oxidative stress, and cardiac dysfunction were compromised by Ulk1 gene silencing both in vitro and in vivo, consolidating a pivotal role of ULK1 in Rg3-elicited myocardial protection against HF. Mechanistically, we demonstrated that Rg3 activated mitophagy through inducing ULK1-mediated phosphorylation of FUNDC1 at Ser17 site, not Ser13 site.
CONCLUSIONS Together these observations demonstrated that Rg3 acts as a ULK1 activator for the precise treatment of HF, which binds to ULK1 to activate FUNDC1-mediated mitophagy. Since mitophagy downregulation are observed in various pathological conditions in the heart, pharmacological intervention of Rg3 that activates mitophagy may contribute to curing a broad spectrum of heart diseases via maintaining mitochondria homeostasis and energy metabolism.
GW34-e1147
Meiqi Miao
Heilongjiang University of Traditional Chinese Medicine
OBJECTIVES In order to advance the research progress of combining Chinese and Western medicine in the prevention and treatment of MetS and to provide new ideas for it.
METHODS By outlining the process and mechanism of cellular autophagy, focusing on describing its relationship with the main pathological mechanisms of MetS, and based on modern medical theory and the direction of Chinese medicine understanding, we review the preventive and curative effects of Chinese medicine whole formula and its single active ingredient on MetS through the cellular autophagy pathway.
RESULTS MetS leads to an increased risk of cardiovascular disease and is now a global problem. Autophagy is a dynamic process necessary for the maintenance of energy metabolism in the body. Defects in autophagic homeostasis in the body are closely related to metabolic abnormalities, and the imbalance of energy metabolism caused by autophagy dysregulation is closely related to the main pathological mechanisms of MetS. The whole formula of TCM and the main chemical active ingredients of its single herbs can regulate cellular autophagy and intervene in the development of MetS through anti-inflammation, anti-oxidative stress and regulation of glucolipid metabolism, fully demonstrating its multi-pathway, multi-target and multi-mechanism synergistic regulation. Therefore, the addition of Chinese medicine in clinical practice is expected to bring into full play the interventional effects of Chinese medicine on MetS while Western medicine achieves significant efficacy in a single disease, and the combined treatment of MetS with Chinese and Western medicine will be a promising development direction. The understanding of autophagy in modern medicine is still in progress, and the current treatment methods based on autophagic pathways (such as autophagy enhancers) to improve the metabolic symptoms of MetS have certain clinical effects, but there are still some questions and side effects. The research of autophagy mechanism in Chinese medicine to prevent and treat MetS is also in its initial stage, and there are still many questions that need to be addressed by researchers as far as the current situation is concerned. Therefore, how to regulate autophagy homeostasis, determine its threshold value, and prevent the deterioration of MetS due to defective or excessive autophagy becomes the focus of future research in this field.
CONCLUSIONS In conclusion, this paper summarizes the relationship between cellular autophagy pathway and MetS, and the current status of research on the prevention and treatment of MetS based on autophagy pathway in Chinese medicine, which provides a new idea for the prevention and treatment of MetS in Chinese medicine, and provides a scientific basis for advancing the experimental research and clinical treatment of MetS by combining Chinese and Western medicine.
GW34-e1188
Zhiyuan Zhang, Yuanlong Hu, Xinhai Cui, Mengkai Lu, Chao Li
Shandong University of Traditional Chinese Medicine
OBJECTIVES Astragaloside IV (ASIV) is the primary pharmacologically active compound found in Astragalus propinquus Schischkin, which has potential protective effects on cardiac function. However, there are almost no systematic evaluations of ASIV for the treatment of heart failure (HF).
METHODS Preclinical studies published before December 27th, 2022, were retrieved from PubMed, Web of Science, MEDLINE, SinoMed, Chinese National Knowledge Infrastructure (CNKI), VIP information database, and Wanfang Data information site. The quality of included research was evaluated using SYRCLE’s RoB tool. Review Manager 5.4.1 was used to perform meta-analyses of cardiac function parameters and other indicators. Regression analysis was conducted to observe the dose-efficacy relationship.
RESULTS Nineteen studies involving a total of 489 animals were analyzed in this study. The findings revealed that ASIV exhibited positive effects on various indicators of cardiac function when compared to the control group. These indicators included left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular pressure change rate (±dp/dtmax), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), heart weight/body weight (HW/BW), and left ventricular weight/body weight (LVW/BW). Furthermore, the regression analysis conducted demonstrated that the effectiveness of ASIV in treating heart failure was dependent on the dosage administered.
CONCLUSIONS This is the first meta-analysis evaluating ASIV for HF treatment. Findings suggest that ASIV can inhibit cardiac hypertrophy by reducing cardiac preload and afterload, thereby protecting cardiac function.
GW34-e1294
Menghui Du1, Xiujuan Yan1, Yu Bai1, Jiong Zhang1, Chunying Si2, Tan Wang1, Jie Sun1, Xianghua Liu1, Aishe Gao1, Fang Chen1
1Department of Medical School, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, P.R. China
2The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, P.R. China
OBJECTIVES We have already established a novel herbal screening system for selecting special herbs on calcified aortic valve calcification (CAVD) by Constructing a stable pGL4.10-RLUC-RAGE/CDH11 dual fluorophorence reporter gene vector. The test results show that Puerarin may have effect on aortic valve calcification. In this study, we further investigated the effects of Puerarin against aortic valve calcification via animal experiments.
METHODS Fifty ApoE−/− mice were randomly divided into 5 groups: Control, Model (normal saline of 0.1 mL/10g/d), the puerarin groups (200 mg/kg/d), FPS-ZM1 group (FPS, 1 mg/kg/d of FPS-ZM1) and Rosuvastatin group (ST, 1.6 mg/kg/d of Rosuvastatin calcium). Except for the Control, all mice in the other 4 groups were given free consumption of high-cholesterol diet for 36 weeks to construct calcified aortic valve disease (CAVD) model. Mental state and body weight were observed daily. Cardiac ultrasonography was performed to test Transvalvular pressure difference, peak flow velocity and so on. Blood glucose, blood lipids, blood calcium and phosphorus, alkaline phosphatase (ALP), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) were monitored. HE staining and Alizarin red staining of AV have proceeded. The expression of calcification-related osteocalcin, Runx2, RAGE and CDH11 in the valve was measured by western blot. The expressions of IL-1β, IL-6, and TNF-α in serum were detected by ELISA.
RESULTS The body weight of mice consuming high-cholesterol diet was generally higher than that of the control group (P<0.05). The levels of blood lipids, blood glucose and blood calcium were generally increased in all experimental groups compared to the control (P<0.05). Blood ALP was significantly higher in the model group (P<0.05) and puerarin could reduce the level of ALP. The ultrasonic examination of the heart in the experimental group exhibited symptoms in different degrees while the control was more normal and the symptoms were relieved in puerarin group and ST group (P<0.05). HE staining and Alizarin Red staining showed the points of calcification and lipid deposition in the model group, accompanied by a large number of neutrophils, lymphocytes and other inflammatory infiltrates in the experimental groups. The calcification was reduced in puerarin group, ST group and FPS group (P<0.05). The expressions of calcification related protein osteocalcin, Runx2, RAGE and CDH11 were decreased in puerarin group, ST group and FPS group by western blot (P<0.05). IL-1β, IL-6, and TNF-α were decreased in puerarin group, ST group and FPS group (P<0.05).
CONCLUSIONS High-cholesterol diet and aging promote calcification of the aortic valve. Our novel herbal screening system can effectively select special herbs for CAVD. Puerarin can improve the symptoms of CAVD by reducing inflammatory response and partially by inhibiting RAGE and CDH11.
GW34-e1297
Fang Chen1, Yu Bai1, Menghui Du1, Chunying Si2, Tan Wang1, Jie Sun1, Xianghua Liu1, Aishe Gao1
1Department of medical school, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, P.R. China
2The First Affiliated Hospital of He’nan University of Chinese Medicine, Zhengzhou, Henan, P.R. China
OBJECTIVES Decotion of Huatan Huoxuejiedu is the classical clinic treatment of chest Bi syndrome at the First Affiliated Hospital of Henan University of Traditional Chinese Medicine. This decotion can effectively improved the symptoms of chest Bi by clinical observation. In this study, we investigated the effects and possible mechanisms of Huatan Huoxuejiedu Decotion against Aortic valve calcification via network pharmacological analysis and animal experiment.
METHODS Bioinformatic methods were used to find the effective ingrendients of Huatan Huoxuejiedu Decotion and genes related to the drug targets. 70 ApoE−/− mice were randomly divided into 7 groups: Control, Model (normal saline of 0.1 mL/10g/d), the low, medium and high dose groups of decotion (JDF-L, M, H, 2 g/kg, 4 g/kg and 8 g/kg of the decotion per day), FPS-ZM1 group (FPS, 1 mg/kg/d of FPS-ZM1) and Rosuvastatin group (ST, 1.6 mg/kg/d of Rosuvastatin calcium). Except for the Control, all mice in the other 6 groups were given free consumption of high-fat diet for 36 weeks. Mental state and body weight were observed daily. At the end of 36 week, Cardiac ultrasonography was performed to test Transvalvular pressure difference, peak flow velocity and so on. Blood glucose (Glu), blood lipids, blood calcium (Ca) and phosphorus (P), alkaline phosphatase (ALP), alanine aminotransferase (ALT), blood urea nitrogen (BUN) were monitored. HE staining and Alizarin red staining of AV were proceeded. The expression of osteocalcin, Runx2, and RAGE, MAPK/NF-κB, JAK/STAT expression in valve were measured by western blot. The expressions of inflammatory cytokines in serum were detected by ELISA.
RESULTS Network pharmacology showed that Decotion of Huatan Huoxuejiedu could retard CAVD progress by AGE/RAGE axis and subsequent MAPK/NF-κB, JAK/STAT pathways. Animal experiment showed the body weight of mice consuming high-fat diet was generally higher than that of the control group (P<0.05). Compared with the Control group, the levels of HDL and P in all the drug administration group and the model group were decreased, and the levels of TG, TC, LDL, Ca, ALT and BUN were generally increased. Blood ALP was significantly higher in the model group and the JDF-L group (P<0.05), while ALP levels were significantly lower in the remaining groups (P<0.05). The ultrasonic examination of the heart in the experimental group exhibited symptoms in different degrees while control was more normal and the symptoms relieved in JDF-L, M, H groups (P<0.05). HE staining and Alizarin Red staining showed the points of calcification and lipid deposition in the model group, accompanied by a large number of neutrophils, lymphocytes and other inflammatory infiltrates. The calcification was reduced most in JDF-H group (P<0.01). The expressions of calcification related protein osteocalcin, Runx2 and pathway related protein RAGE, p38MAPK, JAK, p-STAT3, STAT3, STAT5, p-STAT5, NF-κB (p65), ERK and Jun in JDF-H, statin and FPS group were decreased by western-blot (P<0.05). IL-1β, IL-6, and TNF-α were decreased in JDF-L, M, H groups (P<0.05), especially for the JDF-H group (P<0.01).
CONCLUSIONS High-fat diet and aging promote calcification of the aortic valve. Huatan Huoxuejiedu decotion, FPS-ZM1 and statin can improve the symptoms of CAVD especially for the JDF-H group. Huatan Huoxuejiedu decotion may exhibit anti-CAVD effect via RAGE related pathways and decreasing of inflammatory cytokine release.
CARDIOVASCULAR PREVENTION AND REHABILITATION
EPIDEMIOLOGY AND EVIDENCE-BASED MEDICINE
GW34-e0075
Zhenhong Ou1, Xiaoqing Liu2, Yunlin Chen2, Fangchao Wang1, Boli Ran1, Kui Cui1, Yuehui Yin2
1Chongqing General Hospital
2The Second Affiliated Hospital of Chongqing Medical University
OBJECTIVES Intensive lipid-lowering using proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors reduces the risk of major adverse cardiovascular events (MACEs) in patients with high-risk or established atherosclerotic cardiovascular disease (ASCVD). But time to benefit (TTB) for the addition of PCSK9 inhibitors is not to be investigated. We performed this meta-analysis to evaluate the TTB for prevention of a MACE with the addition of PCSK9 inhibitors upon standard therapy.
METHODS MEDLINE, Embase, CENTRAL and Web of Science were searched for Randomized controlled trials that compared the addition of PCSK9 inhibitors with placebo upon standard treatment in adults with high-risk or established ASCVD until November 18, 2022. Kaplan-Meier curves were extracted to reconstruct individual survival data. Individual TTB and confidence intervals under the specific absolute risk reduction (ARR) threshold at each trial were calculated by Weibull curve fitting and Markov chain Monte Carlo methods. A random-effects meta-analysis was conducted to estimate the overall TTB.
RESULTS Seven trials randomizing 56954 adults (mean age, 60.9 years; 27.8% were woman) were included in the analysis. Similar MACEs commonly including myocardial infarct, stroke and cardiovascular death were defined in each trial. The addition of PCSK9 inhibitors to standard treatments significantly reduced the hazard of MACE by 19% (hazard ratio, 0.81; 95% CI, 0.77–0.85; P<0.001). Overall, 2.6 (95% CI, 1.2–6.3) months was the average needed to prevent 1 MACE for 1000 patients (ARR, 0.001) treated with PCSK9 inhibitors. Similarly, 4.3 (95% CI, 2.4–8.4), 9.1 (95% CI, 5.4–15.8) and 16.6 (95% CI, 10.4–27.8) months were estimated to avoid 1 MACE for 500 (ARR, 0.002), 200 (ARR, 0.005) and 100 (ARR, 0.01) patients, respectively.
CONCLUSIONS In patients with high-risk or established ASCVD, the addition of PCSK9 inhibitors upon standard therapy may need approximately 3 months at least to produce additional cardiovascular benefits and are more likely to benefit individuals with a life expectancy of longer than 1.5 years.
GW34-e0091
Zhen Hu1, Xin Wang1, Congyi Zheng1, Linfeng Zhang1, Zuo Chen1, Haoqi Zhou2, Xue Cao1, Yixin Tian1, Runqing Gu1,3, Ye Tian1, Lan Shao1, Zengwu Wang1
1Division of Prevention and Community Health, 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, Beijing 102308, China
2Department of Biostatistics, Peking University, Beijing 100191, China
3School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
OBJECTIVES Both medication and non-medication therapies are effective approaches to control blood pressure (BP) in hypertension patients. However, the association of joint changes in antihypertensive medication use and healthy lifestyle index (HLI) with BP control among hypertension patients is not reported, which needs to be validated by prospective intervention studies. We examined the association of antihypertensive medication use and HLI with BP control among employees with hypertension in China based on a workplace-based multicomponent intervention program.
METHODS Between January 2013 and December 2014, a cluster randomized clinical trial of a workplace-based multicomponent intervention program was conducted in 60 workplaces across 20 urban areas in China. Workplaces were randomly divided into intervention (n=40) and control (n=20) groups. Basic information on employees at each workplace was collected by trained professionals, including sociodemographic characteristics, medical history, family history, lifestyle behaviors, medication status and physical measurements. After baseline, the intervention group received a 2-year intervention to achieve BP control, which included: (1) a workplace wellness program for all employees; (2) a guidelines-oriented hypertension management protocol. HLI including nonsmoking, nondrinking, adequate physical activity, weight within reference range and balanced diet, were coded on a 5-point scale (range, 0–5, with higher score indicating a healthier lifestyle). Antihypertensive medication use was defined as taking drug within the last 2 weeks. Changes in HLI, antihypertensive medication use and BP control from baseline to 24 months were measured after the intervention.
RESULTS Overall, 4655 employees were included (mean [standard deviation] age, 46.3 [7.6] years; 3547 men [82.3%]). After 24 months of the intervention, there was a significant improvement in lifestyle [smoking (0.65, 95% CI, 0.43∼0.99; P=0.045), drinking (OR=0.52, 95% CI, 0.40∼0.68; P<0.001), regular exercise (OR=3.10, 95% CI, 2.53∼3.78; P<0.001), excessive intake of fatty food (OR=0.17, 95% CI, 0.06∼0.52; P=0.002), restrictive use of salt (OR=0.26, 95% CI, 0.12∼0.56; P=0.001)]. Compare to employees with a deteriorating lifestyle after the intervention, those with an improved lifestyle had a higher BP control. In the intervention group, compared with employees not using antihypertensive medication, those who consistent used (OR, 2.34; 95% CI, 1.16∼4.72; P=0.017) or changed from not use to use antihypertensive medication (OR, 2.24; 95% CI, 1.08∼4.62; P=0.030) had higher BP control. Compared with those having lower HLI, participants with a same (OR, 1.38; 95% CI, 0.99∼1.93; P=0.056) or high (OR, 1.79; 95% CI, 1.27∼2.53; P<0.001) HLI had higher BP control. Those who used antihypertensive medication and had a high HLI had the highest BP control (OR, 1.88; 95% CI, 1.32∼2.67, P<0.001). Subgroup analysis also showed the consistent effect as the above.
CONCLUSIONS These findings suggest that adherence to antihypertensive medication treatment and healthy lifestyle were associated with a significant improvement in BP control among employees with hypertension.
GW34-e0122
Xue Cao, Yixin Tian, 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 Elaborating and understanding disparities in the burden of cardiovasular disease (CVD) attributable to high fasting plasma glucose (FPG) is important to improve diabetes prevention and cardiovascular health. In this study, we estimate the CVD burden attributable to high FPG at national and provincial levels in China.
METHODS We pooled data on people aged 25 years and older from population-based studied that had collected data on FPG levels through measurement of its biomarkers. The temporal-spatial Bayesian hierarchical model was used to estimate age-specific, sex-specific, province-specific, and year-specific average FPG levels from 2010 to 2018. Then we estimate population attributable fraction for CVDs by age and sex for 31 provinces. The mortality data for CVD at the provincial level were obtained from surveillance systems, which were used to compute the portion of deaths and years of life lost (YLLs) due to CVD that could be attributed to high FPG using the counterfactual scenario of theoretical minimum risk level. We also decomposed trends in attributable burdens into four explanatory components, including population growth, population aging, risk exposure to FPG, and in risk-deleted mortality rates for CVD.
RESULTS In 2018, an estimated total of 512.29 thousand (95% UI 488.60 to 538.65) adults aged 25 or older in China were attributable to high FPG, with 281.54 thousand (95% UI 267.89 to 295.05) of these deaths occurring in men and 229.75 thousand (95% UI 210.98 to 251.89) in women. High FPG accounted for 1093.45 crude YLLs per 100,000 people (95% UI 1059.13 to 1131.73) due to FPG-related CVD in 2018, with substantial variation across provinces. The age-standardised CVD mortality rate attributable to high FPG increased by 3.99%, from 41.93 per 100,000 people (95% UI 40.07 to 43.88) in 2010 to 43.60 per 100,000 (95% UI 41.77 to 45.62) in 2018. For specific causes, ischaemic heart disease was the most important contributor to FPG-related CVD deaths (254.13 thousand [95% UI 235.63 to 274.51]) in 2018, followed by ischemic stroke (139.95 thousand [95% UI 128.14 to 152.81]) and hemorrhagic stroke (117.56 thousand [95% UI 112.65 to 123.23]). In 2018, the highest age-standardised CVD mortality rate attributable to high FPG was observed in the high-middle SDI region and the middle SDI region. By province, the age-standardised mortality rate due to FPG-related CVD in both sexes combined varied from 21.31 per 100,000 people in Tibet to 77.66 per 100,000 people in Heilongjiang in 2018. Nationally, compared to 2010, exposure to high FPG and population aging in 2018 were the primary drivers of increased FPG-related deaths due to CVD, and the proportion of FPG-related CVD death attributed to population ageing in 31 provinces ranged from −3.10 in Hainan to 58.36% in Shanghai.
CONCLUSIONS The CVD burden attributable to high FPG is still large in China, and varied markedly across regions and provinces. Population ageing was associated with substantial changes in the number of FPG-related CVD deaths between 2010 and 2018. Findings in this study call for renewed efforts to implement population-specific tailored measures for diabetes prevention and cardiovascular health.
GW34-e0125
Yi Ren
Institute of Microcirculation, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China
OBJECTIVES High blood pressure is a key pathogenetic factor that contributes to the deterioration of kidney function. However, the incidence trend of hypertension-related chronic kidney disease (CKD) has rarely been studied; therefore, we aimed to analyze the global, regional, and national patterns, temporal trends as well as burden of hypertension-related CKD.
METHODS We extracted data on hypertension-related CKD from the Global Burden of Disease (GBD) study database, including the incidence, prevalence, disability-adjusted life years (DALYs), and mortality numbers and rates (per 100,000 population) and further described according to year, location, sex, age, and socio-demographic index (SDI). The estimated annual percentage changes (EAPCs) were calculated to assess the variation in incidence, DALYs, and mortality. We used an age-period-cohort (APC) model framework to analyze the underlying trends in prevalence by age, period, and birth cohort. Nordpred APC analysis was performed to predict the future morbidity and mortality of hypertension-related CKD.
RESULTS In 2019, a total of over 1.57 million new hypertension-related CKD cases were reported worldwide, a 161.97% increase from 1990. Compared to 1990, the age-standardized incidence rates (ASIR) increased in all 21 regions in 2019. In all countries and territories except Iceland, the EAPC in ASIR and the lower boundary of its 95% confidence interval (CI) were higher than 0. From 1990 to 2019, the global age-standardized mortality rates (ASMR) from hypertensive heart disease, ischemic heart disease, and stroke attributed to high systolic blood pressure decreased by 21.49% (95% UI: 10.13 to 35.18%), 32.64% (95% UI: 28.74 to 36.81%) and 34.89% (95% UI: 28.69 to 40.87%), respectively, but a similar decrease was not observed for hypertension-related CKD, which actually increased by 17.56% (95% UI: 7.59 to 24.87%). ASIR, age-standardized prevalence rates (ASPR), age-standardized DALYs rates (ASDR), and ASMR were not identical among countries with different SDI regions in 2019; additionally, ASIR and ASMR were significantly different among sexes in all SDI regions in 2019. The predicted incidence and mortality counts globally continue to increase to 2044, and there is an upward trend in ASIR for both men and women.
CONCLUSIONS Between 1990 and 2019, the ASIR of hypertension-related CKD demonstrated an ascending trend, and according to our projections by Norpred APC model, it would remain on the rise for the next 25 years and reach 21.28 (per 100,000 population) in 2044. Blood pressure lowering treatment significantly reduced the risk of major adverse cardiovascular events and stroke in various populations of hypertensive patients; however, there was a lack of overall benefit of blood pressure lowering for CKD. With remarkable global population growth, aging, and an increasing number of patients with hypertension, the burden of disease caused by hypertension-related CKD continues to increase.
GW34-e0158
Yunfei Wu1, Tianshu Han2, Jun Lyu3, Yidan Wang1, Wenbo Qu1, Shanjie Wang1, Feiyuan Han1, Shiqi Yuan4, Xiangwen Xi1, Wenjun Ni1, Yanwen Zhang1, Xueyu Wang1, Shan Zhong1, Minghui Piao1, Bo Yu1, Jinwei Tian1
1Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, 246 Xuefu Road, Harbin 150081, China
2National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
3Department of Clinical Research, The First Affiliated Hospital of Jinan University, 613 West Huangpu Avenue, Guangzhou 510630, China
4Department of Neurology, The First Affiliated Hospital of Jinan University, 613 West Huangpu Avenue, Guangzhou 510630, China
OBJECTIVES The risk of cardiovascular disease (CVD) in cancer survivors is an important area of concern, and there is a lack of relevant prospective studies. A reliable evaluation of CVD risk for sitespecific cancers is therefore crucial to guide the treatment and improve the prognosis of survivors with various site-specific cancers. This study aimed to analyze the risk of a wide range of specific CVDs in survivors with site-specific cancers compared with cancer-free controls.
METHODS Cancer diagnosis was determined by linked data from the Medical Research Information Service and The Information Services Division, while CVD diagnosis was ascertained via record linkage from health episode statistics records and Scottish morbidity records. We used Cox proportional hazards regression to assess the association between cancer sites and CVD outcomes after adjustment for age, sex, Townsend deprivation index, ethnicity, college degree, drinking status, smoking status, physical activity, healthy diet, family history (stroke, heart diseases), and 11 comorbidities (type 2 diabetes, lipidemia, hypertension, chronic obstructive pulmonary disease, chronic kidney disease, thyroid gland disorders, obesity, depression, peptic ulcer, rheumatoid arthritis, gout).
RESULTS Of the 404,727 participants, 62,009 (15.3%) survivors with a diagnosis of cancer and 342,718 (84.7%) controls were followed up for a median of 12.7 years. Risk of pulmonary circulation disease was elevated in survivors with any cancer sites compared with cancer-free controls, especially in thoracic cancer survivors [hazard ratio: 12.89, 95% confidence interval: 11.13–14.94]. Both heart failure and atrial fibrillation were at increased risks at 6 cancer sites, as were acute myocardial infarction and angina at 3 cancer sites. Survivors with digestive, thoracic or hematological cancers had elevated risks of all CVD outcomes.
CONCLUSIONS With risk patterns ranging by cancer sites and particular CVD outcomes, survivors of most site-specific cancers had greater risks of specific CVD than those who had not been diagnosed with cancer, especially digestive, thoracic and hematological cancers. For the expanding population of cancer survivors, strategies to monitor and control cardiovascular risk are needed.
GW34-e0269
Yingjian Deng, Qiang Li, Faguang Zhou, Dong Chang
Xiamen Cardiovascular Hospital of Xiamen University
OBJECTIVES Observational studies suggested that physical activity (PA) and sedentary behavior are associated with the risk of atrial fibrillation (AF). Thus, we performed this Mendelian randomization (MR) study to assess the causal effects of PA and sedentary behavior on the risk of AF.
METHODS A two-sample MR analysis was performed to investigate the associations between PA and sedentary behavior and AF. The summary statistics for PA and sedentary behavior were obtained from different genome-wide association studies (GWASs), and cohorts of vigorous PA (n=251,501), moderate PA (n=343,827), Light PA (n=64,949), television watching (n=437,887), driving (n=310,555), mobile phone use (n=456,972), computer use (n=261,987), and playing computer games (n=462,433) were obtained. Summary data regarding AF were gathered from a meta-analysis on GWASs involving a total of 1,030,836 individuals.
RESULTS The results suggested that vigorous PA (OR 1.64, 95% CI [1.13, 2.40], P=0.01), driving (OR 1.92, 95% CI [1.12, 3.29], P=0.02), mobile phone use (OR 1.21, 95% CI [1.04, 1.40], P=0.01), and playing computer games (OR 1.61, 95% CI [1.16, 2.24], P<0.01) were associated with an increased risk of AF, while no causal associations between other PA or sedentary behavior and AF were found.
CONCLUSIONS The present study demonstrated that vigorous PA, driving, mobile phone use, and playing computer games were associated with an increased risk of AF. The relationship between moderate PA, Light PA, television watching, and computer use with AF needs further investigation in future studies.
GW34-e0270
Xiong Gao, Qiuxia Zhang, Miaomiao Yang, Wei Luo, Yuegang Wang, Jianchen Xiu
Nanfang Hospital of Southern Medical University
OBJECTIVES Observational studies have shown that atrial fibrillation (AF) can lead to cognitive impairment ranging from mild cognitive dysfunction to dementia. Whether this association reflects a causal relationship is still unclear. This study aims to explore the causal relationship between AF and cognitive impairment.
METHODS A two-sample Mendelian randomization (TSMR) analysis is used to assess the potential causality of AF on cognitive dysfunction. Single nucleotide polymorphisms (SNPs) strongly associated with atrial fibrillation were extracted as instrumental variables using a large genome-wide association study (GWAS) pooled dataset of atrial fibrillation (AF). The association of SNPs with Alzheimer’s disease dementia, Parkinson’s disease dementia, vascular dementia, Lewy body dementia, frontotemporal dementia, undefined dementia, and overall cognitive function assessment was then extracted separately from publicly available GWAS data on cognitive dysfunction. The inverse variance-weighted method (IVW) was used for the main analysis, and sensitivity analyses were conducted using Cochran’s Q test, MR-Egger regression, and leave-one-out method. To verify the robustness of the results, replicate analyses and meta-analyses were performed using different GWAS data.
RESULTS In the initial analysis, 101 SNPs were extracted as instrumental variables from a recent meta-analysis of a genome-wide association study involving up to 1,030,836 individuals. The IVW analysis showed no evidence for causal associations between AF and dementia [Dementia (OR, 1.03; 95% CI, 0.97–1.09; P=0.29), Parkinson’s disease dementia (OR, 1.00; 95% CI, 0.78–1.29; P=0.97), vascular dementia (OR, 1.12; 95% CI, 0.96–1.30; P=0.12), or unspecified dementia (OR, 1.01; 95% CI, 0.91–1.12; P=0.80)]. In the replication analysis, 27 SNPs were extracted as instrumental variables from the FinnGen alliance’s AF GWAS data, the IVW analysis are consistent with the initial analysis [Cognitive function (OR, 0.99; 95% CI, 0.98–1.01; P=0.87), Alzheimer’s disease dementia (OR, 0.97; 95% CI, 0.94–1.01; P=0.19), Lewy body dementia (OR, 1.01; 95% CI, 0.89–1.14; P=0.82), or frontotemporal dementia (OR, 0.99; 95% CI, 0.74–1.33; P=0.98)]. Both Mendelian randomization (MR) analyses and meta-analyses showed no evidence of association between genetically predicted AF and different types of dementia or overall cognitive function assessment. MR-Egger regression suggested no horizontal pleiotropy, and leave-one-out analysis showed stable results after individually removing each SNP.
CONCLUSIONS No evidence of a causal relationship between AF and cognitive impairment was found. The associations observed in observational studies can be partially attributed to confounding factors such as shared biology or co-morbidities.
GW34-e0275
Hui Zhang1, Qi Guo1,2
1Jiangwan Hospital of Shanghai Hongkou District
2Shanghai University of Medicine and Health Sciences
OBJECTIVES Cardiovascular disease (CVD) is the leading cause of mortality in patients with end-stage renal disease on hemodialysis (HD), and Ideal cardiovascular health (CVH) metrics is commonly used to assess cardiovascular health status. Epidemiological studies have found that sleep complaints such as obstructive sleep apnea (OSA) and abnormal sleep duration, which are common in HD patients, may increase the risk of cardiovascular disease. Therefore, the purpose of this study was to explore the separated and combined associations of OSA risk and sleep duration with ideal cardiovascular health metrics in HD patients.
METHODS We recruited 880 patients over 18 years old who underwent hemodialysis at least twice a week and obtained informed consent from all participants. After excluding participants with a history of cardiovascular disease and taking sleep medications, 470 HD participants (average: 59.48±12.89 years, 281 men) were included in this study. Sleep duration was measured as self-reported average sleep time during the previous month. OSA risk was evaluated by using STOP-BANG questionnaire. Ideal CVH metrics was defined by the American Heart Association, including 7 modifiable health behaviors and factors, and participants were divided the into three groups by the number of ideal CVH metrics: 0–2 (poor), 3–4 (intermediate), and 5–7 (ideal). Ordinal logistic regression was performed to model the associations of CVH metrics with sleep duration, OSA risk, and their combined effects by adjusting for certain covariates.
RESULTS Compared with patients with ideal CVH, poor and intermediate CVH individuals had poorer CVH indicators including BMI, smoking, physical activity, salty diet, glucose, blood lipids and blood pressure. HD patients with poor and moderate CVH had higher age, spkt/v and potassium, they were also more likely to be male, drinker, fluid overload, shorter sleepers and at higher OSA risk. After adjusting for age, sex, job category, drinker, IPAQ, fluid overload, spkt/v, HDL, and potassium, short sleep duration (<7 h) (OR=0.53; 95% CI [0.30, 0.92]) and OSA risk (OR=0.58; 95% CI [0.32, 0.83]) were negative associated with better CVH (ideal vs. intermediate; intermediate vs. poor), respectively. For HD patients with both short sleep duration (<7 h) and OSA risk, the proportional odds of having better CVH were 72% lower (OR=0.28; [95% CI 0.13, 0.60]).
CONCLUSIONS Short sleep duration (<7 h) and OSA risk were negative associated independently with ideal CVH metrics in HD patients, the combination of short sleep duration (<7 h) and OSA risk significantly further reduced the likelihood of ideal CVH metrics. This study supports population-based prevention programmes in HD patients, improving sleep to minimize the risk of subsequent cardiovascular disease.
GW34-e0283
Zhiyuan Wu1,2, Jinqi Wang1, Haiping Zhang1, Lixin Tao1, Xiuhua Guo1
1Capital Medical University
2Edith Cowan University
OBJECTIVES Arteriosclerosis and atherosclerosis are closely related with cardiovascular disease (CVD) risk. Remnant cholesterol (RC) could predict CVD. However, its effect on joint arteriosclerosis and atherosclerosis progression remains unclear. This study aims to evaluate the association of RC with joint arteriosclerosis and atherosclerosis progression trajectories in the general population.
METHODS This study collected data across five biennial surveys of the Beijing Health Management Cohort from 2010 to 2019. Multi-trajectory model was used to determine the joint arteriosclerosis and atherosclerosis progression patterns by brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI). We also performed discordance analyses for RC vs. low density lipoprotein cholesterol (LDL-C) using ordinal logistics model.
RESULTS A total of 3186 participants were included, with three clusters following distinct arteriosclerosis and atherosclerosis progression patterns identified using a multi-trajectory model. In the multivariable-adjusted ordinal logistics analyses, RC was significantly associated with baPWV and ABI progression (OR: 1.20; 95% CI: 1.13–1.28, per 10 mg/dL). For the discordance analyses, the discordant low RC group was associated with decreased risk compared to the concordant group (OR: 0.73; 95% CI: 0.60–0.89). People with a high RC level were at an increased risk of joint arteriosclerosis and atherosclerosis progression, even with optimal LDL-C.
CONCLUSIONS RC is independently associated with joint arteriosclerosis and atherosclerosis progression beyond LDL-C. RC could be an earlier risk factor than LDL-C of arteriosclerosis and atherosclerosis in the general population.
GW34-e0382
Juanjuan Zheng, Shuangshuang Song, Jiamin Zou, Cheng Liang, Wenyou Wang, Yangyang Zhou, Yuming Zhang, Hong Peng, Wei Eric Wang
Department of Geriatrics, Southwest Hospital, Army Military Medical University
OBJECTIVES Omicron virus infection has been spreading rapidly in China since December 2022, and a part of the infected patients are complicated with myocardial injury. Myocardial injury affects the quality of life and prognosis of patients, and is an important factor in the occurrence of “Long-COVID”. However, the risk factors of myocardial injury caused by Omicron virus infection are still unclear. To explore the risk factors of patients with Omicron virus infection complicated with myocardial injury, thereby providing scientific basis to prevent and treat myocardial injury in clinic.
METHODS Demographic information, clinical signs and symptoms, laboratory examination and other medical records of 691 hospitalized patients with Omicron virus infection in Southwest Hospital from December 1, 2022 to March 3, 2023 were retrospectively collected. Myocardial injury was defined according to whether the hypersensitive troponin was elevated in the first serum examination. The risk factors of myocardial injury were analyzed by multivariate Logistic regression model.
RESULTS Among the 691 Omicron virus infected patients who were tested for hypersensitive troponin, the average age was 50 (40, 59) years, males were 418 (60.49%), and 235 (34.01%) patients were with myocardial injury. Compared with control group, myocardial injury group had a higher median age (53 (45, 63) vs 48 (38, 57), P<0.05); Among them, 160 (68.09%) were males. There were statistically significant differences in admission temperature, maximum body temperature during hospitalization, symptoms on admission (fever, fatigue, poor appetite, cough), cardiovascular diseases (hypertension, diabetes, coronary heart disease), COPD, blood gas analysis, left ventricular ejection fraction (LVEF) and other clinical indicators between the two groups (all P<0.05). There were no statistically significant differences in BMI, vaccination or palpitation between the two groups (P>0.05). NT-proBNP, blood urea, creatinine and glomerular filtration rate were strongly correlated with the increase of troponin (r>0.5, all P<0.001). Multivariate Logistic regression analysis showed that age (OR=1.056, 95% CI=1.040–1.072), male (OR=1.738, 95% CI=1.136–2.658, P<0.05), renal insufficiency (OR=2.318, 95% CI=1.318∼4.076, P<0.05), renal dialysis history (OR=6.566, 95% CI=2.954–14.594, P<0.001), glomerular filtration rate decreased (OR=0.984, 95% CI=0.970∼0.998, P<0.05), anemia (OR=2.512, 95% CI=1.354–4.662, P<0.05), platelet level decreased (OR=0.990, 95% CI=0.982∼0.998, P<0.05) and ST-T changes in ECG (OR=2.308, 95% CI=1.224∼3.395, P<0.05) were independent risk factors for myocardial injury of patients with Omicron virus infection.
CONCLUSIONS Age, male, renal insufficiency, renal dialysis history, decreased glomerular filtration rate, NT-proBNP, anemia, decreased platelet level and ST-T changes in ECG are independent risk factors for Omicron virus infection caused myocardial injury.
GW34-e0555
Zheming Yang1,2, Xiaodong Jia2, Jiayin Li1,2, Zhu Mei1,2, Chenghui Yan2, Yaling Han1,2
1College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China
2National 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 disease (CVD) is a serious condition that poses threats to patients’ quality of life and life expectancy. Cardiac rehabilitation is a crucial treatment option that can improve outcomes for CVD patients. Hybrid comprehensive telerehabilitation (HCTR) is a relatively new approach. In the context of pandemics, HCTR can minimize the risk of cluster infections by reducing hospital visits, while delivering effective rehabilitation care. This study aimed to assess the efficacy and safety of HCTR as a secondary prevention measure for CVD patients compared to usual rehabilitation care.
METHODS We searched Pubmed, Embase, The web of science, The Cochrane Library, and PsychINFO for all related studies up to January 20, 2023. Two reviewers independently screened the titles and abstracts of potentially eligible articles based on the predefined search criteria. Data were analyzed using Comprehensive Meta-Analysis software (RevMan5.3).
RESULTS Eight trials, involving 1578 participants, were included. HCTR and usual rehabilitation care provide similar effects on readmission rates (odds ratio [OR]=0.90 [95% CI 0.69–1.17], P=0.43) and mortality (odds ratio [OR] = 1.06 [95% CI 0.72–1.57], P=0.76). Effects on Short Form-36 Health Status Questionnaire (SF-36) score were also similar (SMD: 1.32 [95% CI −0.48–3.11], P=0.15). Compared with usual rehabilitation care, HCTR can improve peak oxygen uptake (VO2 peak) (SMD: 0.99 [95% CI 0.23–1.74], P=0.01) and 6-minute walking test (6MWT) (SMD: 10.02 [95% CI 5.44–14.60], P<0.001) of patients.
CONCLUSIONS Our findings indicate that HCTR is as effective as traditional rehabilitation care in reducing readmission rates, mortality, and improving quality of life in patients with CVD. However, HCTR offers the added advantage of improving VO2 peak and 6MWT, measurements of cardiorespiratory fitness and functional capacity, respectively. These results suggest that HCTR can be a safe and effective alternative to traditional rehabilitation care, offering numerous benefits for CVD patients.
GW34-e0824
Hualin Wang, Bowen Du, Zhuoyan Li, Yujian Wu, Qianchuo Wang, Jian Wang, Kun Sun
Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University
OBJECTIVES Studies have reported that prenatal exposure to air pollution is associated with elevated blood pressure and impaired cardiometabolic health in children. However, the effects of prenatal air pollution exposure on children’s cardiac structure and function, as well as the susceptible windows for these effects, remain unknown. The objective of this study is to investigate the association between prenatal air pollution exposure with cardiac structure and function in preschool-aged children.
METHODS A total of 1270 mother-offspring pairs from the Shanghai Birth Cohort study were included. Anthropometric assessment and detailed echocardiography examination were conducted in these children at 4 years old. Weekly averaged concentrations of air pollutants including PM2.5, PM10, SO2, NO2, CO and ozone over gestation were assessed based on data from the National Urban Air Quality Real-Time Publishing Platform. Distributed lag non-linear models (DLNMs) were fitted by incorporating multiple linear models and logistic regression models to evaluate weekly exposure-lag-response associations between prenatal air pollution levels and cardiac structure and function, as well as left ventricular hypertrophy (LVH).
RESULTS In this study, we found that higher levels of prenatal exposure to PM2.5, PM10, SO2, and carbon monoxide were associated with increased cardiac wall thickness and decreased cardiac diameter in 4-year-old children. These associations were particularly pronounced during early and mid-pregnancy, with no apparent threshold observed in the concentration-response curve for these pollutants. Furthermore, prenatal exposure to PM2.5, PM10, SO2, NO2, and carbon monoxide during early pregnancy was associated with a higher risk of LVH, with critical windows identified as 1st–12th weeks, 2nd–11th weeks, 3rd–14th weeks, 4th–11th weeks and 1st–15th weeks of gestation, respectively. The strongest effect of each 10 μg/m3 per increment in prenatal exposure to PM2.5, PM10, SO2, NO2 on the risk of LVH displayed in the 1st week (HR:1.10, 95% CI: 1.03–1.17), 8th week (HR:1.07, 95% CI: 1.04–1.10), 7th week (HR:1.21, 95% CI: 1.14–1.29), and 9th week (HR:1.14, 95% CI: 1.05–1.25), respectively. And each 50 μg/m3 increase in exposure to carbon monoxide showed strongest effect on the risk of LVH in 8th–9th weeks (HR:1.07, 95% CI: 1.04–1.09).
CONCLUSIONS Our findings suggest that prenatal exposure to air pollution is associated with cardiac structural changes in preschool-aged children and exposure during early pregnancy is associated with a higher risk of LVH.
GW34-e0955
Chaoqun Ma, Dingyuan Tu
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 Emerging evidence have reported that lifestyle behaviors play critical roles in the pathogenesis of various cardiovascular disorders. The joint associations of anti-inflammatory diet and vigorous leisure-time physical activity (LTPA) with all-cause mortality and cardiovascular disease (CVD) mortality are incompletely understood.
METHODS This secondary data analysis included 16,068 adults from the National Health and Nutrition Examination Survey (2007–2014). Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Participants were categorized into four lifestyle patterns based on the inflammatory properties of the diet and the degree of vigorous LTPA: pro-inflammatory diet and insufficient vigorous LTPA, anti-inflammatory diet and insufficient vigorous LTPA, pro-inflammatory diet and sufficient vigorous LTPA, anti-inflammatory diet and sufficient vigorous LTPA. Multivariable Cox proportional hazards models were used to estimate the hazards ratio (HR) and 95% confidence intervals (CI) for all-cause and CVD mortality. Two-sided P value <0.05 was considered statistically significant.
RESULTS During a median follow-up of 8.5 years, 1904 overall deaths and 484 confirmed CVD deaths were reported. Compared with the pro-inflammatory diet and insufficient vigorous LTPA group (reference), those in the anti-inflammatory diet and sufficient vigorous LTPA group had a significantly lower risk of all-cause (HR, 0.51; 95% CI, 0.32–0.81; P=0.004) and CVD (HR, 0.31; 95% CI, 0.12–0.80; P=0.016) mortality. Similarly, the lifestyle pattern of anti-inflammatory diet and insufficient vigorous LTPA also decreased all-cause (HR, 0.80; 95% CI, 0.69–0.92; P=0.002) and CVD (HR, 0.71; 95% CI, 0.53–0.95; P=0.020) mortality risk. In contrast, all-cause mortality was not significantly reduced in pro-inflammatory diet and sufficient vigorous LTPA group (HR: 0.75, 95% CI: 0.54–1.06, P=0.101), as well as CVD mortality (HR: 0.60, 95% CI: 0.32–1.13, P=0.114). Consistent results were obtained in subgroup and sensitivity analyses.
CONCLUSIONS Adhering to the anti-inflammatory diet and sufficient vigorous LTPA was associated with lower all-cause and CVD mortality. Furthermore, an anti-inflammatory diet can be instrumental in counteracting the harms of insufficient vigorous LTPA, while sufficient vigorous LTPA fails to offset the detrimental effect of pro-inflammatory diet.
GW34-e0991
Hailin Du1, Hongtu Qiao1, Chunxian Lin1, Bin Xue1, Tao Chen1, Shengping Wang1, Wenyong Zhang1,2
1Chengdu Qingbaijiang District People’s Hospital
2Chengdu Second People’s Hospital
OBJECTIVES The aging population, high-altitude terrain, and unique population characteristics in the Garze region have led to a significantly higher prevalence of hypertension compared to other areas. Previous studies have shown that the prevalence of hypertension in the Garze region is 22.9%, higher than 17.9% in Tibetan farming and pastoral areas, and 11.64% in the Han ethnic population. Moreover, the Garze region exhibits characteristics such as low awareness, low control rate, low treatment rate, poor medication adherence, and high morbidity and mortality rates for hypertension. This study aimed to investigate the current status of blood pressure control (achievement rate and non-achievement rate) and medication adherence among hypertensive patients in the multi-ethnic region of Garze, Sichuan, and analyze the main influencing factors among hypertensive patients of different ethnicities. The findings aim to provide data support and theoretical basis for developing intervention measures for hypertensive patients in the multi-ethnic region of Garze.
METHODS A multi-stage stratified cluster random sampling method was employed in this study. Based on the latest population census data in Garze in 2020, 2100 hypertensive patients from Kangding, Jiulong, Dege, and Batang counties were selected for questionnaire surveys, and 2009 valid responses were collected, resulting in a response rate of 95.6%. According to whether blood pressure met the standard (blood pressure standard: systolic pressure <140 mmHg, diastolic pressure <90 mmHg), the patients were divided into an achievement group (n=1033) and a non-achievement group (n=976). The gender, age, ethnicity, education level, marital status, medical history (diabetes, stroke, chronic obstructive pulmonary disease), lifestyle habits (drinking, smoking), BMI index, and medication adherence were analyzed and compared between the two groups. Multivariate logistic regression analysis was conducted to identify potential risk factors.
RESULTS The overall achievement rate of blood pressure control among hypertensive patients was 51.42%. There were no statistically significant differences between the two groups in terms of ethnicity, gender, education level, stroke, or chronic obstructive pulmonary disease (P>0.05). However, there were significant differences (P<0.05) in terms of age, diabetes, BMI index, drinking, smoking, and medication adherence. Regression analysis indicated that age, diabetes, drinking, smoking, BMI index, and medication adherence were independent risk factors for uncontrolled blood pressure in hypertensive patients. Receiver operating characteristic (ROC) analysis showed that age, BMI index, diabetes, and smoking had significantly larger areas under the curve in predicting uncontrolled blood pressure compared to drinking and medication adherence, with statistical significance (P<0.05).
CONCLUSIONS When patients with hypertension have comorbidities such as diabetes, an increased BMI index, older age, smoking, and non-adherence to medication, the risk of inadequate blood pressure control increases. Clinical doctors and public health workers should intervene early for the above-mentioned risk factors to improve the rate of achieving blood pressure control targets in patients.
GW34-e1048
Xin Yin, Yu-Tao Li, Ying Pan, Ting-Ting Wu, Yi-Tong Ma, Xiang Xie
Xinjiang Medical University
OBJECTIVES To further refine the association between sleep duration with all-cause mortality (ACM), cardiovascular events, mortality and stroke, and make it possible to personalize risk prediction.
METHODS A systematic review and meta-analysis of prospective cohort studies that estimate the relation between sleep duration and adverse outcomes was conducted. We searched PubMed, Embase, Web of Science, and Cochrane Library databases for these studies, and extracted data from identified studies up to 1 January 2023. Prospective cohort study with sleep duration as exposure and presenting clear data on adverse outcomes were included in; We took 7–7.9 hours as reference when calculating effect size.
RESULTS A total of 110 research projects involving about 2.28 million people were evaluated. Consistent with previous studies, the risk was lowest at 7–8 hours of sleep. But too much sleep is more harmful than sleep deprivation, showing a “J” shape rather than a “U” shape between the risk and sleep duration. When less than 5 hours or more than 9 hours, the magnitude of the increased risk changed significantly. When sleep duration =6 h, the risk in people aged 40–49.9 years (123% risk for ACM and 125.1% risk for CVD Mortality) was much higher than people aged over 50 years. When sleep duration≥10 h, the risk in people aged 50–54.9 years (153% risk for ACM and 235.6% risk for CVD Mortality) was higher than others. When sleep duration =5 hours and≥9 hours, people aged 40 to 49.9 years unexpectedly had the highest risk of stroke (141.2% at 5 h and 181.1% at 9 h). As the duration of sleep increased, the risk was much higher in women (Sleep duration≥10 h, 178% risk for ACM and 188% risk for CVD Mortality) than in men (Sleep duration≥10 h, 150% risk for ACM and 158% risk for CVD Mortality). We find that when sleep duration was more than 7 hours, the risk of yellow people (Sleep duration≥10 h, 164% risk for ACM and 171% risk for CVD Mortality) was significantly higher than that of white people (Sleep duration≥10 h, 128% risk for ACM and 135.8% risk for CVD Mortality). However, when sleep duration =5 hours and≥9 hours, white people have a higher risk of Stroke (138.7% at 5 h and 146.4% at 9 h) than yellow people (113.4% at 5 h and 131.4% at 9 h). The results of studies with more than 10 years of follow-up were more “conservative” than those with less than 10 years of follow-up. In terms of numbers, the results for the 10,000-plus cohort were more “conservative”. We recommend that even if staying up late is inevitable, you should also ensure at least 5 hours of sleep, and do not sleep in more than 9 hours, especially for yellow women.
CONCLUSIONS More attention should be paid to sleep in middle-aged people. People aged 40–49.9 years, during extreme sleep, has the highest risk of stroke. People aged 50–54.9 years also suffer the highest risk of all-cause and cardiovascular mortality when they experience extreme sleep.
GW34-e1070
Binglu Wang1, Jun Wang2
1Xiang Ya Nursing School of Central South University, Changsha, Hunan 410013, China
2China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China
OBJECTIVES The impact of adherence to plant-based dietary patterns on life expectancy among older adults remains unclear. We aimed to quantify the associations of plant-based dietary patterns with life expectancy among Chinese older adults.
METHODS We used data from Chinese Longitudinal Healthy Longevity Survey (CLHLS, 2008–2018) of 15,706 adults aged 65 years and older (57.48% female). The overall plant-based diet index (PDI), healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI) were assessed using dietary data collected by a simplified and validated food frequency questionnaire (FFQ), which consists of 16 food components: whole grains, vegetable oils, fresh fruit, fresh vegetables, legumes, garlic, nuts, tea, refined grains, preserved vegetables, sugar, meat, fish and aquatic products, eggs, milk or dairy products, and animal fat. Hazard ratios (HRs) of all-cause mortality and the life expectancy by levels of three versions of plant-based diet indices (overall, healthful, and unhealthful) were estimated.
RESULTS During a follow-up of 69,700 person-years, 10,573 deaths were recorded. Compared with the lowest tertile, participants in the highest tertile of PDI and hPDI had lower risk of all-cause mortality (HR=0.92; 95% CI 0.87–0.96 for PDI; HR=0.93, 95% CI, 0.88–0.97 for hPDI), whereas participants with the highest uPDI scores had a 11% (HR=1.11, 95% CI 1.06–1.17) increased mortality risk. We observed gradual gains in life expectancy toward PDI or hPDI dietary patterns, such as, compared with lowest tertile of PDI/hPDI, participants with highest tertile of PDI and hPDI had an average 0.82 (95% CI 0.43–1.21) and 0.68 (95% CI 0.28–1.01) more years of life expectancy at age 65 years, respectively. Compared with lowest tertile of uPDI, those with highest uPDI lost 1.16 (95% CI 0.81–1.50) years in life expectancy. Several sensitivity analyses suggested these results were relatively stable.
CONCLUSIONS Adopting to a high level of plant-based dietary pattern, especially for healthful plant-based dietary pattern, was related to lower risk of all-cause mortality and longer life expectancy, supporting current recommendations to increase intake of healthy plant foods, and reducing intake of unhealthy plant foods for prevention of all-cause mortality.
GW34-e1074
Binglu Wang1, Jun Wang2
1Xiang Ya Nursing School of Central South University, Changsha, Hunan 410013, China
2China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China
OBJECTIVES The effect of plant-based dietary patterns on annual change in cognitive performance is uncertain among Chinese older adults. This study examined the association between plant-based dietary patterns and annual change in cognitive performance.
METHODS Data were from Chinese Longitudinal Healthy Longevity Survey (CLHLS, 2008–2018), a population based, prospective cohort study. Individuals aged 65 years or older who had normal cognition at baseline were included, and followed up until death, discontinuation, or December 2018. A simplified and validated food frequency questionnaire (FFQ) was used to assess the dietary information. Three versions of graded plant-based diets were constructed: an overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). Cognitive performance was measured via the Chinese version of Mini-Mental State Examination. Multivariable generalized linear regression models with repeated measures analyses were used to examine the associations of three versions of plant-base diets with cognitive performance annual change.
RESULTS 8865 participants were included (mean age of 82.63 years), 53.38% were women. Higher healthful-PDI was associated with slower cognitive decline. The annual changes in cognitive performance were −0.67 (95% CI: −0.74, −0.60), −0.61 (95% CI: −0.67, −0.55), and −0.57 (95% CI: −0.63, −0.51) across tertiles of overall PDI (Ptrend=0.0313); −0.71 (95% CI: −0.79, −0.64), −0.60 (95% CI: −0.66, −0.54), and −0.54 (95% CI: −0.61, −0.48) across tertiles of healthful PDI (Ptrend=0.0003). The uPDI was positively associated with cognitive decline, with −0.53 (95% CI: −0.59, −0.47), −0.65 (95% CI: −0.72, −0.58), and −0.68 (95% CI: −0.75, −0.62) across tertiles of unhealthful PDI (Ptrend=0.0022). For sub-domains of cognitive performance, similar results were observed for the following two dimensions: orientation in time and space, and calculation.
CONCLUSIONS Individuals with higher healthful PDI were associated with slower cognitive decline. This study might offer important information to protect older adults against cognitive decline.
GW34-e1098
Binglu Wang1, Jun Wang2
1Xiang Ya Nursing School of Central South University, Changsha, Hunan 410013, China
2China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China
OBJECTIVES The effect of plant-based dietary patterns on annual change in blood pressure remained unclear among Chinese older adults. We aimed to examine the effects of plant-based dietary patterns on blood pressure change rates.
METHODS This study was from the Chinese Longitudinal Healthy Longevity Survey (CLHLS, 2008–2018), a population based, prospective cohort study. A total of 9480 participants aged 65 years or older were included. Three versions of graded plant-based diets were created using a simplified and validated food frequency questionnaire (FFQ): an overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). Multivariable generalized linear regression models with repeated measures analyses were used to examine the associations of three versions of plant-based diets with annual changes of blood pressure (BP).
RESULTS This study evaluated 9480 participants (mean [SD] age of 83.15 [10.92]; 54.83% were female). After adjusting for multiple potential confounders, annual changes in systolic BP (SBP) were −4.36 mmHg (95% CI: −5.07, −3.64), −5.23 mmHg (95% CI: −5.76, −4.70), and −5.39 mmHg (95% CI: −5.90, −4.88) across tertiles of overall PDI (Ptrend=0.0199). Annual changes in diastolic BP (DBP) were −4.69 mmHg (95% CI: −5.43, −3.95), −5.41 mmHg (95% CI: −5.95, −4.87), and −5.80 mmHg (95% CI: −6.31, −5.28) across tertiles of overall PDI (Ptrend=0.0144). Similar results were observed for healthful-PDI. Participants with highest intake of healthful PDI exhibited the greatest decrease in SBP and DBP. Compared with participants with highest intake of unhealthful PDI (top tertile of uPDI), those with lowest intake was associated with −1.03 mmHg (95% CI: −2.08, 0.01) difference in SBP and −1.07 mmHg (95% CI: −2.15, 0.01) difference in DBP, respectively.
CONCLUSIONS Higher healthful plant-based dietary intake was inversely associated with blood pressure change, supporting the beneficial roles of overall and healthful plant-based dietary patterns on blood pressure control among Chinese older adults.
GW34-e1185
Dongsheng Cai1, Jun Chen2, Chenyang Jiang1
1Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
2The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China
OBJECTIVES Recent studies have reported multiple sclerosis (MS) patients are associated with an increased risk of incident atrial fibrillation (AF) and ischemic stroke (IS). However, the underlying mechanism for the relationship remains unclear. This study aims to investigate the causal effect of MS on AF and IS by two-sample Mendelian randomization (MR) analysis.
METHODS The genetically predicted association of MS with AF and IS was evaluated using MR analysis model. A total of 9 MR analysis methods were performed to analyze the final results. The IVW methods was used as the primary outcome. The other MR analysis method (simple mode, weighted mode, simple median, weighted median, penalized weighted median, MR Egger, and MR-Egger (bootstrap)) were performed as the complement to IVW. Also, the robustness of the MR analysis results was assessed using a leave-one-out analysis.
RESULTS The IVW analysis methods indicated that there is no causal relationship between MS and AF, as well as MS and IS, in the FinnGen database (AF: OR, 0.998, 95% CI, 0.977–1.020, P=0.879; IS: OR, 1.013, 95% CI, 0.992–1.034, P=0.225) or the Biobank Japan database (AF: OR, 1.000, 95% CI, 0.942–1.062, P=0.999; IS: OR, 1.001, 95% CI, 0.983–1.020, P=0.909). The other MR analysis method and further leave-one-out sensitivity analysis suggested the results were robust.
CONCLUSIONS This MR study contributes new evidence that there is no genetically predicted risk of AF or IS in patients with MS.
GW34-e1306
Yang Liu1, Weiguo Fan1, Hualong Liu1, Wen Zhuo1, Kui Hong1,2,3, Yan Zheng2,3
1Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
2Department of Genetic Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
3The Jiangxi Key Laboratory of Molecular Medicine, Jiangxi, China
OBJECTIVES Heart disease (HD) is getting attention in solid cancer patients treated with radiotherapy (RT-SCP). The changing trend of death from HD in RT-SCP remains unconcern. To investigate the influence of HD on the death among RT-SCP, we analyzed the causes of death (COD), and assess the trend of HD mortality by year of diagnose.
METHODS Fifteen kinds of RT-SCP were collected from the National Surveillance, Epidemiology, and End Results database. The proportion of COD was calculated among RT-SCP. The statistical method of competitive risk model and cumulative mortality curve were used to evaluate the trend of HD mortality by survival month.
RESULTS The distributions of COD (HD, primary cancer, other causes) were observed in 15 kinds of RT-SCP. Compared to other cancers, the highest mortality was seen in prostate cancer patients (24.9%), and the lowest in brain and central nervous system (CNS) cancer patients (1.6%). In addition, the trends of 5-year cumulative HD mortality declined in all cancer types (2005–2018 vs. 1975–1984), especially in prostate cancer (from 6.50 to 2.10%), which were associated with the higher survival rate and special treatment. And slightly reductions were observed for patients with lung cancer (from 3.15 to 2.82%) and eye/orbit cancer (from 2.24 to 1.97%).
CONCLUSIONS Decreasing trends in 5-year accumulative HD mortality were observed in all kinds of RT-SCP. Notably, the highest rate of death from HD was seen in patients with prostate cancer, while the lowest rate was seen in those with CNS cancer.
GW34-e1412
Yun Liang, Liangmin Guo, Lifeng Chen, Sizhu Guo, Xu Yang
Chengdu Third People’s Hospital
OBJECTIVES The fear of movement (Kinesiophobia) of cardiovascular disease (CVD) patients after admission seriously affects their health recovery and quality of life. The purpose of this study is to assess the global occurrence of kinesiophobia among cardiovascular disease patients by using a meta analysis.
METHODS A search of studies published in Pubmed, Embase, Web of Science and Cochrane databases from the database establishment to June 1, 2023 was completed, mainly including the research on the current situation of kinesiophobia in CVD patients during hospitalization. Literature screening, data extraction, and risk preference assessment were conducted by two researchers independently. We estimated the global prevalence with a random effects model, and conducted the subgroup analysis.
RESULTS A total of 15 studies were included, including 12 cross-sectional studies and 3 Cohort study, and 2741 samples were included. Meta analysis showed that the global prevalencee of kinesiophobia in CVD patients during hospitalization was 61.8% (95% CI: 49.4∼73.5%). Subgroup analysis of regions showed that Europe was 58.9% (95% CI: 41.0∼76.7%), Asia was 66.6% (95% CI: 59.4∼73.9%). Subgroup analysis of subjects howed that CR patients 62.7% (95% CI: 36.6∼88.8%), and CAD patients 57.0% (95% CI: 32.9∼81.1%). The subgroup analysis results of the evaluation tool showed TSK-SV 64.4% (95% CI: 49.3∼79.6%), and TSK-NL 51.7% (95% CI: 34.1∼69.3%).
CONCLUSIONS The study found that the patients with cardiovascular disease had a high prevalence of kinesiophobia during hospitalization, and it is necessary to further explore the risk factors of kinesiophobia. In order to ensure the reliability of the above research conclusions, more literature is needed to support them.
PREVENTION RESEARCH
GW34-e0090
Zhen Hu, Zengwu Wang
Division of Prevention and Community Health, 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-related knowledge, attitude and practice of hypertensive patients can affect the awareness, treatment and control of hypertension. However, little attention has been paid to the association between the change of hypertension preventive KAP and BP control in occupational population using longitudinal data. We assess the effectiveness of a workplace-based multicomponent hypertension intervention program on improving the level of knowledge, attitude and practice of hypertension prevention and it’s association to blood pressure control.
METHODS From January 2013 to December 2014, workplaces across 20 urban regions in China were randomized to either the intervention group (n=40) or control group (n=20) using a cluster randomized control method. All employees in each workplace were asked to complete a cross-sectional survey to screen for hypertension patients. Hypertension patients in the intervention group were given a two-year workplace-based multicomponent hypertension intervention for blood pressure control. The level of knowledge, attitude and practice of hypertension prevention, and blood pressure were assessed before and after intervention in the two groups.
RESULTS Overall, 3331 participants (2658 in the intervention group and 673 in the control group) were included (mean [standard deviation] age, 46.2 [7.7] years; 2723 men [81.7%]). After 24 months of the intervention, the knowledge, attitude and practice (KAP) qualification rate was 63.2% in the intervention groups and 50.1% in the control groups (odds ratio=1.65, 95% CI, 1.36∼2.00, P<0.001). Compared with the control group decreased in the qualified rate of all items in each dimension of KAP, all the items in the intervention group increased to different degrees. The increase of KAP score was associated with the decrease of blood pressure after intervention. For 1 point increase in KAP score, SBP decreased by 0.28 mmHg and DBP decreased by 0.14 mmHg [systolic blood pressure (SBP): β=−0.28, 95% CI: −0.48∼−0.09, P=0.004; diastolic blood pressure (DBP): β=−0.14, 95% CI: −0.26∼−0.02, P=0.024]. SBP and DBP was significantly in manual labor workers (SBP: β=−0.34, 95% CI: −0.59∼−0.09, P=0.008; DBP: β=−0.23, 95% CI: −0.38∼−0.08, P=0.003), workers from SOE (SBP: β=-0.40, 95% CI: −0.64∼−0.16, P=0.001; DBP: β=−0.21, 95% CI: −0.36∼−0.06, P=0.005) and a workplace with an affiliated hospital (SBP: β=−0.31, 95% CI: −0.52∼−0.11, P=0.003; DBP: β=−0.16, 95% CI: −0.28∼−0.03, P=0.016). The improvement of knowledge (SBP: β=−0.29, 95% CI: −0.56∼−0.02, P=0.038; DBP: β=−0.12, 95% CI: −0.29∼0.05, P=0.160), as well as belief (SBP: β=−0.71, 95% CI: −1.25∼−0.18, P=0.009; DBP: β=0.18, 95% CI: −0.23∼0.59, P=0.385) and behavior (SBP: β=−0.73, 95% CI: −1.22∼−0.23, P=0.004; DBP: β=−0.65, 95% CI: −0.97∼−0.33, P<0.001) was gradually strengthened in relation to blood pressure control.
CONCLUSIONS This study found that workplace-based multicomponent hypertension interventions can effectively improve the level of knowledge, attitude and practice among employees, and the improvement of these levels were significantly associated with blood pressure control.
GW34-e0168
Weiya Li, Han Yin, Huan Ma, Qingshan Geng
Guangdong Cardiovascular Institute
OBJECTIVES Cardiopulmonary exercise test (CPET) is the gold standard for evaluating cardiopulmonary capacity. A recent scientific update from the American Heart Association states that cardiopulmonary function may provide additional prognostic value to the risk of death on top of traditional cardiovascular risk factors. Peak oxygen uptake (Peak VO2) is the most important indicator of cardiopulmonary capacity in CPET. However, the predictive value of Peak VO2 for adverse prognosis in Chinese CAD population is still unclear. We aimed to explore the value of Peak VO2 to predict all-cause mortality, cardiovascular mortality, and MACE (major adverse cardiovascular events) in Chinese CAD patients.
METHODS A total of 635 CAD patients who completed CPET at Guangdong Provincial People’s Hospital in China from 2013 to 2020 were included. All participants were classified according to the Peak VO2 quartile (Q1, Q2, Q3, Q4). Cox regression model and receiver operating characteristic (ROC) curve were used to evaluate the predictive value of Peak VO2 to poor prognosis. Restricted Cubic Splines (RCS) were used to determine whether the relationship between Peak VO2 and poor prognosis was clearly linear. Subgroup analysis was performed to assess heterogeneity among different subgroups.
RESULTS After a mean follow-up of 3.4 years, 16 patients experienced all-cause death, 12 experienced cardiovascular death, and 92 had MACE. The highest Peak VO2 group (Q4) had the lowest risk of all-cause mortality (HR, 0.072; 95% CI, 0.009–0.557; P=0.012), cardiovascular mortality risk (no cardiovascular deaths in Q4 group), and MACE (HR, 0.376; 95% CI, 0.214–0.662; P=0.001) after multivariate adjustment. The risk of all-cause and cardiovascular mortality as well as MACE were also lower in Q3 and Q2 than that in Q1 after adjustment. Area under ROC curve analysis showed that Peak VO2 levels had the good discriminant ability of all-cause (AUC=0.808, 95% CI: 0.695∼0.921, P<0.0001), cardiovascular mortality (AUC=0.845, 95% CI: 0.749∼0.94, P<0.0001) and MACE (AUC=0.61, 95% CI: 0.544∼0.676, P=0.0007). Every 1 mL/kg/min increase of Peak VO2 can lower the 24.3% risk of all-cause mortality (HR, 0.757; 95% CI, 0.67–0.855; P<0.001), 27.5% risk of cardiovascular mortality (HR, 0.725; 95% CI, 0.623–0.844; P<0.001) and 9.8% risk of MACE (HR, 0.902; 95% CI, 0.863 to 0.944; P<0.001). According to the results of the RCS curve, the improvement stage of Peak VO2 from low level to medium level can obtain the maximum prognostic benefits for CAD patients. Cut-off values of three endpoints for Peak VO2 were obtained from the ROC curves (all-cause mortality and cardiovascular mortality: Peak VO2=15; For MACE: Peak VO2=14). Cut-off values of Peak VO2 could well identify CAD patients with high risk and poor prognosis. In subgroup analyses, the relationship between Peak VO2 and the risk of poor prognosis was similar, all the P for interactions were >0.05.
CONCLUSIONS In Chinese single-center’s CAD patients, Peak VO2 was significantly negatively associated with all-cause mortality, cardiovascular mortality and MACE. Peak VO2 at 14–15 mL/kg/min may serve as a preliminary threshold for poor prognosis in Chinese CAD patients.
GW34-e0182
Peizhen Zhang
Beijing Sport University
OBJECTIVES In recent years, the public’s physical fitness has been declining, and the recessive obesity has become one of the most easily ignored health problems, among which recessive obesity in women is the more prominent. This paper probes into the effect of different types of exercise training with equal amount, on weight loss in women with recessive obesity, and to provide a reference for the formulation of exercise prescription.
METHODS Forty-five women (21.6±2.1 yrs) with recessive obesity were recruited and participated in the study. They were randomly divided into three groups, a high-intensity interval training (HIIT) group, a moderate-intensity continuous training (MICT) group and a blank control (CONL) group. The exercise intervention last eight weeks. The HIIT group performed an interval cycling session consisting of 4×4 min bouts (4 min of cycling at 85–95% HRmax followed by 3 min of cycling at 50–60% HRmax). The MICT group did equal amount of cycling with HIIT group at 60–75% HRmax. Body composition was determined before and after the exercise intervention to explore the effect of different types of exercise training on recessive obesity in women.
RESULTS After eight-week intervention, (1) Compared with the CONL group, participants in the HIIT and MIIT groups had significant declines in percentage of body fat (PBF) and body fat content, and the decline of PBF (3.6 vs 2.7%) and body fat content (6.6 vs 5.7%) in the HIT group was significantly greater than that in the MIIT group (P<0.05). (2) The HIIT group and MIIT group demonstrated significantly decreased level of waist-to-hip ratio (WHR) compared with CONL group, and the decrease of WHR in the HIIT group was significantly greater than that in the MIIT group (−3.6 vs −2.4%, P<0.05). (3) Participants in the HIIT group and MIIT group had significant reductions in the body weight (1.52 kg, 1.50 kg) and body mass index (BMI) compared with CONL group (P<0.01). There was no significant difference in changes of body weight and BMI between the HIIT group and MIIT group. (4) There was no significant change in skeletal muscle mass in the HIIT, MIIT and CONL groups.
CONCLUSIONS Both MICT and HIIT could reduce fat of women with recessive obesity, which were beneficial to prevent obesity and related diseases in early life. It was suggested that HIIT may be advantageous in reducing the accumulation of abdominal visceral fat in women with recessive obesity when compared to MICT.
GW34-e0480
Taotao Xue, Limin Wang, Zhengjing Huang, Xiao Zhang, Zhenping Zhao, Chun Li, Peng Yin, Mei Zhang
National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Prevention and Control, Beijing Municipality, China
OBJECTIVES Previous studies have shown that improved cardiovascular health (CVH) was associated with a reduced risk of cardiovascular disease (CVD) mortality. However, the mortality risk of CVD may be increased by long-term exposure to fine particulate matter (PM2.5). This study aimed to evaluate the association between CVH (i.e., Life’s Essential 8) and the risk of mortality due to CVD, ischemic heart disease (IHD), and stroke among Chinese adults exposed to different ambient PM2.5 levels.
METHODS This study included 119,899 participants without a history of CVD aged 35 years and above from the fourth field survey of China Chronic Disease and Risk Factors Surveillance (CCDRFS) which was conducted in 298 counties/districts across 31 provinces (or equivalent) in 2013. Cardiovascular disease death was ascertained by linkage to the National Death Registration System database through December 31, 2018. Satellite-based models were applied to estimate average ambient PM2.5 and other pollutant exposures for each participant in the five years before death or the end of follow-up based on their residential address. The participants were categorized into low (PM2.5<39.36 μg/m3) and high (PM2.5=39.36 μg/m3) exposure based on their median PM2.5 exposure. CVH (low, moderate, high) of each participant was evaluated based on Life’s Essential 8 (CVH 2022). We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality of CVD, IHD, and stroke at low and high levels of PM2.5 exposure. These models were adjusted for gender, age, residence, region, education levels, per-capita household income, history of cancer, drinking, O3, SO2, and NO2. The multiplicative interaction terms of PM2.5 and CVH were tested using likelihood ratio tests. In addition, participants were cross-classified into six groups according to CVH and levels of PM2.5 exposure, and the group with low CVH and high PM2.5 exposure was used as the reference to assess the joint associations.
RESULTS During a median follow-up of 5.1 years, 1183 of the 119,899 participants died from CVD, including 425 from IHD and 622 from stroke. Compared with participants with low CVH, high CVH was associated with lower mortality risk for CVD, IHD, and stroke at both low and high levels of PM2.5 exposure, with 69% (HR, 0.31; 95% CI, 0.22–0.43), 65% (HR, 0.35; 95% CI, 0.20–0.63), and 69% (HR, 0.31; 95% CI, 0.19–0.49) lower mortality risk for CVD, IHD, and stroke at high PM2.5 exposure, respectively. Compared with participants with low CVH and high PM2.5 exposure, participants with high CVH and high PM2.5 exposure had lower mortality risk for CVD (HR, 0.34; 95% CI, 0.24–0.47), IHD (HR, 0.40; 95% CI, 0.22–0.71), and stroke (HR, 0.34; 95% CI, 0.21–0.53). The negative association between CVH and mortality risk for CVD (HR, 0.25; 95% CI, 0.17–0.37) and stroke (HR, 0.19; 95% CI, 0.11–0.34) was stronger among participants with high CVH and low PM2.5 exposure. The negative association between CVH and the mortality risk of CVD (P for interaction=0.297), IHD (P for interaction=0.668), and stroke (P for interaction=0.554) was not significantly modified by levels of PM2.5 exposure.
CONCLUSIONS We found that high CVH was associated with lower mortality risk for CVD, IHD, and stroke among Chinese adults at low and high levels of PM2.5 exposure. These findings show that the benefits of high CVH are not altered by living in areas with high PM2.5 concentrations, and maintaining high CVH may be recommended for individuals without a history of CVD to reduce the risk of CVD mortality regardless of their residence.
GW34-e0871
Ziang Li, 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 Despite the increasing incidence and prevalence of degenerative valvular heart disease (VHD), there are currently no effective preventive interventions. Physical activity has been identified as effective in preventing atherosclerotic cardiovascular disease, but its role in preventing degenerative VHD remains uncertain. This study aimed to examine the association between physical activity and incident left-sided degenerative valvular heart disease in middle-aged adults from the UK biobank.
METHODS Data from wrist-worn accelerometer and physical activity questionnaires were utilized to assess the impact of moderate-to-vigorous intensity physical activity (MVPA) volume on the incidence of aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The primary cohort involved 90,865 participants (median age of 63; 43% male) without prevalent VHD and heart failure, who wore accelerometers for one week between 2013 and 2015. The validation cohort included 397,335 participants (median age of 57; 47% male) who met the same exclusion criteria and completed a self-reported questionnaire from 2006 to 2010. The volume of MVPA was categorized based on the American Heart Association’s recommendation (150,300 min/week). Incident VHD were ascertained from hospital admissions and death reports.
RESULTS In the primary cohort, the age- and sex-adjusted incidence rates for AS, AR, and MR were 0.70, 0.29, and 0.86 per 1000 person-years, respectively, during a median follow-up of 8.1 years. The corresponding rates were 0.76, 0.29, and 0.76 over a median follow-up of 13.8 years in the validation cohort. Accelerometer-measured MVPA volume showed a curvilinear relationship with reduced AS risk (nonlinear P<0.001), with the risk reduction plateauing above 300 min/week. Compared to participants with no MVPA, those engaging in 150–299 minutes of MVPA per week showed the most significant risk reduction [1–149 min/week: adjusted hazard ratio (HR), 0.79 (0.58, 1.08); 150–299 min/week: HR, 0.52 (0.36, 0.75);≥300 min/week: HR, 0.57 (0.39, 0.83)]. Similar results were found when repeating the above analyses in self-reported MVPA cohort, with a relatively smaller reduction in HR ratio [1–149 min/week: adjusted hazard ratio (HR), 0.85 (0.77, 0.94); 150–299 min/week: HR, 0.81 (0.73, 0.91);≥300 min/week: HR, 0.87 (0.79, 0.95)]. The association was broadly similar across AS high-risk subgroups (hypertension, obesity, dyslipidemia, and type 2 diabetes). The association remained consistent across AS high-risk subgroups, including hypertension, obesity, dyslipidemia, and type 2 diabetes. No significant association was found between the MVPA volume and the risk of AR and MR in both cohorts.
CONCLUSIONS In this middle-aged prospective cohort study, MVPA were associated with a decreased risk of AS. Individuals who engage in current MVPA recommendations (150–300 min/week) have lowest AS risk throughout the range of MVPA volume. Targeting adherence to objective activity thresholds in future preventive strategies may enhance the effectiveness of reducing AS risk. Additionally, MVPA showed limited effectiveness in preventing valvular regurgitation, indicating various mechanisms in the development of degenerative VHD.
GW34-e0975
Yifang Yuan1,2, Xianghui Zhang1, Yangfeng Wu1,2
1Peking University Clinical Research Center, Peking University First Hospital, Beijing, China
2Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing, China
OBJECTIVES To synthesize the current evidence on the safety of potassium-enriched salt substitute, especially the risk of hyperkalemia, through a systematic review.
METHODS A systematic literature search on potassium-enriched salt substitute and hyperkalemia was performed in Pubmed, Embase, Cochrane library (Central Register of Controlled Trials), China National Knowledge Infrastructure (CNKI). A list of search terms was used in all fields to cover the concepts of potassium-enriched salt substitute and human study. We included studies that reported any adverse events after the use of salt substitute, regardless of study design or duration. We exclude studies which was complicated to evaluate the implementation of salt substitution. Data were extracted independently by two reviewers. The primary outcomes were hyperkalemia and all-cause mortality. We stratified the analysis by study type for each outcome.
RESULTS We identified 47 articles, including 24 case reports, 1 case-control study, 19 RCT trials and 3 non-RCT trials. For hyperkalemia, 44 articles were analyzed, including 24 case reports, 1 case-series, 16 RCT trials and 3 non-RCT trials. A total of 26 patients were reported with salt-substitute-associated hyperkalemia in case reports. The etiology of hyperkalemia differs in acute and chronic clinical settings. Patients with hyperkalemia in chronic settings frequently exhibit underlying comorbidities such as CKD while in acute cases, patients swallowed large quantities of salt substitute by accident, or had acute triggers. The risk factors of hyperkalemia were more frequently observed in chronic cases (CKD/AKI: 50.0% in acute cases vs. 77.8% in chronic cases; eGFR<30 mL/min*1.73 m2: 0 in acute cases vs 46.2% in chronic cases; potassium sparing medications: 37.5% in acute cases vs. 77.8% in chronic cases). A total of 19 trials reported hyperkalemia or serum potassium as one of the study outcomes, including 16 RCTs with a total of 27,325 participants and 3 pre-post single-arm studies with a total of 120 participants. Most RCTs excluded participants with CKD (15/16) and those who used medications that may elevate serum potassium (9/16). Pooled analysis did not suggest a statistical significant increased risk of hyperkalemia (RR 1.63; 95% CI 0.69 to 3.84, I2 71%), though serum potassium was slightly increased (mean difference 0.20 mmol/L; 95% CI 0.06 to 0.34, I2 92%). Six RCTs reported on all-cause mortality, with a pooled RR of 0.89 (95% CI 0.84 to 0.95, I2=0%).
CONCLUSIONS The evidence on the safety of salt substitute from high-quality randomized trials was limited and heterogeneous. Salt substitute may increase serum potassium but not clinical hyperkalemia or all-cause mortality. Most cases of salt-substitute-related hyperkalemia had underlying conditions like CKD or acute ingestion of large amount of salt substitute. More studies on the safety of salt substitute are needed, especially in populations at risk of hyperkalemia like CKD.
GW34-e1160
Na Wang
Beijing An Zhen Hospital, Capital Medical University
OBJECTIVES Understanding how to effectively promote healthy aging and prevent dementia that present symptoms in older adults thus is becoming increasingly important. Thus, there is an immediate need for interventions that target the disease process from its earliest stages as mild cognitive impairment (MCI). Prior studies indicated that olfactory dysfunction may be associated with MCI, but to what extent olfactory dysfunction affect cognitive function of different domains remains unclear and warrants careful investigations. The present study aimed to investigate the association of olfactory dysfunction with MCI, olfactory dysfunction, and all cognitive domains in older adults.
METHODS A total of 934 community-dwelling participants aged≥60 years from the Chinese Multi-provincial Cohort Study assessed olfactory function using the Modified Sniffin’ Sticks identification test and cognitive function using Montreal-Cognitive Assessment v7.1 (MOCA). Olfactory dysfunction was defined as olfactory identification score =3. MOCA included six cognitive domains: executive, visuospatial, language, memory, attention, and orientation. MCI was defined as education modified MOCA score <26. Multivariable regression models were performed to examine the association of olfactory dysfunction with MCI, global cognitive function, or cognitive domains.
RESULTS Overall, 33.5% of the participants (75.3±7.6 years of age; 49.4% men; and 75.9% higher education level) had olfactory dysfunction, and 60.4% MCI. After multivariable adjustment, participants with olfactory dysfunction had 58% higher risk of MCI than those with normal olfactory function (95% confidence interval (CI): 1.17–2.11, P=0.003). Furthermore, olfactory dysfunction was significantly associated with decreased global cognitive function (β=-1.24, 95% CI: −1.72, −0.76). Olfactory dysfunction was associated with decrease of both cognitive domains, with the most decrease of memory cognitive domain (β=−0.26, 95% CI: −0.39, −0.12).
CONCLUSIONS Our findings demonstrated that olfactory dysfunction was associated with MCI, global cognitive function, and all cognitive domains in community-dwelling older adults, suggesting that treatment of olfactory dysfunction is essential to improve cognitive function.
GW34-e1169
Hailong Wang1, Shimei Yu2
1Chongqing University Three Gorges Hospital
2Chongqing Wanzhou First People Hospital
OBJECTIVES Glaucoma is an optic neuropathy characterized by damage to retinal ganglion cells in the inner nuclear layer of the eye, accompanied by structural changes in the optic nerve and loss of visual field, Hypertension (HTN) is not recognized as an independent risk factor for primary open-angle glaucoma (POAG). Extending this, we explored the relationship between HTN, diabetes, and POAG.
METHODS A literature search through databases including PubMed, Medline, and Embase without language restrictions from inception to June 22, 2022 was completed. In all instances, a full text search was done and employed the following terms and keywords in the Medical Subject Headings thesaurus: “hypertension, or HTN,” “high blood pressure, or HBP,” and “open-angle glaucoma, or OAG.” We pooled and analyzed all studies and assessed them for heterogeneity and the quality of the literature.
RESULTS Five cross-sectional studies were included in the met-analysis with 1673 individuals with and 41,732 without POAG. The combined analysis found that the incidence of HTN was higher among the individuals with POAG than among those without (OR 1.55; P<0.00001). There was also a significant difference in the incidence of diabetes among individuals with POAG compared with those without (OR: 1.31; P=0.002).
CONCLUSIONS The present meta-analysis revealed strong and sperate risk factor relationships between hypertension and diabetes and POAG. It remains for future inquiry to assess if these two discriminators function together to further increase the risk of PAOG.
GW34-e1201
Wenyao Peng1, Xueke Bai1, Yang Yang1, Jianlan Cui1, Wei Xu1, Lijuan Song1, Hao Yang1, Wenyan He1, Xingyi Zhang1, Xi Li1,2,3, Jiapeng Lu1
1National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
2Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, Shenzhen, China
3Central China Sub-center of the National Center for Cardiovascular Diseases, Zhengzhou, China
OBJECTIVES Primary prevention is crucial for people with high cardiovascular disease (CVD) risk. However, the combined effects of statin use and healthy lifestyles on the mortality risk in people at high CVD risk remain unknown. There is a lack of whether the primary prevention could offer high-risk people the same survival benefits as those without risk. Thus, this study aimed to examine the joint association of healthy lifestyles and statin use with all-cause and cardiovascular mortality in high-risk individuals, and evaluate the survival benefits by life expectancy.
METHODS During 2015–2021, participants aged 35–75 years from 31 provinces were recruited by China Health Evaluation and risk Reduction through nationwide Teamwork. 265,209 participants at high CVD risk were included for analysis of joint association. 1,366,982 participants at low or moderate risk were included for comparison of life expectancy. Based on number of healthy lifestyles related to smoking, alcohol drinking, physical activity, and diet, we categorized them into: very healthy (3–4), healthy (2), and unhealthy (0–1). Statin use was determined by self-report taking statins in last two weeks.
RESULTS Among the 265,209 included participants with high risk, 6979 deaths were observed, including 3236 CVD deaths during a median 3.6 years of follow-up. Individuals taking statin and with a very healthy lifestyle had the lowest risk of all-cause (HR: 0.70; 95% CI: 0.56–0.87) and CVD mortality (0.56; 0.40–0.78), compared with statin non-users with an unhealthy lifestyle. High-risk participants taking statins and with a very healthy lifestyle had the highest years of life gained (5.90 years at 35-year-old [4.14–7.67; P<0.001]) compared with statin non-users with an unhealthy lifestyle among high-risk people. And their life expectancy was comparable with those without high risk but with a very healthy lifestyle (4.49 vs. 4.68 years).
CONCLUSIONS High-risk participants with combination of preventive medication and multiple healthy lifestyles had lower risk of all-cause and cardiovascular mortality and largest survival benefits. And their life expectancy was comparable with those without high risk but with a very healthy lifestyle. Our findings help high risk population relieve their psychological stress and enhance their health confidence to control CVD risk. People at high risk should be encouraged to take a positive attitude towards their suboptimal health status and follow medical advices to achieve better health status as those with low or moderate risk.
GW34-e1334
Yong Ling, Yiming Wan, Hui Cui, Maryam Zaid
Department of Epidemiology, Fudan University, Shanghai, China
OBJECTIVES The relationship between sedentary behavior (SB) and cardiovascular disease (CVD) remains uncertain, and there is limited evidence regarding how physical activity (PA) interacts with SB on CVD and all-cause mortality (ACM) risk. This study aims to evaluate the association of SB and PA with CVD and ACM risk in a large population of Chinese adults.
METHODS This cohort study enrolled 40,984 participants aged 20 to 74 years from the Shanghai Suburban Adult Cohort and Biobank study, which is a community-based natural population cohort study. SB and PA were assessed using the International Physical Activity Questionnaire. CVD and ACM events were determined using multiple sources of data, including self-reported chronic disease history, the Cardiovascular and Cerebrovascular Disease Registration and Reporting System, the Electronic Medical Record System, and the Cause-of-Death Surveillance System. Cox regression models and restricted cubic splines were utilized for the analyses.
RESULTS A total of 1352 CVD comprising 753 cases of coronary heart disease and 652 cases of stroke and 669 ACMs events occurred. High SB was associated with an increased risk of CVD [HR (95% CI): 1.23 (1.08–1.40)] and ACM [HR (95% CI): 1.49 (1.24–1.79)]. Compared to those with low SB in the regular and high PA categories, the HR for individuals with high SB were observed to be 44% and 11% higher for CVD, and for ACM were observed to be 65% and 33% higher, respectively. Participants with regular PA and high SB had the highest CVD [1.23 (1.03–1.46)] and ACM [2.10 (1.63–2.69)] risk compared to those with high PA and low SB. The continuous relationship between SB and CVD and ACM weakened and even eliminated in the high PA category.
CONCLUSIONS Among Chinese adults, SB was associated with an elevated risk of CVD and ACM. The associations were effectively weakened with higher levels of PA. These results indicate that decreasing SB can reduce the risk of CVD and ACM. Moreover, increasing levels of PA can largely decrease or even eliminate this risk, particularly for individuals who engage in prolonged periods of sitting in their daily routines.
GW34-e1378
Jingnan Liu1, Zijuan Zhang1, Yaxing Cheng1, Zhen Zhou1, Huihui Zhao1,2,3, Xiaoqiao Ren1,2
1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
2Institute of National Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
3Key Laboratory of Basic Research on Prescription and Syndrome, Ministry of Education, Beijing 100029, China
OBJECTIVES Previously, we found that urine color can distinguish the severity of chronic heart failure (CHF) patients, and has early warning value in clinical. It is critical for prognosis to develop new approaches to assess early which CHF patients will likely become clinically severe. Here we compared the differences in clinical characteristics and urine metabolomics of two different urine colors in the CHF patients, to reveal the material basis of urine color as an early warning index.
METHODS We performed clinical characteristics (urine routine, blood routine and blood biochemistry) and 1H NMR metabolomic profiling of urine from 100 CHF patients (48 light urine color cases, 29 mediate urine color cases, and 23 dark urine color cases) and 80 control individuals (45 had metabolomes tests) to identify clinical features and significant metabolomic differential expression patterns between different urine color classes.
RESULTS We found significant differences in the distribution of CKD stages with different urine color in the CHF patients, and significant differences in the distribution of anaemia with different urine color in male CHF patients. The lighter the urine color of CHF patients, the lower the red blood cell, hemoglobin, total bilirubin, direct bilirubin, high sensitivity C-reactive protein, and estimated glomerular filtration rate, while the levels of urea and creatinine increased. At the same time, we found that compared with healthy controls, CHF patients had reduced expression of 11 urine metabolites (Citrate, Glutamine, Aconitate, 2-Oxoglutarate, 3-Hydroxybutyrate, Glycine, N-Acetylglutamate, Creatinine, Hypoxanthine, 1-Methylnicotinamide and Hippurate) and increased expression of 3 urine metabolites (Isoleucine, Glucose and Phenylacetylglycine). Moreover, after correlating their expression with urine color, the expression of 5 urine metabolites (Citrate, Glutamine, Aconitate, Acetoacetate and 3-Hydroxybutyrate) was increased in the dark urine color group compared with the light urine color group in the CHF patients. The difference of metabolite expression between the dark urine color group and the control group was smaller, while the difference between the light urine color group and the control group was greater. TCA cycle metabolites were modified in the CHF patients, indicating that energy metabolism was more altered in the light urine color group.
CONCLUSIONS Our data indicate that CHF patients with different urine color have different clinical characteristics and urine metabolite expression. These findings also partially illuminate that urine color can be used as a material basis for warning index of the severity of chronic heart failure. Therefore, urine color should be systematically registered clinically using an objective color classification system. It provides a simple way to realize the early warning of the severity of CHF patients.
GW34-e1416
Minxian Wang
Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation
OBJECTIVES Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. The objective of this study was to develop a new and improved polygenic score for coronary artery disease (CAD) that incorporates genome-wide association data across ancestries and CAD risk factors, and to assess its performance in identifying individuals at high risk of CAD.
METHODS The new polygenic score, GPSMult, was developed by integrating genetic association data for CAD (>269,000 CAD cases and >1,178,000 controls) from five ancestries and ten related traits from diverse populations. The performance of GPSMult was assessed using UK Biobank participants of European ancestry and four multiethnic, external validation datasets.
RESULTS GPSMult strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10–2.19, P<0.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPSMult was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70–1.76, P<0.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433, and 27,990 participants of African, European, Hispanic, and South Asian ancestry, respectively.
CONCLUSIONS The study developed a new and significantly improved polygenic score for CAD, GPSMult, which incorporates genome-wide association data across five ancestries and ten CAD risk factors. GPSMult significantly improved risk discrimination and reclassification and outperformed all previously available CAD polygenic scores. These findings contribute a new GPSMult for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.
This work was accepted by Nature Medicine recently.
CARDIAC REHABILITATION
GW34-e0058
Xiaoling Liu, Yuqin Shen
Department of Cardiac Rehabilitation, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200092, China
OBJECTIVES Heart failure (HF) is characterized by ventricular remodeling (also called myocardial remodeling). Although aerobic exercise (AET) improves heart failure, including ventricular remodeling or myocardial fibrosis, the mechanisms underlying these different outcomes in the heart remain cryptic. Here, we aim to investigate the role of Smad2 in the mechanism of AET improving heart failure.
METHODS To define the role of Smad2 in the mechanism of exercise ameliorating heart failure, ligation of the left anterior descending (LAD) branch to create an animal model of HF for aerobic exercise intervention, cardiac-specific inhibition of Smad2 induced by intravenous injection of recombinant adeno-associated virus serotype 9 (rAAV9). Cardiac function and ventricular remodeling in mice were assessed by echocardiography, the extent of cardiac fibrosis and cardiac tissue remodeling was measured by histological analysis, mRNA levels of relevant genes were assessed by reverse transcription qPCR, and protein levels were assessed by immunoblotting.
RESULTS Echocardiography revealed that left anterior descending (LAD) branch ligation resulted in more severe cardiac dysfunction reflected by decreased left ventricular ejection fraction (LVEF%, 59.72±4.45 versus 29.11±6.08, P<0.001) and fractional shortening (FS%, 31.03±3.02 versus 13.36±2.76, P<0.001), whereas aerobic exercise training (AET) reverses it (LVEF%, 29.11±6.08 versus 45.81±5.22, P<0.001; FS%, 13.36±2.76 versus 22.27±2.81, P<0.001). AET consistently reduced myocardium fibrosis in HF animals, according to histopathological examination and the transcript levels of collagen III. Smad2 gene mRNA levels indicate that AET boosts Smad2 expression in HF mice. Furthermore, AET affects HF similarly whether Smad2 expression is repressed or not when it occurs. Additionally, Smad2 expression suppression in the heart appears to reduce myocardial fibrosis and remodeling while also enhancing cardiac function in HF, according to echocardiography, histological studies, and transcript levels of associated genes.
CONCLUSIONS AET increases Smad2 expression in HF mice, reduces myocardial fibrosis and remodeling, and enhances cardiac function. This study will enable exercise rehabilitation for heart failure by laying the theoretical groundwork for aerobic exercise to improve ventricular remodeling.
GW34-e0190
Xiaowei Ye1,2, Shiyong Yu1,2, Mengjia Sun1,2, Jie Yang1,2, Lan Huang1,2
1Institute of Cardiovascular Diseases of PLA, The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China
2Department of Cardiology, The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China
OBJECTIVES Cardiorespiratory fitness (CRF) plays an important role in coping with hypoxic stress at high altitude (HA). However, the association of CRF with the development of acute mountain sickness (AMS) is yet to be evaluated. Wearable technology devices provide a feasible assessment of CRF, which is quantifiable as maximal oxygen uptake (VO2max), and may contribute to AMS prediction. To overcome the limitations of clinical VO2max measurement, we aimed to determine the validity of VO2max estimated by the smartwatch test (SWT) that can be self-administered. We also aimed to evaluate the performance of a VO2max-SWT-based model in predicting susceptibility to AMS.
METHODS Both SWT and cardiopulmonary exercise test (CPET) were performed for VO2max measurement in 46 healthy participants at low altitude (LA, 300 m) and subsequently in 41 of them at HA (3900 m) respectively. The characteristics of red blood cells and hemoglobin in all participants were analyzed by routine blood examination before the exercise tests. The Bland-Altman method was used for bias and precision assessment. Multivariate logistic regression was used to analyze the correlation between AMS and the candidate variables. A receiver operating characteristic curve was used to evaluate the efficacy of VO2max in predicting AMS.
RESULTS VO2max decreased after acute HA exposure measured by CPET (25.20 [6.46] vs. 30.17 [5.01], P<0.001) and SWT (26.17 [6.71] vs. 31.28 [5.17], P<0.001). Both at LA and HA, VO2max was slightly overestimated by SWT but had considerable accuracy as the mean absolute percentage error (<7.0%) and mean absolute error (<2.0 mL·kg−1·min−1), with a relatively small bias compared with VO2max-CPET. Twenty of the 46 participants developed AMS at 3900 m, whose VO2max was significantly lower than that of those without AMS (CPET: 27.80 [4.55] vs. 32.00 [4.64], P=0.004; SWT: 28.00 [25.25–32.00] vs. 32.00 [30.00–37.00], P=0.001). VO2max-CPET, VO2max-SWT, and red blood cell distribution width-coefficient of variation (RDW-CV) were independent predictors of AMS. To increase the prediction accuracy, we used combination models. The combination of VO2max-SWT and RDW-CV showed the largest area under the curve of all parameters and models, which increased the area under the curve from 0.785 for VO2max-SWT alone to 0.839.
CONCLUSIONS This study demonstrates that the smartwatch device can be a feasible approach for estimating VO2max. In both LA and HA, VO2max-SWT show a systematic bias toward a calibration point, slightly overestimating the proper VO2max, when investigated in the healthy participants. The SWT-based VO2max at LA is an effective indicator of AMS and helps to better identify susceptible individuals following acute HA exposure, particularly by combining the RDW-CV.
GW34-e0327
Chen Guo, Jin Wei
Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, No.157 Xi Wu Road, Xi’an 710004, Shaanxi Province, PRC
OBJECTIVES Resistance exercise or combined with aerobic exercise is an indispensable mode of exercise rehabilitation for heart failure. Here we elucidate the cardiac effects of different resistance training on heart failure and explore the critical protective regulation of mitophagy.
METHODS The chronic heart failure model was constructed by transverse aortic constriction surgery, followed by 8 weeks of different resistance training, including resistance training (RT), moderate-intensity continuous training combined with resistance training (MRT), and high-intensity interval training combined with resistance training (HRT), and subsequently analyzed the changes of maximum load, cardiac structure and function, and myocardial mitophagic activity. And the role and signaling of mitophagy in exercise protection of heart failure were investigated by knockdown of Hif1α and Parkin genes in primary neonatal cardiomyocytes.
RESULTS Both RT and MRT improved maximum load (P<0.001), myocardial morphology and fibrosis (P<0.001), reduced left ventricular diameter and enhanced left ventricular systolic function (P<0.05) in heart failure mice, and MRT had the most significant effect. But HRT had no obvious protective effect on ventricular diameter and function. Only MRT significantly enhanced myocardial mitophagic activity and HIF1α expression (P<0.05). Reactive oxygen species accumulated, adenosine triphosphate production decreased, and brain natriuretic peptide levels increased in failing cardiomyocytes. The abilities of exercise stimulation to regulate reactive oxygen species, adenosine triphosphate, and brain natriuretic peptide were impaired after knockdown of Hif1α and Parkin genes inhibited mitophagy in failing cardiomyocytes (P<0.05).
CONCLUSIONS Different resistance training provides discrepant cardiovascular effects on heart failure, and MRT exhibits optimal protection. The HIF1α-Parkin-mitophagy pathway is involved in the protection and regulation of exercise on heart failure.
GW34-e0615
Yu-Shan Li1,2, Qiang Ren1,3, Jian Zhang1, Yan-Chun Liang1, Ya-Ling Han1, Quan-Yu Zhang1
1The General Hospital of Northern Theater Command
2Postgraduate Training Base of The General Hospital of Northern Theater Command
3Beifang Hospital of China Medical University
OBJECTIVES Pulmonary ventilation dysfunction often occurs after the index event in patients with coronary artery disease (CAD). However, there is a lack of evidence exploring the association between pulmonary ventilation dysfunction and the prognosis of CAD.
METHODS This retrospective observational study included 3800 CAD patients without a history of pulmonary ventilation disease who received cardiopulmonary exercise testing (CPET) during hospitalization between November 2015 and September 2021. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction (MI), repeat revascularization, and stroke. Propensity score matching (PSM) was conducted to minimize the selection bias among two groups. A subgroup analysis was stratified by smoking status of including patients were also performed.
RESULTS Patients were divided into normal group (n=2159) or abnormal group (n=1641) according to pulmonary ventilation function detected by CPET, including 1469 smokers and 2331 non-smokers. The median follow-up duration was 1237 (25–75% interquartile range 695–1596) days. The primary endpoint event had occurred in 390 patients (10.26%), including 44 (2.45%) patients with death, 40 (2.16%) patients with MI, 303 (16.11%) patients with repeated revascularization, 40 (2.13%) patients with stroke. 1455 patients in each of the two groups were enrolled in the current analysis after PSM, respectively. Pulmonary function was not associated with MACE either before (HR: 1.20, 95% CI: 0.99–1.47; Log-rank P=0.069) or after PSM (HR: 1.01, 95% CI: 0.81–1.27; Log-rank P=0.910). Furthermore, pulmonary ventilation dysfunction was independently and significantly associated with an increased risk of MACE among smoking patients (HR 1.65, 95% CI 1.25–2.18; P<0.001), but not in non-smoking patients (HR 0.81, 95% CI 0.60–1.09; P=0.159). In addition, there was a significant interaction between current smoking status and pulmonary ventilation dysfunction on MACE (P for interaction <0.001).
CONCLUSIONS Pulmonary ventilation dysfunction identified via CPET was independently associated with long-term poor prognosis in smoking patients with CAD, but not in the entire population.
GW34-e0801
Haohan Yu, Pengrui Zhao, Lijuan Hou
College of P.E and Sports, Beijing Normal University
OBJECTIVES Coronary Artery Disease (CAD) is a prevalent non-communicable disease worldwide, with approximately 11.39 million cases reported in China according to the China Cardiovascular Health and Disease Report 2021. In recent years, physical medicine has advanced, and some European and American countries have integrated exercise intervention as the recommended means of cardiac rehabilitation (CR) in category IA. Although Moderate-Intensity Continuous Training (MICT) is currently the main form of exercise rehabilitation, the American Heart Association (AHA) introduced High-Intensity Interval Training (HIIT) for non-acute CAD patients in 2007. Subsequent studies have consistently shown that HIIT is more effective in improving the quality of life (QOL) of patients. Therefore, this study aimed to systematically evaluate and conduct a Meta-analysis to compare the effectiveness of two exercises in improving QOL of patients with coronary artery disease (CAD).
METHODS This study conducted a systematic search of eight electronic databases, including the CNKI, Wanfang database, VIP, MEDLINE, Cochrane Central Register of Controlled Trials, Embase, CINAHL, and Web of Science. The search was conducted for randomized controlled trials of HIIT and MICT for non-acute CAD patients. The search was conducted up to April 30, 2023. Two investigators independently screened the literature and extracted the data based on predefined inclusion and exclusion criteria. The quality of the literature was assessed by the Cochrane evaluation tool. Meta-analysis was conducted using STATA 17.0 software.
RESULTS The meta-analysis revealed that there was no significant statistical difference in the total score of QOL between CAD patients who underwent HIIT or MICT [WMD=0.10, 95% CI (-0.09, 0.29), Z=1.00, P=0.316]. Although the impact of both exercises on the physical component summary (PCS) was not significantly different [SMD=0.30, 95% CI (-0.05, 0.65), Z=1.68, P=0.094], effects of HIIT on the mental component summary (MCS) was more notable [SMD=0.45, 95% CI (0.10, 0.81), Z=2.52, P=0.012]. According to independent index test results, HIIT was found to be more effective than MICT in improving CAD patients’ Role Physical (RP) caused by physical health problems [SMD=0.27, 95% CI (0.002, 0.54), Z=1.98, P=0.048].
CONCLUSIONS (1) Regular exercise can improve QOL and PCS effectively of CAD patients, and types of exercise does not seem to affect the amount of benefit received from exercise; (2) HIIT is more effective in regulating patients’ MCS and mental health, which may result in better compliance compared to MICT; (3) HIIT may be more beneficial for patients in reducing daily functional limitations caused by physiological issues. This is likely due to that HIIT results in greater feedback of internal load and exceeding compensation; (4) Patients with non-acute CAD are at a high risk of exercise-related complications. Differences in physical fitness levels between patients in Europe, US and China may exist. Therefore, it’s important to have a chaperone monitor their physiological load indicators such as HR, VO2 or blood lactate levels in real-time during exercise (National Natural Science Foundation of China grant: no. 31971095).
GW34-e0804
Zulong Xie1, Dongzhi Gou2, Xiaozhu Liu1, Xing Liang1, Guozhu Chen1
1Department of Cardiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
2School of Public Health, Chongqing Medical University, Chongqing 400010, China
OBJECTIVES Regular exercise modulates systemic inflammation and confers protection against cardiac injury during myocardial infarction (MI), yet the underlying mechanism remains elusive. Exosomes serve as an important mediator in inter-organ communication and have shown great potential against cardiovascular diseases including MI. Strikingly, as pleiotropic cells of the innate immune system, macrophages interact with cardiomyocytes and other cells to coordinate post-MI processes within cardiac tissue. In this study, we aimed to investigate the role of exercise-induced exosomes of skeletal muscle in the immunomodulation of macrophages after MI, and explore their implications in cardiac injury repair.
METHODS SD rats underwent 8-week swimming regimen to establish the aerobic exercise model. Exosomes were isolated from the skeletal muscle tissue of exercised rats and their sedentary littermates using gradient centrifugation and identified by transmission electron microscopy, nanoparticle trafficking analysis and western blotting. Exosomes were administrated to rats by intramyocardial injection after inducing myocardial infarction. The curative effects of muscle-derived exosomes on cardiac inflammation and myocardial repair were evaluated. Systemic depletion of macrophages was conducted by clodronate liposomes administration. The regulating effects of exercise-induced exosomes on macrophage polarization were assessed in vitro and in vivo through immunoblotting and flow cytometry. A miRNA profiling assay between skeletal muscle-derived exosomes from exercised and sedentary rats were performed. The screened miRNAs were further verified by miRNA functional experiments. Adeno-associated virus 9 (AAV9) carrying specific sequence targeting the selected miRNA and its downstream gene were used to inhibit their expression levels in hearts.
RESULTS We found that 8-week swimming training reduced infarct rupture, decreased mortality, promoted scar formation, and improved cardiac function 30 days after MI. Injection of skeletal muscle-derived exosomes from exercised rats had similar protective effects on hearts as exercise itself. Systemic depletion of macrophages with clodronate liposomes abolished the curative effects of exercise-induced exosomes of skeletal muscle. Mechanistically, the injected PKH26-labeled exosomes were predominately colocalized with the macrophage marker CD68 in the heart. We observed an attenuated inflammatory response in hearts administrated with exercise-induced exosomes on day 1, followed by a greater transition to the reparative macrophage phenotype (CD68+CD206+) during post-MI days 3–7. Exercise-induced exosomes of skeletal muscle promoted the M1 to M2 polarization transition and attenuated inflammation after lipopolysaccharide stimulation in vitro. miRNA sequencing and bioinformatics analysis implicated miR-203 as a potent candidate mediator of macrophage polarization and myeloid differentiation factor88 (MyD88) as a downstream target. Cardiac-specific inhibition of miR-203 in vivo attenuated exercise-afforded cardioprotection after MI. On the contrary, knock down of MyD88 conferred cardioprotective efficacy and reduced inflammation level in the infarcted rat hearts.
CONCLUSIONS Aerobic exercise improves cardiac repair after MI at least partially via the skeletal muscle secreted exosomes. Exercise-induced exosomes of skeletal muscle exert cardioprotective function via shuttling miR-203 that modifies the polarization status of macrophages, indicating a novel immune link between skeletal muscle and myocardium in the context of post-MI.
GW34-e0831
Jingjin Liu, Yongshun Wang, Qingshan Geng
Shenzhen People’s Hospital
OBJECTIVES High intensity interval training (HIIT) has been found to be more effective in relieving heart failure (HF) symptoms, than moderate intensity continuous aerobic training (MICT). Additionally, higher meteorin-like protein (Metrnl) levels are seen after HIIT versus MICT. We investigated whether Metrnl contributed to post-HF cardiac functional improvements, and the signaling pathways involved.
METHODS Fifty HF patients underwent MICT, and another 50, HIIT, which was followed by cardiac function and serum Metrnl measurements. Metrnl was also measured in both blood and skeletal muscle samples of mice with transverse aortic constriction-induced HF after undergoing HIIT. Afterwards, shRNA-containing adeno-vectors were injected into mice, yielding 5 groups: control, HF, HF+HIIT+scrambled shRNA, HF+HIIT+shMetrnl, and HF+Metrnl (HF+exogenous Metrnl), followed by pressure-volume assessment. Mass spectrometry identified specific signaling pathways associated with increased Metrnl, which was confirmed with biochemical analyses. Glucose metabolism and mitochondrial functioning were evaluated in cardiomyocytes from the 5 groups.
RESULTS Both HF patients and mice had higher circulating Metrnl levels post-HIIT. Metrnl activated AMP-activated kinase (AMPK) in cardiomyocytes, subsequently increasing histone deacetylase 4 (HDAC4) phosphorylation, leading to its cytosolic sequestration and inactivation via binding with chaperone protein 14-3-3. HDAC4 inactivation removed its repression on glucose transporter type 4, which, along with increased mitochondrial complex I-V expression, yielded improved aerobic glucose respiration and alleviation of mitochondrial dysfunction. All these changes ultimately result in improved post-HF cardiac functioning.
CONCLUSIONS HIIT increased skeletal muscle Metrnl production, which then operated on HF hearts to alleviate their functional defects, via increasing aerobic glucose metabolism through AMPK-HDAC4 signaling.
GW34-e0838
Qiang Qen1,2, Yu-Shan Li1,3, Zi-Han Qin4, Jian Zhan1, Yan-Chun Liang1, Quan-Yu Zhan1, Ya-Ling Han1
1Department of Cardiology, The General Hospital of Northern Theater Command
2Beifang Hospital of China Medical University
3Postgraduate Training Base of The General Hospital of Northern Theater Command
4School of Basic Medicine, Air Force Military Medical University
OBJECTIVES To determine the association of cardiopulmonary exercise testing (CPET) parameters with adverse cardiovascular prognosis in coronary artery disease (CAD) patients with high pulse pressure (PP).
METHODS We conducted a study including patients with CAD who underwent PCI and completed CPET during hospitalization between 1 November 2015 and 30 September 2021. They were divided into two groups according to PP, defined as the difference of systolic blood pressure (SBP) minus diastolic blood pressure (DBP) on admission: High PP group (PP of male≥50 mmHg; PP of female≥60 mmHg) and Normal PP group (PP of male <50 mmHg; PP of female <60 mmHg). The study endpoint was the occurrence of the first major adverse cardiac event (MACE) during follow-up, defined as a composite endpoint of all-cause death, myocardial infarction (MI), revascularization and stroke. Univariate and multivariate Cox regression analysis were applied to construct the prognostic risk model and identify optimal predictors of MACE in CAD patients with high PP. Variables with P<0.05 in univariate Cox regression were included in multivariate Cox regression analysis.
RESULTS Totally 2785 patients were enrolled for final inclusion, with 1665 patients in high PP group and 1120 patients in normal PP group. During a median followed-up for 1215 (25–75% interquartile range 687–1586) days, MACE occurred in 383 (13.75%) patients, of which 44 (1.58%) all-cause deaths, 39 (1.40%) MI, 298 (10.70%) revascularization, and 40 (1.44%) strokes. In Cox regression analysis, lower METAT (HR 0.7, 95% CI 0.51–0.95, P=0.022) and lower HRmax (HR:0.99, 95% CI 0.98–1.00, P=0.042) were independent and significantly associated with increased risk of MACE among CAD patients with high PP.
CONCLUSIONS Among patients with high PP undergoing PCI for CAD, the decreased METAT and the decreased HRmax were the risk factors in the long-term prognosis.
GW34-e0849
Yu-Shan Li1,2, Qiang Ren1,3, Jian Zhang1, Yan-Chun Liang1, Ya-Ling Han1, Quan-Yu Zhang1
1General Hospital of Northern Theater Command
2Postgraduate Training Base of the General Hospital of Northern Theater Command, Jinzhou Medical University
3Beifang Hospital of China Medical University
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.
GW34-e1067
Xiaoqing Zhu, Tao Chen, Jun Guo
Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital
OBJECTIVES Moderate-to-vigorous physical activity (MV-PA) during leisure time has been proved to be beneficial to the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). However, the optimal level of MV-PA for reducing adverse outcomes in ASCVD patients is unclear. This study analyzed the dose-response relationship between self-reported MV-PA and mortality in ASCVD patients.
METHODS National Health and Nutrition Examination Survey (NHANES) participants with a history of coronary heart disease (CHD) or stroke (N=1252) in a period from 1999 to 2006, were enrolled and classified into low-active (0 MET-h/week), moderate-active (0< to <7.5 MET-h/week), and high-active (=7.5 MET-h/week) groups. Kaplan-Meier survival curve analysis and multivariate Cox regression models were conducted to compare the contributions of different levels of MV-PA on heart disease, cardiovascular and all-cause mortality at maximum follow-up, 10 years and 5 years respectively. Subgroup analysis, restricted cubic spline curve and propensity score matching were performed to further explore the association between MV-PA dose and adverse outcomes.
RESULTS After a median follow-up of 12.25 years, 287,344 and 805 patients died of heart disease, cardiovascular disease and any cause respectively. The high-active group had the highest event-free survivals at maximum follow-up for all outcomes compared to low-active and moderate-active groups. In multivariate Cox regression analysis, high-active group had decreased risks of heart disease, cardiovascular and all-cause mortality [HR: 0.53, 95% CI: 0.40∼0.72; 0.6 (0.46∼0.78); 0.72 (0.61∼0.85), respectively]; the moderate-active group had decreased risks of all-cause mortality [HR: 0.80, 95% CI: 0.66–0.98], but insignificantly reduced heart disease and cardiovascular mortality at maximum follow-up [0.96 (0.7∼1.32); 0.91 (0.68∼1.22), respectively]. Subgroup analysis and restricted cubic spline curve analysis demonstrated that excessive MV-PA (=15 MET-h/week) further reduced the risks of cardiovascular and all-cause mortality at maximum follow-up, but the benefits of reducing heart disease mortality were not further increased and showed a J-shaped relationship. Similar results were found at 10-years and 5-year follow-up. The effects of MV-PA on lowering the risks of all-cause mortality at maximum follow-up were modified only by age (<70 or≥70 years old), congestive heart failure (CHF) and classifications of ASCVD.
CONCLUSIONS In patients with a history of ASCVD, more MV-PA was associated with lower mortality. The most significant reductions in mortality of MV-PA level occurred between 7.5 and 15 MET-h/week. Patients with complex comorbidities, especially those with concurrent stroke and CHD or CHF, are prone to achieving greater mortality-reducing benefits by increases in MV-PA.
GW34-e1262
Yuanyuan Liu1, Yuanxun Huang1, Xiaofei Han2, Ruofan Li3, Shuai Wang4
1Wuhan University of Engineering Science
2Hubei Sports Vocational College
3Wuhan City Polytechnic
4Hubei University
OBJECTIVES Flavanone is a chemical substance, which has not been found in nature, but in many foods and plants in the existence of flavanone derivatives, these derivatives collectively known as flavanone compounds. 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. 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). The exercise group and gastric perfusion exercise group were trained for 12 weeks. After 12 weeks, four groups of rats were subjected to an exhaustive exercise, and then were anesthetized and killed. The blood was taken out for measurement of various indexes. At the end of the experiment, the experimental data were processed by SPSS Statistical Software. All the data were expressed by means of “±” standard deviation (f ± s). The significant level was <0.05, and the extremely significant level was P<0.01. All the pictures in the paper are processed by Excel.
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.
GW34-e1293
Yuanyuan Liu1, Yuanxun Huang1, Xiaofei Han2, Jia Zhao1, Ke Sun3
1Wuhan University of Engineering Science
2Hubei Sports Vocational College
3Hubei 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 DMSO group were fed with 10 mg/kg·d-1 DMSO solution, DMSO + EC Group 10 mg/kg·d-1 DMSO + 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) 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, effectively reduce the excessive free radical produced by the movement of the body tissue damage. (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.
CONCLUSIONS (1) The duration of exhaustion exercise increased significantly in DMSO group and DMSO-epicatechin group, and there was a significant difference between DMSO-epicatechin group and DMSO group, indicating that epicatechin promoted the locomotor capacity of rats. (2) DMSO-epicatechin has a significant inhibitory effect on the increase of the blood lactate concentration, indicating that epicatechin can effectively reduce the blood lactate concentration and reduce the degree of body fatigue. (3) DMSO-epicatechin can effectively on the high intensity exhaustion exercise caused by the serum GSH-Px activity has obvious inhibitory effect, indicating that epicatechin on the body of the GSH-Px activity, can effectively reduce because high intensity exercise produces excessive free radical damage to the body tissue. (4) The amount of malondialdehyde in both DMSO group and DMSO-epicatechin group was reduced, and there was a significant difference from DMSO group, indicating that epicatechin had a significant inhibitory effect on MDA activity in rats.
GW34-e1362
Qing-an Jiang1, Tao Xu1, Jing Lv1, Xiang Li1, Tingchun Wu1, Yan Zhang2
1Department of Cardiology, NO.2 Affiliated Hospital of Guizhou University of traditional Chinese Medicine
2Outpatient Department, NO.2 Affiliated Hospital of Guizhou University of traditional Chinese Medicine
OBJECTIVES Cardio-telerehabilitation (CTR) programs are a supplement or an alternative to hospital rehabilitation programs providing similar benefits to usual hospital and home care. The main objective of this research was to evaluate the efficacy, feasibility, and adherence of a personalized 12-week CTR program based on a 5G+IoT data web platform connecting a cardiac rehabilitation center and households for low-risk cardiac patients. The secondary aims were to investigate patient satisfaction, identify barriers of implementation and adverse events, and assess cost-effectiveness.
METHODS A study protocol for a single center prospective controlled trial was conducted at a 5G+IoT data web platform with a sample size of (n=60) patients with a diagnosis of low-risk CVD with class I heart failure according to NYHA. Participants receive a personalized 12-week exercise program through a 5G+IoT data web platform that allows health professionals in the cardiac rehabilitation center to generate videos, images, and parameters of each exercise. The outcome measures including efficacy, feasibility, adherence, patient satisfaction, barriers of implementation, adverse events and cost-effectiveness were obtained and compared before and after the completion of the 12-week CTR program.
RESULTS Overall, 60 rehabilitees aged 35 to 70 years (mean age 60, SD 6 years; n=48, 80% men) were included in the study. Decrement in waist circumference (P=0.04) and increment in self-assessed QoL were greater (P=0.03). All rehabilitees achieved statistically significant improvements in the 6-minute walk test (P=0.02). Also the results suggested beneficial effects in biochemical, cardiac function, quality of live and functional capacity, and the effectiveness of the intervention was also proven in patients with heart failure (all P<0.05). The successful delivery of the intervention, the absence of significant adverse effects, and the user satisfaction demonstrated the feasibility of these interventions in cardiac patients (all P<0.05).
CONCLUSIONS This study will add evidence in support of the use of CTR program based on 5G+IoT data web platform as an effective tool in new cardiac rehabilitation programs.
GW34-e1367
Yu Zhao1, Jianchao Li1, Xiaomian Fan2, Rongjing Ding2
1School of Engineering medicine, Beihang University
2Rehabilitation Department of Peking Union Medical College Hospital
OBJECTIVES Cardiac rehabilitation plays a crucial role in reducing disease recurrence, decreasing readmission, and improving quality of life for cardiovascular disease patients. Previous studies have shown that female cardiovascular disease patients have lower participation in cardiac rehabilitation. The study aims to (1) research the gender differences and main impact factors of cardiovascular disease patients’ participation in cardiac rehabilitation; (2) propose effective measures to guide patients of different genders to participate in cardiac rehabilitation.
METHODS Using questionnaire analysis method, a survey questionnaire was designed based on relevant domestic and international research of cardiac rehabilitation in China; The survey was conducted among 225 cardiovascular patients who had visited the Rehabilitation Department and related medical departments of Peking Union Medical College Hospital in October 2022; The results were analyzed using SPSS statistical software, and the significance of differences was analyzed using the independent sample T-test method.
RESULTS (1) Basic information: 175 men and 50 women, with an average age of 57 years (±12.5), including patients after percutaneous Coronary stent, hypertension, myocardial infarction, heart failure, arrhythmia, etc.; (2) The impact factors of the questionnaire survey include: long distance, lack of understanding of cardiac rehabilitation, inconvenient transportation, cost, family responsibilities, time limitations, insufficient energy, self deemed unnecessary, work responsibilities, fatigue caused by exercise training, having already conducted home rehabilitation training, excessive time required, weather, travel, conformity psychology, and being too old; (3) 44% of the total population believe that ‘distance’ is a crucial factor affecting participation in cardiac rehabilitation; The other five main impact factors are: lack of understanding of cardiac rehabilitation (32.4%), having conducted home rehabilitation training (27.2%), inconvenient transportation (25.7%), high cost (24.9%), and family responsibility (22.2%). (4) An independent sample T-test was conducted on the grouping data of male and female patients, and it was found that the five impact factors, namely “insufficient energy, excessive age, fatigue caused by exercise training, conformity psychology, and inconvenient transportation,” showed significant differences between different gender groups (P<0.01); In addition, there were significant differences between gender groups in six impact factors, including “time constraints, lack of understanding of cardiac rehabilitation, excessive time required, weather, family responsibilities, and distance” (P<0.05).
CONCLUSIONS The main impact factors for cardiovascular disease patients to participate in cardiac rehabilitation are distance, lack of understanding of cardiac rehabilitation, home rehabilitation training, inconvenient transportation, high cost, family responsibility, etc. Compared with male cardiovascular disease patients, female patients believe that insufficient energy, excessive age, fatigue caused by exercise training, herd mentality, and inconvenient transportation are the five main factors affecting their participation in cardiac rehabilitation. The results of this study have a certain reference value for the future layout of cardiac rehabilitation centers, the formulation of personalized exercise prescription (exercise intensity, exercise time, etc.), and patients’ cardiac rehabilitation education.
GW34-e1401
Antimo Maisto
World Time Communication
OBJECTIVES MAISTO ANTIMO MD Franco Naccarella., MD FACC FESC FAHA, NASPE HRS, Bruno Gentile MD, Giorgio Liguori, MD, Mattei Gianni PhD, Enrico Drago, MD, FMSI, Andrea Vaccari, MD, CONI. Dott. Andrea Minarini, Dott. Federico Addimando, Dott. Gianpiero De Cicco, Dott. Luciano De Biase FESC SIC. Dott. Massimo Galli, Dott. Alessandro Nobili, Maria Teresa Sandri, Bianalisi International Laboratories. Euro China Bologna Roma Napoli Milano Società per la Ricerca Sanitaria e Università convenzionate/connesse.
METHODS Nell’era COVID 19 e post COVID 19, 34 giovani atleti consecutivi sono stati valutati mediante ECG di cardiologia non invasiva ed ecografia, ecografia polmonare, imaging CAT ed esami del sangue di laboratorio, per controllare i parametri umorali e di immunologia cellulare, rispetto a COV19 e altri diversi infezioni virali/batteriche sistemiche/localizzate.
RESULTS Solo 6/34 erano (Gruppo A) affetti da COVID 19 localizzazioni miocardiche e/o pleuriche/polmonari, confermate da imaging e specifici esami del sangue e 28/36 erano (Gruppo B) affetti da Virus Echo Cosksakie tradizionali, Enterovirus, Mycoplasma, Toxoplasmosi e infezioni da mononucleosi di Ebstein e Barr. Mentre nel gruppo B le lesioni sono guarite insieme al miglioramento clinico in 20 45 giorni, nel gruppo A la lesione è perdurata nel tempo e sono state documentate diverse aritmie sopraventricolari e ventricolari, a riposo o durante il tapis roulant, limitando l’idoneità sportiva agonistica e richiedendo un seguito piùgo.
CONCLUSIONS La diagnosi differenziale tra COVIV 19 e miocardite tradizionale nei soggetti giovani, è obbligatoria perché hanno diversi profili clinici laboratoristici seguono trattamento e prognosi a breve e lungo termine.
CLINICAL RESEARCH ON CARDIOVASCULAR DISEASES
CORONARY HEART DISEASE
GW34-e0026
Jinfeng Tan, Bo Yu
Department of Cardiology, The Second Affiliated Hospital, Harbin Medical University
OBJECTIVES To explore the effect of dexmedetomidine on patients with acute STEMI who underwent emergency PCI under the support of non-invasive ventilation.
METHODS This study is a single-center, prospective, open-label, single-blind, randomized controlled clinical study. A total of 150 patients with acute STEMI who were admitted to the Department of Cardiology of the Second Affiliated Hospital of Harbin Medical University from January 2020 to February 2022 and planned to undergo emergency PCI treatment under the support of NIV were randomly divided into dexmedetomidine group (DEX group, 75 cases) and control group (CON group, 75 cases). Baseline characteristics, examination data and clinical follow-up data of the two groups of patients were collected. ① White blood cell count and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured at baseline (admission) and the next morning; At baseline and immediately after operation, peripheral venous blood was centrifuged and serum was taken to detect tumor necrosis factor-α (TNF-α), Hypersensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), superoxide dismutase (SOD) levels; ② Compare the failure rate of NIV and RASS sedation-agitation score between the two groups. ③ The operation time, CCU stay time and total hospitalization time, satisfaction of interventional physicians, postoperative complications (delirium, malignant arrhythmia, stroke, bleeding) and all-cause mortality within 30 days were compared between the two groups.
RESULTS Baseline characteristics were comparable between the two groups. Compared with CON group, DEX group had lower NIV failure rate (5 (6.67%) vs 14 (18.67%) P=0.027) and lower RASS score (P<0.001); DEX group had a shorter duration of the operation time (P=0.037), the stay time of CCU (P=0.047), but the total hospital stay was not statistically different, the satisfaction of interventional physicians was higher (P=0.019), the postoperative delirium was lower (P=0.028), and malignant arrhythmia was lower (P=0.044). However, there was no statistical difference in all-cause mortality within 30 days. The white blood cell count of the two groups increased the next day compared with the baseline, but compared with the CON group, the white blood cell count of the DEX group was lower the next day (P<0.05); The NT-proBNP level of the two groups decreased from the baseline on the next day, and the NT-proBNP level of the DEX group was lower on the next day (P<0.05); Compared with baseline, TNF immediately after operation in both groups-α. The levels of hs-CRP and MDA increased, but the level of DEX group was lower immediately after operation (P<0.05). Compared with the baseline, the level of SOD in both groups decreased immediately after operation, but the decline in DEX group was lower (P<0.05).
CONCLUSIONS Dexmedetomidine could effectively improve the tolerance of patients with acute STEMI receiving NIV, reduce the proportion of conversion to invasive ventilation, shorten the operation time and CCU stay time, reduce postoperative complications, and reduce oxidative stress and inflammatory reaction, but it did not reduce the 30-day all-cause mortality rate.
GW34-e0047
Kongyong Cui, Fu Rui, KeFei Dou
Cardiometabolic Medicine Center, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Previous studies evaluating the association between prediabetes and clinical events in individuals with coronary artery disease (CAD) reported conflicting results, mainly because of the varied diagnostic tests and glycemic thresholds for prediabetes across these studies. Therefore, we performed this study to evaluate the prognostic impact of prediabetes identified by different glycemic thresholds (according to American Diabetes Association [ADA] or World Health Organization [WHO]/International Expert Committee [IEC] criteria) and diagnostic tests (fasting plasma glucose [FPG] or hemoglobin A1c [HbA1c]) in patients with stable CAD.
METHODS In this prospective cohort study, we consecutively enrolled 4088 stable, angiography-proven CAD nondiabetic patients with a median follow-up period of 3.2 years. During hospitalization, patients received coronary revascularization or optimal medical therapy alone based on recommendations of contemporary guidelines, cardiologist’s discretion and their own preference. Prediabetes was defined according to ADA criteria as FPG 5.6∼6.9 mmol/L and/or HbA1c 5.7∼6.4%, and WHO/IEC criteria as FPG 6.1∼6.9 mmol/L and/or HbA1c 6.0∼6.4%. The primary endpoint was major adverse cardiovascular event (MACE), including all-cause death, myocardial infarction or stroke. Univariable and multivariable Cox regression analyses were performed and Harrell’s C-statistic was calculated for different models.
RESULTS The prevalence of prediabetes defined according to ADA criteria (67%) was double that of WHO/IEC criteria (34%). Compared with patients with normoglycemia, those with WHO/IEC-defined prediabetes were significantly associated with higher 3.2-year risk of MACCE even fully adjusting for other confounding factors (adjusted hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.10–2.06), which was mainly driven by the higher incidence of events in individuals with HbA1c-defined prediabetes (adjusted HR 1.58, 95% CI 1.15–2.16). However, this difference was not found in patients with ADA-defined prediabetes and normoglycemia (adjusted HR 1.17, 95% CI 0.81–1.68). Although FPG was not associated with cardiovascular events, HbA1c improved the risk prediction for MACE in a model of traditional risk factors (ΔC-statistic 0.021, 95% CI 0.002–0.041, P=0.034). Moreover, the optimal cutoff value of HbA1c for predicting MACE was 5.85%, which was close to the threshold recommended by IEC.
CONCLUSIONS This study supports the use of WHO/IEC criteria for the identification of prediabetes in stable CAD patients. HbA1c, rather than FPG, should be considered as a useful marker for risk stratification in this population.
GW34-e0052
Houyong Zhu1, Xiaoqun Xu2, Qilan Chen1, Tielong Chen1, Jinyu Huang3
1Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University
2Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine
3The Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
OBJECTIVES The aim of this study was to assess the association between the inflammation-based Glasgow Outcome Score (GPS) and mortality in patients with cardiovascular disease (CVD).
METHODS This study included 3833 patients (>=20 years old) with CVD in the National Health and Nutrition Survey from 1999 to 2010. The death result is determined by the correlation with the national death index on December 31, 2019. GPS consists of serum C-reactive protein and albumin. The main outcome was all-cause death, including cardiac death and non-cardiac death. The Cox proportional hazards adjusted for demographic factors and traditional cardiovascular risk factors were used to test the impact of GPS level on mortality. The sensitivity analysis included components of CVD, heart failure, coronary heart disease, angina, heart attack, and stroke.
RESULTS Among 3833 CVD patients with a median follow-up of 9.6 years, 2431 all-cause deaths, 822 cardiac deaths, and 1609 non-cardiac deaths were recorded. After full model adjustment, compared with the GPS (0) group, the risk ratio (HR) of all-cause death for GPS (1) and GPS (2) were 1.667 (95% confidence interval (CI), 1.490–1.865) and 2.835 (95% CI, 2.077–3.869), respectively (P for trend<0.001). Compared with the GPS (0) group, the HR of cardiac death for GPS (1) and GPS (2) were 1.693 (95% CI, 1.395–2.053) and 2.268 (95% CI, 1.264–4.070), respectively (P for trend<0.001). Compared with the GPS (0) group, the HR of non-cardiac death for GPS (1) and GPS (2) were 1.656 (95% CI, 1.443–1.901) and 3.136 (95% CI, 2.171–4.530), respectively (P for trend<0.001). The results of the sensitivity analysis were almost consistent with the overall cohort.
CONCLUSIONS Using the US national database, and adjusting for a large number of potential confounders through flexible modeling, we found that GPS was strongly associated with a increased risk of death in patients with CVD and that the higher GPS level was associated with an increased risk of death, and this score, which consists of readily available biomarkers, may in the future be used for risk stratification and potentially for improving patient outcomes.
GW34-e0069
Zhenwei Wang, Naifeng Liu
Zhongda Hospital, School of Medicine, Southeast University
OBJECTIVES Although current evidence suggests a causal association between lipoprotein(a) [Lp(a)] and cardiovascular disease, there is still no consensus on its association with coronary severity in new-onset acute myocardial infarction (AMI).
METHODS In this large cross-sectional study, we enrolled 2740 patients with new-onset AMI from the Zhongda Hospital affiliated to Southeast University. Lp(a) was considered as an exposure variable. Gensini score, left main disease and three-vessel disease were used to assess coronary severity. Multivariate logistic regression, restricted cubic spline (RCS) models, threshold effects and receiver operator characteristic (ROC) curve were used to analyze the association of Lp(a) with coronary severity.
RESULTS Multivariate adjusted models showed that Lp(a) was independently associated with Gensini score (=100), left main disease and three-vessel disease [Q4 vs Q1, OR (95% CI), P value: 2.301 (1.770, 2.992), P<0.001; 1.743 (1.174, 2.587), P=0.006; 1.431 (1.128, 1.816), P=0.003; respectively], and the associations persisted in sensitivity analyses or in most subgroups (P<0.05). Additionally, the RCS showed that Lp(a) was nonlinearly associated with Gensini score (continuous variable), Gensini score (=100) and three-vessel disease (P for nonlinearity<0.05). Threshold effects analysis showed that Lp(a) above the inflection point was positively associated with Gensini score (continuous variable) as well as the risk of Gensini score (=100) and three-vessel diseas. And the ROC also confirmed the diagnostic efficacy of Lp(a) for Gensini score (=100), left main disease and three-vessel disease.
CONCLUSIONS Lp(a) was closely associated with coronary severity in patients with new-onset AMI.
GW34-e0070
Zhenwei Wang, Naifeng Liu
Zhongda Hospital, School of Medicine, Southeast University
OBJECTIVES Although dyslipidemia increases the risk of coronary heart disease (CHD) and its adverse prognosis, the association between the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) and major adverse cardiovascular and cerebrovascular events (MACCE) after percutaneous coronary intervention (PCI) in patients with CHD has not been adequately demonstrated. Therefore, the aim of this study was to assess the role of LDL-C/HDL-C in the risk of MACCE after PCI in patients with CHD.
METHODS In this large cohort observational study, we enrolled 2226 patients with CHD treated with PCI. LDL-C/HDL-C was considered as an exposure variable and MACCE was considered as an outcome variable. Univariate and multivariate Logistic regression models and subgroup analyses were used to assess the relationship between LDL-C/HDL-C and risk of MACCE.
RESULTS A total of 2226 patients (mean age: 60.02 years; 68.00% male) were included in the analysis, and 373 patients suffered MACC. Patients who developed MACCE had higher levels of LDL-C/HDL-C compared to patients who did not develop MACCE [(2.79±1.15) vs (2.64±1.09), P=0.023]. Univariate Logistic regression analysis showed a correlation between LDL-C/HDL-C and the risk of MACCE (OR: 1.121, 95% CI: 1.019–1.233, P=0.019). Multivariate Logistic regression analysis showed that higher levels of LDL-C/HDL-C remained strongly associated with higher risk of MACCE after stepwise adjustment for confounding variables [Model 4: T3 vs T1, OR: 1.455, 95% CI: 1.095–1.933, P=0.010; per unit increase, OR: 1.158, 95% CI: 1.047–1.281, P=0.004]. Further subgroup analysis showed that the association between LDL-C/HDL-C and MACCE risk remained in the subgroup = 60 years, male, without diabetes, and with hypertension (P<0.05).
CONCLUSIONS Higher LDL-C/HDL-C was closely associated with a higher risk of MACCE after PCI in patients with CHD.
GW34-e0073
Wenchang Nie, Jian Liu
Peking University People’s Hospital
OBJECTIVES The activity of platelet surface membrane protein P2Y12 receptor may affect the platelet activity, but there is still no consistent conclusion on the influence of the variation of its coding gene. In this study, the variation of single nucleotide polymorphism (SNP) in the P2RY12 gene was detected and compared, aiming to clarify the effect of morphism of the P2RY12 gene on high platelet reactivity (HPR).
METHODS This study is an observational study. Patients who are admitted due to chest pain and planned to undergo coronary angiography from December 2020 to September 2022 were admitted. All patients take aspirin and a P2Y12 receptor inhibitor. According to the determination results of vasodilation-stimulated phosphoprotein and light transmittance aggregation, the patients were divided into HPR and non-HPR group. The phenotypes of two loss of function (LOF) alleles (rs4244285, rs4986893) of CYP2C19 gene and six SNP sites (rs680969, rs6785930, rs5853517, rs6787801, rs1491974, rs4603933) of P2RY12 gene were detected. The difference of locus variation between the two groups was corrected by clinical and known gene variation factors to clarify the influence of P2RY12 gene SNP variation on HPR.
RESULTS 1. This study finally included 112 patients, of which 62 cases (55.4%) were in the HPR group. Between the two groups, there were no significant differences in age, sex, smoking history, comorbidities, et al (P>0.05). 2. Carrying the LOF allele of the CYP2C19 gene would increase the risk of HPR, but there is no significant difference [odds ratio (OR) 1.859, 95% confidence interval (CI): 0.873∼3.956, P=0.108]. 3. Among the 6 SNP sites of the P2RY12 gene, single factor Logistic analysis showed that the rs6785930 mutation may increase the risk of HPR (OR 2.125, 95% CI: 0.979∼4.613, P=0.057), and the wild type of rs6809699 was only 2 cases, all of which showed HPR, other SNPs do not show relevance with HPR (rs5853517: OR 0.612, 95% CI: 0.054∼6.954, P=0.692; rs6787801: OR 0.617, 95% CI: 0.267∼1.422, P=0.256; rs1481974: OR 0.662, 95% CI2: 0.27 1.611, P=0.363; rs4603933: OR 0.819, 95% CI: 0.132∼5.105, P=0.831). The three SNP loci of rs6809699, rs5853517, and rs4603933 constituted three common haplotypes, and the distribution frequency in the enrolled patients was 94.0%, but there were no significant differences among the three haplotypes among different platelet reactivity groups (P>0.05). 4. The results of binomial Logistic regression analysis showed that among the clinical and known genetic factors, gender, creatinine, CYP2C19 gene LOF allele carrier status, age, and hemoglobin concentration had a certain impact on HPR. The above factors were used to correct the influence of SNPs, it was found that rs6785930 was an independent risk factor for HPR (OR 2.64, 95% CI: 1.087∼5.639, P=0.045).
CONCLUSIONS This study suggests that the variation of SNP site rs6785930 in P2RY12 gene is an independent predictor of ADP-induced HPR. Three haplotypes consisting of SNP sites rs6809699, rs5853517, and rs4603933 of the P2RY12 gene were common in the enrolled population, but no effect of these three haplotypes on HPR was found. P2RY12 gene polymorphism may affect the occurrence of HPR to some extent.
GW34-e0077
Wen Pan, Haixiang Xu, Jianhua Fan, Cheng Chang, Licheng Lu, Jianfeng Qian, Qingjun Liu
Department of Cardiology, Kunshan Hospital of Traditional Chinese Medicine
OBJECTIVES To investigate the impact of regional collaborative network on the rescue of patients with ST-elevation myocardial infarction (STEMI) first visit to non-percutaneous coronary intervention (PCI) hospitals.
METHODS Data from the database of chest pain center in Kunshan Hospital of Traditional Chinese Medicine were analyzed. Patients were divided into observation group and control group according to the time of establishment of the regional collaborative rescue network. Key time points and complications during hospitalization were collected and analyzed.
RESULTS A total of 152 STEMI patients were included in the study. Compared to control group, time of symptom to balloon (S-B), time of first medical contact (FMC) to balloon (FMC-B) and inter-hospital referral time in observation group were significantly shorter [(314.03±209.26) min vs (451.27±290.44) min, P=0.001], [(115.32±54.73) min vs (191.67±130.30) min, P=0.001], [(55.09±37.23) min vs (112.67±95.90) min, P=0.001], but time of symptom to FMC (S-FMC) were not statistically significant [(210.27±217.07) min vs (239.61±200.92) min, P=0.136]. The incidence of heart failure and total complications during hospitalization decreased [7(8.14%) vs 13(19.70%), P=0.037] and [14(16.28%) vs 24(36.36%), P=0.004]. However no statistically significant difference were observed in rate of death during hospitalization [2(2.33%) vs 3(4.55%), P=0.450], ventricular fibrillation [2(2.33%) vs 3(4.55%), P=0.450], left ventricular thrombosis [2(2.33%) vs 4(6.06%), P=0.244] and recurrent myocardial infarction [1(1.16%) vs 1(1.52%), P=0.851].
CONCLUSIONS Regional cooperative rescue network could significantly shorten the total ischemic time and referral time of patients with STEMI and reduce the incidence of heart failure during hospitalization.
GW34-e0113
Jiachen Luo
Shanghai Tenth People’s Hospital
OBJECTIVES To investigate the predictive value and prognostic impact of stress hyperglycemia ratio (SHR) for new-onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI).
METHODS This retrospective study included 2145 AMI patients without AF history between February 2014 and March 2018. SHR was calculated using fasting blood glucose (mmol/L)/[1.59*HbA1c (%)–2.59]. Association between SHR and post-MI NOAF was assessed with multivariable logistic regression analyses. The primary outcome was a composite of cardiac death, heart failure hospitalization, recurrent MI, and ischemic stroke (MACE). Cox regression-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated for MACE.
RESULTS A total of 245 (11.4%) patients developed NOAF. In the multivariable logistic regression analyses, SHR (each 10% increase) was significantly associated with increased risks of NOAF in the whole population (OR: 1.05, 95% CI: 1.01–1.10), particularly in non-diabetic individuals (OR: 1.08, 95% CI: 1.01–1.17). During a median follow-up of 2.7 years, 370 (18.5%) MACEs were recorded. The optimal cut-off value of SHR for MACE prediction was 1.119. Patients with both high SHR (≥1.119) and NOAF possessed the highest risk of MACE compared to those with neither high SHR nor NOAF after multivariable adjustment (HR: 2.18, 95% CI: 1.39–3.42), especially for the diabetics (HR: 2.63, 95% CI: 1.41–4.91). Similar findings were observed using competing-risk models.
CONCLUSIONS The SHR is an independent predictor of post-MI NOAF in non-diabetic individuals. Diabetic patients with both high SHR and NOAF had the highest risk of MACE, suggesting that therapies targeting SHR may be considered in these patients.
GW34-e0140
Yiming Chen, Yafeng Zhou
Dushu Lake Hospital Affiliated to Soochow University
OBJECTIVES The interpretation of 12-lead electrocardiogram (ECG) in patients with acute ischemic cardiomyopathy is divided into waveform and vector. At present, clinical practice still focuses on the morphology and characteristic waveform of ECG. For patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), the diagnostic efficacy of traditional ECG is not sensitive and specific. Plane QRS-T angle (PQRS-Ta) can be used as a supplement to the current diagnostic criteria of ECG.
METHODS The patients with recurrent chest pain in our hospital were analyzed retrospectively, and the plane QRS-T angle of the patients was calculated. The main results were as follows: (1) the clinical indexes of the two groups were analyzed according to the angle of QRS-T. (2) All patients were divided into three groups according to the final diagnosis. The diagnostic efficacy of QRS-T angle combined with standard ECG diagnostic criteria was analyzed, and the incremental diagnostic value of the new standard relative to the original standard was calculated. (3) The patients were scored by Gensini, and the differences of plane QRS-T angle among patients with different scores were compared. (4) The frequency of MACE was recorded, and the prognostic effect of QRS-T angle on the study population was analyzed.
RESULTS After analyzing the data, there was a difference in the value of plane QRS-T angle between NSTE-ACS population and non-ACS population (P<0.001). The role of plane QRS-T angle in the diagnosis of NSTE-ACS was evaluated, and it was found that every 1° increase of plane QRS-T angle increased the risk of NSTE-ACS by 2.5% (χ2, 27.59, P<0.001). The diagnostic accuracy of AUC quantified plane QRS-T angle combined with standard ECG in the diagnosis of NSTE-ACS was 0.68 (CI [0.64~0.70]). Through the analysis of NRI and IDI index, the relative NRI of the new model to the original model is 6.67%, 95% CI is 3.91%, and the CI is 9.42% (P<0.001). The IDI is 6.30%, the CI is 4.65%, and the CI is 7.95% (P<0.001). The new model improves the prediction effect by 6%. The analysis of patients in different groups of Gensini scores showed that when the QRS-T angle increased by 1°, the Gensini score increased by 0.199 points (95% CIRV 0.149) (Fidel 60.975 (P<0.001). The patients were divided into three groups according to the plane QRS-T angle. Compared with the prognosis of the three groups, there was a statistical difference in the overall survival time among the three groups (χ2=19.090, P<0.001).
CONCLUSIONS Compared with the original standard, the new diagnostic standard can improve the diagnostic efficiency of ECG. QRS-T angle can predict the prognosis of patients with NSTE-ACS. The higher the value of QRS-T angle, the greater the probability of major adverse cardiovascular events (MACE) in patients with non-ST segment elevation acute coronary syndrome.
GW34-e0155
Mowei Kong
Guizhou International General Hospital (GIGH)
OBJECTIVES The risk of complications associated with metal-eluting stents in clinical use remains high. However, the new generation of absorbable stents launched to solve this problem has a short time to market, inconsistent research conclusions, and unclear scope of application. The purpose of this manuscript is to explore the safety, compatibility, and long-term prognosis of bioresorbable stents (BRS) in the treatment of low-risk coronary syndrome (ACS), and to inform future clinical practice.
METHODS A single enrollment of patients with low- and medium-risk acute coronary syndrome (ACS) recruited consecutively between January 2019 and December 2022 who received metal-drug-eluting stent (DES) or bioresorbable stent (BRS) percutaneous coronary intervention (PCI) was analyzed. The survival performance and complications of the two groups at up to 3 years of follow-up were compared and analyzed by collecting basic data of patients with implanted DES (control group) and patients with implanted BRS (observation group) and conducting clinical follow-up. The primary clinical endpoint was the device-oriented composite endpoint (DoCE), which represented patients experiencing one of the following events: cardiac death, scaffold thrombosis (ScT), target vascular myocardial infarction (TV-MI), and clinically driven targeted lesion revascularization (TLR). Secondary endpoints included: coronary artery bypass grafting, target vascular revascularization (TVR), and noncardiac death. Compare changes in serum inflammatory markers in patients after stent implantation to infer stent compatibility.
RESULTS A total of 128 patients with an average age of (63±10) years were included in this study, including 95 (74%) males. A total of 201 lesion vessels were treated, of which 87 (43%) were implanted with BRS stents and 114 (57%) were implanted with DES stents. A total of 97 patients completed a full 3-year follow-up, with 5 (17%) patients in the observation group achieving DoCE and 7 (16%) patients in the control group achieving DoCE. At 1 year of follow-up, there were 7 (15%) and 6 (10%) patients in the observation group and 6 (10%) in the control group, respectively, and there was a <statistically significant difference in the number of patients with target vascular revascularization (TVR) between the two groups at 2 years of follow-up (P<0.05).
CONCLUSIONS 1. In patients with intermediate and low-risk ACS, the time to reach DoCE after BRS treatment is earlier than that of DES patients, but there is no significant difference in the final number. 2. In the compatibility test, BRS has a stronger compatibility affinity than DES. 3. At up to 3 years of follow-up, the type and number of complications were similar in both groups. In the BRS group, individual patients still had stent collapse and chronic coronary vascular occlusion.
GW34-e0183
Bin Wang, Xiaochen Liu, Wen Hao, Qingjie Xin, Jingyao Fan, Xiao Wang, Shaoping Nie
Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
OBJECTIVES The circadian rhythm of myocardial infarction (MI) in obstructive sleep apnea (OSA) patients remains controversial and no studies have directly evaluated the relationship between nocturnal hypoxemia and the circadian rhythm of MI. Therefore, we conducted a post hoc analysis of OSA-ACS study, including 1927 patients admitted for ACS (NCT03362385). To investigate the diurnal variations of MI in patients with OSA and evaluate the association of nocturnal hypoxemia and MI onset during the night.
METHODS In this prospective cohort study, we consecutively recruited 2160 ACS patients with portable sleep monitoring between June 2015 and January 2020. The time of MI onset was clearly identified by patient’s report of the chest pain that prompted hospital admission. The difference in circadian variation of MI onset was evaluated between severe/moderate OSA and non/mild OSA patients. We also investigate the predictive value of OSA and nocturnal hypoxemia in the occurrence of nocturnal MI by multiple logistic regression.
RESULTS Among 713 patients enrolled, 398 (55.8%) had severe/moderate OSA (apnea-hypopnea index ≥15 events·h−1). In severe/moderate OSA group, the MI onset during bedtime was significant increased between midnight to 5:59 AM in 6-h epochs analysis (26.9 vs 18.4%, P=0.008) and 10 PM to 5:59 AM in 8-h epochs analysis (37.2 vs 29.5%, P=0.032). Nocturnal hypoxemia was associated with greater MI occurrence from midnight to 6 AM in both minimum SaO2≤86% model (adjusted OR 1.70, 95% CI: 1.16–2.47, P=0.006) and TSA90≥2% model (adjusted OR 1.54, 95% CI: 1.04–2.27, P=0.03).
CONCLUSIONS Patients with severe/moderate OSA further increases the peak of MI onset between midnight to 5:59 AM. Furthermore, severe/moderate OSA and nocturnal hypoxemia are independent risk factors for the occurrence of nocturnal MI.d.
GW34-e0184
He Lv, Xinyu Li, Zengduoji Ren, Aijie Hou, Yunqi Shi, Qiang Fu
The People’s Hospital of China Medical University, The People’s Hospital of Liaoning Province
OBJECTIVES Currently, there are plentiful factors that can affect the value of FFR, such as the tortuosity of blood vessels or the hydrostatic pressure. Conversely, there exist few studies on the effect of characteristics of pressure wire on FFR. This study aimed to analyze the relationship between the arc length, chord length and distortion degree of pressure wire and FFR.
METHODS We used a quantitative method about tortuosity index (TI) based on a combination of local and global centerline features to measure the TI (namely WTI), arc length and chord length of pressure wire.
RESULTS We performed FFR measurements and WTI calculations on 58 patients with 58 coronary vessels (mean of FFR, WTI, arc length and chord length: 0.83, 0.89, 423.20 and 295.73, median of the ratio between arc length and chord length: 1.29). Two left circumflex branches and 1 obtuse marginal branch were excluded in the process of analysis. There was no correlation between FFR and the arc length, chord length or ratio about pressure wire. In 17 right coronary arteries (mean of WTI: 1.01), WTI had negative linear correlation with FFR (r=0.569, P<0.05). Further, WTI was positively correlated (r=0.429, P<0.01) with FFR with 38 left anterior descending coronary arteries (mean of WTI: 0.86).
CONCLUSIONS In the study, the mean of WTI in right coronary arteries was higher than left anterior descending branches, and they are consistent with the distortion of the vessels intuitively. Based on the above results, we think there may be a threshold value of WTI. In other words, when WTI is less than the value, FFR could be positively correlated with WTI and when WTI is higher than the value, FFR could have negative correlation with WTI.
GW34-e0205
Chen Chang1, Ruping Cai2, Qiang Wu3,4, Qiang Su1
1Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin 541000, China
2Department of Rehabilitation Medicine, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530000, China
3Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, Beijing 100048, China
4Journal of Geriatric Cardiology Editorial Office, Chinese PLA General Hospital, Beijing 100853, China
OBJECTIVES Cardiovascular diseases especially acute myocardial infarction are the leading cause of disability and death. Atherosclerosis is the pathological basis of AMI, and chronic inflammation can accelerate the process. Ulcerative colitis is a chronic inflammatory disease associated with immunity with possible risks contributing to AMI development. However, controversy continues to surround the relationship between these two diseases. The present study unravels the pathogenesis of AMI and UC, which may provide a new perspective on the clinical management of patients with these comorbidities.
METHODS Download microarray datasets GSE66360 and GSE87473 from gene expression omnibus database. Identification of common differentially expressed genes (co-DEGs) in AMI and UC followed, the following analysis was carried out: enrichment analysis, protein-protein interaction network construction, hub gene identified and co-expression analysis.
RESULTS Totally 267 co-DEGs (233 upregulated and 34 downregulated) were screened for further analysis. GO enrichment analysis emphasizes the important role of chemokines and cytokines in these two diseases. In addition, lipopolysaccharide-mediated signaling pathway is closely related to both. KEGG enrichment analysis reveals that lipid and atherosclerosis, NF-κB, TNF and IL-17 signaling pathways are the core mechanisms involved in the progression of these two diseases. Finally, 11 hub genes were identified with cytoHubba, including TNF, IL1B, TLR2, CXCL8, STAT3, MMP9, ITGAX, CCL4, CSF1R, ICAM1, and CXCL1.
CONCLUSIONS This study reveals a co-pathogenesis mechanism of AMI and UC regulated for specific hub genes, which not only provides new ideas for further mechanistic studies, but also provides new perspectives on the clinical management of patients suffering from these comorbidities.
GW34-e0225
Mingzhi Cui1, Haohong Qi1, Ting Zhang2, Shixiong Wang1, Shaobin Jia1, Guangzhi Cong1
1Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
2Ningxia University, Yinchuan, Ningxia 750000, China
OBJECTIVES HIV infection increases the risk of acute myocardial infarction (AMI). However, little is known about its effect on in-hospital outcomes and temporal trends in AMI patients undergoing percutaneous coronary intervention (PCI).
METHODS AMI patients who underwent PCI were queried from the National Inpatient Sample Database (2003–2015) and stratified into three groups: symptomatic, asymptomatic, and HIV-negative. After 1:2 case-control matching (CCM), logistic regression analysis was conducted to determine how HIV infection affected in-hospital outcomes, including mortality, bleeding, cardiac shock, acute kidney injury, length of stay, and the number of procedures on this discharge. We also observed the temporal trends of in-hospital outcomes from 2003 to 2015 grouped by HIV status.
RESULTS A weighted national estimate of 2,191,129 AMI cases included 2,178,995 HIV/AIDS-negative cases, 4994 asymptomatic HIV cases, and 7140 symptomatic HIV cases. Symptomatic but not asymptomatic HIV patients endured an over tripled in-hospital mortality (OR 3.55, 95% CI 2.51–5.01), over two-fold of the acute kidney injury (OR 2.61, 95% CI 2.02–3.38) and the cardiac shock risk (OR 2.19, 95% CI 1.54–3.10), a longer length of hospital stay (beta 1.26, 95% CI 0.99–1.53), and had more procedures (beta 1.30, 95% CI 1.15–1.45). The higher risk of in-hospital mortality, cardiac shock, and acute kidney injury risk related to symptomatic HIV in AMI patients who underwent PCI lasted from 2003 to 2015.
CONCLUSIONS In AMI patients undergoing PCI procedures, symptomatic HIV infection is associated with higher in-hospital mortality, cardiac shock, acute kidney injury, a more extended hospital stay, and more procedures. These disparities related to symptomatic HIV infection lasted from 2003 to 2015. More attention should be paid to symptomatic HIV patients when they are comorbid with AMI and timely PCI procedures.
GW34-e0230
Kongyong Cui1, Rui Fu1, Yuejin Yang2, Kefei Dou1
1Cardiometabolic Medicine Center, Department of Cardiology, FuWai Hospital, National Center for Cardiovascular Diseases
2Coronary Heart Disease Center, Department of Cardiology, FuWai Hospital, National Center for Cardiovascular Diseases
OBJECTIVES Stress hyperglycemia was positively associated with poor prognosis in individuals with acute myocardial infarction (AMI). However, admission glucose and stress hyperglycemia ratio (SHR) may not be the best indicator of stress hyperglycemia. We performed this study to evaluate the comparative prognostic value of different measures of hyperglycemia (fasting SHR, fasting plasma glucose [FPG], and hemoglobin A1c [HbA1c]) for in-hospital mortality in AMI patients with or without diabetes.
METHODS In this prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) registry, 5308 AMI patients including 2081 with diabetes and 3227 without diabetes were evaluated. Fasting SHR was calculated using the formula [(first FPG (mmol/L))/(1.59×HbA1c (%)–2.59)]. According to the quartiles of fasting SHR, FPG and HbA1c, diabetic and non-diabetic patients were divided into four groups, respectively. The primary endpoint was in-hospital mortality.
RESULTS Overall, 225 (4.2%) patients died during hospitalization. Individuals in quartile 4 had a significantly higher rate of in-hospital mortality compared with those in quartile 1 in diabetic cohort (9.7 vs. 2.0%; adjusted odds ratio [OR] 4.070, 95% CI 2.014–8.228) and nondiabetic cohort (8.8 vs. 2.2%; adjusted OR 2.976, 95% CI 1.695–5.224). Fasting SHR was also correlated with higher in-hospital mortality when treated as a continuous variable in diabetic and nondiabetic patients. Similar results were observed for FPG either as a continuous variable or a categorical variable. In addition, fasting SHR and FPG, rather than HbA1c, had a moderate predictive value for in-hospital mortality in patients with diabetes (areas under the curve [AUC] for fasting SHR: 0.702; FPG: 0.689) and without diabetes (AUC for fasting SHR: 0.690; FPG: 0.693). The AUC for fasting SHR was not significantly different from that of FPG in diabetic and nondiabetic patients. Moreover, adding fasting SHR or FPG to the original model led to a significant improvement in C-statistic regardless of diabetic status.
CONCLUSIONS This study indicated that, in individuals with AMI, fasting SHR as well as FPG was strongly associated with in-hospital mortality regardless of glucose metabolism status. Fasting SHR and FPG might be considered as a useful marker for risk stratification in this population.
GW34-e0233
Yujie Chen, Chaoyang Lin, Luo Ben, Zhiwei Chen, Jinhua Huang, Enhui Yao
Department of Cardiology, Fujian Medical University Union Hospital, Fujian Institute of Coronary Artery Disease, Fujian Heart Medical Center, Fuzhou, China
OBJECTIVES Given the absence of permanent implants and lower cost, percutaneous transluminal coronary angioplasty by drug-coated balloon (DCB-PTCA) has rapidly expanded in indications and utilization, while a high incidence of target vessel restenosis has been observed during follow-up. This study was designed to explore the relationship between wall motion abnormalities (WMA) and prognosis after DCB-PTCA.
METHODS We performed a retrospective analysis of 192 patients and 222 lesioned vessels from January 2016 to June 2022. The patients received DCB-PTCA at the Cardiovascular Department of the Union Hospital of Fujian Medical University. We compared the clinical characteristics and analyzed coronary angiograms using Quantitative Coronary Angiography (QCA) software. Generalized estimating equations (GEEs) were used to test outcomes.
RESULTS Patients were classified into two groups according to echocardiography performed prior to the initial coronary angiography: those (n=56) with and those (n=166) without WMA. QCA analysis of the target vessels showed that (i) the quantitative flow ratio (QFR) calculated instantaneously after DCB-PTCA indicated that the coronary function in both groups had recovered to an optimal level without a significant difference, and that (ii) the prevalence of functional restenosis was higher in the WMA group than in the without WMA group (14 (25%) vs. 19 (11.4%), P=0.014), as was the prevalence of target vessel failure (TVF) (19.6 vs. 7.8%, P=0.014). Univariable and multivariate analyses showed that WMA was independently associated with the occurrence of functional restenosis [(odds ratio (OR): 3.285, 95% confidence interval (95% CI): 1.119–9.644, P=0.030) and TVF (OR: 6.108, 95% CI: 1.659–22.494, P=0.007)].
CONCLUSIONS WMA on echocardiography was an independent risk factor for poor prognosis after DCB-PTCA and was associated with a high incidence of functional restenosis and TVF events.
GW34-e0237
Guyu Zeng, Jinqing Yuan
Fuwai Hospital
OBJECTIVES Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors of cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI).
METHODS From a large cohort study, 10,435 eligible patients undergoing PCI from January 2013 to December 2013 were included for our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60–90; ≥90 mL/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)].
RESULTS Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR<60 mL/min/1.73 m2 or elevated Lp(a) (logarithm form or ≥30 mg/dL) conferred a significantly higher MACCE risk. Higher Lp(a) (≥30 mg/dL) was significantly associated with increased risk of MACCE in patients with eGFR<60 mL/min/1.73 m2 [hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.25–2.58, P=0.002]. However, this association was weakened in subjects with only mild renal impairment (HR 1.24, 95% CI 1.07–1.44, P=0.005) and diminished in those with normal renal function (HR 1.03, 95% CI 0.91–1.16, P=0.605). A significant interaction for MACCE between renal categories and Lp(a) dichotomy was observed (P=0.036). Patients with concomitant Lp(a) ≥30 mg/dL and eGFR<60 mL/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without (HR 1.75, 95% CI 1.33–2.31, P<0.001).
CONCLUSIONS The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population.
GW34-e0251
Ziyu An1, Jinfan Tian1, Xin Zhao1, Mingduo Zhang1, Lijun Zhang2, Xueyao Yang1, Libo Liu3, Xiantao Song1
1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
2Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
3Department of Cardiology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong 271000, P.R. China
OBJECTIVES Machine learning (ML) based CT angiographic-derived flow reserve fraction (CT-FFR) can effectively improve the efficiency of diagnosing coronary heart disease and may be a new non-invasive diagnostic and functional assessment modality for coronary artery disease (CAD). This meta-analysis evaluated the diagnostic accuracy of ML-based CT-FFR and compared it with coronary CT angiography (CCTA) using invasive FFR as reference.
METHODS We used the PubMed and Cochrane Library databases to search for relevant articles published between January 2008 and April 9th, 2022, with the following parameters: ‘machine learning’ AND “‘computed tomography angiography’ AND ‘fractional flow reserve’” or ‘CT-FFR’ or ‘FFR-CT’. We calculated combined sensitivity and specificity estimates based on the corresponding 95% confidence intervals (CI) and the pooled subject operating characteristic curves (sROC).
RESULTS A total of 162 potentially relevant publications were screened. After exclusion based on title, abstract, and text, a total of 13 studies (and 3902 vessels) were included in the final analysis. The included studies were published between 2018 and 2022. Study populations encompassed patients undergoing assessments for suspected or known CAD. Amongst the final studies, 13 had ML-based CT-FFR data, and 12 had CCTA data. Using FFR as a reference standard, CT-FFR based on ML had higher specificity and discriminatory power to detect hemodynamic coronary stenosis than CCTA did alone. ML-based CT-FFR had a lower sensitivity than CCTA (0.80 versus 0.87, P<0.01;). However, ML-based CT-FFR had higher specificity than CCTA (0.86 versus 0.35. P<0.01;), and ML-based CT-FFR also had a higher AUC than CCTA (0.86 versus 0.8, P<0.01;). Analysis of each vessel showed a combined Positive likelihood ratio (PLRs) of 5.8 versus 1.3 (P=0.03) for CT-FFR and CCTA, respectively. The combined Negative likelihood ratio (NLRs) for CT-FFR and CCTA were 0.22 and 0.36 (P=0.64), respectively.
CONCLUSIONS In conclusion, current data suggest ML-based CT-FFR has a higher diagnostic performance than CCTA alone for patients with hemodynamically significant CAD. More diagnostic performance clinical trials are needed before this technology can be fully applied to clinical practice or used to inform future decisions.
GW34-e0252
Chonghuai Gu
Anqing Municipal Hospital
OBJECTIVES To study the clinical efficacy of Dapagliflozin in patients with coronary heart disease (CHD) combined with Heart Failure with Reduced Ejection Fraction (HFrEF) and type 2 diabetes mellitus (T2DM) who have CHD.
METHODS A retrospective analysis of 202 patients with CHD and T2DM who were hospitalized in our department of cardiovascular medicine and underwent PCI treatment from November 2019 to November 2022 was conducted. Patients were divided into two groups according to whether they received Dapagliflozin treatment: the Dapagliflozin group (n=100) and the control group (n=102). A subgroup analysis was performed on the 80 HFrEF patients in the total population, which was also divided into two groups: the Dapagliflozin group (n=44) and the control group (n=36). The incidence of major adverse cardiovascular events (MACE) during hospitalization and the median follow-up period (224.5 days) was recorded and analyzed in both the total population and the subgroup.
RESULTS The results of the analysis of the total patient population showed no statistical differences between the two groups in baseline data and related clinical treatment conditions (P>0.05). The follow-up period event analysis showed that the overall MACE event rate in the Dapagliflozin group was lower than that in the control group (6.00 vs. 17.65%), but not statistically significant (P=0.071). The COX regression analysis of MACE events showed that the use of Dapagliflozin was an independent protective factor for MACE events [HR=0.166, 95% CI (0.026–0.953), P=0.047]. In the HFrEF subgroup analysis, there was no significant difference between the two groups in the baseline data analysis (P>0.05). The COX regression analysis in the subgroup analysis showed that the use of Dapagliflozin was a strong protective factor for the HFrEF subgroup during the follow-up period [HR=0.250, 95% CI (0.017–0.518), P<0.001]. Further analysis using the Kaplan-Meier method showed that the event rate in the Dapagliflozin group was significantly lower than that in the control group.
CONCLUSIONS The use of Dapagliflozin in patients with CHD combined with HFrEF and T2DM may be effective in reducing the incidence of MACE.
GW34-e0254
Donyor Yusupov1, Umida Kamilova2
1Fergana Branch of the Republican Scientific Center for Emergency Medical Care
2Republican Specialized Scientific and Practical Center of Therapy and Medical Rehabilitation
OBJECTIVES Evaluation of indicators of coagulation hemostasis and humoral markers of endothelial dysfunction in patients with myocardial infarction after COVID-19.
METHODS As part of the study, 130 patients with myocardial infarction after COVID-19 were examined. The average age of the examined was 51.8±6.7 years. Women made up – 64 (60.95%), men – 41 (39.05%). The following laboratory studies were carried out: complete blood count, coagulogram, enzyme immunoassay for determination of D-dimer (JSC Vector-Best, Russia), highly sensitive C reactive protein (CRP) (Demeditec Diagnostics, Germany), endothelin-1 (Elabscience, USA), von Willebrand factor (VWF) (Elabscience, USA), thrombomodulin (Elabscience, USA).
RESULTS In the blood of patients with myocardial infarction after COVID-19, a significant increase in the level of CRP, fibrinogen and D-dimer was observed. Highly sensitive CRP was 6.03±0.88 mg/mL, fibrinogen – 398.71±8.14 mg/dL, D-dimer – 214.55±4.73 ng/mL, while in patients with MI the level of highly sensitive CRP increased by 2 times amounting to 12.8±0.70 mg/L (P<0.01), the level of fibrinogen and D-dimer increased by 13.4% and 31%, amounting to 503.6±9.6 mg/dL and 248.72±8.03 mg/mL. The study of indicators of inflammation and coagulation hemostasis in patients with myocardial infarction after COVID-19, depending on the occurrence of cardiovascular risk factors in one person, showed that the level of highly sensitive CRP in persons with 3 and 4 risk factors increased almost 2 times, amounting to 13.2±0, 3 and 14.7±1.5 mg/L (P<0.01) versus 7.9±0.75 in individuals with 1 risk factor. The same dynamics was observed in relation to the indicators of fibrinogen and D-dimer, the level of fibrinogen and D-dimer significantly increased by 13.4% and 31% in patients with 3 risk factors and by 55.7% and 34.1% in patients with 4 risk factors. In patients with normal CRP levels (less than 6 mg/L), the level of endothelin-1 was 86.41±2.27 pg/mL, VWF – 128.67±1.76% and thrombomodulin 1384±14.9 pg/mL (P<0.01), in the group of patients with elevated CRP (more than 6 mg/L) these values were 104.71±4.21 pg/mL for endothelin-1 (P<0.01), for VWF – 140.21±6.04% (P<0.05) and thrombomodulin – 1424±16.2 pg/mL (P<0.01). In patients with normal fibrinogen levels (less than 400 mg/dL), endothelin-1 was 82.81±3.12 pg/mL, VWF was 122.69±4.8%, and thrombomodulin was 1384±19.2 pg/mL and. In the group of patients with elevated fibrinogen levels (more than 400 mg/dL), these values were 28.5% (P<0.01), 23.5% (P<0.05), and 15.7% (P<0.05) is higher, respectively, than in patients with normal fibrinogen levels. Similarly, in patients with normal levels of D-dimer (less than 0.6 mg/L), the endothelin-1 index was 85.44±2.82 pg/mL, VWF – 116.78±5.95% and 1215.9±24, 7 pg/mL and, while in the group of patients with elevated levels of D-dimer, these values were significantly higher for endothelin-1 by 30.8% (P<0.01), for VWF by 28.7% (P<0.01) and for thrombomodulin by 18.6% (P<0.05), respectively, compared with those in patients with normal D-dimer levels.
CONCLUSIONS In patients with MI after COVID-19, there was a significant increase in the level of coagulation hemostasis and inflammation, characterized by a significant increase in fibrinogen and D-dimer, a highly sensitive CRP.
GW34-e0260
Xunxun Feng, Yang Liu, Qianyun Guo, Yujie Zhou
Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Beijing Institute of Heart Lung and Blood Vessel Disease, Clinical Center for Coronary Heart Disease, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
OBJECTIVES In recent years, the significance of triglycerides (TG) in atherosclerotic cardiovascular disease and the associated clinical practice has been paid increasing attention. The atherogenic index of plasma (AIP) is a novel biomarker associated with atherosclerosis, and an important risk factor for atherosclerosis, but its relation with cardiovascular prognosis in prediabetic patients with unstable angina pectoris (UAP) is still uncertain.
METHODS This study included 1096 prediabetic patients with UAP who were subjected to follow-up for a maximum of 30 months, with cardiac death, refractory angina, and non-fatal myocardial infarction (MI) being the primary cardiovascular endpoints. Cox proportional risk model was employed to evaluate the relations between AIP as a continuous variable and research results.
RESULTS A significantly increased AIP was observed for the group with primary cardiovascular endpoints. Kaplan–Meier curves corresponding to these endpoints revealed pronounced differences between these two AIP groups (Log-rank P<0.001). Multivariate Cox proportional hazards analyses highlighted AIP as being independent related to this primary endpoint (HR 1.308, 95% CI: 1.213–1.412, P<0.001). AIP addition to the baseline risk model improved the prediction of the primary endpoint (AUC: baseline model, 0.622, vs. baseline model+AIP, 0.739, P<0.001).
CONCLUSIONS As a composite lipid index, AIP is closely related to the prognosis of prediabetic patients with UAP, and it has the potential to be a convenient and valuable clinical reference index.
GW34-e0277
Jianjun Dai, Weihua Hong, Shujun Li
Boji Hospital in Bazhong city Sichuan Province China
OBJECTIVES To investigate the changes of myocardial enzymes after laparoscopic cholecystectomy. Methods 200 patients receiving cholecystectomy in our hospital were collected and randomly divided into two groups: study group (receiving laparoscopic cholecystectomy) and control group (receiving open cholecystectomy) by EXCELL software. The myocardial enzyme changes of the study group and the control group were analyzed 24 h before and after operation. Results There were no differences in CK, CKMB and LDH between the two groups before operation (P>0.05). 24hCK, CKMB and LDH increased after operation between the two groups, and there were differences (P<0.05); there was no significant difference in troponin T between the two groups 24 h after surgery (P>0.05). Compared with cholecystectomy, laparoscopic cholecystectomy has less trauma to myocardial tissue and is a safe surgical method for patients with underlying heart diseases.
METHODS Two-hundred patients undergoing myocardial ischemia and cholecystectomy from January 2016 to December 2016 were collected and grouped by random numbers by EXCELL software: study group (undergoing laparoscopic cholecystectomy) and control group (undergoing open cholecystectomy). The mean age and gender of the study group were (54.5±17.4), 59 males and 41 females, respectively, and the mean age and gender of the control group were (53.1±15.1), 50 males and 50 females, respectively. There was no difference in the gender and age between the two groups. 1.1 Time of blood collection: all patients before and 24 h after surgery. 6 mL per blood draw, after centrifugation, serum was taken. 1.2 Observation index: To analyze the changes of myocardial enzymes before and 24 h after surgery. 1.3 Statistical analysis: SPSS17.0 software, measurement data (x-±s), t-test, P<0.05 as significant difference.
RESULTS The myocardial enzymes before and 24 h after surgery: CK, CKMB, and LDH were different between the two groups (P>0.05); CK, CKMB, and LDH increased at 24 h after the operation (P<0.05). Study and control groups: cTnT before and after surgery: cTnT (P>0.05); 24 h cTnT (P>0.05).
CONCLUSIONS The results showed that creatine kinase, creatine kinase isoenzyme and lactate dehydrogenase increased between the two groups at 24 h after surgery (P<0.05). Creatine kinase is widely found in muscle tissues such as skeletal muscle and cardiac muscle, and creatine kinase is significantly increased during myocardial infarction. Lactate dehydrogenase is widely found in the cytoplasm of heart and liver cells, lactate dehydrogenase is elevated after tissue injury, and lactate dehydrogenase has the highest content of skeletal muscle, liver and heart in human tissues. In clinical work, creatine kinase and lactate dehydrogenase are not specific enough to diagnose myocardial injury, and we believe that this may be related to the size of surgical trauma, with the higher the expression of creatine kinase and lactate dehydrogenase. Creatine kinase isozymes are mainly distributed in myocardial tissue, reaching a peak 24 h after MI. However, the specificity of creatine kinase isoenzyme for the diagnosis of myocardial infarction is only 64~85%, and 6 tests and collaborative determination of myocardial zymography are needed.
GW34-e0292
Xinying Zhang, Nailiang Tian
Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, No. 68 Changle Road, Qinhuai District, Nanjing 210006, China
OBJECTIVES Acute kidney injury (AKI) commonly occurs after cardiac interventional procedures. The prevalence and clinical outcomes in these patients with acute myocardial infarction (AMI) after undergoing intra-aortic balloon pump (IABP) implantation still remained unknown. This study is aimed to investigate the incidence, risk predictors, and prognosis of AKI in the specific patient populations.
METHODS We retrospectively enrolled 319 AMI cases who received intra-aortic balloon pump (IABP) implantation successfully between January 2017 and December 2021. The diagnostic criteria of AKI referred to the Kidney Disease Improving Global Outcomes (KDIGO). The composite endpoint included all-cause mortality, recurrent myocardial infarction (RMI), rehospitalization for heart failure (RHF) and target vessel revascularization (TVR).
RESULTS A total of 139 cases (43.6%) developed acute kidney injury, showing much higher incidence of major adverse cardiovascular events (MACE) [hazard ratio (HR): 1.50 (1.02–2.19), P=0.036], which might mainly result from the significantly enhanced risk of all-cause mortality [HR:1.59 (1.06–2.40), P=0.025]. The multivariable regression indicated that antibiotic [odds ratio (OR): 2.07, 95% CI (1.14–3.74), P=0.016], utilized duration of IABP [OR: 1.24, 95% CI (1.15–1.41), P<0.001], and the initial SCr [OR: 1.01, 95% CI (1.0–1.01), P=0.01] were independent risk predictors of AKI, whereas emergency PCI was the potential protective factor instead [OR: 0.35, 95% CI: 0.18–0.69, P=0.003].
CONCLUSIONS The AMI patients received IABP implantation were at high risk of AKI. It is very important to assess renal function before and after IABP implantation and further preventive measures and close monitoring should also be undertaken.
GW34-e0295
Yuxiang Chen1,2,3, Jiaxin Zhong1,2,3, Lihua Chen1,2,3, Ruijin Hong1,2,3, Yuanming Yan1,2,3, Lianglong Chen1,2,3, Qin Chen1,2,3, Yukun Luo1,2,3
1Department of Cardiology, Fujian Medical University Union Hospital
2Fujian Institute of Coronary Heart Disease
3Fujian Heart Medical Center
OBJECTIVES The effect of percutaneous coronary intervention (PCI) on the prognosis of patients with coronary artery disease (CAD) is subject to variation over time, particularly in the presence of comorbidities such as diabetes mellitus (DM). Further confirmation is needed of the prognostic implication of post-PCI physiological assessments. We aimed to investigate the impact of PCI and DM on short- and long-term prognosis in coronary artery disease using three-vessel quantitative flow ratio (3V-QFR) assessment.
METHODS This is a retrospective analysis of 2440 vessels in 1181 patients who underwent PCI. The enrolled were classified into the nondiabetic and diabetic groups, further divided into two groups according to the cut-off of 3V-QFR. The median of the post-PCI 3V-QFR value (2.94) was selected as the cut-off point. The primary outcome was 5-year major adverse cardiac events (MACE), defined as a composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization.
RESULTS DM patients with a low 3V-QFR (<2.94) had the highest incidence of 5-year MACE in all groups. The landmark analysis showed that the post-PCI 3V-QFR value was negatively associated with the risk of MACE in the short-term follow-up, whereas DM appeared to be a main risk factor for MACE in the long-term prognosis.
CONCLUSIONS Both DM and low post-PCI 3V-QFR are significantly associated with an increased risk of MACE during follow-up. However, the impact of DM or low post-PCI 3V-QFR on MACE varies over time. In the short-term, low post-PCI 3V-QFR is a primary predictor of high risk for MACE, whereas in the long-term, DM emerges as the dominant factor in predicting a high incidence of MACE.
GW34-e0296
Dabei Cai1,2, Qianwen Chen1, Qingqing Gu1, Tingting Xiao1, Lipeng Mao1,2, Boyu Chi1,2, Ailin Zou1, Yu Wang1, Yuan Ji1, Ling Sun1,2, Qingjie Wang1,2
1Department of Cardiology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China
2Graduate School of Dalian Medical University, Dalian Medical University, Dalian, Liaoning 116000, China
OBJECTIVES Gender is a vital factor for the development and treatment of cardiovascular diseases. This study aimed to evaluate the differences between gender and the prognosis of patients with acute myocardial infarction (AMI).
METHODS AMI patients who had been registered in the Medical Information Mart for Intensive Care (MIMIC) III and IV database were enrolled. The primary study endpoint was 1-year all-cause mortality. The secondary study endpoints were in hospital all-cause mortality, 28-day all-cause mortality, in-hospital complications of acute kidney injury (AKI) and ventricular arrhythmias (VA). The enrolled patients were divided into two groups according to gender. Kaplan-Meier analysis was used to assess survival rate between the two group. Cox regression and Logistic regression were performed to evaluate whether gender was associated with the prognosis of AMI patients.
RESULTS A total of 4890 patients with AMI were enrolled through screening of the MIMIC database, including 3211 (65.7%) male and 1679 (34.3%) female patients. At 1-year follow-up, 722 (22.5%) men and 558 (33.2%) women died, and after analysis and adjustment, the risk of all-cause mortality was reduced by 17.9% in men [Hazard Ratio (HR)=0.821, 95% confidence interval (CI): 0.684–0.987]. Kaplan-Meier survival analysis showed a higher 1-year survival rate in the male group compared with the female group (HR=0.532, 95% CI: 0.444–0.638, log-rank P<0.0001). AKI occurred in a cumulative total of 1373 (28%) patients during hospitalization (female, 28.8% versus male, 27.7%, P=0.458); the difference was not statistically significant. VA occurred in a cumulative total of 748 (15.3%) patients (women, 12.3% versus men, 16.9%, P<0.001). After adjusting for multi-factor analysis, men with AMI had a 25% increased risk of hospitalization for VA compared to women [odds ratio (OR)=1.250, 95% CI: 1.030–1.518].
CONCLUSIONS Women had a higher 1-year mortality after AMI compared with men. However, they had a lower risk of VA during AMI compared with men.
GW34-e0297
Dabei Cai1,2, Tingting Xiao1, Qianwen Chen1, Qingqing Gu1, Lipeng Mao1,2, Boyu Chi1,2, Ailin Zou1, Yu Wang1, Yuan Ji1, Ling Sun1,2, Qingjie Wang1,2
1Department of Cardiology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China
2Graduate School of Dalian Medical University, Dalian Medical University, Dalian, Liaoning 116000, China
OBJECTIVES The Nomogram model has been widely used in clinical practice. Patients with heart failure (HF), as the end stage of cardiovascular disease, have an extremely poor clinical prognosis. The purpose of this study was to develop a nomogram model for identifying the risk of all-cause mortality in patients with HF in the hospital.
METHODS Patients with heart failure who had been registered in the Medical Information Mart for Intensive Care (MIMIC) III and IV databases were included. The primary outcome was the occurrence of all-cause mortality during hospitalization. We developed the first Logistic Regression (LR1) model and the second LR (LR2) model for HF patients in the MIMIC-IV database. All variables adjusted for multiple factors with P-value still less than 0.001 will be selected as predictors. HF patients in the MIMIC-III database were used for model testing. The area under the receiver operating characteristic curve (AUC) was used to compare the discrimination of each model and the calibration curve was used to assess the fit of the models. Decision curve analysis (DCA) was performed to estimate the clinical utility of the predictive models based on threshold probabilities to demonstrate the net benefit of the intervention. Nomograms were used as a visualization of the results of the LR models.
RESULTS A total of 16,908 subjects with HF were enrolled through screening of the MIMIC database, of which 2283 (13.5%) patients experienced in-hospital death. We assigned patients from the MIMIC-IV database to the training cohort, which was used to develop the model in the training cohort. Simultaneously, the MIMIC-III patient data performed the performance testing function of the model. Sixteen thousand nine hundred and eight patients and 48 variables were included in the univariate and multifactorial LR model analysis. Twenty-one variables were independently associated with prognosis. Finally, 11 continuous variables were selected to develop LR1 model, which had AUCs of 0.753 (95% CI: 0.738~0.768) and 0.751 (95% CI: 0.735~0.767) in the training and test cohorts, respectively. and presented as nomograms. The AUC of the LR2 model developed basis on LR1 model was 0.782 (95% CI: 0.769–0.796) and 0.766 (95% CI: 0.751–0.781) in the training and the test cohort, respectively. An online risk assessment system was also developed.
CONCLUSIONS A new risk prediction tool and an online risk assessment system were developed to predict mortality in patients with HF, which performed well and might be used to guide clinical practice.
GW34-e0298
Lihua Chen1,2,3, Jiaxin Zhong1,2,3, Yuxiang Chen1,2,3, Laicheng Wang1,2,3, Ruijin Hong1,2,3, Yuanming Yan1,2,3, Lianglong Chen1,2,3, Qin Chen1,2,3, Yukun Luo1,2,3
1Department of Cardiology, Fujian Medical University Union Hospital
2Fujian Institute of Coronary Heart Disease
3Fujian Heart Medical Center
OBJECTIVES To investigate the prognostic value of the consistency between residual quantitative flow ratio (QFR) and post-percutaneous coronary intervention (PCI) QFR in patients undergoing revascularization.
METHODS This is a single-center, retrospective, observational study. All enrolled patients are divided into five groups according to the value of ΔQFR (defined as the value of post-PCI QFR minus residual QFR): 1. Over-anticipated group: ΔQFR≥0.1; 2. Slightly over-anticipated group: 0<ΔQFR<0.1; 3. Consistent group: ΔQFR=0; 4. Slightly under-anticipated group: −0.1<ΔQFR<0; 5. Under-anticipated group: ΔQFR≤−0.1. The primary outcome was 5-year target vessel failure (TVF), defined as a composite of cardiogenic death, target vessel-related myocardial infarction, target vessel revascularization, and in-stent restenosis.
RESULTS A total of 1373 patients were included in the final analysis. Pre-PCI QFR and post-PCI QFR were significantly different in five groups. TVF occurred within 5 years in 196 patients in all groups. The consistent group had the lowest incidence of TVF and the under-anticipated group had the highest risk of TVF. The incidence of TVF was significantly higher in the under-anticipated group than in the consistent group (P=0.003), whereas no statistical differences were found when comparing the under-anticipated group with the other three groups. Restricted cubic spline regression analysis showed that the risk of TVF was non-linearly related to ΔQFR. Multivariate Cox regression model revealed that ΔQFR≤−0.1 was the independent risk factor for TVF.
CONCLUSIONS The consistency between residual QFR and post-PCI QFR may be associated with the long-term prognosis of patients. Patients whose post-PCI QFR is significantly lower than the residual QFR may be at higher risk of TVF. The aggressive PCI strategy in lesions anticipated to have less functional benefit may not result in a better clinical outcome.
GW34-e0309
Yueying Wang, Weiwei Quan, Ruiyan Zhang
Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
OBJECTIVES Obstructive sleep apnea (OSA) is associated with acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of coronary events, especially during deep sleeping time. This study sought to investigate the circadian variation of onset of acute myocardial infarction (AMI) in OSA patients and its long-term prognosis.
METHODS We prospectively enrolled 397 patients with AMI, for which the time of onset of chest pain was clearly identified. All subjects were categorized into non-OSA (n=280) and OSA (n=117) groups. The association between AMI onset time and major adverse cardiovascular and cerebrovascular events (MACCEs) was estimated by Cox proportional hazards regression.
RESULTS AMI onset occurred from midnight to 5:59 a.m. in 33% of OSA patients, as compared with 15% in non-OSA patients (P<0.01). For OSA people, the relative risk of AMI from midnight to 5:59 a.m. was 2.717 (95% CI 1.616–4.568) compared with non-OSA patients. After a median of 2.89±0.78 years follow-up, symptom onset time was significantly associated with risks of MACCEs in OSA patients, but not in non-OSA patients. The hazard ratios (HRs) for OSA patients were 4.683 (95% CI 2.024–21.409) for midnight to 5:59 a.m., and 6.964 (95% CI 1.379–35.169) for 6 p.m. to midnight as compared with AMI presenting during noon to 5:59 p.m.
CONCLUSIONS Patients with OSA showed a peak incidence of AMI during the deep night, which was independently associated with adverse events.
GW34-e0319
Xiao-Feng Su, Xu Chen, Tao Zhang, Jun-Mei Song, Liu Xin, Xing-Li Xu, Na Fan
Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
OBJECTIVES Acute myocardial infarction (AMI) remains a critical disease, characterized by a high fatality rate in several countries. In clinical practice, the incidence of AMI is increased in patients with chronic kidney disease (CKD). However, the early diagnosis of AMI in the above group of patients is still poor. Therefore, the current study aimed to evaluate all associated risk factors and indicators to establish a scoring model for the early diagnosis of AMI in patients with CKD.
METHODS In the present study, a total of 829 patients with CKD, defined by an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 or 60–90 mL/min/1.73 m2 for patients with mildly reduced kidney function, who attended the Sichuan Provincial People’s Hospital (SPPH) between January 2018 and November 2022 were enrolled. All patients underwent coronary angiography due to the presence of typical or atypical symptoms of AMI. Patients were divided into the following two groups: The training cohort, including 255 participants with AMI and 242 without AMI; and the testing cohort, including 165 and 167 subjects with and without AMI, respectively. Furthermore, a forward stepwise regression model and a multivariable logistic regression model, named SPPH-AMI-model, were constructed to select significant predictors and assist the diagnosis of AMI in patients with CKD, respectively.
RESULTS The following factors were evaluated in the model: Smoking status, high sensitivity cardiac troponin I, serum creatinine and uric acid levels, history of percutaneous coronary intervention and electrocardiogram. Additionally, the area under the curve (AUC) of the receiver operating characteristic curve were determined in the risk model in the training set [AUC, 0.78; 95% confidence interval (CI), 0.74–0.82) vs the testing set (AUC, 0.74; 95% CI, 0.69–0.79) vs the combined set (AUC, 0.76; 95% CI, 0.73–0.80). Finally, the sensitivity and specificity rates were 71.12 and 71.21%, respectively, the percentage of cases correctly classified was 71.14%, while positive and negative predictive values of 71.63 and 70.70%, respectively, were also recorded.
CONCLUSIONS The results of the current study suggested that the SPPH-AMI-model could be currently considered as the only risk scoring system for the early diagnosis of AMI in patients with CKD. This method could help clinicians and emergency physicians to quickly and accurately diagnose AMI in patients with CKD to promote the immediate and effective treatment of these patients.
GW34-e0326
Pengsheng Chen1,2, John Eikelboom3, Yi Xu1, Wenhao Zhang1, Jianling Bai4, Jun Wang1, Tong Wang1,5, Kun Liu6, Xin Chen7, Xiaoyan Wang8, Li Zhu9, Xin Zhao10, Naiquan Yang11, Jun Jiang12, Jun Pu13, Meng Jiang13, Jun Zhu14, Xiangqing Kong1, Chunjian Li1
1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University
2Department of Cardiology, XuZhou Central Hospital
3Department of Medicine, McMaster University or Thrombosis Service, Hamilton General Hospital
4Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing
5Department of Cardiology, The First People’s Hospital of Yancheng
6Department of Cardiology, The First People’s Hospital of Lianyungang
7Department of Cardiology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University
8Department of Cardiology, Affiliated Hospital of Jiangnan University
9Department of Cardiology, Taizhou People’s Hospital
10Department of Cardiology, The Second Hospital of Dalian Medical University
11Department of Cardiology, Huai’an Second People’s Hospital Affiliated to Xuzhou Medical University
12Department of Cardiology, Zhejiang University School of Medicine
13Department of Cardiology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital
14Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases
OBJECTIVES It is uncertain whether adjunctive thrombolysis is beneficial for patients with STEMI undergoing primary PCI (PPCI) within 120 minutes of presentation.
METHODS OPTIMA-5 is an open-label, prospective, multicenter, randomized, controlled study. We enrolled patients aged 18–75 who were within 12 hours of symptom onset of STEMI and expected to undergo PPCI within 120 minutes. Patients 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 infarct-related artery (IRA) 60 minutes after thrombolysis. Cardiac magnetic resonance was performed 5 days after randomization. The safety endpoint was major bleeding (BARC≥3) during 30-day follow-up.
RESULTS Two hundred and eighty-three patients were screened and 200 were randomized. The median symptom to thrombolysis time was 252.5 minutes and thrombolysis to coronary arteriography was 50.0 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.
CONCLUSIONS 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).
GW34-e0329
Jia Cheng, Zixuan Zhang, Hongyang Shu, Weijian Hang, Na Li, Jinzhao Zhao, Zhichao Xiao, Ning Zhou
Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
OBJECTIVES Coronary heart disease (CHD) remains the leading cause of mortality in China. The treatment strategies are still far from satisfactory. Hence, this study was carried out to evaluate the long-term outcomes of nicorandil and dihydropyridine calcium channel blockers in Chinese patients with CHD.
METHODS From August 2002 to March 2020, the medical records from tertiary healthcare institutions were reviewed. Patients with CHD or angina pectoris who met the following criteria were included: aged ≥18 years, hospitalized for the treatment of CHD or angina pectoris, treated with dihydropyridine calcium channel blockers (DHP-CCBs) with or without nicorandil at discharge, and over 2 times of admission records. Patients were divided into two groups based on the prescription of DHP-CCBs with or without nicorandil on discharge. Outcomes were the rates of individual components of MACE including myocardial infarction (MI), stroke, and all-cause mortality at 3-year of follow-up. Propensity score matching (PSM) was performed to adjust for difference in baseline characteristics. The rates of events were analyzed by Kaplan–Meir survival curves and the log-rank test. P≤0.05 indicated statistical significance.
RESULTS A total of 137,714 patients were screened based on the HIS and EMR systems, 7413 patients were included in the analysis cohort, among which 1843 patients received DHP-CCBs plus nicorandil (N+C group) while 5570 received DHP-CCBs without nicorandil (C group). The median follow-up durations were 10.2 months (interquartile range [IQR]: 2.8–20.9) and 7.6 months (IQR: 1.4–17.0) for patients in the N+C group and the C groups, respectively. All variables were matched between patients in the two groups after PSM (all P>0.05). Kaplan-Meir analysis showed that the stroke-free rates were significantly higher in the N+C group than those in the C group in both unadjusted and matched cohort (both log-rank P<0.0001). The MI-free survival curves were comparable in the two groups before and after PSM (unadjusted HR 1.10, 95% CI 0.92–1.32, log-rank P=0.2941; PSM-adjusted HR 1.21, 95% CI 0.91–1.61, log-rank P=0.1845). The crude (log-rank P=0.1856) and PSM-adjusted (log-rank P=0.5283) overall survival curves have no significant difference between two groups. The incidence density of stroke (P<0.0001) was lower in the N+C group but showed similar in two groups regarding MI (P=0.2831) and all-cause mortality (P=0.4711). The E-values for the sensitivity analysis using PSM trimming or limiting patients admitted after nicorandil entered the Chinese market were both 2.99 of stroke-free survival rates. The E-values reflected the robustness of the findings.
CONCLUSIONS The treatment of DHP-CCBs plus nicorandil was associated with a lower risk of stroke in CHD patients in 3 years. CHD patients received DHP-CCBs with or without nicorandil were not associated with the risk of MI or mortality.
GW34-e0349
Qianhui Wang
Xinjiang Medical University
OBJECTIVES The predictive value of lipoprotein-associated phospholipase A2 (Lp-PLA2) for the development of new-onset atrial fibrillation (NOAF) after acute myocardial infarction (AMI) during hospitalization is unclear. This study aimed to investigate the association between serum Lp-PLA2 concentration and NOAF during hospitalization.
METHODS From January 2021 to August 2021, a total of 303 patients with AMI who underwent percutaneous coronary intervention (PCI) therapy were included in this study. Serum Lp-PLA2 concentration was measured by enzyme-linked immunosorbent assay (ELISA) kits. Logistic regression analysis was used to analysis the association between Lp-PLA2 and post-AMI NOAF during hospitalization.
RESULTS Serum Lp-PLA2 concentrations were significantly higher in patients who developed NOAF than those who did not, and were positively associated with high-sensitivity C-reactive protein (hs-CRP). The receiver operating characteristic (ROC) curve showed a significant discriminative value of Lp-PLA2 for the incidence of post-AMI NOAF during hospitalization. The optimal cut-off point was calculated as 228.8 pg/mL, with a sensitivity and specificity of 76.47% and 80.30%, respectively. And all patients were divided into two subgroups based on the cut-off point. Multivariate logistic regression analysis showed that serum Lp-PLA2 was independently associated with the incidence of post-AMI NOAF during hospitalization.
CONCLUSIONS Serum Lp-PLA2 was an important risk factor for risk stratification for the incidence of post-AMI NOAF during hospitalization.
GW34-e0351
Can Feng1, Panxiang Liu2, Bing Yang2, Guohua Lliu2
1Department of Cardiology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine
2School of Computer Science and Technology, Donghua University
OBJECTIVES This study uses machine learning methods to explore the practical value of using circulating cell-free DNA (cfDNA) data to predict the degree of coronary artery stenosis in patients with suspected coronary artery disease (CAD). To facilitate reliable comparison, we further combined circulating cfDNA data with other clinical data to train machine learning models for prediction, providing new ideas for the noninvasive detection of coronary artery stenosis.
METHODS We studied 183 patients with chest discomfort who underwent coronary angiography (CAG), taking a complete medical history and performing a comprehensive physical examination. Based on the CAG results, patients were divided into the CAD group (degree of stenosis greater than or equal to 50%) and the non-CAD group (degree of stenosis less than 50%). We employed four machine learning methods, decision tree, random forest, light gradient boosting machine (LightGBM), and convolutional neural network (CNN), whose quantitative performance was evaluated on the test dataset by F1-Score, overall prediction accuracy, and area under the receiver operating characteristic curve (AUC).
RESULTS We found that using circulating cfDNA data alone to predict the degree of coronary artery stenosis has potential. LightGBM had the highest accuracy of 0.59±0.02, and the AUC of the CNN method was the largest, at 0.66±0.01. When we combined other clinical data with circulating cfDNA for analysis, the prediction was improved. CNN had the highest accuracy of 0.74±0.01, and the AUC of the random forest method was the largest, at 0.78±0.02.
CONCLUSIONS Our research not only validates the practical value of circulating cfDNA in predicting the degree of coronary artery stenosis but also provides reliable comparative information for choosing between popular machine learning methods that process both circulating cfDNA data and clinical data, which will facilitate the noninvasive early detection of CAD.
GW34-e0358
Siyu Kong1, Shijie Yu2, Weibin He1, Weikun Chen1, Yeshen Zhang1, Yining Dai1, Pengcheng He1, Yuanhui Liu1, Chongyang Duan2, Ning Tan1
1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University
2Department of Biostatistics, School of Public Health, Southern Medical University
OBJECTIVES Low serum albumin-to-creatinine ratio (sACR) is proven to be a predictor of poor short-term and long-term outcomes in patients with acute myocardial infarction. However, its association with pulmonary infection and major adverse cardiovascular events (MACE) during hospitalization and long-term all-cause mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) remains unclear.
METHODS In this multicenter observational cohort study, we enrolled patients with STEMI undergoing PCI from 2010 to 2020. The patients were categorized into three groups according to sACR tertiles. The primary endpoint was the occurrence of pulmonary infection during hospitalization, and the secondary endpoint was in-hospital MACE, composed of all-cause mortality, stroke, target vessel revascularization, recurrent myocardial infarction, and follow-up all-cause mortality.
RESULTS A total of 4507 patients were finally included, with 522 (11.6%) developing pulmonary infection and 223 (4.9%) developing in-hospital MACE. Patients with a higher sACR had a lower rate of pulmonary infection (22.8%, 7.3%, and 4.7%, P<0.001) and in-hospital MACE (10.1%, 2.7%, and 2.1%, P<0.001) than patients with a lower sACR. Multivariate logistic regression analysis demonstrated that higher sACR was a significant predictor of lower risk of pulmonary infection (odds ratio [OR]=0.96, 95% confidence interval [CI] 0.94–0.97, P<0.001) and in-hospital MACE (OR=0.95, 95% CI 0.92–0.97, P<0.001) after adjusting for potential confounding factors. The cubic spline models demonstrated a U-shape relationship between sACR and pulmonary infection (P=0.039). Receiver operating characteristic curve analysis demonstrated sACR has a good predictive value for pulmonary infection of 0.73 (95% CI 0.70–0.75, P<0.001) and in-hospital MACE of 0.72 (95% CI 0.69–0.76, P<0.001). Kaplan–Meier survival analysis showed that patients with a higher sACR had a higher cumulative survival rate (P<0.001). Cox regression analysis showed that a decreased sACR was an independent predictor of long-term all-cause mortality (hazard ratio [HR]=0.96, 95% CI 0.95–0.98, P<0.001).
CONCLUSIONS The lower sACR was proven to be independently associated with the higher risk of pulmonary infection and MACE during hospitalization and follow-up all-cause mortality for patients with STEMI undergoing PCI, indicating that sACR was a useful biomarker to identify both short-term and long-term prognosis for patients with STEMI undergoing PCI.
GW34-e0365
Lijun Cui
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University
OBJECTIVES This study used CZT-SPECT to evaluate the prevalence and characteristics of coronary microvascular dysfunction (CMD) and myocardial area at risk (AAR) in acute myocardial infarction (AMI) patients who received primary percutaneous coronary intervention (PCI).
METHODS This was a single-center cross-sectional retrospective study. Eighty-three patients received primary PCI for acute myocardial infarction. Subsequently, a rest/stress dynamic and routine gated myocardial perfusion imaging one week after PCI. The CMD group was defined as: the residual stenosis of infarct-related artery (IRA) <50% and myocardial Flow Reserve (MFR) <2.0 in this corresponding territory; While MFR ≥2.0 of IRA pertained to the normal control group.
RESULTS A total of 53 patients with a mean age of 57.06±11.99 years were recruited, of whom 81.1% were STEMI. The proportion of patients with CMD was 79.2% (42/53). The time of pain to SPECT imaging was 7.50±1.27 days in CMD group and 7.45±1.86 days in controls. CMD patients had a higher body mass index (BMI) than controls (26.48±3.26 vs 24.36±2.73, P<0.05), and a higher proportion of STEMI, TIMI 0 grade of infarct relate artery (IRA) prior PCI than controls (88.1 vs 54.5%, 61.9 vs 18.2% respectively) (all P<0.05). No significant difference was identified in the rest-myocardial blood flow (MBF) of IRA between the two groups, whereas the stress-MBF and MFR of IRA, Rest-AAR, Stress-AAR in the CMD group were remarkably lowered (P<0.01). Higher BMI (OR:1.332, 95% CI: 1.008–1.760) and Stress-AAR (OR:1.994, 95% CI: 1.122–3.543) were used as independent predictors of CMD occurrence (P<0.05).
CONCLUSIONS The prevalence of CMD is high in AMI patients who received primary PCI. Each 1 kg/m2 increase in BMI was associated with a 1.3-fold increase in CMD risk. A 5% increase in Stress-AAR was associated with a nearly 2-fold increase in CMD risk. Increased BMI and stress-AAR predicts decreased coronary reserve function.
GW34-e0379
Xiliang Zhao, Yong Zeng
Beijing Anzhen Hospital
OBJECTIVES The GREAT study is designed to establish a large cohort of Chinese patients with angina pectoris and compare the effectiveness of different anti-angina regimens with the help of electronic patient-reported outcomes (e-PROs), using the Seattle Angina Questionnaire (SAQ) to assess health status.
METHODS A total of 1556 patients with angina pectoris enrolled from 10 hospitals between September 2021 and May 2022. Patients were followed up every 3 months from baseline to 12 months to observe the difference in the therapeutic effectiveness of the drugs. To focus specifically on health status changes attributable to anti-angina regimens, patients who using nicorandil or beta-adrenergic receptor blockers (BBs) were included in the analysis. The SAQ was a 19-item questionnaire assessing angina in 5 domains, including physical limitation (PL), angina stability (AS), angina frequency (AF), treatment satisfaction (TS), and quality-of-life scores (QoL). The scores range from 0 to 100 for each domain with higher score indicating better health status and fewer symptoms. The SAQ summary score (SAQ-SS) averages the domains of PL, AF, and QoL to provide an overall metric of angina severity. In this analysis, we reported changes in health status of nicorandil and BBs between baseline and 3, 6, or 9 months, as measured by the SAQ. The changes of SAQ from baseline at each visit for two groups were compared using Mann-Whitney U test. P≤0.05 will be considered as statistically significant for the differences tested.
RESULTS Among the 1556 patients, the mean age of the patients was 60.3±10.0 years and the majority of them were male (71.5%). The demographic details were published in the study protocol article1. For this analysis, we identified a total number of 1217 patients into three groups according to the anti-angina regimens, among whom 692 (44.5%) used BB no nicorandil (BBs group), 205 (13.2%) used nicorandil no BB (nicorandil group) and 320 (20.6%) used both BBs and nicorandil (B+N group). Patients in the nicorandil group experienced greater improvements than patients in the BBs group (change in SAQ-SS: 15.9±13.5 vs 12.6±14.6 P=0.004; 18.1±13 vs 14.5±13.3, P<0.001; 17.3±12.9 vs 15.2±13.6, P=0.014) at 3, 6, and 9 months, separately. We also evaluated the changes of health status between patients using BBs plus nicorandil and patients using BBs no nicorandil. The SAQ-SS significantly and progressively increased from 58.8±13.5 at baseline to 76.2±8.1 at the 9-month of follow-up in B+N group. Compared to the BBs group, patients in the B+N group showed significant improvement in the change in SAQ-SS at 3 (P=0.005), 6 (P<0.001), and 9 months (P=0.003), separately.
CONCLUSIONS The current findings showed that an increase in self-reported health status was observed in angina pectoris patients using nicorandil plus BBs compared with those using BBs or nicorandil alone. This study is ongoing and further results will be released at the completion of the study.
Reference
1. Zhao, X., et al. Adv Ther 40, 1899–1912 (2023).
GW34-e0428
Liying Cheng1, Peihua Zhao2, Lifeng Han1, Xiumei Gao1
1Tianjin University of Traditional Chinese Medicine
2Jinghai District People’s Hospital of Tianjin
OBJECTIVES Therapeutic targeting of the metabolites, which are significantly correlated with the changes in different subsets of monocytes, may be a novel therapeutical strategy after AMI.
METHODS We studied 170 patients with primary AMI and 53 patients with unstable angina (UA), who were planning to undergo percutaneous coronary intervention (PCI). Peripheral blood sampling was performed during the onset of AMI, UA and 1, 3, 5 days after PCI. In addition, 55 healthy volunteers served as controls. Firstly, three monocyte subsets (CD14++CD16−, CD14+CD16+ and CD14+CD16++) were measured by flow cytometry. Secondly, metabolomics study on plasma samples of these peripheral blood were performed on liquid chromatography combined with mass spectrometry. Both supervised and unsupervised multivariate computational analyses were used to highlight differential plasma metabolites.
RESULTS Compared with healthy volunteers, circulating CD14++CD16− monocytes increased in AMI onset patients significantly, while decreased in post-PCI 1d and post-PCI 5d, respectively. It is worth to note that the circulating CD14++CD16− monocytes could achieve peaking on post-PCI 3d. Importantly, the peak levels of CD14++CD16− monocytes were positively associated with the extent of propionylcarnitine and butylcarnitine significantly. While, the peak levels of CD14+CD16+ and CD14+CD16++ monocytes were positively associated with the content of linoleylcarnitine significantly. The similar trend was also observed in UA patients with UA, merely a lower degree than in patients with AMI.
CONCLUSIONS The variation tendency of the content on propionylcarnitine, butylcarnitine, and linolenylcarnitine were strongly associated with pro-inflammatory and anti-inflammatory monocyte subsets after AMI, indicating that the manipulation of these metabolites could be a novel therapeutic target for salvaging ischemic damage.
GW34-e0438
Dali Zhang, Pengxiao Li, Yi Li, Yaling Han
The Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
OBJECTIVES Elderly patients with acute coronary syndrome (ACS) tend to choose clopidogrel over potent P2Y12 receptor inhibitor such as ticagrelor after percutaneous coronary intervention (PCI) in China considering higher risks of bleeding. CYP2C19 genotype is regarded as a major factor influencing the efficacy of clopidogrel. The present study aims to investigate the efficacy and safety of ticagrelor relative to clopidogrel in elderly ACS patients after PCI in China with reduced CYP2C19 metabolism.
METHODS Between January 2016 and March 2019, 2751 ACS patients over 65 years old with CYP2C19 loss-of-function (LOF) variants after PCI were enrolled. All patients were treated with aspirin and P2Y12 receptor inhibitor, among whom 2056 received clopidogrel and 695 received ticagrelor. Net adverse clinical events (NACE), a composite of cardiac death, myocardial infarction (MI), ischemic stroke, target vessel revascularization and clinically relevant bleeding including Bleeding Academic Research Consortium (BARC) types 2, 3, 5 bleeding were compared between the two groups at 12 months after PCI. Propensity score matching (PSM) was conducted to balance the baseline characteristics between two groups.
RESULTS Before and after PSM, NACE was significantly increased in ticagrelor group compared with clopidogrel group at 12 months post PCI (Before PSM, 15.18 vs. 25.61% P<0.001; After PSM, 11.66 vs. 26.01% P<0.001). MACE was comparable between the two groups (Before PSM, 5.45 vs. 5.32% P>0.999; After PSM, 3.59 vs. 5.38% P=0.146). BARC types 2, 3, 5 bleeding events were significantly increased in patients treated with ticagrelor relative to clopidogrel (Before PSM, 10.31 vs. 21.01% P<0.001; After PSM, 8.22 vs. 21.38% P<0.001), which mainly attributed to a higher incidence of BARC type 2 bleeding events in ticagrelor group (Before PSM, 8.12 vs. 18.56% P<0.001; After PSM, 6.43 vs. 18.83% P<0.001).
CONCLUSIONS In the present real-world study, selection of ticagrelor over clopidogrel showed a significant increase in NACE with a higher incidence of bleeding and similar ischemic events in elderly ACS patients carrying CYP2C19 LOF variants after PCI.
GW34-e0449
Zixiang Ye1,2, Jingang Zheng2
1Peking University China-Japan Friendship School of Clinical Medicine
2China-Japan Friendship Hospital
OBJECTIVES Patients with ST-segment elevation myocardial infarction (STEMI) have a very high mortality rate. Percutaneous coronary intervention (PCI) is the primary treatment option within a specified time. However, STEMI patients often have a poor prognosis even after timely PCI. This study aims to establish a new machine learning model to predict 1- and 5-year major adverse cardiovascular events (MACE) after primary PCI in STEMI patients.
METHODS This study included 866 STEMI patients who underwent primary PCI between January 2015 and December 2019 at China-Japan Friendship Hospital. The patients were randomly divided into training and test sets in a 7:3 ratio. The Boruta algorithm was used for feature selection. Eight machine learning algorithms, including logistic regression, random forest (RF), decision tree, K-nearest neighbors, gradient boosting decision tree machine, support vector machine, neural network, and extreme gradient boosting (XGBoost), were used to construct predictive models for in-hospital mortality. The performance was evaluated by the area under the receiver operating characteristic curve (AUC). The Shapley additive explanations (SHAP) algorithm was applied to explain the model visually.
RESULTS A total of 25 variables, including the value of fibrinogen and fibrin degradation products before PCI, age, and triglyceride, were selected for the machine learning model development process for 1-year MACE prediction. For 5-year MACE prediction model establishment, 30 variables, including age, BNP peak value, and eGFR, were selected. XGBoost had the highest predictive performance for 1-year MACE according to the results of AUC (0.768), while RF had the highest predictive performance for 5-year MACE (AUC 0.772). The SHAP method reveals the top 20 factors based on the importance ranking.
CONCLUSIONS Machine learning algorithms can be reliable tools for accurately predicting the 1-and 5-year MACE risk for STEMI patients undergoing primary PCI. This contributed to improving the prognosis of high-risk STEMI patients and providing guidance for the precise management and implementation of early interventions.
GW34-e0465
Nan Zhang1, Zhihao Wei2, Yunpeng Zhang1, Qingling Zhang1, Ziliang Chen1, Gary Tse1, Guangping Li1, Tong Liu1, Shouling Wu3
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
2Department of Preventive Medicine, School of Public Health, North China University of Science and Technology, Tangshan 063210, China
3Department of Cardiology, Kailuan Hospital, North China University of Science and Technology, Tangshan City, China
OBJECTIVES To examine the associations between Life’s Essential 8 (LE8) and the risk of incident atherosclerotic cardiovascular diseases (ASCVD) and ASCVD-related mortality among cancer patients.
METHODS A total of 4424 ASCVD-free adult participants with newly diagnosed cancer were enrolled from the Kailuan cohort, between 2006 and 2020. The LE8 score (range 0–100) was measured according to the American Heart Association definitions, including four health behaviors (diet, physical activity, nicotine exposure, and sleep) and four healthy factors (body mass index, non-HDL cholesterol, blood glucose, and blood pressure), and was categorized according to tertiles. Multivariable competing risk analyses and restricted cubic spline analyses were used to calculate hazard ratios (HRs) and 95% CIs and explore linear and nonlinear relationships between LE8 and ASCVD, respectively.
RESULTS Over a median follow-up of 2.89 (0.95, 6.94) years, 218 (5.0%) incident ASCVD events and 157 (3.5%) ASCVD-death were observed. The mean total LE8 score at baseline was 59.63±11.48. The result showed that a higher LE8 score was associated with a decreased risk of ASCVD among cancer patients, which was consistent across different models and through comprehensive sensitivity analyses. In the fully adjusted competing risk model, compared to patients in tertile 1 of LE8 score, patients in tertile 3 had 46% lower risks of developing ASCVD events (HR, 0.54; 95% CI, 0.39–0.75) and 40% lower ASCVD related-mortality (HR, 0.60; 95% CI, 0.41–0.88). Multivariable adjusted restricted cubic spline analyses identified a linear association between overall LE8 score and health factor score with ASCVD (Poverall<0.01), whereas no association was found between health behavior score with ASCVD (Poverall and Pnonlinearity>0.05). The inverse association between LE8 and ASCVD was observed for both genders, but was more prominent among individuals who were <60 years and those with digestive cancers and respiratory cancers.
CONCLUSIONS Life’s Essential 8 score was inversely associated with incident ASCVD and ASCVD-related mortality among cancer patients. Primordial prevention strategies to prevent the initial occurrence of risk factors and interventions to mitigate established risk factors should be strongly considered for cancer patients.
GW34-e0499
Yang Zhang1, Bangguo Yang2, Yicong Ye1, Xiliang Zhao1, Yaodong Ding1, Yi Ye1, Liang Zhang1, Dawei Tan1, Gong Zhang3, Xiaoyu Duan4, Quan Li1, Yong Zeng1
1Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
2Department of Cardiology, Fuwai Yunnan cardiovascular Hospital, Kunming, China
3Division of Cardiology, Beijing Daxing District People’s Hospital, Beijing, China
4General Medicine Department, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
OBJECTIVES In patients with at least one coronary received FFR assessment, a noteworthy proportion of adverse events occured in vessels that were not FFR-measured. However, the effect of these non-target vessel-related events on the evaluation of FFR-related benefits remains unknown.
METHODS In this retrospective study, vessels with FFR measurement were grouped as FFR-based approach and non-compliant with FFR based on whether received FFR-based treatment. Using inverse probability of treatment weighting (IPTW) to account for potential confounding, we investigated the association between compliance with FFR and 5-year target vessel failure (TVF), non-target vessel failure (NTVF), and vessel-oriented composite endpoint (VOCE).
RESULTS Of the 1119 enrolled vessels, 201 did not undergo FFR-based treatment. Potential reasons for non-compliance may include lesion length (adjusted odds ratio [OR]: OR: 1.05; 95% CI: 1.02–1.09; P=0.002), moderate-to-severe calcification (adjusted OR: 1.12; 95% CI: 1.01–1.23; P=0.025), and target lesion location (adjusted OR: 0.97; 95% CI: 0.95–0.99; P=0.011). After IPTW adjustment, a significantly lower hazard of TVF was observed in FFR-based approach group (adjusted hazard ratio [HR]: 0.56; 95% CI: 0.34–0.92). While, the in-group difference in hazard of VOCEs was nonsignificant (adjusted HR: 0.69; 95% CI: 0.45–1.05). In landmark analyses (between 12 and 60 months after index procedure), the rates of TVF were lower in FFR-based group compared to non-compliance group (10.0 versus 15.1%; P=0.037). However, no significant in-group difference was observed regarding VOCEs within the 12–60 months’ follow-up period (15.7 versus 19.0%; P=0.095).
CONCLUSIONS The deviations from established threshold in applying FFR within routine clinical practice are not infrequent, with numerous potential lesion characteristics correlated with this occurrence. In patients with coronary artery disease subject to FFR testing, FFR-based approach yields a sustained clinical benefit, as compare with non-compliant with FFR in terms of the risk of cardiac death, target vessel-related myocardial infarction, and unplanned target vessel revascularization. While, the dilution of non-target vessel-related events renders the difference favoring the FFR-based approach nonsignificant.
GW34-e0517
Tong Gao
Beijing Tsinghua Changgung Hospital
OBJECTIVES The meta-analysis was performed to investigate the efficacy and safety of P2Y12 inhibitors versus aspirin in the post-percutaneous coronary intervention (PCI) population after completing dual antiplatelet therapy (DAPT).
METHODS Studies were searched in electronic databases from January 1, 2015 to November 20, 2022. We performed a meta-analysis to estimate the effect of P2Y12 inhibitor monotherapy on clinical end points in the post-PCI patients after a period of DAPT, using trial-level data with consistent end-point definitions. The primary outcome was major adverse cardiac events. Odd ratio (OR) was pooled with 95% confidence interval (CI) for dichotomous data. This study is registered with INPLASY 2022120011.
RESULTS Five studies involving 24,460 participants were included. The risk of MACE was lower in patients who received a P2Y12 inhibitor than in patients who received aspirin (OR 0.70 [95% CI 0.60–0.80], I2=0%, P<0.00001) monotherapy. A subgroup analysis of MACE according to the characteristics of patients showed findings were consistent with the primary analysis. The risk of major bleeding was similar in patients who received a P2Y12 inhibitor and those who received aspirin (OR 0.86 [95% CI 0.53–1.39], I2=57%, P=0.54). The risk of major bleeding was borderline increased in patients who received ticagrelor versus aspirin (OR 1.81 [95% CI 0.99–3.31], P=0.05).
CONCLUSIONS P2Y12 inhibitor monotherapy is potentially superior than aspirin for MACE, repeat revascularization and stroke in the post-PCI population without an increased risk of major bleeding.
GW34-e0531
Zhou Xinbin
First Affiliated Hospital of Zhejiang Chinese Medical University
OBJECTIVES In-stent restenosis (ISR) remains the leading problem after percutaneous coronary intervention (PCI). Thiazolidinediones (TZDs) including rosiglitazone and pioglitazone has been shown in some studies to be associated with reduced ISR and target lesion revascularization (TLR), however the evidence is mixed especially between rosiglitazone and pioglitazone. To evaluate the effects of TZDs in the prevention of ISR and TLR after PCI and to further investigate the differences between rosiglitazone and pioglitazone.
METHODS We systematically searched Embase, Pubmed, the Cochrane Library, and ClinicalTrials.gov through January 2017. Randomized controlled trials (RCTs) investigating the effects of TZDs for ISR after PCI were identified. The primary outcomes were rates of ISR and TLR. Secondary outcomes included major adverse cardiac events (MACE) and late lumen loss (LLL), minimum lumen diameter (MLD) and percentage stenosis (PS) during follow-up.
RESULTS Fourteen RCTs with a total of 1350 patients were finally included. At the overall term follow-up, TZDs treatment is associated with significantly reduced risk of TLR (RR: 0.45, 95% CI: 0.30–0.67, P<0.05 for pioglitazone, RR: 0.68, 95% CI: 0.46–1.00, P<0.05 for rosiglitazone). Pioglitazone is associated with significantly reduced risks of ISR (RR: 0.47, 95% CI: 0.27–0.81, P=0.006), and MACE (RR: 0.44, 95% CI: 0.30–0.64, P<0.05). Pioglitazone also resulted in less LLL, greater MLD and lower PS (P<0.05 for all). No significant relationship was found between rosiglitazone and ISR (RR: 0.91, 95% CI: 0.39–2.12, P=0.823) and MACE (RR: 0.73, 95% CI: 0.53–1.00, P=0.053).
CONCLUSIONS TZDs treatment is associated with significant reduction in ISR, TLR, MACE for patients after PCI. Pioglitazone treatment seems to have more beneficial effects than rosiglitazone and no significantly increased cardiovascular risk was detected for both agents.
GW34-e0537
Ling-Feng Yang
The First Affiliated Hospital of Zhejiang Chinese Medical University
OBJECTIVES De winter ECG pattern was once regarded as a static ECG phenomenon and predictive for proximal LAD occlusion. However, we demonstrate an atypical example of this pattern, revealing that de Winter pattern can evolve dynamically and LMCA can be the infarct-related artery (IRA).
METHODS A 45-year-old man with no past history had a sudden attack of chest pain accompanied by sweating and nausea. Thirty minutes later, he was admitted to the emergency department (ED). He was hemodynamically unstable at arrival, with BP of 72/48 mmHg and HR of 60 bpm. The first electrocardiogram (ECG) was immediately performed, demonstrating upsloping ST-segment depression (STD) at the J point followed by tall, symmetrical T wave in leads V2–V5, as well as ST-segment elevation (STE) in aVR lead, which was immediately recognized as de Winter ECG pattern1.
RESULTS The de Winter ECG pattern, a rare ECG manifestation, was observed in nearly 2% of the patients with acute anterior myocardial infarction (MI). Considering its high accuracy of the prediction for acute proximal LAD occlusion, this ECG pattern is regarded as a ‘STEMI equivalent’. Previous studies revealed that this ECG pattern was a static electrocardiogram2. But, several cases have been reported showing that this ECG phenomenon can be transient. Xu et al. reviewed the electrocardiograms of 441 patients with anterior myocardial infarction and found that 15 cases (3.4%) showed de Winter ECG pattern, of which 13 cases evolved into STEMI3. The median time of the evolvement was 114 min. Likewise, STEMI pattern can evolve into de Winter pattern. In a case of total proximal LAD occlusion, Zhao et al. observed the de Winter pattern after STE, which coincided to spontaneous coronary recanalization4.
CONCLUSIONS De Winter ECG pattern is of great significance for the identification of high-risk Non-ST-segment elevation acute coronary syndrome (NSTE-ACS), and is helpful for the localization of severe stenosis in the proximal LAD or LMCA. When de Winter ECG pattern is observed, reperfusion therapy should be performed as soon as possible to prevent further evolution of the electrocardiogram and avoid a disastrous outcome.
References
1. de Winter RJ, Verouden NJ, Wellens HJ, Wilde AA. A new ECG sign of proximal LAD occlusion. N Engl J Med 2008;359:2071-3.
2. Verouden NJ, Koch KT, Peters RJ, Henriques JP, Baan J, van der Schaaf RJ, Vis MM, Tijssen JG, Piek JJ, Wellens HJ, Wilde AA, de Winter RJ. Persistent precordial “hyperacute’’ T-waves signify proximal left anterior descending artery occlusion. Heart 2009;95:1701-1706.
3. Xu J, Wang A, Liu L, Chen Z. The de winter electrocardiogram pattern is a transient electrocardiographic phenomenon that presents at the early stage of ST-segment elevation myocardial infarction. Clin Cardiol 2018;41:1177-1184.
4. Zhao YT, Wang L, Yi Z. Evolvement to the de Winter electrocardiographic pattern. Am J Emerg Med 2016;34:330-2.
GW34-e0587
Yuanhui Liu, Pengcheng He, Ning Tan
Guangdong Provincial People’s Hospital
OBJECTIVES Both glucose and albumin are associated with chronic inflammation, which plays a vital role in post-contrast acute kidney injury (PC-AKI). However, the relationship between the combination of random glucose and albumin and PC-AKI remains unclear. Current study aims to explore the relationship between random glucose to albumin ratio (RAR) and the incidence of PC-AKI after percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI).
METHODS STEMI patients who underwent PCI were consecutively enrolled from January, 01 2010 to February, 28 2020. All patients were categorized into T1, T2, and T3 groups, respectively, based on RAR value (RAR<3.377; 3.377≤RAR≤4.579; RAR>4.579). The primary outcome was the incidence of PC-AKI, which is defined as an increase in serum creatinine of more than 44.2 μmol/L (0.5 mg/dL) from baseline during the initial 48–72 hours after contrast exposure. The incidence of major adverse clinical events (MACE) was the second endpoint, which included all-cause mortality, recurrent of myocardial infarction, stroke, or target vessel revascularization during hospitalization. The association between RAR and PC-AKI was assessed by multivariable logistic regression analysis.
RESULTS A total of 2924 patients with STEMI undergoing PCI were finally included. The incidence of PC-AKI increased in a stepwise manner with the increasing tertile of RAR (3.2 vs 4.8 vs 10.6%, P<0.001). Multivariable regression analysis demonstrated that RAR (as a continuous variable) was associated with the incidence of PC-AKI (OR=1.07, 95% CI=1.01–1.14, P=0.021) and in-hospital MACE (OR=1.09, 95% CI=1.02–1.16, P=0.011); RAR, as a categorical variable, was significantly associated with in-hospital MACE (T3 vs. T1, OR=1.80, 95% CI=1.08–2.99, P=0.024) in multivariable regression analyses. Receiver operating characteristic curve analysis showed that RAR exhibited a value for PC-AKI (area under the curve (AUC)=0.666, 95% CI=0.625–0.708), and in-hospital MACE (AUC=0.662, 95% CI=0.619–0.706). In addition, the AUC of RAR for predicting PC-AKI in the no diabetes subgroup was significantly higher compared to that in the diabetes subgroup (AUC: 0.640 vs. 0.611, P=0.021).
CONCLUSIONS The high value of RAR was significantly associated with the increasing risk of PC-AKI and in-hospital MACE after PCI in patients with STEMI.
GW34-e0605
Jiang Zaixin
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES To investigate the long-term clinical outcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in the absence of traditional cardiovascular risk factors (CVRFs).
METHODS The Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) registry study was a large-scale, multicenter, prospective, real-world practice observational study. This study was conducted in 14,032 consecutive CAD patients who were survived until hospital discharge between January 2012 and March 2014 at 107 centers in China. We selected patients with ACS undergoing PCI completing 5 year follow up from OPT-CAD registry study. The clinical outcomes among patients with CVRFs and at least one CVRFs cohorts were compared. The primary endpoint was major adverse cardiac or cerebral events (MACCEs), defined as a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke or unstable angina requiring unplanned revascularization. An exploratory multivariable Cox proportional hazards regression analysis was performed to identify demographic and clinical independent predictors of the endpoint.
RESULTS Among 5688 patients with ACS undergoing PCI, 392 (6.9%) were CVRFs-free cohort and 5296 (93.1%) were at least one CVRFs cohort. During 5-year follow-up, the MACCEs occurred in 72 patients in the CVRFs-absent ACS cohort and 1051 patients in the CVRFs-present ACS cohort. There was no significant difference in the rate of MACCEs between cohorts (18.4 vs. 19.8%, log-rank P=0.57). Multivariable Cox proportional hazards regression analysis indicated that age was independent predictor of MACCEs in the CVRFs-absent ACS cohort (HR, 1.03; 95% CI, 1.01–1.05; P=0.005).
CONCLUSIONS Among ACS patients treated with PCI, the CVRFs-absent patients cohort, compared with those with CVRFs, a similar risk of recurrent cardiovascular events was observed at 5 year.
GW34-e0619
Liu Haiwei, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Although drug-eluting stents have shown a beneficial effect in reducing cardiac events, studies comparing clinical outcomes in patients with long coronary lesions are limited. The thin-strut everolimus-eluting bioresorbable polymer SYNERGY stent (Boston Scientific Corporation, Marlborough, MA) demonstrated favorable clinical outcomes in the EVOLVE II and EVOLVE China randomized trials. In the present post-hoc analysis, we compared clinical outcomes in patients implanted with short- versus long-SYNERGY stent(s).
METHODS The SYNERGY everolimus-eluting platinum-chromium coronary stent system was specifically designed to improve healing and potentially reduce the risk of thrombosis and the associated need for prolonged dual antiplatelet therapy (DAPT). The thin-strut SYNERGY stent has an abluminal coating of everolimus in a bioabsorbable poly(D,L-lactide-co-glycolide) polymer. The study device and implantation procedure have been described previously. A pooled analysis was performed using the 1-year clinical data from 303 patients enrolled in the EVOLVE China randomized and SYNERGY China non-randomized trials evaluating safety of the SYNERGY stent. The trials are registered at www.clinicaltrials.gov (NCT02499692 for SYNERGY China and NCT01966159 for EVOLVE China). Inclusion and exclusion criteria as well as endpoint definitions were similar. Patients 18–75 years of age were eligible for inclusion if they presented with symptomatic coronary artery disease or silent ischemia, had de novo lesion(s) ≤34 mm in length in the native coronary arteries with reference vessel diameter ≥2.25 mm to ≤4.0 mm, and stenosis ≥50% and <100% with Thrombolysis in Myocardial Infarction (TIMI) flow >1. Target lesion failure (TLF) was defined as ischemia-driven target lesion revascularization (TLR), target-vessel-related myocardial infarction (MI), or cardiac death. The study population included a subgroup of patients with short (at least one SYNERGY stent ≤28 mm) and long stents (at least one SYNERGY stent ≥28 mm).
RESULTS Of 303 patients, 62 patients were treated with long SYNERGY stents and 241 patients with short SYNERGY stents. Overall baseline clinical and lesion characteristics between subgroups were well matched. However, the rate of technical success was significantly higher in patients with short versus long stents (99.5 vs. 95.0%; P=0.03). Clinical procedural success was 100.0% in both subgroups. Aspirin usage was similar in short versus long stent subgroups at discharge and 1-year (discharge: 99.6 vs 100.0%, P=1.00; 1-year: 96.7 vs 100.0%, P=0.37). Kaplan-Meier curves for TLF through 1-year were flat and parallel for shortversus long stent subgroups after 30 days, showing accrual of very few events in the short stent subgroup after 9 months (3.8 vs 4.8%; HR: 1.50, 95% CI: 0.40–5.66; P=0.55). TLF rate to 1-year was 3.8% in the short stent subgroup, which was primarily driven by TLR. Conversely, the TLF rate of 4.8% in patients with long stents was due to a higher incidence of MI. There were no cardiac deaths, and the rates of revascularization and MI were not statistically significant. Notably, there was no incidence of definite or probable stent thrombosis through 1-year follow-up in both subgroups. Additional clinical outcomes at 1-year post-SYNERGY stent implantation were comparable in short versus long lesions.
CONCLUSIONS In this analysis, SYNERGY demonstrated comparable outcomes at 1-year in patients treated withshort- versus long-stents. Additional studies are warranted to confirm the safety and effectiveness of SYNERGY everolimus-eluting bioabsorbable polymer stent in patients undergoing percutaneous coronary intervention for long coronary lesions.
GW34-e0667
Liu Xian, Wang Yingdong, Wang Bin, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES To investigate the feasibility of neo-commissural alignment by withdrawing and readvancing the delivery system during transcatheter aortic valve replacement (TAVR) with self-expanding prosthesis.
METHODS TAVR was performed in five patients with severe aortic valve stenosis by the femoral approach. The delivery catheter was withdrawn and readvanced with the opposite orientation when The Venus-A plus transcatheter heart valve (THV) centre marker was found to be overlapped with or close to the left marker at the aortic annulus level on the fluoroscopic image at the projection of the right and left coronary cusps superimposing. Neo-commissural alignment was evaluated by comparing the aortic computed tomography before TAVR with it after TAVR.
RESULTS The THV centre marker was overlapped with or close to the right marker at the aortic annulus level on the fluoroscopic image at the projection of the right and left coronary cusps superimposing in all the present five patients after withdrawing and readvancing the delivery system. The commissural angle deviation before vs. post TAVR was 12.3±7.0°. Three of five patients had neo-commissural alignment. Two of five patients had mild neo-commissural misalignment.
CONCLUSIONS It is possible to obtain the neo-commissural alignment by controlling delivery catheter insertion orientation using the markers on the inflow of Venus-A plus valve.
GW34-e0669
Wang Yingdong
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Acute chest pain is one of the main reasons why patients are admitted to the emergency department. The two most dangerous causes are acute aortic syndrome and acute coronary syndrome. However, these two diseases require two completely different treatments. Similar symptoms make it hard to tell one from another, the first assessment of patients with severe chest pain may be insufficient. Some patients with type A aortic dissection (TAAD) who have manifestations of acute myocardial infarction may be transferred to catheterization laboratories for coronary angiography. We retrospectively analyzed the angiographic characteristics of patients with Stanford type A aortic dissection (TAAD) presenting as acute myocardial infarction (AMI) to find evidence for timely correction of the misdiagnosis.
METHODS The angiographic characteristics of patients with TAAD are summarized as follows: (1) catheters cannot be advanced to the coronary ostia easily; (2) large swing of catheters in the aorta; (3) aortic angiography shows a non-smooth aortic wall; (4) coronary “thin strip of stenosis”; (5) pseudo-occlusion of the coronary ostium.
RESULTS Nineteen TAAD patients presenting as AMI were included in our study, and seven patients had coronary stenosis at the time of emergency angiography. Five of the six patients (83.3%) with both coronary stenosis and TAAD angiographic characteristics had coronary intervention performed erroneously because the TAAD specific angiographic characteristics were neglected. One patient without TAAD angiographic characteristics underwent stent implantation because a primary lesion was found in the middle of the left anterior descending artery. Fourteen of the nineteen (73.7%) patients had at least one of the five TAAD angiographic characteristics.
CONCLUSIONS If TAAD patients present with AMI manifestations and coronary artery stenosis, the incidence of interventional therapy for coronary disease is high and TAAD angiographic characteristics are inclined to be neglected. Angiographic characteristics summarized in this paper may be useful for identifying these patients.
GW34-e0691
Na Kun, Li Yi, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES In current clinical practice, controversy remains regarding the clinical benefits of prolonged DAPT in acute coronary syndrome (ACS) patients facing high risks of both ischemia and bleeding (“bi-risk”) following percutaneous coronary intervention (PCI). This study was designed to explore the feasibility of identifying a population of birisk ACS patients after PCI based on the OPT-BIRISK criteria, with an additional focus on extended dual antiplatelet therapy (DAPT) treatment safety and efficacy beyond 12 months in these bi-risk ACS after PCI under real-world conditions.
METHODS This was a post-hoc analysis of the Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study, comparing extended DAPT and single antiplatelet therapy (SAPT) at 12–24 months in ACS patients undergoing PCI complicated with both ischemic and bleeding risk defined by OPT-BIRISK criteria without premature DAPT discontinuation before 9 months or major clinical adverse events within 12 months. Ischemic event incidence within 12–24 months, defined as a composite of stroke, myocardial infarction, and cardiac death events, was the primary study outcome. Groups were balanced through propensity score matching (PSM). Ischemic events, BARC 2, 3, 5 bleeding events and BARC 3, 5 bleeding events at 5 years were analyized for the external validation of the OPT-BIRISK criteria to identify a bi-risk ACS patients.
RESULTS In total, this analysis evaluated 7049 ACS patients undergoing PCI, of whom 4146 were bi-risk patients (58.8%) and 2903 were not (41.2%). Significant differences in ischemic event frequency at 5 years were observed between these two groups (11.70 vs. 5.55%, P<0.001), with siginificantly elevated BARC 2, 3, 5 bleeding incidence in the bi-risk group (6.90 vs. 4.03%, P<0.001) than non bi-risk group. Among the bi-risk patients without any clinical adverse events within 12 months that underwent extended DAPT treatment (n=2374, 75.7%) exhibited a lower risk of stroke at 12–24 months (1.10 vs. 2.10%, P=0.036) relative to those that underwent SAPT (n=763, 24.3%), while bleeding risk did not differ significantly between these groups. PSM cohort analysis results were consistent with those of overall group analyses.
CONCLUSIONS The OPT-BIRISK criteria exhibit better performance as a means of identifying bi-risk ACS patients at 5 years following PCI. Prolonged DAPT beyond 12 months after PCI was associated with a significant decrease in ischemic stroke without any corresponding rise in bleeding risk at 12–24 months among bi-risk ACS patients able to tolerate a standard 12-month DAPT.
GW34-e0699
Dan Deng, Zhihui Zhang
Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University
OBJECTIVES To describe the characteristics of sleep duration, and to explore its association with coronary heart disease (CHD) among non-hospitalized adults in the US.
METHODS A population-based cross-sectional study involving 39,603 participants from the 2005–2018 National Health and Nutrition Examination Survey (NHANES) in the US. Sleep duration and prevalence of CHD were investigated in people aged 20 years and older. Multivariable logistic regression and restricted cubic spline (RCS) analyses were adopted to explore the relationship between CHD and sleep duration. Forest plot was used to show the relationship between each subgroup and sleep duration.
RESULTS In the study population, a sleep duration of 5–7 hours was most common, accounting for 44.96%. Men had 0.17 hours less sleep than women (95% confidence interval [CI]: 0.14–0.21). Among races, Black participants had the shortest average sleep duration (6.77 h, 95% CI: 6.70–6.83). People with college graduate education or above had the longest sleep duration (7.23 h, 95% CI: 7.19–7.27). RCS analysis showed an L-shaped relationship between sleep duration and CHD, where sleeping <6.4 h significantly increased the risk of CHD (P<0.001).
CONCLUSIONS Among US adults the relationship between sleep duration and CHD is complex and varies by sex, race, and age. Different lifestyles should be recommended according to the characteristics of different populations.
GW34-e0700
Su Xiaolin, Li Yi, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES The Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) risk score performed better than the Global Acute Coronary Event Registration (GRACE) score in predicting long-term ischemic events. The optimal dual antiplatelet therapy (DAPT) duration for patients with acute coronary syndrome (ACS) at higher ischemic risk is still a matter of concern. We aimed to investigate the clinical impact of extended dual antiplatelet therapy on patients with ACS at medium or high ischemic risk stratified by the OPT-CAD risk score.
METHODS In this post hoc analysis of OPT-CAD study, 7456 patients with ACS were divided into low-risk (n=4280) and medium- or high-risk (n=3176) groups based on the OPT-CAD risk score at hospital discharge. Patients at medium or high ischemic risk who completed 1-year DAPT without any adverse events (n=2164) were analyzed. The primary endpoint was ischemic events, which was defined as the composite of cardiac death, myocardial infarction or stroke occurring within 2 years. Second endpoints included the components of ischemic events, all-cause death, and Bleeding Academic Research Consortium (BARC) types 3–5 bleeding.
RESULTS Medium- or high-risk patients had a significantly higher incidence of ischemic events at 2 years compared to the low-risk ones (P<0.05). For medium- or high-risk patients, extended DAPT beyond 12 months was associated with lower risk of cardiac death (0.92 vs. 2.23%, P=0.017), without excessive risk of BARC) types 3–5 major bleeding (0.61 vs. 0.37%, P=0.511). Moreover, extended DAPT showed a trend towards reducing ischemic events (3.13 vs. 4.84%, P=0.066) and all-cause mortality (1.54 vs. 2.61%, P=0.106), although it was not statistically significant.
CONCLUSIONS ACS patients with medium- or high-ischemic risk may benefit from extended DAPT beyond 1 year. However, further studies in large-scale randomized trials are needed to confirm the findings.
GW34-e0701
Su Xiaolin, Li Yi, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Predicting and preventing ischemic complications is an important issue in the long-term management for acute myocardial infarction (AMI) patients. The Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) risk score was established to predict 1-year ischemic events in patients with CAD. We aimed to assess the predictive performance of the OPT-CAD score for 1- and 5-year ischemic events in AMI patients.
METHODS In this post hoc analysis of OPT-CAD study, 3293 AMI patients were divided into low- (0–90 points, n=1529), medium- (91–150 points, n=1583) and high-risk (≥151 points, n=181) groups according to the OPT-CAD risk score at hospital discharge. All patients were followed-up for 5 years. The primary endpoint was ischemic events, which was defined as the composite of cardiac death, myocardial infarction or stroke. The second endpoint was all-cause death.
RESULTS The OPT-CAD risk score demonstrated good predictive performance for 1-year ischemic events and all-cause death [AUC=0.701 (95% CI: 0.660–0.742) and 0.768 (95% CI: 0.723–0.814), respectively]. Compared to GRACE score, OPT-CAD risk score had a better discrimination in predicting 5-year ischemic events and all-cause death (ischemic events: 0.684 vs. 0.623, all-cause death: 0.740 vs. 0.681). At 5 years, low-, medium- and high-risk patients experienced significant differences in ischemic events (6.28%, 15.10%, and 34.81%, respectively, P<0.001) and all-cause death (3.14%, 11.24%, and 32.04%, respectively, P<0.001).
CONCLUSIONS The OPT-CAD risk score showed good discrimination performance for 1- and 5-year ischemic events and all-cause death in AMI patients.
GW34-e0703
Xu Ying, Li Yi, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES 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 in people, HDL-C as a “good cholesterol” has been questioned. This study aimed to investigate the relationship between HDL-C levels and the prognosis of patients with coronary heart disease (CHD) who underwent percutaneous coronary intervention (PCI) and whether this association is affected by diabetes mellitus (DM).
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. 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 There were 1955 DM patients (25.24%) and 5792 patients without DM (74.76%). The average age of DM patients was 61.90±10.04 years old, with 1369 males (70.03%), 1375 hypertension (70.33%), 687 hyperlipidemia (35.14%) and 684 smoking (34.99%), while non-DM patients were 60.15±10.90 years old, with 4492 male (77.56%), 3220 hypertension (55.59%), 1608 hyperlipidemia (27.76%) and 2606 smoking (44.99%). There was no significant difference in outcomes in DM patients (P>0.05). Non-DM patients had the lowest risk of ischemic events and all-cause mortality in the range of 1.01 mmol/L≤HDL-C≤1.22 mmol/L (P<0.05), and all bleeding was greatly reduced with the increase of HDL-C level (P=0.0092). Using RCS showed that nonlinear relationship between ischemic events and HDL-C in DM patients with a U-shaped curve (Pnonlinear=0.02), while no such link was found in non-DM patients.
CONCLUSIONS Results of our study suggested that high HDL-C levels are associated with higher ischemic events risk in CHD patients undergoing PCI with DM.
GW34-e0705
Xu Ying, Li Yi, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Prior studies have reported lower cardiovascular risk with higher high density lipoprotein cholesterol (HDL-C) levels, but recent studies have found that high levels of HDL-C may be a marker of increased risk of cardiovascular diseases. However, it is not clear whether this is the case in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). This study aimed to investigate the relationship between HDL-C levels and the prognosis of CHD patients undergoing PCI in a real-world setting in China.
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 and divided into quartile groups based on HDL-C levels. The primary outcomes were ischemic events including the composite of cardiac death, myocardial infarction, 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 HDL-C levels and outcomes.
RESULTS Patients were divided into Q1:HDL-C<0.83 mmol/L (N=1912), Q2:0.83 mmol/L ≤HDL-C≤0.99 mmol/L (N=1866), Q3:1.00 mmol/L ≤HDL-C≤1.21 mmol/L (N=2013) and Q4: HDL-C≥1.22 mmol/L (N=1956). The average age of patients was 60.60±10.73 years old, with 5861 males (75.66%), 1955 diabetes mellitus (DM) (25.24%), 4595 hypertension (59.31%), 2295 hyperlipidemia (29.62%) and 3290 smoking (42.47%). As HDL-C levels increased, patients were likely to be older and female, with a decline in body mass index, combined DM, hypertension, hyperlipidemia, smoking, previous MI and previous PCI proportion (P<0.05). When HDL-C levels rose, patients were less likely to use β-blockers, Angiotensin converting enzyme inhibitors or Angiotensin receptor blockers and more likely to use proton pump inhibitors (P<0.05). There was no significant difference in ischemic events, and the incidence of all bleeding was considerably decreased with the rise of HDL-C levels (P=0.0013). RCS was used to test the nonlinear relationship between HDL-C levels and the risk of outcomes. The nonlinear relationship between ischemic events, all-cause mortality and HDL-C was found to be evident, ischemic events were connected with HDL-C in a U-shaped relationship, and both lower and higher HDL-C levels were associated with an increased risk of ischemic events (P nonlinear=0.032).
CONCLUSIONS In this study, we found a U-shaped association between ischemic events and HDL-C in CHD patients undergoing PCI. And elevated HDL-C levels were associated with lower all bleeding risk.
GW34-e0706
Xu Ying, Li Yi, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, 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±10.85 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±8.96 years old, with 586 DM (31.07%), 1331 hypertension (70.57%), 623 hyperlipidemia (33.03%) and 189 smoking (10.02%). With higher HDL-C levels, the male and female patients were likely to be older, with a decline in body mass index, combined with lower DM, hyperlipidemia and smoking (P<0.05). 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 between outcomes and HDL-C did not hold in females, and the risk of bleeding increased with the rise of HDL-C levels.
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.
GW34-e0710
Xu Ying, Li Yi, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Prior studies have shown that high density lipoprotein cholesterol (HDL-C) levels are inversely associated with cardiovascular disease (CVD). However, recent research has shown that there is a U-shaped association between HDL-C levels and prognosis in the population free of CVD and people with a high risk of CVD. It is unclear whether this association exists in patients with coronary heart disease (CHD) who underwent percutaneous coronary intervention (PCI), and whether different BMI influences this link.
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 4627 patients with BMI<25 kg/m2 and 3116 patients with BMI≥25 kg/m2. 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 patients with BMI<25 kg/m2 was 61.63±10.59 years old, with 3516 males (75.99%), 1055 diabetes mellitus (DM) (22.80%), 2543 hypertension (54.96%), 1203 hyperlipidemia (26.00%) and 1925 smoking (41.60%), while the patients with BMI≥25 kg/m2 were 59.06±10.77 years old, with 2343 males (75.19%), 899 DM (28.85%), 2048 hypertension (65.73%), 1091 hyperlipidemia (35.01%) and 1364 smoking (43.77%). The difference of all-cause mortality between the two groups in patients with BMI<25 kg/m2 was statistically significant, the event rate was the lowest in the HDL-C range of 1.03 mmol/L–1.24 mmol/L (P=0.0084). And patients with BMI≥25 kg/m2 had a lower risk of all bleeding when HDL-C level was higher (P=0.0218). There was a U-shaped correlation between the risk of all-cause mortality and HDL-C levels in patients with BMI<25 kg/m2 (P non-linear=0.0045), with higher or lower HDL-C levels associated with an increased risk. No nonlinear relationship between outcomes and HDL-C was seen in patients with BMI≥25 kg/m2.
CONCLUSIONS Our results showed a U-shaped association between HDL-C level and all-cause mortality in patients with BMI<25 kg/m2 but not in those with BMI≥25 kg/m2.
GW34-e0713
Tienan Zhou1,2, Qian Wang1,2, Yasong Wang1,2, Xiaozeng Wang1,2
1Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110016, China
2National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, Shenyang, Liaoning 110016, China
OBJECTIVES To explore the efficacy and safety of a reduced dose (80% of the recommended dose) of bivalirudin without post-procedure infusion for 3–4 h in patients with acute coronary syndrome (ACS) undergoing elective percutaneous coronary intervention (PCI), which provides a new strategy and theoretical basis for the rational use of bivalirudin in patients with ACS undergoing elective PCI.
METHODS This was a single-center, retrospective study. A total of 2087 patients with ACS were retrospectively enrolled between January 2019 and February 2021. Patients who met the inclusion criteria and no exclusion criteria were divided into reduced-dose and recommended-dose groups for analysis. Confounders were corrected using propensity score matching. The incidence of net adverse clinical events (NACE), major adverse cardiovascular events (MACE), and Bleeding Academic Research Consortium (BARC) type 2–5 bleeding events were observed 30 days postoperatively.
RESULTS One thousand nine hundred and ninety-two patients were enrolled, including 833 patients in the reduced-dose group and 1159 patients in the recommended-dose group. Further, 1584 patients (792 per group) were obtained after propensity score matching. The results after propensity score matching were as follows: the basic characteristics of the two groups were balanced and comparable (P>0.05). The activated clotting time (ACT) after 5 min in the reduced-dose group was 349.30±47.60 s, which was statistically lower than that in the recommended-dose group, 353.41±44.89 s (P=0.021). There was no significant difference in the proportion of ACT values of ≥250 s after 5 min between the two groups (P>0.05). There were no significant differences in NACE, MACE, and BARC type 2–5 bleeding events between the two groups (5.1 vs. 4.5%, P=0.638; 0.0 vs. 0.1%, P=1.000; 0.3 vs. 0.5%, P=0.687). There were no statistically significant differences in cumulative NACE and cumulative bleeding events between the two groups at 30 days (P=0.633 and P=0.715, respectively).
CONCLUSIONS In patients with acute coronary syndrome undergoing elective PCI, 80% of the recommended dose of bivalirudin without post-procedure infusion can be used for anticoagulation without increasing the risk of thrombosis and bleeding.
GW34-e0721
Yuanting Cui, Yanxiu Chen, Pinliang Liao, Ping Zhu
Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University
OBJECTIVES In patients with complete left bundle branch block (CLBBB), the electrocardiogram (ECG) manifestations of acute myocardial infarction (AMI) are usually masked. In the past, several ECG signs of AMI in CLBBB patients have been proposed, including Sgarbossa rule and BARCELONA algorithm, but their diagnostic efficiency in different populations is not satisfactory. The purpose of this study is to further verify the above ECG rules.
METHODS This study included 100 CLBBB patients hospitalized in the Department of Cardiology, Southwest Hospital from 2016 to 2020. The patients were divided into acute myocardial infarction (AMI) group and non myocardial infarction (No MI) group. The ECG waveform data were collected to verify the sensitivity and specificity of BARCELONA algorithm, Sgarbossa scoring system and modified Sgarbossa rule III (Smith III) in the diagnosis of AMI.
RESULTS There was no significant difference in clinical baseline data between AMI group and No MI group. The comparative analysis of receiver operating characteristic curve (ROC) between the two groups showed that the area under the curve (AUC) of BARCELONA algorithm was similar to that of Sgarbossa scoring system, with no significant difference (BARCELONA vs. Sgarbossa≥5, 0.73 vs. 0.66, P=0.61; BARCELONA vs. Sgarbossa≥3, 0.73 vs. 0.76, P=0.39). The AUC range of Smith III rule is larger than that of BARCELONA algorithm (BARCELONA vs. Smith III, 0.73 vs. 0.85, P=0.0022). The above results show that in terms of comprehensive sensitivity and specificity, BARCELONA algorithm is close to Sgarbossa scoring system in the diagnosis of AMI in patients with CLBBB, while Smith III has stronger diagnostic efficiency.
CONCLUSIONS The results of this study indicated that for the ECG diagnosis of AMI in CLBBB patients, the diagnostic efficiency of BARCELONA algorithm is equivalent to Sgarbossa scoring system, and Smith III rule has stronger diagnostic efficiency than BARCELONA algorithm. Sgarbossa score ≥3 is more suitable for the diagnosis of AMI.
GW34-e0742
Liao Jia, Li Yi, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES The OPT-CAD score constitutes a novel tool in predicting long-term ischemic events which performed better than the GRACE score among patients with coronary artery disease (CAD). We aimed to evaluate the relationship between the two scores and complexity of CAD in patients with acute coronary syndrome (ACS).
METHODS In 2016–2019, 10,877 ACS patients undergoing coronary angiography at the General Hospital of Northern Theater Command were enrolled. For all patients, the OPT-CAD and GRACE score were calculated on admission using specified variables. The complexity of CAD was assessed using the SYNTAX score. We applied a three-piecewise linear regression model using a smoothing function to examine the non-linear association between OPT-CAD, GRACE score and SYNTAX score. The ability of the two scores to predict the complexity of CAD (SYNTAX score ≥33) was evaluated using a receiver operating characteristic (ROC) curve analysis.
RESULTS The mean age of the study cohort was 60.5±10.5 years, and 74.2% of participants were male. The mean OPT-CAD, GRACE, SYNTAX score were 82.6±28.5, 122±33.2, 15.3±8.9, respectively. There was a non-linear association between the GRACE and SYNTAX score, with the SYNTAX score remaining relatively stable until reaching a GRACE score of around 100, after which it increased rapidly (P for non-linearity=0.0013). However, no evidence of non-linear association was found between the OPT-CAD and SYNTAX score (P for non-linearity=0.5534). Both clinical scores can predict the complexity of CAD (SYNTAX score ≥33) moderately well (area under the curve [AUC] for OPT-CAD score: 0.62, 95% CI: 0.60–0.65, P<0.01; GRACE score: AUC 0.58, 95% CI: 0.57–0.61, P<0.01). On comparison of the two risk scores, the discriminatory accuracy of the OPT-CAD score was also significantly superior to the GRACE score (P<0.01).
CONCLUSIONS Compared with the GRACE score, the OPT-CAD score showed better correlation with the SYNTAX score, indicating that it may serve as a preliminary evaluation tool for the complexity of CAD in ACS patients prior to coronary angiography.
GW34-e0745
Liao Jia, Li Yi, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Inflammation and remnant cholesterol (RC) are considered the principal residual risk factors. We aimed to evaluate the relative importance of high-sensitivity C-reactive protein (hsCRP) and RC as residual risk for ischemic events among acute coronary syndrome (ACS) patients with different levels of low-density lipoprotein cholesterol (LDL-C) control.
METHODS In 2016–2019, 6638 ACS patients at the General Hospital of Northern Theater Command were enrolled. According to the levels of LDL-C, all patients were divided into high LDL-C group (LDL-C≥100 mg/dL) and low LDL-C group (LDL-C<100 mg/dL). RC was calculated from non-high-density lipoprotein cholesterol (non-HDL-C) minus LDL-C determined by the Sampson formula. Baseline RC and hsCRP concentrations were measured and their quartiles were used for categorizations. Ischemic events were defined as the composite of cardiac death, myocardial infarction or stroke. Cox proportional hazard models were performed to calculate the hazard ratios (HR) and 95% confidence intervals (CI) across quartiles of hsCRP and RC.
RESULTS The mean age of the study cohort was 60.6±10.8 years. During the 1-year follow-up, a total of 254 (3.8%) cases of ischemic events were recorded. Among high LDL-C group, multivariate Cox analysis showed that elevated RC levels were significantly associated with an increased risk of ischemic events (highest RC quartile vs lowest RC quartile, HR 3.59, 95% CI 1.63–7.92, P=0.002), while high hsCRP levels were related to a slightly but non-significantly increased ischemic events risk (highest hsCRP quartile vs lowest hsCRP quartile, HR 1.25, 95% CI 0.73–2.12, P=0.417). By contrast, among low LDL-C group, multivariate Cox analysis showed that elevated hsCRP levels were significantly associated with an increased risk of ischemic events (HR 4.86, 95% CI 2.85–8.29; P<0.001), while high RC levels were related to a slightly but non-significantly increased ischemic events risk (HR 1.16, 95% CI 0.63–2.12; P=0.641).
CONCLUSIONS Among ACS patients with LDL-C levels <100 mg/dL, hsCRP was a more potent predictor for residual risk of subsequent ischemic events compared to RC. Conversely, among ACS patients with LDL-C levels ≥100 mg/dL, RC was found to be a stronger predictor than hsCRP.
GW34-e0771
Ying Pan, Ying-Ying Zheng, Ting-Ting Wu, Xiang Xie
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan Road, Urumqi 830054, P.R. China
OBJECTIVES Prior studies had shown that prognostic nutritional index (PNI) is associated with cardiovascular diseases. This study was to evaluate the relationship between PNI and adverse clinical outcomes in coronary artery disease (CAD) patients.
METHODS A prospective cohort study of CAD participants was performed from December 2016 to October 2021. The primary exposure was PNI levels. The primary outcome measure was mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary outcome measures were major adverse cardiovascular and cerebrovascular events (MACCE) and major adverse cardiovascular events (MACE).
RESULTS In 14,983 participants followed for a median of 24 months, a total of 448 ACM, 333 CM, 1162 MACE and 1276 MACCE were recorded. The incidence of ACM in the low PNI (<51.35) is 338 (4.5%), medium PNI (51.35–59.80) is 77 (1.3%), and high PNI (>59.80) is 33 (2.2%). Kaplan-Meier analysis showed that the high PNI had a significantly lower cumulative event-free survival rate, compared with that in the low tertile or in the high tertile (P<0.05). Moreover, after adjusting traditional cardiovascular risk factors, there was a J-shaped relationship between PNI levels and ACM, with the lowest risk at Medium PNI level. Similar results were observed in the occurrence of CM, MACE and MACCE.
CONCLUSIONS A non-linear J-shaped association was identified between PNI levels and adverse clinical outcomes in CAD.
GW34-e0793
Qinxue Li, Jinqing Yuan
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
OBJECTIVES Triglyceride-glucose (TyG) index is a proven non-invasive alternative indicator of insulin resistance. There is an interconnection between insulin resistance and inflammation, and high sensitivity C-reactive protein (hsCRP) is one of the most commonly used biomarkers of systemic inflammation. We aimed to investigate the combined association of TyG and hsCRP with adverse outcomes in patients with chronic coronary syndrome (CCS).
METHODS This is a secondary analysis of a multicenter prospective cohort study. A total of 9421 patients with CCS were finally included in this study. The primary endpoint was defined as a composite of the major adverse cardiovascular events (MACE) covering all-cause death, non-fatal myocardial infarction, and revascularization. Kaplan-Meier analysis and Cox regression models were used to evaluate the relationship between TyG, hsCRP, and cardiovascular events. The C-statistic and net reclassification improvement (NRI) were calculated to assess the additive effect of adding TyG and hs-CRP to the baseline model on clinical outcomes.
RESULTS During the 2-year follow-up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into 3 groups according to TyG levels. Compared to the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group (adjusted HR 1.283, 95% CI 1.037–1.587, P=0.022). In addition, there was a significantly higher risk of MACE in the TyG T3 group with a higher level of hsCRP (>3 mg/L) (adjusted HR 1.735, 95% CI 1.126–2.674, P=0.012). However, the association between TyG and MACE was attenuated with hsCRP ≤ 3 mg/L (adjusted HR 1.077, 95% CI 0.834–1.391, P=0.568). When patients were divided into 6 groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3&hsCRP>3 mg/L group had a significantly higher risk of MACE than those in the TyG T1&hsCRP≤3 mg/L group (adjusted HR: 1.577, 95% CI: 1.180–2.108, P=0.002). The Cox regression analysis of secondary endpoints showed that all-cause mortality and myocardial infarction appeared to be the main contributors to the increased risk of MACE. The simultaneous addition of TyG and hsCRP to the baseline model improves the predictive ability of outcome risk in patients with CCS [C-statistic increased from 0.637 to 0.643, P=0.040; continuous NRI (95% CI): 0.131 (0.052–0.210), P=0.001].
CONCLUSIONS Elevated TyG index serves as a strong predictor of poor prognosis in patients with CCS. Additionally, participants with concurrently elevated hsCRP and TyG had worse clinical outcomes. The concurrent assessment of TyG and hsCRP may be valuable in identifying high-risk groups among CCS patients.
GW34-e0814
Wang Yanbo, Hao Guozhen, Gu Xinshun, Jiang Yunfa, Liu Changchang, Su Lifang
Second Hospital of Hebei Medical University
OBJECTIVES To investigate the the safety and efficacy of indobufen in patients with ST segment elevation myocardial infarction (STEMI) undergoing early intervention after thrombolysis.
METHODS The patients with STEMI who had underwent early intervention after thrombolysis in the Chest Pain Center of the Second Hospital of Hebei Medical University from January 2020 to December 2021 were retrospectively selected. Patients were divided into indoibufen group and aspirin group according to the use of antiplatelet drugs. Propensity score matching (PSM) was applied for 1:1 matching between the indoibufen group and aspirin group. The clinical baseline data, reperfusion treatments, medicine uses and laboratory examination results of the two groups were recorded and compared. The incidences of major adverse cardiac events (MACE) and bleeding events during hospitalization were compared between the two groups.
RESULTS Totally 170 patients with STEMI were enrolled, including 30 patients in the indoibufen group and 140 patients in the aspirin group. After propensity score matching, 30 matching pairs were generated. There was no significant difference between the baseline data of indobufen group and interventional therapy (P>0.05). There was no significant difference in blood routine examination, blood coagulation function, renal function and uric acid level between the two groups before discharge (P>0.05). There was no significant difference in the incidence of MACE between the two groups during hospitalization (P>0.05). The positive rate of fecal occult blood (26.7 vs 66.7%, P=0.002) and the incidence of gastrointestinal bleeding (0 vs 20%, P=0.024) in indobufen group were significantly lower than those in aspirin group.
CONCLUSIONS For STEMI patients receiving early interventional therapy after thrombolysis, the application of indobufen is helpful to reduce gastrointestinal mucosal damage, reduce the incidence of gastrointestinal bleeding, and its anti ischemic effect is similar to that of aspirin.
GW34-e0817
Yanbo Wang, Changchang Liu, Lifang Su, Qing Zhou
Second Hospital of Hebei Medical University
OBJECTIVES To investigate the relationship between coronary myocardial bridge (MB) and left ventricular diastolic dysfunction.
METHODS The consecutive patients with MB diagnosed by coronary angiography who were hospitalized in the Fifth Department of Cardiovascular Internal Medicine of the Second Hospital of Hebei Medical University due to chest distress and chest pain from January 2019 to October 2022 were retrospectively selected. The patients hospitalized at the same time with normal coronary angiography were taken as the control group. The baseline data, laboratory results and echocardiographic parameters were compared between the two groups. Logistic regression was used to analyze the related factors of left ventricular diastolic dysfunction.
RESULTS Totally 134 patients were enrolled, including 64 patients with normal coronary artery and 70 patients with MB. The proportion of male patients (51.4 vs. 32.8%, P=0.029) and hyperlipidemia (8.6 vs. 0%, P=0.029) in the MB group were higher than those in the control group. Systolic blood pressure and diastolic blood pressure in MB group were lower than those in control group (P<0.05). The value of e’ in MB group was lower than that in control group (6.33±1.55 vs 7.42±2.18, P=0.001), and E/e’ was higher than that in control group (11.48±3.30 vs 10.16±2.94, P=0.016). The incidence of left ventricular diastolic dysfunction in MB group was higher than that in control group (51.4 vs. 32.8%, P=0.029). Multivariate logistic regression analysis showed that MB and old age were associated with abnormal left ventricular diastolic function (P<0.05).
CONCLUSIONS Coronary myocardial bridge and old age are related to abnormal left ventricular diastolic function.
GW34-e0850
Zhiyu Liu1,2,3, Yunzhe Wang1,2,3, Ruochen Xu4, Yan Lü1,2,3, Fengyi Yu1,2,3, Junnan Tang1,2,3, Jinying Zhang1,2,3
1Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
2Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
3Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450018, China
4Department of Medical Genetics & Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
OBJECTIVES Diabetic mellitus had been proposed as a contributor in the pathogenesis of coronary artery disease (CAD) and inflammation reaction, and it had been reported that the patients with diabetic nephropathy (DN) have a higher risk of developing coronary artery disease. However, the relationship of DN and long-term adverse outcomes in CAD patients after percutaneous coronary intervention (PCI) was still undiscovered.
METHODS A number of 892 CAD patients enrolled in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2016. We collected the clinical database before PCI and follow up medical plan. The patients were divided into two groups, diabetic nephropathy group (n=341) and non-diabetic nephropathy (n=551). The primary outcome was major adverse cardiac and stroke events (MACE) after PCI. The average follow-up time was 1125±715 days.
RESULTS We found that there were significant differences between the two groups in the incidences of MACE in None DN group vs. DN group, 40.3 vs. 52.2% (P=0.001), and in cardiovascular death events and all cause death, (5.6 vs. 20.5%, P<0.001; and 4.4 vs. 13.5%, P<0.001). In DN group, the risk of MACE event was elevated to 143.9% (HR=1.439, 95% CI: 1.180–1.755, P<0.001) in Cox univariate regression analyses; after adjusting co-variables, Cox multivariate regression analyses demonstrated that DN was an independent predictor for MACE (HR=1.376, 95% CI: 1.101–1.720, P=0.005) in CAD patients after PCI, also in cardiovascular death events (HR=1.964, 95% CI: 1.223–3.156, P=0.005) and all cause death (HR=1.919, 95% CI: 1.123–3.277, P=0.017).
CONCLUSIONS This study suggests that DN is an independent and novel predictor of long-term adverse outcomes in CAD with DM patients who underwent PCI.
GW34-e0865
Yang Li1, Miaohan Qiu1, Yu Xue2, Kai Xu1, Yaling Han1, Yi Li1
1Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
2China Medical University
OBJECTIVES The optimal periprocedural antithrombotic strategy in patients with acute coronary syndrome (ACS) during percutaneous coronary intervention (PCI) remains strongly debated. The safety and effectiveness of bivalirudin plus ticagrelor versus bivalirudin plus clopidogrel in patients with ACS submitted to PCI in the real world was determined.
METHODS Between March 2016 and March 2019, 7234 patients with ACS, who had undergone PCI and received bivalirudin peri-procedurally and prescribed ticagrelor or clopidogrel, were enrolled in a single-center, all comer, modern retrospective cohort study. Incidences of 12-month ischemia (cardiac death, myocardial infarction (MI), or stroke), all-cause death, Bleeding Academic Research Consortium (BARC) type 2, 3, 5 bleeding and BARC type 3, 5 bleeding were compared between different groups.
RESULTS In total, 4960 of patients received bivalirudin plus clopidogrel and 2274 of patients received bivalirudin plus ticagrelor. Compared with bivalirudin plus clopidogrel, bivalirudin plus ticagrelor was associated with lower ischemic events (1.74 vs. 2.84%, P=0.02) and stroke (0.05 vs. 1.01%, P<0.001) within 12 months after PCI without excessive risk of bleeding (BARC type 2, 3, 5 bleeding: 4.49 vs. 3.76%, P=0.22; BARC type 3, 5 bleeding: 2.84 vs. 2.02%, P=0.08). The beneficial effects of bivalirudin plus ticagrelor were consistent among subgroups.
CONCLUSIONS As an initial treatment strategy, bivalirudin plus ticagrelor could reduce the 12-month risk of ischemic events compared with bivalirudin plus clopidogrel significantly without the expense of increased bleeding risk in patients with ACS undergone PCI.
GW34-e0866
Rutao Wang, Wangwei Yang, Fangjun Mou, Jianzheng Liu, Zhiyong Yin, Yi Liu, Chao Gao, Ling Tao
Xijing Hospital
OBJECTIVES The efficacy and safety of treatment with drug-coated balloon (DCB) in a large real-world population is limited. We aimed to report and compare 3-year clinical outcomes between DCB treatment for in-stent restenosis (ISR) and de novo disease, and identify the risk factors of adverse events after DCB intervention.
METHODS Patients treated with DCBs from the prospective CAGE FREE Registry were included. The primary outcome was vessel-oriented composite endpoint (VoCE) at 3 years, defined as a composite of vessel-related cardiac death, vessel-related myocardial infarction (MI), and target vessel revascularization (TVR).
RESULTS A total of 2473 patients with 2804 lesions (1669 [59.5%] with de novo lesions vs. 1135 [40.5%] with ISR) were included. Overall, the rate of 3-year VoCE was 12.1% (vessel-related cardiac death: 3.0%, vessel-related MI: 2.2%, and TVR: 7.8%). Patients with ISR treated with DCB had a higher rate of 3-year VoCE than those with de novo lesions (16.8 vs. 8.9%, IPTW adjusted HR: 1.79, 95% CI: 1.37–2.35, P<0.001). In terms of procedure-related factors, TIMI flow after PCI<grade 3 and residual stenosis were independent risk factors of 3-year VoCE for both patients with de novo lesions and those with ISR.
CONCLUSIONS Patients with ISR treated with DCB had a higher rate of 3-year VoCE than those with de novo lesions. DCB appears to be an attractive alternative treatment for de novo coronary lesions. A lower residual stenosis combined with TIMI flow grade 3 should be attempted after DCB angioplasty.
GW34-e0868
Yang Li, Kai Xu, Yu Xue, Yi Fang, Yaling Han
Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES To investigate the effects of metformin on renal function in acute coronary syndrome (ACS) patients with normal renal function and type 2 diabetes mellitus (DM) during the perioperative period of percutaneous coronary intervention.
METHODS From May 2017 to December 2018, 412 ACS patients with normal renal function and type 2 DM who were treated with metformin and received coronary angiography or percutaneous coronary intervention (PCI) in our hospital were prospectively enrolled. Changes of renal and liver function, urinary routine and blood test were examined before and 1, 3 and 30 days after angiography.
RESULTS Of 412 patients, the average dose of contrast agent was 105.0±64.8 mL. Before intervention, serum creatinine (Scr) level was 67.3±14.3 mmol/L, serum urea nitrogen level was 6.1±1.6 mmol/L, cystatin C level was 0.8±0.2 mg/L, and eGFR was 101.8±14.8 mL/min−1·1.73 m−2. On one day after intervention, Scr level was 62.7±14.7 mmol/L, serum urea nitrogen level was 5.1±0.9 mmol/L, cystatin C level was 0.7±0.1 mg/L, and eGFR were 111.1±26.2 mL/min−1·1.73 m−2. There were no significant changes in the above indexes compared with those before angiography. No significant difference was observed in renal function between the 3 and 30 days after intervention and that before angiography. The urine specific gravity, urinary protein, microalbumin and urinary ketone post 1 day, 3 and 30 days after intervention had no significant changes compared with those before angiography. Subgroup analysis showed that there was no significant difference in renal function and urinary routine examination results between males and females, and between patients ≥65 years and <65 years before and after coronary intervention.
CONCLUSIONS It was safe to continue metformin treatment in ACS patients with normal renal function and type 2 DM during the perioperative period of PCI.
GW34-e0869
Rutao Wang, Wangwei Yang, Jianzheng Liu, Fangjun Mou, Zhiyong Yin, Yi Liu, Chao Gao, Ling Tao
Department of Cardiology, Xijing Hospital
OBJECTIVES The optimal angiographic results after DCB treatment recommended by current consensus were derived from plain old balloon angioplasty data, the criteria for optimal angiographic results after DCB treatment has not yet been fully investigated.
METHODS Patients with ISR and/or de novo lesions from the prospective DCB treated all-comers CAGE FREE Registry were included. The primary outcome was the vessel-oriented composite endpoint (VoCE) at 3 years, defined as a composite of vessel-related cardiac death, vessel-related myocardial infarction, and target vessel revascularization. The optimal angiographic results to avoid bailout stenting, such as cut-off values of residual stenosis, Thrombolysis In Myocardial Infarction (TIMI) flow grade, and dissection were also explored.
RESULTS In total, 2473 patients with 2804 lesions (1669 [59.5%] with de novo lesions vs. 1135 [40.5%] with ISR) were enrolled. The 3-year VoCE was 12.1% in the overall cohort. For de novo lesions, patients with residual stenosis ≤25% had the lowest risk of adverse events, followed by those with residual stenosis between 25–40% and lastly patients with residual stenosis >40%. In patients with ISR, the optimal cutoff value was 23% for residual stenosis after DCB angioplasty. Patients with residual stenosis of ≤23% had the lowest rate of 3-year VoCE, whereas those with residual stenosis of >34% had the highest rate of 3-year VoCE. TIMI flow less than grade 3 was an independent risk factor of 3-year VoCE in both ISR patients (adjusted HR: 0.43, 95% CI: 0.21–0.90, P=0.024) and those with de novo lesions (adjusted HR: 0.48, 95% CI: 0.27–0.87, P=0.015). There was no significant difference for 3-year VoCE between patients without dissection and those with type A-C dissection in both patients with de novo lesions and those with ISR.
CONCLUSIONS Residual stenosis ≤25% in patients with de novo lesions, whereas ≤23% in ISR patients, combined with TIMI flow grade 3 and no greater than type C dissection were considered optimized DCB treatment. Residual stenosis at least ≤40% for de novo lesions and ≤34% for ISR lesions should be attempted, otherwise the bailout stenting strategy should be recommended.
GW34-e0898
Jiancai Yu, Wanzhong Peng, Yongxing Liu, Zesheng Xu
Department of Cardiology, Cangzhou Central Hospital
OBJECTIVES CYP2C19 gene detection guide antiplatelet upgrade therapy can ruduce readmission of unstable angina pectoris (UAP). We explore the efficacy of CYP2C19 gene detection on the control of UAP and underlying mechanism.
METHODS A total of 200 patients undergoing PCI in Cangzhou Central Hospital from January 2019 to January 2022 were randomly divided into the observation group and control group according to whether CYP2C19 gene detection was performed. Were randomly divided into the observation and control group. Before PCI, aspirin combined with clopidogrel was given in both groups, and the dosage reached 300 mg each. After PCI, in observation group, different metabolic types were distinguished according to the detection of CYP2C19 gene: the patients with low reaction after platelet function test (PFT) of intermediate metabolic type and the patients with slow metabolic type of CYP2C19 gene were considered as clopidogrel resistance, and the clopidogrel in the dual antiplatelet was adjusted to telogrel; The control group together with patients in observation group with fast metabolic type of CYP2C19 gene were still treated with aspirin and clopidogrel. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), platelet derived growth factor (PDGF) and soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion factor-1 (sVCAM-1) were observed before PCI and at 24 hours, 7 days, 28 days after PCI. Seattle angina questionnaire (SAQ) score was used to evaluate the quality of life with UAP. Major adverse cardiovascular events (MACE) were observed within 12 months after PCI.
RESULTS (1) The level of IL-6, TNF-α, PDGF and sICAM-1, sVCAM-1 in both groups at 24 hour after PCI were higher than that before PCI (P<0.05); appeal inflammation indicators in observation group were lower than control group at the corresponding time points (7 d and 28 d after PCI, P<0.05). (2) The SAQ score was higher in observation group than control group (P<0.05). (3) Due to reduce UAP (18.6 vs 6.1% P<0.05), the sum MACE in observation group was less than control group (10.2 vs 32.0% P<0.05).
CONCLUSIONS CYP2C19 genotype detection to guide antiplatelet upgrade therapy can improve the quality of life with UAP and reduce MACE may be related to relieve inflammatory reaction.
GW34-e0909
Xiaoyu Qu1,2, Hong-Gang Sui1,2, Tienan Zhou1,2, Lei Zhang1,2, Xiaozeng Wang1,2
1Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110016, China
2National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110012, China
OBJECTIVES This study will evaluate the efficacy and safety of rivaroxaban combined with clopidogrel and aspirin combined with clopidogrel in patients with coronary heart disease (CHD) and gastrointestinal disease after percutaneous coronary intervention (PCI).
METHODS Patients who met the inclusion and exclusion criteria were divided into rivaroxaban group and aspirin group according to the application of antithrombotic drugs. Propensity score matching was used to adjust for confounding factors. The primary endpoint was the incidence of net adverse clinical events (NACE) and Bleeding Academic Research Consortium (BARC) type 1–5 bleeding events within 30 days after PCI. The secondary endpoints were the composite end point of NACE and BARC type 1–5 bleeding events within 6 months after PCI.
RESULTS A total of 840 patients with CHD and gastrointestinal diseases undergoing PCI from April 2021 to March 2023 were included in this study. After propensity score matching, 339 patients were obtained in each group. Compared with the aspirin group, the rivaroxaban group had a significantly higher GRACE score, proportion of patients with gastric mucosal erosion, previous gastrointestinal bleeding, and baseline medication (P<0.05). The proportion of patients with hypertension and gastrointestinal dysfunction in the rivaroxaban group was significantly lower than that in the aspirin group (P<0.05). Comparison of laboratory examination results: there was no significant difference between the two groups (P>0.05). Compared with the rivaroxaban group, the number of stents implanted, the proportion of patients with left main coronary artery disease and multivessel disease were higher in the aspirin group (P<0.05), and the other data were not significantly different (P>0.05). There were no significant differences in baseline characteristics and PCI baseline characteristics between the two groups (P>0.05). As of April 23, 2023, 840 patients had completed 30 days of follow-up and 582 had completed 6 months of extended follow-up. There was no significant difference in the incidence of NACE and bleeding events defined by BARC at 30 days after PCI between the two groups (9.4 vs. 6.9%, P=0.185; 8.6 vs. 6.6%, P=0.271). There was no significant difference in the incidence of NACE and bleeding events defined by BARC between the two groups at 6 months after PCI (P>0.05). And there was no significant difference in the incidence of NACE and bleeding events defined by BARC between the two groups (9.7 vs. 6.5%, P=0.122; 8.8 vs. 6.2%, P=0.190). There was no significant difference in the incidence of gastrointestinal bleeding events between the two groups (P>0.05). In the subgroup analysis, there was no significant difference in the incidence of NACE and BARC 1–5 bleeding events at 30 days after PCI (P>0.05).
CONCLUSIONS In patients with CHD and gastrointestinal diseases undergoing PCI, rivaroxaban plus clopidogrel did not increase ischemic events compared with standard dual antiplatelet therapy, and bleeding events were similar in the two groups. Rivaroxaban plus clopidogrel can be used as an alternative to standard dual antiplatelet therapy in patients with CHD undergo PCI who are intolerant to aspirin therapy.
GW34-e0917
Jilang Zeng1,2, Yifei Xiang1,2, Lichuan Chen1,2, Kaiyang Lin2, Yansong Guo2
1Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University
2Fujian Provincial Hospital
OBJECTIVES Previous studies have demonstrated that the systemic inflammatory state plays a significant role in the occurrence and progression of contrast-associated acute kidney injury (CA-AKI). The modified systemic inflammation score (mSIS), which is constructed based on the albumin and neutrophil-to-lymphocyte ratio (NLR), has recently been introduced as a novel inflammatory marker. The primary objective of this study was to explore the association between mSIS and CA-AKI among patients undergoing elective percutaneous coronary intervention (PCI).
METHODS This study included 5725 patients undergoing elective PCI between January 2012 and December 2018. CA-AKI was defined as an increase in ≥0.3 mg/dL or ≥50% from the baseline serum creatinine levels within 48 h after the PCI procedures. The mSIS consisted of two components: albumin and NLR. According to previous studies, albumin and NLR were analyzed as categorical variables. Albumin was dichotomized based on its reference range lower limit of 40 g/L (Reference range, 40–55 g/L), while NLR was dichotomized using the receiver operating characteristic (ROC) curve-determined optimal cutoff value of 2.38 [area under the curve (AUC): 0.619, 95% confidence interval (CI): 0.589–0.649]. Based on these cutoff values and previous studies, we defined mSIS as follows: patients with albumin ≤40 and NLR >2.38 scored 0; patients with either albumin ≤40 or NLR >2.38 scored 1; patients with albumin >40 and NLR ≤2.38 scored 2. Subsequently, to better understand the severity of inflammation in each patient, we further classified the patients into high-risk group (score of 0) and low-risk group (score of 1 or 2). The relationship between mSIS and CA-AKI was determined by three logistic regression models. ROC analysis and Delong’s test were performed to compare the diagnostic performance of mSIS and other inflammatory indicators [including lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI)].
RESULTS A total of 349 (6.1%) patients developed CA-AKI during hospitalization, and the incidence of CA-AKI was significantly higher in the high-risk group than in the low-risk group (12.6 vs 4.5%, P<0.001). Besides, compared to the low-risk group, the high-risk group was consistently linked to a higher risk of CA-AKI across all three models. In Model 3, after fully adjusting for covariates, the high-risk group exhibited an odds ratio (OR) of 1.63 for the risk of CA-AKI (95% CI: 1.23–2.15, P<0.001, vs low-risk group). ROC analysis showed that among the five inflammatory markers, the mSIS had the greatest AUC (AUC: 0.650, 95% CI: 0.621–0.678). Delong’s test further indicated that the AUC of the mSIS was significantly better than the other four inflammatory markers [ΔAUC=0.091, P<0.001, vs PLR; ΔAUC=0.054, P<0.001, vs LMR; ΔAUC=0.047, P<0.001, vs SII; ΔAUC=0.036, P=0.008, vs SIRI)].
CONCLUSIONS The mSIS was closely associated with CA-AKI in patients treated with elective PCI. Thus, more attention should be paid to exploring the potential benefits of anti-inflammatory strategies in preventing CA-AKI.
GW34-e0924
Tiantong Yu, Shuai Zhao, Chengxiang Li, Kun Lian
Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, P. R. China
OBJECTIVES Percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) gains some breakthrough by using Drug-eluting stent (DES), which also accounts for some negative outcomes. Drug coated balloon (DCB) is an attractive approach in not only the in-stent restenosis (ISR) but also in CTO. There is no study that addresses the efficiency and safety between the DES vs. DCB in CTO lesion, so we design this study to fill the vacancy.
METHODS We retrospectively collected clinical data of patients who underwent successful PCI for at least 1 CTO lesion that treated by DCB only and their counterpart which treated by DES only at Xijing Hospital in the period from Apr. 2018 to Nov. 2021. Detailed baseline characteristics, angiographic and procedural details, in-hospital complications, and 1 month and 1 year follow-up data were collected. A sequential nearest neighbor propensity score matching was performed because the included cohort was nonrandomized, and unbalanced baseline characteristics may have existed and lead to selection bias influenced the decision to treat.
RESULTS A total of 650 patients underwent CTO-PCI attempts. The DCB group had more patients with diabetes (52.1 vs. 35.2%, P=0.028). After propensity score matching, 96 patients were included in the DCB and DES group at 1:1 ratio, and baseline data were balanced and comparable. The majority of patients in both groups were female (85.4% in both). The right coronary artery was the most common lesion site (52.1 vs. 58.3%, respectively; P=0.538). Major adverse cardiac event (MACE) in 1 month (10.4 vs. 8.3%; P=0.726) and 1 year (16.7 vs. 10.4%; P=0. 0.371) was similar in the two groups. LVEF<40% was independent risk factor of 1 year MACE (OR=3.74, 95% CI 1.01–13.88; P<0.05), while DCB treatment did not increase the incidence of MACE at 1 year compared with DES (OR=1.72, 95% CI 0.52–5.70; P=0.375).
CONCLUSIONS DCB, compared with DES, is a good choice when satisfactory pre-dilation results are obtained and economic considerations are not taken into account.
GW34-e0926
Yang Li, Yu Sun, Kai Xu, Yaling Han
Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES The optimal management strategy for the treatment of chronic total occlusion (CTO) has been inconsistent.
METHODS A 63-year-old male was presented to our hospital due to chest distress for 4 years and aggravation (Canadian Cardiovascular Society Class III) for 2 months with no obvious improvement of symptoms after optimal medical therapy. Eight months ago, diagnostic coronary angiogram revealed CTO of the LAD with grade 2 Werner collateral channels from the posterior branches of left ventricular (LV), and critical stenosis in the left circumflex artery (LCX) and right coronary artery (RCA), and 3 stents were implanted in LCX and RCA in another hospital. The patient received optimal medical management since that time. However, the patient was admitted to our hospital for further intervention due to the recurrent symptom of chest distress for 2 months. The troponin level of the patient slightly increased (0.10 ngmL, reference value: 0–0.04 ng/mL). We evaluated the patient with treadmill exercise test and the results were positive. Because of the essential of assessment of myocardial ischemia and viability in CTO-subtended territories for determining appropriate therapies, and the lack of correlation between collateral flow and myocardial viability, we performed CMR on the patient. CMR imaging showed subendocardial infarction in the anteroseptal and apical LV walls, with decreased myocardial strain in these segments. The extent of late gadolinium enhancement (LGE) was 20.4%. According to previous study, the optimal cut-off value of LGE extent could be 50% to detect segments that will functionally recover by revascularization in CTO patients. At the heart-team meeting the patient was discussed by considering symptoms, angiographic and CMR results, and the PCI of the LAD-CTO was scheduled utilizing a primary antegrade strategy. A flexible tip wire Fielder XT-R failed to track the microchannel, then by antegrade wire escalation a Gaia third wire was introduced due to the difficulty in LAD-CTO penetration using the Gaia first and second wires, and a parallel wire technique was performed together with the Gaia second wire to successfully reach the distal section of the LAD. PCI was then performed with deployment of 3 drug eluting stents (3.0×36 mm, 3.0×36 mm and 4.0×14 mm) after rotational atherectomy and TIMI III flow was ensured after stent implantation.
RESULTS Four months after the procedure, the patient’s symptoms improved, and there was initially a small increment in LV function. CMR imaging revealed that myocardial strain improved significantly in the anteroseptal and apical LV walls. The patient remained free of chest distress (NYHA class I) in 1-year clinical follow-up (Seattle Angina Questionnaire: angina frequency: baseline, 40; follow-up, 100; physical limitation: baseline, 46.67; follow-up, 73.33; quality of life: baseline, 25; follow-up, 75; anginal stability: baseline, 0; follow-up, 100; treatment satisfaction: baseline, 29.41; follow-up: 76.47).
CONCLUSIONS Therefore, CMR helps to identify patients who are more likely to benefit from CTO PCI by demonstrating pre-procedural myocardial viability and inducible perfusion defect in the CTO territory.
GW34-e0937
Jilang Zeng1,2, Liwei Zhang1,2, Junhan Chen1,2, Kaiyang Lin2, Guo Yansong2
1Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University
2Fujian Provincial Hospital
OBJECTIVES Recent studies have shown that variations in thyroid hormone levels, even within the reference range, were related to adverse cardiovascular and renal events. This association may be due to decreased deiodinase activity, hindering the peripheral conversion of free thyroxine (FT4) to free triiodothyronine (FT3). The FT3 to FT4 ratio (FT3/FT4) is considered an indirect indicator of T4 to T3 conversion and peripheral deiodinase activity. Besides, it has been reported that a decreased FT3/FT4 was observed in certain clinical settings and was associated with poor outcomes. Here, we aimed to investigate the predictive value of the FT3/FT4 for contrast-associated acute kidney injury (CA-AKI) in euthyroid patients treated with elective percutaneous coronary intervention (PCI).
METHODS A total of 3116 euthyroid patients undergoing elective PCI were included from January 2012 to December 2018. Patients were determined to be euthyroid if their serum levels of FT3, FT4, and thyroid-stimulating hormone (TSH) fell within the normal range. According to the Acute Kidney Injury Network (AKIN), CA-AKI was defined as an increase in serum creatinine (SCr) ≥0.3 mg/dL or ≥50% than baseline SCr within 48 h after the PCI procedures. All patients were categorized into two groups according to their median FT3/FT4: low FT3/FT4 group (<0.28) and high FT3/FT4 group (≥0.28). Restricted cubic spline (RCS) regression was applied to explore the non-linear association between FT3/FT4 and CA-AKI. Meanwhile, multivariable logistic regression models were performed to determine the predictive value of FT3/FT4 for CA-AKI.
RESULTS Among the 3116 patients, 160 (5.1%) developed CA-AKI. RCS in logistic regression analysis indicated a negative and linear association between FT3/FT4 and CA-AKI (P for nonlinearity=0.2624). In the unadjusted logistic model, patients in the low FT3/FT4 group showed a 2.44-fold increased risk of developing CA-AKI in comparison to those in the high FT3/FT4 group [odds ratio (OR): 2.44, 95% confidence interval (CI): 1.74–3.47, P<0.001]. Additionally, the lower FT3/FT4 still exhibited a positive association with an increased risk of CA-AKI in the fully adjusted model [adjusted OR: 1.51, 95% CI: 1.04–2.22, P=0.033, vs high FT3/FT4 group]. Subgroup analysis further demonstrated the stability of the results, and no significant interaction effects were observed in any of the subgroups (all P for interaction>0.05).
CONCLUSIONS In patients with normal thyroid function undergoing elective PCI, low levels of FT3/FT4 were independently associated with an increased risk of CA-AKI. Routine assessment of FT3/FT4 may aid in identifying high-risk individuals within this specific population.
GW34-e0942
Enmin Xie, Jingang Zheng
Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
OBJECTIVES The role of activation of the coagulation and fibrinolysis system in the pathogenesis and prognosis of ST-segment elevation myocardial infarction (STEMI) has drawn wide attention. However, there is limited research on the usefulness of the D-dimer to fibrinogen ratio (DFR) for predicting adverse outcomes in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI). The present study aimed to evaluate the association between admission DFR and long-term major adverse cardiovascular events (MACE) in STEMI patients undergoing pPCI.
METHODS This retrospective cohort study recruited consecutive patients diagnosed with STEMI and undergoing pPCI between January 2015 and December 2018 at China-Japan Friendship Hospital. Patients with a pain-to-balloon time exceeding 24 hours, a medical history of coronary artery bypass grafting or stent implantation, lack of dual antiplatelet therapy, left main disease requiring coronary artery bypass grafting, missing detailed data, or in-hospital mortality were excluded from the investigation. Patients who did not participate in follow-up after discharge were also excluded. The analysis involved categorizing patients into three groups based on their admission DFR values: DFR≤0.083 (tertile 1), 0.083–0.138 (tertile 2), and DFR>0.114 (tertile 3). The primary outcome measured was long-term MACE, which included cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Multivariable Cox regression analyses were conducted to assess the relationship between admission DFR and MACE.
RESULTS Of the 667 enrolled patients, 78.5% were male, and the mean age was 60.7±13.1 years. During the median follow-up of 4.5 years, 97 (14.5%) MACEs occurred. The incidence of long-term MACE increased from the highest tertile to the lowest tertile of DFR (8.5 vs 13.4 vs 21.6%, P<0.001). Receiver operating characteristic curve analysis showed that DFR had excellent predictive ability for MACE (AUC 0.675, 95% CI 0.624–0.726, P<0.001). Multivariable Cox regression analysis revealed that the highest tertile of DFR was independently associated with a significantly increased risk of long-term all-cause death compared to the lowest tertile (hazard ratio 2.760, 95% CI 1.242–6.136, P=0.008).
CONCLUSIONS Our results demonstrated that DFR may be useful for predicting adverse outcomes in patients with STEMI undergoing pPCI.
GW34-e0943
Enmin Xie, Jingang Zheng
Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
OBJECTIVES No-reflow phenomenon after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) patients is associated with poor prognosis. Early identification of high-risk patients of no-reflow is critical. The activation of the coagulation and fibrinolysis systems in the no-reflow phenomenon of STEMI has received significant attention. This present study aims to assess the association between admission D-dimer to fibrinogen ratio (DFR) and no-reflow in STEMI patients undergoing primary PCI.
METHODS In this retrospective cohort study, we recruited consecutive patients diagnosed with STEMI and undergoing pPCI, between January 2015 and December 2019, at the China-Japan Friendship Hospital. Patients who had a pain-to-balloon period exceeding 24 hours, had a medical history of coronary artery bypass grafting or stent implantation, lacked dual antiplatelet therapy treatment, had left main disease necessitating coronary artery bypass grafting, had missing detailed data, or passed away during their hospitalization were excluded from our investigation. In addition, patients who did not engage in follow-up after discharge were excluded. Basing our analysis on admission DFR levels, patients were categorized into one of the following three groups: DFR≤0.084 (tertile 1), 0.084–0.136 (tertile 2), and DFR>0.114 (tertile 3). The primary outcome was no-reflow, defined as thrombolysis in myocardial infarction (TIMI) flow grade 0–2 after primary PCI. Multivariable logistic regression analyses were performed to determine the relationship between admission DFR and no-reflow.
RESULTS Of the 866 patients included in the study, 21.6% were female, and the mean age was 60.4±13.1 years. The incidence of no-reflow exhibited an upward trend as the DFR tertile increased with rates of 9.2%, 17.1%, and 19.9% for the lowest, middle, and highest tertiles, respectively (P=0.001). Using unadjusted analyses, we observed that the highest tertile of DFR was associated with an elevated risk of no-reflow (odd ratio [OR] 2.461, 95% confidence interval [CI] 1.499–4.038, P<0.001). Upon adjustment for gender, hypertension, diabetes, cerebrovascular disease, smoking, the absence of pre-infarction angina, hemoglobin, estimated glomerular filtration rate, and fibrinogen, comparable findings persisted (adjusted OR 2.407, 95% CI 1.459–3.970, P=0.001). Further adjustment for angiographic findings, including initial TIMI flow grade ≤1, TIMI thrombus score ≥4, and Gensini Score, revealed that the highest tertile of DFR remained an independent predictor of no-reflow (adjusted OR 2.405, 95% CI 1.440–4.016, P=0.001).
CONCLUSIONS Our study results suggest that admission DFR can be utilized as an independent predictor of no-reflow in patients with STEMI undergoing primary PCI. The findings highlight the potential role of DFR in risk stratification protocols for such patients.
GW34-e0945
Enmin Xie, Jingang Zheng
Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
OBJECTIVES Glucose and lipid metabolism play a crucial role in the development and prognosis of coronary heart disease. Recent studies have identified the ratio of plasma glycosylated hemoglobin A1c (HbA1c) to apolipoprotein A-1 (ApoA-1) as a novel and independent indicator for evaluating unfavorable outcomes in patients with acute coronary syndrome. Importantly, this indicator remains significant even after adjusting for traditional cardiovascular risk factors and coronary severity scores. The objective of this study was to examine the relationship between the HbA1c/ApoA-1 ratio and long-term mortality in patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI).
METHODS In this retrospective analysis, a consecutive series of patients diagnosed with STEMI and undergoing primary PCI at China-Japan Friendship Hospital between January 2015 and December 2018 were included. Several exclusion criteria were applied, including a history of coronary artery bypass grafting or stent implantation, pain-to-balloon time exceeding 24 hours, treatment without dual antiplatelet therapy, significant left main disease requiring coronary artery bypass grafting, missing data, and in-hospital mortality. The patients were divided into three groups based on tertiles of their admission HbA1c/ApoA-1 ratio: tertile 1 (≤4.79), tertile 2 (4.70–5.95), and tertile 3 (>5.95). The primary outcome measure was long-term mortality.
RESULTS Among the 680 patients enrolled in the study, the average age was 60.3±13.3 years, with 77.9% of them being male. Throughout a median follow-up period of 4.5 years (interquartile range: 3.4–5.7 years), a total of 48 deaths were recorded, accounting for a mortality rate of 7.1%. The incidence of long-term mortality exhibited an upward trend as the HbA1c/ApoA-1 ratio tertile increased with rates of 2.6%, 7.5%, and 11.0% for the lowest, middle, and highest tertiles, respectively (P=0.001). In the initial unadjusted analysis, the highest tertile of the HbA1c/ApoA-1 ratio demonstrated an elevated risk of long-term mortality when compared to the lowest tertile (hazard ratio [HR]: 4.040, 95% confidence interval [CI]: 1.656–9.855, P=0.002). This association remained statistically significant after adjusting for various confounding factors including age, gender, hypertension, diabetes, cerebrovascular disease, smoking, and fibrinogen (adjusted HR: 4.563, 95% CI: 1.738–11.979, P=0.002). Furthermore, the independent predictive significance of the highest tertile of the HbA1c/ApoA-1 ratio for long-term mortality persisted even after additional adjustment for angiographic findings including initial thrombolysis in myocardial infarction (TIMI) flow grade ≤1, TIMI thrombus score ≥4, and Gensini Score (adjusted HR: 4.435, 95% CI: 1.670–11.781, P=0.003).
CONCLUSIONS This study presented empirical findings supporting the independent association between the HbA1c/ApoA-1 ratio and an increased risk of long-term mortality in patients with STEMI who undergo primary PCI. These findings emphasize the potential significance of integrating the HbA1c/ApoA-1 ratio into risk assessment methodologies for STEMI patients undergoing primary PCI.
GW34-e0950
Li-Wei Zhang1,2,3, Li-Chuan Chen1,2,3, Wen-Jia Liang1,2,3, Kai-Yang Lin1,2,3, Yan-Song Guo1,2,3
1Shengli Clinical Medical College of Fujian Medical University
2Fujian Provincial Key Laboratory of Cardiovascular Disease
3Fujian Heart Failure Center Alliance
OBJECTIVES Malignant ventricular arrhythmias are common complications of acute myocardial infarction (AMI), and significantly increase the mortality of patients with AMI. Dead cells may slow conduction and lead to the arrhythmogenic substrate. Neutrophils (NE) are rapidly recruited and accumulate in the infarcted myocardium within minutes of the onset of ischemia, and their abundance peaks 24h later. Myocardial ischemia may simultaneously induce arrhythmia and massive myocardial leukocyte changes. Recent evidence has shown that the immune system is integral to the cardiac electrical conduction system. However, the association between neutrophils and Malignant ventricular arrhythmias after acute Ml is still a gap.
METHODS We retrospectively observed 2729 patients with AMI and received the percutaneous coronary intervention (PCI) from January 2016 to December 2018 in a tertiary center. Logistics regression models were applied to investigate the association of NE with malignant ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) as well as in-hospital mortality.
RESULTS The incidence of malignant ventricular arrhythmias was 7.101% (n=194). Patients were divided by NE of 7.5×109/L. Unadjusted logistics analysis showed that high NE level (>7.5×109/L) was associated with malignant ventricular arrhythmias (OR: 1.79, 95% CI: 1.34–2.40, P<0.001) and in-hospital mortality (OR: 2.17, 95% CI: 1.40–3.40, P<0.001) in patients with AMI. Fully adjusted logistics analysis indicated that the differences were still significant between high NE level (>7.5×109/L) and malignant ventricular arrhythmias (OR: 1.60, 95% CI: 1.02–2.48, P=0.038) and in-hospital mortality (OR: 2.60, 95% CI: 1.16–5.93, P=0.021).
CONCLUSIONS High neutrophils were associated with a higher risk of malignant ventricular arrhythmias and In-hospital mortality in patients with acute myocardial infarction.
GW34-e0951
Li-Wei Zhang1,2,3, Li-Chuan Chen1,2,3, Jun-Han Chen1,2,3, Kai-Yang Lin1,2,3, Yan-Song Guo1,2,3
1Shengli Clinical Medical College of Fujian Medical University
2Fujian Provincial Key Laboratory of Cardiovascular Disease
3Fujian Heart Failure Center Alliance
OBJECTIVES Previous studies have shown that cholinesterase (ChE) is associated with poor prognosis of cardiovascular disease. However, as a common complication of coronary procedures, the association between ChE and contrast-associated acute kidney injury (CA-AKI) is not well known. This study sought to investigate the predictive value of ChE for CA-AKI after percutaneous coronary intervention (PCI).
METHODS We retrospectively observed consenting patients from January 2012 to December 2018. CI-AKI was defined as an increase in serum creatinine ≥50% or 0.3 mg/dL within 48 h after contrast medium exposure. Variables that were found to be statistically significant (P<0.05) in the univariate analysis and of great clinical significance were included in the multiple logistic regression analysis.
RESULTS A total of 1749 patients were included, of which 211 (12.1%) patients developed CA-AKI. ROC analysis showed an AUC of 0.656 (for ChE, 95% CI, 0.616–0.696) in predicting CA-AKI. Cut-off was determined according to ROC curves and patients were divided into the low-ChE group (<7500 U/L, n=558) and high-ChE group (≥7500 U/L, n=1191). Restricted cubic spline (RCS) in logistics regression analysis revealed the linear relationship between ChE and CA-AKI risk (P for non-linearity 0.3951). In the univariate logistic analysis, the low-ChE group was strongly correlated with CA-AKI compared with the high-ChE group (OR, 2.83; 95% CI, 2.12–3.80; P<0.001). Furthermore, after adjusting for potential confounding factors, multivariate logistic regression showed that the association between low cholinesterase and CA-AKI remained significant (OR, 2.22; 95% CI, 1.33–3.69; P=0.002).
CONCLUSIONS Lower cholinesterase was associated with a higher risk of CA-AKI after PCI.
GW34-e0959
Liu Haiwei, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES To evaluate the safety and effectiveness of sirolimus-coated balloon (SeQuent SCB) compared with paclitaxel-coated balloon (SeQuent Please Neo) for the treatment of drug-eluting stent (DES) in-stent restenosis (ISR).
METHODS Two hundred and fifty-eight patients with DES ISR were enrolled in a prospective, randomized, multicenter trial to compare SeQuent SCB with a clinically proven SeQuent Please Neo in coronary DES ISR. The primary endpoint was in-segment late lumen loss at 9 months.
RESULTS At 9 months, in-segment late lumen loss in the SeQuent SCB group was noninferior to that of the SeQuent Please Neo group (0.22 mm vs. 0.19 mm, P=0.817). Minimal lumen diameter pre/post-procedure, and at the 9-month follow-up were similar between groups. There was no significant difference in the occurrence of adverse events and serious adverse events between the SeQuent SCB and SeQuent Please Neo groups throughout the clinical trial period.
CONCLUSIONS The effectiveness and safety of the SeQuent SCB for the treatment of in-stent restenosis lesions in the coronary arteries are not inferior to those of the SeQuent Please Neo, which is available and in widespread clinical use. The results of the study support the use of this product in a large patient population. The effectiveness and safety of the SeQuent SCB for the treatment of in-stent restenosis lesions in the coronary arteries are not inferior to those of the SeQuent Please Neo, which is available and in widespread clinical use. The results of the study support the use of this product in a large patient population.
GW34-e0960
Liu Haiwei, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES The thin-strut SYNERGY stent has an abluminal everolimus-eluting bioabsorbable polymer coating designed to facilitate vascular healing and reduce risk of stent thrombosis. In the EVOLVE China trial (NCT01966159), SYNERGY was non-inferior to the durable polymer PROMUS Element Plus (PE+) everolimus-eluting stent for the primary end point of 9-month in-stent late loss in Chinese population. This final report of the EVOLVE China trial includes the prespecified long-term clinical outcomes at 5 years of both SYNERGY and PE+ groups.
METHODS The EVOLVE China trial was a prospective, multicenter, non-inferiority trial that compared the safety and efficacy of SYNERGY with PE+ for up to 5 years. Patients with 1 or 2 de novo native coronary artery lesions (length: ≤34 mm; diameter: 2.25–4.0 mm) were randomized in a 1:1 ratio to treatment with SYNERGY or PE+. The prespecified long-term clinical outcomes included major adverse cardiac events (MACE, defined as a composite of death, myocardial infarction or target vessel revascularization), target lesion failure (TLF), target lesion revascularization (TLR), death, myocardial infarction (MI), and stent thrombosis within 5 years after the index procedure.
RESULTS A total of 412 patients were randomized at 14 Chinese sites to receive SYNERGY (N=205) or PE+ (N=207). Five-year MACE was observed in 9.1% SYNERGY and 13.8% PE+ treated patients (RR 0.67 [95% CI 0.37, 1.22], P=0.19), TLF was observed in 6.6% SYNERGY and 9.5% PE+ treated patients (RR 0.73 [95% CI 0.36, 1.50], P=0.39). There were no significant differences in the rates of cardiac death, TLR, MI, and stent thrombosis (ST). No cardiac deaths or ST were reported with SYNERGY through 5 years.
CONCLUSIONS The present study demonstrated that SYNERGY had comparable five-year rates of MACE, TLF and ST to PE+ among patients with de novo coronary artery disease, indicating favorable long-term safety and efficacy of SYNERGY in de novo coronary lesions.
Classifications: bioabsorbable polymer, coronary artery disease, drug-eluting stents, randomized controlled trial.
GW34-e0961
Liu Haiwei, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Evidences about the choices of P2Y12 receptor inhibitors as a component of dual antiplatelet therapy (DAPT) in patients with left main (LM) disease undergoing percutaneous coronary intervention (PCI) are insufficient. This study aimed to evaluate long-term clinical outcomes of ticagrelor- versus clopidogrel-based DAPT strategy in acute coronary syndrome (ACS) patients undergoing LM PCI.
METHODS A total of 1163 patients discharged alive post-ACS who underwent LM PCI and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, including cardiac death, myocardial infarction and/or stroke. Secondary outcomes included all-cause mortality and Bleeding Academic Research Consortium (BARC) type 2, 3, 5 and type 3, 5 bleeding. Propensity score matching (PSM) was conducted between two groups to adjust bias from confounders.
RESULTS The ticagrelor group comprised 529 (45.49%) patients and the clopidogrel group comprised 634 (54.51%) patients. During the follow-up period, ticagrelor significantly reduced the rate of ischemic events in comparison with clopidogrel both before (1.32 vs 3.63%, P=0.01) and after PSM (1.41 vs 4.00%, P=0.02). The rates of BARC defined type 2, 3, 5 bleeding and type 3, 5 bleeding were similar between ticagrelor group and clopidogrel group irrespective before or after PSM adjustment (P>0.05 for all).
CONCLUSIONS Among ACS patients with LM PCI, ticagrelor use, compared with clopidogrel, was associated with ischemic events benefit without an excessive risk of bleeding complications at 12 months.
GW34-e0962
Li-Wei Zhang1,2,3, Ji-Lang Zeng1,2,3, Jun-Han Chen1,2,3, Kai-Yang Lin1,2,3, Yan-Song Guo1,2,3
1Shengli Clinical Medical College of Fujian Medical University
2Fujian Provincial Key Laboratory of Cardiovascular Disease
3Fujian Heart Failure Center Alliance
OBJECTIVES Malnutrition is one of the most important risk factors for poor outcomes in patients with coronary artery disease (CAD). Cholinesterase is a simple and stable biomarker of nutritional status, and previous studies have confirmed the relationship between cholinesterase and the prognosis of patients with acute heart failure. However, few studies have focused on the prognostic value of cholinesterase in patients with CAD. This study sought to investigate the prognosis predictive value of cholinesterase for patients with CAD after percutaneous coronary intervention (PCI).
METHODS We conducted a observational study that included consenting patients with CAD and undergoing PCI between January 2017 and December 2018. The primary outcome was long-term mortality. Variables that were found to be statistically significant (P<0.05) in the univariate analysis and of great clinical significance were included in the multivariate COX regression analysis.
RESULTS After a median follow-up of 29.6 months, 113 (6.8%) patients died. The time-dependent ROC analysis demonstrated that ChE had a powerful prognostic value for all-cause mortality, with an AUC of 0.785 (95% CI: 0.721–0.849) at 1 year, 0.782 (95% CI: 0.727–0.836) at 2 years, and 0.752 (95% CI: 0.691–0.813) at 3 years. In addition, the time-dependent AUCs of ChE at all time points were comparable to those of other nutritional markers (including CONUT, GNRI, and PNI). RCS in COX regression analysis indicated a linear association between ChE and mortality (P for nonlinearity=0.7302). Furthermore, after adjusting for potential confounding factors, COX regression analysis showed that the low cholinesterase group (<7.5 kU/L) was associated with an increased risk of mortality [adjust hazard ratio (HR): 1.70, 95% CI: 1.14–2.53, P<0.001]. The Kaplan-Meier curves likewise showed that patients with lower ChE levels had significantly higher rates of all-cause death than those in the high ChE group (log-rank P<0.001).
CONCLUSIONS Cholinesterase was a useful prognostic marker for the prediction of adverse outcomes in patients with CAD and undergoing PCI.
GW34-e0973
Li-Wei Zhang1,2,3, Ji-Lang Zeng1,2,3, Chang-Xi Wang1,2,3, Kai-Yang Lin1,2,3, Yan-Song Guo1,2,3
1Shengli Clinical Medical College of Fujian Medical University
2Fujian Provincial Key Laboratory of Cardiovascular Disease
3Fujian Heart Failure Center Alliance
OBJECTIVES To investigate the predictive value of triglyceride-glucose (TyG) index on the occurrence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention (PCI).
METHODS We retrospectively observed consenting patients from January 2012 to December 2018. TyG index was calculated using the following formula: TyG=ln [triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The endpoint event was the occurrence of CI-AKI, defined as an increase in serum creatinine ≥50% or 0.3 mg/dL within 48 h after contrast medium exposure. Univariate and multivariate logistic regression analyses were used to assess whether TyG index was an independent risk factor for CI-AKI.
RESULTS A total of 5744 patients who received PCI were ultimately enrolled in this study, and 344 (5.99%) of them developed CI-AKI. Patients who eventually developed CI-AKI were older, more likely to have hypertension, diabetes mellitus, atrial fibrillation, congestive heart failure and poorer NYHA class than those who did not. Multivariate logistic regression analysis showed that independent risk factors for CI-AKI included TyG index (OR=1.29, 95% CI=1.04–1.61, P=0.019), age >75 years (OR=1.35, 95% CI=1.02–1.77, P=0.033), hypertension (OR=1.33, 95% CI=1.02–1.74, P=0.038), atrial fibrillation (OR=1.97, 95% CI=1.39–2.80, P<0.001), LVEF (OR=0.96, 95% CI=0.94–0.98, P<0.001), albumin (OR=0.94, 95% CI=0.91–0.97, P<0.001), and D-dimer (OR=1.09, 95% CI=1.02–1.17, P<0.001). After adjusting for age >75 years, hypertension, AF, LVEF, albumin, and D-dimer, there was a linear relationship between TyG index and CI-AKI risk.
CONCLUSIONS In patients undergoing PCI, an elevated TyG index is closely associated with a higher incidence of CI-AKI and is an independent risk factor for the development of CI-AKI.
GW34-e0979
Xuanchang Liu1,2, Zichen Liu3, Junjie Zhang4, Bin Liu5, Ziqi Li1, Haiyan Wu1, Yu Gao1, Cong Wu1, Yang Li1, Yi Fang1, Quanmin Jing1, Yaling Han1, Kai Xu1
1General Hospital of Northern Theater Command
2Jinzhou Medical University
3Johns Hopkins University
4Nanjing First Hospital
5Second Hospital of Jilin University
OBJECTIVES There are various different criteria for using Intravascular Ultrasound (IVUS) to judge the lesion to be hemodynamically significant or not. IVUS had an advantage on identifying calcification component. Obtained from IVUS, the minimal luminal area (MLA) and plaque burden (PB) which is critical to optimize stent deploying have been proved to have moderate correlation with FFR. And recently the researchers focused on the artery geometry and applied fluid dynamics or computational algorithm on estimating a more precise virtual FFR derived from IVUS. Various attempts to discover the effect of plaque component on the functional significance of the lesion with virtual histology IVUS or radiofrequency IVUS didn’t reach a consensus. We conducted this study to determine whether the grayscale IVUS could better identify a hemodynamical significant plaque with the plaque component taken into account through the method of support vector machine of machine learning. We want to determine that with the plaque components and calcification taken into account additionally, whether the performance of prediction could be improved.
METHODS This is a retrospective and multi-center study. The patients who underwent IVUS and FFR measurement in General Hospital of Northern Theater Command, Shenyang, China, The Second Norman Bethune Hospital of Jilin University, Changchun, China and Nanjing First Hospital, Nanjing, China, from 2016 to 2022 were included, all with IVUS and Fractional flow Reserve (FFR) measured. Calcification score was defined as the radian of the dark regions behind the calcium components. No calcium and no corresponding dark regions was defined as 0, the radian <90° as 1, over 90° and below 180° as 2, over 180° and below 270° as 3, and over 270° as 4. Classification was realized via the Support Vector Machine (SVM). The SVM was a binary classifier. Two models were trained. The first model the input items were all the extracted features from IVUS including lesion position, intima area and diameter, adventitia area and diameter, PB, MLA, calcification score, attenuation score and plaque characteristics. The second model plaque characteristics and calcification score were excluded from the input items. Output result was set as FFR negative (FFR>0.80) or positive (FFR≤0.80). The dataset of 30 lesions was divided into a training set of 24 and a test set of 6 randomly and the randomization was performed with the table of random digit. Randomization was performed 10 times individually for each group, thus 10 results on different test sets for each model were generated. And by comparing the two models output performance the effect of plaque characteristics and calcification volume on hemodynamical significance could be identified.
RESULTS The plaque components (P<0.001) and calcification volume (P<0.001) were different between the FFR positive and FFR negative group, and calcification was more frequently observed in the FFR positive group (P<0.001). The model including plaque component and calcification compared to the other one, it’s found that the accuracy (70 vs 47%, P=0.02), precision (71 vs 49%, P=0.03) and F1 score (82 vs 59%, P=0.02) improved.
CONCLUSIONS The plaque components were different in the hemodynamical significant lesions, and with that taken into account the SVM model showed improved performance to classify the stenosis. This indicates that plaque composition or calcification may have a potential effect on hemodynamic significance, and to get a more precise ultrasound derived flow reserve, plaque composition or calcification should be taken into account.
GW34-e1018
Hongyu Lu1,2, Yibo He1,2, Zhou Ziyou1,3, Xiayan Xu1,3, Yun Xie1,4, Jin Liu1,5, Yong Liu1,2, Jiyan Chen1,2
1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
2Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China Guangdong Academy of Medical Sciences, Guangzhou 510080, China
3School of Medicine, South China University of Technology, Guangzhou 510006
4School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
5The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China
OBJECTIVES The aim of this study was to investigate the effect of low-grade inflammation on the relationship between type2 diabetes (T2DM) and all-cause mortality in old patients with coronary artery disease (CAD).
METHODS In this study, we enrolled 8571 old patients with CAD (Aged>60 years). Patients with active inflammation (hs-CRP>10 mg/L were excluded. Based on the median values of hs-CRP, patients were categorized as low-grade inflammation (LGI) and non-low-grade inflammation (NLGI) groups. According to the presence of T2DM, CAD patients were further divided into NLGI/T2DM, NLGI/non-T2DM, LGI/T2DM and LGI/non-T2DM groups. The primary endpoint was follow-up all-cause mortality.
RESULTS During a mean follow-up of 3.82 years, a total of 968 (11.3%) deaths were recorded. The median value of hs-CRP was 1.70[mg/L]. The presence of LGI was associated with worse prognosis in CAD patients with or without T2DM [in T2DM adjusted HR: 1.42, 95% confidence interval (CI): 1.16–1.75, P=0.001; in non-T2DM adjusted HR: 1.23, 95% confidence interval (CI): 1.03–1.48, P=0.023; P for interaction<0.001]. However, there was no difference in all-cause mortality between diabetic and non-diabetic in patients without the presence of LGI [adjusted HR: 1.13, 95% CI: 0.91–1.40, P=0.268], while in patients with in low-grade inflammation, T2DM had a significantly higher risk of all-cause mortality comparing with non-T2DM patients [adjusted HR: 1.28, 95% CI: 1.09–1.52, P=0.003].
CONCLUSIONS In old patients with CAD, the presence of LGI is associated with worse clinical outcomes both in T2DM and Non-T2DM groups. The prognostic impact of DM was significant only in the old CAD population with low-grade inflammation.
GW34-e1019
Liang Geng, Shangwei Huang, Liming Gao, Yunkai Wang, Jiming Li, Wei Guo, Lijie Wang, Jimin Li, Lan Ma, Xiaoyan He, Qi Zhang, Ying Li
Department of Cardiology, East Hospital, Tongji University, Shanghai
OBJECTIVES Previous studies have shown that cardiopulmonary exercise testing has incremental values in evaluating coronary artery disease patients. However, the functional relevance of cardiopulmonary exercise testing parameters remains controversial. We sought to explore the roles of cardiopulmonary exercise testing in determining the functional significance of coronary artery disease, using quantitative flow ratio as the reference.
METHODS Murray-law based quantitative flow ratio were off-line analyzed in 135 patients with coronary artery disease who underwent a cardiopulmonary exercise testing examination. For the patients with multivessel disease, the lowest quantitative flow ratio was recorded as the final value for following analysis. The functional significance was defined as quantitative flow ratio≤0.8. Cardiopulmonary exercise testing indicators of all subjects were prospectively collected. The presence of O2-pulse plateau was identified by two experienced physicians based on visual assessment.
RESULTS Fourteen patients had quantitative flow ratio-defined flow-limiting vessels (10.4%), whereas the presence of O2-pulse plateau was observed in 29 patients. The prevalence of O2-pulse plateau was higher in patients with quantitative flow ratio ≤0.8 compared with those without (71.4 vs 15.7%, P<0.05). There was a trend towards patients with quantitative flow ratio ≤0.8 having a lower HRmax (114±16 vs 123±17, P=0.06). No differences were found in other cardiopulmonary exercise testing indicators, including PeakVO2, PeakVO2% predicted, VE/VCO2slope, ΔVO2/ΔWR, PeakVO2/HR and Peak SBP.
CONCLUSIONS Among all the cardiopulmonary exercise testing variables, only the presence of O2-pulse plateau is associated with functionally significant coronary stenosis.
GW34-e1020
Hongyu Lu1,2, Yibo He1,2, Ziyou Zhou1,3, Xiayan Xu1,3, Yun Xie1,4, Jin Liu1,5, Yong Liu1,2, Jiyan Chen1,2
1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
2Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China Guangdong Academy of Medical Sciences, Guangzhou 510080, China
3School of Medicine, South China University of Technology, Guangzhou 510006
4School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
5The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China
OBJECTIVES Low-grade inflammation (LGI) is a non-overt inflammatory state commonly presented in patients with coronary artery disease and correlated with adverse prognosis. However, whether the impact of LGI on the prognosis varies in young and old patients remains unknown.
METHODS In this study, we enrolled patients with coronary artery disease undergoing percutaneous coronary intervention. Patients with active inflammation (hs-CRP>10 mg/L) were excluded. Patients were classified as young (<60 years) and old (≥60 years) group. Low grade inflammation defined as hs-CRP≥2 mg/L. The association between all-cause mortality and LGI was detected by Cox proportional hazards regression analysis. Interaction effect analyses were performed to evaluate the different impact of LGI in young and old patients underwent PCI.
RESULTS A total of 21,235 patients underwent PCI (mean age 69.2±11.0 years, 77.1% were men) were included in the study. 6384 (49.4%) old patients were accompanied by low-grade inflammation, and 4060 (48.9%) young patients had low-grade inflammation. During a mean follow-up of 4.67 years, a total of 2129 patients died. Cox regression model demonstrated that LGI had no effect on prognosis in young patients while significantly increased the risk of all-cause mortality in olde patients underwent PCI [young adjusted HR. 1.12, 95% confidence interval (CI): 0.94–1.34, P=0.215; old adjusted HR: 1.22, 95% confidence interval (CI): 1.10–1.35), P=<0.001. Significant interaction between LGI and age on prognosis was detected in patients undergoing PCI [P for interaction=0.034].
CONCLUSIONS LGI is common in both young and old patients underwent PCI, but only increases the prognostic risk in old patients. Attention and early intervention on LGI should be considered in old patients receiving PCI.
GW34-e1021
Ganjian Zhao, Yulu Zuo, Mengmeng Zhao, Dongmei Xia, Jinpeng Yang, Ying Liu, Duo Li, Chaoxin Xu, Shuna Tan, Wenqing Li, Cuiping Zhao
Hui Ya Hospital of The First Affiliated Hospital, Sun Yat-sen University
OBJECTIVES To explore the relationship between the number of coronary stents and clinical manifestations such as angina pectoris and long-term prognosis. To determine whether Wuling capsule can effectively improve the symptoms of depression and physical diseases such as angina pectoris in patients with coronary heart disease, verify whether Wuling capsule has better therapeutic effect on the psychological and cardiac conditions of patients with different stent numbers, and improve long-term prognosis.
METHODS One hundred and eighty outpatients and in patients with coronary heart disease complicated with depression in Hui Ya Hospital of The First Affiliated Hospital, Sun Yat-sen University from October 2021 to January 2023 were selected. Patients with NYHA functional classes III and IV, allergy to Wuling capsule components, and depression with HAMD (Hamilton Depression Scale) score greater than 17 during the study were excluded. The patients were randomly divided into control group (C0: No stent, C1: 1 stent, C2: with more than 2 stents) versus the treatment group (T0: No stent, T1: 1 stent, T2: with more than 2 stents). Both groups were given conventional drug therapy and psychological counseling for coronary heart disease. The treatment group was additionally given Wuling capsule 3 tablets each time, 3 times a day for 3 months. HAMD, SAQ (Seattle Angina Scale) score, HRV (heart rate variability) and 6MWT (6-minute walk test) were used to evaluate.
RESULTS (1) There was no significant difference in gender, age, cardiac function, hypertension, diabetes, hyperlipidemia, liver and kidney function, smoking among the groups (P>0.05). (2) Before intervention, the HAMD score of group C1 and C2 was significantly higher than that of group C0 (P<0.05), while the SAQ score, HRV and 6MWT index of group C1 and C2 were significantly lower than that of group C0 (P<0.05). In the treatment groups (T0, T1, T2), the scores of HAMD in T1 and T2 were significantly higher than those in T0 (P<0.05), and the scores of SAQ, HRV and 6MWT in T2 were significantly lower than those in T1 (P<0.05). (3) After 1–3 months of routine drug treatment and psychological intervention, the scores of HAMD in C0, C1 and C2 groups tended to decrease, while the scores of SAQ, 6MWT and HRV increased. (4) After treatment with Wuling capsule, the HAMD scores of the treatment group (T0, T1, T2) were significantly lower than those of the control group (C0, C1, C2) (P<0.05), and the SAQ scores, 6MWT, HRV were significantly higher (P<0.05). (5) In the observation and treatment group (T0, T1, T2), the scores of HAMD decreased significantly (P<0.05), and the scores of SAQ, 6MWT and HRV increased significantly (P<0.05).
CONCLUSIONS The more the number of coronary stents, the more severe the limitation of physical activity, the worse the cognition of disease, the more severe the depression, and the worse the long-term prognosis. Wuling capsule can be used as an adjuvant therapy to help patients effectively relieve psychological stress and physical symptoms, thereby improving the quality of life and therapeutic effect of patients and improving long-term prognosis.
GW34-e1028
Junhan Chen1,2, Wenjia Liang1,2, Xiaofang Chen1,2, Yansong Guo1,2
1Shengli Clinical Medical College of Fujian Medical University
2Fujian Provincial Hospital
OBJECTIVES Neutrophils, monocytes, and lymphocytes are well-known inflammatory biomarkers that are highly correlated with contrast-associated acute kidney injury (CA-AKI). The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. We hypothesized that SIRI has predictive value for CA-AKI and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI).
METHODS We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. SIRI = neutrophil×monocyte/lymphocyte. CA-AKI was defined as an increase of 50% or 0.3 mg/dL in SCr from baseline within 48 hours after contrast exposure. Patients were divided into high SIRI group and low SIRI group according to the best cut-off value of SIRI, which was obtained from ROC curve.
RESULTS The incidence of CA-AKI was 6.1% (n=352). The best cut-off value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590–0.651, P<0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI>1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI≤1.39) (odds ratio=1.642, 95% CI: 1.274–2.116, P<0.001). In addition, COX regression analysis showed that SIRI >1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95% CI: 1.188–1.765; P<0.001]. Besides, according to the Kaplan-Meier survival curve, the cumulative rate of mortality was likewise shown to be considerably higher in the high SIRI group than in the low one.
CONCLUSIONS High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.
GW34-e1033
Xinya Dai1,2, Tong Liu1,2
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 300211, China
2Cardiovascular Center, Korea University Guro Hospital, Seoul 08308, Republic of Korea
OBJECTIVES It has been confirmed that high-sensitive C-reactive protein (hs-CRP) to high-density lipoprotein cholesterol (HDL-C) ratio (CHR) is associated with the presence and severity of coronary artery disease (CAD). However, to the best of our knowledge, the relationship between CHR and long-term mortality in CAD patients following percutaneous coronary intervention (PCI) has not been reported. Therefore, we aimed to assess the correlation between the CHR and long-term mortality in patients with CAD after undergoing PCI in our study that enrolled a large number of patients.
METHODS A total of 3260 post-PCI patients with CAD were enrolled in the KUGH-percutaneous coronary intervention registry since 2004 (#KUGH10045). The median follow-up time was 89.63 months. Patients were divided into three groups according to CHR tertiles: group 1 (<0.830, N=1089), group 2 (0.830–3.782, N=1085) and group 3 (>3.782, N=1086). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). Kaplan-Meier plots and long-rank tests were employed to investigate survival differences among the groups. Adjusted multivariable Cox analysis was employed to investigate the relationship of CHR with ACM and CM. Restricted cubic spline was further used to discern non-linear relationship between and long-term mortality. Sensitivity analysis was used to check the robustness of study results.
RESULTS In our study, ACM occurred in 277 patients: 49 (4.5%) in group 1, 80 (7.4%) in group 2, and 148 (13.6%) in group 3 (P<0.001); CM occurred in 135 patients: 17 (1.6%) in group 1, 37 (3.4%) in group 2 and 81 (7.6%) in group 3 (P<0.001). Kaplan-Meier analysis revealed significant differences in long-term ACM and CM among the CHR tertiles (log-rank test: P<0.001). In the fully-adjusted Cox regression model, individuals in the highest tertile of MLR had higher risk of ACM (HR=1.51, 95% CI: 1.01–2.26) and CM (HR=2.40, 95% CI: 1.26–4.59) than those in the lowest tertile. Furthermore, the restricted cubic spline curve indicated that there was not a significant non-linear association between CHR and long-term mortality (ACM and CM, P>0.05). The risk of ACM (RR=1.40, 95% CI 1.15–1.71) and CM (RR=1.83, 95% CI 1.38–2.43) increased by 40% and 83% per 10-fold change in CHR with a linear manner, respectively.
CONCLUSIONS Our study demonstrated that increased baseline MHR was significantly related to long-term ACM and CM in CAD patients following PCI, independent of established risk factors.
GW34-e1042
Junhan Chen1,2, Wenjia Liang1,2, Hongkui Chen1,2, Yansong Guo1,2
1Shengli Clinical Medical College of Fujian Medical University
2Fujian Provincial Hospital
OBJECTIVES Liver dysfunction is prevalent with kidney injury and can lead to poor prognosis. The albumin-bilirubin (ALBI) score is considered an effective and convenient scoring system for assessing liver function. We hypothesized that the ALBI score was predictive of contrast-associated acute kidney injury (CA-AKI) occurrence and long-term mortality in patients with diabetes undergoing elective percutaneous coronary intervention (PCI).
METHODS We retrospectively observed 2005 patients with diabetes undergoing elective PCI from 2012 to 2018. The ALBI score=0.66×ln[bilirubin (μmol/L)] – 0.085×[albumin (g/L)]. CA-AKI is defined as a 50% or 0.3 mg/dL increase in baseline serum creatinine levels within 48 hours of contrast exposure. Patients were divided into 3 groups according to the tertiles of the ALBI score.
RESULTS The incidence of CA-AKI was 7.6% (n=154). After adjusting for potential confounding factors, multivariate analysis showed that compared with Tertile 1 and 2 groups, Tertile 3 group exhibited a markedly elevated risk of CA-AKI in diabetics undergoing elective percutaneous coronary intervention (OR=2.242, 95% CI: 1.334–3.768, P=0.002). At a median follow-up of 2.8 years, Kaplan-Meier curve showed a significant increase in mortality for Tertile 2 and 3 groups compared to Tertile 1 group. Similarly, in multivariate Cox regression analysis, Tertile 2 and 3 groups remained independent risk factors for long-term mortality (HR=1.671, 95% CI: 1.060–2.632, P=0.027; HR=1.875, 95% CI: 1.181–2.976, P=0.008, respectively). Furthermore, considering the ALBI score as a continuous variable, the occurrence of CA-AKI and long-term mortality were positively correlated with the ALBI score (OR=1.511, 95% CI: 1.171–1.950, per 1-point increment; P=0.001; HR=1.334, 95% CI: 1.071–1.662, per 1-point increment; P=0.01).
CONCLUSIONS The increase in the ALBI score was positively associated with the occurrence of CA-AKI and long-term mortality in patients with diabetes undergoing elective PCI.
GW34-e1061
Jia-Cong Nong, Ya-Jie Guo, Yi Xu, Xiao-Han Kong, Tian Xu, Pei-Na Meng, Wei You, Zhi-Ming Wu, Xiang-Qi Wu, Fei Ye
Nanjing First Hospital
OBJECTIVES Although patients are undergoing similar long-term lipid-lowering therapy (LLT) with statins, the outcomes of coronary plaque in acute coronary syndrome (ACS) patients with or without chronic kidney disease (CKD) are different. We used a novel artificial intelligence (AI) to analyse the changes in nonculprit subclinical atherosclerosis (nCSA) morphology and composition in patients with mild CKD by optical flow ratio (OFR) software based on optical coherence tomography (OCT) data.
METHODS A total of 184 ACS patients with at least one nCSA in addition to culprit lesion without treatment were detected by OCT at baseline and at the 1-year follow-up, who were divided into the G1 group (n=106, estimated glomerular filtration rate (eGFR)> 90 mL/min per 1.73 m2) and the G2 group (n=78, 60≤eGFR<90 mL/min per 1.73 m2). Normalized total atheroma volume (TAVn) of nCSA were the primary endpoint. Secondary endpoints included percent atheroma volume (PAV), each component in nCSA, and major adverse cardiac events (MACEs) related to nCSA at the 5-year follow-up. Plaque regression (PR) was defined as any decrease in TAVn; otherwise, it was defined as plaque progression (PP).
RESULTS Although low-density lipoprotein cholesterol (LDL-C) levels were similar between the G1 and the G2 groups at baseline (2.05 (1.65, 2.80) mmol/L vs. 2.01 (1.62, 2.97) mmol/L, P=0.837) and the 1-year follow-up (1.70 (1.43, 2.13) mmonl/L vs. 1.69 (1.42, 2.10) mmol/L, P=0.504), patients in the G2 group showed more PP in nCSA (TAVn; 120.37±44.12 mm3 vs 125.16±45.30 mm3, P<0.05) compared with that in the G1 group (TAVn; 109.52±37.10 mm3 vs 110.45±39.12 mm3, P>0.05) from baseline to the 1-year follow-up, which was mainly due to an increase in changes of calcium TAVn (Calcium ΔTAVn; 0.05[−0.12, 0.76] mm3 vs 0.56[0.05, 3.03] mm3, P<0.001). Changes of maximal calcium thickness (ΔMaxCT; 9.05[−8.50, 26.10] mm vs 0.00[−0.12, 0.16] mm, P=0.026) were higher and changes of distance from calcified surface to contralateral coronary media membrane at crossectional maximal calcium area (ΔC-to-M) were decreased (–0.12[−0.31, 0.00] mm vs 0.00[−0.10, 0.08] mm, P<0.001) in the G2 group than in the G1 group. Major adverse cardiac events (MACEs) related to nCSA at the 5-year follow-up were higher in the G2 group compared to that in the G 1 group (30.8 vs 5.8%, P=0.045).
CONCLUSIONS Despite a comparable reduction in LDL-C levels after lipid lowering therapy, more PP with an increase in the calcium component of nCSA and a higher corresponding incidence of MACEs at the 5-year follow-up was observed in mild CKD patients.
GW34-e1093
Ho Ying Edwina Sze, Kai-Hang Yiu
Division of Cardiology, Department of Medicine, the University of Hong Kong, Queen Mary Hospital
OBJECTIVES Computational pressure-flow dynamics derived fractional flow reserve (caFFR) is a novel index to assess the severity of coronary artery stenoses without requirement of invasive pressure wire and hyperaemic stimulus in fractional flow reserve (FFR) measurement. Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) is the most and second most common acute coronary syndrome, respectively. The clinical value of caFFR in patients presenting with NSTEMI and UA has not been validated. The aim of this study is to investigate the prognostic value of caFFR among NSTEMI and UA patients.
METHODS A total of 1449 vessels in 483 patients that presented with NSTEMI or UA (mean age=67.0±12.3, 67.9% male) were analysed and included for caFFR. Vessels were said to be adherent to caFFR if ischemic vessels, defined by caFFR≤0.8 were treated with PCI and non-ischemic vessels, defined by caFFR>0.8 were not treated by PCI. Otherwise, they were considered non-adherent to caFFR. The primary endpoint was the vessel-oriented composite endpoint (VOCE), defined as vessel-related cardiovascular mortality, vessel-related myocardial infarction (MI) and unplanned revascularisation at median 4.4 years follow-up. Survival curves were constructed using Kaplan-Meier estimates and differences between groups were tested using the log-rank test. Cox proportional hazards model was used to evaluate the association of adherence-to-caFFR with the risk of VOCE, with parameters with P<0.1 upon univariate analysis entered into multivariable Cox model.
RESULTS Among the 1449 vessels, caFFR was analysable in 1020 (70.4%) vessels, with 801 (78.5%) vessels receiving treatment adherent to caFFR and 219 (21.5%) vessels receiving treatment non-adherent to caFFR. Adherent vessels had significantly lower incidence rates of VOCE (8.6 vs 17.4%; P<0.001), cardiovascular mortality (3.0 vs 7.3%, P=0.004) and MI (2.0 vs 9.1%, P<0.001) after median 4.4 years compared to non-adherent vessels. After multivariate adjustment, adherent vessels had a significantly lower risk than non-adherent vessels in terms of VOCE (HR 0.47; 95% [Cl] 0.32–0.70; P<0.001), vessel-related cardiovascular mortality (HR 0.40; 95% Cl 0.21–0.76; P=0.005) and vessel-related MI (HR 0.22; 95% Cl 0.11–0.42; P<0.001).
CONCLUSIONS In both NSTEMI and UA patients, revascularization adherent to caFFR guidelines significantly reduces the risk of VOCE. The findings support the potential use of caFFR in treatment guidance of NSTEMI and UA patients.
GW34-e1106
Wei Wei, Yunkai Wang, Qi Zhang
Shanghai East Hospital
OBJECTIVES Despite primary interventional treatment and improvements in pharmacological agents, residual risk of ischemic cardiovascular events following acute myocardial infarction (AMI) remains high. There is a strong necessity to develop methods for estimating putative patients who are at high risk for occurrence of new events and premature death and optimize therapies and outcomes. S100a8a9, Ca2+ binding proteins belonging to the S100 family, was identified to play a critical role in modulating the inflammatory response by stimulating leukocyte recruitment and inducing cytokine secretion. The aim of this study was to investigate the prognostic implication of S100a8a9 level in patients after acute myocardial infarction (AMI).
METHODS This prospective study analyzed data from a total of 1312 consecutive patients hospitalizing with ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction from August 2013 and June 2016. S100a8a9 levels were analyzed in serum obtained from AMI patients. The S100a8a9 concentration at baseline. The primary end points were major adverse cardiovascular events (MACE), including all-cause mortality, hospitalization for heart failure (HF), or recurrent myocardial infarction (MI).
RESULTS The study included 1312 AMI patients, the patient population was predominantly male (63.4%) with a median age of 66 years (IQR: 57–76 years), and 58.5% were STEMI patients. During a follow-up of 2 years, 117 patients died, and 377 patients reached the combined end points of MACE. Patients with elevated S100a8a9 levels had increased risk of MACE, all-cause mortality, recurrent MI and hospitalization for HF (log-rank test, P<.0001). After multivariable adjustment for baseline clinical characteristics and established biomarkers, S100a8a9 concentration in the higher tertile was independently associated with an increased risk of MACE and its individual components (Ptrend<.001). After the addition of S100a8a9 to the reference model, S100A8/A9 showed additive prognostic significance for long-term clinical outcomes.
CONCLUSIONS The present study herein showed that elevated levels of circulating S100a8a9 level independently predicts all-cause mortality and cardiovascular events in AMI patients independent of established conventional risk factors. These findings highlight the need for future studies focused on S100a8a9 of the long-term risk of patients after AMI.
GW34-e1142
Dongdong Sun
Department of Geriatrics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
OBJECTIVES The optimal timing of intervention in non-ST-elevation myocardial infarction (NSTEMI) remains uncertain.
METHODS Patients with NSTEMI (n=554) from 2011 to 2021 in Daping Hospital of Third Military Medical University were divided into three groups based on the timing of intervention including an immediate intervention group (<2h, n=105), an early intervention group (2–24h, n=251) and the delayed intervention group (24–72h, n=198). Clinical outcomes were all-cause death, new heart failure, new MI, stroke, repeat intervention, readmission because of unstable angina or a composite of those at up to 10-year follow up. Primary outcomes based on the timing of intervention were assessed by comparison of Kaplan-Meier. Multivariable analyses of correlates of MACE events were performed using Cox backward stepwise multiple logistic regression.
RESULTS The median follow-up time of all patients was 3.75 years. Delayed invasive treatment improved the MACE outcome compared to the immediate invasive treatment strategy (HR 0.456, 95% CI 0.296–0.704, P for interaction<0.001). The early and delayed invasive treatment was both found to be protective against readmission because of unstable angina. These effects were more pronounced in the early follow-up. The median follow-up time of the first 5 years patients was 1.34 (0.78, 2.35). Early and delayed invasive treatment improved the MACE outcome compared to the immediate invasive treatment strategy. The survival free from readmission because of unstable angina were significantly lower than immediate invasive group.
CONCLUSIONS An immediate invasive strategy did not have an advantage over an early or delayed invasive strategy in reducing primary clinical outcomes for high-riske NSTEMI patients. An immediate invasive strategy might increase the rate of MACE and readmission because of unstable angina. These effects were more obvious in the early follow-up and female subgroup.
GW34-e1149
Yuanhui Liu, Pengcheng He, Ning Tan
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
OBJECTIVES Procedural anticoagulation is essential before and during percutaneous coronary intervention (PCI) to prevent thrombus formation. Current guidelines do not recommend routine use of parenteral anticoagulation therapy (PACT) after primary PCI due to the potential increase of bleeding events without improving clinical outcomes. However, the effect of PACT in high thrombotic risk (HTR) patients with ST-segment elevation myocardial infarction (STEMI) after primary PCI remained unclear.
METHODS This cohort study included 2001 HTR patients with STEMI underwent primary PCI at 4 medical centers in China. Patients who received PACT after PCI were classified into the PACT group. Patients only receiving PACT during PCI were classified into the non-PACT group. The primary outcomes included in hospital major adverse clinical events (MACE), which comprising all cause mortality, stroke, target vessel revascularization, or recurrent myocardial infarction, and net adverse clinical events (NACE), which comprising MACE and major bleeding as defined by the Bleeding Academic Research Consortium definition (grades 3–5). Multivariate analysis and the propensity score analysis were performed.
RESULTS Among the included patients, 473 (23.64%) received PACT, while 1528 (73.36%) did not. There were no significant differences between the PACT and non-PACT groups in terms of in hospital all-cause mortality (2.1 vs. 2.3%; P=0.821), major bleeding (11.8 vs. 13.5%; P=0.637), MACE (3.0 vs. 3.9%; P=0.361), and NACE (4.2 vs. 5.0%; P=0.507). Univariate analysis revealed that PACT was not associated with an increased incidence of in hospital all-cause mortality (adjusted odds ratio [OR]=0.92; 95% CI, 0.45–1.87; P=0.821), major bleeding (OR=0.92; 95% CI, 0.37–2.29; P=0.857), MACE (OR=0.76; 95% CI, 0.42–1.37; P=0.363), and NACE (OR=0.84; 95% CI, 0.51–1.40; P=0.508). Multivariate analysis and the propensity score analysis confirmed these primary analyses.
CONCLUSIONS PACT was not associated with a significantly lower risk of in hospital MACE or NACE in HTR patients with STEMI undergoing primary PCI. Our findings raise important questions about the current practice of parenteral anticoagulation therapy after PCI while we await randomized trials of this practice.
GW34-e1178
Jing Pan, Chuang Li, Yuting Ren, Yumeng Liu, Cuncun Hua, Lefeng Wang
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
OBJECTIVES For patients with acute myocardial infarction, early revascularization is the most important treatment. But the optimal revascularization approach of non-culprit vessels, especially for the patients with different killip classes, is still controversial. To investigate whether multi-vessel revascularization improves long-term prognosis compared with infarct-related artery (IRA) only revascularization among AMI patients with different killip classes and multi-vessel coronary artery disease (CAD).
METHODS Clinical data from 646 patients presenting with AMI and multi-vessel CAD between November 2014 and November 2020 in Beijing Chaoyang hospital were retrospectively analyzed. Patients were divided into two groups: the IRA-only revascularization group (n=416) and the multi-vessel revascularization group (n=230). Multi-vessel revascularization was performed either before or after hospital discharge. The primary endpoint was cardiovascular death, and the secondary endpoint was the composite of all-cause death, myocardial infarction, ischemia-driven revascularization, heart failure or refractory angina and each of the components was also assessed individually.
RESULTS In the following 3–9 years, the primary outcome had showed up in 7 of the 230 patients (3%) in the multi-vessel revascularization group as compared with 40 of the 416 patients (9.6%) in the IRA-only revascularization group (HR, 0.284; 95% CI, 0.120–0.669; P=0.004). But multi-vessel revascularization was associated with higher ischemia-driven revascularization than IRA-only revascularization (26.1 vs 16.8%; P=0.005). There was no significant reduction in the rate of myocardial infarction, heart failure, refractory angina or the composite of all those components. According to the Killip classes, patients were subdivided into the Killip I-II group and the Killip III-IV group. For the Killip I-II group (n=533), 2.6% of the patients had the primary endpoint in the multi-vessel revascularization group versus 9.5% in the IRA-only revascularization group (HR: 0.236; 95% CI: 0.083–0.667; P=0.006), but the rate of patients having ischemia-driven revascularization in the multi-vessel revascularization group is still high (26.5 vs 17.8%; P=0.017). Base on the propensity-score matching method, the difference in the above data still have statistical significance (3 vs 8.4%; HR, 0.313; 95% CI, 0.103–0.953; P=0.041; and 28.1 vs 18.7%; P=0.039, respectively). There was also no significant reduction in myocardial infarction, heart failure, refractory angina or the composite of all those components. In Killip III-IV patients (n=113), there was no statistical significance in either the primary endpoint or the secondary endpoint.
CONCLUSIONS For patients presenting with AMI and multi-vessel CAD, especially for Killip I-II patients, multi-vessel revascularization significantly lowered the rate of cardiovascular death and increased the rate of ischemia-driven revascularization compared with only treated with the IRA. For patients with Killip III-IV, there were no significant differences in the primary endpoint and the secondary endpoint between the groups. In view of the small number of Killip III-IV patients in this study, larger clinical trials are required to confirm this result and specifically figure out whether multi-vessel revascularization is associated with improved survival for Killip III-IV patients or not.
GW34-e1191
Jiafu Wang1, Xixiang Tang2, Suhua Li1
1Department of Cardiovascular Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
2VIP Medical Service Center, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
OBJECTIVES Coronary artery disease (CAD), as the primary risk factor for the development of heart failure (HF), continues to be the leading cause of death worldwide, posing a significant burden on global health. Accumulated evidences have demonstrated that the altered circulating immune cell subtypes was associated with CAD. In this study, we aim to investigate the circulating immune phenotype, particularly the alterations in T lymphocytes and their subsets, in patients with CAD with varying severity levels.
METHODS A total of 189 hospitalized patients were included in this prospective observational study conducted in the third affiliated hospital of Sun Yat-sen University between May 2022 and May 2023. Participant demographics, clinical, and laboratory examinations were collected. Echocardiography, coronary angiography and NT-proBNP were performed to assess the severity of the disease. Flow cytometry was used to assess the levels of circulating immune cells, particularly T lymphocytes and their subsets. We compared the alterations of circulating immune cells in patients without CAD, with CAD and with CAD and HF. Correlation analysis and multivariate logistic regression analysis was used to identify factors associated with severity of CAD.clinical, and laboratory characteristics.
RESULTS The subjects were divided into three groups: non-CAD group (n=36), CAD group (n=74) and CAD with HF group (n=39). As the severity of the disease increased, the patients demonstrated older age, higher levels of HbA1c, aggravated renal function, elevated pro-BNP, and worsened cardiac structure and function (all P<0.05). Routine blood test showed that the total of lymphocytes remarkerly reduced in the CAD with HF group (P<0.05). With an increase in disease severity, analysis of the immune phenotype revealed a significant decrease in the proportion of T lymphocytes (47.40±15.32 vs. 41.13±11.89 vs. 34.26±15.92, repectively, P=0.003) and B cells (13.68±5.74 vs. 11.23±5.23 vs. 10.25±5.51, repectively, P=0.019), while the proportions of CD45+ cells and monocytes remained unchanged among various groups. Notably, the proportions of mucosa-associated invariant T (MAIT) cells exhibited a notable decrease as the severity of the disease increased (4.66±2.72 vs. 2.24±1.81 vs. 0.93±0.79, repectively, P<0.001), while there was an increase in CD27-MAIT cells with disease severity (51.91±17.04 vs. 54.36±16.90 vs. 61.44±14.40, repectively, P<0.001). No significant variations were observed in the subsets of T lymphocytes or the expression intensities of surface molecules CXCR4, HLA-DR, and MR1 in T lymphocytes, B cells, and monocytes. Additionally, correlation analysis revealed that the proportions of MAIT cells were positively related to the level of eGFR (r=0.195, P=0.045), while negectively associated with HbA1c (r=−0.227, P=0.006) and pro-BNP (r=−0.202, P=0.028). In the multivariate logistic regression analysis, the proportions of MAIT cells were independently associated with the risk of CAD and HF (OR=0.442, 95% CI=0.273–0.717, P=0.001) and CAD (OR=0.697, 95% CI=0.531–0.915, P=0.009), after adjusting for multiple confounding factors.
CONCLUSIONS In summary, the severity of CAD is associated with a significant decrease in the ratios of T lymphocytes and MAIT cells in circulation.
GW34-e1195
Wenxi Dang1,2, Hongwei Li1,2
1Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
2Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease, Beijing, China
OBJECTIVES G protein-coupled receptor autoantibodies (GPCR-AAs) are present in patients with various cardiovascular diseases. However, the predictive value of GPCR-AAs for the occurrence of major adverse cardiovascular events (MACEs) in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear.
METHODS A total of 436 patients with STEMI who underwent primary percutaneous coronary intervention (PPCI) for a 1-year follow-up were included in the study. The outcomes were all-cause death, nonfatal myocardial infarction (MI), revascularization, and cardiac rehospitalization. The levels of β1-, β2-, α1-adrenergic receptor autoantibodies (β1-, β2-, α1-AA), angiotensin II type 1 receptor autoantibodies (AT1-AA), and M2-muscarinic receptor autoantibodies (M2-AA) were measured by ELISA from the patients’ sera collected on admission.
RESULTS Compared with the non-MACE group, the optical density values and positivity rates of the β1-AA levels and M2-AA levels in patients with STEMI were significantly higher in the MACE group. The patients with β1-AA positivity had significantly higher incidences of composite MACEs. Multivariate Cox regression analysis revealed that β1-AA OD value, hypertension, diabetes mellitus, and left main trunk/triple vessel diseases were regarded as predictors for the incidence of MACEs in patients with STEMI. β2-AA, AT1-AA, and α1-AA cannot predict MACEs. Additionally, the β1-AA OD value was able to predict MACEs, with an area under the curve (AUC) of 0.788 (95% CI, 0.73–0.85, P<0.001).
CONCLUSIONS GPCR-AAs have different predictive effects on the 1-year MACEs of patients with STEMI. The β1-AA levels might be a valid predictor of MACEs. β1-AA can also be a new biomarker for preventing MACEs after PPCI in patients with STEMI.
GW34-e1197
Wenxi Dang
Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
OBJECTIVES Microvascular obstruction (MVO) reflect the cardiac injury. G protein-coupled receptor autoantibodies (GPCR-AAs) are present in various cardiovascular diseases. However, the relationship between GPCR-AAs and MVO in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI) remains unknown.
METHODS This prospective study included 160 patients with STEMI who underwent PPCI. Patients’ sera were collected to detect the levels of β1-adrenergic receptor autoantibodies (β1-AA), β2-adrenergic receptor autoantibody (β2-AA), M2-muscarinic receptor autoantibody (M2-AA), angiotensin II type 1 receptor autoantibody (AT1-AA), and α1-adrenergic receptor autoantibody (α1-AA). Cardiovascular magnetic resonance was performed within 5–7 days after PPCI to determine microvascular obstruction (MVO). Echocardiography was performed within 24 h after PPCI and at the 6-month follow-up.
RESULTS The optical density values and positivity rates of β1-AA in patients with MVO were significantly higher than those in patients without MVO. Additionally, β1-AA levels were negatively correlated with the left ventricular ejection fraction. β1-AA and β2-AA levels positively correlated with N-terminal pro-B type natriuretic peptide (NT-proBNP) levels. AT1-AA, M2-AA, and α1-AA levels were positively correlated with glycated hemoglobin levels and negatively correlated with high-density lipoprotein cholesterol and apolipoprotein A1 levels. Multivariate logistic regression analysis revealed that β1-AA and peak troponin I (pTNI) levels were significantly associated with the incidence of MVO. Moreover, combination of β1-AA and pTNI has the highest predictive power to predict MVO. The restricted cubic splines showed that the association between β1-AA and MVO was linear after full adjustment.
CONCLUSIONS GPCR-AAs are associated with worse cardiac function and glycolipid metabolism dysfunction in patients with STEMI after PPCI. Several GPCR-AAs have relationship with MVO and LV remodeling. The combination of β1-AA and pTNI showed the highest ability to predict MVO, and β1-AA is significant for evaluating the short-term prognosis of PPCI and provide the opportunities to improve MVO at early stage.
GW34-e1198
Changling Li1, Yumeng Hu2, Liang Dong1, Jun Jiang1, Yong Sun1, Lijiang Tang3, Changqing Du3, Da Yin4, Wenbing Jiang5, Xiaochang Leng2, Fan Jiang6, Yibin Pan7, Xuejun Jiang8, Zhong Zhou9, Jianping Xiang2, Jian’an Wang1
1Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
2ArteryFlow Technology Co., Ltd., Hangzhou, China
3Department of Cardiology, Zhejiang Hospital, Hangzhou, China
4Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
5Department of Cardiology, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, China
6Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China
7Department of Cardiology, Jinhua Municipal Central Hospital, Jinhua, China
8Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
9Department of Cardiology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China
OBJECTIVES This study aimed to evaluate the feasibility and accuracy of a novel noninvasive technique, called AccuFFRct, for computing Fractional Flow Reserve (FFR) from coronary CTA images to detect lesion-specific ischemia in coronary artery stenosis.
METHODS A total of 339 patients with 404 vessels were prospectively enrolled in this study. CT-FFR values were calculated using a new computational fluid dynamics-based method (AccuFFR®ct, version 1.0, ArteryFlow, Hangzhou, China) for each lesion and compared with invasive FFR values measured using a wire as a reference. The performance of AccuFFRct was analyzed for all lesions, including “gray zone” lesions, calcification lesions, and different types of lesions.
RESULTS When using FFR≤0.8 as a reference, the per-patient and per-vessel diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for AccuFFRct were 90.3%, 91.4%, 89.5%, 85.9%, and 93.7%, and 90.6%, 90.9%, 90.4%, 85.3%, and 94.2%, respectively. The direct correlations between computed AccuFFRct and measured FFR were 0.74 on a per-patient basis and 0.75 on a per-vessel basis. The area under the curve (AUC) values of AccuFFRct for per-patient and per-vessel basis were 0.92 and 0.93, respectively. The diagnostic accuracy of “gray-zone” lesions (FFR 0.75~0.85) was not significantly different from the other two groups. There was no significant difference in the diagnostic efficacy of CT-FFR between vessels with Agatston calcium score ≥400 and <400. The diagnostic accuracy of AccuFFRct for different types of lesions, including General, Tandem, Bifurcation, Calcified, and Diffuse lesions, was 93.2%, 91.7%, 84.6%, 88.7%, and 92.9%, respectively.
CONCLUSIONS AccuFFRct, computed from coronary CTA images, can be used as a computational tool to detect lesion-specific ischemia in coronary artery stenosis, surpassing the assessment of CTA imaging stenosis alone. It shows a particular diagnostic ability for gray zone, highly calcified plaque vessels, and lesions with different degrees of stenosis and vascular location. The study confirms the potential of AccuFFRct as a noninvasive alternative to invasive FFR for detecting ischemia in coronary artery disease.
GW34-e1216
Ying Pan, Ying-Ying Zheng, Ting-Ting Wu, Xiang Xie
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan Road, Urumqi 830054, P.R. China
OBJECTIVES The association between C-reactive protein-albumin-lymphocyte (CALLY) index and coronary artery disease (CAD) remains unclear. The present study aims to explore the relation between CALLY index and adverse clinical outcomes in CAD patients.
METHODS From December 2016 to October 2021, a total of 3799 CAD patients were prospectively enrolled and divided into four groups according to (CALLY) index: Q1(≤0.69), Q2(0.69–2.44), Q3(2.44–9.52), Q4(>9.52). All-cause mortality (ACM) and cardiac mortality (CM) were recorded as the primary endpoints. The secondary endpoints were major adverse cardiovascular events (MACE) and major adverse cardiovascular and cerebrovascular events (MACCE). The average follow-up time was 24 months.
RESULTS We found that there were significant differences between the four groups in the incidences of ACM (P<0.001), CM (P<0.001), MACE (P=0.002) and MACCE (P=0.002). As determined by multivariate Cox regression analyses comparing the patients in the highest-Q4 group to patients in the lowest-Q1 group, the risk of ACM, CM, MACE and MACCE in highest-Q4 group decreased 73.7% (hazard risk [HR]=0.263, 95% CI: 0.147–0.468, P<0.001), 70.6% (HR=0.294, 95% CI: 0.150–0.579, P<0.001), 37.4% (HR=0.626, 95% CI: 0.422–0.929, P=0.020) and 41.5% (HR=0.585, 95% CI: 0.401–0.856, P=0.006), respectively.
CONCLUSIONS This study indicated that CALLY index was an independent and significant indicator of adverse clinical outcomes in CAD patients.
GW34-e1220
Xing Liang, QiaoLing Ye, Zulong Xie, Minming Zheng, Guozhu Chen
The Second Affiliated Hospital of Chongqing Medical University
OBJECTIVES Coronary microvascular dysfunction has been shown to increase the risk of cardiovascular events regardless of the epicardial disease status after a primary percutaneous intervention (PCI) in the setting of acute myocardial infarction. Retinal structural and blood flow changes associated with coronary disease are increasingly reported. To investigate retinal and optic disk microcirculation by using optical coherence tomography angiography (OCTA) in order to predict cardiovascular risk profiles of patients with coronary microcirculation dysfunction (CMD) after acute myocardial infarction (AMI) which accepted PPCI. To fund a novel and non-invasive method for assessment of CMD after AMI.
METHODS This observational clinical cohort study included 140 AMI patients (280 eyes). Retinal OCT-A was performed for each patient within 2–3 days after PPCI using the swept-source optical coherence tomography (SS-OCT). Superficial retinal capillary plexus (SCP) vascular density was measured. The Coronary microcirculation disorders were diagnosed and evaluated by TIMI flow grade, TIMI corrected frame count (CTFC) and myocardial blush grading (MBG). The results of retinal OCTA were compared between the CMD group and the non-CMD group.
RESULTS CMD occurred in 61 patients (43.6%). CMD was significantly associated with age, diabetes, Total ischemic time, Killip grade, left ventricular ejection fraction (LVEF), LDL-C, Lp(a) and NT-proBNP. CMD patients had significantly lower retinal vascular density (RVD) and more frequent low RVD (87 vs 32%, P<0.001), including reductions in mean vessel density both at the deep vascular complex (DVC) and superficial vascular complex (SVC) of the macula. And also, significantly larger foveal avascular zone (FAZ). The association between RVD and CTFC was confirmed by a moderate correlation (Spearman r ¼ 0.52, P<0.001). After 1 month standard DAPT, statins and other drugs, an increase in RVD and a decrease in FAZ were observed.
CONCLUSIONS Measurements of the RVD and FAZ may be useful and sensitive predictors of retinal and choroidal circulation impairment in AMI patients with CMD. OCTA is non-contact, non-invasive, fast and cheap inspection method which easy to repeat. AMI Patients with CMD have higher rates of reinfarction, cardiogenic shock, and heart failure. But, CMD is reversible. Continuous observation and adjustment of treatment plan are expected to improve the prognosis and survival rate of patients. Retinal OCTA, therefore, has potential as a biomarker of coronary disease, with developing evidence in AMI.
GW34-e1233
Yipu Ding1,2, Zinuan Liu1, Ran Xin1,2, Dongkai Shan1, Xi Wang1, Ziqiang Guo1, Junjie Yang1, Yundai Chen1,3
1Senior Department of Cardiology, the Sixth Medical Center of PLA General Hospital
2School of Medicine, Nankai University
3Department of Cardiology, the First Medical Center of PLA General Hospital
OBJECTIVES This study aims to investigate the association between computational fluid dynamics (CFD) parameters derived from coronary computed tomography angiography (CCTA) and acute coronary syndrome (ACS). Furthermore, the ability of CFD parameters in the identification of high-risk plaques that caused subsequent ACS was evaluated.
METHODS Thirty-seven patients who presented with clearly documented ACS at the Chinese PLA General Hospital between January 2015 and September 2022 and available CCTA images acquired at least 1 week before the development of ACS were included. Their clinical characteristics were collected. The plaques detected from CCTA images were divided into two groups: culprit plaques (n=37) and non-culprit (n=42) plaques. Anatomical parameters including plaque length, diameter stenosis, and high-risk plaque (HRP) were assessed. CFD parameters, including wall shear stress (WSS) and axial plaque stress (APS), were calculated. Univariate and multivariate logistic regression were used to identify risk factors for ACS. Furthermore, the predictive efficacy for ACS was compared among the three models (model 1: clinical characteristics, model 2: model 1+anatomical parameters, and model 3: model 2+CFD parameters). R 4.2.0 was used to create the receiver operating characteristic (ROC) curves, and to calculate the area under the curve (AUC), net reclassification index (NRI), and integrated discrimination improvement index (IDI).
RESULTS A significantly higher proportion of severe stenosis was observed in culprit plaques compared to the non-culprit plaques (P=0.033). No significant difference was observed in the presence of high-risk plaque (HRP) or plaque length between the two groups. The APSmin was lower in the culprit plaque group than in the non-culprit plaque group. While both |APS|max and WSSmax displayed higher values in culprit plaques, the difference was not statistically significant. In the univariate logistic analysis, vessel location, severe stenosis, |APS|max, APSmin, and WSSmax showed a significant association with ACS events. Multivariate logistic analysis further revealed that vessel location (HR=6.14, 95% CI: 2.09–18.07, P=0.001), APS min (HR=3.17, 95% CI: 1.01–9.93, P=0.047), and WSSmax (HR=6.99, 95% CI: 1.36–35.91, P=0.020) were independently correlated with the occurrence of ACS events. Adding CFD parameters, including |APS|max, APSmin, and WSSmax, to model 2 significantly improved the predictive efficacy for ACS events (AUC=0.862, 95% CI: 0.782–0.942 vs. AUC=0.781, 95% CI: 0.681–0.881, P=0.044), with better discrimination (IDI=0.888, P<0.001) and reclassification abilities (NRI=0.138, P<0.001).
CONCLUSIONS CFD parameters derived from CCTA are associated with occurrence of ACS events. The multi-utilization of coronary hemodynamic parameters can enhance the predictive value for ACS events compared to the clinical characteristics and anatomical parameters.
GW34-e1235
Ruirui Chen, Yan Li
Department of Cardiology, Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi
OBJECTIVES Drug-coated balloon (DCB) appears as an alternative to the drug-eluting stent (DES) in patients with de novo small vessel coronary artery disease. This study aimed to assess the efficacy and safety of DCB versus DES in primary percutaneous coronary intervention (PCI) for patients suffering from ST-Segment elevation myocardial infarction (STEMI) with de novo coronary lesions in large vessels.
METHODS A database search was conducted using PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov for trials comparing DCB-only with DES in treating de novo coronary lesions in large vessels. Efficacy outcomes included coronary angiography (CAG) follow-up minimal lumen diameter (MLD) and late luminal loss (LLL). Safety outcomes included target lesion failure (TLF: cardiac death, myocardial infarction [MI], target lesion revascularization [TLR]) and their individual components.
RESULTS We included 4 randomized control trials (RCTs) with 459 patients, of which 228 and 231 patients were in the DCB-only and DES groups, respectively. MLD in the DCB group was statistically significantly smaller than in the DES group (MD: −0.13, 95% CI: −0.25 to −0.02, P=0.02, I2=0%). LLL was statistically significantly lower in the DCB group than in the DES group (MD: −0.12, 95% CI: −0.24 to −0.00, P=0.04, I2=71%). TLF (RR: 0.88, 95% CI: 0.42–1.86, P=0.74, I2=0%), cardiac death (RR: 0.76, 95% CI: 0.16–3.73, P=0.74, I2=0%), MI (RR: 0.74, 95% CI: 0.25–2.20, P=0.59, I2=0%), and TLR (RR: 1.17, 95% CI: 0.42–3.29, P=0.76, I2=0%), were not statistically significantly different between two groups.
CONCLUSIONS DCB-only is the same safety as DES in treating de novo coronary lesions in large vessels for patients with STEMI. DCB-only improve the LLL at 6–12 months follow-up compared to DES.
GW34-e1263
Gangzhen Qian, Zhihu Zhang
Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University
OBJECTIVES Although immediate and satisfactory revascularization of major epicardial arteries is applied, coronary microvascular diseases (CMVD) after ST-segment elevation myocardial infarction (STEMI) still affects the long-term outcomes of these patients. The index of microcirculatory resistance (IMR) is a feasible and effective tool to assess CMVD in patients suffered from STEMI, but the use of IMR in urgent conditions is limited because of its hyperemia-dependent nature. Recently, some computational flow dynamics indices have been reported to compensate these flaws. The wire-free, adenosine-free, and sensor-free angio-derived microcirculatory resistance (AMR) based on a single angiographic view was found to be a feasible alternative to the pressure wire and hyperemia-based IMR, but its prognostic value in STEMI population remains controversial. We investigated the prognostic potential of AMR as a wire/sensor-free and hyperemic agent-free tool in patients with STEMI.
METHODS Patients with STEMI who underwent successful percutaneous coronary intervention (PCI) were enrolled in this single-center, retrospective, observational study (n=232). AMR of the infarct-related artery (IRA) was calculated based on patients’ last coronary angiography before discharge on a machine-learning manner (together with μQFR). Follow-up was performed by outpatient visits or telephone contacts. The primary outcome was a composite of all-cause death or readmission for heart failure during our follow-up. The reproducibility of AMR is also tested.
RESULTS At a median follow-up of 1.7 years (interquartile range, 1.1–3.6 years), a primary end-point event (all-cause death or readmission for heart failure) had occurred in 26 patients in the high-AMR group and in 11 patients in the low-AMR group. Patients with STEMI with IRA’s AMR≥2.58 mmHg*s/cm showed a significantly higher risk for all-cause death or readmission for heart failure than did those with IRA’s AMR<2.58 mmHg*s/cm (hazard ratio, 2.317; 95% confidence interval, 1.216–4.413; P=0.0161). In addition to significantly increased risk for composite outcome, patients in high-AMR group showed significantly higher risk for readmission for heart failure alone than did those with patients in low-AMR group (P=0.027). Inter-operator reproducibility also showed a good correlation (r=0.72, P<0.0001).
CONCLUSIONS AMR measured after PCI can predict the risk of all-cause death or readmission for heart failure in patients with STEMI.
GW34-e1313
Galina Kukharchik, Daria Nedbaeva, Olga Sirotkina, Tatyana Vavilova
Almazov National Medical Research Centre
OBJECTIVES Acute coronary syndrome (ACS) is a high-risk condition, related to the activity of procoagulant mechanisms and platelets. From a clinical standpoint, elevated platelet activation and hypercoagulation may be associated with adverse cardiovascular events in patients with ACS. Routine coagulation and platelet tests may not allow a relevant characterization of the hemostatic balance. In contrast, thrombin generation assay (TGA) is a global assay that reflects the result of procoagulant and anticoagulant activities in blood. Platelet function testing plays an important role in determining responsiveness to antiplatelet therapy. The aim of the study was to assess the prognostic value of platelet reactivity and TGA.
METHODS We included 67 patients (mean age 65±10 years), admitted with unstable angina. All patients underwent standard platelet function test (impedance aggregometry with ADP and collagen) and thrombin generation assay (TGA) in platelet poor plasma. Control group included 29 healthy donors (40±14 years).
RESULTS We registered 6-months adverse cardiovascular outcomes (myocardial infarction and unstable angina) in 6 patients. High platelet reactivity was associated with adverse outcomes (the median value of platelet reactivity (ADP, 5 mkmol/L) in this group was 3 [2; 3, 5] vs 2 [2; 3]). TGA results in our study were not associated with prognosis. At the same time, we observed lower TGA results in patients with unstable angina comparing to control group: Peak thrombin: 159 [70; 211] nM vs 274 [213; 413] nM, VI: 29, 3±21, 9 nM/min vs 84, 7±43, 7 nM/min, ETP: 2203, 6 [1432, 7; 2618, 8] nM vs 2760, 8 [2639, 7; 3023, 4] nM, prolonged time to peak 9, 7 [8, 3; 11, 7] min vs 5, 9 [5, 1; 6, 6] min and prolonged Lag time: 3, 9 [3, 2; 5, 3] vs 2, 1 [1, 9; 2, 4] (P<0, 05). These results are most likely associated with the clinical stabilization (TGA was performed after revascularization when there was no substrate for thrombus formation). It may also indicate the effectiveness of antithrombotic therapy.
CONCLUSIONS Platelet function may be considered as prognostic biomarker, while TGA in our study did not show prognostic value. Both tests can be used to assess the effectiveness of treatment. However, given the limitations of the study, prospective follow-up and further studies are needed.
GW34-e1335
Hao-Yu Wang, Kefei Dou
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES The present study sought to determine the rate and prognostic implications of post-procedural physiologically significant residual ischemia according to Murray law-based quantitative flow ratio (μQFR) after left main (LM) bifurcation percutaneous coronary intervention (PCI).
METHODS Consecutive patients undergoing LM bifurcation stenting at a large tertiary care center between January 2014 and December 2016 with available post-PCI μQFR were included. Physiologically significant residual ischemia was defined by post-PCI μQFR values ≤0.80 in the left anterior descending (LAD) or circumflex artery (LCX). The primary outcome was 3-year cardiovascular death. The major secondary outcome was 3-year bifurcation oriented composite endpoint (BOCE).
RESULTS Among 1170 included patients with analyzable post-PCI μQFR, 155 (13.2%) had residual ischemia in either LAD or LCX. Patients with vs. those without residual ischemia had a higher risk of 3-year cardiovascular mortality (5.4 vs. 1.3%; adjusted hazard ratio [HR] 3.20, 95% confidence interval [CI]: 1.16–8.80). The 3-year risk of BOCE was significantly higher in the residual ischemia group (17.8 vs. 5.8%; adjusted HR 2.79, 95% CI: 1.68–4.64), driven by higher incidence of the composite of cardiovascular death and target bifurcation-related myocardial infarction (14.0 vs. 3.3%; adjusted HR 4.06, 95% CI: 2.22–7.42). A significant, inverse association was observed between continuous post-PCI μQFR and the risk of clinical outcomes (per 0.1 μQFR decrease, HR of cardiovascular death 1.27, 95% CI: 1.00–1.62; HR of BOCE 1.29, 95% CI: 1.14–1.47).
CONCLUSIONS After angiographically successful LM bifurcation PCI, residual ischemia assessed by μQFR was identified in 13.2% of patients and was associated with higher risk of 3-year cardiovascular death, indicating the superior prognostic value of post-PCI physiological assessment.
GW34-e1347
Haoyu Wang, Kefei Dou
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Functional complete revascularization (FCR) after percutaneous coronary intervention (PCI) as determined by the residual functional SYNTAX score (rFSS) based on pressure wire fractional flow reserve assessment has been associated with an improved prognosis. To determine the rates and clinical implications of FCR as assessed by the quantitative flow ratio (QFR), and to determine the outcomes of pre-PCI QFR guidance compared with standard angiography guidance in patients achieving and not achieving FCR after PCI.
METHODS In the randomized, sham-controlled, blinded, multicenter FAVOR III China trial, QFR-guided PCI reduced the 1-year rate of major adverse cardiac events (MACE) compared with angiography-guided PCI. In the present pre-specified sub-study, the incidence of MACE was compared according to the presence of post-PCI FCR (rFSS=0 based on core laboratory-assessed QFR) in the QFR-guided and angiography-guided groups.
RESULTS Among 3781 patients with available rFSS assessments, 3221 (85.2%) achieved FCR, including 88.1% after QFR guidance and 82.2% after angiography guidance (P<0.001). Patients with FCR had a markedly lower rate of 1-year MACE compared with those with functional incomplete revascularization (FIR; rFSS≥1) (5.1 vs. 19.7%, P<0.001). Prognostic models including the rFSS had higher discrimination and reclassification ability than those with the anatomic rSS. The relative risks for 1-year MACE with QFR-guided compared with the angiography-guided lesion selection were consistent in patients achieving FCR (4.1 vs. 6.3%; HR 0.65, 95% CI: 0.47–0.88) and in those with FIR (18.7 vs. 20.4%; HR 0.90, 95% CI: 0.61–1.32) (Pinteraction=0.19).
CONCLUSIONS In this large-scale trial, achieving FCR after PCI was associated with markedly lower 1-year rates of MACE. Compared with standard angiography guidance, QFR-guided PCI lesion selection improved the likelihood of achieving FCR and improved 1-year clinical outcomes in patients with both FCR and FIR. A QFR-guided lesion selection strategy for PCI is more likely to achieve physiologically precise (appropriate) vessel treatment and FCR, both of which contribute to greater 1-year event-free survival after QFR-guided PCI compared with angiography-guided PCI.
GW34-e1375
Haoyu Wang
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Numerous risk scores have been developed to predict adverse outcomes after ACS or percutaneous coronary intervention (PCI). The PRAISE score score is a machine-learning-based model for predicting 1-year all-cause death, myocardial infarction (MI), and BARC type 3/5 bleeding based on several large international cohorts. We aimed to validate the PRAISE score in a real-world Asian population.
METHODS A total of 6412 consecutive patients undergoing PCI for ACS were prospectively included from Fuwai PCI registry. We intended to validate the performance of the PRAISE score across all three endpoints: all-cause mortality, recurrent acute MI (AMI), and major bleeding one year after discharge. The PRAISE risk prediction model includes 25 variables, with clinical, anatomical, and procedural risk factors assessed at patient discharge; it displays accurate discriminative capabilities to predict patient prognosis after ACS. Patients were stratified into low-, medium-, and high-risk thresholds. The thresholds for low-, medium-, and high-risk stratification were 1.3% and 3.0% for all-cause mortality, 2.0% and 4.5% for MI, and 1.9% and 3.2% for major bleeding, respectively.
RESULTS The PRAISE scores were compared with established scoring systems (GRACE 2.0, PRECISE-DAPT, and PARIS) to evaluate their discrimination, calibration, and reclassification. The risk of all-cause mortality (HR: 12.24, 95% CI: 5.32–28.15), recurrent acute MI (HR: 3.92, 95% CI: 1.76–8.73), and major bleeding (0.6 vs. 0.2%, HR: 3.57, 95% CI: 1.09–11.69, P=0.036) were greater in the high-risk group than in the low-risk group. The C-statistics for death, MI and major bleeding were 0.75 (0.67–0.83), 0.61 (0.52–0.69), and 0.62 (0.46–0.77), respectively. The observed to expected (O: E) ratio of death, MI, and major bleeding were 0.427, 0.260, and 0.106, respectively. The Hosmer-Lemeshow GOF test P-values for all-cause mortality, recurrent AMI, and major bleeding were all <0.001. Compared with the GRACE score, the IDI of PRIASE score in predicting mortality was less than 0 (–0.0899, 95% CI: −0.1495 to −0.0304, P=0.003). The PRAISE score had a comparable discriminative capacity to other scores for MI and major bleeding in terms of IDI. Based on the decision curve analysis, the PRAISE score displayed a slightly greater net benefit for the 1-year risk of death (5–10%) than the GRACE score did. For instance, at a 6% 1-year death risk threshold, 0.6 in 1000 patients had a better net benefit when compared with the “treat none” strategy, 56.6 in 1000 patients would benefit when compared with the “treat all” scenario, and 0.6 in 1000 patients would benefit when compared with the GRACE score.
CONCLUSIONS The PRAISE score showed limited potential for risk prediction in our validation ACS cohort, as a result, new prediction models or model re-fitting are required with improved discrimination and accuracy in risk prediction. Although machine learning approaches enable the analysis of large data sets, identification of new associations, and improvement of previous prognostic models and diagnostic accuracy, its application in creating a new risk score, the PRAISE score, for stratification in patients with ACS is insufficient to translate into meaningful clinical changes, such as improved discrimination and accuracy in risk prediction.
GW34-e1376
Aizezi Aibibanmu1, Yitong Ma2
1Aibibanmu×Aizezi
2Ma-yitong
OBJECTIVES Triglyceride-glucose (TyG) index is a simple and sensitive alternative index of insulin resistance, which has been proven to predict cardiovascular outcomes in patients with coronary heart disease. The purpose of this study was to explore the predictive value of TyG index combined with SYNTAX score in adverse cardiovascular events after revascularization in patients with multi-vessel coronary artery disease (MVCD).
METHODS Clinical data and follow-up data of 2429 MVCD patients before and after operation were collected, and a retrospective cohort study was conducted. Use a Cox proportional risk regression model to estimate the relative risk ratio (HR) between the TyG index and SYNTAX score and cardiovascular adverse events, and explore the potential nonlinear relationship between the TyG index and cardiovascular adverse events using a restricted cubic bar graph (RCS). Randomly divide patients into a training group and a validation group in a 7:3 ratio. Use the Least Absolute Shrinkage Selection Operator (LASSO) regression model in the training set for variable selection and prediction feature construction. Use the C index, ROC curve, and calibration curve to verify the predictive value of the TyG index and SYNTAX score model for MACCEs events in patients in the training and validation set at 1, 3 and 5 years; The reclassification improvement index (NRI), comprehensive discriminant improvement index (IDI) and decision analysis curve analysis nomogram model were used to predict the efficacy and net income of MACCEs events in patients with training sets and verification sets 1, 3 and 5 years after surgery. The KM survival curve is used to verify the survival difference between high risk and low risk in the linear graph model score.
RESULTS After adjusting for potential confounding factors, the COX risk regression model showed that the TyG index and SYNTAX score were independent influencing factors for postoperative MACCE events in MVCD patients (HR=2.12, 95% CI: 1.81–2.49, HR=1.07, 95% CI: 1.06–1.09). Use LASSO regression to screen out seven variables and use them to generate a prognostic model and construct a Nomogram. In the training set, the combined model of TyG index and SYNTAX score outperformed other models in predicting MACCEs time in MVCD patients, such as C-index (0.848 vs. 0.872 vs. 0.887 vs. 0.895, P<0.001), and the same was true in the validation set, such as C-index (0.870 vs. 0.881 vs. 0.887 vs. 0.893, P<0.001). The AUCs for predicting MACCE events in patients at 1, 3, and 5 years after surgery in the training and testing sets were (78.4, 88.4, 86.6) and (75.3, 85.5, and 87.9), and the time-dependent AUC (>0.7) indicated satisfactory discriminative ability of the TyG index and SYNTAX score joint model. The combination model in the training set evaluated the NRI (0.073, P=0.003)/IDI (0.076, P=0.002) of postoperative MACCEs, and the NRI (0.034, P=0.247)/IDI (0.031, P=0.331) in the validation set. Furthermore, DCA showed that the TyG index and SYNTAX score joint model was clinically useful and had better discriminative ability to recognize patients at high risk than the other traditional risk factor models. The calibration plots showed favorable consistency between the prediction of the TyG index and SYNTAX score joint model in both the training and validation cohorts.
CONCLUSIONS The TyG index SYNTAX combination model shows excellent performance in predicting MACCEs events in patients with various vascular diseases in comparison to traditional risk factor models.
GW34-e1383
Aizezi Aibibanmu1, Yitong Ma2
1Aibibanmu×Aizezi
2Ma-yitong
OBJECTIVES Stress hyperglycemia is a powerful predictor of adverse outcomes in patients with acute myocardial infarction (AMI). However, the relationship between SHR and the morphology and characteristics of vulnerable plaques in patients with acute myocardial infarction (AMI) has not been fully studied.
METHODS Nine hundred and forty-six patients with acute myocardial infarction diagnosed in the First Affiliated Hospital of Xinjiang Medical University from January 2017 to January 2019 were included in the retrospective study. Optical coherence tomography was performed before intervention. All patients were divided into three groups according to the third quartile of SHR (SHR1, SHR2 and SHR3). Patients with plaque rupture (PR) and plaque erosion (PE) were divided into three groups across the SHR tertiles. Baseline clinical data and culprit plaque characteristics were compared between the three groups, and all patients were followed up for major adverse cardiovascular events (MACE) and all-cause mortality, MACEs were defned as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischaemic stroke.
RESULTS In fully adjusted analyses, the middle tertile of SHR was signifcantly associated with greater rates of MACEs in patients with PR but not in those with PE (SHR1, HR: 2.01, 95% CI: 1.25–1.88, P=0.015). Cox regression models indicated a signifcantly higher HR for MACEs in patients in the middle tertile of SHR than in those in the low tertile of SHR after full additional adjustment (HR: 2.31, 95% CI: 1.10–1.29, P=0.018). However, being in the high tertile of SHR independently and signifcantly increased the risk of major bleeding events among patients with PE (HR: 1.65, 95% CI: 1.21–1.65, P=0.016). The area under the receiver operating characteristic curve for predicting MACEs to evaluate the diagnostic value of the SHR index combined with the morphologica characteristics of plaque after full adjustment was 0.881 (sensitivity=81.74%, specifcity=78.04%, cut-of level=0.70). Kaplan–Meier curves were generated for the cumulative incidence of MACEs for up to a median of 2 years stratifed by tertiles of SHR among the PR and PE subgroups. Among patients with PR, there were signifcant diferences among the tertiles of SHR (P=0.015).
CONCLUSIONS Microstructural OCT features of culprit lesions in combination with the SHR, can be used in clinical practice to support risk stratifcation and predict adverse events in patients with STEMI.
GW34-e1386
Aizezi Aibibanmu1, Yitong Ma2
1Aibibanmu×Aizezi
2Ma-yitong
OBJECTIVES This study applied IVUS calculated by machine learning algorithm to explore the predictive effect of functional SYNTAX score calculated based on IVUS algorithm on the clinical prognosis of patients with three branches of disease.
METHODS Nine hundred and forty-six patients with coronary heart disease diagnosed by invasive coronary angiography (defined as three vessel stenosis>50%) from a single center were included retrospectively, excluding patients with previous revascularization, previous coronary occlusion and left main artery disease. Two independent clinicians calculated the SYNTAX score of the above patients, and according to the SYNTAX score, the patients were divided into low SS group (0~22, n=490), medium SS group (23~32, n=371) and high SS group (≥33, n=85). IVUS is calculated by machine learning algorithm, and the minimum lumen area of each diseased vessel is recorded. The SYNTAX score was calculated only for lesions with a minimum lumen area<4.0 mm2. The primary clinical endpoint mace was defined as a composite endpoint composed of all-cause death, nonfatal myocardial infarction and emergency revascularization.
RESULTS After calculating the IVUS threshold by machine learning, 8.4% (79/946) of the patients were reclassified to the low-risk group. During the median follow-up period of 24 months, the overall MACE rate of the study patients was 30.3%. Compared with the low SS group, the incidence of MACE in the medium and high SS group was significantly higher (18.0% (88/490) vs. 6.2% (23/371) vs. 85.9% (73/85), P<0.001). Meanwhile, ROC analysis showed that the SYNTAX score included in IVUS could better predict mace than that based on a single SYNTAX score (IVUS+SS: AUC: 0.72 vs. SS: AUC: 0.61, P=0.01).
CONCLUSIONS Using machine learning algorithm to calculate IVUS and apply it to SYNTAX score calculation is a better predictor of mace incidence in patients with three vessel lesions. It was found that compared with the traditional SYNTAX score, it can better predict the occurrence of MACE events, and may change the revascularization strategy of these patients.
GW34-e1408
Haoyu Wang
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Functional complete revascularization (FCR) after percutaneous coronary intervention (PCI) as determined by the residual functional SYNTAX score (rFSS) based on pressure wire fractional flow reserve assessment has been associated with an improved prognosis. We aimed to determine the rates and clinical implications of FCR as assessed by the quantitative flow ratio (QFR), and to determine the outcomes of pre-PCI QFR guidance compared with standard angiography guidance in patients achieving and not achieving FCR after PCI.
METHODS In the randomized, sham-controlled, blinded, multicenter FAVOR III China trial, QFR-guided PCI reduced the 1-year rate of major adverse cardiac events (MACE) compared with angiography-guided PCI. In the present pre-specified sub-study, the incidence of MACE was compared according to the presence of post-PCI FCR (rFSS=0 based on core laboratory-assessed QFR) in the QFR-guided and angiography-guided groups.
RESULTS Among 3781 patients with available rFSS assessments, 3,221 (85.2%) achieved FCR, including 88.1% after QFR guidance and 82.2% after angiography guidance (P<0.001). Patients with FCR had a markedly lower rate of 1-year MACE compared with those with functional incomplete revascularization (FIR; rFSS ≥1) (5.1 vs. 19.7%, P<0.001). Prognostic models including the rFSS had higher discrimination and reclassification ability than those with the anatomic rSS. The relative risks for 1-year MACE with QFR-guided compared with the angiography-guided lesion selection were consistent in patients achieving FCR (4.1 vs. 6.3%; HR 0.65, 95% CI: 0.47–0.88) and in those with FIR (18.7 vs. 20.4%; HR 0.90, 95% CI: 0.61–1.32) (Pinteraction=0.19).
CONCLUSIONS In this large-scale trial, achieving FCR after PCI was associated with markedly lower 1-year rates of MACE. Compared with standard angiography guidance, QFR-guided PCI lesion selection improved the likelihood of achieving FCR and improved 1-year clinical outcomes in patients with both FCR and FIR.
GW34-e1409
Haoyu Wang, Kefei Dou
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) for left main coronary artery disease (LMCAD) may be particularly deleterious in patients with recent myocardial infarction (MI). We sought to determine the rates and prognostic relevance of PMI using different definitions and biomarker thresholds after PCI for LMCAD in patients with recent MI.
METHODS Between January 2004 and December 2016, 442 patients underwent PCI for LMCAD at a median of 3 days after presentation with MI. A total of 350 patients presented with elevated cardiac biomarker levels (349 with serial creatine kinase–myocardial band [CK-MB] and 219 with serial cardiac troponin I (cTnI) values) that were stable or falling before the PCI. In this cohort, PMI within 48 hours of PCI was adjudicated using Society for Cardiovascular Angiography & Interventions (SCAI), Academic Research Consortium 2 (ARC-2), and fourth Universal Definition of Myocardial Infarction (UDMI) criteria. The primary and secondary end points were 3-year rates of cardiovascular (CV) and all-cause death.
RESULTS An incremental post-PCI rise in CK-MB starting at ≥10×URL from baseline was significantly associated with 3-year CV death (adjusted hazard ratio [aHR]: 7.96; 95% confidence interval [CI]: 2.89–21.90), whereas CV death was not associated with any threshold elevation of cTnI. The frequencies of PMI according to the fourth UDMI, ARC-2, and SCAI definitions were 19.4%, 12.3%, and 8.6%, respectively. PMI by all 3 definitions was significantly associated with 3-year CV death, with SCAI having the strongest relationship (aHR: 6.34; 95% CI: 2.47–16.27) compared with ARC-2 (aHR: 2.82; 95% CI: 1.15–6.96) and fourth UDMI (aHR: 2.65; 95% CI: 1.14–6.14).
CONCLUSIONS In patients with recent MI undergoing PCI for LMCAD, an incremental elevation in post-procedural CK-MB ≥10×URL as a stand-alone measure was strongly predictive of 3-year CV and all-cause death, whereas no cTnI elevations of any level were prognostic. All three contemporary PMI definitions in widespread use were associated with 3-year mortality after PCI in this high-risk cohort. The SCAI definition was most strongly related to early and late mortality, and the subset of SCAI PMI events largely explained the prognostic correlations from PMI definitions also incorporating lesser degrees of myonecrosis. These findings may inform prognostic guidance for clinical care pathways and the use and interpretation of endpoints in comparative randomized trials.
GW34-e1414
Bayi Xu
Department of Cardiology, the First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
OBJECTIVES This study aims to establish a machine learning (ML)-aided risk stratification system to rank the risk factors of ischemic heart disease (IHD) in southern Chinese and further explore the potential molecular mechanisms through ML and weighted gene co-expression network analysis (WGCNA).
METHODS A total of 7089 patients with angiographic IHD were included, consisting of 1829 acute myocardial infarction (AMI), 3559 newly diagnosed coronary artery disease (NCAD), and 1701 previously diagnosed CAD (PCAD), as well as 1239 controls. Twenty-five easily obtained and noninvasive variables (including demographics and clinical data) were collected for analysis. The risk factors of IHD were identified using univariate analysis and then multivariate logistic regression (LR) analysis. Combined with the significant risk factors selected by LR, eight ML models were used to identify individuals with IHD and predict risk. The best-performing model was then used to rank the importance of risk factors. Additionally, ML, WGCNA, and immune infiltration analysis were used to reveal the potential co-pathophysiological association between AMI and type 2 diabetes mellitus (T2DM).
RESULTS Age, male sex, smoking, hypertension, T2DM, fasting blood glucose (FBG), hemoglobin A1c (HbAlc), hyperlipidemia, hyperuricemia, and hyperhomocysteinemia were identified as the main risk factors of IHD in southern Chinese. Among the eight ML algorithms, random forest exhibited the best performance, and the ranking of variable importance showed that FBG or HbAlc was the top-ranked modifiable risk factor for AMI, NCAD, and PCAD, accounting for 18–23% of the variables’ importance. The ML, WGCNA, and immune infiltration analysis indicated that chronic inflammation and immune response may be the fundamental pathology of T2DM-related AMI. The implicated genes may be FOSL2, MAP3K8, THBS1, ZFP36, and IGFBP7, and the associated immune cells may be monocytes, activated mast cells, eosinophils, and neutrophils.
CONCLUSIONS FBG/HbAlc was the most important modifiable risk factor for IHD in southern Chinese populations, and its underlying molecular mechanism may be chronic inflammation and immune response. Machine learning and WGCNA were found to be efficient tools in identifying crucial risk factors and genes of IHD, providing a time-saving and economical option for preventing and intervening in IHD.
HYPERTENSION
GW34-e0027
Chuanwei Li1, Jun Xiao1, Chunyu Zeng2
1Department of Cardiology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing University
2Department of Cardiology, Daping Hospital, The Third Military Medical University (Army Medical University)
OBJECTIVES The occurrence and severity of radial-related vascular complications (VCs) were significantly lower than the femoral access, but their happen still worse the clinical outcome. However, data regarding the predictors of radial access site complications are limited. The aim of the study was to investigate the predictors of VC occurrence in the era of transradial access.
METHODS We conducted a retrospective case-control study who underwent the percutaneous coronary diagnostical or therapeutical study in Daping hospital according to the including and exclusion criteria. The demographic characteristics, VC types, ankle brachial index and coronary artery stenosis severity were compared between the two groups.
RESULTS We enrolled 300 subjects with VCs and 300 age- and sex-matched subjects without VCs as control. There were no differences in the baseline characteristics or comorbidities between the groups. Compared to the control group, the VC group have a higher portion of left radial access (6.0%) and previous radial artery puncture history (29.7 vs. 18.3%, P=0.001). The ABI was significantly lower than the non-VC group (1.17±0.17 vs. 1.2±0.14, P=0.000). In multivariate logistical regression analysis, ABI (OR=0.060 95% CI: 0.014–0.249, P=0.000), procedure performed by junior operators (OR=1.892, 95% CI: 1.314–2.745, P=0.001) and previous access on the same radial artery (OR=1.795, 95% CI: 1.190–2.707, P=0.005) were found independently associated with the VC occurrence.
CONCLUSIONS Patients with lower ABI and history of previous radial access carry a higher risk of radial access VC. Routine ABI measurement before the procedures may predict the VC risk.
GW34-e0032
Xintian Cai
Xinjiang Medical University
OBJECTIVES The purpose of this study was to investigate the relationship between the sarcopenia index (SI) and stroke risk in elderly patients with hypertension.
METHODS This study included 5145 stroke-free elderly hypertensive patients. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident stroke.
RESULTS Over a median follow-up of 38 months, we identified 607 (11.80%) individuals with total stroke, of whom 507 (9.85%) had ischemic stroke and 93 (1.81%) had hemorrhagic stroke. The risk of developing stroke decreased with each quartile of SI; after adjustment for multiple confounders, the HRs for the Q4 group versus the Q1 group were 0.46 (95% CI, 0.35–0.59) for total stroke, 0.46 (95% CI, 0.35–0.61) for ischemic stroke, and 0.33 (95% CI, 0.17–0.64) for hemorrhagic stroke. Restricted cubic spline analysis also demonstrated a cumulative increase in the risk of total stroke with decreases in the SI. The addition of SI to the conventional model for total stroke improved (Δ C-statistics=0.02), an integrated discrimination improvement of 0.03 (95% CI, 0.02–0.04), and a net reclassification improvement of 0.17 (95% CI, 0.10–0.23). Similar results were observed for ischemic stroke and hemorrhagic stroke.
CONCLUSIONS This study found that elevated SI was negatively associated with the risk of stroke in elderly patients with hypertension. Uncovering the causality behind the relationship requires further prospective study.
GW34-e0062
Congcong Ding, Xiao Huang, Huihui Bao, Xiaoshu Cheng
The Second Affiliated Hospital of Nanchang University
OBJECTIVES Total homocysteine (tHcy) and kidney function are both associated with the risk of mortality, but the degree to which kidney function modifies the impact of tHcy on mortality remains unknown. This study aimed to investigate whether and to what extent kidney function mediates the association of tHcy with mortality, and whether tHcy and kidney function jointly contribute to the risk of all-cause and cause-specific mortality in hypertensive patients.
METHODS This prospective cohort study included a total of 14,225 hypertensive adults (mean age 63.8 years; 47.2% male) from the China H-type Hypertension Registry Study. Mediation analysis was conducted to explore the mediating effects of kidney function evaluated by estimated glomerular filtration rate (eGFR) on the association between tHcy and mortality. Cox proportional hazard regression was used to analyze the separate and combined association of tHcy and eGFR with all-cause and cause-specific mortality.
RESULTS During a median follow-up of 4.0 years, 805 deaths were identified, including 397 deaths from cardiovascular disease (CVD). There were significant, positive relationships of plasma tHcy with all-cause mortality (per 5 μmol/L; HR: 1.09; 95% CI: 1.07, 1.11), CVD mortality (HR: 1.11; 95% CI: 1.08, 1.13), and non-CVD mortality (HR: 1.07; 95% CI: 1.04, 1.10). After adjustment for eGFR, these relationships were substantially attenuated but remained significant. The proportions of eGFR mediating these relationships were 39.1%, 35.7%, and 49.7%, respectively. There were additive interactions between tHcy and eGFR. Compared with those with low tHcy (<15 μmol/L) and high eGFR (≥90 mL·min−1·1.73 m−2), participants with high tHcy (≥20 μmol/L) and low eGFR (<60 mL·min−1·1.73 m−2) had the highest risk of all-cause mortality (HR: 4.89; 95% CI: 3.81, 6.28), CVD mortality (HR: 5.80; 95% CI: 4.01, 8.40), and non-CVD mortality (HR: 4.25; 95% CI: 3.02, 5.97).
CONCLUSIONS Among Chinese hypertensive adults, high tHcy and impaired kidney function were independently and jointly associated with higher risks of all-cause and cause-specific mortality. Kidney function explained most (nearly 40%) of the increased risk of mortality conferred by high tHcy. The simultaneous detection and control of tHcy and renal function have important implications as an intervention strategy for healthy aging in patients with hypertension.
GW34-e0152
Zhoufei Fang1,2,3,4,5,6
1Department of Cardiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China
2Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China
3Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
4Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
5Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fujian Province, Fuzhou, People’s Republic of China
6The First Clinical Medical College of Fujian Medical University
OBJECTIVES Renal Artery Sympathetic Denervation (RDN) can reduce blood pressure. However, different studies used different ablation catheters (single electrode, multi-electrode), and the scope of ablation was also different (renal artery trunk and branches). There are few studies comparing the superiority and inferiority of different ablation catheters and different procedures in terms of antihypertensive efficacy.
METHODS Fifty-three patients with RHT were divided into a spiral multi-electrode radiofrequency ablation group (SMRA, n=28) and a 3D reconstruction radiofrequency ablation group (3DRA, n=25). SMRA group used a stereospiral multi-electrode ablation catheter with a controlled ablation temperature of 60°C and an ablation time of 120 seconds per site. 3DRA group used a NavStar pressure-monitored perfusion monopolar ablation catheter with a controlled ablation temperature of 40°C, an ablation time of 40 seconds per site, and an ablation energy of 12W. Baseline, RDN parameters and complications were compared between the two groups. Home blood pressure, 24h-ambulatory blood pressure, type of anti-hypertensive drugs taken and serum creatinine were followed up at 1 month, 3 months, 6 months, 12 months and 24 months after the RDN procedure, respectively.
RESULTS There were no differences in baseline characteristics between the two groups. 23.14±2.00 months of follow-up in SMRA group with a total of 25.86±8.61 loci ablated. 19.28±7.40 months of follow-up in 3DRA group with a total of 21.04±6.47 loci ablated. Home SBP was significantly lower in both groups at 1 month after RDN treatment compared to baseline. The proportion of people with 24h ambulatory SBP attainment was significantly higher in both groups and was maintained for 24 months. There were no differences in home and 24h ambulatory SBP, DBP, and Scr between the two groups at each follow-up time point. Two cases of severe renal artery complications with implanted vascular stents and 1 case of femoral artery pseudoaneurysm were seen in the 3DRA group. At follow-up, 1 (1.9%) patient died of unexplained death and 1 (1.9%) patient developed heart failure in 3DRA group and 1 (1.9%) patient died of unexplained death in SMRA group.
CONCLUSIONS Spiral multi-electrode radiofrequency ablation and 3D reconstruction radiofrequency ablation of the renal artery applied to RDN have comparable efficacy in lowering systolic blood pressure and have enough safety.
GW34-e0165
Rong Cao1,2, Gang Sun2, Xiaomin Yang3
1Graduate School of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China
2Research Institute of Hypertension, Department of Cardiovascular Medicine, The Second Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, China
3General Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Zhejiang, China
OBJECTIVES Ambulatory arterial stiffness index (AASI), a surrogate marker of arterial stiffness derived from ambulatory blood pressure (BP), which is calculated as 1 minus the linear slope of diastolic BP on systolic BP. Our study aim was to investigate the association between AASI and BP variation parameters, evaluated by both circadian rhythms and 24h weighted coefficient of variation (wCoV) in a population of normotension, untreated hypertension, controlled hypertension, uncontrolled hypertension, white coat hypertension and white coat uncontrolled hypertension.
METHODS This study was conducted in the Hypertension Research Institute of the Second Affiliated Hospital of Baotou Medical College, Inner Mongolia, China, between October 2021 and October 2022. Six hundred and ten subjects (48.7% female, age 60.9±13.2 years), who underwent 24h ambulatory blood pressure monitoring were included.
RESULTS AASI was significantly higher in reverse-dipping than other dipping patterns, both in systolic and diastolic BP (P<.05). Univariate analysis showed 24h wCoV in diastolic BP were closely correlated to AASI (P<.05). AASI values increased with the age, both in female and male; When taking dipping pattern in systolic BP as reference groups, reverse-dipping pattern (coef=0.039, 95% Cl 0.001~0.077, P=.04) was associated with AASI; Taking dipping pattern in diastolic BP as reference groups, reverse-dipping (coef=0.065, 95% Cl 0.029~0.1, P<.001) and extreme-dipping patterns (coef=−0.08, 95% Cl −0.142 to −0.018, P=.01) were associated with AASI. In a multiple linear regression analysis, circadian rhythms and 24h wCoV in diastolic BP were independently associated with AASI after adjusted for multiple confounders (β=−0.003, 95% Cl −0.004 to −0.001, P<.001; β=−1.86, 95% Cl −2.28 to −1.44, P<.001); the association between circadian rhythms and AASI were consistent across subgroups defined according to age, sex, BP phenotypes, smoking status, and white coat effect (P for interaction all>0.05).
CONCLUSIONS In subjects of different BP phenotypes, AASI was significantly associated with circadian rhythms and 24h wCoV.
GW34-e0166
Rong Cao1,2, Gang Sun2, Xiaomin Yang3
1Graduate School of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China
2Research Institute of Hypertension, Department of Cardiovascular Medicine, The Second Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, China
3General Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Zhejiang, China
OBJECTIVES Ambulatory arterial stiffness index (AASI), a surrogate marker of arterial stiffness derived from ambulatory blood pressure (BP), which is calculated as 1 minus the linear slope of diastolic BP on systolic BP. Our study aim was to investigate the association between AASI and BP variation parameters, evaluated by both circadian rhythms and 24h weighted coefficient of variation (wCoV) in a population of normotension, untreated hypertension, controlled hypertension, uncontrolled hypertension, white coat hypertension and white coat uncontrolled hypertension.
METHODS This study was conducted in the Hypertension Research Institute of the Second Affiliated Hospital of Baotou Medical College, Inner Mongolia, China, between October 2021 and October 2022. Six hundred and ten subjects (48.7% female, age 60.9±13.2 years), who underwent 24h ambulatory blood pressure monitoring were included.
RESULTS AASI was significantly higher in reverse-dipping than other dipping patterns, both in systolic and diastolic BP (P<.05). Univariate analysis showed 24h wCoV in diastolic BP were closely correlated to AASI (P<.05). AASI values increased with the age, both in female and male; When taking dipping pattern in systolic BP as reference groups, reverse-dipping pattern (coef=0.039, 95% Cl 0.001~0.077, P=.04) was associated with AASI; Taking dipping pattern in diastolic BP as reference groups, reverse-dipping (coef=0.065, 95% Cl 0.029~0.1, P<.001) and extreme-dipping patterns (coef=−0.08, 95% Cl −0.142~−0.018, P=.01) were associated with AASI. In a multiple linear regression analysis, circadian rhythms and 24h wCoV in diastolic BP were independently associated with AASI after adjusted for multiple confounders (β=−0.003, 95% Cl −0.004~−0.001, P<.001; β=−1.86, 95% Cl −2.28~−1.44, P<.001); the association between circadian rhythms and AASI were consistent across subgroups defined according to age, sex, BP phenotypes, smoking status, and white coat effect (P for interaction all>0.05).
CONCLUSIONS In subjects of different BP phenotypes, AASI was significantly associated with circadian rhythms and 24h wCoV.
GW34-e0198
Yan Yang, Pingjin Gao
Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
OBJECTIVES The impact of blood pressure (BP) control and its timing on left ventricular (LV) structure and function remains unclear. The present study was to evaluate whether BP control correlated with conventional LV geometry and function indexes or global longitudinal strain (GLS) progression, and when echocardiographic changes would occur in essential hypertension.
METHODS A total of 62 participants (mean age 55.2±11.5, male 71.0%) with uncontrolled hypertension were enrolled in the longitudinal study. Patients were followed up at the 6-month and 18-month, when echocardiographic measurements were performed and BP control was evaluated during the follow up period.
RESULTS At the 6- and 18-month examination, we divided the hypertensive patients into two groups as BP controlled and uncontrolled group. Patients with BP uncontrolled (n=33) had higher LV mass index (118.5±35.2 vs. 99.2±25.0, P=0.02), higher left atrial volume index (27.6±4.7 vs. 24.8±4.1, P=0.01), worse GLS (−18.2±2.4 vs. −20.0±2.5, P=0.005) and GLS changes (1.1±2.9 vs. −0.9±2.0, P=0.003) compared with controlled BP (n=29) at the 6-month follow-up examination. Patients with uncontrolled BP (n=25) had higher LV mass index (125.8±27.8 vs. 101.4±21.7, P=0.001), higher LV mass index changes (5.6±14.0 vs. −4.3±13.0, P=0.01), higher relative wall thickness (0.45±0.07 vs. 0.41±0.05, P=0.01), higher E/e’ (11.6±3.7 vs. 9.7±2.8, P=0.046), worse GLS (–18.8±3.5 vs. −20.1±3.1, P=0.02) and GLS changes (0.9±2.5 vs. −0.6±2.0, P=0.02) compared to BP controlled group (n=24) at the 18-month follow-up examination. GLS changes were associated with BP control (β=0.370, P=0.004 at the 6-month examination and β=0.324, P=0.02 at the 18-month examination, respectively) in stepwise multivariate regression analysis. LV mass index changes was corelated with systolic BP (β=0.426, P=0.003) at the 18-month follow-up examination in stepwise multivariate regression analysis. Neither was GLS changes nor LV mass index changes were related to antihypertensive medication class, including combination therapy in 6- or18-month follow up examination.
CONCLUSIONS Our findings offer new clinical evidence on the association of BP control with echocardiographic changes in hypertensive patients, and, in particular, support the view that GLS progression was earlier and subtler than conventional LV geometry and function parameters. GLS changes were significant between BP controlled and uncontrolled patients even in 6-month follow-up period.
GW34-e0256
Congcong Ding1, Tianyu Cao2, Xiaoshu Cheng1, Xiao Huang1
1The Second Affiliated Hospital of Nanchang University
2University of California Santa Barbara
OBJECTIVES It is unclear whether central systolic blood pressure (cSBP) is an independent predictor of stroke above and beyond brachial systolic blood pressure (bSBP). This study aimed to investigate the difference between cSBP and bSBP in predicting first stroke and the joint effect of cSBP and bSBP on the risk of first stroke in hypertensive adults.
METHODS A total of 8122 hypertensive adults without stroke history were included in this study. cSBP was measured noninvasively using A-Pulse CASPro device. The outcome were first stroke (overall and subtypes).
RESULTS During a median follow-up of 4.4 years, 579 first stroke were identified. The per SD increment of cSBP (HR: 1.16, 95% CI: 1.07, 1.26) and bSBP (HR: 1.16, 95% CI: 1.07, 1.26) was significantly associated with higher risk of first stroke. The differences in areas under the curves, continuous net reclassification indices, and integrated discrimination indices of bSBP and cSBP models for predicting first stroke were 0.003 (95% CI: −0.003, 0.008), 0.007 (95% CI: −0.058, 0.071), and −0.0002 (95% CI: −0.0028, 0.0013), respectively. When cSBP and bSBP were evaluated jointly, participants in the highest tertiles of both cSBP and bSBP had the highest risk of first stroke compared with their counterparts (HR: 1.59, 95% CI: 1.29, 1.96; P-interaction=0.034). Similar results were found for ischemic stroke and hemorrhagic stroke.
CONCLUSIONS Although cSBP was not found to be superior to bSBP in predicting first stroke, cSBP and bSBP were jointly associated with the risk of first stroke among hypertensive adults.
GW34-e0341
Jin-Yu Sun, Yang Hua, Wei Sun, Xiang-Qing Kong
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University
OBJECTIVES This study aims to investigate the cross-sectional and longitudinal association between waist circumference and hypertension using nationally representative samples.
METHODS We included a total of 36776 participants from the China Health and Nutrition Survey (CHNS), the China Health and Retirement Longitudinal Study (CHARLS), and the National Health and Nutrition Examination Survey (NHANES). Participants were grouped based on their baseline hypertension status, and we compared differences in waist circumference, body mass index (BMI), and cardiovascular metabolic profiles between the groups. We used Pearson correlation to analyze the correlation coefficient between waist circumference and systolic/diastolic blood pressure, and logistic regression to evaluate the cross-sectional association between waist circumference and hypertension. We represented the effect size using odds ratios (OR) and 95% confidence intervals (CI). For the longitudinal analysis, we included a total of 9429 baseline normotensive individuals with follow-up data from the CHNS and CHARLS surveys. We compared the incidence of hypertension, BMI, and cardiovascular metabolic profiles between groups categorized by waist circumference quartiles. We analyzed time-dependent changes in the incidence of hypertension among individuals with different waist circumferences using the Kaplan-Meier method. We used Cox regression to evaluate the association between waist circumference and new-onset hypertension, represented by hazard ratios (HR) and 95% CI. We used restricted cubic spline to evaluate the dose-response relationship between continuous changes in waist circumference and the incidence of hypertension. Finally, we conducted subgroup analyses based on Cox regression for different BMI and gender groups.
RESULTS The baseline hypertension group showed significantly higher BMI, waist circumference, and prevalence of abdominal obesity than the non-hypertension group. There was a significant correlation between waist circumference and systolic/diastolic blood pressure (Pearson test P<0.01). Logistic regression showed that waist circumference was significantly associated with hypertension with ORs (95% CI) for CHNS, CHARLS, and NHANES surveys of 1.30 (1.19~1.42), 1.44 (1.35~1.53), and 1.22 (1.13~1.33), when adjusting for age, gender, education level, and BMI. The average follow-up time for baseline normotensive participants in the CHNS and CHARLS was 3.8 years, and a total of 2592 (27.5%) new-onset hypertension occurred. Cox regression showed that when adjusting for age, gender, education level, and BMI, the HRs (95% CI) for CHNS and CHARLS were 1.13 (1.03~1.24) and 1.22 (1.13~1.32), respectively. In the pooled analysis, the Cox regression showed that every 10 cm increase in waist circumference will increase the risk of hypertension by 21% (95% CI=14~28%). Restricted cubic splines showed a significant linear dose-response relationship between waist circumference and the incidence of hypertension. Subgroup analysis suggested that the correlation between waist circumference and the incidence of hypertension remained in individuals with normal BMI.
CONCLUSIONS High waist circumference is an independent risk factor for hypertension. Every 10 cm increase in waist circumference is estimated to increase the risk of hypertension by 21%. Even in individuals with normal BMI, high waist circumference still poses a risk for the development of hypertension. This study clarifies the cross-sectional and longitudinal correlation between waist circumference and hypertension and provides evidence for the routine measurement of waist circumference in clinical practice.
GW34-e0347
Yumeng Shi, Chao Yu, Tao Wang, Lingjuan Zhu, Wei Zhou, Huihui Bao, Xiaoshu Cheng
The Second Affiliated Hospital of Nanchang University
OBJECTIVES The triglyceride–glucose (TyG) index is associated with chronic kidney disease (CKD); however, the impact of TyG index variations on CKD progression remains unexplored. To investigate the effects of the TyG index and its dynamic changes on CKD progression.
METHODS This prospective cohort study included data from 8418 hypertensive participants of the China H-type Hypertension Registry, a prospective observational study conducted in Wuyuan, Jiangxi Province, People’s Republic of China, that reflects real-world conditions. The exposure variable in this study was defined as the difference between the TyG index at the last visit from that at baseline as: TyG=ln[triglyceride (mg/dL) × FPG (mg/dL)/2]. The study’s outcome variable was the progression of CKD, defined as follows: for subjects with an estimated glomerular filtration rate (eGFR) ≥60 mL/min, a ≥30% decrease in eGFR with a final follow-up value <60 mL/min; for those with an eGFR <60 mL/min, a ≥50% decrease in eGFR; or terminal renal failure requiring dialysis.
RESULTS In this cohort of 8418 hypertensive patients (age, mean±SD, 63.08±8.65 years), 46.71% were male. During a mean follow-up period of 48 months, 1077 patients were diagnosed with CKD progression. In the stepwise adjusted model, the TyG index was significantly associated with CKD progression. The hazard ratio (HR [95% CI]) for each additional unit of change in the TyG index was 1.17 (1.09–1.26), 1.15 (1.07–1.24), and 1.11 (1.03–1.20) in Models 1, 2, and 3, respectively. In the fully adjusted Model 3, patients with a TyG index <0 exhibited a significantly decreased 13% risk of CKD progression (HR: 0.87, 95% CI: 0.76–0.98) compared to those in the TyG≥0 group. Subgroup analyses showed that changes in the TyG index significantly increased the risk of CKD progression only in patients with DBP <90 mmHg.
CONCLUSIONS Our findings suggest that TyG variability may serve as a useful tool for identifying individuals at risk of CKD progression, particularly hypertensive patients with normal DBP levels. Therefore, the TyG index, a simple and cost-effective biomarker, has significant implications in clinical practice and public health policy for the prevention of CKD progression and CKD-associated complications.
GW34-e0350
Qianhui Wang
Xinjiang Medical University
OBJECTIVES This study aimed to investigate the correlation between serum Klotho protein concentration and hypertension in postmenopausal women.
METHODS A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016, with a total of 1713 postmenopausal women included. Multivariate logistic regression models were used to assess the association between serum Klotho concentration and hypertension in this population.
RESULTS Weighted analysis revealed a notable hypertension prevalecne rate of 53.44% in the study participants. Those in the lower quartile of serum Klotho concentration had a higher prevalence of hypertension than those in higher quartiles (Q1: 62.29% vs. Q2: 47.33% vs. Q3: 47.33% vs. Q4: 55.02, P<0.001). Furthermore, multivariate logistic regression analysis confirmed that a higher quartile of serum Klotho concentration was significantly associated with a reduced risk of postmenopausal hypertension when compared to those in the lowest quartile. Consistent findings were observed in subgroup analysis of individuals aged>65 years, obesity, nonsmokers, individuals without diabetes and coronary heart disease, and those with higher levels of estradiol and estimated glomerular filitration rate. These results suggest that there is a significant association between serum Klotho concentration and postmenopausal hypertension.
CONCLUSIONS The present study demonstrated a significant inverse correlation between serum Klotho concentration and hypertension among postmenopausal women. As such, serum Klotho concentration may serve as a valuable biomarker for risk stratification in this population at risk of developing hypertension.
GW34-e0369
Qianhui Wang
Xinjiang Medical University
OBJECTIVES The well-established association between insulin resistance (IR) and hypertension has led to the use of triglyceride glucose-body mass index (TyG-BMI) as a readily avaliable and effective indicator of IR in clinical settings. The objective of this study is to explore the correlation between TyG-BMI and hypertension in postmenopausal women.
METHODS In this study, we conducted a cross-sectional analysis of 2183 postmenopausal women participants from the National Health and Nutrition Examination Survey (NHANES) 2013–2016. We utilized logistic regression models to examine the association between TyG-BMI and postmenopausal hypertension, adjusting for various confounding factors. Furthermore, to explore the possible dose-response relationship, we employed multivariate adjusted restricted cubic spline (RCS) analysis. Additionally, receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of TyG-BMI for postmenopausal hypertension.
RESULTS The overall weighted prevalence of hypertension was 58.02%, and participants in the highest quartile of TyG-BMI had significantly higher rate than that in other quartiles (Q1: 45.13% vs. Q2: 57.96% vs. Q3: 60.13% vs. Q4: 73.19%, P<0.001). After fully adjusting for potential confounding factors, participants in the Q4 group had over a threefold risk of hypertension compared to the Q1 group (OR: 3.26, 95% CI: 1.83–5.80, P<0.001). RCS analysis revealed a significant non-linear dose-response association between TyG-BMI and postmenopausal hypertension. ROC curve demonstrated significant diagnostic value of TyG-BMI for postmenopausal hypertension, with an area under curve (AUC) of 0.60 (95% CI: 0.58–0.63, P<0.001). The calculated cut-off point was found to be 225.90, with sensitivity and specificity value of 76.69% and 39.04%, respectively. Subgroup analysis demonstrated that postmenopausal women who were younger (<60 years), never smoking, and displayed an e-GFR>90 mL/min/1.73 m2 in the Q4 group had significantly higher hypertension risk compared their counterparts in the Q1 group (P for interaction <0.05).
CONCLUSIONS In a large-scale population of postmenopausal women in the US, it has been determined that TyG-BMI is positively associated with hypertension. TyG-BMI may serve as a clinically useful tool for identifying individuals with an elevated risk of developing hypertension among postmenopausal women.
GW34-e0815
Tao Liu, Xiexiong Zhao, Weihong Jiang
The Third Xiangya Hospital, Central South University, Changsha, China (Mainland)
OBJECTIVES Doctor-patient communication, as well as medication adherence, are of great significance for blood pressure control in hypertensive patients. This study aims to investigate the current status of doctor-patient communication and medication adherence among hypertensive patients, explore the effect of doctor-patient communication on blood pressure control, and clarify the role of medication adherence in the effect of doctor-patient communication on blood pressure control.
METHODS Five hundred and forty-six hypertensive patients were selected from randomly chosen 10 community hospitals using convenience sampling method. Face-to-face interviews were conducted using the Set Elicit Give Understand End framework (SEGUE), self-made questionnaires and Morisky Medication Adherence Scale-8 (MMAS-8) to assess doctor-patient communication, hypertension-related communication content and medication adherence, respectively. The status quo of doctor-patient communication and medication adherence were described. Doctor-patient communication was considered “good” if the total score of SEGUE was ≥80, medication adherence was considered “good” if the total score of MMAS-was >6, and good blood pressure control was evaluated with blood pressure<140/90 mmHg. Using binary logistic regression to analyze the effect of doctor-patient communication on blood pressure control, stepwise regression was to used to delineate the role of medication adherence in the effect of doctor-patient communication on blood pressure control.
RESULTS (1) The current state of doctor-patient communication, the average score of SEGUE framework was 68.80±16.17, and 70.7% of the patients had poor doctor-patient communication. BMI<28 Kg/m2 (P<0.001), shorter hypertension course (P=0.045), fewer types of antihypertensive drugs (P=0.005), higher education level (P<0.001) and higher monthly income (P<0.001) were associated with better doctor-patient communication. The hypertension-related communication content between doctors and hypertensive patients has been judged to be inadequate and imperfect. (2) The current state of medication adherence, the median number of MMAS-8 score was 6.00 (IQR: 4.50–8.00), and the proportion of patients with poor medication adherence was 52.7%. Female (P=0.003), fewer types of antihypertensive drugs (P<0.001), higher educational level (P<0.001) and higher monthly income (P<0.001) were associated with better medication adherence. (3) The effect of doctor-patient communication on blood pressure control, the average SBP of patients with good doctor-patient communication was 135.39±13.16 mmHg, while the average SBP of patients with poor doctor-patient communication was 153.89±18.39 mmHg (P<0.001). The average DBP of patients with good doctor-patient communication is 80.53±9.75 mmHg, while the average DBP of patients with poor doctor-patient communication is 86.84±9.86 mmHg (P<0.001). The blood pressure control rate of patients with good doctor-patient communication is 62.5%, while the blood pressure control rate of patients with poor doctor-patient communication is 21.2%. Both univariate logistic and multivariate logistic analyses showed that patients with better doctor-patient communication had better blood pressure control (OR=6.179, P<0.001; OR=5.835, P<0.001). (4) The role of medication adherence in the effect of doctor-patient communication on blood pressure control, the total effect value of doctor-patient communication on blood pressure control was 0.447, the direct effect value was 0.335, and the mediating effect value of medication adherence in doctor-patient communication on blood pressure control was 0.113, accounting for 25.3% of the total effect.
CONCLUSIONS Doctor-patient communication has a significant positive effect on blood pressure control in hypertensive patients. Medication adherence plays a mediating role in the effect of doctor-patient communication on blood pressure control, and is a partial mediator.
GW34-e0933
Xihan Fan, Jie Deng, Yirui Yang, Hongen Zheng, Jiguo Zhou, Wei Chen
The First Affiliated Hospital of Kunming Medical University
OBJECTIVES To quantify the severity of diffuse myocardial fibrosis in patients with hypertension by extracellular volume fraction (ECV) derived from late iodine enhancement (LIE) via Dual-layer Spectral Detector CT (SDCT).
METHODS The validation group consisted of 1 patient with aortic stenosis, 3 with hypertension and 6 healthy subjects. All subjects completed cardiac magnetic resonance (CMR) and SDCT examination, and CMR-ECV and CT-ECV were calculated by T1 mapping and LIE images, respectively, and were compared. Then, 25 subjects with hypertension were included as the case group, which were divided into two subgroups based on left ventricular ejection fraction (LVEF), hypertensive patients with preserved LVEF (LVEF≥50%, n=14, Gp) and patients with reduced LVEF (40%<LVEF<50%, n=11, Gr). Twenty subjects without heart disease and hypertension were enrolled as the control group (Gc). Patients and controls underwent LIE to calculate CT-ECV according to the American Heart Association 16-segment models. Statistical analysis included paired t-test, Bland-Altman analysis, intra-class correlation coefficients (ICC), independent samples t test, Welch ANOVA test and Kruskal-Wasllis test.
RESULTS In the validation group, there were no significant difference between CT-ECV and CMR-ECV (29.66±4.17 vs 29.38±4.57, P>0.05) and CT-ECV correlated with CMR-ECV (r=0.946, P<0.001). CT-ECV matched well with CMR-ECV with insignificant bias (0.3%; 95% CI: −2.4–2.9%). The inter- and intra-observer agreement for CT-ECV were 0.902 and 0.946, respectively. Compared with the control group, the CT-ECV were increased in patients with hypertension 28.72 (1.97) vs. 27.00±1.32, P<0.05. Based on subgroup analysis, compared with the control group, the CT-ECV were only increased in the patients with reduced LVEF 29.97 (1.68) vs. 27.00±1.32, P<0.05, but not in the patients with preserved LVEF 28.37 (2.51) vs. 27.00±1.32, P>0.05.
CONCLUSIONS CT-ECV derived from LIE via SDCT is a reliable imaging marker with good repeatability for quantifying diffuse myocardial fibrosis. Furthermore, CT-ECV was found to be increased in hypertensive patients with reduced LVEF.
GW34-e0974
Yifang Yuan1,2, Aoming Jin1, Bruce Neal3,4, Xiangxian Feng5, Qianku Qiao6, Hongxia Wang7, Ruijuan Zhang8, Huijuan Li1, Pei Gao2, Gaoqiang Xie1, Hai Fang9, Minghui Zhao10, Runlin Gao11, Junshi Chen12, Paul Elliott13,14,15, Darwin Labarthe13, Yangfeng Wu1,2
1Peking University Clinical Research Center, Peking University First Hospital, Beijing, China
2Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing, China
3The George Institute for Global Health, University of New South Wales, Sydney, Australia
4School of Public Health, Imperial College London, London, UK
5Changzhi Medical College, Shanxi, China
6Yangcheng Ophthalmic Hospital, Shanxi, China
7Department of Nutrition and Food Safety, Hohhot Center for Disease Control and Prevention, Inner Mongolia, China
8Department of Public Health, Xi’an Jiaotong University, Shaanxi, China
9China Center for Health Development Studies, Peking University, Beijing, China
10Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
11Department of Cardiology, Fuwai Hospital, Peking Union Medical College, Beijing, China
12China National Food Safety Risk Assessment Center, Beijing, China
13Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
14UK Dementia Research Institute at Imperial College London, London, UK
15British Heart Foundation Centre for Research Excellence, Imperial College London, London, UK
OBJECTIVES Recent trials found that salt substitution could significantly reduce blood pressure and cardiovascular risk, with more frequent biochemical hyperkalemia but no detectable effect on clinical outcomes. However, benefits and risks of salt substitution was unclear on individuals at risk of hyperkalemia, including those with renal disease, taking medications that may elevate serum potassium and baseline biochemical hyperkalemia. The aim of the study was to investigate the impact of salt substitution on blood pressure, cardiovascular outcomes and biochemical hyperkalemia in participants with and without risk of hyperkalemia at baseline.
METHODS This was a post-hoc analysis of DECIDE-Salt trial, a cluster-randomized, 2×2 factorial randomized trial conducted from September 2017 to October 2020 (NCT03290716). We randomized 48 residential elderly care facilities in China, with 1612 participants aged 55 years and older, to salt substitute (62.5% NaCl and 25% KCl) versus usual salt for 2 years. Subgroup analysis was performed in participants with and without risk of hyperkalemia at baseline. The primary outcome was systolic blood pressure. Secondary efficacy outcomes included diastolic blood pressure, major adverse cardiovascular events (comprising non-fatal stroke, non-fatal myocardial infarction, hospitalized non-fatal heart failure or vascular death). Safety outcome was biochemical hyperkalemia.
RESULTS Of the 1612 eligible participants enrolled, with 229 (14.2%) participants were identified as at risk of hyperkalemia at baseline, including 88 (5.5%) with renal disease, 112 (6.9%) on ACEI/ARB, 27 (1.7%) on beta-blockers, 10 (0.6%) on potassium-sparing diuretics, and 34 (2.1%) with baseline biochemical hyperkalemia. After adjustment of age, sex, center, baseline blood pressure, antihypertensive medications, salt substitute compared to usual salt lowered mean systolic blood pressure by −5.2 mmHg (95% CI −10.1 to −0.3; P=0.038) in participants with risk of hyperkalemia, which did not differ from the results in participants without risk of hyperkalemia (–7.6 mmHg (95% CI −11.0 to −4.3; P for interaction=0.26). MACE was reduced with a borderline statistical significance with salt substitute in those at risk of hyperkalemia (2.6 versus 5.2 per 100 pt-yrs, HR 0.39, 95% CI 0.13–1.14; P=0.09), comparable to those without (P for interaction=0.43). The presence of baseline risk of hyperkalemia was not associated with a difference in the risk observed with salt substitute over usual salt for new-onset biochemical hyperkalemia at follow-up (RR, 1.84; 95% CI, 0.53–6.35 for participants with baseline high risk of hyperkalemia; vs RR, 3.71; 95% CI, 1.74–7.92 for participants without baseline high risk of hyperkalemia; P for interaction=0.28). Nor did the change of serum potassium (mean difference 0.22;95% CI, 0.05–0.37, P=0.006 for participants with baseline high risk of hyperkalemia; vs 0.27;95% CI, 0.16–0.37, P<0.001 for participants without baseline high risk of hyperkalemia; P for interaction=0.47).
CONCLUSIONS Compared with usual salt, salt substitute lowered blood pressure and reduced cardiovascular risk among participants at risk of hyperkalemia. The presence of risk of hyperkalemia with salt substitution was not associated with a difference in the detection of biochemical hyperkalemia at follow-up.
GW34-e1017
Ai Chen, Liangdi Xie
The First Affiliated Hospital of Fujian Medical University
OBJECTIVES The impact of elevated resting heart rate (RHR) on arterial stiffness (AS), manifesting as increased carotid-femoral pulse wave velocity (cfPWV), in hypertension is unclear. This study aimed to analyze effect of RHR on AS and construct a nomogram to estimate hypertensive AS risk.
METHODS One thousand five hundred and seventy-two hypertensives were divided into 4 groups based on RHR quartiles. Demographic and clinical features were measured, and AS was assessed by measuring cfPWV. The least absolute shrinkage and selection operator (LASSO) and univariate logistics regression were used to develop the nomogram. Calibration curve, decision curve analysis (DCA) and receiver operating characteristic (ROC) were applied to evaluate calibration and clinical usefulness. Interaction and stepwise logistics regression analysis were performed to identify the independent variables associated with AS.
RESULTS The nomogram included 6 predictors, of which the calibration curve showed good agreement between predicted and actual AS probability. The area under ROC curve (AUC) was 0.865, and after bootstrapping 1000 sample, internal validation showed a good C-index of 0.823. Elevated ORs for AS were demonstrated from Q1 to Q4, and in aged 55–74 yr and diabetics, those of RHR ≥Q4 were more likely to suffer AS.
CONCLUSIONS Increased RHR is associated with a high risk of AS in hypertensives. We proposed a nomogram which evaluated AS risk rapidly in Chinese hypertensives. Furthermore, in hypertensives, RHR ≥80 bmp independently predicts AS and in those who are also diabetics, age of 55–74 yr, RHR determination should be recommended to better stratify the cardiovascular risk.
GW34-e1114
Xianghui Zhang1, Yifang Yuan1, Hongxia Wang2, Xiangxian Feng3, Qianku Qiao4, Ruijuan Zhang5, Jiayu Li1, Huijuan Li1, Yangfeng Wu1
1Peking University Clinical Research Center, Peking University First Hospital, Beijing, China
2Department of Nutrition and Food Safety, Hohhot Center for Disease Control and Prevention, Inner Mongolia, China
3Changzhi Medical College, Shanxi, China
4Yangcheng Ophthalmic Hospital, Shanxi, China
5Department of Public Health, Xi’an Jiaotong University, Shaaxi, China
OBJECTIVES Salt substitution has been proved effective in reducing mean blood pressure (BP) and cardiovascular events. However, no study to date have reported its effect on hypertension control rate. Thus, we access the effect of salt substitute strategy on improving blood pressure control among the hypertensive elderly living in residential facilities.
METHODS This was a post-hoc analysis of DECIDE-Salt trial (The Diet, ExerCIse and carDiovascular hEalth (DECIDE)–Salt Reduction Strategies for Seniors in Residential Facilities), a cluster-randomized, 2×2 factorial randomized trial conducted from September 2017 to October 2020 (NCT03290716). We randomized 48 residential elderly care facilities in China, with 1612 participants aged 55 years and older, to salt substitute (62.5% NaCl and 25% KCl) versus usual salt for 2 years. For the present study, participants with hypertension at baseline were included, defined as BP >=140/90 mmHg or on anti-hypertension medication. The primary outcome was the change in hypertension control rate from baseline to 24 months among participants with hypertension in the salt substitute and usual salt groups. The secondary outcome was the change in hypertension control rate from baseline to 12 months and blood pressure level. Hypertension control rate was defined as the proportion of participants with well-controlled BP (<140/90 mmHg). To assess the effect of salt substitution versus usual salt on hypertension control rate and blood pressure, we performed generalized Linear Mixed-Effects Model and Linear Mixed-Effects Model accounting for cluster effect, adjusting for age, sex, education, drinking, BMI, physical activity and anti-hypertension medication use. Complete records analyses were used for main analysis. Last observation carried forward approach and multiple imputation were also used to handle missing BP values during follow-up for sensitivity analysis.
RESULTS A total of 1001 participants (507 in usual salt group and 494 in salt substitute group) were included (mean [SD] age, 70.8 [9.2] years; 776 men [77.5%]). Hypertension control rate at baseline was 25.7% in the salt substitute group and 26.5% in the usual salt group. After 24 months of intervention, the hypertension control rate for the salt substitute group compared with the usual salt group was significantly higher (49.7 vs 38.7%; RR, 1.71; 95% CI, 1.01–2.90; P=0.045). Hypertension control rate at 12 months was also significantly improved in the salt substitute group (43.0 vs 33.4%; RR, 1.69; 95% CI, 1.05–2.74; P=0.032). The intervention effect on systolic blood pressure was −6.3 mmHg (95% CI, −9.4 to −3.3, P<0.001) and on diastolic blood pressure was −1.9 mmHg (95% CI, −3.4 to −0.3, P=0.025). Sensitivity analyses for primary and secondary outcomes showed similar results.
CONCLUSIONS Replace usual salt with salt substitute was an effective strategy to improve hypertension control and lower blood pressure among older hypertension people.
GW34-e1222
Run Lin1,2, Jilin Li2, Wei Wang2, Jun Cai3, Weiwen Li1,2, Ying Lin1,2, Jinhao Chen1,2, Youren Chen2
1Shantou University Medical College, Shantou, Guangdong, China
2Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
3Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
OBJECTIVES Increased resting heart rate has been shown to be associated with poor prognosis. However, the long-term effects of cumulative resting heart rate (cumRHR) on cardiovascular events and all-cause mortality in elderly hypertensive populations remain unclear.
METHODS This post-hoc analysis of Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial enrolled 7517 patients who had not experienced cardiovascular events and not used beta-blockers, measured resting heart rates at 0, 3, 6, 9, and 12 months. Cumulative resting heart rate exposure refers to the weighted average of resting heart rate for each time interval. Participants were grouped into four quartiles (Q1, Q2, Q3, and Q4) based on their cumRHR. The primary outcome was a composite of cardiovascular events. The secondary outcomes were major cardiovascular events (MACEs), stroke, and all-cause death. The Fine-Gray subdistribution hazard model and natural spline functions were used to assess the relationship between cumRHR and outcomes.
RESULTS Among the 7517 participants in this study, mean age was 66.19 years and 53.48% were female. Over a median follow-up of 3.33 years, a U-shaped association with primary outcome was observed with higher risk in those with both very low and very high cumRHR levels compared with Q3 group (72–76 bpm). After adjustment for multiple potential confounders, participants in Q4 group (>76 bpm) were associated with increased risk of primary outcomes (HR: 2.07; 95% CI: 1.36, 3.15, P<0.001), MACEs (HR: 1.87; 95% CI: 1.16, 2.99, P=0.009) and stroke (HR: 3.21; 95% CI: 1.35, 7.63, P=0.008) compared with the Q3 group. Participants in Q1 group (<68 bpm) were also associated with increased risk of primary outcomes (HR: 1.75; 95% CI: 1.13, 2.72, P=0.01) compared with the Q3 group. However, this trend was not observed in all-cause mortality.
CONCLUSIONS Cumulative resting heart rate may be an independent risk factor for cardiovascular events and stroke in elderly hypertensive patients. Monitoring and maintaining an appropriate range of resting heart rate can provide guidance for the treatment of hypertension.
GW34-e1226
Qianhui Wang
Xinjiang Medical University
OBJECTIVES The Systemic Immune-inflammation Index (SII), a novel inflammatory marker, has exhibited promising prognostic value among hypertensive patients. However, its potential prognostic implications in postmenopausal women patients with hypertension have yet to be explored.
METHODS We conducted a prospective cohort study involving 1386 participants, all of whom were postmenopausal women diagnosed with hypertension. Data was obtained from the National Health and Nutritional Examination Surveys (NHANES) conducted between 2013 and 2016. Cox proportional hazards models were used to assess the predictive value of SII for all-cause mortality.
RESULTS Over a median follow-up period of 4.67 years, a total of 154 deaths from all causes were recorded. In the fully adjusted Cox regression analysis, participants belonging to the highest quartile of SII exhibited a 3.1-fold higher risk of mortality from all causes compared to those in the lowest quartile (HR=3.10, 95% CI: 1.48–6.48, P=0.015). Furthermore, after controling for confounding factors, each unit increase in SII was associated with a 36% increased risk of all-cause mortality (HR=1.36, 95% CI: 1.21–1.53, P<0.001). Restricted cubic spline analysis demonstrated a linear dose-response relationship between SII and all-cause mortality, with a threshod value of 1.04. Below this predefined threshold, there was no significant association with all-cause mortality when SII increased by one unit (HR=2.62, 95% CI: 0.28–24.30, P=0.396). However, beyond this threshold, a discernible pattern emerged wherein higher values of SII were correlated with an elevated risk of death from any cause (HR=1.44, 95% CI: 1.23–1.68, P<0.001). The robustness of the results in subgroup and sensitivity analyses lends support to the validity and reliability of the findings.
CONCLUSIONS Elevated baseline SII, wheter considered as a continuous or categorical variable, was significantly associated with an increased risk of all-cause mortality in postmenopausal women with hypertension.
GW34-e1338
Chengkun Kou, Xu Zhao, Xin Fan, Xin Lin, Qiongying Wang, Jing Yu
Lanzhou University Second Hospital
OBJECTIVES Salt is a widely used condiment throughout the world. Sodium chloride is the main salt component. Sodium is an essential macronutrient that maintains fluid balance and cellular homeostasis. It is suggested that dietary sodium may influence cognition by cerebrovascular and cerebral blood flow. This study aimed to assess the relationship between dietary sodium/potassium intake and cognition in elderly individuals with hypertension.
METHODS We designed a cross-sectional study based on the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Cognitive performance was assessed using the Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer’s Disease test (CERAD), and Animal Fluency Test (AFT). Multivariate logistic regression and restricted cubic spline (RCS) was used to assess the relationship between dietary sodium/potassium intake and cognition.
RESULTS After excluding participants with incomplete data, 1670 out of 2276 participants had confirmed hypertension. Compared with the lowest quartile of dietary sodium, the lowest weighted odds ratio (OR) of cognitive impairment in DSST was observed in Q4 (OR=0.45, 0.29–0.70), and a similar trend was observed in AFT (OR=0.34, 0.18–0.65). After adjusting the covariates, the lowest weighted multivariate adjusted OR of cognitive impairment in DSST were also observed in Q4 (OR=0.47, 0.26–0.84) compared with the lowest quartile of dietary sodium. The RCS results showed that dietary sodium was U-shaped and associated with the risk of cognitive impairment in the DSST (Pnon–linearity=0.0067). No significant association was observed between dietary potassium and cognitive performance.
CONCLUSIONS Too high and too low dietary sodium levels were associated with impairment of specific processing speed, sustained attention, and working memory for hypertension among the elderly in the United States. However, no association was observed between the dietary potassium intake and cognition.
GW34-e1343
Caie Li, Qiongying Wang, Jing Yu
Lanzhou University Second Hospital
OBJECTIVES Drug-induced hypertension (HTN) related to small molecular tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) is one of the important issues of onco-hypertension. Due to the high incidence of hypertension induced by targeted anti-tumor drugs, it is believed that DI-HTN may be a biological marker for efficacy of anti-VEGF therapy. However, different studies have not yet reached a consistent conclusion. The current study was therefore designed to discuss the epidemiological relationship between hypertension and cancer, and to investigate the incidence of DI-HTN related to apatinib, an small molecular TKI targeting VEGF, in the treatment of patients with solid tumor in real world and its associated factors. Furthermore, to determine whether apatinib-induced hypertension is associated with prognosis of patients.
METHODS We retrospectively collected the medical records of patients with solid tumor treated with apatinib in Lanzhou University Second Hospital and Gansu Provincial Cancer Hospital, from Oct 1st 2014 to Jun 30st 2019. The patients were then prospectively followed to determine the disease state, time of disease progression and death, as well as whether or not have newly initiated HTN. The mean follow-up was 16.5 month, with the longest follow-up of 48 months. The apatinib-induced HTN was defined as either newly initiated HTN in patients with normal blood pressure or increases of antihypertensive intensity in patients with pre-existed HTN. The prognosis of patients was estimated with progression-free survival (PFS) and overall survival (OS).
RESULTS A total of 400 patients were enrolled, of whom 136 (34%) were diagnosed with HTN induced by apatinib. The primary tumor in 40% of the patients were gastrointestinal cancer, followed by hepatobiliary cancer (14.5%) and lung cancer (13.3%). Patients in HTN group were older (P=0.03), more frequently with proteinuria (P=0.035) and higher dosage of apatinib (P=0.024). The survival analysis showed that apatinib-induced HTN was associated with significantly longer PFS, as well as OS (both P<0.01), the differences existed both in univariate and multivariate analyses. The subgroup analyses were performed in patients with gastrointestinal cancer, hepatobiliary cancer, and lung cancer, all showed consistent results.
CONCLUSIONS HTN is one of the most common side effects of apatinib in the treatment of solid tumors, with an incidence of as high as 34% in real world. Apatinib-induced HTN is significantly associated with better anti-tumor efficacy in patients with solid tumors. Given that there is still no effective predictive biomarker for apatinib, drug-induced HTN may be used as an surrogate one. The development of new antihypertensive drugs with better antihypertensive effects while no influences on antitumor activity, is in urgent need.
ARRHYTHMIAS
GW34-e0021
Wang Danning
The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong
OBJECTIVES Atrial fibrillation (AF) is associated with high mortality and morbidity rates. In terms of the underlying pathophysiology, AF is complex and remains unclear. Necroptosis plays an essential role in the pathogenesis of various cardiovascular diseases. This study aims to investigate the role of necroptosis and analyze the interaction between necroptosis and AF.
METHODS GSE79768 and GSE41177 from the Gene Expression Omnibus (GEO) database were downloaded, and necroptosis-related differentially expressed genes (NRDEGs) were identified between AF and healthy groups. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were then used to conduct functional enrichment analyses of these genes. The CIBERSORT algorithm was used to reveal the patterns of immune cell infiltration in AF and exam the correlation between hub genes and immune cells to explain the underlying mechanism. Then, a lncRNA-associated ceRNA network was constructed by using Cytoscape underlying the interaction generated from the miRcode, miRTarBase, and TarBase databases.
RESULTS There were a total of 34 DEGs identified. Necroptosis and inflammation were mainly controlled by these DEGs. MAPK8, MAP3K7, CD40, CASP8, MYC, HSP90AA1, BCL2L11and DIABLO were identified as the top 8 hub genes associated with AF. The relationship between AF and the hub genes in patients was further confirmed in the STRING database. The immune cell infiltration analysis indicated that B cells memory, Eosinophil, T cells follicular helper, and Neutrophils were significantly activated in atrial fibrillation. It was found that the hub genes in GSE79768 were strongly correlated with immune cell infiltration. B cells naïve and B cells memory, Plasma cells, and Macrophages M2, T cells CD8 and Mast cells activated, Mast cells resting and Mast cells activated showed a negative correlation (P<0.01), Mast cells activated and Eosinophils, B cells memory and T cells CD4 naïve showed a positive correlation (P<0.01). Finally, 43 lncRNAs were identified in AF. Seven lncRNAs (SLFNL1-AS1, LINC01132, PCBP1-AS1, LINC01816, LINC02035, MYLK-AS1, TERC) regulate the hub-gene through has-mir-34c-5p.
CONCLUSIONS MAPK8, MAP3K7, CD40, and CASP8 may act as critical regulators in the necroptosis of cardiomyocytes in AF patients. It involves mechanisms such as humoral immunity, cellular immunity, and inflammatory response, but the fundamental biological function of these genes remains unclear. Our present study may pave the way for further research into the necroptosis of AF.
GW34-e0034
Jiang Jiang
Fuwai Hospital
OBJECTIVES In patients with no history of atrial fibrillation (AF), device-detected atrial high rate episodes (AHRE) was associated with an increased thromboembolic risk. While limited data regarding the long-term prognosis of patients with AHRE were controversial. This study aimed to explore whether the device-detected AHRE can predict mortality outcomes.
METHODS This observational study included patients with ICD or CRT-D implantation and no history of AF/atrial flutter (AFL). During follow-up, patients with at least 1 day with AHRE duration ≥15 minutes were identified. The primary outcome was cardiac mortality and the secondary outcome was all-cause mortality.
RESULTS During a mean follow-up of 4.2 years, AHRE was detected in 124 of 343 (36.2%) patients. A total of 44 death events (44/124, 35.5%) occurred in 124 patients with AHRE, which was significantly higher than those free of AHRE (43/219, 19.6%, P=0.001). In multivariate analysis adjusting for variables with clinical and statistical significance, patients with AHRE were significantly associated with a higher risk of cardiac (HR: 2.40, 95% CI: 1.23–4.67, P=0.010) and all-cause mortality (HR: 2.31, 95% CI: 1.49–3.59, P<0.001). Notably, the risk of remaining patients with AHRE in cardiac and all-cause mortality was further increased after excluding the patients diagnosed with clinical AF during subsequent follow-ups.
CONCLUSIONS AHRE is prevalent in ICD or CRT-D-implanted patients with no history of clinical AF/AFL and is associated with more than twice the risk of cardiac and all-cause mortality.
GW34-e0040
Xiaoqin Li, Biao Fu
Chongqing General Hospital
OBJECTIVES The diameter of the left atrium (LA) is a major index of prediction for LA fibrosis and increased risk of atrial fibrillation (AF) recurrenceafter catheter ablation. However, an unenlarged LA may not be associated with good results in some cases of AF ablation.
METHODS Patients with persistent fibrillation who underwent catheter ablation in our center were analyzed in this retrospective study. Comprehensive low voltage mapped in LA is considered a fibrotic LA. The patients with fibrotic but unenlarged LA, normal LA, and fibrotic tissue with enlarged LA were included in Groups A, B, and C, respectively. We compared clinical features, electrophysiological findings, immediate ablation results, and follow-up outcomes in three groups.
RESULTS We enrolled 9 patients in Group A, 38 in Group B, and 12 in Group C. There were greater proportions of women, low ventricular rates, and high CHA2DS2-VASC scores in the patients with fibrotic LA (Groups A and C). At the end of procedure, all of the patients saw restored sinus rhythm, and the rate of sinus rhythm was lower in Groups A and C than in Group B. Atrial-ventricular block and very-early-stage recurrence were more common in Group A. Sinus rhythm maintenance and LA reversion were rarer in Group A than in Group B or C.
CONCLUSIONS A fibrotic but unenlarged LA was more likely to be seen in female with high CHADS2VA2S score. Low voltage in small left atrium in patients with persistent AF that carries a poor prognosis for AF ablation, maybe due to presentation at advanced stages of atrial fibrosis.
GW34-e0059
Kexin Wang, Mingjia Xu, Weizhu Ju, Minglong Chen
The First Affiliated Hospital of Nanjing Medical University
OBJECTIVES Endovascular left atrial appendage occlusion (LAAO) is associated with a high incidence of peri-procedure silent cerebral embolisms (SCE), while the recommended activated clotting time (ACT) level by the expert consensus is lower than that in atrial fibrillation (AF) ablation. The aim of our study is to investigate whether raising the targeted ACT level during LAAO to the same level as AF ablation could decrease the incidence of SCE.
METHODS Consecutive AF patients receiving LAAO between January 2021 and December 2022 were included and categorized into two groups based on the time of enrollment. Patients enrolled in 2021 (group 250) maintained a target ACT level of ≥250 s during LAAO procedure, while patients enrolled in 2022 (group 300) maintained the peri-procedure ACT ≥300 s. All patients underwent cerebral magnetic resonance imaging (MRI) before and after the procedure.
RESULTS A total of 81 patients were included (38 in the group 250 and 43 in the group 300). After inverse probability of treatment weighting (IPTW), patients in the group 250 showed a significantly lower incidence of SCE than group 300 (IPTW P=0.038). Only a stable high ACT pattern could decrease the risk of SCE. No significant differences were found between other ACT change patterns on the SCE incidence.
CONCLUSIONS Raising the peri-procedure ACT level to 300 seconds could decrease the risk of the SCE without increasing the major bleeding events. The findings imply that maintaining a stable high ACT level is important for preventing minor thromboembolism in LAAO.
GW34-e0060
Kexin Wang, Caiyi Jin, Weizhu Ju, Minglong Chen
Division of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
OBJECTIVES Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. General anesthesia (GA) resolves the problem of pain intolerability and provides regular respiratory mode which might improve the catheter maneuverability of AF ablation. This study aims to compare the procedural performance of PVI under GA versus conscious sedation (CS) from multiple perspectives, including lesion quality and ablation efficiency, using the AIFV system.
METHODS A total of 36 consecutive patients undergoing first AF ablation under GA were enrolled in GA group. Another 109 patients receiving AF ablation under CS in the same period were selected as the control group. After propensity score matching, 29 matched pairs with similar baseline characteristics were available for further analysis. The AIFV system was used to evaluate six procedural parameters in each PVI procedure.
RESULTS Compared with CS, PVI under GA had a significantly shorter total PVI time (51.4 min vs. 67.8 min; P=0.003) and higher radiofrequency ratio (62.6 vs. 55.8%; P=0.032). The number of gaps (1.0 vs. 3.0; P<0.001) and the rate of break point were significantly lower in the GA group. GA was also associated with a higher effective ablation-index ratio (87.5 vs. 74.1%; P<0.001) and effective force-over-time ratio (85.3 vs. 69.2%; P=0.001). After a medium follow-up time of 24 months, 12/29 (41.4%) patients in the CS group and 6/29 (20.7%) patients in the GA group suffered from AF recurrence (P=0.156).
CONCLUSIONS GA improves the lesion quality and procedural efficiency of PVI from multiple perspectives evaluated by the AIFV system.
GW34-e0108
Wenhui Wang1, Linlin Liu2, Lu Jin3, Bei Tian4, Zhongping Ning4, Xinming Li4
1Center of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
2Tongji University School of Medicine, Shanghai, China
3Department of Cardiology, Anda Hospital, Shanghai, China
4Department of Cardiology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
OBJECTIVES Patients with atrial fibrillation (AF) suffer a higher risk of death, and it is necessary to develop prediction tools for mortality risk in critically ill patients with AF. This study aimed to develop a novel predictive nomogram of in-hospital mortality after 48 hours in the coronary care unit (CCU) for patients with AF.
METHODS We collected information on CCU patients with AF from the “Medical Information Mart for Intensive Care-III” database and developed a nomogram model for predicting the all-cause mortality risk after 48 hours in the hospital. Key variables were selected by univariate logistic and least absolute shrinkage and selection operator regression. The independent predictors with P<0.05 were screened out by multivariate logistic regression (backward stepwise procedure). A predictive nomogram was constructed using these independent predictors, and the model calibration and discrimination were evaluated.
RESULTS This study finally enrolled 1248 CCU patients with AF, and the in-hospital mortality was 17% (209/1248). The predictive nomogram was constructed by 13 selected independent predictors, including age, smoking status, acute kidney injury, chronic obstructive pulmonary disease, ventricular arrhythmia, shock, urea, red cell distribution width, leucocytosis, continuous renal replacement therapy, continuous positive airway pressure, anticoagulation, and heart rate. The area under the curve of the nomogram was 0.803 (95% confidence interval 0.771–0.835). The nomogram was verified to have good accuracy and calibration.
CONCLUSIONS This study developed a novel nomogram with thirteen variables that could predict potential in-hospital mortality after 48 hours in CCU patients with AF.
GW34-e0112
Jiachen Luo
Shanghai Tenth People’s Hospital
OBJECTIVES The 4S-AF scheme (Stroke risk [St], Symptom severity [Sy], Severity of atrial fibrillation burden [Sb], Substrate [Su]) is a novel approach for the holistic characterization of AF. We aimed to investigate if the 4S-AF scheme would be useful for AF characterization and provide prognostic implications in acute myocardial infarction (AMI) patients with new-onset atrial fibrillation (NOAF).
METHODS We included 262 patients with post-MI NOAF who had complete data for the 4S-AF scheme evaluation between February 2014 and March 2018. The 4S-AF scheme score was calculated as a sum of each domain with a maximum of 9. The primary outcome was all-cause death.
RESULTS Of 262 patients (66.0% males, mean age 74.5±10.4 years) were analyzed. The mean 4S-AF scheme score was 5.0±1.6. There were 62 (27.3%) all-cause deaths during a median follow-up of 2.6 years. In multivariable Cox regression models, each 1-point increase in the 4S-AF scheme score was significantly associated with 39% increased all-cause mortality (HR: 1.39, 95% CI: 1.16–1.67, P<0.001), which was mainly driven by the Sb (HR: 1.43, 95% CI: 1.05–1.95, P=0.025) and Su (HR: 1.53, 95% CI: 1.17–2.02, P=0.002) domains. Adding the 4S-AF scheme score on top of the Global Registry of Acute Coronary Events score could significantly improve its discriminative capability (C-index from 0.713 to 0.761, P=0.039) and reclassification performance (continuous net reclassification improvement: 41.0% [95% CI: 12.5–69.6]; integrated discrimination improvement: 5.1% [95% CI: 2.2–8.1]) for all-cause mortality.
CONCLUSIONS Characterization of NOAF using the 4S-AF scheme aids in the risk stratification of AMI patients with NOAF.
GW34-e0120
Zhongli Chen1, Xuan Ma2, Shihua Zhao2, Keping Chen1
1Fuwai Hospital, CAMS and PUMC, State Key Laboratory of Cardiovascular Disease, Cardiac Arrhythmia Center, Beijing, China
2Fuwai Hospital, CAMS and PUMC, Department of Magnetic Resonance Imaging, Beijing, China
OBJECTIVES LBBAP emerges as a novel approach for CRT in patients with dyssynchronous heart failure, but the information on baseline myocardial characteristics was limited to identify LBBAP-CRT responders. We aimed to explore the value of cardiac magnetic resonance (CMR)-derived scar burden for identifying candidates who might benefit from cardiac resynchronization therapy (CRT) via left bundle branch area pacing (LBBAP).
METHODS Consecutive patients with traditional CRT indications who underwent CMR examination and successful LBBAP-CRT were retrospectively analyzed. CMR late gadolinium enhancement (LGE) was used for scar assessment. Echocardiographic/clinical response and adverse prognosis (including the composite outcome of all-cause death, heart transplantation, and heart failure rehospitalization) were evaluated.
RESULTS A total of 54 patients were included. LBBAP-CRT generated significant overall QRS duration reduction and left ventricular ejection fraction (LVEF) improvement, with an echocardiographic response rate of 70.4%. LGE-based global, septal, and lateral scar burden was significantly higher in non-responders. Septal scar burden was significantly lower in those with Strauss left bundle branch block (LBBB) morphology. In multivariate analysis incorporating previously defined clinical and LGE parameters, septal scar burden strongly correlated with LVEF improvement. Compared with clinical parameters, global, septal, and lateral scar burden demonstrated decent discriminability of echocardiographic (Area under a receiver operating characteristic (AUC-ROC) curve 0.821, 0.842, and 0.764, respectively) and clinical response (AUC-ROC: 0.779, 0.791, and 0.723, respectively). A cut-off value of 6.99% for septal LGE extent provided >80% sensitivity and specificity for the prediction of echocardiographic response to CRT, with a better likelihood ratio than Strauss LBBB. After a median follow-up time of 20.3 (11.5–38.7) months, higher global, septal, and lateral scar burdens were also predictive of adverse prognosis (log-rank: all P<0.05).
CONCLUSIONS Lower scar burden was associated with higher response probability in HF patients who received LBBAP-CRT. The pre-procedure CMR scar evaluation might provide useful information beyond electrocardiograms morphology for clinicians for identifying potential responders to LBBAP-CRT. Future prospective studies are warranted to further explore the efficacy of pre-procedure CMR-scar evaluation for optimizing the selection of LBBAP-CRT candidates.
GW34-e0132
Yujie Cui, Yafeng Zhou
Dushu Lake Hospital Affiliated to Soochow University
OBJECTIVES Atrial fibrillation (AF) and heart failure (HF) frequently coexist, resulting in adverse outcomes. However, controversies remain regarding the efficacy of catheter ablation (CA) in AF patients with severe left ventricular dysfunction. The purpose of this study was to perform a meta-analysis of prospective randomized controlled trials to evaluate the efficacy of CA versus medical therapy (MT) in AF patients with left ventricular ejection fraction (LVEF) ≤45%.
METHODS We searched the literature for studies that compared CA to MT in AF patients with LVEF ≤45%. A meta-analysis of 7 clinical trials was performed, including 1163 patients with AF and HF. Subgroup analysis was performed based on baseline LVEF.
RESULTS We found that CA was associated with lower all-cause mortality (RR: 0.52, 95% CI: 0.37–0.72; P<0.01) and greater improvements in LVEF (mean difference: 4.80%, 95% CI: 2.29–7.31%; P<0.01) compared to MT. Patients in the CA group had a lower risk of HF hospitalization and AF recurrence and a significantly better quality of life than those in the MT group. The results of subgroup analysis indicated that patients with milder left ventricular dysfunction better improved LVEF after AF ablation (mean difference: 6.53%, 95% CI: 6.18–6.88%; P<0.01) compared to patients with more severe disease (mean difference: 2.02%, 95% CI: 0.87–3.16%; P<0.01).
CONCLUSIONS Our meta-analysis demonstrated that CA was associated with significant improvements in outcomes of AF patients with LVEF ≤45%. Additionally, AF patients with milder left ventricular dysfunction could benefit more from CA.
GW34-e0172
Jingcheng Chen1,2, Gang Yang1, Hongwu Chen1, Weizhu Ju1, Hailei Liu1, Mingfang Li1, Minglong Chen1
1The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China
2The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Jiangsu, China
OBJECTIVES The initiation and maintenance of paroxysmal atrial fibrillation (PAF) was supposed to be the interaction between the pulmonary vein (PV) triggers and pulmonary vein antrum (PVA) substrate. The investigation of electrical substrate at antrum area was very rare. The present study aimed to investigate the anisotropical electrical properties of PVA by extremely high-density mapping.
METHODS High-density mapping of the left atrium was performed in 18 PAF patients with 9 age and sex matched patients with paroxysmal supraventricular tachycardia (PSVT). Each PVA was divided into 8 segments while PV was into 4. The electrophysiological properties were assessed by slow conduction, complex fractionated electrograms and effective refractory period (ERP).
RESULTS The slow conduction was more prevelanced at PVA (43.17±19.50 versus 14.67±13.04%, P<0.001) and PV (61.94±16.36 versus 9.11±9.00%, P=0.001) in PAF patients as compared with PSVT patients during sinus rhythm (SR). These findings were consistent with that during coronary sinus proximal/distal pacing. The area of complex fractionated electograms was significantly larger in PAF during SR at PVA (105.25 [2.30, 203.30] versus 0.00 [0.00, 41.40] mm2, P=0.038) and PV (213.80 [70.05, 459.55] versus 26.30 [0.00, 241.3] mm2, P=0.045). ERP of PVA was much longer in PAF than the control patients, (260 [230, 280] versus 220 [190, 250] ms, P=0.001), (230 [205, 250] versus 200 [190, 220] ms, P=0.007), with pacing at the drive length of 600 ms and 400 ms, respectively. In contrast, the ERP difference inside the PVs between the two groups was contradictory to that of PVA (220 [170, 240] versus 230 [220, 250] ms at 600 ms, P=0.058; 200 [190, 225] versus 210 [200, 220] ms at 400 ms, P=0.006).
CONCLUSIONS PAF patients have the elctrical PV antrum in terms of slow conduction, complex fractionated electrograms and ERP dispersion.
GW34-e0174
Qingqing Gu1,2, Qianwen Chen1,2
1Department of Cardiology, the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China
2Dalian Medical University, Dalian 116000, Liaoning, China
OBJECTIVES Atrial fibrillation (AF) is one of the most common arrhythmias in clinical practice, with a high incidence and increased risk of death. The purpose of this study was to explore the association between triglycerides (TG) and the risk of recurrence after AF.
METHODS A retrospective study was conducted. The hospitalized patients diagnosed with AF who underwent catheter ablation from April, 2008 to June, 2021 in the department of cardiology in the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University were selected as the research objects. According to electrocardiogram during one-year follow-up, the patients were divided into SR maintenance group and AF recurrence group. The difference in patients’ TG levels between the sinus rate (SR) maintenance group and AF recurrence group was compare. Univariate and multivariable Cox models were constructed to examine the association of TG levels and AF recurrence. Kaplan-Meier survival curve was used to evaluate the effects of TG levels on patients with AF in ratio of AF recurrence.
RESULTS A total of 402 AF patients were enrolled in this study, of which 79 patients (19.7%) underwent recurrence of AF. Compared with the SR maintenance group, the level of TG was higher (mmol/L: 1.68±1.15 vs. 1.52±0.91) in AF recurrence group. In univariate analysis, TG level is significantly associated with recurrence of AF (P=0.024, odds ratio [OR] 1.251, 95% confidence interval [CI] 1.030–1.519). The association between TG level and recurrence of AF remained significant on multivariate analysis (P=0.033, OR 1.251, 95% CI 1.019–1.536). The adjusted hazard ratios (aHR) of recurrent AF across three groups of TG level were 1.0 (reference), 2.331 (95% CI 1.141–4.762, P=0.02), and 2.857 (95% CI 1.332–6.199, P=0.007). A similar effect was observed when TG was analyzed as continuous variable (aHR per unit increase, 1.256; 95% CI 1.029–1.533, P=0.025). Kaplan-Meier survival curve analysis indicated that the recurrence rate after catheter ablation in AF patients with medium and high TG level was significantly higher than that in patients with low TG level (Log-Rank: χ2=7.540, P=0.023).
CONCLUSIONS Our data suggest that elevated TG level measured prior to catheter ablation are associated with an increased risk of AF recurrence.
GW34-e0202
Leyi Zhu1, Shihua Zhao1, Minjie Lu1, Zhe Zheng2
1Department of Magnetic Resonance Imaging, Fuwai Hospital
2Department of Cardiac Surgery, Fuwai Hospital
OBJECTIVES To investigate the clinical value of three-dimensional (3D) high-resolution late gadolinium enhancement magnetic resonance imaging (LGE-MRI) in accessing left atrial myocardial fibrosis in patients with atrial fibrillation (AF).
METHODS A total of 35 AF patients referred for hybrid surgical ablation were prospectively enrolled in this study. 3D-LGE-MRI images were acquired by the Siemens 3.0 T machine and analyzed by using ADAS post-processing software independently by two experienced radiologists to obtain parameters such as the area and the area percentage of LGE. Image quality was evaluated by two radiologists. Regional analysis was performed by one radiologist at ten left atrial segments. The Kappa test was used to assess the agreement for scoring image quality, and the interclass correlation coefficient (ICC) was used to evaluate the interobserver agreement of LGE parameters. The parameters of left atrial morphology, area (and area percentage) of LGE, and location of LGE were compared between patients with persistent AF and paroxysmal AF by using the t-test or Mann-Whitney U test.
RESULTS Images of 34 patients (97%) were considered of diagnostic value. The scores of the overall image quality and the clarity of the left atrial wall evaluated by two radiologists were (2.88±0.64) points and (3.26±0.75) points (radiologist 1), (2.97±0.58) points and (3.24±0.70) points (radiologist 2), respectively. The corresponding Kappa values were 0.724 and 0.859. Both the area and the area percentage of LGE showed good consistency among observers, and the ICCs were 0.969 and 0.950, respectively. Compared with patients with paroxysmal AF, patients with persistent AF had a higher Utah stage and more severe myocardial fibrosis in the right inferior pulmonary vein antrum and the left atrial septum (all P<0.05).
CONCLUSIONS 3D high-resolution LGE-MRI provides a non-invasive way to visualize and quantify left atrial myocardial fibrosis. The extent of left atrial fibrosis in patients with persistent AF is more severe than that in patients with paroxysmal AF, with a preferential distribution in the right inferior pulmonary vein antrum and the left atrial septum.
GW34-e0210
Ziwei Zhu, Xiaowei Zhang
Lanzhou University Second Hospital
OBJECTIVES Left atrial appendage closure (LAAC) reduces the risk of long-term disability or death caused by thromboembolism in elderly patients with atrial fibrillation, and greatly reduces the risk of bleeding. The impact of LAAC on quality of life (QoL) and symptoms has not been well characterized. The purpose of this study was to evaluate the QoL of patients receiving LAAC and the influencing factors.
METHODS This study enrolled 213 patients (Average age is 65) who received LAAC in the Department of Cardiovascular Medicine of Lanzhou University Second Hospital between 2019 and 2022. All patients received physical examination, biochemical testing, transesophageal echocardiography, the 36 Item Short-Form Health Survey (SF-36).
RESULTS The 213 LAAC patients were divided into two groups based on their SF-36 total scores: the QoLlow group (QoL≤682.00, n=107) group; and the QoLhigh group (QoL>682.00, n=106). There were significant statistical differences among the two groups in the nine dimensions of SF-36. After adjusting for confounding variables, logistic regression revealed that a high CHA2DS2-VASc score (OR=1.578, 95% CI: 1.246–1.997) and left ventricular ejection fraction (OR=1.032, 95% CI: 1.001–1.064) were risk factors of low QoL.
CONCLUSIONS CHA2DS2-VASc score is a risk factor of QoL and left ventricular ejection fraction also had a negative effect on QoL of patients who underwent LAAC.
GW34-e0265
Shen Lishui1,2, Yao Yan2
1Shanghai Tenth People’s Hospital
2Fuwai Hospital
OBJECTIVES Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a refractory structural heart disease with a high risk of sudden cardiac death. The T-peak to T-end interval (Tpe) on electrocardiogram can reflect the transmural dispersion of ventricular repolarization, which can be used to as a predictor for malignant arrhythmias and all-cause mortality in a variety of heart diseases. However, its prognostic value in ARVC has not been reported. The purpose of this study was to evaluate the level of Tpe and its risk stratification value in patients with ARVC.
METHODS From October 2001 to January 2019, patients with definite ARVC and an implanted implantable cardioverter-defibrillator (ICD) were enrolled. Baseline data, ECG data and device interrogations information were collected. The primary end point was appropriate ICD shock and second endpoint was all-cause mortality. The patients were divided into three groups according to the level of Tpe and heart rate-corrected Tpe (Tpec). Kaplan-Meier curve analysis was used to compare the differences of clinical endpoints. Multivariate Cox proportional hazards model was performed to reveal the clinical variables which could independently predict the primary endpoints.
RESULTS A total of 102 patients met the inclusion criteria (age 43±14 years, 72 males). The Tpe and Tpec levels in ARVC were 106±32 ms and 111±35 ms, respectively. During device follow-up of 51±38 months, 48 patients occurred appropriate ICD shock therapy. The 5-year appropriate ICD shock therapy rate in the highest Tpec group (>120.6 ms) was 2.56 times that of the lowest group (<92.5 ms). During the mortality follow-up of 77±44 months, 23 patients died. The 5-year mortality in the highest Tpec group was four times that of the lowest group. Univariable cox analysis showed that a longer Tpec could predict appropriate ICD shock and all-cause mortality (P<0.01 for each endpoint). After correction for other covariant predictors, Tpec remained its prediction for shock therapy (HR 1.15, 95% CI 1.05–1.25, P=0.002) and overall mortality (HR 1.20, 95% CI 1.07–1.33, P=0.001).
CONCLUSIONS In patients with ARVC and an implanted ICD, Tpec independently predicts both life-threatening ventricular tachyarrhythmias and overall death.
GW34-e0266
Shen Lishui1,2, Yao Yan2
1Shanghai Tenth People’s Hospital
2Fuwai Hospital
OBJECTIVES Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive loss of right ventricular myocardium and replacement by fibrofatty tissue. In ARVC, biventricular involvement is not rare, while limited data reported the clinical characteristics and long-term prognosis in this population. This study aimed to explore the clinical features in Chinese ARVC population and analyze the clinical phenotypic differences and long-term prognosis in different ARVC subtypes.
METHODS From June 2007 to February 2017, consecutive patients with a definite diagnosis of ARVC according to the 2010 revised task force criteria and a cardiac magnetic resonance imaging examination were retrospectively enrolled. According to left ventricular ejection fraction (LVEF), patients were divided into RV group (isolated right ventricular involvement) and BiV group (biventricular involvement). The baseline clinical data and long-term outcomes were collected for analysis. The primary endpoints were all-cause mortality, heart transplantation and the composite endpoint (all-cause mortality or heart transplantation). The secondary endpoint was ventricular tachycardia. Multivariate Cox regression analysis was performed to determine the clinical variables independently predicting the composite endpoint.
RESULTS A total of 255 patients (aged 37±15 years, males 183) met the inclusion criteria, including 137 patients in BIV group and 118 patients in RV group. Compared with RV group, BIV group patients had older age, longer disease course, higher incidence of heart failure (28 vs. 8%, P<0.001) and syncope (33 vs. 21%, P=0.038), prolonged cardiac depolarization (116±44 ms vs. 105±25 ms, P=0.010), more frequent T wave inversion (44 vs. 19%, P<0.001) in lead V4-V6 on ECG, higher proportion of lower QRS wave voltage (39 vs. 15%, P<0.001) in limb leads, 001) and much lower right ventricular ejection fraction (28±9% vs. 31±9%, P=0.009). During a median follow-up of 66 months, 31 patients died (21 in BIV group and 10 in RV group) and 28 patients received heart transplantations (20 in BIV group and 8 in RV group). Ninety-nine cases (72%) in BIV group and 89 cases (75%) in RV group occurred VT events. The cumulative survival, heart transplantation free survival and composite endpoint free survival in BIV group were significantly lower than those in RV group (log rank P<0.05), while there was no difference in the cumulative ventricular tachycardia free survival between these 2 groups. Multivariate regression analysis indicated that syncope history (HR 2.63, 95% CI 1.27–5.42, P=0.009), cardiac arrest history (HR 6.68, 95% CI 3.44–12.98, P<0.001) and left ventricular ejection fraction (LVEF) (HR 0.96, 95% CI 0.94–0.99, P<0.001) were independent predictors of composite endpoint in patients with ARVC and BiV involvement, and an ICD implantation significantly improved the prognosis (HR 0.27, 95% CI 0.10–0.76, P=0.012).
CONCLUSIONS Biventricular involvement is a common feature in ARVC with more severe clinical manifestations and higher risks of all-cause mortality, heart transplantation and the composite endpoint. Syncope, cardiac arrest, LVEF and ICD implantation could independently predict the composite endpoint in this population.
GW34-e0267
Shen Lishui1,2, Yao Yan2
1Shanghai Tenth People’s Hospital
2Fuwai Hospital
OBJECTIVES Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) have a high risk of ventricular tachycardia (VT) and radiofrequency catheter ablation can reduce the VT burden in these patients. Currently, limited data reported the electrophysiological characteristics and ablation outcomes in patients with ARVC and biventricular involvement. The purpose of this study was to investigate the clinical characteristics, ablation efficacy and predictors of VT recurrence in this population.
METHODS From July 2010 to March 2018, consecutive ARVC patients with cardiac magnetic resonance imaging data and undergoing catheter ablation for sustained VT in our hospital were enrolled. According to left ventricular ejection fraction (LVEF), patients were divided into RV group (isolated right ventricular involvement) and BiV group (biventricular involvement). The primary endpoint was VT recurrence, and the secondary endpoints were all-cause mortality, heart transplantation, and the composite endpoint of mortality or heart transplantation. The differences of electrophysiological mapping, catheter ablation and long-term outcomes between these two groups were analyzed. Multivariate Cox regression analysis was used to find out the predictors for VT recurrence in BiV population.
RESULTS A total of 98 patients (aged 36±14 years, male 85) met the inclusion criteria, including 50 patients biventricular involvement and 48 with isolated right ventricular involvement. The BIV group had a shorter clinical VT cycle length (305±73 ms vs. 342±70 ms, P=0.036) and a higher VT induction rate during electrophysiological stimulation (90 vs. 69%, P=0.009). In BiV group, VT mainly originated from the right ventricle (48/50, 96%), and 30% of patients (15/50) presented left ventricular (LV) arrhythmias (12 with premature ventricular contraction; 10 with VT). Compared with RV-VT, the LV-VT showed a much shorter cycle length (268±29 ms vs. 302±49 ms, P=0.040), 30% of them were complicated with hemodynamic abnormalities, and the VT critical sites mainly located in LV basal inferior wall and LV basal free wall. There was no significant difference in acute ablation success and cumulative VT free survival between these 2 groups. The mean follow-up duration for composite endpoint was 73±26 months. The incidence of composite endpoint in BiV group was significantly higher than that in RV group (log rank P=0.037). Multivariate Cox regression analysis showed that age (HR 0.96, 95% CI 0.93–1.00, P=0.041), right ventricular ejection fraction (HR 0.93, 95% CI 0.86–0.98, P=0.015) and acute complete ablation success (HR 0.18, 95% CI 0.07–0.45, P<0.001) were independent predictors of VT recurrence in patients with ARVC and BiV involvement.
CONCLUSIONS Patients with ARVC and biventricular involvement had faster clinical VT and higher VT inducibility, but showed a comparable acute and long-term outcomes of VT ablation. Age, right ventricular ejection fraction and the acute ablation efficacy independently predicted the VT recurrence in this population.
GW34-e0315
Sijia Lai1, Dayang Wang1,2, Guozhong Pan1, Wenhua Peng1
1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
2Institute of Cardiovascular Disease, Beijing University of Chinese Medicine, Beijing, China
OBJECTIVES Superior vena cava (SVC) syndrome is a rare complication typically caused by extrinsic compression or intravascular obstruction, inflammation or injury. It is characterized by dyspnea, facial or neck edema, distended neck and chest veins, headache, blurry vision, decreased level of consciousness, stridor, cough, and dysphagia. SVC thrombosis without any typical SVC manifestation occurs extremely rarely, which may mislead clinical judgments. In this less frequent clinical case, we present a case of “asymptomatic” SVC thrombosis occlusion along with a complete atrioventricular block.
METHODS A 62-year-old male presented with progressive palpitations and dizziness upon admission. Electrocardiogram showed a third-degree atrioventricular block, but permanent pacemaker implantation failed due to SVC occlusion. Subclavian venography combined with contrast-enhanced computed tomography scanning confirmed SVC thrombosis occlusion, with circuitous and thickened collateral veins under the right chest wall. A permanent leadless pacemaker was successfully implanted through the inferior vena cava, relieving the patient’s palpitations and dizziness.
RESULTS The patient’s condition improved, and follow-up examinations at 1-month and 6-month intervals showed no signs of recurrence of palpitations or dizziness, which suggests that previous dizziness and palpitations were mainly caused by complete atrioventricular block.
CONCLUSIONS Chronic SVC occlusion can be asymptomatic or mildly symptomatic in the condition of extensive venous collateral circulation, and comprehensive evaluations and examinations should be carried out on SVC thrombosis with atrioventricular block to exclude vasculitis or other diseases. Early treatment of the primary disease may be effective, but in some cases, pacemaker implantation is necessary.
GW34-e0338
Chuxian Guo, Long Yang
Cardiology Department, Guizhou Provincial People’s Hospital, Guiyang, China
OBJECTIVES Whether cardiac computed tomography (CCT) provides a sensitive means of detecting left atrial appendage (LAA) thrombus in patients undergoing catheter ablation is conflicting. This study aims to determine the accuracy of CCT for detecting LAA thrombus in patients with non-valvular atrial fibrillation (NVAF), using transesophageal echocardiography (TEE) as the reference standard.
METHODS Six hundred ninety-one patients (male: 60.8%, age: 61±11 years) who had both TEE and CCT before catheter ablation of NVAF were retrospectively included. The CCT protocol consisted of one angiographic phase and one delayed scan 30 seconds later. The thrombus dimension and location, the LAA filling and emptying flow velocity were assessed by TEE.
RESULTS Visually identified LAA thrombus by CCT with a sensitivity, specificity, positive predictive value, and negative predictive value of 68.5%, 99.5%, 92.5%, and 97.4%, respectively. Of the 54(7.8%) patients with LAA thrombi identified by TEE, 27(50.0%) were located at the LAA ostium, and 27(50.0%) were in the LAA. The CCT detected 13(35.1%) of the LAA-ostium thrombi but 24(64.9%) of those in the LAA (P=0.003). Using TEE as the gold standard, patients in the CCT false-negative group had faster LAA filling and emptying velocities (0.53±0.15 m/s vs. 0.38±0.19 m/s; 0.55±0.21 m/s vs. 0.37±0.14 m/s), smaller diameters (8±1 mm vs. 14±9 mm) (all P<0.05). After correcting for confounding factors, the LAA-ostium thrombus (OR=7.813, 95% CI 1.225–49.825, P=0.030) and the diameter of thrombus and were independent predictors for the false-negative results of CCT. CCT was not able to identify thrombi located at LAA ostium with the LAA mean flow velocity higher than 0.35 m/s and diameters shorter than 10 mm.
CONCLUSIONS CCT with a 30s delay scan remains limited for the detection of LAA thrombus in patients with NVAF, especially LAA-ostium thrombi with smaller sizes and higher LAA flow velocity.
GW34-e0368
Shandong Yu
Beijing Friendship Hospital, Capital Medical
OBJECTIVES Observational studies indicate that serum urate level is associated with atrial fibrillation (AF). However, whether this association is causal remains controversial, due to confounding factors and reverse causality. We aim to evaluate the causal relationship of genetically predicted serum urate level with AF.
METHODS A bidirectional Mendelian randomization (MR) study was performed. Instrumental variables were obtained from Global Urate Genetics Consortium (110,347 individuals). We obtained summary statistics of AF from a multi-ethnic GWAS meta-analysis for AF. The study investigated >588,190 individuals (65,446 AF cases). Inverse-variance-weighted method was applied to obtain MR estimates and other statistical methods were conducted in the sensitivity analyses. The reverse MR analysis was performed to evaluate the effect of AF on serum urate levels.
RESULTS Genetically determined serum urate level was not associated with AF [odds ratio (OR), 1.06; 95% confidence interval (CI), 0.99–1.12; P=0.09]. The main results kept robust in the most sensitivity analyses. Multivariable MR analyses suggested that the association pattern did not change, after adjusting for BMI [odds ratio (OR), 1.04; 95% confidence interval (CI), 0.98–1.10; P=0.18], HbA1c [odds ratio (OR), 1.04; 95% confidence interval (CI), 0.96–1.11; P=0.33], hypertension [odds ratio (OR), 1.02; 95% confidence interval (CI), 0.95–1.10; P=0.53] and LDL-C [odds ratio (OR), 1.01; 95% confidence interval (CI), 0.94–1.07; P=0.75]. No consistent evidence was found for the causal effect of HF on serum urate levels [odds ratio (OR), 1.00; 95% confidence interval (CI), 0.98–1.03; P=0.95].
CONCLUSIONS Our MR study supports no bidirectional causal effect of serum urate levels and AF.
GW34-e0404
Wenxiu Li, Runqin Li, Wenqiang Wang, Xiaoxuan Zheng
Taiyuan Central Hospital
OBJECTIVES Correlation analysis of Lp(a) and heart failure combined with persistent atrial fibrillation.
METHODS In this study, Eighty patients with cardiac insufficiency diagnosed and treated at Taiyuan Hospital of Peking University First Hospital from February 2019 to February 2022 were enrolled. Based on the presence or absence of a history of Persistent atrial fibrillation, 39 patients had cardiac insufficiency combined with Persistent atrial fibrillation (AF group) and 41 patients did not have combined atrial fibrillation (non-AF group). The differences in blood biochemical parameters, cardiac function parameters and Lp(a) levels between the two groups were examined and compared, and the diagnostic value of Lp(a) was determined using the subject operating characteristic (ROC) curve.
RESULTS The differences in LDL and Lp(a) levels between patients in the AF group at admission compared with those in the non-AF group were statistically significant (P<0.05). Comparison of cardiac function between the two groups at admission, NT-proBNP levels were higher in the AF group than in the non-AF group, with no statistically significant difference (P>0.05); the AF group patients’ LVEF is lower than the non-AF group patients, but left atrial size is higher in AF group, with statistically significant differences (both P<0.05). Multi-factor binary logistic regression model analysis showed that elevated Lp(a) levels, LVEF, and left atrial size were independent risk factors for the development of Persistent AF in patients with HF (P<0.05). ROC curve analysis of the diagnostic value of Lp(a) for AF in combination with cardiac insufficiency.
CONCLUSIONS Serum Lp(a) levels can be used as a predictor of the risk of Persistent AF in patients with cardiac insufficiency.
GW34-e0420
Peng Liu1,2
1Beijing Tsinghua Changgung Hospital
2Ordos Central Hospital
OBJECTIVES Paroxysmal atrial tachycardia (PAT) was defined as 3 or more consecutive premature atrial contractions lasting less than 30 seconds. It has been proved that PAT was associated with atrial fibrillation (AF). But it remains unclear whether P wave indices on ECG can predict the occurrence of AF in PAT patients. This study intended to investigate the predictive value of P wave indices to AF in PAT patients.
METHODS A retrospective cohort study of 889 patients diagnosed with PAT by 24-hour ECG monitoring in 2015–2020 was conducted. P wave indices including maximum P wave duration (Pmax), minimum P wave duration (Pmin), and P wave dispersion (Pdis) were measured in sinus rhythm by ECG. Endpoint for the study was clinical AF. Multivariate regression was used to analyze the correlation between the P wave indices and AF.
RESULTS During a mean follow-up period of 50.3 months, 58 patients occurred AF (6.5%). Increased Pmax was associated with high risk of AF occurrence (HR=1.021; 95% CI, 1.001–1.042; P=0.041). But there was no significantly relation between Pmin and AF (HR=1.003; 95% CI, 0.992–1.014; P=0.564). Pdis also had no statistical predictive value on AF occurrence (HR=1.004; 95% CI, 0.992–1.106; P=0.494).
CONCLUSIONS Increased Pmax was a predictive factor to AF in patients with PAT. But Pmin and Pdis had no predictive value.
GW34-e0439
Zhao Zixu, Jiang Chao, He Liu, Dai Wenli, Zuo Song, Guo Xueyuan, Li Songnan, Jiang Chenxi, Liu Nian, Tang Ribo, Long Deyong, Du Xin, Song Caihua, Dong Jianzeng, Ma Changsheng
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
OBJECTIVES The association between sodium-glucose cotransporter 2 inhibitor (SGLT2i) and atrial fibrillation (AF) recurrence after catheter ablation (CA) among diabetic patients with AF remains unclear.
METHODS AF patients undergoing initial CA with diabetic history from the China AF registry were included. Patients using SGLT2i were identified and matched by propensity score with non-SGLT2i patients in a 1:3 ratio. The main outcome was AF recurrence during the 18-month follow-up. The survival rate was analyzed by plotting Kaplan-Meier (K-M) curves to compare outcomes between the 2 groups. Univariable and multivariable Cox regression analyses were applied to assess the association between SGLT2i and AF recurrence. Hazard ratios (HRs) with 95% confidence intervals (CIs) were reported. Literature was searched in PubMed, EMBASE, and other resources, including observational studies that compared the impact of SGLT2i with non-SGLT2i on AF recurrence for diabetic patients with AF undergoing CA. We used a random-effects model to analyze our results in consideration of clinical diversity and odds ratio (OR) with 95% CIs for the outcome of interests.
RESULTS A total of 138 diabetic patients with SGLT2i therapy and 387 without SGLT2i were analyzed. Differences in all variables in the baseline between the 2 groups were well-balanced after propensity score matching. AF recurrence occurred in 37 patients (26.8%) in the SGLT2i group and 152 patients (39.3%) in the non-SGLT2i group during a total of 593.3 person-year follow-up. The SGLT2i group was associated with lower AF recurrence compared to the non-SGLT2i group (Hazard Ratio 0.63, 95% Confidence Interval 0.44–0.90, P=0.007). After adjustment for parameters including age, sex, BMI, AF types, AF duration, diabetes duration, LAD, left ventricular ejection fraction, and hemoglobin A1c, our results remained solid. SGLT2i (HR 0.58, 95% CI 0.42–0.84, P<0.001) was independently associated with a lower risk of AF recurrence. In addition, our subgroup analysis showed that patients with larger BMI (≥24 kg/m2), persistent AF and longer AF duration (>1 year) seemed to benefit more from SGLT2i therapy after AF ablation (P for interaction <0.05). A total of 4 studies were analyzed in our meta-analysis demonstrating that SGLT2i was associated with lower AF recurrence after CA (Odds Ratio 0.61, 95% Confidence Interval, 0.54–0.69; P<0.001, I2=0.0%).
CONCLUSIONS Our prospective study coupled with a meta-analysis demonstrated a lower risk of AF recurrence with the use of SGLT2i among diabetic patients after AF ablation. Further RCTs are warranted to fully assess the impact of SGLT2i on AF recurrence after CA in patients with or without diabetes.
GW34-e0454
Caiyi Lu, Zhanpeng Ye, Chongchong Wang, Meixiang He, Huiling Zheng, Yuexia Ding, Chanfang Hu, Huan He, Shujing Dai, Weihong Jing, Longhu Li, Guoyong Liu
Barcelona Heart Center of the Fifth Affiliated Hospital of Guangzhou Medical University, Guangdong Province, P.R. China
OBJECTIVES This study aims to verify the feasibility, adaptability, and progressiveness of the left bundle branch region pacing operation using the diaphragm isometric positioning method for the first time.
METHODS Under the guidance of 30-degree fluoroscopy in the right anterior oblique position, after the 315 fixed curved sheath tube crossed the tricuspid valve, the initial pacing point was determined by using the diaphragm isometric positioning method, including the following four steps: 1. Freeze the 30-degree fluoroscopy image in the right anterior oblique position, find the intersection point between the diaphragm and the cardiac shadow at the apex (anterior intersection point) and the intersection point with the left edge of the spine (posterior intersection point), and connect the anterior and posterior intersection points to obtain the bottom line of the diaphragm. 2. Draw a vertical bisection line from the midpoint of the diaphragm baseline to the upper edge of the diaphragm. The location of left bundle branch pacing lead is located 1.5 cm from the upper edge of the diaphragm. 3. Observe and remember the distance relationship between this point and nearby characteristic fixed structures as a guide for subsequent wire positioning operations. 4. If the pacing at this point is not successful, replace the front, back, and upper and lower positioning points 2–5 mm away from the point to complete the 3830 pacing electrode implantation operation.
RESULTS A total of 12 consecutive adult patients with indications for dual-chamber pacemakers were selected, with a gender ratio of 5/7 and an age of 74.0±6.9 years (65–86). There were 7 cases of sick sinus syndrome (58.3%), 3 cases of atrioventricular block (25.0%), and 2 cases of heart failure resynchronization pacing (16.7%). There were 6 cases (50.0%) with hypertension, 9 cases (75.0%) with coronary heart disease, and 3 cases (25.0%) with diabetes. There were no complications such as surgical infection, pericardial tamponade, pneumothorax, elevated pacing threshold, and electrode dislocation. 9/12 cases (75%) had successful first localization, with an average localization frequency of 1.2±0.5 times (1–3). There were 0 cases of localization failure, and 4 cases (33.3%) had positive left bundle branch potential. The pacing target localization time was 4.08±0.90 seconds (3–5), the first implantation time of the lead was 4.18±1.22 minutes (3–5), the successful implantation time of the lead was 5.5±2.5 minutes (2.5–11.5), and the sheath localization and lead implantation fluoroscopy time was 3.32±0.76 minutes (2.5–5.1). Pacing parameters in the left bundle branch area: threshold 0.56±0.17 V (0.3–0.8), impedance 839.42±93.91 ohms (687–936), perception 13.14±2.95 mV (9.5–17.5). Pacing effect in the left bundle branch area: the peak of the pacing QRS wave is 71.58±4.83 ms (63–77), the width of the pacing QRS is 98.50±5.89 ms (93–110), the amplitude of the V1 lead R wave is 0.52±0.14 ms (0.3–0.7), and the width is 65.83±5.78 ms (58–72).
CONCLUSIONS The use of the diaphragmatic equipartition positioning method for left bundle branch area pacing has the advantages of simple operation, accurate positioning, easy learning, and promotion. Its clinical application prospects, advantages, and limitations need to be verified through large-scale controlled studies.
GW34-e0456
Huaiyang Chen1,2, Yunbin Xiao1,2
1The school of Pediatrics, Hengyang Medical School, University of South China
2Department of Cardiology, Hunan Children’s Hospital
OBJECTIVES Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a kind of cardiomyopathy with autosomal dominant transmission. It is characterized by the gradual replacement of right ventricular myocardial tissue with fatty and/or fibrous tissue, leading to right ventricular structure remodeling, malignant ventricular arrhythmia and sudden cardiac death. To date, more than twenty pathogenic gene mutations have been associated with ARVC, and PKP2, DSP, DSG2, DSC2, TMEM43 and JUP were identified as causative factors for ARVC with sufficient evidence.
METHODS Three members of a family (including proband, sister, mother) underwent whole-exome sequencing and mutational analysis. It includes mutation validation and cosegregation analysis, region analysis, protein secondary structure analysis, mutation validation and cosegregation analysis.
RESULTS Through whole-exome sequencing, this study found that the pediatric patient has several gene mutations, and such genes included JUP, MYL4, PKP2, KCNA5, and PRDM16. According to ACMG standards and ClinGen General Recommendations for Using ACMG/AMP Criteria by Sequence Variant Interpretation working group, we categorized p.R320C (c.958C>T) in JUP as variants of uncertain significance (VUS) (PM2 supporting, PP3A2, PP3B1), c.212T>G (p.M71R) in MYL4 as VUS (PM2 supporting, PP3A1, PP3B1), c.725C>T (p.T242M) in PKP2 as VUS (PM2 supporting, PP3A2, PP3B3), c.196C>T (p.P66S) in KCNA5 as VUS (PM2 supporting, PP3A2, PP3B2) and c.885-4G>A in PRDM16 as VUS (PM2 supporting, PP3A2, PP3C3). Then, we predicted the pathogenicity of these mutated genes via online computational prediction tools and performed Sanger sequencing of the proband and her family. We found that R320 was located in the conserved region via multiple sequence alignment. Meanwhile, we performed computational prediction using FannsDB and PolyPhen-2 online tools to confirm the pathogenicity of c.958C>T, which is predicted to be probably damaging with a score of 1.000.
CONCLUSIONS This study identified a novel mutation, p.R320C, in the JUP gene of a pediatric ARVC patient, which will contribute to the genetic diagnosis and counseling of ARVC.
GW34-e0457
Huaiyang Chen1,2, Yunbin Xiao1,2
1The school of Pediatrics, Hengyang Medical School, University of South China
2Department of Cardiology, Hunan Children’s Hospital
OBJECTIVES Valvular heart disease (VHD) often coexists with atrial fibrillation (AF). AF worsens prognosis in patients with VHD, meanwhile, VHD adds to the stroke risk in AF patients. It’s important for AF patients with valvular lesions to accept anticoagulant therapy, however, the efficacy and safety of novel oral anticoagulants (NOACs) are not clear in AF patients with VHD.
METHODS This study searched Pubmed and Embase from Jan 1, 2000 to Mar 17, 2017, limiting searches to randomized controlled trials of AF patients with VHD who were randomized to receive NOAC or warfarin. We performed a meta-analysis of all 13,803 participants included in six studies, calculated risk ratios (RRs) and 95% confidence intervals (CIs) for each outcome, and compared pooled outcomes and tested for heterogeneity.
RESULTS Eight thousand and fifty-four participants received NOAC therapy and 5747 participants received warfarin. Compared with warfarin, the risk of stroke/SSE in patients treated with higher-dose (RR 0.69, 95% CI 0.57–0.84) and combined dose (RR 0.76, 95% CI 0.64–0.90) of NOAC was lower, but no protective effect of NOAC dose in preventing all-cause death seemed to be present in AF patients with VHD (RR 0.85, 95% CI 0.69–1.06; RR 0.76, 95% CI 0.57–1.01, respectively). ICH was lower with NOAC than with warfarin irrespective of doses of NOAC (RR 0.41, 95% CI 0.19–0.88; RR 0.44, 95% CI 0.74–0.81, respectively). All-cause death in patients on NOAC versus warfarin was similar (RR 1.00, 95% CI 0.90–1.12; RR 0.99, 95% CI 0.90–1.10, respectively).
CONCLUSIONS NOAC is recommended preferentially in AF patients with VHD.
GW34-e0466
Nan Zhang1, Yajuan Yang1,2, Yongtai Gong3, Wenping Zhao4, Gang Xu1, Ruxing Wang2, 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
2Department of Cardiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
3Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin 150000, China
4Affiliated Hospital of Hebei University, Baoding 071000, China
OBJECTIVES This study aimed to identify risk factors for amiodarone-induced torsades de pointes (TdP) in patients with atrial fibrillation (AF).
METHODS Atrial fibrillation patients with and without amiodarone-induced TdP (1:4) were enrolled from the Second Hospital of Tianjin Medical University, Wuxi People’s Hospital Affiliated to Nanjing Medical University, the First Affiliated Hospital of Harbin Medical University, and Affiliated Hospital of Hebei University, up to July 2022. Baseline clinical characteristic and sinus electrocardiogram (ECG) obtained after cardioversion of AF of the included patients were analyzed retrospectively.
RESULTS A total of 8 and 32 AF patients with and without amiodarone-induced TdP were included, respectively. Compared to those without TdP, patients with TdP presented with significantly lower left ventricular ejection fraction [55.15, (57.50, 73.75) % vs. 63.0 (60.0, 65.0) %; P=0.02], interventricular septal thickness (8.00±1.85 mm vs. 10.01±1.56 mm, P=0.02), left ventricular posterior wall thickness (7.96±1.47 mm vs. 9.50±1.19 mm, P=0.02), and serum level of albumin (35.15±3.95 g/L vs. 39.61±2.85 g/L, P<0.01), as well as enlarged left ventricular end-diastolic diameter (55.18±6.56 vs. 44.49±4.47, P<0.01). As for the ECG characteristics, TdP patients had a significantly longer mean QT interval (V2: 635.60±185.44 ms vs. 464.22±90.51 ms, P<0.01), QTc interval (V2: 681.20±155.30 ms vs. 492.39±52.93 ms, P<0.01), T peak to end interval (V2: 196.93±87.01 ms vs. 120.30±65.49 ms, P<0.01), corrected T peak to end interval (V2: 208.53±82.44 ms vs. 126.94±61.05 ms, P<0.01), a higher T peak to end interval/QT ratio (V5: 0.32±0.12 vs. 0.24±0.06, P=0.02) and iCEB (V2: 5.61±1.62 vs. 4.24±0.96, P<0.01) compared with the non-TdP controls. In addition, compared to the non-TdP controls, the incidence of biphasic T wave (50.0 vs. 12.5%, P=0.04), inverted T wave (75.0 vs. 31.3%, P=0.03), T-wave alternans (37.5 vs. 0.0%, P<0.01) and short-long-short cycle (87.5 vs. 0.0%, P<0.01) were significantly higher among patients with amiodarone-induced TdP.
CONCLUSIONS Atrial fibrillation patients with baseline cardiac remodeling, as well as prolongation of QT (c) and Tp-Te (c) interval, higher T peak to end interval/QT ratio, and T wave abnormalities in post-cardioversion ECG may be at higher risk of developing TdP when treated with amiodarone.
GW34-e0467
Nan Zhang1, Xuhong Geng2, Wenhua Song1, Siyao Cheng2, Yi Zheng1, Xiaotong Ma2, Li Wang2, Xuan Li2, 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 300211, China
2Department of Function, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
OBJECTIVES To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs).
METHODS This was an observational study conducted in the Fourth Hospital of Hebei Medical University, China. Cancer patients initiating ICI treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICI initiation and post-treatment ECG were analyzed, mainly focusing on the arrhythmias incidence and alterations of ECG parameters.
RESULTS A total of 87 patients were included in this study (median age, [63 (57, 68)] years; male, 75.9%). Nearly half of the patients (44.8%) presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline, among which, the prevalence of hypertension was the highest (41.4%). The incidence of abnormal ECG increased from 31.0% at baseline to 65.5% after receiving an average of 5.0±2.7 cycles of ICI treatment (P<0.001). The incidence of sinus dysrhythmias was significantly increased after ICI treatment (9.2 vs. 23.0%, P=0.023), of which only the incidence of sinus tachycardia was significantly increased (2.3 vs. 11.5%), but not sinus bradycardia (6.9 vs. 11.5%, P=0.388). There was also a significantly increased incidence of ST-T changes after ICI therapy (17.2 vs. 31.0%, P=0.012), of which only the T wave changes incidence increased significantly (13.8 vs. 29.9%, P=0.001), but not ST change (9.2 vs. 11.5%, P=0.754). The incidence of extra-systole was significantly increased after ICI treatment (0.0 vs. 9.2%, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after treatment with ICI (52.00±22.69° vs. 56.94±21.01°, P=0.043). After ICI treatment, the average heart rate was significantly increased (pre- vs. post-treatment, 75.64±13.37 bpm vs. 79.07±15.37 bpm; P=0.029). The Sokolow-Lyon index (2.33±0.75 mV vs. 2.21±0.81 mV) and QTc interval (428.00±30.05 ms vs. 431.44±36.04 ms) all showed signs of change after treatment, but did not reached the traditional significant level (P<0.05).
CONCLUSIONS The incidence of abnormal ECG was significantly increased after ICI treatment, especially for sinus tachycardia, extra-systole and T wave change; the P wave axis and heart rate was also significantly increased after treatment. These findings suggest that it is important to perform regular ECG monitoring in patients receiving ICIs.
GW34-e0471
Jing Yang, Ping Zhang
Beijing Tsinghua Changgung Hospital
OBJECTIVES T wave alternans (TWA) is a risk factor for life-threatening arrhythmic events (LAEs) in long QT syndrome (LQTS) patients. Few small-sample studies have quantified the TWA value by 24-hour ambulatory recordings or exercise stress tests, and the cut-off point of TWA≥47 mV was based on myocardial infarction patients (ATRAMI study). In our study, we aimed (1) to compare the predictive model of LAE according to the TWA value measured by 24-hour ambulatory recordings superior and exercise stress; (2) to propose a new cutpoint for abnormality in LQTS patients; (3) to evaluate the association of TWA with LAE.
METHODS The study cohort consisted of 116 LQTS patients referred to the cardiology department of Beijing Tsinghua Changgung Hospital. All participants underwent 24-hour ambulatory 12-lead ECG recordings (SEER 12 Ambulatory Recorder; GE Healthcare; USA) and/or exercise stress tests (CASE&T2100-ST2, GE Healthcare; USA). Peak TWA was measured by Modified Moving Average (MMA) algorithm software (Milwaukee WI, GE Healthcare; USA). The primary endpoint was life-threatening arrhythmic events (LAE), which was defined as arrhythmogenic syncope, sustained ventricular tachycardia (SVT), appropriate implantable cardioverter-defibrillators (ICDs) shocks, aborted sudden cardiac death or sudden cardiac death.
RESULTS In total, 32 LQTS patients (32/116, 27.1%) developed LAEs during follow-up duration of 26.2±29.4 months. Peak TWA value quantified by 24-hour ambulatory recordings in LQTS patients with LAEs (LQTS-LAE group) exhibited significant higher compared with LQTS without LAE (LQTS-non-LAE group) (86.7±68.5 vs. 46.9±18.1, P<0.01). Whereas no statistical difference in TWA measured by exercise stress tests was revealed between two groups (80.4±35.8 vs. 82.1±42.9, P=0.99). Receiver-operating characteristic curve (ROC) analysis was applied to the association of peak TWA with LAE in LQTS patients. The area under ROC was 0.747 (95% confidence interval, 0.60–0.896) by 24-hour ambulatory recordings and 0.517 (95% confidence interval, 0.33–0.704) by exercise stress tests. The new cut point peak TWA value of 55.5 μV computed by 24-hour ambulatory recordings with a sensitivity of 70.0% and a specificity of 77.4%. Univariate Cox regression analysis was performed demonstrating that TWA≥55.5 uV was significant predictor of LAEs [HR: 4.84 (2.22–10.50), P<0.001].
CONCLUSIONS Peak TWA measured by 24-hour ambulatory recordings was superior to exercise stress tests as a risk stratification marker in LQTS patients. A new TWA cut point for abnormality in LQTS patients could be applied for clinical assessment.
GW34-e0482
Kun Li, Ping Zhang
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.
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 2–5 BCEs, 3 (4%) patients with 6–10 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 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.
GW34-e0488
Changjin Li
Department of Cardiovascular Medicine, Changhai Hospital, Naval Medical University, No. 168, Changhai Road, Yangpu District, Shanghai 200433, China
OBJECTIVES This study aims to investigate the risk factors related to the recurrence of non-valvular atrial fibrillation (NVAF) after the one-stop procedure combining catheter ablation (CA) and left atrial appendage closure (LAAC).
METHODS A total of 148 patients who underwent the one-stop procedure in our hospital were included from January 2020 to December 2021. After a one-year follow-up, the patients were divided into the sinus rhythm (SR) group and the recurrence of the atrial fibrillation (RAF) group according to the results of a Holter electrocardiogram.
RESULTS Preoperative clinical variables, left atrial volume (LAV) and brain natriuretic peptide (BNP) one-year after the procedure were collected and compared. Univariate analysis showed obesity, hypertension, preoperative LAV, BNP, and creatinine had significant differences (P<0.05) between two groups. One year after the one-stop procedure, the LAV of the SR group was lower than that before the procedure (P<0.05), whereas there was no difference in RAF group. In the multivariate model (Logistic regression), preoperative LAV (OR=2.057, P=0.047) and BNP (OR=1.041, P=0.028) were two predictors for recurrence of AF after one-stop procedure. The receiver operating characteristics (ROC) revealed that LAV levels>62.50 mL were associated with AF recurrence after one-stop procedure.
CONCLUSIONS Seventy three percent of patients were still free of AF recurrences one-year after the one-stop procedure. Preoperative LAV and BNP grades are two independent risk factors for AF recurrence after the one-stop procedure in patients with NVAF.
GW34-e0493
Tingting Lv, Ying Yang, Ping Zhang
Beijing Tsinghua Changgung Hospital
OBJECTIVES Diagnosis is particularly challenging in concealed or asymptomatic long QT syndrome (LQTS). Provocative testing, unmasking the characterization of LQTS, is a promising alternative method for the diagnosis of LQTS, but without uniform standards.
METHODS A comprehensive search was conducted in PubMed, Embase and the Cochrane Library through Oct. 14, 2021. Fixed effects model was used to assess the effect of the provocative testing on QTc interval.
RESULTS A total of 22 studies with 1137 LQTS patients were included. At baseline, QTc interval was 40 ms longer in LQTS patients than in control (MD 40.54, 95% CI 37.43–43.65, P<0.001). Compared to control group, LQTS patients had 28 ms longer ΔQTc upon standing (MD 28.82, 95% CI 23.05–34.58, P<0.001), nearly 30 ms longer both at peak exercise (MD 27.31, 95% CI 21.51–33.11, P<0.001) and recovery 4–5 min (MD 29.85, 95% CI 24.36–35.35, P<0.001). With epinephrine infusion, QTc interval was prolonged both in control and LQTS patients, most obviously in LQT1 (MD 68.26, 95% CI 58.91–77.60, P<0.001) and LQT2 (MD 60.17, 95% CI 50.18–70.16, P<0.001). Subgroup analysis showed QTc interval response to abrupt stand testing and exercise testing varied between LQT1, LQT2 and LQT3, named Type I, Type II and Type III.
CONCLUSIONS QTc trend Type I and Type III during abrupt stand testing and exercise testing can be used to propose a prospective evaluation of LQT1 and LQT3, respectively. Type II QTc trend combined epinephrine infusion testing could distinguish LQT2 from control. A preliminary diagnostic workflow was proposed but deserves further evaluation.
GW34-e0502
Yanhong Chen
Wuhan Asia Heart Hospital
OBJECTIVES Marshall bundle (MB) epicardial connections are utilized in atrial tachycardias (LATs) post atrial fibrillation (AF) ablation. This study sought to classify MB mediated LATs, according to their activation patterns and electrophysiological characteristics.
METHODS From 2019 to 2021, 28 cases of MB-mediated LATs post AF ablation were included in this study. All patients were mapped with ultra-high density system (Rhythmia). MB related LATs was considered if the activation map and propagation showed a reentrant left atrial circuit using possible MB related epicardial connections. MB related reentrant LATs was diagnosed based on: 1) The activation map and propagation showed a re-entrant circuit using possible MB epicardial connections. That is, a pseudo-focal AT pattern which showed an epicardial–endocardial breakthrough (EEB) site >10 mm remote from the collision site, and the EEB site was located along the LA ridge, colocalizing with the anatomical location of the VOM. 2) Entrainment mapping suggested that the MB was in the active part of the circuit. 3) In some patients combined endocardial and epicardial mapping indicated the involvement of MB in the reentrant circuit. 4) the LATs could be terminated on the ethanol infusion of VoM or epicardial ablation of MB area.
RESULTS Three activation patterns were identified: 1) peri-mitral macro-reentry (PM LAT) (n=20, 71.4%); 2) LAA-related localized reentry (n=5, 17.6%), and 3) LPV-related localized reentry (n=3, 10.7%). Endocardial mapping showed pseudo-focal LA activation pattern, while multi-site entrainment pacing suggested a reentrant mechanism. Earliest activation sites (EAS) colocalized with MB-LA epicardial-endocardial breakthrough (EEB) sites, where long-term fragmented potentials were recorded. Low-voltage area caused by previous ablation was consistently found at LA ridge, where near-field potentials were complicated with sharp far-field MB potentials. All tachycardias were successfully terminated with ethanol infusion of the VOM or epicardial ablation within the MB area.
CONCLUSIONS Three types of MB-Mediated LATs post AF-ablation were identified. Reentrant loops were closely related with MB distribution, as well as with the range and depth of previous ablation lesions. Ethanol infusion of VOM was effective in eliminating these tachycardias.
GW34-e0526
Xin-Yao Li
The First Affiliated Hospital of Zhejiang Chinese Medical University
OBJECTIVES Obstructive sleep apnea (OSA) is correlated with atrial fibrillation (AF). If treating OSA with continuous positive airway pressure (CPAP) potentially ameliorates AF isn’t well acknowledged. We aimed to highlight the role of treating OSA with CPAP in patients with AF to predict the outcome if CPAP therapy could reckon the association with lower recurrence or progression of AF.
METHODS This analysis looked up studies in Cochrane library, PubMed, EMBASE, EBSCO, and Web of Science from inception to January, 2019 to valuate AF recurrence or progression in CPAP users, CPAP nonusers and non-OSA patients.
RESULTS Ten observational cohort studies with 15,060 patients were recruited. CPAP therapy lessened the risk of AF recurrence or progression by 62% in a random effects model (24.8 vs 40.8%, Risk Ratio=0.62, 95% confidence interval 0.53–0.82, P=0.02). Compare with non-OSA patients, AF recurrence or progression is much higher in CPAP nonusers (40.6 vs 21.1%, RR=3.65, P=0.0003, 95% CI=0.39–0.76). However, AF recurrence or progression in CPAP group was similar to that in the non-OSA group (24.0 vs 21.1%, RR=0.88, P=0.37, 95% CI=0.86–1.47). Begg’s correlation test and Egger’s regression test uncovered no publication bias for this analysis.
CONCLUSIONS OSA is a salient factor in the progression or recurrence of AF. CPAP therapy for OSA may contribute to AF subjects even if radiofrequency ablation (RFA) or direct current cardioversion is not conducted.
GW34-e0528
Xinbin Zhou
First Affiliated Hospital of Zhejiang Chinese Medical University
OBJECTIVES The effectiveness of restoring the sinus rhythm by catheter ablation relative to that of medical rate control for persistent atrial fibrillation (AF) patients with heart failure (HF) remains to be defined.
METHODS We systematically searched Embase, Pubmed, the Cochrane Library, and ClinicalTrials.gov for articles that compared the outcomes of interest between catheter ablation and medical rate control therapy in persistent AF patients with HF and left ventricular systolic dysfunction (LVSD). The primary endpoint was the change in the left ventricular ejection fraction (LVEF) following catheter ablation or medical rate control therapy relative to baseline. Other endpoints included changes in cardiac function and exercise capacity, including the New York Heart Association (NYHA) class, the brain natriuretic peptide (BNP) level, the peak oxygen consumption (peak VO2), the 6-minute walk test (6MWT) results, and quality of life (QOL).
RESULTS Three randomized controlled trials (RCTs) with 143 patients were included. At the overall term follow-up, catheter ablation significantly improved the LVEF (mean difference [MD]: 6.22%; 95% confidence interval [CI]: 0.7–11.74, P=0.03) and peak VO2 (MD: 2.81 mL/kg/min; 95% CI: 0.78–4.85, P=0.007) and reduced the NYHA class (MD: 0.9; 95% CI: 0.59–1.21, P<0.001) and the Minnesota Living with Heart Failure Questionnaires (MLHFQ) scores (MD: 11.05; 95% CI: 19.45–2.66, P=0.01) compared with the medical rate control for persistent AF patients with HF. Alterations in parameters, such as the BNP level, 6MWT, and Short Form-36 (SF-36) questionnaire scores also revealed trends that favored catheter ablation therapy, although these differences were not significant.
CONCLUSIONS Catheter ablation resulted in improved LVEF, cardiac function, exercise capacity, and QOL for persistent AF patients with HF compared with the medical rate control strategy.
GW34-e0581
Lianfeng Liu
School of Clinical Medicine, Tsinghua University
OBJECTIVES Although pulmonary vein isolation (PVI) remains the cornerstone of atrial fibrillation (AF) ablation. The left atrium posterior wall is an arrhythmogenic substrate that contributes to the development of AF. It remains unclear whether additional left atrial posterior wall isolation (LAPWI) beyond PVI is beneficial in atrial fibrillation (AF) patients. This study evaluated the impact of adjunctive left atrium posterior wall isolation (PWI) on clinical outcomes of atrial fibrillation (AF) patients.
METHODS PubMed, EMBASE, and Cochrane Library databases were searched for studies comparing the outcomes of AF with and without PWI. The efficacy outcomes were recurrence of all atrial arrhythmia (AA), atrial fibrillation (AF), and atrial flutter (AFL)/atrial tachycardia (AT).
RESULTS A total of 16 studies (5 RCTs and 11 original researches) with 3319 patients with AF were included. Twelve studies included persistent/long-standing persistent atrial fibrillation patients, 2 studies with paroxysmal AF patients, 2 studies with paroxysmal AF and persistent AF concurrently. Mean follow-up was 14.4 months. In AF patients, adjunctive PWI obviously reduced the recurrence of all atrial arrhythmias (OR, 0.60; 95% CI, 0.51–0.70; P<.001; I2=83%) and the recurrence of AF (OR, 0.58; 95% CI, 0.47–0.70; P<.001; I2=73%); however, adjunctive PWI was not associated with substantially lower recurrence of atrial flutter (AFL)/atrial tachycardia (AT) (OR, 1.28; 95% CI, 0.94–1.73; P=0.11; I2=51%). The incidence of procedural adverse events between the PVI only and PWI+PVI was similar. PVI+PWI needed longer procedural time and fluoroscopy time.
CONCLUSIONS In patients with AF, adjunctive PWI was associated with decreased recurrence of AF and atrial arrhythmias compared with PVI alone without an increased risk of procedural adverse events. More RCTs are needed to verify the conclusion.
GW34-e0611
Xuan Fengqi
Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Catheter ablation failure poses a clinical challenge for epicardial or intramural ventricular arrhythmia (VA); however, guidewire ablation within the coronary venous system (CVS) may be effective and safe for targeting VAs.
METHODS The ex vivo phase included four steps. In step 1, the steam pop incidence rates during guidewire ablation at power settings of 5, 10, 15, 20, and 25 W were analyzed using 10- and 20-mm-tip guidewires. In step 2, guidewire ablation was performed for application durations of 10, 20, 30, 40, 50, 60, and 90 s, and the lesion size was measured. In step 3, the effects of saline infusion (0, 1, 2, 3, and 4 mL/min) on lesion dimensions and steam pop formation were examined. In step 4, an orthogonal array was constructed to obtain the optimal guidewire ablation parameters. In the in vivo phase, guidewire ablation within the CVS was performed in three dogs, and the lesion features in 10 days after ablation were observed.
RESULTS In step 1, the steam pop incidence rates at 5, 10, 15, 20, and 25 W were 0%, 0%, 12.5%, 62.5%, and 100% using the 10-mm-tip guidewires and 0%, 0%, 0%, 25%, and 75% using the 20-mm-tip guidewires, respectively. In step 2, we found that the lesion areas increased with an increase in the ablation duration (the maximum lesion diameters at 30, 60, and 90 s were 4.9±0.4, 7.0±0.8, and 9.2±0.7 mm in the 10-mm group and 3.2±0.5, 4.5±0.4, and 5.3±0.7 mm in the 20-mm-tip group, respectively). In step 3, we observed that saline infusion was negatively correlated with ablation lesions but had a lower risk of steam pop. The optimal parameters for the 20-mm-tip guidewire ablation were 15 W, 50 s, and 2 mL/min or 20 W, 70 s, 2 mL/min. In the in vivo phase, effective ablation lesions with maximum and minimum diameters of 3.2±0.3 and 2.8±0.5 mm, respectively, were created by the guidewires during the 10-day observation period after ablation.
CONCLUSIONS This novel radiofrequency guidewire ablation technique can feasibly create effective lesions within the CVS, which may improve the efficacy of catheter ablation for challenging epicardial or intramural VA.
GW34-e0722
Hongsen Wang1, Lijie Mi2, Yue Zhang3, Tao Chen1, Xiangmin Shi1, Jun Guo1
1Sixth Medical Center of Chinese PLA General Hospital
2Fuwai Hospital
3Southern Medical School
OBJECTIVES To explore intelligent diagnostic model for supraventricular tachycardia (SVT) mechanisms based on 12-lead wearable electrocardiogram (ECG) devices.
METHODS The 356 SVT wearable ECGs before were selected as a training set to construct an intelligent classification model. Patients diagnosed as SVT receiving electrophysiology study (EPS) and radiofrequency ablation (RA) from October 2021 to December 2022 were selected as the model validation set. The changes of ECG parameters before and during induced tachycardia were compared. Based on Dense Net, with sinus rhythm ECGs added to enhance training, an intelligent diagnosis model for classification of SVT mechanisms were conducted and validated. Further, 3-lead ECG signals from II, III, and V1 were extracted to build a classification model and its efficacy was compared with the 12-lead model.
RESULTS A total of 101 patients were included as the validation set, 68 of whom were diagnosed as atrioventricular nodal re-entrant tachycardia (AVNRT) and 33 were diagnosed as atrioventricular re-entrant tachycardia (AVRT) during EPS. The pre-trained model has an accuracy of 0.7982 and an F1 score of 0.8195 for differentiating AVNRT, an accuracy of 0.8035 and an F1 score of 0.4167 for AVRT. Finally, the total F1 scores of the 3-lead and 12-lead intelligent diagnostic models in the validation set were 0.5897 and 0.5680, respectively. The P-values of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) were 0.714 and 0.817, respectively.
CONCLUSIONS Based on Dense Net, an intelligent diagnostic model of wearable ECG for classification of SVT mechanisms is established with certain accuracy.
GW34-e0723
Yan Liu, Zhiyuan Song
Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University
OBJECTIVES To investigate the correlation between the heparin dose and activated clotting time (ACT) during left atrial appendage occlusion (LAAC) in patients with non-valvular atrial fibrillation (NVAF) under different antithrombotic management backgrounds and to provide evidence for the rational use of heparin in LAAC.
METHODS Patients with NVAF who underwent LAAC in our hospital from February 2017 to March 2021 were evaluated. The patients were grouped according to the type of antithrombotic therapy they received before LAAC and the international normalised ratio (INR) into the following groups: patients on antiplatelet drugs, patients on non-vitamin K antagonist oral anticoagulants, patients with a warfarin INR<1.8, and patients with a warfarin INR≥1.8. The heparin doses were 100, 100, 100, and 80 U/kg, respectively. To measure ACT, venous blood samples were collected at 15 minutes after administering the drug.
RESULTS The study enrolled 435 patients, comprising 135, 155, 107, and 78 in the antiplatelet drug, non-vitamin K antagonist oral anticoagulant, warfarin INR<1.8, and, warfarin INR≥1.8 groups, respectively. At baseline, the proportion of patients with coronary heart disease was significantly lower in the warfarin INR<1.8 group than in the other three groups (P<0.01), while there were no significant differences in other parameters among the groups (P>0.05). The heparin dose was significantly lower in the warfarin INR≥1.8 group (80.25±2.84 U/kg) than in the other three groups (P<0.001). There was no significant difference in the ACT among the four groups (P>0.05). LAAC was completed in all 435 patients without perioperative bleeding or thromboembolic complications.
CONCLUSIONS For patients not taking warfarin or with an INR<1.8 on warfarin before LAAC, it is reasonable to use heparin at a dose of 100 U/kg. It is safe and effective to reduce the heparin dose by 20% in patients with an INR≥1.8.
GW34-e0750
Jin Zhen
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES To evaluate the efficacy and safety of radiofrequency catheter ablation (RFCA) in the treatment of ventricular arrhythmia (VA) after myocardial infarction (MI).
METHODS The RFCA and follow-up results of 31 patients with VA after MI from September 2003 to March 2021 were analyzed retrospectively.
RESULTS The average age of the patients was 61±10 years old. 30 patients were male. The average left ventricular end-diastolic diameter was 59.0±7.5 (48–82) mm, and the left ventricular ejection fraction was 44.5±9.9 (29% 58%). Implantable Cardioverter Defibrillator (ICD) was implanted in 7 patients before or after ablation procedures. In the 23 patients with old myocardial infarction (OMI) and sustained monomorphic ventricular tachycardia (VT), the strategies of mapping and ablation were voltage mapping in sinus rhythm to identify the possible VT substrate, and activation mapping and/or entrainment mapping during VT were also used in some cases. In the 8 patients with acute myocardial infarction (AMI) and electrical storm (ES), the premature ventricular contractions (PVCs) triggering polymorphic VT or ventricular fibrillation (VF) were mapped and ablated. Acute complete success achieved in 29 of the 31 patients, and acute partial success in 1 patient. No serious complications such as pericardial tamponade occurred during and after ablation procedures. The average follow-up time was 56.3±42.3 months in 29 patients with successful follow-up. VA recurred in 5 of 21 cases (23.8%) in OMI group and in 2 of 8 (25.0%) patients in AMI group.
CONCLUSIONS The electrical mechanism and ablation targets were different between OMI with VT and AMI with VA electrical storm. Catheter ablation is a safe and effective method for the treatment of VA after AMI and OMI.
GW34-e0753
Huiyuan Qin, Ming Chu
The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
OBJECTIVES The clinical relevance and underlying mechanisms by which atrial fibrillation can cause stroke are relatively well established, but the definition and underlying mechanisms of post-stroke atrial fibrillation are uncertain. Among the patients, 20–30% had diagnosed atrial fibrillation before the stroke (known atrial fibrillation, KAF). Interestingly, up to 24% of the remaining 70–80% was newly diagnosed with AF after prolonged ECG monitoring (AF detected after stroke, AFDAS).
METHODS To investigate the differences of population distribution characteristics and clinical risks between atrial fibrillation detected after stroke (AFDAS) and known atrial fibrillation (KAF), an observational retrospective epidemiological study including 363 patients with atrial fibrillation and ischemic stroke from three hospitals was conducted.
RESULTS Patients with 242 KAF and 121 AFDAS were included in the analysis. The interval time (38.70 months) of AF after ischemic stroke in patients with AFDAS was significantly shorter than that (69.25 months) of stroke after AF in patients with KAF. In addition, AFDAS patients had a smaller left atrium diameter (LAD) than KAF patients (42.78±6.26 vs 46.18±7.15 with P<0.001), suggesting that electrical remodeling rather than structural remodeling was the main cause of atrial fibrillation in AFDAS. There was no significant difference in age, gender, comorbidities (hypertension, diabetes, coronary heart disease, etc.), CHA2DS2VASc score and HASBLED score between the two groups. Interestingly, we found AFDAS predominantly involved the left insula (18.2 vs 10.7%, P=0.049) while KAF mainly affected the right hemisphere area (40.5 vs 28.1% with P=0.031). We conducted a subgroup analysis of AFDAS patients according to the presence or not of left insular involvement and found that patients with left insular damage had significantly earlier onset of AF (9.01±14.40 months vs 33.40±74.10 months, P=0.021), but the LAD is numerically similar among two subgroups with 42.81 mm in left insula and 42.77 mm in the other group. Such results of subgroup analysis further revealed that left insular damage was more likely to promote atrial electrical remodeling rather than structural remodeling through autonomic nerves, thereby causing the occurrence of atrial fibrillation. In order to further investigate the risk factors for AF in AFDAS patients, clinical baseline data that did not affect the occurrence of AF in AFDAS patients over time, such as sex, hypertension, CAD, HF, TG TC, BNP, insular damage etc. were included in the proportional hazard regression model. The results showed that the ischemic stroke region involving the insula, higher cholesterol, and with CAD comorbidities are risk factors for atrial fibrillation in AFDAS patients. Insula injury risk was much higher than the other two risk factors with HR=12.621, 95% CI (1.213, 131.365). Interval between AFDAS and stroke was a key factor in identifying the etiology of AFDAS.
CONCLUSIONS AFDAS and KAF patients had different characteristics and risk factors and insular cortex and limbic system damage were risk factors for atrial fibrillation after ischemic stroke.
GW34-e0756
Li Feng, Li Hui
The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
OBJECTIVES Obstructive sleep apnea (OSA) is an independent 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 PubMed, Cochrane Library, Web of Science and Embase 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 significantly associated with a lower AF recurrence rate (risk ratio [RR], 0.58; P=0.000). TSA indicated the firm evidence favoring CPAP group in terms of the risk of AF recurrence. 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 reduction of AF recurrence after ablation for AF patients with OSA. The CPAP treatment strategy and the non-PAF proportion may be the potential determinants of outcome impact on AF recurrence for AF patients with OSA after ablation.
GW34-e0784
Chen Sanbao
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Bachmann’s bundle (BB) is the main pathway of interatrial connection that could be involved in the development of atrial fibrillation (AF). Based on this hypothesis, we raised a novel ablation strategy, BB modification in addition to circumferential pulmonary vein isolation (CPVI-BB) in patients with AF.
METHODS A retrospective cohort of patients with AF who underwent CPVI-BB or CPVI alone from March 2018 to July 2021 were enrolled in our study. Propensity score matching was performed in patients with paroxysmal AF and persistent AF, respectively, to reduce the risk of selection bias between the treatment strategy (CPVI-BB or CPVI alone). The primary endpoint was overall freedom from atrial arrhythmias recurrence through 12 months of follow-up.
RESULTS Our propensity score-matched cohort included 82 patients with paroxysmal AF (CPVI group: n=41, CPVI-BB group: n=41) and 168 patients with persistent AF (CPVI group: n=84, CPVI-BB group: n=84). Among patients with persistent AF, one-year freedom from atrial arrhythmias recurrence rate was 83.3% in the CPVI-BB group and 70.2% in the CPVI group (log-rank P=0.047). Among patients with paroxysmal AF, no significant difference was found in the primary endpoint between two groups (85.4% in the CPVI-BB group vs. 80.5% in the CPVI group, log-rank P=0.581). In addition, procedure-related complications and recurrence of atrial tachycardia or atrial flutter were similar between two treatment group, regardless of the type of AF.
CONCLUSIONS BB modification in addition to CPVI is an effective approach in increasing maintenance of sinus rhythm in patients with persistent AF, while it does not improve the clinical outcomes of radiofrequency catheter ablation in patients with paroxysmal AF.
GW34-e0785
Chen Sanbao
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Pulmonary vein isolation (PVI) with wide antral ablation leads to better clinical outcomes for the treatment of atrial fibrillation (AF), but the isolation lesion is invisible in conventional cryoballoon ablation (CB-A). We aimed to prospectively investigate the efficacy of the wide PVI including intervenous carina region guided by high-density mapping compared to PVI alone without mapping system.
METHODS We conducted a propensity score-matched comparison of 69 patients who underwent a wide antral cryoballoon ablation guided by high-density mapping (mapping group) and 129 controls undergoing conventional CB-A in the same period (no mapping group). The primary outcome was clinical recurrence of documented atrial arrhythmias >30 s during 1-year follow-up.
RESULTS Of 69 patients in the mapping group, residual local potential at carina region was found in 16 patients (23.2%) and additional cryothermal applications were performed to achieve carina isolation. Compared with no mapping group, the use of mapping system in the mapping group was associated with longer fluoroscopic time (27.64±8.22 min vs. 23.27±7.05, P<0.001) and more fluoroscopic exposure (340 (186–589) vs. 248 (130–429), P=0.011). However, no significant differences between groups were found in procedure duration and left atrial dwell time (101.88±20.08 vs. 100.71±19.87, P=0.694; 81.81±18.61 vs. 78.11±17.08, P=0.161). The rate of 12-month freedom from clinical recurrence was 85.5% in the mapping group and 70.5% in the no mapping group (log-rank P=0.017). After controlling for baseline characteristics, mapping group exhibited a hazard ratio of 0.42 in freedom from AF (P=0.031).
CONCLUSIONS Voltage mapping after cryoballoon PVI can identify residual potential at PV antrum and additional cryoablation guided by mapping leads to improved freedom from AF compared to conventional PVI without mapping system.
GW34-e0786
Li Sainan
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Left ventricular summit (LVS) is a common origin of idiopathic ventricular arrhythmia (VA). The VA originated from LVS can be ablated via endocardial approach, pericardiocentesis, and coronary venous system. The adjacent structures of LVS are various and the different characteristics of these structures may influence the efficacy and safety of radiofrequency ablation. This research aims to investigate the anatomical characteristics and radiofrequency ablation lesion formation of LVS and its adjacent structures.
METHODS Twelve fresh swine hearts were dissected and the images of coronary CTA were reviewed to measure the depth of myocardium and epicardial fat tissue at the 1/4, 1/2 and 3/4 angle of LVS and at the distance of 0.0, 0.5, 1.0, 1.5, 2.0, 2.5 cm from apex of LVS. The relationship between coronary arteries and veins and between left ventricular myocardium and the adjacent structures, such as LCC and GCV, were observed and analyzed. Radiofrequency ablation was performed on 17 fresh in-vitro swine hearts at LCC, GCV, left ventricular anterior wall (LVAW), accessible area (AA) and inaccessible area (IAA) of LVS, and the endocardium of RVOT and LVOT. The occurrence of steam pop and myocardial lesion was recorded and the depth of myocardial ablation lesion was measured.
RESULTS The thickness of adipose tissue showed a negative correlation with the distance to LVS apex, while the thickness of myocardium presented a positive correlation (Coronary CTA: adipose tissue: y=15.961–4.636×, r=0.782, P<0.001; myocardium: y=5.690+3.002×, r=0.780, P>0.001. Swine heart: adipose tissue: y=6.493–2.392×, r=0.781, P>0.001; myocardium: y=9.904+5.462×, r=0.751, P>0.001). There was adipose tissue [thickness: swine heart: 1.59±1.38 mm, coronary CTA: 2.54 (1.43, 3.86) mm] between GCV/AIV and myocardium, and there were fibrous tissue (thickness: 1.51±0.82 mm) between LCC and myocardium. When the distance was ≤3 cm to the LVS apex, 18 (90%) patients had a cross between GCV and LCX, with the cross points at 24.20±4.74 mm, but only 6 (30%) patients had a cross between AIV and LAD. Among 263 ablation points, 29 (11.0%) had steam pops occurrence (AA: 21/39, IAA: 5/29, RVOT: 3/35, GCV: 2/31, LCC: 1/34, LVAW: 1/43) and 70 (26.6%) had no visible myocardial lesion (IAA: 26/43, AA: 21/39, GCV: 13/31, LCC: 10/34). For those with visible myocardial lesion, the average depth of myocardial lesion was <4 mm at LVOT, RVOT and LVAW, 2~4 mm at LCC and GCV, and >2 mm at AA and IAA.
CONCLUSIONS In LVS, the farther away from the LVS apex, the thinner the adipose tissue and the thicker the myocardium. There was adipose tissue between GCV/AIV and LV myocardium and fibrous tissue between LCC and LV myocardium. AA and IAA are prone to steam pop. Radiofrequency ablation at IAA, AA, GCV and LCC may not cause visible myocardial lesion, and the depth of myocardial lesion was more superficial at these sites if there were visible ones.
GW34-e0788
Li Sainan
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES Ventricular tachycardia is a common complication after surgical repair of congenital heart disease and is becoming the major factors threatening the long-term survival of patients with repaired congenital heart disease. This research aims to investigate the clinical characteristics and long-term ablation outcomes of ventricular tachycardia (VT) in patients with surgical repaired congenital heart disease.
METHODS Nineteen patients having surgical repaired congenital heart disease and undergoing radiofrequency catheter ablation for VT were retrospectively reviewed. The baseline information, clinical manifestation, electrophysiologic study findings, characteristics of catheter ablation, as well as acute success and complication of catheter ablation of each patient were collected. Long-term follow up was performed on all patients to define the long-term outcomes of radiofrequency catheter ablation.
RESULTS Among 19 patients in this research, there were 17 patients with repaired tetralogy of Fallot, 1 patient with repaired trilogy of Fallot and 1 with repaired congenital pulmonary stenosis. Scar in right ventricular outflow tract and ventricular septum were mapped in all patients (19/19), consistent with incision at the right ventricular outflow tract and the repairing patch at the ventricular septum defect, specifically, while the non-surgery related scars were found in 3 patients (at the right ventricular apex in 2 patients and at the right ventricular anterior wall in 1 patient). The acute success was achieved in 18 (94.7%) patients after the first ablation, however 9 patients still had VT episodes during follow-up. After one or more times of ablation, the long-term success was achieved in 14 patients (73.7%). When compared with patients having only the surgery-related scars, those with non-surgery related scars underwent surgery repair at older age (38.0±6.6 years old vs. 6.00±5.37 years old, P=0.002), and in these patients, the dimension of RA was larger (RA: 48.7±7.0 mm vs. 39.6±5.5 mm, P=0.033) and the long-term success rate after radiofrequency ablation was lower (0.0 vs. 87.5%, P=0.010).
CONCLUSIONS The scar of right ventricular outflow tract incision and ventricular septum defect patch can be found in all patients with surgical repaired tetralogy of Fallot, trilogy of Fallot or congenital pulmonary stenosis, but some patients may also present non-surgery related scar. The long-term success after one or more times of radiofrequency ablation was high. Compared with patients having only surgery-related scars, those patients with non-surgery related scars often underwent surgery at older age, and had larger right atrium and lower long-term success.
GW34-e0791
Chenyuan Wang
Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES The effect of percutaneous LAAO on LA structural are incompletely understood. There are few data on LA structural and functional after LAAO. And most of the studies did not take into account the influence of time factor. We aimed to investigate the course of changes in LA structure and LV function over time after percutaneous LAAO.
METHODS We retrospectively reviewed 183 consecutive patients in the Department of Cardiology, General Hospital of Northern Theater Command from January 2017 to December 2019 undergoing left atrial appendage occlusion. The generalized estimation equation was used to analyze the changes of left atrial structure and left ventricular function with time.
RESULTS The results showed that the LA diameter of patients in LAAO group increased 1 month after operation (P=0.013), and there was no significant change in the long-term compared with that before operation (P=0.135). In the LAAO+CA group, there was no significant change in the LA diameter at 1 month after operation (P=0.096), but the LA diameter decreased over long-term (P=0.001), and the ejection fraction (EF) increased (P=0.004). Patients with sinus rhythm maintained increased EF at 1 month after operation and long-term (P=0.01, P=0.01), and LA diameter decreased at long-term (P=0.046). The LA diameter increased transiently (P=0.01) in patients with continuous non-sinus rhythm after operation, and remained unchanged for a long time.
CONCLUSIONS Patients with LAAO will experience transient LA diameter enlargement 1 month after operation, but in the long run, the LA diameter enlargement and EF does not change significantly. Patients with LAAO+CA had no significant change in LA diameter 1 month after operation, long-term LA diameter decreased and EF increased, LA diameter decreased event was advanced to 1 month after operation in patients who maintained sinus rhythm.
GW34-e0792
Chenyuan Wang
Department of Cardiology, General Hospital of Northern Theater Command
OBJECTIVES Left atrial appendage occlusion (LAAO) is not inferior to warfarin in preventing stroke in AF patients. However, adverse events with LAAO remain, like device-related thrombus (DRT), ischemic stroke, death, peri-device leak (PDL), or exposure shoulder part of occluders. Undersizing may result in device embolization or PDL, while aggressive oversizing may cause tamponade or embolization due to exposure shoulder part of occluders. Among those, Choosing the proper device size is important to achieve optimal apposition of the device and hooks against the Left atrial appendage (LAA) wall. But at present, there is not much related research. Therefore, in this study, we analyzed the relationship between the composite event of DRT, ischemic stroke, death, PDL, or exposure shoulder part of occluders and morphological index and compression degree of LAA. According to the analysis results, our suggestions on device selection are reported.
METHODS We retrospectively reviewed 85 consecutive patients in the Department of Cardiology, General Hospital of Northern Theater Command from January 2017 to December 2019 undergoing left atrial appendage occlusion using watchman device. The canonical correlation analysis (CCA) was conducted to explore and quantify the strength of the multivariate relationship between morphological indexes of the LAA and adverse events.
RESULTS LAA ostium (P=0.007), depth (P=0.028) and shape (P=0.023) were related to the occurrence of composite event. The degree of compression can predict compound events. The compression degree (P=0.012) and risk score (P=0.005) are the predictor of composite event. The receiver operating curve (ROC) analysis showed that the area under curve (AUC) of compression degree and risk score were 0.688 (P=0.012), 0.726 (P=0.002), respectively. And optimal threshold of ROC for compression degree and risk score are 0.184 and 3.245.
CONCLUSIONS The Larger LAA was associated with a higher risk of the composite event. For watchman device, compression degree and risk score may predict the postoperative composite event.
GW34-e0820
Zhou Xu
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
OBJECTIVES Previous clinical studies suggest that plasma trimethylamine N-oxide (TMAO) concentration in patients with paroxysmal atrial fibrillation correlate with heart rate variability (HRV). As an indicator of autonomic function, TMAO may potentially contribute to the development of atrial arrhythmia by influencing sympathetic nerve activity. However, the specific mechanism between atrial arrhythmia and sympathetic nerves system is unknown.
METHODS The study employed a new model of atrial cardiomyopathy with spontaneous atrial fibrillation. In the acute experiment, TMAO (100 μmol/0.5 mL) was intraperitoneally injected, and the electrocardiogram was recorded before and after the injection to analyze heart rate variability. In the chronic experiment, 8-week-old mice fed with plus 1.3% high choline diet were used to establish high TMAO model. The electrocardiogram was recorded every week. The atrial arrhythmia events were identified and HRV analysis was employed to indicate autonomic nervous function. At the end of the experiment, heart, LSG and paraventricular nucleus (PVN) tissues were excised for pathological and molecular analyses.
RESULTS Compared to the control group, the acute experimental group showed a significant decrease in SDNN values, indicating an increase in sympathetic nervous activity. The chronic group exhibited a significant increase in atrial arrhythmia events compared to the control. Proinflammatory markers and c-fos in the LSG were determined to be significantly upregulated in both groups, as evidenced by immunofluorescence analysis and relative mRNA levels. Particularly, c-fos and proinflammatory markers expression in PVN was significantly increased in the chronic experimental group, as confirmed by both immunofluorescence staining and Western Blot analysis. The echocardiography results of the chronic group revealed a modest reduction in ejection fraction when compared to the control group (57.22 vs 50.09%, P=0.0289). However, there were no statistically significant differences observed in the changes of left atrial transverse diameter (2.350 vs 2.268, P=0.6322) and left atrial MASSON staining (41.62 vs 44.77%, P=0.1108), which suggests the role of TMAO, the activator of sympathetic nerves, could lead to increased susceptibility of atrial fibrillation.
CONCLUSIONS The present study demonstrated that TMAO significantly promoted atrial arrythmias by activating neuroinflammation within the left stellate ganglia (LSG).
GW34-e0892
Xin Jiang, Lan Zhao
Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University
OBJECTIVES The aim of this study was to investigate the application of three-dimensional modeling techniques in the preoperative prediction of atrial fibrillation (AF), and evaluate its effectiveness and clinical significance in the management of AF patients.
METHODS A systematic review and analysis of relevant literature were conducted to collect studies on the use of three-dimensional modeling techniques for the preoperative prediction of atrial fibrillation. These studies encompassed aspects such as cardiac structure reconstruction, cardiac electrophysiological simulation, atrial fibrillation source localization, treatment planning, and navigation.
RESULTS Significant progress has been made in the preoperative prediction of atrial fibrillation using three-dimensional modeling techniques. By reconstructing the three-dimensional structure of the heart, physicians can gain more accurate insights into the anatomical features and tissue distribution of the heart. Combined with electrophysiological simulation, the occurrence and propagation patterns of atrial fibrillation can be predicted, aiding in the formulation of individualized treatment strategies. Furthermore, three-dimensional modeling techniques can assist in the localization of atrial fibrillation sources, identification of critical sites, and targeted therapies. In terms of treatment planning and navigation, three-dimensional modeling provides visualized procedural pathways and treatment areas, enhancing the accuracy and safety of surgeries.
CONCLUSIONS The preoperative prediction of atrial fibrillation using three-dimensional modeling techniques holds significant clinical significance. It provides physicians with comprehensive and precise information regarding cardiac structure and electrophysiology, facilitating the understanding of disease mechanisms and the localization of pathological sites. Individualized treatment strategies based on three-dimensional modeling can improve treatment outcomes and quality of life for atrial fibrillation patients. However, further research and clinical validation are necessary to ensure the reliability and effectiveness of three-dimensional modeling techniques in the preoperative prediction of atrial fibrillation.
GW34-e0906
Weiguo Wei, Yang Chu, Feng Wu, Min Fan, Haiming Cui
Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
OBJECTIVES Compared with AAD catheter ablation is more effective in maintaining sinus rhythm, reducing af recurrence, improving quality of life, and reducing cardiovascular risk, and can further delay the progression of Af, reverse the increase in atrioventricular volume. Under normal circumstances, no general anesthesia is used in domestic AF Radiofrequency ablation. It is commonly used in combination with analgesics and sedatives such as fentanyl and midazolam. However, adverse reactions are more likely to occur, it has been reported that the incidence of related adverse reactions can reach 30%. Acupuncture and moxibustion can dredge meridians and regulate qi and blood. It was used more than 2000 years ago to eliminate or alleviate various types of pain, it is also used to inhibit and prevent some kinds of injury pain. Acupuncture anesthesia can not only effectively improve the high incidence of adverse drug reactions, but also provide a new solution for patients allergic to narcotic drugs. ECG is a routine examination for patients with atrial fibrillation. Electroencephalography (EEG), also as a bioelectrical signal examination, has no experience in patients with arrhythmias.
METHODS We included a 70-year-old male patient with persistent atrial fibrillation who had EEG and ECG examination both before combined with linear ablation of left atrium and Marshall intravenous absolute alcohol ablation. We used acupuncture anesthesia because the patient was allergic to fentanyl.
RESULTS 1. Recovery of sinus rhythm after ECG surgery in this patient with atrial fibrillation; 2. No adverse effects such as nausea and vomiting after acupuncture anesthesia; 3. Most significant correlation between δ wave and atrial fibrillation in the EEG results; the EEG difference before and after surgery was mainly concentrated in the central brain area, parietal lobe and occipital lobe.
CONCLUSIONS In this case, the use of acupuncture anesthesia in radio-frequency ablation was reported for the first time, and the effect was significant, and there were no obvious adverse reactions of postoperative anesthesia. The effect of acupuncture anesthesia combined with radiofrequency ablation was evaluated by the combination of EEG and ECG for the first time, and it was obvious that the preoperative EEG signal δ wave in patients with atrial fibrillation was significantly abnormal. Moreover, the difference in the expression of brain channels in the central cerebral region, parietal lobe and occipital lobe before and after surgery may indicate that the occurrence of atrial fibrillation is related to the expression of brain electrical signals.
GW34-e1000
Maoxiang Zhao1, Yang Li2, Shouling Wu3, Hao Xue2
1Department of Cardiology, the First Medical Center, Chinese People’s Liberation Army Hospital, Medical School of Chinese People’s Liberation Army, 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
3Department of Cardiology, Kailuan Hospital, Tangshan, China
OBJECTIVES Cardiac conduction disease can lead to syncope, heart failure, and death. The only available therapy is pacemaker implantation, with no established prevention strategies. The present study aimed to determine the association between type 2 diabetes and cardiac conduction diseases.
METHODS This study included 101,080 participants free of prevalent diabetes and cardiac conduction diseases at baseline from the Kailuan Study. All participants were monitored biennially until 31 December 2020. During follow-up, 10,744 participants were diagnosed as having type 2 diabetes. For each case subject, one control subject was randomly selected, matched for age (± 1 years) and sex. The final analysis comprised 10,744 case-control pairs. Cox regression models with age as the underlying time scale were used to evaluate the hazard ratios (HR) and 95% CIs of incident cardiac conduction diseases among patients with new-onset type 2 diabetes versus control subjects.
RESULTS During a median follow-up of 5.69 years, 571 incident events occurred, including 164 atrioventricular block (AVB), 414 bundle-branch block (BBB), 274 right bundle-branch block (RBBB) and 210 left bundle-branch block (LBBB). After adjustment for potential confounders, participants with type 2 diabetes diagnosed had the greater relative risks for most outcomes relative to controls with hazard ratio of 1.40 (95% CI 1.00, 1.96) for AVB, 1.41 (95% CI 1.18, 1.67) for conduction diseases, 1.42 (95% CI 1.16, 1.75) for BBB and 1.69 (95% CI 1.15, 2.49) for LBBB. In contrast, no association between randomization assignment and right bundle-branch block was observed. These results persisted when participants with history of CVD was excluded in the outcome and when considering all-cause death as a competing risk.
CONCLUSIONS During a median follow-up of 5.69 years, 571 incident events occurred, including 164 atrioventricular block (AVB), 414 bundle-branch block (BBB), 274 right bundle-branch block (RBBB) and 210 left bundle-branch block (LBBB). After adjustment for potential confounders, participants with type 2 diabetes diagnosed had the greater relative risks for most outcomes relative to controls with hazard ratio of 1.40 (95% CI 1.00, 1.96) for AVB, 1.41 (95% CI 1.18, 1.67) for conduction diseases, 1.42 (95% CI 1.16, 1.75) for BBB and 1.69 (95% CI 1.15, 2.49) for LBBB. In contrast, no association between randomization assignment and right bundle-branch block was observed. These results persisted when participants with history of CVD was excluded in the outcome and when considering all-cause death as a competing risk.
GW34-e1004
Fei Liu, Yue Huang, Chenglin Li, Xiaolei Yang, Yunlong Xia
First Affiliated Hospital of Dalian Medical University
OBJECTIVES First-degree atrioventricular block (I°AVB) and atrial remodeling are independent predictive factors for various adverse cardiovascular events. This study aims to explore the association between atrial remodeling and I°AVB and further investigate the prognostic implication of atrial remodeling in I°AVB patients, thereby elucidating its clinical value.
METHODS A retrospective analysis was conducted on 15,793 patients who were hospitalized due to cardiovascular diseases in the First Affiliated Hospital of Dalian Medical University from January 2012 to August 2021. Based on the PR interval, the patients were divided into the I°AVB group (PR interval>200 ms, 616 cases) and the non-I°AVB group (PR interval≤200 ms, 15,177 cases). The differences in P-wave parameters (P-wave duration in lead II, P wave terminal force in lead V1 (PTFV1), P-wave amplitude in lead I, P-wave dispersion) and left atrial diameter between the two groups were analyzed. Further follow-up of patients with I°AVB was performed and the endpoint is occurrence of new-onset atrial fibrillation (AF) or ischemic stroke during follow-up. Cox regression analysis was used to evaluate the relationship between atrial remodeling-related parameters and the occurrence of AF and stroke after adjusting for confounding factors in I°AVB patients.
RESULTS Compared to patients with a normal PR interval, I°AVB patients exhibited more pronounced atrial remodeling. The P-wave duration, PTFV1, P-wave dispersion, and left atrial diameter were significantly increased (P<0.001), while the P-wave amplitude was significantly decreased in I°AVB patients (p<0.001). Moreover, the proportion of I°AVB patients with P-wave duration>120 ms, absolute PTFV1>4000 μV*ms, and left atrial enlargement was significantly higher (P<0.001). Binary logistic regression analysis revealed that prolonged P-wave duration (OR=1.034, 95% CI 1.028–1.040), abnormal PTFV1 (OR=1.378, 95% CI 1.105–1.719), increased P-wave dispersion (OR=1.007, 95% CI 1.004–1.010), left atrial enlargement (OR=1.067, 95% CI 1.043–1.092), and decreased P-wave amplitude in lead I (OR=0.991, 95% CI 0.988–0.994) were all significantly associated with I°AVB (P<0.05). Multivariable Cox regression analysis showed that prolonged P-wave duration (AF: HR=5.110, 95% CI 2.355–11.088; ischemic stroke: HR=3.340, 95% CI 1.419–7.859), abnormal PTFV1 (AF: HR=3.665, 95% CI 1.680–7.994; ischemic stroke: HR=3.652, 95% CI 1.494–8.926), and left atrial enlargement (AF: HR=3.885, 95% CI 1.680–8.982; ischemic stroke: HR=2.880, 95% CI 1.139–7.277) were independent risk factors for AF and ischemic stroke in I°AVB patients (P<0.05). However, in I°AVB patients, increased P-wave dispersion was only independently associated with AF (HR=5.734, 95% CI 2.426–13.551, P<0.05) and not with ischemic stroke, while increased P-wave amplitude was not associated with AF or ischemic stroke in multivariable analysis.
CONCLUSIONS Atrial remodeling is significantly pronounced in patients with I°AVB. Abnormal parameters associated with atrial remodeling serve as independent risk factors for AF and ischemic stroke in these patients. This underscores the importance of early assessment of atrial remodeling to stratify I°AVB patients with high-risk cardiovascular diseases.
GW34-e1046
Sun Mingyu
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China
OBJECTIVES The aim of this study was to assess the efficacy and safety of “one-stop” procedures that combined radiofrequency catheter ablation (RFCA) and left atrial appendage closure (LAAC) with the Watchman device by guidance of intracardiac echocardiography (ICE) vs transesophageal echocardiography (TEE) in patients with atrial fibrillation.
METHODS This study was a prospective, single-center study. Patients who underwent “one-stop” procedures by guidance of ICE in our center between January 2021 and October 2022 was reviewed retrospectively. Cardiac computed tomography angiogram and TEE was performed before the procedure in all patients. LAAC was performed after RFCA. Complications were continuously monitored by ultrasound or fluoroscopy throughout the procedure. TEE was performed at 3 months after the procedure. Outpatient and transtelephonic follow-up were carried out to evaluate arrhythmia recurrence and clinical events.
RESULTS A total of 302 patients with AF were enrolled. One hundred and ninety-three procedures were TEE guided and 109 were ICE guided. Patient characteristics were similar between the ICE and TEE groups. Intraprocedural thrombus formation in left atrial appendage (LAA) was observed in 3 (1.46%) patients in ICE group and 15 (11.63%) patients in TEE group (P<0.05) before LAAC. Total fluoroscopy time and dose in ICE group were less than those in TEE group. The total “one-stop” turnaround time and LAAC procedure time in ICE group were significantly shorter than those in TEE group (P>0.05). Postoperative esophagus discomfort, nausea and vomiting, and hypotension were more often seen in TEE group (P<0.001). There was no significant difference in matched cases between ICE and fluoroscopy measurements (P=0.082). The TEE results related to LAAC and clinical events were similar between the two groups during follow up (P>0.05).
CONCLUSIONS ICE-guided “one-stop” procedure was safe and feasible with less radiation exposure, shorter turnaround time and fewer complications and intraoperative thrombus formations compared with the TEE group. ICE offered accurate measurements in LAA dimension during LAAC. Echocardiography during the “one-stop” procedures was necessary to rule out the intraoperative thrombus.
GW34-e1056
Shengjie Wu1,2, Wenxuan Shang1,2, Lan Su1,2, Yang Ye3, Guosheng Fu3, Weijian Huang1,2
1Department of Cardiology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
2Key Lab of Cardiovascular Disease of Wenzhou, Wenzhou, China
3Department of Cardiology, Sir Run Run Shaw Hospital, Affiliated to Medical College of Zhejiang University, Hangzhou, China
OBJECTIVES Female seems to derive more benefit from biventricular pacing, however, the sex-specific difference in conduction system pacing (CSP) has not been well established. To investigate sex differences in clinic benefits in patients with left bundle branch block (LBBB) who received CSP and assess the influenced factors.
METHODS This prospective, observational study from two centers focuses on nonischemic cardiomyopathy patients with left ventricular ejection fractions (LVEF) ≤40% and typical LBBB who underwent CSP. Serial follow-up was conducted to evaluate LVEF improvements and the composite endpoint of death or heart failure hospitalization (HFH). Mediation analysis was employed to explore the indirect effects of potential mediators on the relationship between gender and LVEF super-response.
RESULTS Of the 176 patients analyzed, there were no significant differences in pharmacotherapy and comorbidities between sexes, except for paced QRS duration (pQRSd) and left ventricular end-diastolic diameter (LVEDd). Among 171 patients who complete a specific period of follow-up (6–12 months), super-response was observed in 120 (70%), with a higher occurrence in female (78%) compared to male (63%). Multivariate analysis revealed that female-sex cannot predict super echocardiographic response with OR (95% CI) of 1.447 (0.682–3.068) after adjusting the confounding factors. The incidence of death or HFH was lower in females (7.1 Vs 13%), although statistical significance was not reached (Log-rank P=0.216). Notably, in females, the super-response showed a prominent and antecedent difference compared to males at the same electrocardiography and/or echocardiographic parameters value. Mediation analysis suggested that LVEDd explained 26.07% of the indirect effects between gender and super-response, whereas pQRSd explained 27.98%.
CONCLUSIONS Our study suggests that female is likely to benefit more from CSP, and this difference is partly driven by pQRSd and LVEDd.
GW34-e1066
Wenxiu Li, Runqin Li, Wenqiang Wang
Taiyuan Central Hospital
OBJECTIVES To investigate the correlation between the morphology and size of the left auricle and the occurrence of heart failure in patients with atrial fibrillation.
METHODS Two hundred patients with AF diagnosed and treated at Taiyuan Hospital of Peking University First Hospital from November 2022 to November 2024 were enrolled in this study. According to the presence or absence of a history of heart failure, one group of patients had HF combined with AF (HF group), and the other group had patients without HF combined (non-HF group). All patients underwent multi-layer spiral CT enhancement scans, and the scanned images were reconstructed in three dimensions by post-processing techniques for pulmonary veins and left atrium, and the original images were reconstructed in 75% phase and transferred to Philips EBW 4.5 workstation for post-processing. Volume reproduction, multiplanar reconstruction and other post-processing methods were used to observe and analyze the morphology of the left heart ear from multiple angles and in all directions. Any differences in left auricular morphology and left auricular caliber between the groups were analyzed to explore the correlation between the changes in left auricular morphology and size caused and the occurrence of heart failure in patients with atrial fibrillation. Patients who underwent radiofrequency ablation within the two groups were followed up for 1 year, and patients with AF recurrence after 1 year were counted. Multi-factor logistic regression analysis was used to clarify whether factors such as heart failure, left auricular size, morphology, type and duration of AF were risk factors for AF recurrence.
RESULTS The caliber of the left auricle was larger in patients with persistent AF than in patients with paroxysmal AF. The larger the caliber of the left heart ear, the greater the likelihood of heart failure. Patients in the high-risk CHA2DS2-VASc group had a larger left auricular caliber than those in the low-risk group. Left ear morphologic features were associated with the risk of recurrence after radiofrequency ablation of atrial fibrillation.
CONCLUSIONS There is a correlation between left auricular morphology, size, and the development of heart failure in patients with atrial fibrillation. Early cardiac radiofrequency ablation is recommended in patients with AF with cauliflower- and chicken-wing-shaped left ear morphology to delay the progression of heart failure and myocardial remodeling.
GW34-e1068
Shengjie Wu1,2, Wenxuan Shang1,2, Lan Su1,2, Dingzhou Wang1,2, Lei Xu1,2, Weijian Huang1,2
1Department of Cardiology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
2Key Lab of Cardiovascular Disease of Wenzhou, Wenzhou, China
OBJECTIVES This study aimed to assess the predictive ability of various measures of electrical delay for echocardiographic-defined super-response in patients undergoing Left bundle branch pacing (LBBP).
METHODS This observational study included consecutive patients with LVEF ≤40% and typical left bundle branch block (LBBB) who were referred for LBBP. Clinical data, including electrocardiographic data and electrocardiogram measurements, were collected pre- and post-procedure. Feature selection and model building were performed using Lasso regression model. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were employed to evaluate and compare the performance of the model and various measures.
RESULTS Among 83 patients (mean age 69.8±9.7 years; mean Stim-LVAT 78.05±10.10 ms; 54% men), Stim-LVAT and LVEDd showed early and sustained reductions during the serial follow-up. Pearson’s analysis revealed positive correlations between Stim-LVAT with QRS duration, paced QRS duration, and LVEDD (r=0.446, P>0.001; r=0.485, P>0.001; r=0.490, P>0.001; respectively). The positive echocardiographic super-response was observed in 66% of patients. Using Lasso regression analysis, we identified two predictors (Stim-LVAT and paced QRS duration) that were incorporated into the predict model. The Bootstrap resampling (times=500) ROC analysis demonstrated that a single parameter, Stim-LVAT, exhibited comparable performance to the final Lasso regression model in achieving effective discrimination for super-response (AUC: 0.794 95% CI: 0.673–0.889; AUC: 0.799 95% CI: 0.668–0.889; P=0.351 for all comparisons). Furthermore, the DCA revealed that both the Stim-LVAT and the final model yielded favorable net benefits.
CONCLUSIONS Stim-LVAT has a significant association with heart size and exhibits dynamic changes during follow-up. A short Stim-LVAT has a detrimental effect on echocardiographic super-response to LBBP in patients with true LBBB, which may be a useful predictor to identify LBBP response in these patients.
GW34-e1078
Fengyu Huang, Yue Zhong, Ran Zhang, Wenjuan Bai, Li Rao
West China Hospital of Sichuan University
OBJECTIVES Atrial fibrillation (AF) is a heterogeneous disease, and the association between AF phenotypes and outcome of different catheter ablation strategies remains unclear. We sought to assess whether AF phenotypes derived from cluster analysis had different ablation patterns and outcomes.
METHODS Hierarchical clustering was performed on 59 baseline variables from 1102 AF patients undergoing catheter ablation. Multivariate logistic regression models were used to evaluate the association between identified clusters and clinical outcomes. Ablation strategies were compared within each cluster regarding early ablation success and adverse events.
RESULTS Five statistically driven cluster could be identified: (1) younger age cluster (n=404); (2) elderly with increased prevalence of chronic disease cluster (n=438); (3) high prevalence of sinus node dysfunction cluster (n=160); (4) heart failure cluster (n=80); (5) prior coronary artery revascularization cluster (n=20). Compared with cluster 1, the adjusted risk of composite major adverse cardiovascular or neurological events at 24-month follow-up was 2.33 (95% CI, 1.17–4.64, P=0.016) for Cluster 2, 2.58 (95% CI, 1.12–5.93, P=0.025) for Cluster 3, 4.83 (95% CI, 2.02–11.57, P<0.001) for Cluster 4, and 4.84 (95% CI, 1.17–20.01, P=0.030) for Cluster 5. Patients in cluster 2 had more chances to achieve early ablation success by pulmonary veins isolation alone than extensive ablation strategies (OR, 1.97; 95% CI, 1.28–3.03).
CONCLUSIONS Cluster analysis could identify phenotypes of AF with different profiles on the efficacy of ablation strategies and the risk of adverse outcomes. These phenotypes might inform the individualized treatment decision for AF patients.
GW34-e1080
Qing Yan, Jiaqi Liang, Yide Yuan, Jiahong Xue
Xi’an Jiaotong University Second Affiliated Hospital
OBJECTIVES The triglyceride-glucose index is a new surrogate marker for insulin resistance. This study aims to explore the relationship between the cumulative triglyceride-glucose index and atrial fibrillation recurrence after radiofrequency catheter ablation.
METHODS A total of 576 atrial fibrillation patients who underwent radio-frequency catheter ablation at the Second Affiliated Hospital of Xi’an Jiaotong University were included in this study. Participants were grouped based on their cumulative triglyceride-glucose index tertiles in the 3 months after ablation. Cox regression and restricted cubic spline analyses were used to determine the relationship between the cumulative triglyceride-glucose index and AF recurrence. And the predictive value of all risk factors was assessed using the receiver operating curve analysis.
RESULTS Finally, 375 completed the study (age: 63.23±10.73, 64.27% male). The risk of atrial fibrillation recurrence increased with the cumulative triglyceride-glucose index tertiles. After adjusting for potential confounders, patients in the medium (HR=4.949, 95 CI:1.778–13.778, P=0.002) and high (HR=8.716, 95 CI:3.371–22.536, P<0.001) cumulative triglyceride-glucose index group had a higher risk of atrial fibrillation recurrence than the low cumulative triglyceride-glucose group. The restricted cubic spline regression model also showed an increased risk of atrial fibrillation recurrence with an increase in the cumulative triglyceride-glucose index. When considering the cumulative triglyceride-glucose index, left atrial diameter, and lactate dehydrogenase as a comprehensive factor, the model could effectively predict atrial fibrillation recurrence after radiofrequency catheter ablation (AUC=0.847, 95 CI: 0.797–0.897, P<0.001).
CONCLUSIONS The cumulative triglyceride-glucose index is a risk factor for atrial fibrillation recurrence after radiofrequency catheter ablation. Monitoring the longitudinal triglyceride-glucose index may assist with optimized-for-risk stratification and outcome prediction for atrial fibrillation recurrence.
GW34-e1085
Shuyu Jin, Yumei Xue
Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
OBJECTIVES We aimed to evaluate the effectiveness and safety of high-power, short-duration (HPSD) radiofrequency catheter ablation (RFA) guided by a relatively low ablation index (AI) for persistent atrial fibrillation (PeAF) patients.
METHODS The HPSD RFA strategy was performed in PeAF patients under-going first ablation. Guided by AI, PVI was performed at 40–50 W targeting AI values of 350–400 at the anterior, 350–420 at the superior and inferior wall of the PV, and 320–380 at the posterior wall of the LA with a CF of 5–15 g and irrigation flow rate of 15–30 mL/min per site (ST catheter at 30 mL/min; STSF catheter at 15 mL/min; specific sites adjusted according to operators’ experience), and an inter-lesion distance (ILD) of 4 mm. For additional ablation, the power output of the mitral isthmus (MI) and posterior wall isolation were 40–50 W with AI values of 350–400, that of the cavotricuspid isthmus (CTI) was 35 W was 35 W, and that of the coronary sinus was 25 W.
RESULTS A total of 240 PeAF patients underwent RFA and completed one-year follow-up. The mean left atrial (LA) size was 40.81±5.06 mm and the duration of AF history was longer. After a single procedure, the early recurrence rate was 38.75% and the long-term recurrence rate was 33.33%, with the majority of early or late recurrences being AF. The areas in which touch-up ablation was most commonly performed were the left superior pulmonary veins, the LA roof, the cavotricuspid isthmus and the mitral isthmus. Following multivariable analysis, LA size was an independent risk factor for atrial arrhythmia recurrence within a one-year follow-up [hazard ratio (HR) 1.07, P=0.01]. Moreover, the HPSD RFA strategy proved to be safe, with a low complication rate (0.83%) and no atrioesophageal fistula or steam pops occurring.
CONCLUSIONS Under the guidance of relatively low AI values, the HPSD RFA strategy appeared to be feasible, effective and safe in PeAF patients. LA size was an independent risk factor for late atrial arrhythmia recurrence.
GW34-e1172
Chen Songwen, Xiaofeng Lu, Shaowen Liu
Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine
OBJECTIVES Premature ventricular complexes (PVC) originating from proximal left anterior fascicle (LAF), with unique electrocardiographic characteristics, could be eliminated safely from right coronary cusp (RCC). This study was performed to evaluate the feasibility and effectiveness of mapping and ablation only at RCC for eliminating proximal LAF-PVC based on the electrocardiographic characteristics.
METHODS The proximal LAF-PVC was defined as PVC-QRS with prominent inferior frontal plane QRS axis and with right bundle branch block, and with the QRS duration difference (between PVC and sinus rhythm) <15 ms. The study group consisted of consecutive patients with proximal LAF-PVC, which was prospectively mapped and ablated only at RCC. The pre-study group and control group consisted of patients with proximal LAF-PVC, which was mapped and ablated at left ventricle and RCC before or during the study period.
RESULTS The radiofrequency applications and catheter reposition of study group were less than that of control group (P=0.014; and P=0.015). In comparison with control group, the mapping time (12.7±6.3 minutes vs. 52.4±46.1 minutes, P=0.021), ablation time (188.6±84.6 seconds vs. 399.7±190.9 seconds, P=0.008), and procedure time (47.4±6.4 minutes vs. 90.0±47.7 minutes, P=0.017) of study group were shorter. The mapping time and procedure time of study group were also shorter than that of pre-study group (both P<0.001).
CONCLUSIONS Under the guidance of electrocardiographic characteristics, mapping and ablation only at RCC was a simple, safe, and effective method for elimination of proximal LAF-PVC. Retrograde transaortic manipulation could be avoided in this procedure workflow.
GW34-e1184
Yichen Zhao, Can Zhou, Cheng Zhao, Qing Ye, Jianzeng Dong, Jiangang Wang
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Left atrial appendage (LAA) played an important role in regulating left atrial function, and much evidence supports the possibility that changes in left atrial structure may cause or worsen mitral regurgitation. This study intended to investigate the outcomes of patients with mitral regurgitation who underwent left atrial appendage closure (resection or endocardial closure) during isolated surgical ablations.
METHODS Patients with mild or moderate mitral regurgitation who received isolated surgical ablations for atrial fibrillation in our center from 2013 to 2022 were referred. During follow-up, each clinical visit was composed of medical interrogation, a 24 h Holter, and an echocardiographic evaluation. Death, atrial fibrillation, worsening of mitral regurgitation, and stroke were evaluated as outcomes. Freedom from outcomes whose results were adjusted by inverse probability of treatment weighting for casual effects after acquiring propensity scores.
RESULTS A total of 456 patients were enrolled in this study. During a median follow-up of 48 months, 30 deaths and 11 cases of stroke were observed. After adjustments, no significant differences in terms of death or stroke were observed among three groups. Patients who underwent resection or endocardial closure during surgical ablations had a higher risk of mitral regurgitation worsening during follow-up (P<0.05). During the whole follow-up, patients who underwent left atrial appendage interventions showed significantly larger left atrial and mitral annular diameters, as well as lower tethering height than those who had left atrial appendage preserved (all P<0.05).
CONCLUSIONS Mitral regurgitation was more likely to get worse when patients with fundamental mitral diseases underwent LAA interventions during isolated surgical AF ablations. In the absence of LAA, the dilation of the left atrium and mitral annulus may ultimately lead to the worsening of regurgitation.
GW34-e1224
Xixiang Tang1, Wang Jiafu2, Ouyang Xiaolan2, Chen Qian2, Wu Bingyuan2, Peng Long2, Li Suhua2
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 12,13-diHOME has potential in protecting against metabolic disorders and heart disease, but its relationship with atrial fibrillation (AF) remains unknown. To determine whether 12,13-diHOME levels are associated with left atrial (LA) remodeling and post-ablation recurrence in patients with AF.
METHODS A single-center prospective study conducted from September 2020 to March 2023. Adult patients underwent percutaneous catheter ablation for AF, paroxysmal supraventricular tachycardia (PSVT), or idiopathic premature ventricular complexes (PVC) were recruited from September 2020 to March 2023. AF patients were considered as study group, while PSVT and PVC patients were considered as control group. The levels of serum 12,13-diHOME in PV and CS blood samples were examined using 12,13-diHOME enzyme-linked immunosorbent assay (ELISA) Kit. The predictive role of 12,13-diHOME on the AF and the post-ablation recurrence rate of AF within 12 months was analyzed.
RESULTS A total of 222 subjects (103 non-AF controls and 119 AF patients) were included for analysis. Levels of 12,13-diHOME were lower in the CS sample of AF patients compared to controls (84.32±20.13 vs. 96.24±23.56 pg/mL, respectively, P<0.01), and were significantly correlated to adverse remodeling of the LA. Over 1-year follow-up, post-ablation recurrence of AF occurred in 20 patients (16.8%). The basal level of 12,13-diHOME in CS was significantly reduced in patients with recurrence compared to those without recurrence (61.10±8.07 vs. 89.01±18.52 pg/mL, respectively, P<0.01). Furthermore, ROC analysis found that the AUC of 12,13-diHOME in CS for predicting recurrence of AF was significantly higher than that in PV [0.910 (95% CI: 0.855–0.965) vs. 0.500 (95% CI: 0.352–0.649), respectively, P<0.01]. Multivariable regression analyses further demonstrated that 12,13-diHOME in CS was associated with the post-ablation recurrence of AF [OR (95% CI)=0.668 (0.476–0.936), P=0.019] after adjusting for other confounding.
CONCLUSIONS The levels of CS 12,13-diHOME levels were associated with adverse LA remodeling, and 1-year post-ablation recurrence of AF. These findings suggest that CS 12,13-diHOME levels may provide diagnostic and prognostic information in patients with AF.
GW34-e1256
Ziyong Hao, Bin Liu, Lisheng Jiang, Ben He
Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES The combination of catheter ablation (CA) and left atrial appendage occlusion (LAAO) in a “one-stop” approach offers comprehensive management for patients with atrial fibrillation (AF). However, the safety and efficacy of the combined procedure compared to LAAO alone remains unclear.
METHODS Patients with AF at increased stroke risk who received LAAO were divided into either combined (CA and LAAO) procedure or LAAO alone group. Propensity score matching was used to balance the baseline characteristics.
RESULTS A total of 707 AF patients at high risk of stroke who received LAAO procedure at a single center from 2017 to 2022 were consecutively enrolled in this study. After 1:1 propensity score matching, 166 patients who underwent LAAO alone (n=83) or the combined procedure (n=83) were analyzed. Successful LAAO was achieved in all (100%) patients, with a low incidence of periprocedural complications in both groups (2.4 vs. 4.8%, LAAO vs. combined, P=0.68). The incidence of peri-device leak post-LAAO was significantly higher in the combined group (25.3 vs. 43.4%, P=0.01). After a median follow-up of 2 years, the incidence of adverse events was low and comparable between the two groups (14.5 vs. 8.4%, HR: 0.51 [95% CI: 0.20–1.31], P=0.17). However, the rate of HF rehospitalization was significantly lower in the combined group (10.8 vs. 2.4%, HR: 0.21 [95% CI: 0.06–0.67], P=0.02).
CONCLUSIONS Combining CA and LAAO in a “one-stop” approach is safe and brings additional benefit in relieving symptoms of heart failure, although peri-device leak was more common compared to LAAO alone.
GW34-e1277
Maoxiang Zhao1, Yang Li2, Shouling Wu3, Hao Xue2
1Department of Cardiology, the First Medical Center, Chinese People’s Liberation Army Hospital, Medical School of Chinese People’s Liberation Army, 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
3Department of Cardiology, Kailuan Hospital, Tangshan, China
OBJECTIVES Cardiac conduction disease can lead to syncope, heart failure, and death. The only available therapy is pacemaker implantation, with no established prevention strategies. The present study aimed to determine the association between type 2 diabetes and cardiac conduction diseases.
METHODS This study included 101,080 participants free of prevalent diabetes and cardiac conduction diseases at baseline from the Kailuan Study. All participants were monitored biennially until 31 December 2020. During follow-up, 10,744 participants were diagnosed as having type 2 diabetes. For each case subject, one control subject was randomly selected, matched for age (±1 years) and sex. The final analysis comprised 10,744 case-control pairs. Cox regression models with age as the underlying time scale were used to evaluate the hazard ratios (HR) and 95% CIs of incident cardiac conduction diseases among patients with new-onset type 2 diabetes versus control subjects.
RESULTS During a median follow-up of 5.69 years, 571 incident events occurred, including 164 atrioventricular block (AVB), 414 bundle-branch block (BBB), 274 right bundle-branch block (RBBB) and 210 left bundle-branch block (LBBB). After adjustment for potential confounders, participants with type 2 diabetes diagnosed had the greater relative risks for most outcomes relative to controls with hazard ratio of 1.40 (95% CI 1.00, 1.96) for AVB, 1.41 (95% CI 1.18, 1.67) for conduction diseases, 1.42 (95% CI 1.16, 1.75) for BBB and 1.69 (95% CI 1.15, 2.49) for LBBB. In contrast, no association between randomization assignment and right bundle-branch block was observed. These results persisted when participants with history of CVD was excluded in the outcome and when considering all-cause death as a competing risk.
CONCLUSIONS In this study, participants with type 2 diabetes are at an increased risk of cardiac conduction disease, but not associated with the development of right bundle block. The findings of our study highlight the need to allocate more medical resources to the prevention of type 2 diabetes.
GW34-e1319
Chen Liao1, Weiguo Fan1, Jinzhu Hu1, Qiongqiong Zhou1, Kui Hong1,2,3
1Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Jiangxi, China
2Department of Genetic Medicine, the Second Affiliated Hospital of Nanchang University, Jiangxi, China
3The Jiangxi Key Laboratory of Molecular Medicine, Jiangxi, China
OBJECTIVES The prevalence and anticoagulant efficiency of left atrial thrombus/left atrial appendage thrombus (LAT/LAAT) are closely related to the selection of transesophageal echocardiography (TEE) in clinical practice. However, they are currently debated. This analysis mainly aims to summarize the LAT/LAAT prevalence and resolution in atrial fibrillation (AF) and/or atrial flutter (AFL) patients, so as to inform the selection of preoperative TEE.
METHODS This analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Eligible studies were systematically retrieved in PubMed, Embase, Web of Science and Cochrane Library.
RESULTS Totally, 189 articles with 146,653 patients were analyzed. The overall prevalence and resolution rate of LAT/LAAT were 7.3% (95% confidence interval [CI]: 6.6–8.0%) and 67.6% (95% CI: 59.7–75.5%) respectively, with a low prevalence (0.3%) detected only in CHA2DS2-VASC score of 0 patients. Meanwhile, 22 prevalence associated factors were found, including CHA2DS2-VASC score (containing its 8 components except gender) and 11 new factors (creatinine, d-dimer, brain natriuretic peptide, C-reactive protein, glomerular filtration rate, left atrial diameter, ejection fraction, left atrial appendage velocity, non-paroxysmal AF, chronic kidney disease and anticoagulants) independent of it. Among them, three most influential factors, heart failure (odds ratio [OR]: 3.28, 2.47–4.35), non-paroxysmal AF (OR: 2.51, 2.03–3.10) and CHA2DS2-VASC ≥2 (OR: 2.55, 1.97–3.30) increased the LAT risk by over 2.5 folds.
CONCLUSIONS TEE screening prior to ablation or cardioversion might be skippable only for CHA2DS2-VASC score of 0 patients and beneficial for most AF/AFL patients, especially those with the three most influential LAT risk factors, heart failure, non-paroxysmal AF and CHA2DS2-VASC ≥2. Further clinical studies were needed to confirm it.
GW34-e1322
Yong Zhou, Qiming Liu
Department of Cardiovascular Medicine, the Second Xiangya Hospital of Central South University, Changsha City, Hunan Province 410011, China
OBJECTIVES Previous epidemiological studies have indicated a potential association between atrial fibrillation and type 1 diabetes (T1D). However, the evidence from observational studies regarding the causal relationship between T1D and the risk of atrial fibrillation is still inconclusive. This study aimed to explore the potential association between T1D and atrial fibrillation.
METHODS We extracted genome-wide association study data for T1D and atrial fibrillation from individuals of European ancestry. A two-sample Mendelian randomization analysis was conducted using single nucleotide polymorphisms (SNPs) that were independently associated with T1D, as identified from a genome-wide association meta-analysis, as instrumental variables. Various methods of mendelian randomization analysis were employed to evaluate the potential association between T1D and atrial fibrillation. The causal effects were primarily estimated using inverse variance weighted methods, supported by several sensitivity and validation analyses.
RESULTS The instrumental variable weighted analysis (OR=1.006, 95% CI=0.989–1.023, P=0.476), MR-Egger regression (OR=1.016, 95% CI=0.978–1.160, P=0.797), and weighted median estimator (OR=1.006, 95% CI=0.987–1.024, P=0.552) all indicated no evidence of a causal relationship between T1D and atrial fibrillation, while the consistent direction of effects was observed. These findings were consistent in the sensitivity analyses and validation analyses.
CONCLUSIONS The findings from our Mendelian randomization analysis did not reveal a potential causal effect between T1D and atrial fibrillation. Additional studies involving larger sample sizes and a comprehensive approach that integrates epidemiological and genetic factors are necessary to validate and corroborate our findings.
GW34-e1354
Jiahong Xue, Yuan Li
The Second Affiliated Hospital of Xi’an Jiaotong University, Department of Cardiovascular Medicine
OBJECTIVES Atrial fibrillation (AF) is one of the most common arrhythmias. Ischemic stroke is widely found in the complication of AF with high disability and fatality rate. Rivaroxaban, as one of novel oral anticoagulants, has been shown to be safer and less inferior than the classical anticoagulant warfarin in ischemic stroke prevention and the hemorrhagic outcomes in AF patients. It is recommended that the standard dose of rivaroxaban is 20 md/d. Some studies from Japan, South Korea and Taiwan of China have proposed that low-dose rivaroxaban (15 mg/d and 10 mg/d when CrCl<50 mL/kg/min) may be as effective as 20 mg/d rivaroxaban or warfarin in the Asian AF population. In real world of our country, however, 10 mg/d rivaroxaban was used in AF patients with normal CrCl. Whether widely prescribed 10 mg/d rivaroxaban is also not inferior to warfarin in preventing stroke in patients with NVAF, we are aimed to explore it in present study.
METHODS In the retrospective cohort study, a total of 17,798 NVAF patients in the Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2020 were collected. Patients were divided into 10 mg/d oral low-dose rivaroxaban group (n=1100) and warfarin group (n=124) according to inclusion and exclusion standard. Demographic and clinical data of the two groups were collected, and telephone follow-up and medical records were collected. The occurrences of ischemic stroke and bleeding events were compared between the two groups. In order to eliminate confounding factors between two groups, propensity score matching was introduced. After matching two groups of data, statistical analysis was conducted.
RESULTS
1) After an average follow-up of 2 and a half years, there were 11 total bleeding events in the 10 mg/d rivaroxaban group and 10 total bleeding events in the warfarin group. There were no significant differences in the risk of total bleeding events between 10 mg/d rivaroxaban group and the warfarin group by Kaplan-Meier survival analysis (HR=1.704, 95% CI=0.710–4.091, P=0.212), nor there were significant differences in the risk of mild, moderate, or severe bleeding between the two groups.
2) After an average follow-up of 2 and a half years, stroke events occurred in 4 patients in the 10 mg/d rivaroxaban group and 3 patients in the warfarin group. Myocardial infarction occurred 1 case in each group. Kaplan-Meier showed no significant difference in the risk of ischemic stroke between 10 mg/d rivaroxaban group and the warfarin group (HR=2.006, 95% CI=0.442–9.103, P=0.351).
3) Age subgroup analysis showed that there was no statistically difference in the risk of bleeding and stroke events between 10 mg/d rivaroxaban group and warfarin group in the AF subgroup with aged less than 75 years or older.
4) Female AF subgroup analysis showed that bleeding events seemed to slightly lower in the rivaroxaban group than in the warfarin group, but not reaching statistically significant (P=0.063). In the male AF subgroup, the risks of bleeding and stroke events were not different in the 10 mg/d rivaroxaban group compared with the warfarin group.
5) The subgroup based on CHA2DS2-VASc score<2 or ≥2 suggested that there also were no statistical differences in the risk of bleeding and stroke events between 10 mg/d rivaroxaban group and warfarin group.
CONCLUSIONS 1) Compared with warfarin, 10 mg/d low-dose rivaroxaban is not inferior in the prevention of NVAF bleeding and stroke. 2) Women taking rivaroxaban may have slightly lower bleeding events than warfarin, and rivaroxaban may be safer for women.
GW34-e1399
Christopher Tze Wei Tsang1,3, Jia-Yi Huang1,2, Qing-Wen Ren1,2, Xin Xu1,2, Mei-Zhen Wu1,2, Yuen Ching Ng3, Yap-Hang Chan1, Kai-Hang Yiu1,2
1Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
2Division of Cardiovascular Medicine, Cardiac and Vascular Centre, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
3The Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
OBJECTIVES Triglyceride-glucose index (TyG) has been proposed to be a surrogate marker of insulin resistance. It is recognised that insulin resistance may predispose individuals to metabolic disorders as well as cardiovascular and cerebrovascular complications. Previous studies have demonstrated the prognostic implication of TyG in diabetics and the general population, but the association between TyG and adverse outcomes in patients with atrial fibrillation (AF) remains unclear.
METHODS Patients with newly diagnosed AF from 1998–2021 (n=58,930) were included in this Hong Kong population-based cohort study. TyG was calculated by ln [fasting TG (mg/dL)×FBG (mg/dL)/2], and patients were grouped according to TyG quartiles. We followed up patients until occurrence of outcomes, death or 1st September, 2022. The primary outcomes were incident ischaemic stroke (IS) and incident haemorrhagic stroke (HS). We evaluated the associations of TyG with IS and HS by categories using multivariate Cox proportional hazards regression model.
RESULTS The median age of the cohort was 76.5 years old and 31,244 (53.0%) were male. Over a median follow-up of 3.6 years, 7127 (12.1%) incident IS and 2677 (4.5%) incident HS occurred. Multivariate analysis indicated that increased TyG at quartiles 3 and 4 were significantly associated with higher risks of incident ischaemic stroke (HR: 1.09 [1.02–1.17], P<0.05, 1.14 [1.06–1.22], P<0.001, respectively) when compared to those in quartile 1. However, there is no significant association between TyG and incident haemorrhagic stroke (Q2: HR: 1.02 [0.91–1.14], P=0.72; Q3: HR: 1.05 [0.94–1.17], P=0.37; Q4: HR: 1.01 [0.90–1.13], P=0.94).
CONCLUSIONS TyG is a significant predictor of incident ischaemic stroke but not incident haemorrhagic stroke in patients with new-onset AF.
HEART FAILURE
GW34-e0051
Yulong Ge, Xiaoqiang Liu, Hangwei Chen, Gonghao Li, Xing Xing, Junyi Liu, Chunxia Zhang, Ying Zhuge, Fang Wang
Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES Heart failure is one of the most common and deadly diseases in the world, and its pathogenesis is still unknown. We aimed to explore the relationship between serum scavenger receptor SSC5D levels and heart failure (HF).
METHODS We retrospectively enrolled 276 patients diagnosed with HF or normal during hospitalization between September 2020 and December 2022. Previously published RNA sequencing (RNA-seq) data were re-analyzed to confirm the expression profile of SSC5D in failing and non-failing human and mouse heart tissues. Quantitative real-time polymerase chain reaction assay was used to quantify Ssc5d mRNA levels in murine heart tissue after myocardial infarction (MI) and transverse aortic constriction (TAC) surgery.
RESULTS To understand the HF-induced secretome profile, 1755 secretory proteins were investigated using human dilated cardiomyopathy RNA-seq data, and the results indicated that SSC5D levels were significantly elevated in failing hearts compared to nonfailing hearts in humans and mice. Using single-cell RNA sequencing data, we demonstrated that Ssc5d is predominantly expressed in cardiac fibroblasts. In a murine model of MI or TAC, Ssc5d mRNA levels were markedly increased compared with those in the sham group. Similarly, serum SSC5D levels were considerably elevated in the HF group compared with the control group [15,789.35 (10,745.32–23,110.65) pg/mL, 95% CI, (16,263.01–19,655.43) vs 8938.72 (6154.97–12,778.81) pg/mL, 95% CI, (9337.50–11,142.93); P<0.0001]. Moreover, serum SSC5D levels were positively correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) (R=0.4, P=7.9e-12), and inversely correlated with left ventricular ejection fraction (LVEF) (R=−0.46, P=9.8e-16).
CONCLUSIONS We concluded that SSC5D was a specific responder to HF. Serum SSC5D may function as a novel biomarker, and therapeutic target for patients with HF.
GW34-e0063
Zhenbang Gu1, Wengen Zhu1,2,3
1Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University
2NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University)
3National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases
OBJECTIVES Transthyretin amyloid cardiomyopathy (ATTR-CM) is often found in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence regarding ATTR-CM and prognosis in HFpEF remains scarce. This study sought to determine whether the ATTR-CM burden was associated with clinical outcomes in patients with HFpEF.
METHODS We evaluated the associations of baseline ATTR-CM score with adverse outcomes in HFpEF patients from the TOPCAT trial using the Cox proportional hazards model or the competing risk regression model. The discriminatory ability of the ATTR-CM score was assessed using the area under the time-dependent receiver operating characteristic curve (AUC).
RESULTS We included 870 HFpEF patients, 18.9% of which had an ATTR-CM score ≥6. The incidence rates of the primary outcome, all-cause mortality, cardiovascular death, HF hospitalization, any hospitalization, and stroke were 18.1, 13.3, 8.2, 11.1, 42.7, and 2.9 per 100 person-years in patients with ATTR-CM score ≥6, respectively. Per 1 increment in the ATTR-CM score was significantly associated with an increased risk of the primary outcome (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.12–1.27) with an AUC of 0.652 (0.594–0.711), whereas patients with ATTR-CM score ≥6 presented higher risks of the primary outcome (adjusted HR 2.20, 95% CI 1.65–2.95). Similar results were observed towards the secondary outcomes including all-cause mortality, cardiovascular death, HF hospitalization, and any hospitalization, and stroke.
CONCLUSIONS The simple ATTR-CM score identified an 18.9% ATTR-CM burden in HFpEF patients, and a higher ATTR-CM burden might predict adverse outcomes with moderate discriminatory abilities in HFpEF.
GW34-e0099
Zhou Liu1, Siyue Zheng2, Yazhe Zhang1, Ming Gong1, Hongjia Zhang1
1Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University
2School of Medicine and Health Management, Tongji Medical College of Huazhong University of Science and Technology
OBJECTIVES A huge gap exists between the needs of patients with end-stage heart failure and the number of gold-standard heart transplants. Over the past 30 years, the revolutionary treatment strategy employing a ventricular assist device (VAD) has developed rapidly and has been widely used in clinical practice. Little analysis has been done on the application and publication trends in the VAD field. This work aimed to help researchers grasp a complete picture of global VAD research. We revealed the research dynamics in the field of VAD according to different factors, including countries, institutions, journals, and scholars, and highlighted the relevant research trends.
METHODS Generally, bibliometrics is considered to be an advanced method used to understand the developmental stages in various emerging disciplines. We retrieved the core collection of Web of Science to determine the VAD research published from 1992 to 2022. We performed the analysis and data visualization using CiteSpace, Scimago Graphica and VOSviewer.
RESULTS We identified a total of 13,274 publications, which were published in 1129 journals and came from 6351 institutions in 86 countries. Among them, the United States has contributed the most to VAD research, and almost all of the top 10 authors and institutions contributing to VAD research are from the United States. China is the only developing country among the top 10 countries contributing to VAD research, and its publications have increased significantly in recent years. In the last five years, VAD research has focused on right heart failure, outcomes, impact and risk factors, society, and guidelines.
CONCLUSIONS Our work is the first to analyze VAD research according to bibliometrics, which identified prominent countries, institutions, journals, and authors to indicate the future direction of VAD research. In recent years, the prevention, diagnosis, and treatment of right heart failure after left VAD implantation, the risk factors of death and adverse events, and outcomes of patients with VAD implantation have received growing attention. Additionally, societies and their databases have added more value to VAD research. More work can be done in these areas to further improve VAD and the management and prognosis of patients after implantation. Although VAD research in China started late, with the growing emphasis on heart failure and heart transplantation, it has gradually accelerated its research process in this field. By the beginning of 2023, three devices have been verified and launched in China, which are beginning to be applied in clinical practice. Because of the large number of heart failure patients, we expect that there will be a peak of development of VAD in China in the next 10 years.
GW34-e0244
Zhongli Chen1, Xuan Ma2, Shihua Zhao2, Keping Chen1
1Fuwai Hospital, CAMS and PUMC, State Key Laboratory of Cardiovascular Disease, Cardiac Arrhythmia Center, Beijing, China
2Fuwai Hospital, CAMS and PUMC, Department of Magnetic Resonance Imaging, Beijing, China
OBJECTIVES Whether left bundle branch area pacing (LBBAP) have similar benefit compared with biventricular pacing (BVP) for cardiac resynchronization therapy (CRT) in nonischemic cardiomyopathy (NICM) with different septal scar burden is still unknown. This study aims to assess the effect of the septal scar on the response to LBBAP and BVP for CRT.
METHODS We retrospectively included nonischemic cardiomyopathy (NICM) patients with wide QRS complex and CRT indications who underwent pre-procedure cardiac magnetic resonance (CMR) examination and received either BVP or LBBAP. Late gadolinium enhancement (LGE) was analyzed for scar quantification. CRT response was defined as an absolute increase of ≥5% in left ventricular ejection fraction (LVEF) at 6 months follow-up.
RESULTS A total of 147 patients were included. Fifty-one patients (34.7%) had LBBAP, and 96 (65.3%) had BVP. As septal LGE extent increased, LVEF improvement at 6-month follow-up gradually decreased in the BVP group whereas dropped sharply in the LBBAP group. The nonlinear inverse relationship between the relative benefit of LBBAP versus BVP for response and septal LGE extent, as well as cut-off points (4.4%, 13.3%) of septal LGE extent, were determined using a restricted cubic spline model. Among patients with low septal scar extent (<4.4%), LBBAP was associated with higher response odds than BVP [Odds Ratio (OR) 3.87, 95% confidence interval (CI): 0.99–15.17, P=0.052]. In the medium septal scar extent (4.4–13.3%) group, response odds did not differ between LBBAP and BVP (OR 2.00, 95% CI: 0.41–9.74, P=0.391). Among patients with high septal scar extent (>13.3%), BVP was associated with higher response odds (OR 0.12, 95% CI: 0.03–0.54, P=0.006).
CONCLUSIONS Response to LBBAP and BVP among NICM patients might be impacted by septal scar burden.
GW34-e0246
Gulnosa Zakirova, Umida Kamilova, Dylafruz Masharipova, Saida Beknazarova, Dilnosa Tagaeva
Republican Specialized Scientific and Practical Medical Center of Therapy and Medical Rehabilitation
OBJECTIVES To assess the prognosis in patients with chronic heart failure (CHF), taking into account the functional state of the kidneys using a mobile application.
METHODS One hundred and fifty patients with ischemic heart disease (IHD) with I-III functional class (FC) of CHF were examined. All patients underwent: a six-minute walk test, results of the clinical assessment scale, the level of serum creatinine (Cr), glomerular filtration rate (eGFR) according to the CKD-EPI formula in mL/min, and echocardiography were determined.
RESULTS To create a mobile application with an assessment of the significance of parameters in predicting the course of CHF, taking into account kidney function, a heterogeneous sequential procedure was used with the development of diagnostic tables (DT) taking into account the criteria for kidney dysfunction. This ensured the phasing of work in the mobile application: the first was the determination of the severity of clinical signs of CHF with the calculation of the severity and determination of the information content of each symptom; the second stage is to determine the severity of kidney dysfunction, with the inclusion of signs that had a high diagnostic and prognostic significance; the third stage is the choice of patient management tactics based on the sum of combinations of diagnostic thresholds. At the 1st stage, we determined:
A. Definition of the functional class of CHF;
B. Determining the stage of CHF;
C. Determination of the ejection fraction of the left ventricle;
D. Determination of clinical signs of kidney dysfunction (KD), while D1 – early signs of KD (at least 3 signs), if present, the D2 window opens – late signs of KD (at least 2 signs. At stage 2, the following gradations were determined according to the criteria for kidney dysfunction:
E. Determination of the severity of the course of DP according to GFR – C1 Stage of CKD – eGFR mL/min/1.73 m2>90; C2 Stage of CKD – eGFR mL/min/1.73 m2=90–60; C3A Stage CKD – eGFR mL/min/1.73 m2=45–59; C3B Stage CKD – eGFR mL/min/1.73 m2=30–44; C4 CKD stage – eGFR mL/min/1.73 m2=15–29; C5 – CKD stage – eGFR mL/min/1.73 m2 <15; E2. Determination of the severity of the course of DP by albuminuria – Al1<30 mg/g or <3 mg/mmol; Al2 30–300 mg/g or 3–30 mg/mmol; Al3 >300 mg/g or >30 mg/mmol. At stage 3, depending on the combination of diagnostic criteria, the tactics of managing patients is determined.
CONCLUSIONS In CHF patients, assessment of the prognosis taking into account the functional state of the kidneys using a mobile application makes it possible to early diagnose prognostically unfavorable criteria, determine the tactics of patient management and develop preventive measures.
GW34-e0253
Song Zou1,2, Yu-Hao Wan1,2, Ke Chai3, Chen Meng3,4, Ting Wang3, Si-Ming Wang5, Jian-Ping Cai5, Hua Wang1,2,3, Jie-Fu Yang1,2,3
1Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science & Peking Union Medical College, P.R. China
2Graduate School of Peking Union Medical College, Chinese Academy of Medical Science, P.R. China
3Department of Cardiology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P.R. China
4Peking University Fifth School of Clinical Medicine, P.R. China
5The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, P.R. China
OBJECTIVES The metabolomic characteristics between stage B and stage C patients with heart failure with preserved ejection fraction (HFpEF) remain unclear. We aim to investigate the metabonomic characteristics between stage B and stage C HFpEF patients and to screen metabolites mostly relevant to HFpEF progression.
METHODS Ninety-seven stage B and 31 stage C HFpEF patients were screened from previous longitudinal cohort of comprehensive geriatric evaluations. Metabolites in serum were identified and quantified with Biocrates MxP® Quant 500 Kit. Differential analysis was performed with Mann-Whitney U test. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and metabolite set enrichment analysis (MSEA) was performed with MetaboAnalyst web server. Least absolute shrinkage and selection operator (LASSO) logistic regression model was constructed to screen metabolites mostly relevant to HFpEF progression.
RESULTS Two hundred and eight differential metabolites of 19 categories were identified, among which 202 metabolites increased and 6 metabolites decreased. KEGG pathway enrichment analysis revealed differential metabolites were significantly enriched in 15 metabolic pathways, among which 10 pathways were implicated in amino acid metabolism. MSEA demonstrated differential metabolites were most significantly enriched in muscles and renal disease states. LASSO logistic regression model showed metabolites, FA 18:0, dopamine, cystine and carnosine, were mostly relevant to HFpEF progression.
CONCLUSIONS Compared with stage B HFpEF patients, metabolites and related pathways altered extensively in stage C individuals. Perturbed lipid metabolism, renal dysfunction, increased proteolysis of muscles, oxidative stress, neurohumoral factors, bile acids metabolism, polyamine metabolism and energetic metabolism may be the causes of the progression of HFpEF.
GW34-e0278
Gulnosa Zakirova, Umida Kamilova, Izzatulla Karimov
Republican Specialized Scientific-Practical Medical Center of Therapy and Medical Rehabilitation, Tashkent, Uzbekistan
OBJECTIVES Early identification of the kidney dysfunction by measurement of fermenturia level and glomerular filtration velocity (GFV) in the patients of functional class (FC) II-III of chronic heart failure (CHF).
METHODS The study included 52 patients with ischemic heart disease with FC II (n=27) and III CHF (n=25). Control group included 20 healthy persons. All the patients were performed complex clinical examination, measurement of blood serum creatinin level, residual nitrogen and urine enzymes concentrations: alaninaminotransferase (ALT), aspartataminotransferase (AST), alkaline phosphatase (AP), cholinesterase.
RESULTS There was found preservation of normal findings of GFV and residual nitrogen content in the blood serum in the patients with FC II and III CHF, however GFV in the patients with FC II and III CHF reliably lower by 17, 4% and 35, 1%, respectively, and residual nitrogen level was reliably higher by 61, 4% and 85, 7%, respectively, in comparison with control group (P<0.05). In the patients with FC II CHF there was noted reliable (P<0.05) increase in fermenturia level in comparison with control group: ALT-by 52, 2%, AST – by 39%, AP – by 82, 7%, CE – by 37, 8%. In the patients with FC III of CHF there was revealed reliable increase in ALT, AST, AP, CE by 87, 0%, 52%, 114, 8%, and 53%, respectively, (P<0.01) that indicated about damage of congruentness of cytoplasmatic membranes of tubular epithelium of the kidney tubules.
CONCLUSIONS There was noted reduction in GFV and increase in residual nitrogen levels in rising of FC of CHF without clinical manifestations of kidney dysfunction. It was established that in patients with FC II and III of CHF there was noted reliable increase in urine levels of enzymes, that is early sign of the impairment of tubuloepithelial kidney apparatus and it may be considered as predictor of kidney dysfunction in the patients with CHF.
GW34-e0333
Hangtian Yu, Yan Zhao, Angwei Gong, Suaidan Zhang, Bing Xiao
Department of Cardiology, The Second Hospital of Hebei Medical University, Hebei 050000, People’s Republic of China
OBJECTIVES To elucidate the causal relationship between serum lipid levels and heart failure (HF) risk and the potential mediating effect of coronary artery disease (CAD).
METHODS We primarily used the inverse variance weighting (IVW) method in univariate Mendelian randomization (MR) analysis to examine the association between lipids [including triglycerides (TG), low-density lipoprotein cholesterol (LDL cholesterol), high-density lipoprotein cholesterol (HDL cholesterol), apolipoprotein AI (Apo-AI), and apolipoprotein B (Apo-B)] and HF risk. The instrumental variables for the lipid exposures and CAD were obtained from the UK Biobank. HF data were obtained from the HERMES Consortium. Additionally, sensitivity analysis was performed to assess the robustness of the results. Finally, we performed a mediation analysis to assess the role of CAD as a mediator in the relationship between blood lipids and the risk of HF.
RESULTS Univariable MR analysis showed significant associations between blood lipids and HF risk. TG [odds ratio (OR)=1.15, 95% confidence interval (CI): 1.09–1.21, P=3.32×10−7], LDL cholesterol (OR=1.15, 95% CI: 1.05–1.25, P=1.47×10−3), and Apo-B (OR=1.16, 95% CI: 1.07–1.26, P=1.99×10−4) were positively associated with an increased risk of HF. Mediation analysis revealed that CAD mediated 11%, 17%, and 24% of the relationships between TG, LDL cholesterol, and Apo-B, respectively, and HF.
CONCLUSIONS In conclusion, our univariable MR study provided robust evidence of a positive association between triglycerides, LDL cholesterol, and Apo-B levels and the risk of HF. The findings also suggested that CAD partially mediated these associations. Furthermore, these results provide indirect evidence for the involvement of serum lipid levels in the development and progression of nonischemic HF.
GW34-e0375
Yingwen Lin1,2,3, Hengli Zhao1,2,3,4, Dongtu Hu1,2,3, Jia Huang5, You Peng6, Juncong Li1,2,3, Dingli Xu1,2,3, Qingchun Zeng1,2,3
1State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University
2Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University
3Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)
4School of Laboratory Medicine and Biotechnology, Southern Medical University
5Department of Radiology, The Third Affiliated Hospital of Guangzhou Medical University
6Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University
OBJECTIVES Management of heart failure with preserved ejection fraction (HFpEF) is centered on the assessment of volume status. However, it has not been fully investigated whether clinically overt congestion assessed by physical signs as well as its variation over time is associated with long-term outcomes.
METHODS Latent class analysis (LCA) was employed to identify potential subgroups with or without clinically overt congestion based on the physical signs of congestion in HFpEF patients. Variation in congestion status was determined by the baseline and the first follow-up latent classes. The primary endpoint was defined as the composite of cardiovascular death, hospitalization for heart failure and aborted cardiac arrest. Kaplan-Meier plots and Cox proportional-hazards models were used to evaluate the association of phenotypes with outcomes of interests as well as the treatment effect of spironolactone.
RESULTS Two subgroups were identified, with 675 (20.9%) in the overt congestion group and 2556 (79.1%) in the non-congestion group at baseline. Physical signs of congestion were much more common in the group of overt congestion than in non-congestion. During the study period, 191 patients in the overt congestion group (28.3%) and 416 in the non-congestion group (16.3%) had at least one primary-endpoint events. Compared to non-congestion, overt congestion was significantly associated with increased risk for the primary endpoint, all-cause death and all-cause hospitalization after multivariable adjustment (adjusted P<0.05 for all comparisons). During follow-up, 2417 patients (74.8%) remain non-congestion, 463 (14.3%) had congestion remission, 139 (4.3%) had new-onset congestion, and 212 (6.6%) had persistent overt congestion. After adjusting for confounding factors, as compared with those who remain non-congestion, patients with persistent congestion had a 78%, 77%, and 60% increase in the risk of primary-endpoint events, all-cause death and all-cause hospitalization, respectively. In the subgroup of persistent congestion, the risks for the primary outcome were reduced significantly with spironolactone treatment compared with placebo (HR 0.58, 95% CI 0.36–0.93).
CONCLUSIONS In patients with HFpEF, baseline and persistent congestion status were both independently prognostic of subsequent adverse outcomes. Spironolactone therapy had a favorable effect regarding the primary composite endpoint in HFpEF patients with persistent congestion status.
GW34-e0459
Qing Yang, Xin Quan, Yan Liang
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Poor left ventricular ejection fraction (LVEF) levels have been shown to be independently linked to the formation of left ventricular (LV) thrombus in previous studies. The evidence relating LVEF to LV thrombus outcomes, however, is still limited.
METHODS We enrolled patients prospectively from 2020 to 2022 and retrospectively from 2013 to 2019 at the National Center of Cardiovascular Diseases of China. Patients with a history of LV thrombus <3 months were included. The primary efficacy outcome was the rate of thrombus resolution at 12 weeks. Restricted cubic splines were applied to depict the relationship between LVEF levels and thrombus resolution. The hazard ratio (HR) and 95% confidence intervals (CIs) were estimated with adjustment for covariates using Cox regression models.
RESULTS A total of 380 patients who were taking oral anticoagulants for 12 weeks were included in the study. The median baseline LVEF was 30 (25, 40)%, with a median LV end-diastolic diameter of 62 mm. The majority of them (82.6%) had heart failure. Patients with LVEF ≤ 30% experienced a greater rate of thrombus resolution than those with LVEF>30% (78.5 vs 63.9%, P=0.002). At 12 weeks, 187 (49.2%) patients’ LVEF levels increased by more than 10%, and 124 (66.3%) out of them had a baseline LVEF ≤ 30% (P<0.001). The median LVEF variation was larger in patients with LVEF ≤ 30% (+4 vs +1%, P<0.001). After adjusting ten potential factors including diameter or thickness of thrombi in multivariate analysis, lower baseline LVEF levels were related to greater thrombus resolution (HR 0.98, 95% CI 0.97–0.99, P=0.039), whereas no significant difference was identified in LVEF variations during follow-ups (HR 0.99, 95% CI 0.98–1.00, P=0.198).
CONCLUSIONS We found that patients with LV thrombus had a relatively low LVEF. Patients who had LVEF of less than 30% showed a higher thrombus resolution than those with LVEF of more than 30%, though no significant relationship was observed between LVEF changes and thrombus resolution at 12 weeks. Large randomized controlled studies are required to generalize our findings.
Keywords Left ventricular thrombus; left ventricular ejection fraction.
GW34-e0463
Xiaodong Peng, Tiannan Jiang, Liu He, Changsheng Ma
Department of Cardiology, Beijing AnZhen Hospital, Capital Medical University
OBJECTIVES Left ventricular ejection fraction (LVEF) is inadequate for accurately predicting treatment outcomes and risk stratification in patients with heart failure (HF). To address this issue, data-driven cluster analysis has emerged as a promising approach for reclassifying patients with HF based on their specific characteristics. Despite its effectiveness in general HF populations, there is currently a lack of evidence regarding its applicability to patients with both atrial fibrillation (AF) and concomitant HF, who represent a unique but common subgroup of patients.
METHODS Participants with AF and comorbid HF were enrolled from China-AF registry. To generate novel phenotypes, thirty-three clinical features were included in the hierarchical cluster process. Different phenotypes groups were compared with respect to composite events (cardiovascular mortality, cardiovascular readmission and thromboembolism), all-cause mortality, cardiovascular mortality, cardiovascular readmission, thromboembolism, major bleeding and AF recurrence, using survival analysis.
RESULTS A total of 2980 AF patients with comorbid HF were enrolled, with a median follow-up of 51.2 months, and were grouped into four clusters by hierarchical cluster analysis. Significantly different prognosis was demonstrated by clusters, even after stratified by LVEF (reduced EF, mildly reduced EF and preserved EF). Generally, Cluster 1 represented a group with old age and complex comorbidities; Cluster 2 had the average-level clinical characteristics; Cluster 3 were more likely to be young and have impaired systolic function; Cluster 4 showed a group with preserved EF and mild HF symptoms. Compared with Cluster 4, who exhibited the least serious overall outcomes, Cluster 1 had the worst prognosis (adjusted HR=0.68 for composite events, 95% CI 0.59–0.80, P<0.001; adjusted HR=0.34 for all-cause mortality, 95% CI 0.27–0.44, P<0.001). The composite outcomes show notable disparities between individuals who did not undergo radiofrequency catheter ablation (RFCA) at baseline (log-rank P<0.001), whereas the disparity in prognosis significantly diminishes among those who have undergone RFCA (log-rank P=0.222).
CONCLUSIONS Four clinical phenotypes of AF patients with HF that identified by a data-driven approach, exhibited distinct clinical prognosis, even after stratified by LVEF level, emphasizing the heterogeneity of these patients and need for more tailoring prognosis assessment beyond the measure of LVEF. RFCA may offer advantages to patients with both AF and HF, particularly in those who exhibit a more severe clinical profile and poorer prognosis.
GW34-e0475
Ting Zhou
Union Hospital Affiliated to Huazhong University of Science and Technology
OBJECTIVES Cardiac fibrosis is characteristic of the end stage in nearly all forms of heart disease, which is a leading cause of morbidity and mortality worldwide. Adoptive immunotherapy with of polyclonal regulatory T cells (Tregs) is a promising treatment for cardiac fibrosis. However, polyclonal Tregs encompass many specificities and could potentially be globally immunosuppressive. In the present study, we engineered Treg with a chimeric antigen receptor (CAR) against fibroblast activation protein (FAP), and confirmed the efficacy of redirected Treg-cell immunotherapy to specifically regulate cardiac fibroblasts and target pathologic cardiac fibrosis in the local microenvironment.
METHODS We developed a lentivirus CAR construct specific for the mouse FAP, comprising a FAP single chain variable fragment (scFv) with the CD8α hinge, transmembrane regions, the CD3ς, 4-1BB activation domains, and a green fluorescent protein (GFP) label. In order to specifically label activated cardiac fibroblast, we crossed B6.129S-Postn tm2.1 (cre/Esr1*) Jmol/J male mice with B6.Cg-Gt (ROSA) 26Sor tm9 (CAG-tdTomato) Hze/J female mice to reproduce Postn MCM; R26ERFP mice. In order to induce injury and fibrosis, Postn MCM; R26ERFP mice were subjected to sham or myocardial infarction (MI) surgery for 4 weeks. Primary mouse Treg cells were isolated from spleen and lymph nodes, and activated with IL-2 and CD3/CD28, followed by transfected with mock lentivirus or CAR lentivirus. Flow cytometry was used to sort GFP+Tregs and confirm the functional stability of FAP CAR Treg by testing the expression of effector molecules: CD4, CD25, CD69, IL-10, Foxp3 and Helios. To exam the efficacy of FAP CAR Treg in vitro, reprogrammed Treg or polyclonal Tregs were co-cultured with cardiac fibroblasts (CFs) and vascular endothelial cell (ECs), followed by treatment with transforming growth factor-β (TGF-β). Real-time polymerase chain reaction (RT-PCR) and western blotting were used to analyze the expression of fibrotic markers-α-smooth muscle actin (α-SMA), periostin, vimentin, FAP. Endothelial cell tube formation experiment was utilized to analyze angiogenesis. To exam the efficacy of CAR Treg in vivo, 5×10^5 engineered Treg or polyclonal Tregs were adoptively transferred into Postn MCM; R26ERFP mice in the 3 days and 14 days after sham or MI surgery. Echocardiography, histology and immunohistochemistry analysis were utilized to evaluate cardiac function, left ventricular fibrosis, angiogenesis, inflammation, and TGF-β system. Enzyme linked immunosorbent assays (ELISA) were utilized to detect potential itself cardiotoxicities by testing serum cytokine levels.
RESULTS The transduction protocol does not affect the Treg functional phenotype, as evidenced by normal expression of effector molecules: CD4, CD25, CD69, IL-10, Foxp3 and Helios. Compared with polyclonal Tregs, FAP CAR Treg significantly alleviates the expression of fibrosis related genes in CFs induced by TGF-β, and promoted ECs tube formation in vitro. Adoptive transferred GFP-labelled FAP CAR Treg accumulates in heart and co-locates with RFP-labelled CFs, and results in a more significant reduction in cardiac fibrosis and restoration of cardiac function after injury compared with that of polyclonal Tregs. This reduction in fibrosis was associated with attenuated inflammatory cell numbers, reduced CFs numbers, attenuated activity of the TGF-β system, and increased angiogenesis. Besides, compared with polyclonal Tregs, FAP CAR Tregs may have numerous advantages, such as a need for fewer cells and reduced risk of nonspecific immune suppression, and adoptive transfer of FAP CAR Treg was used safely and effectively, and does not cause inflammatory factor storm.
CONCLUSIONS Our results demonstrate that use of CAR technology to generate potent, functional, and stable FAP CAR Tregs markedly holds promise as a therapeutic platform to treat cardiac fibrosis and heart failure.
GW34-e0476
Hangtain Yu, Shuaidan Zhang, Yan Zhao, Angwei Gong
The Second Hospital of Hebei Medical University
OBJECTIVES The purpose of this study was to investigate the associations between aspirin use and cardiovascular diseases (CVDs) using univariate Mendelian randomization (MR) analysis, focusing on outcomes such as hypertension, atrial fibrillation (AF), heart failure (HF), rheumatic valvular disease, cardiovascular death, cardiomyopathy, aortic aneurysm, and venous thromboembolism.
METHODS We performed an MR analysis to assess the causal relationship between aspirin use and the selected CVDs, mainly using the Inverse Variance Weighted (IVW) method. Genetic data associated with aspirin use and CVDs outcomes were obtained from large-scale genetic studies and genome-wide association studies. Odds ratios (ORs), P-values, and confidence intervals (CIs) were calculated to assess the strength and significance of the associations. Sensitivity analyses, including MR-PRESSO, Cochran’s Q test, and the MR-Egger method, were conducted to ensure the robustness of our findings.
RESULTS Our findings indicate significant associations between aspirin use and several CVDs. We observed that aspirin use was associated with an increased risk of hypertension (OR=1.83, P=2.42×10−14, 95% CI: 1.57–2.14), AF (OR=1.83, P=6.10×10−4, 95% CI: 1.57–2.14), HF (OR=587.98, P=2.77×10−12, 95% CI: 98.34–3515.56), and rheumatic valvular disease (OR=544.61, P=1.12×10−2, 95% CI: 4.18–70,962.27). Additionally, a slight association between aspirin use and increased risk of cardiovascular death was observed (OR=1.06, P=1.27×10−8, 95% CI: 1.04–1.08). Importantly, sensitivity analyses confirmed the robustness and reliability of our results.
CONCLUSIONS In summary, our univariate Mendelian randomization analysis suggests a potential tendency towards an increased risk of hypertension, atrial fibrillation, heart failure (HF), rheumatic valvular disease, and cardiovascular death in association with the use of aspirin.
GW34-e0481
He Yuan1, Xiao qun Wang1,2
1Institute of Cardiovascular Diseases, Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China
2Department of Cardiology, Rui Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China
OBJECTIVES Due to advancements in medical treatments, a significant portion of patients with heart failure (HF) have achieved improved ejection fraction (EF), referred to as HF with recovered EF (HFrecEF). Insulin resistance (IR) is common in HF and strongly linked to prognosis. This study examines the connection between IR and the occurrence of HFrecEF in nondiabetic patients.
METHODS A consecutive enrollment of 262 nondiabetic patients with HF and reduced EF (HFrEF) was conducted. They were divided into HFrecEF (follow-up EF>40% and ≥10% absolute increase) or persistently HFrEF based on repeat echocardiograms after 12 months. IR was estimated using an updated homeostasis model assessment for IR (HOMA2-IR).
RESULTS Median HOMA2-IR was 1.05 (IQR, 0.67–1.63) in our nondiabetic HF patient cohort. During the follow-up period, 121 individuals (odds ratio [OR], 46.2% [95% consecutive enrollment of 262 nondiabetic patients with HF and reduced EF (HFrEF) was conducted. They were divided into HFrecEF (follow-up EF>40% and ≥10% absolute increase) or persistently HFrEF based on repeat echocardiograms after 12 months. IR was estimated using an updated homeostasis model assessment for IR (HOMA2-IR). CI 40.2–52.2]) developed HFrecEF. Compared to HFrEF patients, HFrecEF patients had significantly lower HOMA2-IR levels (0.92 [IQR, 0.61–1.37] vs. 1.14 [IQR, 0.75–1.78], P=0.007), particularly in nonischemic HF. The log2-transformed HOMA2-IR exhibited an inverse correlation with EF improvements (Pearson’s r=−0.25, P<0.001). In the full adjustment model, patients with HOMA2-IR ≥1.4 showed a 62.9% (OR, 0.371 [95% CI, 0.167–0.789]) lower chance of HFrecEF compared to those with HOMA2-IR<1.4. After multivariable adjustment, a doubling of HOMA2-IR was linked to a 42.8% (OR, 0.572 [95% CI, 0.385–0.827]) reduced incidence of HFrecEF.
CONCLUSIONS This study demonstrates an independent association between IR and impaired development of HFrecEF in nondiabetic patients.
GW34-e0573
Ying Gu, Jianhua Li, Lei Wang
Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine
OBJECTIVES Left bundle branch area pacing (LBBAP) has been demonstrated to be an effective treatment to realize cardiac resynchronization therapy (CRT). Yet, the efficacy and safety of ventricular arrhythmia sensing by LBBAP connected to implantable cardioverter defibrillator (ICD) remains unknown. We aimed to identify the feasibility of LBBAP lead connected to ICD in CRT-D indicated patients.
METHODS The present study retrospectively enrolled 5 heart failure patients with LVEF≤35%, complete left bundle branch block and indicated for CRT-D. Patients were implanted with a single or dual-chamber DF-1 ICD connected to the LBBAP lead (RV IS-1 port), and the defibrillation lead (RV DF-1 port), and the atrial lead (RA port) with dual-chamber ICD. A DF-1 lead was implanted at the right ventricular (RV) apex, and an LBBAP lead through the interventricular septum. All patients were followed during 6 months.
RESULTS All five heart failure patients successfully implanted with ICD via LBBAP, with two persistent atrial fibrillation (AF) patients operated by single-chamber ICD. Significant decreased median QRSd was observed by LBBAP, from 158 ms to 114 ms (P=0.004). The median left ventricular activation time (LVAT) was recorded as the interval from the pacing stimulus to the peak of the R wave in lead V5, which was 78 ms (73, 87). No significant difference was found regarding capture threshold, R-wave sensing and impendence of LBB area lead at baseline and 6-month follow up visit. No arrhythmic event, either ventricular tachycardia or fibrillation, was documented during the 6-month following period. Median LVEF markedly increased from 30 to 46% (P=0.026), and median LVEDd decreased from 75 mm to 62 mm (P=0.028) at 6 months.
CONCLUSIONS Ventricular arrhythmia sensing and defibrillation could be realized by LBBAP lead connected to single or dual-chamber ICD. Additionally, cardiac function was significantly improved after 6-month of LBBAP implantation.
GW34-e0596
Xiaodong Jia, Kun Na, Zhu Mei, Haibo Yu, Chenhui Yan
National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES The occurrence of residual risk for death or rehospitalization remains high in severe heart failure (HF) patients with an implantable cardioverter defibrillator (ICD). Therefore, it is crucial to identify patients with a poor prognosis. Adiponectin (APN) exerts its influence on the cardiovascular system through various biological processes. To evaluate the long-term predictive value of serum APN in severe HF patients with an implantable cardioverter defibrillator (ICD).
METHODS In 2017–2019, severe heart failure patients (defined as left ventricular ejection fraction (LVEF) ≤35%) with subcutaneous ICD were enrolled consecutively. Serum adiponectin (APN) levels were quantified using an ELISA system (R&D Systems; Minneapolis, MN, USA). The primary endpoint was defined as a composite outcome of all-cause death or rehospitalization for heart failure (HF) within a 4-year period. Secondary endpoints included all-cause death, cardiac death, and HF rehospitalization.
RESULTS A total of consecutive 164 sever HF patients with ICD were enrolled. Mean follow-up duration was 35.3-months (23.7 mo-48.9 mo). all-cause mortality occurred in 29 patients (17.68%) among the patients, and 32 patients (19.51%) rehospitalization for heart failure. Incidence of all-cause mortality (24.09 vs. 11.11%, P=0.023) and Rehospitalization for HF (26.50 vs. 12.35%, P=0.022) increased significantly in patients with APN levels above 3233 pg/mL. After adjusting the model (age, sex, hypertension, diabetes) and the model combined with (NT-proBNP, LVEF, LDL-C), the risk of all-cause death or Rehospitalization for HF was increased by 4.1% (HR: 3.41, [95% CI, 1.86–6.26]) and 1.7% (HR: 3.17, [95% CI, 1.73–5.81]), respectively, per pg/mL of APN. The best APN cutoff for predicting all-cause or Rehospitalization for HF was 6390 pg/mL (area under the curve:0.68, sensitive:0.49, and specificity:0.81). APN level ≥6390 pg/mL was an independent predictor of all-cause mortality or Rehospitalization (HR: 0.68 [95% CI 0.58–0.77]).
CONCLUSIONS Increased circulating APN level was associated with higher risk for all-cause death or rehospitalization for HF and may be an additive prognostic marker in severe HF with an ICD implantation.
GW34-e0610
Shuaidan Zhang, Yan Zhao, Hangtian Yu, Angwei Gong, Chengjian Guan, Shuchen Chen, Bing Xiao
The Second Hospital of Hebei Medical University
OBJECTIVES The purpose of this study is to explore the effects of hypothyroidism and thyroid hormone replacement therapy (THRT) on the risk of Cardiovascular diseases (CVDs) including, MI (myocardial infarction), HF (heart failure), cardiac death using Mendelian randomization analysis.
METHODS Genetic instrumental variables related to hypothyroidism, levothyroxine (L-T4), and adverse cardiovascular events (MACEs) were obtained from large publicly available genome-wide association study (GWAS). Two-sample Mendelian randomization (MR) analysis was performed using inverse variance weighting (IVW) as the primary method and complemented by several other estimators. To ensure the reliability of our findings, we performed MR-Egger regression, Cochran’s Q statistic, and leave-one-out analysis. Additionally, multivariable mendelian randomization (MVMR) was applied to adjust for confunding factors including Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP), Metformin, and Body Mass Index (BMI). Mediation analysis was also conducted to assess the mediating effects of stroke, atrial fibrillation (AF) and bradycardia on the relationship between L-T4, hypothyroidism and HF, MI.
RESULTS Genetically predicted hypothyroidism and L-T4 were significantly associated with MI [LT4: odds ratio (OR) 3.754, 95% confidence interval (CI): 1.799–7.799; hypothyroidism: OR: 1.102, 95% CI: 1.033–1.176]. Moreover, genetically predicted L-T4 had a significant relationship with HF (OR: 2.568, 95% CI: 1.361–4.843). However, no association was observed between hypothyroidism and HF, as well as between hypothyroidism, L-T4, and cardiac death. When adjusted for confounding factors, the results were stable. Additionally, mediation analysis indicated that AF and stroke may serve as potential mediators in the relationship between L-T4 and HF or MI.
CONCLUSIONS Our study suggests an positive association between hypothyroidism and MI, and highligths the potential risks of CVDs associated with the use of L-T4.
GW34-e0632
Iokfai Cheang, Xu Zhu, Shengen Liao, Rongeong Gao, Xinli Li
The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital
OBJECTIVES Epicardial adipose tissue has unique metabolic activity, and its volume is associated with composite cardiovascular events in patients with chronic heart failure (CHF). The purpose of this study is to explore the association of ventricle epicardial fat volume (EFV) calculated by cardiac magnetic resonance and serum metabolic markers in CHF patients, and focused on its relationship with the triglyceride-glucose (TyG) index, which is a surrogate index of insulin resistance.
METHODS In total, 516 CHF patients were enrolled (age ≥18 years, with confirmed diagnosis of heart failure). EFV were measured using short-axis cine by cardiac magnetic resonance. The TyG index was calculated as log [fasting triglycerides * fasting glucose (mg/dL)/2]. Spearman correlation, multivariate linear regression, and restricted cubic spline (RCS) regression analysis were used to investigate their association.
RESULTS According to the quartile grouping, there were significant differences between the groups in the metabolism-related indexes. Spearman correlation analysis showed that TyG index was significantly correlated with the EFV in CHF patients (r=0.247, P<0.001). Further analysis showed that TyG index levels were significantly associated with EFV as both continuous variables (Unstandardized β=6.556, P<0.001) and across the increasing quartiles (β=7.50, 95% CI (1.41, 13.59), P<0.05). RCS demonstrated there were a positive trend and linear association between EFV and TyG index in CHF patients (P for nonlinearity=0.941).
CONCLUSIONS In patients with CHF, the TyG index was positively and linearly associated with the EFV, which supports the metabolic roles of epicardial adipose tissue regarding insulin resistance.
GW34-e0634
He Ze Fan, Zu Yi Yuan, Juan Zhou
Department of Cardiovascular Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, PR China
OBJECTIVES Both the serum klotho (sKI) levels and a healthy lifestyle are inversely associated with heart failure (HF). However, it remains unclear whether sKI could mediate the association between a healthy lifestyle and HF.
METHODS We performed the cross-sectional study using the data from the 2007–2016 National Health and Nutrition Examination Survey (NHANES) cycle to address this knowledge gap. A total of 7959 participants were included. A healthy lifestyle score (HLS) was calculated based on the following 6 lifestyle factors: smoking status, body mass index, physical activity, healthy diet score, drinking status, and sleep duration. Each metric was categorized as unhealthy or healthy and assigned 0 and 1, respectively. The overall HLS score was calculated as the sum of the score for each of the 6 metrics (range 0–6). The total HLS score was then categorized into poor (0–1), intermediate (2–3), and ideal.
RESULTS Multivariable linear regressions revealed that for every 1-point increase in HLS, sKI increased by 22.13 pg/mL. Compared with participants who maintained only 0 or 1 healthy lifestyle, those who maintained 4 or more healthy lifestyles had an elevated sKI of 72.49 pg/mL. Furthermore, HLS was significantly associated with a lower risk of HF (Odds ratio, OR=0.87, 95% CI=0.76–0.99). However, after additional adjustment of the mediating variable Klotho on top of Model 3, this association became insignificant (OR=0.88, 95% CI=0.77–1.01). sKI was also negatively associated with the prevalence of HF (OR=0.92, 95%=0.87–0.97). After additional adjustment of the independent variable HLS on top of Model 3, the OR value and 95% CI of sKI did not change. Mediation analysis revealed that sKI had a statistical effect on the association between HLS and HF (average causal mediation effect, ACME=−0.0005, P=0.02). We observed that 12.5% of the association between HLS and heart failure was mediated through sKI.
CONCLUSIONS In conclusion, adherence to a healthy lifestyle was associated with a higher level of sKI, thereby reducing the risk of HF.
GW34-e0693
Wenjie Li, Wang Zhiyan, Dong Jianzeng, Du Xin
Ahzhen Hospital
OBJECTIVES Relationship between body mass index (BMI), frailty, and clinical adverse events remains unclear in patients with heart failure with preserved ejection fraction (HFpEF).
METHODS We used data of 1715 participants enrolled from America in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) study and 1487 patients with HFpEF in the Chinese registry study the Heat Failure Registry of Patient Outcomes (HERO). We described distribution of BMI and frailty index (FI) for the two population and evaluated the relationship between BMI and frailty using multivariate restricted cubic spline logistic regression. Association between frailty and BMI categories and primary outcomes including HF hospitalization, aborted sudden death, and cardiovascular death, all-cause mortality, and HF hospitalization were analyzed by Cox Hazard Proportional models.
RESULTS The patients mean age were 72±11 years for both study population, with 50% and 46% female, respectively for the TOPCAT study and the HERO study. Patients in the TOPCAT study had a higher mean BMI (33.9 versus 24 Kg/m2), with 72.3% versus 52.9% defined as moderately to severely frail (FI >0.3). In the TOPCAT study, risk of frailty rose as BMI increased, but not in the HERO study. Patients with frailty were at significant higher risk for the primary composite outcomes [HR 1.81, 1.44–2.28], all-cause mortality [HR1.72, 1.32–2.23], and heart failure hospitalization [HR1.81, 1.39–2.37] in the TOPCAT study. The corresponding numbers in the HERO study were 1.23(1.04–1.46), 2.21(1.62–3.03), and 1.10(0.90–1.34) respectively. The association of frailty with clinical outcomes did not vary with BMI categories in the two studies.
CONCLUSIONS BMI distribution, association between BMI and frailty risk were different between the two study population. Frailty was associated with clinical adverse events and this association was consistent across different BMI categories in both studies.
GW34-e0726
Xiaohan Qin, Jinzhi Lai, Dingding Zhang, Jiaqi Wang, Jiaqi Yu, Keyue Sun, Deyan Yang, Jingbo Fan, Lihua Zhang, Zhongwei Cheng, Kangan Cheng, Peng Gao, Hua Deng, Quan Fang, Taibo Chen, Yongtai Liu
Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College
OBJECTIVES Left atrial (LA) function was impaired in both atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). The diagnosis of HFpEF was still challenging, especially in AF patients. In this study, we aimed to evaluate whether LA compliance (LAC) could facilitate the diagnosis of HFpEF in patients with paroxysmal atrial fibrillation (pxAF).
METHODS One hundred and ninety pxAF patients were enrolled and performed baseline transthoracic echocardiography (TTE). LAC was measured in all patients and HFpEF was ascertained based on the H2FPEF score (38 high-probability of HFpEF [hp-HFpEF], 152 medium/low-probability of HFpEF [lp-HFpEF]).
RESULTS The left ventricular diastolic function and LA function were significantly altered in hp-HFpEF group compared to the lp-HFpEF ones. Mitral annular early diastolic peak velocity (MVE’) (6.33 [5.38–7.31] vs. 8.35 [7.31–9.35], P<0.001), LA reservoir strain (27.68±12.70 vs. 35.00±11.27, P=0.007) and LAC (2.66 [2.29–3.07] vs. 4.31 [3.41–5.69], P<0.001) were significantly impaired in hp-HFpEF patients. Of all echocardiographic indices, the ratio of LA volume change to E/MVE’ as a surrogate of LAC showed the greatest diagnostic performance to discriminate hp-HFpEF from lp-HFpEF in patients with pxAF (AUC=0.843, P<0.0001, LR+ 4.8, LR− 0.25). Furthermore, combining MVE’ and LAC revealed the highest diagnostic efficiency (LR+ 9.20) than any single variable.
CONCLUSIONS LAC analysed by conventional echocardiography provided added value as a non-invasive, easy-to-use approach for discriminating hp-HFpEF from lp-HFpEF in patients with pxAF. Meanwhile, combination of LAC and MVE’ offered preferable diagnostic ability than any single one.
GW34-e0828
Jia Shi1, Mengjiao Shao2, Baopeng Tang1
1The First Affiliated Hospital of Xinjiang Medical University
2The Fifth Affiliated Hospital of Sun Yat-sen University
OBJECTIVES Inflammation and cardiac fibrosis are important pathogenic drivers of heart failure. The influence of the fibrosis-4 index (FIB-4) and the systemic immune inflammation index (SII), which are accurately represent the changes of inflammation and fibrosis, on left ventricular reverse remodeling (LVRR) in patients with heart failure (HFrEF) is not known. Here, we investigated the association of the baseline inflammation-fibrosis combined index (IFCI) with LVRR and subsequent prognosis.
METHODS This retrospective cohort study involved 895 consecutive patients with HFrEF. Demographic and clinical data were collected by cardiovascular doctors. Logistic regression, receiver operating characteristic (ROC) curve, and Kaplan–Meier analyses were performed to assess the predictive value of IFCI in LVRR.
RESULTS A total of 895 patients were included in our study, 344 (38.4%) patients had LVRR after 6 months. After ROC analysis and the DeLong test, the IFCI had the largest AUC of 0.835 (95% CI: 0.809–0.860). In multivariate-adjusted logistic regression analyses, the FIB-4, SII, and IFCI were predictive of LVRR (P value<0.05). Further analysis revealed that the IFCI was associated with a 3.898-fold higher risk of non-LVRR (OR=3.898, 95% CI: 3.064–4.958, P<0.001). Moreover, an increased IFCI predicted a poor prognosis in HFrEF patients. The highest risk of composite cardiac events (HR=2.167, 95% CI: 1.631–2.879, P<0.001) was observed in the top IFCI-tertile group, and similar results were found regarding independent risk factors of all-cause death.
CONCLUSIONS In summary, this study indicated that increased FIB-4, SII and IFCI at admission offer good predictability regarding LVRR. After adjusting for potential risks, the IFCI exhibited the best performance in estimating LVRR and predicting the risk of all-cause mortality or composite cardiovascular events due to HFrEF patients and could be used as a novel marker.
GW34-e0846
Junyan Xia, Jun Teng, Yun Cai, Qian Lin
Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
OBJECTIVES Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) frequently coexist as they share similar clinical symptoms, risk factors, and cardiac structure. The number of studies investigating the relationship between HFpEF and AF studies has grown significantly. Therefore, we conducted a bibliometric analysis to provide a comprehensive overview of knowledge structure and research hotspots in this field.
METHODS We systematically searched of the Web of Science Core Collection database for publications related to HFpEF with AF and performed a bibliometric analysis by CiteSpace, VOSviewers, Bibliometrix, and Excel 2019.
RESULTS Our search yielded 774 publications on HFpEF with AF, with studies on this topic gradually increasing since 2004. Most publications originated from the United States, while the Netherlands had the highest average article citations and the most international collaborations. The most prolific institution was Mayo Clinic, and the highest h-index author was Carolyn S. P. Lam from the University of Groningen. The European Journal of Heart Failure was found to be the most influential journal in this field. Based on co-cited references and keywords analysis, pathophysiological mechanisms, risk factors (such as obesity), therapeutic interventions (such as catheter ablation), and auxiliary tests (such as echocardiography) were identified as hotspots and frontiers in HFpEF with AF research.
CONCLUSIONS Recent research on HFpEF with AF focused on investigating pathophysiology, the impacts and mechanisms of obesity, efficacy and safety of rhythm control and medication, and echocardiography diagnostics.
GW34-e0855
Chen-die Yang, Xiao-qun Wang
Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine
OBJECTIVES With advanced guideline-directed therapies, a substantial portion of heart failure (HF) patients have experienced improvement of ejection fraction (EF), termed HFimpEF. We sought to investigate the association between visit-to-visit glycemic variability (GV) and the incidence of HFimpEF.
METHODS From January 2013 to December 2020, 951 hospitalized HF patients with reduced EF (HFrEF, EF≤ 40%) were consecutively enrolled and followed up for around 12 months. The incidence of HFimpEF, defined as (1) an absolute EF improvement ≥10% and (2) a second EF>40% and its relationship with visit-to-visit fasting plasma glucose (FPG) variability were analyzed.
RESULTS A total of 519 HFrEF patients were finally enrolled. During a mean follow-up of 12.2±0.6 months, 218 (42.0%) patients developed HFimpEF. Multivariate analysis showed visit-to-visit FPG variability was independently associated with incidence of HFimpEF after adjustment for baseline HBA1c, mean FPG during follow-up and other traditional risk factors (odds ratio [OR] for highest vs. lowest quartile of CV of FPG: 0.487 [95% CI 0.257~0.910]). Assessing FPG variability by alternative measures yielded similar results. Subgroup analysis revealed the relationship between GV and HFimpEF was only observed in HF of ischemic etiology and the association persisted significant irrespective of glycemic levels and diabetic conditions.
CONCLUSIONS This study reveals that greater visit-to-visit FPG variability is associated with compromised development of HFimpEF independent of mean glycemic levels and diabetic conditions. Therapies targeted at improving GV might provide favorable effects on myocardial recovery in HF patients even without diabetes.
GW34-e0859
Chen-die Yang, Xiao-qun 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 6–12 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 Type 2 diabetic patients with uncontrolled HbA1c levels were associated with compromised development of HFrecEF and worse clinical outcomes.
GW34-e0863
Chen-die Yang, Xiao-qun 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 have experienced recovery of cardiac function and ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is quite prevalent in HF and tightly related with prognosis. This study mainly investigates the relationship between insulin resistance and the incidence of HFrecEF in non-diabetic patients.
METHODS In the study, a total of 262 non-diabetic HF patients with reduced EF (HFrEF) were consecutively enrolled. Patients were classified into HFrecEF (follow-up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment (HOMA2-IR).
RESULTS The median HOMA2-IR level was 1.05 (IQR 0.67~1.63) in our cohort of non-diabetic HF patients. During follow-up, 121 (46.2% [95% CI 40.2~52.2%]) patients developed HFrecEF. Compared with HFrEF patients, HFrecEF patients had significantly lower HOMA2-IR levels (0.92 [IQR 0.61~1.37] vs. 1.14 [IQR 0.75~1.78], P=0.007), especially in HF of nonischemic etiology. Log2-transformed HOMA2-IR was inversely correlated to improvements in EF (Pearson’s r=−0.25, P<0.001). After multivariable adjustment, a doubling of HOMA2-IR was associated with a 42.8% decreased likelihood of HFrecEF (OR 0.572 [95% CI 0.385~0.827]).
CONCLUSIONS In conclusion, this study reveals that insulin resistance is independently associated with compromised development of HFrecEF in non-diabetic patients.
GW34-e0864
Chen-die Yang, Xiao-qun Wang
Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine
OBJECTIVES Left ventricular (LV) diastolic dysfunction (LVDD) is the defining feature of heart failure with preserved ejection fraction (HFpEF), and predicts subsequent incident heart failure (HF) and all-cause mortality. Mounting evidence reveals that cardiometabolic risk factors play critical roles in the development of LVDD. In this study, we sought to investigate the relation between serum uric acid (SUA) level and the progression of LVDD in apparently healthy patients.
METHODS A total of 1082 apparently healthy subjects without diagnosed cardiovascular disease and LVDD were consecutively enrolled. SUA levels were measured and repeat echocardiography and tissue Doppler imaging (TDI) were performed at baseline and during 1-year follow-up.
RESULTS By dividing the study population based on quartiles of SUA, we found subjects in higher quartiles had greater increases in TDI-derived early diastolic velocity (e′) and E (peak LV filling velocity)/e′ratios during 1-year follow-up. After multivariate adjustment, high SUA persisted to be an independent predictor for the subsequent worsening of LVDD (odds ratio: 1.351 [95% CI 1.125~1.625], per 100 μmol/L SUA). Subgroup analysis suggested that the association between SUA and LVDD development was more pronounced in subjects without other cardiometabolic risk factors involved. Factor analysis demonstrated that high SUA was the major cardiometabolic attribute in patients with LVDD progression.
CONCLUSIONS Our findings suggest that high SUA is an independent cardiometabolic risk factor for the progression of LVDD in apparently healthy subjects.
GW34-e0953
Yuling Zha1,2, Jun Li2, Yuping Zhou2
1Graduate School, Beijing University of Chinese Medicine
2Department of Cardiology, Guang’ anmen Hospital, China Academy of Chinese Medicine Sciences
OBJECTIVES To observe the correlation between Ghrelin, MSTN, appetite, nutritional status, hemoglobin, albumin, blood lipids, and other indicators in patients with chronic heart failure (CHF) and malnutrition, and to focus on exploring the role of the inflammation Ghrelin/MSTN appetite improvement/muscle growth axis in the development of CHF patients into malnutrition.
METHODS This is a prospective cross-sectional Observational study. This study collected the general information and physicochemical indicators of 128 patients with CHF, and used enzyme-linked immunosorbent assay to measure the levels of growth hormone releasing peptide (GHRL) and muscle growth inhibitor (MSTN), According to the score of the MNA-SF scale, the patients were divided into CHF malnourished group and CHF non malnourished group. The difference of detection indicators between the two groups was compared, and the predictive indicators affecting malnutrition in CHF patients were analyzed through binary logistic regression analysis, drawing Receiver operating characteristic and other methods. And analyze the clinical characteristics of 107 CHF patients with malnutrition.
RESULTS (1) A total of 128 patients with CHF were collected in this study, including 107 patients with CHF combined with malnutrition risk and 21 patients with CHF but not combined with malnutrition risk. (2) The average age of the CHF combined with malnutrition group was higher than that of the non malnutrition group, with a very significant difference (P<0.01). The Hs-CRP, MSTN, and Minnesota quality of life scores in the CHF combined with malnutrition group were significantly higher than those in the non malnutrition group (P<0.05). The BMI, body weight, MNA-SF scale score, simple anorexia scale score, simple appetite scale score, and abdominal circumference, albumin, prealbumin of the CHF combined malnutrition group were all lower than the three scale scores of the CHF non combined malnutrition group, with a very significant difference (P<0.01). The diameter of the right upper limb, hemoglobin, GHRL of the CHF combined with malnutrition group were significantly lower than those of the non malnutrition group (P<0.05). (3) Age, simple anorexia scale score, MSTN, and the diameter of the right upper limb have AUC areas of 0.72, 0.156, 0.647, and 0.362 for malnutrition in CHF patients, respectively. (4) There is a positive correlation between MSTN and CRP, Hs-CRP, and there is a significant difference between MSTN and CRP (P<0.05). There is a negative correlation between GHRL and CRP, Hs-CRP, and there is a significant difference between GHRL and CRP (P<0.05). There is a negative correlation between MSTN and GHRL, and there is no significant difference between the two (P>0.05). (5) There was a significant difference in MNA-SF scale scores and simple appetite scale scores among CHF patients with malnutrition due to different functional levels (P<0.01).
CONCLUSIONS (1) The higher the degree of cardiac function deterioration in CHF patients, the poorer their appetite. (2) Age, MSTN, right upper limb diameter, and simple anorexia scale scores can independently predict malnutrition in CHF patients. (3) Cardio cerebral Vascular disease, endocrine metabolic disorders, Hypoproteinemia, inflammation, etc. are the main complications of CHF patients with malnutrition; (4) Inflammation affects the appetite and nutritional status of CHF patients, and promotes the progression of CHF.
GW34-e0968
An-Tian Chen, Jian Zhang, Yuhui Zhang
Fuwai Hospital, CAMS & PUMC
OBJECTIVES Heart failure (HF) is a growing epidemic and global concern.
METHODS Using Asia data from the Global Burden of Disease (GBD) study spanning 1990–2019, we assessed the prevalence, etiology, morbidity, and trends of HF. Of note, Asia includes Australasia in this study.
RESULTS In 2019, there were an estimated 31.89 million HF cases across Asia, with females accounting for 50.93% of the cases. Females were more prevalent among older adults, while males predominated among the young. The top three causes of HF in Asia were hypertensive heart disease, ischemic heart disease, and COPD. The prevalence of specific causes varied across ages, genders, and regions. Hypertensive and ischemic heart disease were the most predominant causes of HF. Myocarditis and alcoholic cardiomyopathy were more prevalent in males, while non-rheumatic calcific aortic valve disease and endocarditis were more prevalent in females. The estimated morbidity of HF in Asia was 2.87 million YLDs, with females accounting for 1.46 million YLDs. Individuals under 70 years of age contributed 1.22 million YLDs. HF accounted for all estimated YLDs of hypertensive heart disease and the HF contribution to the overall burden varied. Between 1990 and 2019, the number of HF cases in Asia increased by 155.94%, from 12.46 million to 31.89 million. The age-standardized rate of HF per 100,000 people decreased by 4.51% in Asia, from 756.55 in 1990 to 722.45 in 2019, which was more pronounced in females compared to males. Age-standardized HF rates from hypertensive heart disease, ischemic heart disease, COPD, non-rheumatic valvular disease, cardiomyopathy, and myocarditis showed a declining trend in both genders. However, there were increases due to rheumatic heart disease and congenital birth defects in both females and males.
CONCLUSIONS In Asia, while the number of HF cases has increased, the age-standardized prevalence decreased from 1990 to 2019, particularly among females. The etiology of HF is characterized by ischemic heart disease and heart disease, and COPD as the primary causes. The identified sex-specific differences and trends of HF in Asia can inform further public health efforts aimed at alleviating the burden of HF.
GW34-e0990
Qing-wen Ren1,2, Kai-hang Yiu1,2
1The University of Hong Kong
2The University of Hong Kong – Shenzhen Hospital
OBJECTIVES Remnant cholesterol, identified by triglyceride-rich lipoprotein, is increasingly acknowledged as a significant causal risk factor for ischemic heart diseases. The association with cause-specific outcomes in heart failure (HF) settings remains unexplored. This study aims to determine the association between triglyceride levels with all-cause mortality and cardiovascular outcomes among patients with HF.
METHODS One hundred twenty-seven thousand one hundred twenty-four eligible patients with HF from 2000 to 2020 were enrolled. Triglyceride levels associated with risk of mortality were evaluated on a continuous scale using restricted cubic spline curves and by categories using Cox proportional hazards regression model. The outcomes were Atherosclerotic cardiovascular disease (ASCVD), HF, cardiovascular death (CVD) and all-cause mortality.
RESULTS The mean age was 71.4±12.2 years, 51.8% were male. Notably, when we investigated the association of triglyceride levels with admission or death for ASCVD, a positive relationship was seen in high triglyceride levels and ASCVD admission or death while neutral in low triglyceride levels. Conversely, when we investigated the association with readmission or death for HF, an inverse relationship was found where lower triglyceride levels were associated with higher risks of HF readmission or death. Together, the association between triglyceride levels and the risk of all-cause mortality and CVD was a U-shaped curve. The risk of adjusted all-cause mortality reached a nadir between triglyceride levels of 1.2–3.0 mmol/L and was lowest at 1.95 mmol/L.
CONCLUSIONS In the HF population, low and high triglyceride levels were associated with increased risks of all-cause mortality and CVD compared with those with intermediate levels. Triglyceride was positively associated with ASCVD while inversely associated with HF admission or death. A better understanding of the role and contribution of triglyceride levels to adverse outcomes in patients with HF is needed.
GW34-e0992
An-Tian Chen, Jian Zhang, Yuhui Zhang
Fuwai Hospital, CAMS & PUMC
OBJECTIVES Heart failure (HF) is a severe manifestation of multiple cardiovascular diseases and leads to intensive care unit (ICU) admissions and mortality.
METHODS After screening 12,254 HF records from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, the study selected 2343 first ICU admission records of HF patients that stayed between 24 hours and 28 days. Feature selection was carried out using the Least Absolute Shrinkage and Selection Operator (LASSO) regression. The best-performing model was chosen from a set of 15 algorithms including Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Logistic Regression (LR), Ridge Classifier, Light Gradient Boosting Machine (LightGBM), eXtreme Gradient Boosting (XGBoost), Gradient Boosting, Decision Tree (DT), Random Forest (RF), Extremely Randomized Trees (Extra Trees), Adaptive Boosting (AdaBoost), Naive Bayes (NB), Dummy Classifier, K-Nearest Neighbors (KNN), and Linear Kernel Support Vector Machine (SVM). The performance is evaluated by accuracy, sensitivity, precision, F1 score, area under the curve (AUC) of the receiver operating characteristic (ROC), Cohen’s Kappa Score, and Matthews correlation coefficient (MCC). The model was made explainable using the Shapley Additive Explanations (SHAP) approach. A nomogram was created based on logistic regression. Both models were converted into publicly accessible calculators.
RESULTS Seventy-five features were finally selected by referring to clinical experience and publications, including basic information: age, length of stay; vital signs: heart rate (HR), blood pressure (BP), end-tidal CO2 (EtCO2); laboratory tests: blood routine, acid-base balance, liver function, renal function, electrocyte, cardiac markers, coagulation tests, metabolism; hemodynamics: central vein pressure (CVP), pulmonary artery line cm mark, pulmonary artery pressure systolic (PAPs); and respiration: pressure and saturation of O2 and CO2. The LDA model showed the best performance in predicting 28-day all-cause mortality for HF patients in ICU. Lactic acid, HCO3 − (serum), and PCO2 (arterial) were the top three most important features of the LDA model. SHAP approach showed that older patients, patients with longer ICU stays, higher levels of PCO2 (both arterial and venous), lactic acid, partial thromboplastin time (PTT), blood urea nitrogen (BUN), white blood cell (WBC), HR, glucose (serum), and fibrinogen are less likely to survive. Conversely, lower levels of HCO3 −, non-invasive blood pressure mean (NBPm), arterial blood pressure systolic (ABPs), non-invasive blood pressure systolic (NBPs), PO2 (arterial), lymphocyte (differential), neutrophil (absolute), platelet count, and alanine transaminase (ALT) indicate a higher possibility of death. The LDA model was converted into a publicly accessible online calculator and could be accessed at https://tal-cat-28-day-all-cause-mortality-prediction-hf-predict-7rbxqk.streamlit.app/. The nomogram included 14 features and demonstrated excellent performance, which were age, length of stay, ABPs, ALT, BUN, lymphocyte (differential), fibrinogen, HCO3 − (serum), HR, lactate dehydrogenase (LDH), lactic acid, PO2 (arterial), PTT and WBC. The nomogram model was publicly accessible through https://at-c.shinyapps.io/DynNomapp/.
CONCLUSIONS The study developed an LDA model and a nomogram-based logistic regression model for predicting mortality in HF patients in the ICU. The SHAP approach was used to explain the LDA model, enabling better utilization by clinicians. The nomogram-based model demonstrated great performance, making it a useful tool for visualizing prognosis. Both models are available online for clinical use.
GW34-e1065
An-Tian Chen, Jian Zhang, Yuhui Zhang
Fuwai Hospital, CAMS & PUMC
OBJECTIVES Heart failure (HF) often leads to ICU admissions and mortality.
METHODS Patients diagnosed with HF and admitted to the ICU were included, while patients who stayed less than 24 hours or over 28 days were excluded. The primary outcome was all-cause mortality within 28 days. Python and R were used. Feature selection was carried out using LASSO regression. Fifteen models were examined including Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis, Logistic Regression, Ridge Classifier, LightGBM, XGBoost, Gradient Boosting, Decision Tree, Random Forest, Extra Trees, AdaBoost, Naive Bayes, Dummy Classifier, KNN, and SVM. The model was made explainable using the SHAP approach. A nomogram was created based on logistic regression. Both models were converted into publicly accessible calculators.
RESULTS 12,254 ICU admission records were extracted. After selection, the study included 2343 first-admission records, with 1808 surviving and 535 deceased patients. Seventy-five features were initially selected including basic information, vital signs, laboratory tests, hemodynamics, and oxygen status. We applied LASSO regression and determined the shrinkage parameter α to be 0.020 and 44 features were finally selected for model building. The LDA model showed the best performance and the accuracy reached 0.8354 in the training cohort and 0.8563 in testing. It also showed satisfying AUC (training 0.8555, testing 0.8784), recall (training 0.4897, testing 0.5590), precision (training 0.7130, testing 0.7500), F1 score (training 0.5762, testing 0.6406), Cohen’s Kappa Score (training 0.4785, testing 0.5532), and MCC (training 0.4942, testing 0.5625). The accuracy, recall, and MCC of the LDA model were the highest among all 15 algorithms for both the training and testing cohorts. Also, the F1 score and Cohen’s Kappa Score of the LDA model were the highest for the training set. SHAP approach showed that older patients, longer ICU stays, higher levels of PCO2, lactic acid, PTT, BUN, WBC, HR, glucose, and fibrinogen are less likely to survive. Conversely, lower levels of HCO3 −, NBPm, ABPs, NBPs, PO2, lymphocyte, neutrophil, PLT, and ALT indicate a higher possibility of death. The LDA model was converted into a publicly accessible online calculator and could be accessed at https://tal-cat-28-day-all-cause-mortality-prediction-hf-predict-7rbxqk.streamlit.app/. Univariable analysis was performed between the survival and non-survival groups in the training cohort. Features that differed significantly between groups (P-value<0.05) were subjected to multiple logistic regression. The nomogram built on multiple logistic regression included 14 features and demonstrated excellent performance, which were age, length of stay, ABPs, ALT, BUN, lymphocyte, fibrinogen, HCO3 −, HR, LDH, lactic acid, PO2, PTT, and WBC. The AUC of the nomogram is 0.852 in training and 0.855 in the internal validation cohort. The calibration curve showed good consistency both in the training and internal validation cohort. Decision curve analysis was also adopted, indicating that 75% is a preferable threshold. The nomogram was publicly accessible through https://at-c.shinyapps.io/DynNomapp/.
CONCLUSIONS The study developed an LDA model and a nomogram model for predicting mortality in HF patients in the ICU. The SHAP approach was used to explain the LDA model, enabling better utilization by clinicians. Both models are available online for clinical use.
GW34-e1143
Liyan Huang, Yuhui Zhang, Jian Zhang
Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
OBJECTIVES Heart failure (HF) may entail high risk of venous thromboembolism (VTE), and in-hospital thromboprophylaxis is recommended in such patients. However, optimal duration of thromboprophylaxis is unclear, since risk of VTE could persist several weeks after discharge. We sought to investigate the benefit-risk profile of extended-duration thromboprophylaxis in hospitalized HF patients.
METHODS Electronic databases (PubMed/Medline, Cochrane, EMBASE, ClinicalTrials.gov) were searched from inception to Nov.25th 2021. We included randomized clinical trials reporting use of extended-duration thromboprophylaxis for prevention of VTE in hospitalized HF patients. We performed conventional and cumulative meta-analysis, trial sequential analysis (TSA) to determine whether extended-duration thromboprophylaxis would prevent VTE or VTE-related death, and to determine the safety of extended-duration thromboprophylaxis on major bleedings.
RESULTS Of 654 citations identified, 56 full texts were assessed for eligibility. In the 3 studies satisfying inclusion criteria, extended-duration thromboprophylaxis did not reduce VTE/VTE-related death compared with standard-duration anticoagulation (2.85 versus 3.51%; risk ratio [RR]: 0.82; 95% confidence interval [CI]: 0.66–1.03). However, extended anticoagulation increased risk of major bleeding (1.37 versus 0.52%; RR: 2.57; 95% CI: 1.66–3.97) in conventional and cumulative meta-analysis. TSA of risk of progression to VTE/VTE-related death showed that the required information size had not been achieved; extended-duration thromboprophylaxis did not prevent patients from VTE/VTE-related death. TSA of risk of progression to major bleeding showed that extended-duration thromboprophylaxis increased major bleeding risk compared to standard-duration anticoagulation.
CONCLUSIONS In conclusion, in hospitalized HF patients, post-discharge thromboprophylaxis for several weeks did not reduce VTE or VTE-related death events, while increasing risk of major bleeding.
GW34-e1163
Chao Sun, Renjie Gu, Qiming Liu
The Second Xiangya Hospital of Central South University
OBJECTIVES Acute heart failure (AHF) is a serious disease associated with high mortality. The effect of lactate dehydrogenase to albumin ratio (LAR) on the survival of patients with AHF is unclear. We aimed to analyze the impact of LAR on survival of intensive care unit patients with AHF.
METHODS The eligible patients in our study were obtained from Monitoring in Intensive Care Database III (MIMIC-III) database. Clinical data and demographic information were queried and collected for each patient using standard SQL commands in our study. Multivariate logistic regression models and smooth curve fitting were used to determine whether LAR score could be an independent indicator for the prognosis of patients with AHF. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of LAR to discriminate between survivors and non-survivors. All the statistical analyses were conducted by R software (4.1.1).
RESULTS The study included 2177 patients after screening all patients in the database. The mean age of enrolled patients was 69.88 for survivors and 71.95 for non-survivors. In the survivor group, the mean LAR ratio was 13.44, while in the death group, the value was 17.38. The association of LAR and in-hospital mortality was almost linear by smooth curve fitting (P<0.001). Multivariate logistic regression indicated LAR could be an independent risk factor to predict the prognosis of patients with AHF (odds ratios=1.09; P<0.001). The area under curve was 0.85 (P<0.001) by ROC analysis, and the most sensitive cutoff value for the LAR was 14.5, with a sensitivity of 91.8%, specificity of 65.6%.
CONCLUSIONS LAR ratio is an independent risk factor associated with increased in-hospital mortality rates in patients with AHF.
GW34-e1168
Hai-Yue Yang1,2,3, Kai-Hang Yiu2,3, Qing-Wen Ren2,3
1Bachelor of Medicine and Bachelor of Surgery, The University of Hong Kong
2Cardiology Division, Department of Medicine, The University of Hong Kong Shen Zhen Hospital, Shen Zhen, China
3Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
OBJECTIVES Global attention on the correlation between sleep disorders and heart failure (HF) has been relatively limited in the past. Despite a growing interest in recent years, there remains a paucity of research specifically examining the impact of insomnia on HF outcomes. Our study therefore aims to investigate the prospective association between insomnia and the risk of all-cause mortality, cardiovascular death, and HF rehospitalization in patients with HF.
METHODS Using a territory-wide database, the Clinical Data Analysis and Reporting System (CDARS), developed by the Hong Kong Hospital Authority, we identified patients diagnosed with HF from 1993 to 2020. Propensity score matching was employed to balance the differences between patient groups presenting with and without insomnia. Subsequently, we applied Cox proportional-hazard models to analyze the association between insomnia and the risk of all-cause mortality, cardiovascular death, and HF rehospitalization in patients with HF. Adjustments were made for various covariates including demographics, comorbidities and drug prescriptions, and multi-adjusted hazard ratios were calculated. Furthermore, cumulative incidence curves were plotted to illustrate the differences between the cumulative incidences of the two interested outcomes in patients with and without insomnia.
RESULTS Among the 261,633 HF patients (age>18 years; mean [SD] age, 72.5 [12.3] years; 52.4% female), 19,487 were diagnosed with insomnia. Remarkably, a positive relationship was detected between insomnia and the risks of all-cause mortality, cardiovascular death, and HF rehospitalization in HF patients, demonstrating increased risks of over 14% (HR: 1.14, 95% CI: 1.12 – 1.17), 13% (HR: 1.13, 95% CI: 1.09 – 1.16), 23% (HR: 1.23, 95% CI: 1.19 – 1.28), respectively, compared with those without insomnia. The cumulative incidence curves also revealed a higher incidence of all 3 outcomes in patients with insomnia without overlapping, further substantiating our findings and reinforcing the credibility of our results.
CONCLUSIONS Our study thus indicated a significant association between insomnia and increased risk of adverse outcomes, such as all-cause mortality, cardiovascular death, and HF rehospitalization, in patients with heart failure. Consequently, the importance of public awareness campaigns and regular screening protocols for insomnia in HF patients or at-risk populations must not be underestimated in future healthcare practices.
GW34-e1215
Scott D Solomon1, Muthiah Vaduganathan1, Carolyn S P Lam2, Bertram Pitt3, Michele Sennii4, Faiez Zannad5, Adriaan A Voors6, Brian Claggett1, Pardeep S Jhund7, Akshay S Desai1, I I van Gameren8, James Karen Lay-Flurrie8, F do Amarante8, Pragasam Viswanathan8, John J V McMurray7
1Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America
2National Heart Centre Singapore & Duke-National University of Singapore, Singapore, Singapore
3University of Michigan, School of Medicine, Ann Arbor, United States of America
4Papa Giovanni XXIII Hospital, Bergamo, Italy
5University of Lorraine, Nancy, France
6University Medical Center Groningen, Groningen, Netherlands (The)
7University of Glasgow, Glasgow, United Kingdom of Great Britain & Northern Ireland
8Bayer, Leverkusen, Germany
BACKGROUND While mineralocorticoid receptor antagonists (MRAs) are guideline-recommended medical therapy for patients with HF with reduced ejection fraction, their role in heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) remains uncertain. Finerenone is a non-steroidal MRA with favorable cardiovascular and renal effects in patients with type 2 diabetes and chronic kidney disease.
METHODS FINEARTS-HF is a global randomized clinical trial comparing finerenone with placebo in patients with HFmrEF/HFpEF. Eligible participants were in New York Heart Association (NYHA) functional class II–IV and had a left ventricular ejection fraction (LVEF) ≥ 40%, elevated natriuretic peptides, and evidence of structural heart disease. Patients could be enrolled either in hospital or as an outpatient. The primary endpoint is a composite of cardiovascular death and total (first and recurrent) worsening HF events (HF hospitalizations or urgent HF visits).
RESULTS We randomized 6016 patients (mean age 72±10 years; 45% women, 41% type 2 diabetes, LVEF 53±8%) from 635 sites across 37 countries. 12% were enrolled in hospital, 8% were enrolled within 7 days of a HF hospitalization or urgent HF visit, 34% were enrolled between 8 and 90 days of a HF hospitalization or urgent HF visit, and 46% had no recent HF hospitalization or urgent HF visit. 19% had an LVEF≥60%. Comorbidities were common and 54% of patients had a history of atrial fibrillation/flutter. Baseline Characteristics differed substantially by enrollment subgroup. Participants in FINEARTS-HF represent a higher risk cohort with worse functional class and higher natriuretic peptides than in prior trials of HFmrEF/HFpEF.
CONCLUSIONS FINEARTS-HF has enrolled a broad global population of patients with HFmrEF/HFpEF. Over half were enrolled during or within 90 days of an episode of worsening HF. We will present the design and baseline data from FINEARTS-HF in the context of other contemporary trials in similar patients.
GW34-e1229
Ruting Wang1, Kai Huang1, Hangfeng Ying1, Jiahao Duan1, Qinwen Feng1, Chun Yang2, Ling Yang1
1Department of Cardiology, The First People’s Hospital of Changzhou, Changzhou 213003, China
2Department of Anesthesiology and Perioperative Medicine, Jiangsu Province Hospital, Nanjing 210029, China
OBJECTIVES The objective of this study is to analyze the sarcopenia index (SI), based on serum creatinine to cystatin C ratio, in heart failure (HF) patients, especially HF with preserved ejection fraction (HFpEF) patients, and to develop a prediction model for the diagnosis of HFpEF.
METHODS There were 229 HF patients and 73 healthy controls (HCs) enrolled in this study, and their baseline information were collected upon admission. Binary logistic regression analysis was used to screen the risk factors of HFpEF. A prediction model was further optimized by the least absolute shrinkage and selection operator (LASSO), displayed by nomogram and verified internally by the bootstrap sampling method (Bootstrap). Moreover, the predictive performance was measured using receiver-operating-characteristics (ROC), calibration curve, and decision curve analysis (DCA).
RESULTS SI was significantly different between the HF and HC groups (67.9±13.0 vs. 98.6±31.5). Multivariate logistic regression analysis showed that a low level of SI (OR 0.921, 95% CI 0.879–0.965, P=0.001) was an independent risk factor for HF. Atrial fibrillation (AF) (OR 6.336, 95% CI 2.511–15.988, P<0.001), systolic blood pressure (SBP) (OR 1.027, 95% CI 1.004–1.051, P=0.022), N-terminal brain natriuretic peptide precursor (NT-proBNP) (OR 0.136, 95% CI 0.046–0.401, P<0.001), and SI (OR 0.948, 95% CI 0.914–0.983, P=0.004) were independently associated with HFpEF. Nine predictor variables, including age, gender, SBP, smoking, NT-proBNP, SI, hemoglobin (Hb), QRS interval (electrocardiogram-related parameters), and AF, were included in the prediction model for the diagnosis of HFpEF compared with heart failure with reduced ejection fraction (HFrEF). The area under the curve (AUC) in the original data was 0.902, and the calibration curve was approximately distributed along the reference line in Bootstrap (500 resamplings). The prediction models with the additional features of AF and SI showed a significantly higher value of AUC (0.902 vs. 0.855, P<0.01).
CONCLUSIONS Low SI is an independent risk factor for hospitalized HF patients, especially HFpEF patients. HFpEF was better identified using the diagnostic prediction model, and the diagnostic efficacy of the model was significantly improved by two features, including SI and AF.
GW34-e1244
Yanxuan Li, Zihan Li, Daoyuan Si, Ping Yang
Department of Cardiovascular Medicine, China-Japan Union Hospital of Jilin University, Changchun, China
OBJECTIVES Heart failure (HF) patients without atrial fibrillation (AF) are at risk of thrombus-associated events (TAE) and they might potentially benefit from anticoagulant therapy. However, a scoring system for thrombus-associated risk stratification in this population remains uncertain.
METHODS We included 461 patients hospitalized for HF without AF in our center from 2017 to 2019, conducting a median follow-up of 47 months. Cox regression model was applied to validate the association between TAE and adverse prognoses (including death, cardiovascular death or hospitalization for HF) by adjusting the models stepwise, and to explore the independent risk factors at baseline of TAE using a univariate-to-multivariate approach. The independent risk factors and CHA2DS2VASc were used to form new scoring systems for thrombus-associated risk stratification, and Receiver Operating Curve (ROC) analysis was applied to evaluate their discrimination.
RESULTS First, TAE [Hazard ratio (HR) 2.869, 95% confidence interval (CI) 2.139–3.848; HR 3.345, 95% CI 2.381–4.699; HR 4.973, 95% CI 3.704–6.676, respectively] and some of the included events [including myocardial infarction (HR 2.829, 95% CI 2.028–3.946; HR 3.641, 95% CI 2.517–5.267; HR 4.513, 95% CI 3.244–6.280, respectively), composite events of myocardial infarction and ischemic stroke (HR 3.130, 95% CI 2.287–4.284; HR 3.494, 95% CI 2.439–5.004; HR 5.279, 95% CI 3.853–7.233, respectively), and intracardiac thrombus (HR 2.907, 95% CI 1.390–6.081; HR 3.109, 95% CI 1.392–6.947; HR 4.050, 95% CI 1.957–8.384, respectively)] during follow-up were independent risk factors of death, cardiovascular death and hospitalization for HF. Second, the independent risk factors of TAE included hypertension (HR 1.563, 95% CI 1.012–2.413), atrial arrhythmia excluding AF (AAexAF) (HR 2.013, 95% CI 1.058–3.831), ischemic stroke or its history (HR 2.325, 95% CI 1.481–3.651), and vascular disease (HR 1.604, 95% CI 1.043–2.467) at baseline in multivariate Cox regression model; the independent risk factors of composite events of TAE and death (TAE-D) included age (HR 1.018, 95% CI 1.004–1.032), ischemic stroke or its history (HR 1.618, 95% CI 1.194–2.191, P=0.002), ejection fraction {(10, 25] vs. (40, 55] HR 2.127, 95% CI 1.458–3.104; (25, 40] vs. (40, 55] HR 1.081, 95% CI 0.820–1.425}, and creatinine clearance (HR 0.993, 95% CI 0.987–0.998) in multivariate Cox regression model. Third, patients with CHA2DS2VASc≥4 bore higher risk of TAE (HR 2.098, 95% CI 1.422–3.097), and TAE-D (HR 1.840, 95% CI 1.449–2.337) compared with those with CHA2DS2VASc <4. Incorporation of AAexAF (2 points) into CHA2DS2VASc increased the area under the ROC significantly in predicting TAE-D [from 0.656 (95% CI 0.606–0.706) to 0.673 (95% CI 0.624–0.723), P=0.017], but not significantly in predicting TAE [from 0.601 (95% CI 0.538–0.665) to 0.618 (95% CI 556–681), P=0.114].
CONCLUSIONS TAE are independent risk factors of adverse prognoses in the population hospitalized for HF without AF, who might benefit from anticoagulant therapy. Hypertension, AAexAF, ischemic stroke or its history, and vascular disease are independent risk factors of TAE. Meanwhile, age, ejection fraction, and creatinine clearance might be the potential risk factors of TAE. CHA2DS2VASc carries a modest predictive value on TAE and TAE-D, and incorporation of AAexAF (2 points) slightly improves its predictive value.
GW34-e1301
Fei Si, Qian Liu, Jing Yu
Hypertension Center, Lanzhou University Second Hospital
OBJECTIVES Renal Denervation (RDN) is currently an emerging method for the treatment of heart failure with reduced ejection fraction (HFrEF). To evaluate the effects of RDN on cardiac function and cardiovascular neurohormones in HFrEF, a meta-analysis was performed.
METHODS We searched PubMed database, Embase, Web of Science, and CNKI, A total of 6 randomized controlled trials, involving 197 patients, were included in this meta-analysis. Outcomes included left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), 6-minutes walk test (6MWT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) or Brain natriuretic peptide (BNP) level, plasma renin, aldosterone (ALD), and norepinephrine (NE) levels, heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP).
RESULTS The results showed that RDN significantly increased LVEF (WMD=6.30%, 95% CI [4.64, 7.96], P<0.01). RDN significantly decreased LVEDD (WMD=−3.55 mm, 95% CI [−5.51, −1.59], P<0.01) and LVESD (WMD=−4.13 mm, 95% CI [−6.08, −2.18], P<0.01) and BNP levels (SMD=−1.24, (95% CI [−1.57, −0.90], P<0.01). RDN improved the 6MWT distance (WMD=51.25 m, 95% CI [8.30, 94.20], P<0.05). For cardiovascular neurohormones levels, RDN significantly decreased the plasma renin level (WMD=−1.60 μg/(L×h), 95% CI [−2.53, −0.67], P<0.01) and ALD level (WMD=−50.62 ng/L, 95% CI [−66.01, −35.24], P<0.01) and NE level (WMD=−67.99 pg/mL, 95% CI [−100.50, −35.48], P<0.01). RDN decreased HR (WMD=−7.22 bpm, 95% CI [−9.84, −4.60], P<0.01). In addition, we found no significant effects of RDN on SBP/DBP in HFrEF patients (WMD=−2.53 mmHg, 95% CI [−6.52, 1.47], P=0.21)/(WMD=−1.49 mmHg, 95% CI [−4.00, 1.02], P=0.25).
CONCLUSIONS In conclusion, our meta-analysis showed that RDN enhanced cardiac function and decreased plasma renin, ALD and NE levels without affecting blood pressure in patients with HFrEF.
GW34-e1302
Maria Gordeeva1, Irina Serdiukova2, Alexander Krasichkov2, Elena Parmon1
1Federal State Budgetary Institution “Almazov National Medical Research Center”
2Radio Engineering Systems Department, Saint Petersburg Electrotechnical University “LETI”
OBJECTIVES The key investigation for the assessment of the left ventricular ejection fraction (EF) is echocardiography, however, this method is not a screening method, especially in individuals with mildly reduced ejection fraction (mrEF). At the same time, an ECG is performed in almost all patients with suspected cardiovascular disease and as part of a preventive examination. It is known that traditional ECG-pattern associated with a decrease in EF have a low diagnostic value. Recently, new ECG-patterns associated with depolarization abnormality (fragmentation of the QRS complex (fQRS) and early repolarization pattern (ERP)) have been actively studied.
The aim of study is investigated ECG-pattern of depolarization abnormalities (fQRS and ERP) in patients with a mrEF.
METHODS The study included 148 patients with ischemic and non-ischemic cardiomyopathy. According to the level of EF, patients were divided into three groups: patients with low EF (lEF) (less than 40%): 31 (25 men, mean age 52.0±15.6); patients with mrEF (49–40%): 29 (23 men, mean age 54.7±12.4); patients with preserved EF (pEF) (more than 50%): 88 (57 men, mean age 58.2±12.0) – control group. We used the criteria by Das M. et al, 2006 to identify fQRS and the criteria by Macfarlane P.W. et al., 2015 to identify ERP.
RESULTS In the 1st group (lEF), fQRS was registered in 16 (51.6%) patients, in the 2nd group (mrEF) – in 13 (44.8%), in the 3d (pEF) in 2 (13.6%), P<0.001. ERP in the 1st group (lEF) was registered in 2 (6.5%), in the 2nd group (mrEF) – in 2 (6.9%), in the 3d group (pEF) ERP – in 11 (12.5%), P=0, 5. As a result of the ROC analysis, a relationship was found between fQRS and an intermediate decrease EF (40–49%).
CONCLUSIONS The greatest difficulty for the early detection of heart failure is the group of patients with a mrEF. FQRS has shown its predictive value in identifying these patients. This ECG-pattern must be analyzed to assess the risk of heart failure.
GW34-e1310
Zhaochong Tan1, Ying Huang1, Kui Hong1,2,3
1Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
2Department of Genetic Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
3Jiangxi Key Laboratory of Molecular Medicine, Nanchang, Jiangxi 330006, China
OBJECTIVES This study aimed to assess whether the white blood cell (WBC) count predicts in-hospital death and all-cause death in intensive care unit (ICU) patients with heart failure (HF).
METHODS Data were collected from the Medical Information Mart for Intensive Care III (MIMIC-III) database consisting of critically ill participants between 2001 and 2012 at the Beth Israel Deaconess Medical Centre in Boston.
Participants: A total of 4084 patients with HF were enrolled from the MIMIC-III database.
Primary and secondary outcome: in-hospital death, 30-day all-cause death, and 12-month all-cause death.
RESULTS The numbers of in-hospital deaths, 30-day all-cause deaths, and 12-month all-cause deaths were 774 (18.95%), 1056 (25.86%) and 1720 (42.12%), respectively. In a multiple regression analysis adjusted for confounding factors, HF patients with WBC count ≥6 K/μL, the odds ratio (OR) and 95% confidence interval (CI) for in-hospital death, 30-day all-cause death, and 12-month all-cause death were 1.02 (1.01, 1.03), 1.03 (1.02, 1.04) and 1.02 (1.01, 1.03), respectively, after adjusting for confounding factors, and these values increased each 1 K/μL increase in WBC count (All P<0.05). Inverse findings were observed among HF patients with WBC count<6 K/μL, and the ORs for the risks of above each outcome were 0.76 (0.66, 0.87), 0.84 (0.74, 0.96) and 0.82 (0.72, 0.93), respectively (All P<0.05).
CONCLUSIONS We found that WBC count exhibited a U-shaped relationship with in-hospital death and all-cause death among ICU patients with HF. “WBC count=6 K/μL” might be the critical threshold that HF patients have the lowest risk for in-hospital death and all-cause death.
GW34-e1312
Zhaochong Tan1, Yang Liu1, Kui Hong1,2,3
1Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Jiangxi, China
2Department of Genetic Medicine, the Second Affiliated Hospital of Nanchang University, Jiangxi, China
3The Jiangxi Key Laboratory of Molecular Medicine, Jiangxi, China
OBJECTIVES To assess whether serum chloride predicts risk of death in intensive care unit (ICU) patients with heart failure (HF) and the effect of bicarbonate on the efficacy of serum chlorine in predicting risk of death in ICU patients.
METHODS A total of 9364 HF patients hospitalized in the ICU were enrolled. Patients were divided into hypochloremia (< 96 mEq/L), normal chloride (96–108 mEq/L), and hyperchloremia (> 108 mEq/L) groups. Similarly, we divided the serum bicarbonate level into three groups: low bicarbonate (< 22 mEq/L), medium bicarbonate (22–26 mEq/L), and high bicarbonate (> 26 mEq/L). The outcome of this study was in-hospital mortality. Then, we analyzed the association between abnormal serum chloride and mortality according to the category of serum bicarbonate and assessed the interaction effect. Restricted cubic spline (RCS) was used to show possible nonlinear associations.
RESULTS In the overall study population, hypochloremia was associated with a higher risk of in-hospital mortality than normal chloride (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.26–1.86, P<0.001), hyperchloremia was not significantly related to in-hospital mortality (OR 1.00, 95% CI 0.85–1.19, P=0.962). However, a linear association between serum chlorine and in-hospital mortality was found in the low and normal bicarbonate groups (all P for nonlinear>0.05).
CONCLUSIONS Hypochloremia is associated with in-hospital mortality and longer hospital stay in critically ill patients with HF. In addition, risk of death in the low and medium serum bicarbonate groups decreased with increasing serum chloride level.
GW34-e1358
You Jieyun, Geng Li, Huang Jing, Shen Yunli, Guo Wei, Zhang Qi
Department of Cardiovascular Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
OBJECTIVES Cardiogenic shock is a life-threatening condition associated with poor prognosis. One of the key therapeutic strategies of cardiogenic shock is fluid management. However, the optimal approach to fluid management in this setting remains controversial. Extravascular lung water index (EVLWI) is an effective parameter for assessing the degree of pulmonary edema, which is a hallmark of cardiogenic shock. We aim to evaluate whether EVLWI-guided fluid management could improve fluid management and clinical outcomes of cardiogenic shock.
METHODS To provide precise hemodynamic parameters, including EVLWI, we utilized the pulse index continuous cardiac output (PiCCO) system. A total of 200 patients with cardiogenic shock were prospectively enrolled between 2018 and 2022. After 1:1 propensity score matching, patients were assigned to either the EVLWI group or the control group at a 1:1 ratio. The 30-day major adverse cardiovascular events and parameters related to cardiac function were compared during the clinical follow-up.
RESULTS EVLWI-guided fluid management reduced 30-day all-cause mortality, 30-day cardiac death, and 30-day readmission rate for heart failure (P<0.01). The levels of pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and serum creatinine (Scr) were improved more immediately and significantly in the EVLWI group, accompanied by optimization of hemodynamic parameters (P<0.05).
CONCLUSIONS EVLWI-guided fluid management optimized the therapeutic interventions for patients with cardiogenic shock and improved their clinical outcomes.
GW34-e1379
Hailin Zhang, Lishan Zeng, Dajun Chai
The First Affiliated Hospital, Fujian Medical University
OBJECTIVES The impairment of cardiac function continues to progress after acute myocardial infarction (AMI). Lactate dehydrogenase (LDH) is an important enzyme related to energy metabolism and is elevated in many diseases. Therefore, our study was conducted to explore the effective clinical predictors of changes in cardiac function after AMI.
METHODS Six hundred and ten patients diagnosed with AMI between November 2007 and January 2021 and underwent echocardiographic review at least 6 months after discharge were included in this retrospective cohort study. Patients were divided into the follow-up cardiac insufficiency group and the follow-up normal cardiac function group according to their heart failure-related symptoms and left ventricular ejection fraction (LVEF) values at follow-up, and into the high LDH group and the normal LDH group according to their baseline serum LDH values. Two-way repeated measures ANOVA was used to assess the main and interaction effects of two factors, baseline serum LDH and time, on cardiac structure and function in patients with AMI. Multiple regression analysis was used to investigate the effect of baseline serum LDH on post-infarcted cardiac function at follow-up.
RESULTS The average age at baseline was 64.80±11.24 years and the average follow-up duration was 2.13±1.41 years. Compared with the follow-up normal heart function group, the follow-up cardiac insufficiency group had significantly higher male and STEMI proportions, heart rate, troponin I, NT-Pro-BNP, neutrophil count, monocyte count, C-reactive protein, alanine aminotransferase, aspartate aminotransferase, LDH, urea nitrogen, creatinine, uric acid, and fasting glucose, and significantly lower systolic blood pressure (all P<0.05). The median levels were 524.00 (353.25, 829.50) and 197.00 (171.25, 224.00) U/L in high LDH group and normal LDH group. Two-way repeated measures ANOVA revealed there was a significant interaction between different LDH groups and different time points for echocardiographic estimated heart rate (HR-echo), left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs), left ventricular end-diastolic volume (LVVd), left ventricular end-systolic volume (LVVs), interventricular septum thickness (IVST), and E/e (all P<0.05), indicating that the changes in these indicators over time were more pronounced in the high LDH group. Patients in the high LDH group had a lower LVEF both at baseline and at follow-up (P<0.001). The LVDd and LVVd of patients in the high LDH group were not significantly different from those in the normal LDH group at baseline, but were further expanded in the high LDH group (all P<0.001) and reduced in the normal LDH group (P<0.001 and P=0.079, respectively) at follow-up. Patients in high serum LDH group had a higher risk of being diagnosed with cardiac insufficiency during follow-up, with an adjusted odds ratio (OR) of 2.617 (95% confidence interval (CI): 1.025–6.681, P=0.044) in a forward stepwise method of binary logistic regression, independent of all the confounding factors described above. In ordered logistic regression, the quartile subgroup of follow-up LVEF tended to decrease with increasing of baseline serum LDH, with an OR of 1.336 (95% CI: 1.216–1.468, P<0.001) for each 100 U/L increase in baseline serum LDH.
CONCLUSIONS Longitudinal changes in cardiac function is independently associated with baseline serum LDH in patients with AMI. LDH can be considered when predicting long-term changes in cardiac function after AMI.
GW34-e1397
You Jieyun, Geng Li, Huang Jing, Zhang Qi, Guo Wei
Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai 200120, China
OBJECTIVES Acute myocardial infarction complicated by cardiogenic shock (AMICS) is a life-threatening condition associated with poor prognosis. The optimal approach to fluid management in this setting remains controversial. We aimed to evaluate the effects of pulse index continuous cardiac output (PiCCO) monitoring in improving clinical outcomes of patients with AMICS and treated by primary percutaneous coronary intervention (PCI).
METHODS After 1:1 propensity score matching, 50 AMICS patients in the PiCCO group and 50 AMICS patients in the control group were enrolled from June 2016 to June 2021 in our hospital. The baseline characteristics, treatment, and clinical outcomes during hospitalization and at 30 d clinical follow-up were compared.
RESULTS No statistically significant differences in baseline characteristics were discernible between the two groups. Inotropes and vasopressors were more prescribed in the PiCCO group (both P<0.05). Compared with the control group, allcause death (16 vs. 34%, P=0.024), cardiac death (14 vs. 30%, P=0.042) and readmission rate (2 vs. 14%, P=0.027) at 30 d clinical follow-up were significantly reduced in the PiCCO group, respectively. The duration of first hospitalization was significantly shortened [(17.60±1.06) d vs. (24.32±2.19) d, P<0.001] in the PiCCO group. Additionally, we observed a low rate of procedure-related complications in the PiCCO group.
CONCLUSIONS PiCCO monitoring for AMICS patients post-primary PCI exerts beneficial effects and improves the short-term clinical outcomes.
BLOOD LIPIDS AND ATHEROSCLEROSIS
GW34-e0024
Hongwei Li1, Kexin Wen1, Qi Guo1, Shan Xie2, Xiangkun Xie1, Chen Qian1, Liu Wenhao1, Jiang Yuan1, Wenya Chen3, Dengfeng Geng1, Yuling Zhang1
1Department of Cardiovascular Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou 510120, China
2School of Systems Science and Engineering, Sun Yat-sen University, Guangzhou 510120, China
3Department of Cardiology, People’s Hospital of Yangjiang, Yangjiang, China
OBJECTIVES The therapeutic effect of statin use may inverse the association between traditional cardiovascular risk factors and coronary heart disease (CHD) risk. An unbias selection of risk factors by machine learning model is required for better diagnostic performance of CHD.
METHODS There were 817 statin users hospitalized in the Sun Yat-sen Memorial Hospital included. Patients were divided into non-CHD and CHD groups. Both area under curves (AUC)-increasing and tradition decision tree model were compared in their diagnostic capability and the identification of high-risk clinical patterns. The minimum error in the cross validation, xerror, decides the model truncation to avoid overfitting. The logistic regression models were performed to verify the association between cardiovascular risk factors and CHD.
RESULTS The statin users with CHD showed lower total cholesterol (TC), low-density lipoprotein-cholesterol (LDLC) and diabetes prevalence but higher high-density lipoprotein-cholesterol (HDLC). For objective risk factor selection, the AUC-increasing decision tree model and the traditional model were performed with similar diagnostic capability. The AUC-increasing model before truncation (AUC: 0.769, xerror: 0.877) and the traditional model after truncation (AUC: 0.658, xerror: 0.806) were chosen because of the minimum xerror. A clinical pattern characterized by high LDLC and another pattern with low apolipoprotein A1 (APOA1), identified by 2 tree models, were independently associated with CHD.
CONCLUSIONS High LDLC levels and low APOA1 levels remain to be independent cardiovascular risk factors in statin users. The CART-based decision tree model might be a useful tool for cardiovascular risk factor selection when serum markers were affected by pharmacological effect.
GW34-e0157
Zixiang Ye, Jingang Zheng
Peking University China-Japan Friendship School of Clinical Medicine
OBJECTIVES This study aimed to explore the association between the triglyceride glucose index (TyG) and the risk of in-hospital and one-year mortality in patients with chronic kidney disease (CKD) and cardiovascular disease (CAD) admitted to the intensive care unit (ICU).
METHODS The data for the study were taken from the Medical Information Mart for Intensive Care-IV database which contained over 50,000 ICU admissions from 2008 to 2019. The Boruta algorithm was used for feature selection. The study used univariable and multivariable logistic regression analysis, Cox regression analysis, and 3-knotted multivariate restricted cubic spline regression to evaluate the association between the TyG index and mortality risk.
RESULTS After applying inclusion and exclusion criteria, 639 CKD patients with CAD were included in the study with a median TyG index of 9.1 [8.6, 9.5]. The TyG index was nonlinearly associated with in-hospital and one-year mortality risk in populations within the specified range.
CONCLUSIONS This study shows that TyG is a predictor of one-year mortality and in-hospital mortality in ICU patients with CAD and CKD and inform the development of new interventions to improve outcomes. In the high-risk group, TyG might be a valuable tool for risk categorization and management. Further research is required to confirm these results and identify the mechanisms behind the link between TyG and mortality in CAD and CKD patients.
GW34-e0167
Liang Xu, Yunjie Yin, Yanchun Chen
Department of Cardiology, Yixing People’s Hospital
OBJECTIVES In-stent restenosis (ISR) is one of the common long-term complications after percutaneous coronary intervention (PCI). Therefore, we investigate the risk factors of ISR and its correlation with residual cholesterol (RC) in coronary heart disease (CHD) with LDL-C compliance after PCI.
METHODS A total of 239 CHD patients hospitalized in the Department of Cardiology, Yixing People’s Hospital from January 2015 to October 2022 were recruited. All patients had a previous stent placement and coronary angiography will be reviewed in hospitalization. Fasting blood routine and biochemical indicators were tested. According to the results of coronary angiography during hospitalization, they were divided into ISR group and non-ISR group. IBM SPSS Statistics 16.0 software was used to analyze the risk factors of ISR.
RESULTS There were no significant differences between non-ISR and ISR groups in gender, hypertension, stent implantation time, TG, HDL-C, LDL-C, Lp-a (P>0.01), but there were significant differences in age, diabetes, smoking, TC, RC, multi vessel lesions, number of stents, and total length of stents (P<0.05). Calculate the RC interquartile spacing and divide it into four groups (Q1-Q4) based on the interquartile spacing. The incidence rate of ISR among the four groups was 20%, 14.8%, 22% and 40.7%, respectively, with statistical significance (P<0.05); Spearman correlation analysis indicated that there was a correlation between RC and ISR, with a correlation coefficient of 0.179, P<0.05; The ROC of RC was 0.636 (95% CI 0.572–0.697, P<0.05). By Joden index, the cut-off for RC is 0.47 mmol/L, sensitivity and specificity were 51.72% and 75.14%, respectively; Logistic regression analysis showed that Age, smoking, multiple vessel lesions, total stent length, and RC were risk factors for ISR (P<0.05). Patients with RC higher than 0.47 mmol/L were 3.416 times more likely to incur ISR than those with RC lower than 0.47 mmol/L (P=0.003).
CONCLUSIONS There is a relationship between RC and ISR in CHD with LDL-C compliance after PCI, and RC is an independent risk factor for the occurrence of ISR after PCI.
GW34-e0186
Wenhua Zhu, Lihong Wu, Lizheng Fang, Jingjing Xia, Jia Zhang, Junlu Zhang, Yue Zhu, Liying Chen
Sir Run Run Shaw Hospital and Institute of Clinical Medicine, Zhejiang University School of Medicine
OBJECTIVES To investigate and establish the relationship between brachial–ankle pulse wave velocity (baPWV) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) for assessing early stage of progression of arteriosclerosis.
METHODS We enrolled 9708 urban healthy individuals who received health check-ups at our center. BaPWV was measured and the results were divided into strata 0, 1, and 2. NT-pro BNP was measured by radioimmunoassay (RIA). Cardiovascular metabolic parameters were evaluated using standard methods.
RESULTS BaPWV was positively significantly correlated with NT-proBNP in general populations (P<0.001) with β-value of baPWV being 0.137, 0.178, 0.123 ingeneral, male and female. (P<0.001). NT-proBNP level gradually increased along with the escalation of baPWV stratum (P<0.01). Logistic regression analysis showed that the odds ratio (OR) of dumb variables (T2, T3) of baPWV with NT-proBNPwere 2.25 and 5.46 in general, 3.78 and 8.82 in males, 1.42 and 3.40 in females, respectively (P<0.001). After adding baPWV related factors, logistic regression analysis showed that baPWV still significantly and uniformly affected NT-proBNP (P<0.001), with the odds ratio (OR) of dumb variables (T2, T3) of baPWV with NT-proBNP were 2.17 and 4.98 in general, 3.14 and 6.76 in males, 1.34 and 3.05 in females, respectively (P<0.001).
CONCLUSIONS BaPWV is closely and independently related to NT-proBNP in individuals with and without high metabolic risk factors. Increased baPWV possibly underlies the increase in the NT-proBNP level in populations. BaPWV may play a critical role in the escalation of NT-proBNP level.
GW34-e0310
Qiaoli Su1, Ying Liu2, Guogang Zhang3, Li Xu4, Min Wang5, Shifang Mei5, Genevieve Garon5, Yanzhen Wu6, Qiang Lv7, Changsheng Ma7
1West China Hospital of Sichuan University
2The People’s Hospital of Liaoning Province
3The Third Xiangya Hospital of Central South University
4Wuhan Puren Hospital
5Sanofi Medical
6Sanofi Research and Development (R&D)
7Beijing Anzhen Hospital
OBJECTIVES This study aimed to compare the efficacy and safety of single-pill combination (SPC) of rosuvastatin 10 mg/ezetimibe 10 mg (R10/E10) versus rosuvastatin 10 mg (R10) in Chinese patients with primary hypercholesterolemia inadequately controlled by statin.
METHODS This was a randomized, double-blind, active-controlled, parallel-design Phase 3 study. Patients were screened and entered a run-in period with 4-week treatment of R10. Then those who had an inadequately controlled low-density lipoprotein cholesterol (LDL-C) (LDL-C ≥2.6 mmol/L and ≤4.9 mmol/L) were further 1:1 randomized and receive R10/E10 SPC or R10 in an 8 weeks double-blind period. Primary objective was to demonstrate the superiority of SPC R10/E10 compared to R10 in the reduction of LDL-C after 8 weeks. Secondary objectives included evaluation of the proportion of participants who attain LDL-C goal, the effect in reduction of LDL-C at Week 4, the effect on other lipid parameters at week 4 and week 8, and the safetyof SPC (R10/E10) and R10. Treatment-emergent adverse events (TEAEs), adverse events of adverse events of special interest (AESI), laboratory test and vital signs were monitored until 2 weeks after the end of the treatment.
RESULTS Of 305 participants enrolled, 153 were randomized to R10/E10 treatment and 152 to R10 treatment. All participants in both groups were Asian. The baseline characteristics were generally similar between treatment groups. Superiority of SPC R10/E10 over R10 at week 8 of primary analysis was demonstrated with LS mean difference of percent change in LDL-C −13.85% (95% CI: −20.15 to −7.56%; P<0.0001). The percent change in LDL-C levels from baseline to week 4 was also significantly greater in the R10/E10 group (LS mean: −22.90%, 95% CI: −26.86 to −18.94%) versus the R10 group (LS mean: −8.50%, 95% CI: −12.51 to −4.49%), with a LS mean difference of −14.40% (95% CI: −20.04 to −8.75%, P<0.0001). The proportion of participants who achieved LDL-C target at week 8 was significantly greater in the R10/E10 group (n=80 [54.1%]) than in the R10 group (n=42 [29.2%]) with an odds ratio (OR) of 2.80 (95% CI: 1.70–4.61; P<0.0001). TEAEs were reported during double-blind period with similar incidence across both intervention groups. Forty-four (28.9%) and 35(23.0%) participants reported at least 1 TEAE during the double-blind period in the R10/E10 and R10 groups, respectively. Two (1.3%) participants in the R10 group experienced an AESI of blood creatine kinase increased. No other AESI reported. No unexpected or new safety findings were reported.
CONCLUSIONS Rosuvastatin 10 mg and ezetimibe 10 mg as a single pill combination demonstrated greater LDL-C reduction in patients with primary hypercholesterolemia not adequately controlled on statin therapy in China compared with rosuvastatin 10 monotherapy without increased safety findings.
GW34-e0462
Yuzhi Huang
The First Affiliated Hospital of Xian Jiaotong University
OBJECTIVES Atherosclerosis disease, the major complication of CKD (chronic kidney disease), is the leading cause of death in these group. An important mechanism linking the two disease is inflammation. MiR-423-5p is an inflammation-related microRNA, but the relationship of circulating miR-423-5p and carotid atherosclerosis in patients with CKD has not been reported. We aim to determine whether circulating miR-423-5p plays a crucial link between CKD and carotid atherosclerosis.
METHODS In this study, we recruited 375 participants to perform a cross-section investigation. The primary results were defined as the occurrence of carotid plaque and maximum carotid plaque thickness. The miR-423-5p expression levels were determined by qPCR analysis. In vivo, we constructed mice model of CKD by 5/6 nephrectomy. Next-generation high-throughput RNA sequencing (RNA-seq) is used to excavate the differentially expressed genes (DEGs) between sham and CKD group of mice. Bioinformatics analysis is used to screen predicted target genes of miR-423-5p from DEGs.
RESULTS In study of population, we determined that circulating exosomal miR-423-5p levels were significantly elevated in patients with non-dialysis CKD compared with non-CKD group (P<0.001). While, the dialysis-dependent patients with ESRD (end stage renal disease) had lower circulating exosomal miR-423-5p levels, compared with non-dialysis CKD (P=0.006). After excluding the influence of dialysis patients, linear regression analysis suggested that the circulating exosomal miR-423-5p level is negatively correlated with eGFR (P<0.001). And, we found the trend of changes for miR-423-5p in plasma is same as it in exosome. Next, the logistic regression demonstrated that the higher plasma miR-423-5p levels were independently and significantly associated with a higher risk of carotid plaque (highest vs. lowest: OR=2.95, 95% CI=1.22–7.14, P=0.016). The multivariate linear regression showed that the levels of circulating plasma miR-423-5p were positively correlated with maximum carotid plaque thickness (P=0.014). Besides, there was a positive relationship between circulating plasma miR-423-5p and inflammation biomarkers. In vivo, same as CKD patients, the circulating exosomal miR-423-5p levels were also eleveted in CKD mice. And, the results of RNA-seq and bioinformatics analysis showed that the predicted target genes of miR-423-5p could play a role of antioxidative stress in aorta of CKD mice.
CONCLUSIONS Increased circulating miR-423-5p levels were significantly associated with a higher risk for the occurrence of carotid plaque and maximum carotid plaque thickness in CKD patients. And, the predicted target genes of mir-423-4p could be involved in regulation of oxidative stress in aorta of CKD mice.
GW34-e0832
Boning Zhou1,2, Xin Zhang1,2, Jian Shen1,2, Ying Li1,2, Yang Jiao1,2, Jian Wang1,2,3, Xiaoling Hou1, Yongkang Su2, Zhenhong Fu1,2
1Senior Department of Cardiology, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100853, China
2Chinese PLA Medical School, Beijing 100853, China
3Department of Cardiology, Hainan Hospital, Chinese PLA General Hospital, Sanya 572000, Hainan, China
OBJECTIVES Previous studies showed that remnant cholesterol (RC) partially explained the residual risk of cardiovascular disease. We tried to tested the hypothesis that remnant cholesterol is a risk factor for all-cause mortality in oldest-old patients with acute coronary syndrome (ACS).
METHODS Six hundred and ninety-nine oldest-old patients with acute coronary syndrome and undergoing coronary angiography were included in our study. Remnant cholesterol (RC) was calculated by fasting total cholesterol (TC) minus low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). During follow-up, 37 were lost, and 662 were finally available for our statistical analysis. Pearson’s correlation test was used to assess the associations between RC and clinical parameter. Multivariable Cox regression analysis was used to identify the association between RC and all-cause mortality. Receiver operating characteristic (ROC) curve was used to compare the discrimination capacity of RC, TC, HDL-C and LDL-C to predict all-cause mortality.
RESULTS Among the 662 oldest-old patients enrolled, 92.90% accepted statin therapy. The average age was 81.87±2.14 years old. In the fully-adjusted Cox regression model, the Hazard ratio (HR) [95% confidence interval (CI)] of all-cause mortality was 1.17 (1.01, 1.36) for each standard deviation (SD) increase in RC. Compared to tertile 1, the tertile 3 was associated with a 130% increased risk of all-cause mortality (HR: 2.30; 95% CI: 1.45, 3.63). The increased risk of death from tertile 1 to tertile 3 was statistically significant (P for trend<0.001). The subgroup analysis confirmed the significant association between RC and all-cause mortality. ROC curve showed that RC had a better discrimination capacity at predicting all-cause mortality and improved the prognostic value of the Gensini score combined with left ventricular ejection fraction (LVEF).
CONCLUSIONS Remnant cholesterol was an independent risk factor for all-cause mortality in oldest-old patients with ACS in a long-term follow-up.
GW34-e0844
Bryan PY Yan1, Angel Lai1, Zhenna Huang2, Jeff Lange2, Nafeesa Dhalwani2, Wei Xiang2
1Division of Cardiology Department of Medicine & Therapeutics, The Chinese University of Hong Kong
2Amgen Inc.
OBJECTIVES To describe characteristics of patients starting evolocumab therapy and to evaluate effectiveness of evolocumab in reducing low-density lipoprotein cholesterol (LDL-C) in Hong Kong clinical practice.
METHODS The data source, Clinical Data Analysis and Reporting System (CDARS), contains records of all public healthcare administered in Hong Kong dating back to 1993. The study population included adults who initiated evolocumab treatment between May 2016 (date of regulatory approval) and December 2021 (last date for analysis). Patient characteristics, duration of evolocumab treatment, and reduction in LDL-C levels were described for all evolocumab users (referred to as the evolocumab cohort) and evolocumab users with a history of atherosclerotic cardiovascular disease (ASCVD) in prior 3 years (referred to as the evolocumab ASCVD cohort). To provide context for the practice of medicine, characteristics of all ASCVD patients (referred to as the prevalent ASCVD cohort) in CDARS were also described.
RESULTS The evolocumab ASCVD cohort subgroup (n=318 patients) had a median age of 61 years and 74% were men. Nearly all of these patients (>94%) had prior use of lipid-lowering therapy at the initiation of evolocumab treatment and the mean (SD) baseline LDL-C level was 3.1 (1.5) mmol/L. The majority of patients (>80%) had a treatment duration longer than 3 months, and 19% had at least 2 years of evolocumab treatment at the time of analysis. The mean percent change in LDL-C from baseline was −60.4% at 6 months and most patients (73%) achieved LDL-C levels <1.8 mmol/L, and a majority (59%) achieved LDL-C levels <1.4 mmol/L. Similar results were observed for the evolocumab cohort (n=652) as a whole. For context, the prevalent ASCVD cohort consisted of a larger population (n=55, 803) of older patients (median age of 77 years) with a lower proportion of men (61%). Observable clinical differences between the prevalent ASCVD cohort and the evolocumab ASCVD cohort included a higher percentage of patients in the evolocumab cohort with a recent history of percutaneous coronary intervention or coronary artery bypass grafting (44 vs. 13%); comorbidities such as diabetes (13 vs. 4%) and heart failure (7 vs. 2%); and a hospitalized ASCVD event in the prior month (37 vs. 6%). Furthermore, at baseline, the evolocumab ASCVD cohort had a higher mean (SD) baseline LDL-C concentration (3.1 [1.5] mmol/L vs. 2.2 [0.8] mmol/L) than the prevalent ASCVD cohort.
CONCLUSIONS The observed reduction in LDL-C levels following the initiation of evolocumab and the lipid management practices in Hong Kong are consistent with evidence from global clinical studies. Chinese patients in Hong Kong with prior ASCVD who receive evolocumab represent a group at higher risk of subsequent CV events than those not receiving evolocumab; this should be taken into consideration when comparing clinical outcomes between these two cohorts.
GW34-e0877
Sen Liu1,2, Cheng Liu1, Menglong Jin1, Ziyang Liu1, Sifu Luo1, Yaqi Zhou1, Zhenyan Fu1,3
1Heart Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China
2Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu 610500, Sichuan, China
3State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Heart Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China
OBJECTIVES Although high-dose statin therapy stabilizes plaques, the effect of intensive lipid-lowering therapy (LLT) on plaque stabilization remains unclear. There is also uncertainty during LLT regarding which indicators are related to plaque stability, such as high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), or any other. This meta-analysis and meta-regression aimed at assessing the effect of intensive LLT on coronary plaque stabilization of minimum fibrous cap thickness (FCT) derived from optical coherence tomography (OCT) in patients with coronary artery disease (CAD), and evaluating whether the effect was related to CRP, LDL-C, or others change.
METHODS PubMed, Embase, and Cochrane Library were searched from inception to June 1, 2023, for randomized controlled trials (RCTs) without language restrictions if they described the association between intensive LLT, including high-intensity statins therapy or statins in combination with other lipid-lowering medications, with minimum FCT evaluated by OCT. Meta-analyses were performed for standard mean difference (SMD) with continuous variables using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
RESULTS A total of 12 RCTs with 972 patients were identified and included. Meta-analysis showed that, compared with the control, intensive LLT was associated with increased minimum FCT (12 studies with 972 participants; SMD, 0.87; 95% CI, 0.54 to 1.21; P<0.01). Meta-regression showed that, increased minimum FCT was associated with the decreased LDL-C (β, −0.0157; 95% CI, −0.0292 to −0.0023; P=0.025), Total Cholesterol (TC) (β, −0.0154; 95% CI, −0.0303 to −0.0005; P=0.044) and Apolipoprotein B (ApoB) (β, −0.0209; 95% CI, −0.0361 to −0.0057; P=0.022), not associated with the change of hs-CRP/CRP (β, −0.1518; 95% CI, −1.3766 to −1.0730; P=0.772), Triglycerides (TG) (β, −0.0030; 95% CI, −0.0258 to −0.0318; P=0.822), high-density lipoprotein cholesterol (HDL-C) (β, 0.0313; 95% CI, −0.0965 to 0.1590; P=0.608).
CONCLUSIONS Intensive LLT has a beneficial effect on coronary plaque stabilization of minimum FCT derived from OCT in patients with CAD. Coronary plaque stabilization is primarily due to lipid-lowering effect, not anti-inflammatory effect. Moreover, the lipid-lowering effect has nothing to do with the changes in HDL-C and TG, but is mainly related to the reduction of LDL-C, TC and ApoB.
GW34-e1006
Mihail Samnaliev1, Luke Schmerold1, Charlie Nicholls2, Garon Genevieve3, Irfan Khan4, Praveen Potukuchi4
1Axtria, New Jersey, USA
2Sanofi, Reading, UK
3Sanofi, Ontario, Canada
4Sanofi, New Jersey, USA
OBJECTIVES Non-statin lipid-lowering therapy, such as ezetimibe, added to statins, is required in many patients with high cardiovascular (CV) risk for achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals. Fixed-dose combination (FDC) compared with free-combination therapy (FCT) with these agents may result in improved persistence and adherence. The objectives of this study were to: (1) compare persistence/adherence with FDC vs. FCT of rosuvastatin and ezetimibe; (2) evaluate the association between persistence/adherence with these agents and percent reduction in LDL-C from baseline; and (3) evaluate the association between persistence/adherence with these agents and incidence of major adverse CV events (MACE). An exploratory analysis of the association between FDC vs. FCT initiation and MACE was also undertaken.
METHODS The study utilized electronic heath record data from Belgium and France (THIN® database) representing usual clinical practice. Individuals aged ≥18 years who received rosuvastatin and ezetimibe as FDC or FCT between January 1, 2017 and November 30, 2022 were selected. Persistence was defined as the time from treatment initiation to discontinuation, with the latter defined as a gap of ≥45 days in therapy. Adherence was defined as the proportion of days covered (PDC), conditional on no discontinuation, and dichotomized as PDC ≥80%. Re-initiation after discontinuation qualified as a new treatment episode. Propensity score matching or weighting, followed by Cox and logistic regression models, were utilized in subsequent analyses.
RESULTS A total of 15,643 treatment episodes (FDC 11,300; FCT 4343) met selection criteria. Median time to discontinuation was higher with FDC than that with FCT (174 vs. 159 days: unadjusted analysis). In the adjusted Cox model, FDC was associated with higher persistence (lower risk of discontinuation) than FCT with a hazard ratio [HR] of 0.55 (95% confidence interval [CI] 0.52 to 0.59). Adherence was higher with FDC vs. FCT (95.5 vs. 79.9%: unadjusted analysis). In the adjusted logistic model, FDC was associated with higher odds of adherence than FCT (odds ratio [OR] 5.37 [95% CI 4.46 to 6.46]). Patients who were persistent (continuous treatment from initiation to subsequent LDL-C measurement) had greater LDL-C reduction from baseline (10.11% [95% CI 14.48 to 5.74%]) than those not persistent. Patients who were adherent (PDC ≥80% from initiation to subsequent LDL-C measurement) did not have greater LDL-C reduction (6.74% [95% CI 14.59 to –1.10%]) than those not adherent. The association between persistence/adherence and MACE was not significant. Persistence vs. no persistence during past 90 days had OR of 1.21 (95% CI 0.84 to 1.75) for MACE; adherence vs. no adherence during past 6 months had OR of 0.90 (95% CI 0.60 to 1.36) for MACE. In the exploratory analysis, FDC vs. FCT initiation resulted in a lower risk of MACE (HR 0.60 [95% CI 0.41 to 0.88]).
CONCLUSIONS In a usual clinical practice setting, FDC rosuvastatin and ezetimibe compared with FCT with these agents was associated with higher persistence and adherence. As randomized controlled trials support CV event reduction with these agents, FDC compared with FCT based on these agents may also lower the risk of MACE.
GW34-e1071
Xiaofang Chen1, Junhan Chen1, Xiaoling Cai1, Yansong Guo2, Kaiyang Lin2
1Fujian Provincial Hospital; Shengli Clinical Medical College of Fujian Medical University
2Fujian Provincial Hospital
OBJECTIVES High density lipoprotein cholesterol (HDL-C) was considered the “good cholesterol” previously, which was thought the higher HDL-C, the lower the cardiovascular risk. However, recent studies has found that high HDL-C increased poor outcomes in some populations.
METHODS To investigate the association between HDL-C levels and poor outcomes in patients after percutaneous coronary intervention (PCI), we retrospectively analysed 7313 consenting patients undergoing PCI from January 2012 to December 2018. Based on the restricted cubic spline (RCS) analysis, the patients were divided into three groups: HDL-C≤25 mg/dL; 25<HDL-C≤60 mg/dL; HDL-C>60 mg/dL. The primary outcome was all-cause death. The association between HDL-C levels and poor outcomes was assessed by multivariable cox regression analysis.
RESULTS Of study participants, a U-shaped association with outcomes was observed with higher risk in those with both low and high HDL-C levels compared with those with midrange values. Besides, the Kaplan-Meier survival analyses revealed that the high and low HDL-C group had a significant higher cumulative rate of all-cause mortality and cardiovascular mortality than the midrange one. Compared with those with HDL-C levels in the range of 25 to 60 mg/dL in our database after adjustment for confounding factors, low HDL-C levels were associated with risk of all-cause mortality (hazard ratio [HR], 1.96; 95% CI, 1.41, 2.73; P<0.001) and cardiovascular mortality (HR, 1.66; 95% CI, 1.03, 2.67; P=0.037). After the same comparison and adjustment, high HDL-C levels were observed with increased risk of all-cause death (hazard ratio [HR], 1.73; 95% CI, 1.29, 2.32; P<0.001) and cardiovascular death (HR, 1.73; 95% CI, 1.16, 2.58; P=0.007) as well.
CONCLUSIONS Results of this cohort study suggest that both low and high HDL-C levels are associated with higher mortality risk in individuals who undergoing PCI.
GW34-e1154
Yu Zhao1, Zeya Li1, Min Wang2, Qi Chen1, Fu Guosheng2, Rongchong Huang1
1Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
2Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang, China
OBJECTIVES Both Xuezhikang and statins have proven to be effective in reducing cholesterol levels. However, concerns regarding statins’ impact on liver, muscle, and glucose metabolism are prevalent. Thus, we conducted a multicenter retrospective cohort study to evaluate the safety and efficacy of Xuezhikang compared to statins in patients with hypercholesterolemia.
METHODS A total of 2509 patients with hypercholesterolemia were enrolled from 2 centers in China. Of these, 1128 patients received a daily dose of 1.2 g of Xuezhikang and 1381 patients received moderate statin treatment. The primary outcome was defined as the changes of liver transaminases from baseline to the end-point (90 days from the baseline). Secondary outcomes included the incidences of liver transaminases >3 upper limit of normal (ULN), the absolute value of liver transaminases, creatine kinase (CK), HbA1c, fasting blood glucose (FBG) at the end-point, and the changes of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to end-point.
RESULTS After a follow-up duration of 90 days, the changes of AST/ALT from baseline to end-point were lower in Xuezhikang group than in statin group (AST: 0.5 (−3.0, 4.7) vs. 2.1 (−2.0, 7.6) U/L, P<0.001; ALT: 2.0 (−3.0, 8.0) vs. 4.0 (−1.0, 13.0) U/L, P<0.001). Similar effects were observed on the absolute value of ALT at end-point (21.0 (16.0, 34.0) vs. 25.0 (17.0, 39.0) U/L, P<0.001), although baseline ALT were higher in Xuezhikang group than in statin group (21 (15, 37) vs. 19 (13, 28) U/L, P<0.001). In addition, the incidence of ALT >3 ULN was lower with Xuezhikang than with statin (1.6 vs. 3.8%, P=0.035). Although FBG (5.56 (5.1, 6.57) vs. 5.69 (5.07, 7.0) mmol/L, P=0.118) and HbA1c (6.1 (5.6, 7.3) vs. 6.2 (5.6, 7.6) %, P=0.172) were not statistically different between the two groups at baseline, they were higher in the statin group at end-point (FBG: 5.54 (5.08, 6.32) vs. 5.86 (5.25, 7.12) mmol/L, P<0.001; HbA1c: 6.1 (5.6, 6.9) vs. 6.4 (5.8, 7.4) %, P=0.004). The changes of CK were similar in both groups (1.0 (−20.0, 24.5) vs. −3 (−38, 23) U/L, P=0.054). In addition, both treatments produced significant efficacy on LDL-C (Xuezhikang: 3.29±0.89 vs. 2.54±0.70 mmol/L, P<0.001; statin: 3.34±1.05 vs. 2.31±0.73 mmol/L, P<0.001), TC (Xuezhikang: 5.59±1.29 vs. 4.58±1.11 mmol/L, P<0.001; statin: 5.54±1.59 vs. 4.08±1.09 mmol/L, P<0.001) and non-HDL-C (Xuezhikang: 4.31±1.18 vs. 3.31±1.02 mmol/L, P<0.001; statin: 4.34±1.43 vs. 2.88±0.97 mmol/L, P<0.001) from baseline to end-point. However, more patients achieved LDL-C levels<2.6 mmol/L (71.5 vs. 56.6%), <1.8 mmol/L (25.2 vs. 15.3%) and <1.4 mmol/L (7.6 vs. 5.3%) with statin than Xuezhikang (all P<0.001).
CONCLUSIONS In patients with hypercholesterolemia, Xuezhikang has a lower impact on liver function and glucose metabolism compared to statins and definite lipid-lowering efficacy, although the lipid-lowering efficacy is inferior to statins. It suggests that Xuezhikang may be more suitable for people at low-moderate risk of cardiovascular disease considering the safety. The outcome requires further confirmation in large-scale randomized trials.
GW34-e1159
Na Yang
Beijing Anzhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases
OBJECTIVES A large body of evidence has demonstrated the cardio-renal protective effect of glucagon-like peptide-1 receptor antagonist (GLP-1RA) and sodium-glucose cotransporter-2 inhibitor (SGLT-2i) in diabetes patients with cardiovascular disease. The utility of the two type drugs in patients with acute coronary syndrome (ACS) and diabetes in China in unknown.
METHODS The study was based on the China Diabetes Cardiovascular Initiative (CDCV) project, an ongoing collaborative registry and quality improvement project of American Heart Association (AHA), American Diabetes Association (ADA), Chinese Society of Cardiology (CSC), and Chinese Society of Diabetes (CDS). A total of 6144 hospitalized patients with ACS and diabetes from 29 hospitals reported to the registry between December 2021 and April 2023 were included. The current status of the utilization of GLP-1RA and SGLT-2i was analyzed. The variations in the use of GLP-1RA and SGLT-2i across hospitals were examined by aggregating the data to the hospital level.
RESULTS Among 6079 patients who are eligible for GLP-1RA and/or SGLT-2i, only 39.7% were prescribed GLP-1RA or SGLT-2i at discharge. The proportion varied across hospitals, ranging from 8.6% to 100%, with less than 50% of eligible patients receiving GLP-1RA or SGLT-2i at discharge in 65.5% of hospitals, 50–79% of eligible patients receiving GLP-1RA or SGLT-2i at discharge in 31.0% of hospitals, and all the eligible patients receiving GLP-1RA or SGLT-2i at discharge in only 3.5% of hospitals. Among the patients who are eligible for both GLP-1RA and SGLT-2i, only 39.8% received GLP-1RA or SGLT-2i at discharge. Among the patients who are recommended to preferably receive GLP-1RA, only 0.6% received GLP-1RA at discharge. Among the patients who are recommended to preferably receive SGLT-2i, only 42.2% received SGLT-2i at discharge. Among the patients who are not recommended to receive GLP-1RA and SGLT-2i, 3.2% received GLP-1RA or SGLT-2i at discharge.
CONCLUSIONS Large gaps existed in the use of GLP-1RA and SGLT-2i among patients with ACS and diabetes between guideline recommendations and clinical practice in China. There are substantial differences in the use of GLP-1RA and SGLT-2i across hospitals.
GW34-e1183
Yuanlong Hu, Mengkai Lu, Xinhai Cui, Zhiyuan Zhang, Yunlun Li, Chao Li
Shandong University of Traditional Chinese Medicine
OBJECTIVES Lipid-lowering therapy is the backbone of the strategy to reduce cardiovascular morbidity and mortality. However, evidence from observational studies supported a diabetogenic effect of statins. It is worth noting that the diabetogenic effect of other lipid-lowering drugs and the precise cause remain largely unknown. A mendelian randomization (MR) was designed to assess the mediating role of ectopic fat accumulation in association of lipid-lowering drug targets with type 2 diabetes (T2D).
METHODS Lipid-lowering drugs related to reducing low-density lipoprotein cholesterol (LDL-C) or triglyceride (TG) were included in final analyses, including low-density lipoprotein receptor (LDLR) inhibition, HMG-CoA reductase (HMGCR) inhibitors, cholesterol absorption inhibitor, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, antisense oligonucleotide targeting ApoB-100 mRNA, bile acid sequestrant, lipoprotein lipase (LPL) enhancement, angiopoietin-like 3 (ANGPTL3) Inhibitor, and antisense oligonucleotide targeting ApoC-III mRNA. We selected single-nucleotide polymorphisms (SNPs) located within 100 kilobases of target genes and robustly associated with LDL-C or TG levels at genome-wide significance (P<5×10−8). Independent SNPs were identified by linkage disequilibrium clumped at a threshold r2<0.2 within a 250 kilobases window. Positive control analyses were conducted to confirm the reliability of the instrumental variables. The inverse-variance weighted, MR-Egger, weighted median and weighted mode methods were used to assess the causal association of genetically proxied drug targets with T2D risk. Indirect effects and mediated proportion were assessed with the “product of coefficients” method. Standard errors for the indirect effects were derived with the delta method.
RESULTS Genetic mimicry of HMGCR, LDLR and APOB inhibition to a one-SD reduction in LDL-C was causally associated with an increased risk of T2D (HMGCR, odds ratio [OR]=1.34, 95% confidence interval [CI]=1.16 to 1.55, P<0.001, false discovery rate [FDR]<0.001; LDLR, OR=1.20, 95% CI=1.04 to 1.39, P=0.015, FDR=0.034; APOB, OR=1.17, 95% CI=1.09 to 1.27, P<0.001, FDR<0.001). Conversely, genetic mimicry of LPL enhancement equivalent to a one-SD reduction in TG was causally associated with a 36% decrease in T2D risk (OR=0.64, 95% CI=0.57 to 0.71, P<0.001, FDR<0.001). Other genetic mimicries of drug targets (NPC1L1, PCSK9, ABCG5/ABCG8, ANGPTL3 and APOC3) displayed an unremarkable impact regarding T2D risk. Liver fat explained 18.45%, 14.59%, and 4.01% of the total effect of HMGCR, APOB, and LPL on T2D risk, respectively. Additionally, abdominal subcutaneous adipose tissue (ASAT) volume explained 99.17% and 61.82% of the total effect of HMGCR and APOB on T2D risk, respectively.
CONCLUSIONS The diabetogenic effect of HMGCR inhibitors, antisense oligonucleotides targeting ApoB-100 mRNA, and LDLR inhibition could be explained by ASAT and liver fat accumulation, necessitating increased attention in clinical applications. Besides, it is important to note the development of pharmacological approaches that enhance LPL activity. Combining HMGCR inhibitors with LPL enhancement has the potential to mitigate the diabetogenic effect.
GW34-e1279
Aizezi Aibibanmu, Adi Dilare, Yitong Ma
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China
OBJECTIVES Triglyceride-glucose (TyG) index is a simple and sensitive alternative index of insulin resistance, which has been proven to predict cardiovascular outcomes in patients with coronary heart disease. The purpose of this study was to explore the predictive value of TyG index combined with SYNTAX score in adverse cardiovascular events after revascularization in patients with multi-vessel coronary artery disease (MVCD).
METHODS Clinical data and follow-up data of 2429 MVCD patients before and after operation were collected, and a retrospective cohort study was conducted. Use a Cox proportional risk regression model to estimate the relative risk ratio (HR) between the TyG index and SYNTAX score and cardiovascular adverse events, and explore the potential nonlinear relationship between the TyG index and cardiovascular adverse events using a restricted cubic bar graph (RCS). Randomly divide patients into a training group and a validation group in a 7:3 ratio. Use the Least Absolute Shrinkage Selection Operator (LASSO) regression model in the training set for variable selection and prediction feature construction. Use the C index, ROC curve, and calibration curve to verify the predictive value of the TyG index and SYNTAX score model for MACCEs events in patients in the training and validation set at 1, 3 and 5 years; The reclassification improvement index (NRI), comprehensive discriminant improvement index (IDI) and decision analysis curve analysis nomogram model were used to predict the efficacy and net income of MACCEs events in patients with training sets and verification sets 1, 3 and 5 years after surgery. The KM survival curve is used to verify the survival difference between high risk and low risk in the linear graph model score.
RESULTS After adjusting for potential confounding factors, the COX risk regression model showed that the TyG index and SYNTAX score were independent influencing factors for postoperative MACCE events in MVCD patients (HR=2.12, 95% CI: 1.81–2.49, HR=1.07, 95% CI: 1.06–1.09). Use LASSO regression to screen out seven variables and use them to generate a prognostic model and construct a Nomogram. In the training set, the combined model of TyG index and SYNTAX score outperformed other models in predicting MACCEs time in MVCD patients, such as C-index (0.848 vs. 0.872 vs. 0.887 vs. 0.895, P<0.001), and the same was true in the validation set, such as C-index (0.870 vs. 0.881 vs. 0.887 vs. 0.893, P<0.001). The AUCs for predicting MACCE events in patients at 1, 3, and 5 years after surgery in the training and testing sets were (78.4, 88.4, 86.6) and (75.3, 85.5, and 87.9), and the time-dependent AUC (>0.7) indicated satisfactory discriminative ability of the TyG index and SYNTAX score joint model. The combination model in the training set evaluated the NRI (0.073, P=0.003)/IDI (0.076, P=0.002) of postoperative MACCEs, and the NRI (0.034, P=0.247)/IDI (0.031, P=0.331) in the validation set. Furthermore, DCA showed that the TyG index and SYNTAX score joint model was clinically useful and had better discriminative ability to recognize patients at high risk than the other traditional risk factor models. The calibration plots showed favorable consistency between the prediction of the TyG index and SYNTAX score joint model in both the training and validation cohorts.
CONCLUSIONS The TyG index SYNTAX combination model shows excellent performance in predicting MACCEs events in patients with various vascular diseases in comparison to traditional risk factor models.
GW34-e1369
Xiaofang Chen1, Junhan Chen1, Xiaoling Cai1, Yansong Guo2, Kaiyang Lin2
1Fujian Provincial Hospital; Shengli Clinical Medical College of Fujian Medical University
2Fujian Provincial Hospital
OBJECTIVES Atherogenic index of plasma (AIP), always be considered as a predictive lipid index of cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). And contrast-induced acute kidney injury (CI-AKI) is a frequent complication in patients with acute myocardial infarction (AMI) after coronary diagnostic and interventional procedures. Meanwhile, diabetes is a risk factor for cardiovascular diseases. We hypothesized that there exists a correlation between AIP and contrast-induced acute kidney injury in patients with diabetes undergoing PCI.
METHODS To investigate the association between AIP and CI-AKI in patients with diabetes undergoing PCI, we retrospectively analysed 2588 consenting patients with diabetes who undergoing PCI from January 2012 to December 2018. CI-AKI, defined as an absolute SCr increase≥0.3 mg/dL or a relative increase in SCr ≥50% within 48 hours of contrast medium exposure. The AIP was calculated as the base 10 logarithm of the ratio of the plasma concentration of triglycerides to high-density lipoprotein-cholesterol (HDL-C). All the patients were divided into 4 groups based on the AIP quartiles. The primary endpoint was CI-AKI.
RESULTS The incidence of CI-AKI was 9.6% (n=251). At a median follow-up of 3.4 years, the Kaplan-Meier survival analyses revealed that the incidence of the primary outcome increased gradually with rising AIP quartiles. After adjusting for potential confounding factors, multivariate logistics regression analysis suggested that compared with the lowest AIP quartile, the 3rd AIP quartile was associated with increased risk for the CI-AKI (odds ratio [OR]: 1.693, 95% confidence interval [CI]: 1.009 to 2.869, P=0.0498) and the 4th quartile AIP has a significant association with CI-AKI ([OR]: 1.931, 95% [CI]: 1.076 to 3.546, P=0.0303). Subgroup analysis showed that there was no interaction between AIP and variables in subgroup analysis.
CONCLUSIONS The increase in AIP value on admission was strongly associated with the occurrence of CI-AKI in patients with diabetes undergoing PCI.
STRUCTURAL HEART DISEASE
GW34-e0094
Yusi Chen
The Second Xiangya Hospital of Central South University
OBJECTIVES Although epicardial adipose tissue (EAT) is linked to increased survival risk in left heart failure, the association between EAT and right heart failure caused by pulmonary arterial hypertension (PAH) remains unknown. Therefore, we measured the EAT volume (EATV) to assess the potential impact of EATV on right heart structure and function and long-term prognosis in PAH patients.
METHODS A total of 135 patients with PAH and 49 controls underwent cardiac magnetic resonance examination. EATV was quantified and was related to clinical correlates, biomarkers associated with myocardial injury, and cardiac function on cardiac magnetic resonance. Levels of EATV associated with risk of clinical worsening were evaluated on a continuous scale and by prior-defined centile categories with Cox regression models.
RESULTS Compared with the controls, the patients with PAH had a lower EATV (Ln [EATV]: 3.2±0.8 mL vs. 3.5±0.7 mL, P=0.03). The association of levels of EATV with right ventricular end-diastolic volume (P for nonlinear=0.0013), right ventricular end-diastolic volume index (P<0.0001), right ventricular cardiac output (P=0.003), N-terminal pro-brain natriuretic peptide (P=0.03) and the risk of clinical worsening (P=0.01) were U shaped. Compared with individuals with middle-level EATV, the multivariable-adjusted hazard ratio for clinical worsening was 6.2 (95% CI, 1.4 to 28.5) for individuals with low-level EATV and 6.8 for high-level EATV.
CONCLUSIONS PAH patients had decreased EATV compared to controls. EATV showed a U-shaped association with right heart function and biomarkers of myocardial injury in PAH patients. Low and high levels of EATV might reduce long-term event-free survival in PAH patients.
GW34-e0097
Dan Zhang, Xiang Ma
The First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES Acute aortic dissection (AAD) is a serious and life-threatening cardiovascular emergency. The aim of this study was to investigate whether miRNAs in circulating exosomes could serve as novel diagnostic biomarkers for AAD.
METHODS Using miRNA microarray sequencing, the differentially expressed exosomal miRNAs between AAD patients and control subjects were found. In this study, we investigated 8 miRNAs (miR-499a-5p/miR-543/miR-143-3p/miR-4433b-3p/miR-744-5p/miR-4488/miR-202-3p/miR-206), 4 genes (MMP-9/MMP-12/TGF-β/D-Dimer) in AAD (n=75) and Control (n=86) expression levels between the two groups. The combined diagnosis of exosomal miRNAs and gene was performed (AUC>0.8, r>0.5 and P<0.01). The ROC curve was drawn to evaluate the diagnostic efficacy. Predict the gene targets of differentially expressed miRNAs and analyze the functions and signaling pathways of these targets using online databases.
RESULTS The exosomes isolated from the two groups of serum were bilayer membranes with a diameter of about 100 nm. Stably expressed in CD9, CD63 and TSG101. Compared with the control subjects, 8 exosomal miRNAs (miR-499a-5p, miR-543, miR-206, miR-143-3p, miR-4433b-3p, miR-744-5p, miR-4488 and miR-202-3p) were regulated to varying degrees (P<0.05). miR-499a-5p, miR-202-3p and D-Dimer had higher diagnostic efficacy (AUC>0.90). Among them, miR-499a-5p had the highest diagnostic accuracy, reaching 95%, AUC=0.99. Co-diagnosis of positively correlated miRNAs and genes improves the diagnostic performance. The combined diagnostic accuracy of miR-499a-5p and miR-202-3p was 98% (AUC=0.998), and the sensitivity and specificity were 98%. The combined diagnostic accuracy of miR-499a-5p and MMP-9 was 98% (AUC=0.996), and the sensitivity and specificity were 98%. GO enrichment analysis and KEGG signaling pathway analysis, some predicted targets of these miRNAs are involved in the pathophysiological process of AAD.
CONCLUSIONS Serum exosomal miR-499a-5p, miR-143-3p and miR-202-3p can be used as potential diagnostic biomarkers for AAD, and the combination of various markers can coordinate and complement each other, and can significantly improve the diagnosis of aortic dissection sensitivity and specificity.
GW34-e0197
Bowen Lin1, Yunli Shen1, Weifeng Shen2, Yehong Liu1
1Shanghai East Hospital, Shanghai Tongji University
2Ruijin hospital, Shanghai Jiaotong University School of Medicine
OBJECTIVES 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 Serum levels of t-PA were determined in 347 consecutive stable angina patients with (n=183) or without (n=164) AVSc. Outcomes were prospectively recorded as planned clinic evaluations every 6 months up to 7 years. The primary endpoint was a composite of cardiovascular death and rehospitalization due to heart failure. The secondary endpoint included all-cause mortality, cardiovascular death, and rehospitalization due to heart failure.
RESULTS For patients with AVSc, those with higher t-PA levels (>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 0.808 and an integrated discrimination improvement of 0.215 (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.
GW34-e0424
Peijian Wei, Yihang Li, Zhongying Xu, Liang Xu, Junyi Wan, Fengwen Zhang, Fang Fang, Gejun Zhang, Xiangbin Pan
Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
OBJECTIVES Coronary arteries drain into the left ventricle, known as coronary-left ventricular fistula (CLVF), an extremely rare anomalous coronary artery disease. Little is known about the outcomes following transcatheter closure or surgical closure of CLVF.
METHODS This was a single-center retrospective study including 42 consecutive patients who underwent the transcatheter or surgical closure procedure from January 2011 to December 2021. The baseline and anatomic characteristics of the fistulas, procedural outcomes, and late outcomes were summarized and analyzed.
RESULTS The mean age was 31.6±16.2 years old with 28 males (66.7%). Fifteen patients underwent surgical closure (SC group) and the remaining received transcatheter closure (TC group). There were no differences in age, comorbidities, clinical presentations, and anatomic characteristics between the 2 groups. The procedural success rate was similar (93.3 vs 85.2%, P=0.639) without operative and in-hospital mortality in both groups. To note, patients who underwent transcatheter closure had a significantly shorter postoperative in-hospital length of stay (2.11±1.49 vs 7.73±2.37 days, P<0.001). The median follow-up time was 4.6 years (2.5–5.7 years, TC group) and 3.98 years (0.42–7.15 years, SC group), respectively. No difference was observed in the incidence of recanalization of the fistula (7.4 vs 6.7%, P=1) and myocardial infarction (0 vs 0%). Two patients developed cerebral infarction due to discontinuation of anticoagulation in the TC group. Importantly, thrombotic occlusion of the fistulous tract with patent parent coronary artery was found in 7 patients of the TC group.
CONCLUSIONS Both transcatheter and surgical closure are safe and effective for patients with CLVF. Thrombotic occlusion is a noteworthy late complication, whose presence indicates the application of lifelong anticoagulation.
GW34-e0451
Fawang Du
Guizhou Provincial People’s Hospital
OBJECTIVES During TAVR procedures, retrograde crossing of the aortic valve via femoral artery is a crucial step. However, in some instances, retrograde guidewire approach may be difficult due to anatomical limitations of the aortic valve.
METHODS Herein, we report a case of a 75-year-old male patient was diagnosed with severe aortic stenosis with worsening symptoms of dyspnea, lower extremity edema, and paroxysmal nocturnal dyspnea, accompanied by precordial pain. Cardiac-gated computed tomography angiography revealed a Type 0 bicuspid aortic valve with severe stenosis and an annular area of 397 mm2, the Society of Thoracic Surgeons predicted risk was 9.8%, the multi-disciplinary team decided to explore TAVR as an option.
RESULTS During the procedure, the initial 1-hour attempts to deliver a retrograde guidewire across the aortic valve were unsuccessful. Instead, we opted for an anterograde guidewire approach through the atrial septum, which proved successful across the aortic valve. The atrial septum was punctured, and a 0.032-inch hydrophilic guidewire was inserted and advanced through a 5F right coronary catheter, which was then guided through the tricuspid valve to the left ventricle. The catheter was then guided through the aortic valve and into the descending aorta, and the snare technique was used to capture the hydrophilic guidewire. The 6F pigtail catheter was then advanced to the left ventricle, and the hydrophilic guidewire was removed. The Lunderquist guidewire was advanced through the pigtail into the left ventricle, and a 24 mm VitaFlow TAVR valve was delivered over the Lunderquist guidewire and across the aortic valveafter using a 18 mm balloon deflation, the valve was then deployed, and the procedure was successful, with no complications. Post-procedure imaging showed excellent valve function, and the patient experienced significant improvement in symptoms and hemodynamic parameters.
CONCLUSIONS The anterograde guidewire approach across the aortic valve proved to be a feasible alternative approach in TAVR patients who are not suitable candidates for the retrograde guidewire approach across the aortic valve.
GW34-e0461
Teruhiko Imamura, Hayato Fujioka, Mitsuo Sobajima, Nobuyuki Fukuda, Hiroshi Ueno, Koichiro Kinugawa
Second Department of Internal Medicine, University of Toyama
OBJECTIVES Psoas muscle mass is one of the recently-featured index of sarcopenia, which has a negative prognostic impact in patients with a variety of diseases. We investigated the prognostic impact of baseline psoas muscle mass in patients receiving trans-catheter aortic valve replacement (TAVR).
METHODS Patients who received TAVR at our center between 2015 and 2022 were included. Patients received computer tomography imaging on admission as an institutional protocol and psoas muscle mass was measured, which was indexed by body surface area. Patients were followed for four years or until January 2023. The prognostic impact of psoas muscle mass index on 4-year mortality following index discharge was evaluated.
RESULTS A total of 322 patients (85 years, 95 male) were included. Median psoas muscle mass index at baseline was 10.9 (9.0, 13.5) ×10 cm3/m2. A lower psoas muscle mass index tended to be associated with several index of malnutrition and sarcopenia. A psoas muscle mass index was independently associated with 4-year mortality with an adjusted hazard ratio of 0.88 (95% confidence interval 0.79–0.99, P=0.044). Patients with lower psoas muscle mass index (below the statistically calculated cutoff of 10.7 ×10 cm3/m2, N=152) had significantly higher cumulative 4-year mortality compared with others (32 versus 13%, P=0.008).
CONCLUSIONS A lower psoas muscle mass index, which is a recently-featured objective marker of sarcopenia, was associated with mid-term mortality following TAVR in the elderly cohort with severe aortic stenosis. Measurement of psoas muscle mass index prior to TAVR should have clinical implication in shared decision-making among patients, their relatives, and clinicians.
GW34-e0585
Kai Xu1, Xiangbin Pan2, Hong Jiang3, Shaoliang Chen4, Ben He5, Yan Wang6, Jiyan Chen7, Guosheng Fu8, Yaling Han1
1General Hospital of Northern Theater Command, Shenyang, China
2Fuwai Yunnan Cardiovascular Hospital, Kunming, China
3Renmin Hospital of Wuhan University, Hubei General Hospital, Wuhan, China
4Nanjing First Hospital, Nanjing, China
5Shanghai Chest Hospital, Shanghai, China
6Xiamen Cardiovascular Hospital Xiamen University, Xiamen, China
7Guangdong Provincial People’s Hospital, Guangzhou, China
8Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
OBJECTIVES Transcatheter edge-to-edge repair (TEER) is an effective treatment option for selected heart failure patients with severe secondary mitral regurgitation (MR) who remain symptomatic despite guideline-directed medical therapy (GDMT). We here report short-term results of a novel designed mitral TEER system (SQ-Kyrin-M™) for heart failure patients with secondary MR.
METHODS At 18 sites in China, patients with heart failure and moderate-to-severe or severe secondary MR who remained symptomatic despite the use of maximal doses of GDMT were included in the study. The effectiveness (defined as successful implantation of devices and no greater than 2+ paravalvular MR) and safety (defined as periprocedural adverse events such as death, myocardial infarction, stroke, or device related reintervention) end points were measured at 1 month follow-up. In total, 125 patients were enrolled in the study; 83.2% (104/125) patients suffered from acute heart failure within one year before procedure; 56.0% (70/125) patients were in NYHA class III-IV despite GDMT. Anatomical and clinical eligibility for mitral TEER was assessed by an independent eligibility committee (LVEF 41.5±11.9%).
RESULTS Technical success (measured at exit from the catheterization laboratory) was achieved in 100% patients without unplanned surgical intervention. The mean procedure time and device time were 139.2±73.3 min and 62.1±45.7 min, respectively. At one-month follow-up, device success was 98.4% (120/122) and procedural success was 96.7% (118/122) with a 0% mortality; MR≤2+ (assessed by an independent echo corelab) was achieved in 99.2% of study population with 74.2% MR≤1+. Major adverse events occurred in 2.4% (3/125) patients in 30 days follow-up. Myocardial infarction was noted in 1 patient, single leaflet detachment was noted in 1 patient and leaflet perforation was noted in 1 patient. The last two patients were successfully treated through transcatheter re-intervention. NYHA class was improved from 56.0% of patients III-IV grade to 16.4% of patients (P<0.001).
CONCLUSIONS Treatment of secondary MR with SQ-Kyrin-MTM Transcatheter Mitral Valve Repair System seems to be safe and feasible in this cohort of pre-selected symptomatic patients despite maximally tolerated GDMT. Initial efficacy analysis showed encouraging reduction of MR, which may potentially result in improved clinical outcomes.
GW34-e0641
Hairui Wang, Yanping Ruan, Yihua He
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Current research has suggested that genetic factors, environmental factors and maternal factors were associated with increased risk of fetal congenital heart diseases (CHDs). However, few studies have used machine learning to assess prediction models for risk factor of prenatally diagnosed fetal CHDs. This study aimed to establish a fetal CHDs risk prediction model using machine learning (ML) based on Chinese Maternal and Fetal population in a large sample size.
METHODS In this case-control study, a total of 13,870 fetuses were recruited, 7924 normal fetuses and 5946 with CHDs according to the findings of fetal echocardiography. The maternal and paternal factors in the two groups were investigated retrospectively. The dataset was randomly divided into the training set and the test set (80:20, respectively), with 11,096 in the training set, 2774 cases in the test set. We developed prediction models based on the random forest (RF), and extreme gradient boosting (XGBoost), and then performed 5-fold cross-validation to evaluate the stability of the models. The variables were ranked according to their importance by SHAP method, while the contribution of the variables to CHDs risk was verified by the area under the ROC curve.
RESULTS The XGBoost model was found to be superior in predicting CHDs risk and achieved the best performance (AUC=0.619, specificity=0.765, accuracy=0.627). The contribution of independent variables to the model were ranked as follows: progesterone use during early pregnancy, upper respiratory tract infection during early pregnancy, history of spontaneous abortion, anemia, paternal age, method of conception, mental stress during early pregnancy and indoor decoration during pregnancy.
CONCLUSIONS This study showed that XGBoost model had high reliability to assess risk factors of fetal CHDs. The most critical risk factors of fetal CHDs can be found by SHAP method to render the output of the XGBoost model clinically interpretable. Meanwhile, it also suggests that active clinical management of these factors is important to reduce the risk of fetal CHDs.
GW34-e0654
Qianhong Lu1, Junxing Lv1, 2, Yunqing Ye1, Zhe Li1, Weiwei Wang1, Bin Zhang1, Qinghao Zhao1, Zhenyan Zhao1, Haitong Zhang1, Qingrong Liu1, Bincheng Wang1, Zikai Yu1, Shuai Guo1, Zhenya Duan1, Yanyan Zhao3, Runlin Gao1, Haiyan Xu1, Yongjian Wu1
1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China
3Medical Research & Biometrics Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
OBJECTIVES With the aging population worldwide, there is an increasing burden of both valvular heart disease (VHD) and diabetes. The present study aimed to investigate the prevalence of diabetes in different types of VHDs, as well as its relationship with severity of valvular lesions and clinical outcome.
METHODS A total of 11,862 adult patients (≥18 years) with significant (≥moderate) VHD from the China Valvular Heart Disease study between April and June 2018 were included in this analysis. The primary outcome was the composite of all-cause death, hospitalization for heart failure, and myocardial infarction during two-year follow-up.
RESULTS Among 11,862 patients with significant VHD, 14.5% (1721/11,862) had diabetes. Of patients with both VHD and diabetes, the mean age was 66.74±10.64 years, and 57% (981/1721) were male. The prevalences of diabetes were 14.1% (80/568) in aortic stenosis (AS), 10.9% (171/1562) in aortic regurgitation (AR), 6.8% (37/544) in mitral stenosis (MS), 19.1% (563/2943) in mitral regurgitation (MR), 14.6% (285/1956) in tricuspid regurgitation, 5.6% (15/269) in mixed AS and AR, 9.5% (19/200) in mixed MS and MR, and 14.4% (551/3820) in multiple VHD. According to etiology of VHD, individuals with diabetes accounted for 6.7%, 16.7%, 6.2%, 28.7%, 16.5% in patients with rheumatic VHD, degenerative VHD, congenital VHD, ischemic VHD, and functional VHD, respectively. After adjusting patients’ demographics, diabetes was associated with a significantly lower risk of severe valvular lesion in AR (odds ratio [OR]: 0.579, 95% confidence interval [CI]: 0.390–0.860, P=0.007), MR (OR: 0.647, 95% CI: 0.523–0.800, P<0.001), and mixed AR and AS (OR: 0.258, 95% CI: 0.087–0.765, P=0.015). Similar results were obtained in patients with primary VHD (AR, OR: 0.593, 95% CI: 0.371–0.946, P=0.028; MR, OR: 0.680, 95% CI: 0.475–0.973, P=0.035; mixed AR and AS, OR: 0.258, 95% CI: 0.087–0.765, P=0.015), as well as in those with isolated secondary MR (OR: 0.713, 95% CI: 0.538–0.944, P=0.018). In the multivariable Cox proportional hazards model adjusting clinical characteristics and echocardiographic findings, diabetes was an independent predictor of two-year outcome in patients with MR (hazard ratio: 1.345, 95% CI: 1.069–1.692, P=0.011).
CONCLUSIONS Diabetes is common in patients with significant VHD. It was associated with a lower risk of severe left-sided regurgitant valvular diseases, but caused a significantly negative impact on prognosis in patients with MR. Better understanding and management of concomitant VHD and diabetes are needed.
GW34-e0847
Jianming Wang
General Hospital of Northern Theater Command
OBJECTIVES In the past, most of the patients with ASD/PFO and atrial fibrillation were only treated for cardiovascular defects. However, ASD/PFO patients with atrial fibrillation 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. As congenital heart diseases are associated with a higher incidence of atrial fibrillation, simultaneous transcatheter ASD/PFO and left atrial appendage closure (LAAC) has became a new effective treatment. As we reported that simultaneous closure of the LAA with the LACBES occluder and CHD closure is a viable option for patients with nonvalvular atrial fibrillation who are at risk of stroke or systemic embolism, and it is effective and yields excellent short- and mid-term results previously. However, only a limited number of articles involving simultaneous treatment of ASD/PFO and atrial fibrillation vs ASD/PFO closure alone. To report the long-term safety and efficacy of simultaneous percutaneous LAA and ASD/PFO closure vs ASD/PFO closure alone.
METHODS A retrospective study of 27 consecutive patients undergoing LAAC procedures using the ACP2 LAA or LACBES occluders. Data were compared between 25 cases only with ASD/PFO closure and 27 cases with simultaneous percutaneous procedures of LAAC and ASD/PFO closure. All clinical events were obtained by telephone, outpatient visit or case histories, and the follow-ups, including medical treatment and TEE imaging, lacked standardization.
RESULTS Compared to ASD/PFO closure alone group, LAAC and ASD/PFO closure group had and a higher rate of stroke (18.5 vs. 4.0%, P<0.05), but there were no statistical differences in the remaining patient characteristics. During the follow-up period, there were no significant differences between the two groups in embolism events (12.0 vs. 0%, P=0.104), device related thrombus (8.0 vs 3.7%, P=0.602), and cardiac death (4.0 vs. 0%, P=0.481). There were significant differences between the two groups in major bleeding (16 vs. 0%, P<0.05). The observed rate of all thromboembolic events by Kaplan–Meier analysis was decreased by 49.7 and 100% and the observed annual rate of bleeding was reduced by 36.0 and 74.1% in ASD/PFO closure alone group and LAAC and ASD/PFO closure group, respectively.
CONCLUSIONS LAAC with simultaneous interventional occlusion therapy for ASD/PFO has become a new focus of patient care. Although here were no significant differences between the two groups in embolism events, the observed rate of all thromboembolic events generally had been declining in simultaneous percutaneous LAAC combined with ASD/PFO closure group. Simultaneous percutaneous LAAC combined with ASD/PFO 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 PFO/ASD compared with ASD/PFO closure alone group.
GW34-e0860
Yang Li, Bin Wang, Weiwei Zhou, Kai Xu, Yaling Han
General Hospital of Northern Theater Command
OBJECTIVES Coronary artery obstruction (CAO) during or after transcatheter aortic valve replacement is a rare but catastrophic complication, therefore, it is vitally important to recognize and prevent CAO because of its life-threatening nature.
METHODS A 64-year-old male with severe symptomatic aortic stenosis underwent transcatheter aortic valve replacement (TAVR). Transthoracic echocardiography demonstrated the left ventricular diameter in diastole was 65 mm with a left ventricular ejection fraction of 30%. Computed tomography angiography identified the bicuspid aortic valve type 1 with right-left coronary cusp fusion and the high risk of coronary artery obstruction (CAO). No sign of blood flow reduced in the left main artery was observed during 22 mm×40 mm balloon dilatation. Subsequently, a 26 mm retrievable VenusA-Plus self-expandable bioprosthetic valve was deployed under rapid pacing in a satisfactory position. There was no CAO on the angiogram, and the electrocardiogram did not show any ischemic changes. However, an intravascular ultrasound (IVUS) assessment was performed through the jailed system showing the folding of the native leaflet toward the sinus of Valsalva causing its partial obstruction with minimum lumen area of 4.55 mm2, which indicates potential delayed CAO following TAVR using self-expandable bioprosthetic valve. A chimney stent with 4.5 mm×24 mm DES was then implanted. IVUS confirmed good stent expansion, with a minimal luminal area and diameter of 8.40 mm2 and 4.19×2.49 mm, respectively.
RESULTS The patient was asymptomatic at the 6-month follow-up.
CONCLUSIONS IVUS may be regarded as important adjunctive tool to detect the partial CAO after valve implantation and improve clinical outcomes.
GW34-e0867
Jianmin Li1, YuanCheng Fu2, Shujun Li2
1PetroChina Jinxi Gem Flower Hospital
2Bazhong Boji Hospital, Bazhong City, Sichuan Province, China
OBJECTIVES Cardiogenic shock caused by rheumatic valvular heart disease and cardiomyopathy heart failure is a difficult problem in clinical treatment. The main problems are the dose and time of drug application to enable patients to quickly and early restore normal blood pressure level, ensure the oxygen and energy supply of tissues and organs of the whole body, and prevent multiple organ failure. Thirty-two patients with cardiogenic shock were observed in this paper, which were divided into 2 groups. There were 16 participants in each group, one with rheumatic heart disease and one with cardiomyopathy and heart failure. The diagnostic criteria of group A were confirmed by inpatient ultrasonography with rheumatic heart valvular disease with left ventricular EF less than 30%, and group B diagnosed dilated cardiomyopathy with left ventricular EF less than 30%. The index of anti-shock is: the systolic blood pressure is less than or equal to 80/40 mmHg. Anti-shock drugs: norepinephrine and M-hydroxylamine, the correction and recovery of shock indicators systolic and diastolic pressure 95/65 mmHg, to observe the effect of the two groups of drugs in anti-shock optimization.
METHODS In this paper, 32 patients with cardiogenic shock were observed. The antishock effects of norepinephrine and mehydroxyamine were compared. They were divided into 2 groups, with 16 men and 16 women in each group, aged 65–85 years old. 1. The shock produced by rheumatic valvular heart failure is group A, male to female ratio 1:1, anti-shock medication norepinephrine. 2. Cardiomyopathy and heart failure produced shock in group B, 8 men and women, and the drug was M-hydroxylamine. The two groups observed drug comparative analysis.
RESULTS Group A: Rheumatic heart disease and heart failure caused shock: blood pressure 70/40 mmHg, treatment was given 0.9% sodium chloride 50 mL plus norepinephrine 2 mg, intravenous injection of 3 mL first, measured blood pressure 85/55 mmHg, after 10 minutes, intravenous injection of 5 mL, measured blood pressure 105/65 mmHg, blood pressure basically returned to the normal range. Continue pumping at 2 mL/h. Group B: cardiomyopathy, heart failure and shock, blood pressure was 75/45 mmHg, treatment was given 0.9% sodium chloride 50 mL plus m-hydroxylamine 20 mg, the blood pressure was measured 75/50 mmHg after 3 mL intravenous injection, 10 minutes later, the blood pressure was measured 90/55 mmHg after 5 mL intravenous injection, then 5 mL/h intravenous pump.
CONCLUSIONS The antishock effect of norepinephrine for cardiogenic shock and mehydroxyamine for cardiogenic shock in group A was better than mehydroxyamine for cardiogenic shock in group B. The reason is that the first intravenous injection of small doses of drugs can make the blood pressure quickly reach the normal level in A short time, and the effect of the same injection method in group B is worse than that in group A. So norepinephrine and M-hydroxylamine are more effective in anti-cardiogenic shock than m-hydroxylamine.
GW34-e0949
Yi Zhou
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
OBJECTIVES his study aims to explore the pathological characteristics and pathogenesis of functional tricuspid regurgitation (FTR) patients, especially those defined as “massive” or “torrential” according to the new classification system for tricuspid regurgitation. Although previous studies have delved into the pathogenesis of TR, research on the pathological characteristics and pathogenesis of FTR patients is still insufficient. Therefore, this study will use three-dimensional transesophageal echocardiography (3D TEE) to evaluate the morphological features of tricuspid valve apparatus in FTR patients and explain its pathogenesis.
METHODS From June 2020 to August 2022, a total of 322 FTR patients with left heart valve disease were prospectively collected from Tongji Medical College Affiliated Union Hospital at Huazhong University of Science and Technology. Primary tricuspid regurgitation, pulmonary hypertension caused by any reason (primary or secondary), right heart dysfunction caused by any reason, and isolated atrial fibrillation were excluded. All subjects underwent standardized transthoracic echocardiogram (TTE) and 3D TEE examinations, which were grouped according to TR severity as mild-moderate regurgitation group, severe regurgitation group, and massive-torrential regurgitation group. The differences in clinical baseline data, conventional TTE parameters, and morphological features parameters of tricuspid valve apparatus between groups were compared.
RESULTS A total of 322 FTR patients with left heart valve disease were included in this study (152 females; mean age: 53±14 years), including mild-moderate regurgitation group (174 cases), severe regurgitation group (74 cases), and massive-torrential regurgitation group (74 cases). The results showed that with the increase of FTR severity, there were significant changes in the morphological features of tricuspid valve apparatus: ➀ The 3D vena contracta area in the massive-torrential regurgitation group was substantially higher than in the mild-moderate regurgitation group (107.5±20.0 vs 14.1±16.7, P<0.001). Tricuspid annulus: anterolateral-postmedial and anterior-posterior diameter, circumference, area, and ellipticity increased significantly (P<0.001) in the mid-systolic period, while annulus height decreased significantly (P<0.001). Tricuspid valve leaflets: tethering height, angle and volume, leaflets area and thickness increased significantly (P<0.001) in the mid-systolic period, while the length of each leaflet decreased significantly (P<0.001). Chordae tendineae: the length of anterior papillary muscles and septal papillary muscles chord length increased significantly (P<0.01). ➁ The 3D vena contracta area in the massive-torrential regurgitation group was substantially higher than in the severe regurgitation group (107.5±20.0 vs 81.9±7.8, P<0.001). Tricuspid annulus: mid-systolic anterolateral-postmedial and antero-posterior diameter, area, and ellipticity increased significantly (P<0.001), while annular height decreased significantly (P<0.001). Tricuspid leaflets: mid-systolic tethered volume and angle, leaflets area and thickness increased significantly (P<0.001), while the length of each leaflet in mid-diastole decreased (P<0.001). Chordae tendineae: anterior papillary muscles chord length was significantly increased (P<0.001).
CONCLUSIONS There are significant differences in the morphological characteristics of tricuspid valve apparatus between patients with severe and massive-torrential regurgitation and those with mild-moderate regurgitation. With the increase of FTR degree, not only tricuspid annulus parameters but also tricuspid valve leaflets, chordae tendineae, and papillary muscle parameters undergo obvious morphological changes.
GW34-e0989
Ching Yan Zhu, Xin Xu, Jia Yi Huang, Qing Wen Ren, Mei Zhen Wu, Kai Hang Yiu
Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital
OBJECTIVES The significance of bicuspid aortic valve (BAV) morphology in the prognosis of aortic regurgitation (AR) in Asian populations is imperfectly understood. The risk of AR patients with BAV developing postoperative mortality and adverse outcomes after surgical aortic valve replacement (AVR), compared with AR patients with tricuspid aortic valve (TAV), also remains unclear. We endeavored to understand the differences in preoperative characteristics between BAV and TAV patients with AR as well as the incidence of postoperative mortality and adverse outcomes between the two groups.
METHODS Five hundred and eighty-seven patients with AR who have undergone AVR were included in the study, either with BAV (n=110) or TAV (n=477). Pre-operative baseline patient characteristics, as well as post-operative follow-up data, including reports of mortality or adverse events such as heart failure rehospitalization, were collected and analysed.
RESULTS In patients with AR undergoing AVR, compared with those who had TAV, those who had BAV were younger (52.5 years old vs 59.2 years old, P<0.001), and has less heart failure (38.2 vs 49.3%, P=0.04) at baseline. BAV patients with AR presented with significantly more concomitant aortic stenosis (AS) than TAV patients with AR (59.1 vs 15.3%, P<0.001). However, the two groups showed no significant differences in terms of proportion of male patients, BMI, as well as the prevalence of diabetes, hypertension, dyslipidemia, and aortic aneurysm. Patients with AR who had BAV experienced a lower cumulative incidence of postoperative heart failure rehospitalization than those who had TAV (13.6 vs 24.3%, P=0.017). Patients with BAV also had better postoperative survival compared to those with TAV (91.8 vs 85.3% at 2500 days after AVR, P=0.04).
CONCLUSIONS In patients with BAV who had AR requiring valve replacement surgery, despite a higher prevalence of concomitant AS, there was a lower prevalence of preoperative heart failure, as well as a lower risk of heart failure rehospitalization and better survival after surgery compared with patients with TAV who had AR. Our observations suggest that AR patients with TAV undergo surgery at a later stage of disease progression with poorer preoperative characteristics than those with BAV. More timely monitoring and management in AR for patients with TAV is recommended.
GW34-e1125
Kai Xu1, Yujie Zhou2, Mao Chen3, Jianfang Luo4, Jianan Wang5, Jun Jin6, Xiaoping Peng7, Jianzeng Dong8, Yongjun Wang9, Bin Wang1, Quanmin Jing1, Yaling Han1
1General Hospital of Northern Theater Command
2Beijing Anzhen Hospital, Capital Medical University
3West China Hospital of Sichuan University
4Guangdong Provincial People’s Hospital
5The Second Affliated Hospital Zhejiang University School of Medicine
6The Second Clinical Medical College of Army Medical University
7The First Affiliated Hospital of Nanchang University
8The First Affiliated Hospital of Zhengzhou University
9Beljing Tiantan Hospital, Capital Medical University
OBJECTIVES TriGUARD 3™ China Study is a prospective, multi-center, single arm study to demonstrate the safety, efficacy, and performance of the TriGUARD 3™ (TG3) Cerebral Embolic Protection Device in patients undergoing TAVR in China.
METHODS Patients with symptomatic severe aortic stenosis referred for transfemoral TAVR were eligible for participation in the trial. The primary safety end point was device related safety, defined as the composite of the following Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) adjudicated as related to the investigational device, evaluated immediately prior to discharge from index procedure hospitalization or at 7 days post procedure, whichever comes first. MACCE was defined as all-cause mortality, all stroke (disabling and non-disabling), acute kidney injury (stage 3), major vascular complications, compared to the performance goal (PG) derived from the REFLECT phase II trial of 11.6%.
RESULTS A total of 74 patients, including 18 roll-in and 56 subjects, were enrolled in TG3 China Study at 9 investigational centers in China. The mean (±SD) age of the patients was 72.60±7.94 years, 43.24% of the patients were female. NIHSS total score was 0.12±0.44 and Modified Rankin scale score was 0.12±0.66 in the whole cohort. The majority (67.12%) were in New York Heart Association functional class III or IV (NYHA). Device related MACCE was 1.47% (the whole cohort; BAV 2.00%; TAV 0.00%; P=1.000) and the upper bound of the 95% confidence interval (4.33%) was less than the 11.6% performance goal. There was no cardiovascular death, disabling stroke, or acute kidney injury (stage 3) in hospital follow-up. Non-disabling stroke unrelated with TG3 was observed in 1.47% (the whole cohort; BAV 0.00%; TAV 5.55%, P=0.244) of the patients. Major and minor vascular complication at the TG3 access site were occurred in 1.47% (the whole cohort; BAV 2.00%; TAV 0.00%, P =1.000) and 2.94% (the whole cohort; BAV 2.00%; TAV 5.55%, P=0.612), respectively.
CONCLUSIONS TriGUARD 3™ is a safe and effective in patients undergoing TAVR in China.
GW34-e1252
Ziyong Hao, Lisheng Jiang, Ben He
Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES Optimal antithrombotic therapy to prevent device-related thrombus (DRT) after left atrial appendage occlusion (LAAO) remains unknown. This study sought to evaluate the safety and efficacy of three postprocedural medication regimens based on direct oral anticoagulants (DOACs).
METHODS Patients underwent successful Watchman implantation were consecutively enrolled and categorized into three groups (DOAC plus clopidogrel, DOAC plus aspirin and DOAC only). The primary endpoint was DRT, thromboembolic (TE) and major bleeding events.
RESULTS A total of 603 patients (DOAC plus clopidogrel group: n=197, DOAC plus aspirin group: n=119, DOAC only group: n=287) were analyzed in this study. DRT occurred in 23/603 (3.8%) patients (1.5 vs. 4.2 vs. 5.2%, DOAC+clopidogrel vs. DOAC+aspirin vs. DOAC only, P=0.093), and the rate of major bleeding was significantly higher in the DOAC plus aspirin group (1.5 vs. 6.7 vs. 0.7%, P=0.001). Compared with DOAC plus clopidogrel, the risk of DRT was significantly higher in the DOAC only group (OR: 3.54, 95% CI: 1.13–15.58, P=0.050), so was the risk of major bleeding in the DOAC plus aspirin group (OR: 5.08, 95% CI: 1.39–24.24, P=0.021). There were no significant differences in total thromboembolic (TE) events. Combined therapy with DOAC plus aspirin led to a significant increase of the primary composite endpoint (OR: 2.88, 95% CI: 1.21–7.08, P=0.018) compared with DOAC plus clopidogrel, yet there were no significant differences between DOAC only and DOAC plus clopidogrel strategy (OR: 1.48, 95% CI: 0.69–3.40, P=0.328).
CONCLUSIONS Antithrombotic therapy with low-dose DOAC plus clopidogrel reduced the incidence of DRT without a trade-off of bleeding after LAAO.
GW34-e1253
Ziyong Hao, Lisheng Jiang, Ben He
Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES Current risk stratification schemes for stroke in atrial fibrillation are insufficient for accurate assessment of stroke risk.
METHODS We conducted a cross-sectional study to assess the mechanical function of the LAA by measuring the left atrial appendage ejection fraction (LAAEF) and grading the contrast retention (CR) using angiography.
RESULTS A total of 746 patients referred for left atrial appendage occlusion (LAAO) procedure with (n=151; Stroke group) and without (n=595; Control group) a history of stroke were included in the analysis. LAAEF was significantly lower (14% [9–19] vs. 20% [12–33], P<0.001) and Grade 3 CR was more common (66.9 vs. 33.9%, P<0.001) in patients with a history of stroke. Multivariable analysis showed that CR was independently associated with stroke in patients with AF [Grade 2 vs. Grade 1=7.29 (95% CI 2.84–21.65, P<0.001), Grade 3 vs. Grade 1=16.45 (95% CI 6.16–51.02, P<0.001)]. The receiver-operating characteristics curve demonstrated that CR identified patients with stroke more accurately than CHA2D-VASc score (C-statistic: 0.712 vs. 0.512, P<0.001), and the combination of CR and CHA2DS2-VASc score provided the best performance (C-statistic=0.871, P=0.048 [vs. CHA2DS2-VASc score alone]).
CONCLUSIONS Impaired mechanical function of the LAA featured by lower LAAEF and CR is associated with a history of stroke in patients with AF. Assessment of CR using LAA angiography helps improve the stratification scheme for stroke risk prediction.
GW34-e1264
Jiatong Li, Tan Liu, He Li, Mingxing Xie
Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
OBJECTIVES Left atrioventricular valvular regurgitation (LAVVR) recurrence after partial and transitional atrioventricular septal defect (AVSD) repair is the main risk factor associated with reoperation or mortality. The purpose of this study was to identify the risk factors for LAVVR recurrence after transitional and partial AVSD repair at a single institution.
METHODS Records of 157 patients who underwent anatomical repair for partial and transitional AVSD from January 2013 to December 2021 were included in our institutional database. Demographic, operative and echocardiographic reports were reviewed to determine the degree of LAVVR, atrioventricular valve anatomy, survival, reoperation and mortality. Patients were classified as recurrent LAVVR group and no recurrent LAVVR group.
RESULTS After a median follow-up period of 5.8 years, 40 patients had recurrent LAVVR≥moderate. Compared with patients without recurrent LAVVR, those with recurrent LAVVR were more likely to have smaller atrial size, larger left atrioventricular valve (LAVV) cleft width, higher proportions of preoperative LAVVR≥moderate, and immediately postoperative LAVVR≥mild to moderate. Age, height, atrial size, the severity of preoperative LAVVR and immediate postoperative LAVVR, and the LAVV cleft width were significant univariate risk factors for recurrent LAVVR (P<0.05 for all). Cox regression analysis showed that ≥mild to moderate LAVVR postoperatively [hazard ratio (HR) 9.53, 95% confidence interval (CI) 3.78–24.01; P<0.001], the width of LAVV cleft≥1 cm [HR: 3.90, 95% CI: 1.80–8.48; P<0.001], age at first repair [HR: 0.45, 95% CI: 0.31–0.66; P<0.001], were independently associated with the recurrence of LAVVR.
CONCLUSIONS The width of LAVV cleft, ≥mild to moderate LAVVR immediately after surgery, and age at initial surgery indicated high risk for recurrent LAVVR. Middle to long-term outcome in patients with repaired LAVV is favorable, and close surveillance is essential to allow timely reintervention.
GW34-e1303
Jingnan Zhang, Gejun Zhang, Junyi Wan
Fuwai Hospital, National Center for Cardiovascular Disease
OBJECTIVES Quadricuspid aortic valve (QAV) is a rare congenital disease with limited available information. The current study intended to characterize QAV using multi-imaging tests in a large QAV patient population.
METHODS Ninety patients were retrospectively enrolled (mean age 55.2±13.0 years, 62% male) with QAVs. Valve function, left ventricle dimensions [left ventricular end-diastole diameter (LVEDD) and end-systolic diameter (LVESD)] and ejection fraction (LVEF) were assessed with echocardiography. Cardiac computer tomography, or cardiac magnetic resonance scanning, were performed to evaluate anatomical features and aortic dimensions. Aortic dilation was defined as enlargement (>4 cm) of ascending aorta and/or aortic root.
RESULTS Aortic regurgitation (AR) was found in all QAV patients, and more than half (56%) had severe AR. Mean LVEF, LVESD and LVEDD of the cohort were 57.7±9.9%, 42.1±9.8 mm and 58.2±8.8 mm respectively. Reduced LVEF (<50%) occurred in 21.1% (n=19) of patients. Aortic dilation was observed in 37 patients (14 in ascending aorta, 11 in root and 12 in both location). Half of patients (n=45) received valve replacement after initial diagnosis. Regarding combined lesions, 2 patients received surgical aorta repair due to aortic aneurysm. Subaortic fibrotic membrane was diagnosed in 3 patients who received LVOT reconstruction afterwards. Coronary-pulmonary artery fistula was diagnosed in an 18-year male who underwent surgical correction.
CONCLUSIONS Aortic regurgitation is predominant in QAV patients, probably combining with progressive aortic enlargement and other congenital anomalies.
GW34-e1325
Xiaofu Tang1, Weiguo Fan2, Kui Hong2,3,4
1Second Clinical Medical School, Nanchang University, Jiangxi, China
2Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
3Department of Genetic Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
4The Jiangxi Key Laboratory of Molecular Medicine, Jiangxi, China
OBJECTIVES Ventricular arrhythmia (VA) is a significant clinical manifestation in patients with mitral valve prolapse (MVP), which rarely but sometimes leads to sudden cardiac death. There are evidence that abnormal mitral valve structure and myocardial fibrosis mediate the onset of VA. Several observational studies have reported inconsistent results about the value of late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) on VA in patients with mitral valve prolapse.
METHODS We performed a systematic review and meta-analysis of observational studies to assess the association of left ventricular LGE with VA in patients with MVP. We systematically searched PubMed, Embase, and Web of Science for case-control studies, cross-sectional studies, and cohort studies (published from 1993 to 2023, without language restrictions) comparing the incidence of VA between MVP patients present left ventricular LGE and those absent.
RESULTS One thousand four hundred and sixty-four subjects with MVP from 12 observational studies met eligibility criteria, VA episodes were detected in 221 subjects (15.1%). The mete-analysis demonstrated that Left ventricular LGE presence was associated with a increased risk of VA (pooled risk ratio 2.96, 95% CI: 2.26–3.88, P for heterogeneity=0.07, I 2=40%). Six studies reported the data of mitral regurgitation, meta-regression indicated there was no significant impact of the proportion of patients with moderate to severe mitral regurgitation on the association between LGE presence and VA (P=0.079).
CONCLUSIONS Detection of LGE by CMR could help stratification for the risk of VA in patients with MVP.
GW34-e1330
Yun Yang1,2,3, Lingyun Fang1,2,3, Mingxing Xie1,2,3
1Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
2Clinical Research Center for Medical Imaging in Hubei Province
3Hubei Province Key Laboratory of Molecular Imaging
OBJECTIVES Myocardial work derived from noninvasive pressure-strain loop is a novel afterload-independent approach to evaluate left ventricular (LV) performance. The study aimed to assess the myocardial work parameters in patients with primary mitral regurgitation (PMR), and to explore its prognostic value for postoperative LV ejection fraction (LVEF).
METHODS One hundred and four patients with severe PMR undergoing mitral valve operations were prospectively enrolled. Echocardiographic examinations were performed before and one month after operation. Patients were divided into two groups: the group postoperative LVEF≥50% and postoperative LVEF<50%. Logistic analysis was used to determine independent predictors for LV dysfunction (LVEF<50%).
RESULTS LVEF was lower than 50% in 20 (19.23%) patients one month after surgery. Compared with the patients with LVEF≥50%, those with LVEF<50% presented with lower global longitudinal strain, global work index, global constructive work and global work efficiency (P<0.01 for all), and higher global wasted work (P=0.020). Preoperative LV global longitudinal strain (OR=6.63 [1.94, 22.69]; P=0.003), global work index (OR=6.25 [1.82, 21.45]; P=0.004), global constructive work (OR=4.49 [1.32, 15.25]; P=0.016) and global wasted work (OR=3.59 [1.08, 11.88]; P=0.036) were independent predictors of post-operative LV dysfunction.
CONCLUSIONS Myocardial work parameters are independently associated with short-term postoperative LV function. They might help the risk stratification and prognosis discrimination, and further improve the outcomes of patients with PMR.
GW34-e1336
Liying Li1, Ban Chao1,2, Haiyan Ruan1,3, Muxin Zhang1,4, Ziqiong Wang1, Min Ma1, Yi Zheng1, Sen He1
1Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China
2Department of Equipment, Sichuan University West China Hospital, Chengdu, Sichuan, China
3Department of Cardiology, Traditional Chinese Medicine Hospital of Shuangliu District, Chengdu, China
4Department of Cardiology, First People’s Hospital, Longquanyi District, Chengdu, China
OBJECTIVES Albumin to fibrinogen ratio (AFR), a new inflammatory marker, has emerged as a useful indicator to predict adverse outcomes for several diseases. However, whether AFR could be a new useful indicator to predict mortality in HCM patients remains to be evaluated. The study explored the predictive value of AFR for HCM-related death in adult HCM patients.
METHODS A total of 404 HCM patients were eventually enrolled in the study according to the inclusion criteria. Patients were divided into two groups based on the median of baseline AFR. The association between AFR and HCM-related death was analyzed.
RESULTS During a median follow-up of 4.75 years, HCM-related death was observed in 45 patients (11.1%), including 22 (5.4%) HF-related death, 8 (2.0%) stroke-related death, 13 (3.2%) SCD and 2 (0.5%) HCM-related postoperative death. The incidence of HCM-related death was significantly higher in the low AFR group (log-rank P<0.001). With the high AFR group as reference, the unadjusted hazard ratio (HR) for HCM-related death was 2.97 (95% confidence interval [CI]: 1.53–5.75, P=0.001) in the low AFR group, and after adjusting for potentially confounding variables, the adjusted HR for low AFR group was 3.15 (95% CI: 1.56–6.37, P=0.001). No significant interactions between AFR and other variables were observed in subgroup analysis. Sensitivity analyses in patients with normal albumin and fibrinogen showed similar results.
CONCLUSIONS AFR is an independent prognostic factor for HCM-related death, adult HCM patients with a lower AFR have a higher risk of HCM-related death.
GW34-e1413
Xiaolei Wang, Xin Pan, Ben He
Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine
OBJECTIVES Pulmonary vein stenting is an effective therapy for severe pulmonary vein stenosis (PVS), which is primarily limited by restenosis with an overall rate of approximately 22.3% in a recent meta-analysis. Most restenosis requires repeat intervention, however, follow-up outcomes after reintervention remain unsatisfactory. Here we report a modified interventional strategy for recurrent stenosis.
METHODS This was a prospective, randomize, observational study performed from 2018 April to 2022 April in our medical center.
RESULTS Eighty-seven patients with 141 stenosed pulmonary veins underwent intervention with stent procedure, the mean stent diameter was 8.5±0.9 mm (7–10 mm). Twenty-six patients with 35 veins experienced in-stent restenosis (ISR), which occurred 24.8% in our study. A second intervention was then performed in these patients. Randomly assigned to two groups with 1:1, 17 vessels were treated for restenosis with high-pressure balloon angioplasty, while other 18 vessels were treated with modified stent-in-stent technique. Of these lesions, 3 vessels (2 in stent group, 1 in BA group) were procedural unsuccessful due to the guidewire was failure to pass through the stenotic segment. During a mean follow-up of 12 months, 12.5% (2/16) restenosis was found in the stenting group by computed tomography angiography (CTA), while the stenosis recurrence rate was 56.3% (9/16) in the BA group, which displayed recurrent stenosis was more common with BA (RRR 77.8%, P=0.009). After the re-restenosis was occurred in the rest 9 veins, they were then transferred to treat with stent-in-stent implantation to sustain vascular patency and only 2 re-restenosis suspected in the follow-up by imaging examination after next procedure.
CONCLUSIONS Management of ISR remains a challenge. Modified stent-in-stent implantation maybe superior to conventional high-pressure balloon angioplasty.
CARDIOMYOPATHY
GW34-e0030
Zhixiang Dong, Shihua Zhao
Department of Magnetic Resonance Imaging, Fuwai Hospital, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
OBJECTIVES Cardiovascular magnetic resonance feature tracking (CMR-FT) is an emerging tool that can quantitatively describe myocardial deformation and may serve as a more sensitive method to assess ventricular structural or functional alterations. This study aims to determine if right ventricular strain analysis can be used for the identification of revised Task Force Criteria (rTFC) diagnosed arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, and whether RV strain parameters can discriminate these patients incremental to the existing CMR criteria, thus improving the diagnostic yield of CMR in ARVC.
METHODS Eighty rTFC diagnosed ARVC patients (40 possible or borderline and 40 definite) in Fuwai hospital were retrospectively enrolled for analysis. Using CMR-FT, we evaluated RV global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) of all participants.
RESULTS Patients demonstrated significantly impaired global RV strain in all three directions (all P<0.001). ROC analysis indicated that RV GLS was the strongest discriminator between patients and healthy controls [area under the curve (AUC): 0.92]. Using the Youden index, we determined RV GLS≥−20.02% as the diagnostic criterion of ARVC patients. In patients with possible or borderline ARVC, there are 20 (50%) and 14 (35%) participants not fulfilling the existing RV end-diastolic volume index (RVEDVi) and RV ejection fraction (RVEF) major criterion respectively. And in those with no or only minor RVEDVi and RVEF abnormalities, 15 (75%) and 9 (64%) showed impaired RV GLS respectively. When both conventional criteria and RV GLS were considered together, this new diagnostic method demonstrated a sensitivity of 90%, specificity of 83% and diagnostic accuracy of 86%.
CONCLUSIONS Our study showed an improved diagnostic accuracy when both RV GLS and the existing CMR criteria were considered together, especially for those with possible or borderline diagnosis, suggesting the incremental value of strain analysis to the initial assessment of ARVC.
GW34-e0042
Yan Zhang
The people’s Hospital of Yunnan Province
OBJECTIVES The correlation between coronary microcirculation function and left ventricular outflow tract pressure gradient in patients with hypertrophic cardiomyopathy (HCM) was quantitatively evaluated by cardiac magnetic resonance imaging (CMR) combined with delayed enhancement imaging.
METHODS A retrospective analysis of 120 HCM patients and 46 healthy volunteers were admitted to the First People’s Hospital of Yunnan Province from January 2018 to January 2023. All patients received cardiac color ultrasound and CMR examination, cardiac color ultrasound for left ventricular outflow pressure gradient difference (LOVTG peak), CMR including cardiac movie imaging, myocardial resting first perfusion imaging and delayed enhancement imaging (LGE). Left ventricular ejection fraction (LVEF), peak perfusion time (tpeak), maximum ascending slope (Slope), peak myocardial signal intensity (SIpeak), and overall myocardial delayed enhancement (LGE%) were measured using CVI 42. Patients in the HCM group were classified hemodynamically into non-obstructive HCM (LOVTG<30 mmHg), resting obstructive HCM (LOVTG≥30 mmHg) and occult obstructive HCM (LOVTG<30 mmHg at rest but LOVTG≥30 mmHg after excitation)). Several parameters, including tpeak, Slope, SIpeak and LGE%, were compared by one-way analysis of variance and non-parametric test (Kruskal-Wallis). Correlations of tpeak, Slope, and SIpeak with LOVTG peak, and LGE% were analyzed by Spearman.
RESULTS ➀ Between the HCM patients and the control group, the left ventricular mass index (MI), left ventricular end-diastolic wall thickness, left ventricular end-diastolic volume, diastolic volume, left ventricular end-systolic volume, NT-proBNP, CTNI, CK-MB, NYHA cardiac functionIII/IV were significantly increased in the HCM group, with statistical differences between the two groups. ➁ The LGE% of resting obstructive HCM and non-obstructive HCM and occult obstructive HCM was significant. Tpeak, Slope and SIpeak were significantly different between the control group and the HCM group, among which the resting obstructive HCM tpeak was significantly increased, Slope and SIpeak were significantly decreased. There were significant differences in tpeak and SIpeak between obstructive HCM and non-obstructive HCM. There was a significant difference in tpeak between resting obstructive HCM and occult obstructive HCM. ③ There were significant statistical differences in tpeak, Slope and SIpeak between the control and HCM groups, including significantly increased resting obstructive HCM tpeak, decreased Slope and SIpeak, resting obstructive HCM and non-obstructive HCM tpeak and SIpeak, and tpeak between resting obstructive HCM and occult obstructive HCM.
CONCLUSIONS Using the cardiac magnetic resonance of First-pass-perfusion imaging combined with delayed-enhancement imaging can quantitatively evaluate the coronary microvascular function in HCM patients and has the value of early evaluation of microvascular dysfunction.
GW34-e0180
Di Zhou, Minjie Lu
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences
OBJECTIVES Dilated cardiomyopathy (DCM) with a severely reduced left ventricular ejection fraction (LVEF) of ≤35% is associated with a high risk of sudden cardiac death (SCD) and heart failure (HF) events. This study aims to develop a CMR imaging-based risk stratification model for DCM patients with LVEF≤35%, to improve clinical decision-making and ultimately, patient outcomes.
METHODS A total of 937 patients with DCM and LVEF≤35% were retrospectively included in this study. The arrhythmic endpoint was a composite of sudden cardiac death (SCD) or aborted SCD, while the HF endpoint was a composite of HF death or heart transplantation. Survival estimates were calculated by Cox regression analyses and competing risk regression analyses. The external validation sample comprised 335 retrospectively enrolled patients with DCM and LVEF≤35%. Kaplan–Meier survival analyses were assessed for the categories of risk stratified, along with a log-rank test.
RESULTS During a median follow-up of 96.1 months (IQR: 71.8–115.1 months), 129 patients reached the arrhythmic endpoints and 158 patients reached the HF endpoints. A 5% increment in late gadolinium enhancement (LGE) was associated with a 45.6% higher risk of SCD or aborted SCD (C-statistic: 0.72), and a 5 mm/m2 increment in left atrial diameter index (LADi) was associated with a 40% higher risk of HF death or HTx (C-statistic: 0.79). The C-statistics in the external validation cohort were 0.77 and 0.77, respectively. Our CMR-based risk stratification model systematically classified the SCD/aborted SCD and heart failure death/heart transplantation risk for patients with LVEF≤35%. Compared to low risk-SCD patients with LVEF 20–35% and LGE negative, the high risk-SCD patients with LVEF<20% and LGE≥8.9% experienced a 9.27-fold higher risk of arrhythmic events. Patients with LVEF<20% and LADi≥24.4 mm/m2 had the highest risk of HF endpoint (annual event rate: 4.91%, P<0.001).
CONCLUSIONS LGE and LADi are independently risk factors for predicting survival in a large cohort of patients with DCM and LVEF≤35%. Our novel risk stratification may guide timely interventions such as ICD implantation, heart transplantation, LV assist device implementation, or referral for HF specialty care, ultimately improving outcomes for patients with DCM and LVEF≤35%.
GW34-e0217
Xiaojin Feng1, Peijun Liu2, Tianchen Guo1, Xiaohang Liu1, Xinhao Li1, Huaxia Yang3, Wei Chen1, Shuyang Zhang1, Yining Wang2
1Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
2Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
3Department of Rheumatology and Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
OBJECTIVES Patients with systemic lupus erythematosus (SLE) typically develop myocardial fibrosis. However, the connection between myocardial fibrosis and left ventricular (LV) myocardial dysfunction remains unknown. We aim to investigate the association between myocardial dysfunction and the presence, degree, and location of myocardial fibrosis in SLE.
METHODS A hundred and nine SLE patients were screened of whom 74 patients were included. Myocardial fibrosis was evaluated at cardiac magnetic resonance by qualitative and quantitative assessment of late gadolinium enhancement (LGE). Global and regional myocardial work (MW) and strain analyses were performed based on the pressure-strain loop method using speckle tracking echocardiography to quantitatively measure LV myocardial function. MW indices included myocardial work index (WI), constructive work (CW), wasted work (WW), and work efficiency (WE).
RESULTS The incidence of LGE in the myocardium of SLE patients was 68% (50/74). Compared with healthy controls (n=37), LV global functional parameters including global longitudinal strain (LS), peak strain dispersion (PSD), and MW indices were all degraded whether LGE was present or not in SLE patients (all P<0.05). However, regional analysis according to the free wall and septum showed regional function was more damaged in LGE-positive regions compared to LGE-negative regions (LS, −13.6±4.1% versus −15.1±3.6%, P=0.02; WI, 1238±308 mmHg% versus 1360±355 mmHg%, P=0.032; CW, 1523±333 mmHg% versus 1655±375 mmHg%, P=0.03; WE, 88.5±6.4% versus 90.7±4.6%, P=0.024). As for LGE degrees, severe fibrosis was associated with more severe dysfunction compared to moderate fibrosis, including lower global WE (88.4±5.8% versus 91.5±3.1%, P=0.017), LV free-wall (LVFW) WE (88.5±6.3% versus 91.5±3.7%, P=0.038), and septal WE (88.0±6.9% versus 91.3±3.1%, P=0.025). Although LGE was located more in the septum than in the free wall, the effect of LVFW LGE on myocardial function tended to be more pronounced. Patients with LVFW fibrosis had worse global function, including lower global WE (87.4±4.6% versus 90.9±4.8%, P=0.007), higher global WW (156 [138–178] mmHg% versus 125 [82–181] mmHg%, P=0.043), and more increased PSD (74±25 ms versus 55±14 ms, P=0.005), compared with patients without LVFW fibrosis. Meanwhile, the regional function was also more severely affected in patients with LVFW fibrosis (LVFW LS, −13.4±4.6% versus −15.7±3.9%, P=0.037; LVFW WE 87.1±6.2% versus 91.4±4.5%, P=0.002; LVFW WW, 152 [131–193] mmHg% versus 109 [82–185] mmHg%, P=0.02). Furthermore, patients with LVFW-only LGE displayed higher PSD than those with septal-only LGE when fibrosis degrees were comparable (79±29 ms versus 54±15 ms, P=0.039).
CONCLUSIONS In SLE patients, the presence of fibrosis tended to disturb regional myocardial contractile function. The degree of fibrosis affected both global and regional myocardial function. LVFW fibrosis was associated with notable impairment of contractility and synchronization in the global LV and regional LVFW myocardium.
GW34-e0301
Shujuan Yang, Shuiyun Wang, Shihua Zhao
Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College/National Center for Cardiovascular Diseases
OBJECTIVES Left atrial (LA) enlargement and dysfunction are frequently seen in patients with hypertrophic obstructive cardiomyopathy (HOCM). Feature tracking (FT) allows sensitive quantification of LA functional remodeling regardless of LA size. However, the association of preoperative LA strain assessed by cardiac magnetic resonance (CMR)-FT with the late outcome of HOCM patients after surgical myectomy remains unknown. This study aims to investigate the prognostic value of preoperative FT-derived LA strain among patients with HOCM following septal myectomy.
METHODS In this retrospective, single-center study, 802 adult patients with HOCM who underwent septal myectomy from January 2010 through December 2017 were included. All patients underwent preoperative CMR with complete clinical outcome follow-up. Preoperative LA phasic strains were measured using CMR-FT. Primary endpoint included all-cause mortality, heart transplantation, unscheduled hospitalization for heart failure, and stroke. Secondary endpoint included all-cause mortality and heart transplantation.
RESULTS Of the 802 patients in this study, 116 experienced primary endpoints, 38 experienced secondary endpoints, and 18 experienced SCD/aborted SCD during a median follow-up of 56.7 (IQR, 40.2–78.6) months. Among all LA volumetric and functional parameters, LA reservoir strain held the best performance for predicting the occurrence of adverse outcomes. Compared with the group with LA reservoir strain >22.9% (median), the annual event rate of primary endpoint (4.2 vs. 1.7%, P<0.0001), secondary endpoint (1.5 vs. 0.4%, P=0.0005), and sudden cardiac death (SCD) (0.7 vs. 0.2%, P=0.047) was significantly higher in the group with LA reservoir strain ≤22.9%. In multivariable Cox proportional hazards regression analysis, LA reservoir strain ≤22.9% was independently associated with primary endpoint (HR 1.98, 95% CI 1.26–3.11, P=0.003) and secondary endpoint (HR 3.71, 95% CI 1.73–7.92, P=0.001). Incorporating LA reservoir strain, the performance of the 2014 HCM Risk-SCD score improved for sudden cardiac death prediction (C-statistic: from 0.62 to 0.69; log-likelihood: from −110.31 to −108.27, P=0.04).
CONCLUSIONS In patients with HOCM undergoing septal myectomy, reduced preoperative LA reservoir strain assessed by CMR-FT is independently associated with postoperative adverse outcomes. LA reservoir strain shows the potential to optimize the risk stratification of SCD incidents in patients with HOCM after surgical myectomy.
GW34-e0325
Xinyi Li1,2,3, Ziyi Zhang2,3, Xinyi Wang1,2,3, Lei Jiang1,2,3
1South China University of Technology
2Guangdong Provincial People’s Hospital
3Guangdong Cardiovascular Institute
OBJECTIVES Hypoalbuminemia (HA) was extensively used to diagnose malnutrition in older adults. Malnutrition was associated with mortality in elderly patients with cardiovascular diseases. The relationship between HA and clinical outcomes in elderly patients with non-ischemic dilated cardiomyopathy (NIDCM) remains unknown.
METHODS In the present study, a total of 1058 consecutive patients with NIDCM (age ≥60 years) were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to assess the association of HA with clinical outcomes.
RESULTS Patients with HA were older (69.29±6.67 vs. 67.61±5.90 years, P<0.001) and had higher prevalence of in-hospital and long-term death than those without (6.9 vs. 1.7%, 50.7 vs. 35.2%, P<0.001). In addition, more patients in HA group combined a NRS2002 score ≥3 (a tool to identify patients with high risk of malnutrition). Logistic regression analysis showed that HA was significantly related to in-hospital death (OR: 4.334, 95% CI: 2.185~8.597, P<0.001). Kaplan–Meier survival analysis showed that patients with HA had worse prognosis than those with non-HA (log-rank χ2 28.96, P<0.001). After adjusting for age, serum creatinine, HDL-C, AST/ALT ratio, LVEF and diabetes, HA remained an independent predictor for long-term death in multivariate Cox proportional hazard regression model (HR: 1.322, 95% CI: 1.046~1.670, P=0.019).
CONCLUSIONS HA was associated with increased risk of in-hospital and long-term mortality in elderly patients with NIDCM. Clinicians should consider the effect of HA when estimating the prognosis of patients with NIDCM. These findings might support that theory that malnutrition and oxidative stress play key roles in the prognosis of NIDCM.
GW34-e0419
Dong Zhixiang, Zhao Shihua
Department of Magnetic Resonance Imaging, Fuwai Hospital, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College
OBJECTIVES Strain analysis has demonstrated promising future in the diagnosis and prognosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to find out a clinical available strain parameter for the diagnosis of ARVC based on revised Task Force Criteria (rTFC), and to verify its value in the prognosis of the patients.
METHODS CMR images of 247 rTFC diagnosed ARVC patients were retrospectively analyzed. Patients were divided into ‘possible’ (n=25), ‘borderline’ (n=40) and ‘definite’ (n=182) ARVC following rTFC. Using cardiac magnetic resonance feature tracking (CMR-FT), we evaluated biventricular global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) of all participants. Primary outcome was defined as a composite of cardiovascular events including cardiovascular death, heart transplantation, aborted cardiac arrest, ventricular fibrillation/flutter, and appropriate ICD discharge.
RESULTS Patients with definite ARVC had significantly reduced RV global strain in all three directions than possible and borderline ARVC patients (all P<0.01). RV GLS was an independent predictor for presence disease (OR, 1.10 [1.05–1.16]; P<0.01). Patients with ‘possible’ or ‘borderline’ diagnosis were redefined as ‘suspected’ ARVC. The best cut-off values for RV GLS to identify ‘suspected’ ARVC patients and ‘definite’ ARVC patients were −20.02% and −17.32% respectively. During 3.4 (2.0–4.9) years of follow-up, 22% (n=55) of patients developed primary endpoint events. Multivariable analysis showed that RV GLS was independently associated with the occurrence of cardiovascular events (Hazard Ratio, 1.12 [1.05–1.20]; P<0.01). Kaplan-Meier analysis showed that patients with RV GLS≥−17.32% had a higher risk of combined cardiovascular events (log-rank P<0.01).
CONCLUSIONS As a convenient and sensitive imaging method to quantitatively assess right ventricular dysfunction, RV GLS derived from CMR-FT might provide a new insight into the diagnosis and prognosis of ARVC, offering a preferred imaging method in the first visit and follow-up of the disease.
GW34-e0468
Yilu Wang1, Li Wang2, Juan Wang3, Minghu Xiao4, Xiaoying Xi2, Bixi Chen2, Yao Su2, Yu Zhang2, Zhixiang Dong5, Shihua Zhao5, Ping Zhang1, Minfu Yang2
1Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
2Department of Nuclear Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
3Emergency and Critical Care Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
4Department of Echocardiography, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
5Department of Magnetic Resonance Imaging, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
OBJECTIVES Myocardial fibrosis of hypertrophic cardiomyopathy (HCM) leads to heart failure, arrhythmia, and sudden death. To prevent fibrosis and intervene in the reversible phase, an increasing number of studies focus on the activation of fibroblasts, which is the initiation and reversible phase of fibrosis. Fluorine 18 (18F) fibroblast activation protein inhibitor (FAPI) PET/CT imaging can identify fibroblast activation in cardiovascular diseases, including HCM, as we previously reported. A possible explanation for the poorer prognosis observed in HCM patients with sarcomere mutations, which are mainly pathogenic geses, is the hygher prevalence and severity of myocardial fibrosis. However, the presence of more intense fibroblast activation in HCM patients with sarcomere mutations needs further investigation.
METHODS This observational study included HCM patients over 18 years old without surgical or other interventions. FAPI imaging was used to determine the intensity and range of fibroblast activation, and the difference in fibroblast activation between patients with and without sarcomere gene mutations was compared.
RESULTS Among 61 HCM patients, 31 carried sarcomere gene mutations. These patients had significantly higher SUVmax values than those without mutations (8.58±1.71 vs. 7.33±2.59, P=0.031), especially in the non-obstructive subgroup (8.54±1.61 vs. 6.80±1.99, P=0.006). Carrying sarcomere gene mutations was positively correlated with FAPI imaging SUVmax (r=0.263, P=0.041), more significant in the non-obstructive subgroup (r=0.531, P=0.001). In the non-obstructive subgroup, patients with sarcomere gene mutations also had significantly higher TBRmyo values (9.66±1.65 vs. 7.94±2.46, P=0.015) and more uptake in the right ventricle (38.1 vs. 11.1%, P=0.050). After adjusting for confounding factors, carrying sarcomere gene mutations still had a significant impact on SUVmax (P=0.035, r=1.250).
CONCLUSIONS This is the first study to confirm the relationship between sarcomere gene mutations and fibroblast activation in HCM patients using FAPI imaging. Carrying sarcomere gene mutations, the primary pathogenic factor of HCM, is associated with higher intensity of fibroblast activation, particularly evident in non-obstructive patients. The effect of sarcomere gene mutations on fibroblast activation is independent of patient age, sex, disease duration, myocardial thickness, and obstruction. This provides an indication for identifying which type of HCM patients should initiate early inhibition of fibroblast activation and myocardial remodeling therapy. The correlation between the extent of fibroblast activation in HCM hearts and disease duration and left atrial dilation suggests that fibroblast activation occurs throughout the disease course, and corresponding treatment should be continuous.
GW34-e0478
Yilu Wang
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University
OBJECTIVES Hypertrophic cardiomyopathy (HCM) has a high incidence of atrial fibrillation (AF), which is an important cause of ischemic stroke. However, the incidence of ischemic stroke was also higher in patients with HCM without AF. We investigated the incidence and risk factors of ischemic stroke in patients with HCM in the absence of AF.
METHODS HCM without AF outpatients treated in Emergency General Hospital from 2013.9 to 2022.9 was analyzed. Patients were divided into stroke group and non-stroke group according to whether ischemic stroke occurred during follow-up. Cox regression models were used to analyze the independent risk factors of ischemic stroke in HCM patients without AF. ROC curve was used to determine the optimal threshold for the continuity variable.
RESULTS A total of 378 HCM patients without AF were enrolled, with an average follow-up of 7.1±3.7 years, 19 patients (5.03%) experienced ischemic stroke were in the stroke group and 359 patients were in the non-stroke group. The average annual incidence of ischemic stroke was approximately 0.63%. The age of diagnosis in the stroke group was higher than non-stroke group [(52.84±11.12 vs. 47.19±14.53 years, P<0.05), and the diameter of the left atrium was larger than non-stroke group [(42.94±6.84 vs. 39.19±6.25 mm, P<0.05)], erythrocyte sedimentation rate (ESR) level was also higher than non-stroke [(14.47±2.84 vs. 7.63±0.72 mm/h, P<0.05)]. Multivariate Cox regression model analysis showed that smoking history (HR=7.145, 95% CI: 1.499–34.054) and ESR (HR=1.047, 95% CI: 1.010–1.085) were independent risks factors for ischemic stroke in HCM patients without AF. The best predictive threshold of ESR obtained by ROC curve was 11.5 mm/h.
CONCLUSIONS The annual incidence of ischemic stroke of HCM patients without AF in this study is about 0.63%; smoking and increased ESR (over 11.5 mm/h) are independent risk factors for ischemic stroke in HCM patients without AF.
GW34-e0543
Angwei Gong
The Second Hospital of Hebei Medical University
OBJECTIVES The purpose of this study was to investigate the causal relationship between the lipid indicators and hypertrophic obstructive cardiomyopathy using Mendelian randomization analysis, to provide genetic evidence to support the association between lipids and the risk of hypertrophic obstructive cardiomyopathy.
METHODS We employed the two-sample Mendelian randomization analysis to explore the blood lipids’ effect on hypertrophic obstructive cardiomyopathy, including high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides, and apolipoprotein B. We used inverse variance weighed method and weighted median and MR-Egger to study the causal relationship between lipid indicators and hypertrophic obstructive cardiomyopathy, in which inverse variance weighed method was the main method. At the same time, we applied the odds ratios (ORs), P-values, and confidence intervals (CIs) to estimate the strength and significance of the associations between apolipoprotein B and hypertrophic obstructive cardiomyopathy. Our data associated with lipids and hypertrophic obstructive cardiomyopathy were collected from the Genome-wide association study. Sensitivity analyses, including MR-PRESSO, Cochran’s Q test, “leave-one-out”, and the MR-Egger method, were conducted to ensure the robustness of our study.
RESULTS The inverse variance weighted analysis showed a significant negative correlation between apolipoprotein B and hypertrophic obstructive cardiomyopathy, with the odds ratio (OR) of 0.607 [95% confidence interval (CI): 0.413–0.892, P=0.011]. In addition, sensitivity analysis ensured the robustness and reliability of our results.
CONCLUSIONS In summary, our Mendelian randomization analysis shows there may be a negative causal relationship between apolipoprotein B and hypertrophic obstructive cardiomyopathy.
GW34-e0645
Bowen Lou, Zuyi Yuan, Jianqing She
First Affiliated Hospital of Xi’an Jiaotong University
OBJECTIVES Myocarditis has emerged as a rare but lethal Immune checkpoint inhibitor (ICI)-associated toxicity. However, the exact mechanism and the specific therapeutic targets remain underexplored. In this study, we aim to characterize the transcriptomic profiles from ICI related myocarditis.
METHODS PBMC samples were taken from the patient with newly diagnosed lung squamous cell carcinoma before treatment (control), with PD-1 inhibitor therapy who did not develop myocarditis (PD-1), and patients with fulminant ICI related myocarditis during disease remission. Subpopulation determination, functional analysis, single-cell trajectory and cell-cell interaction analysis were performed after scRNA-seq. Then, bulk-RNA sequencing was performed for further validation.
RESULTS We have presented the altered landscape of immune cells and differential genes in ICI related myocarditis during the disease activity and remission using scRNA-seq. Monocyte and NK cell subpopulations as well as B cell contribute to the regulation of innate immunity and inflammation in ICI related myocarditis. With integrated analysis of scRNA-seq and bulk sequencing, we identified S100A protein family as a potential serum marker for ICIs related myocarditis.
CONCLUSIONS By identifying altered pathways and highlighting a catalog of marker genes, this study has created a cell atlas of peripheral blood mononuclear cell during immune checkpoint inhibitor (ICI) related myocarditis, which would shed light on the pathophysiological mechanism and potential therapeutic targets of ICI related myocarditis in continuous exploration.
GW34-e0790
Keying Bi1, Ke Wan2, Yuanwei Xu1, Jie Wang1, Weihao Li1, Yucheng Chen1
1Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
2Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
OBJECTIVES The clinical value of cardiac magnetic resonance (CMR) imaging-derived first-pass perfusion parameters in patients with light-chain (AL) amyloidosis remains unknown.
METHODS This prospective study included 226 patients with biopsy-proven AL amyloidosis who underwent CMR between November 2011 to June 2021, with 43 healthy volunteers as normal controls. pulmonary transit time (PTT), Corrected PTT (PTTc), and pulmonary transit beats (PTB) were quantified and calculated from first-pass perfusion image. All-cause mortality was defined as the primary endpoint. Receiver operating characteristic curve, Kaplan-Meier analysis and Cox regression were used for statistical analyses.
RESULTS PTT [area under the curve (AUC) 0.84], P<0.001, PTTc (AUC 0.84, P<0.001), and PTB (AUC 0.81, P<0.001) were sensitive to identified cardiac involvement in patients with AL amyloidosis. Amongst 226 patients [143 men, 58.80 years±9.86], all-cause death occurred in 166 patients (73.5%) during a median follow-up of 35 months (interquartile range, 25–51 months). In multivariable-adjusted cox regression analysis, PTT was an independent predictor of mortality after adjustment for known clinical [HR 1.061, 95% confidence interval (CI) 1.021–1.102, P=0.003], biochemical (HR 1.055, 95% CI 1.014–1.097, P<0.008), and CMR (HR 1.077, 95% CI 1.034–1.123, P=0.002) risk factors, respectively. In the Kaplan-Meier analysis, PTT cutoff value provided further risk stratification in the subgroup of NYHA class III (P=0.039), Mayo stage 2004 III (P<0.001), and transmural late gadolinium enhancement (LGE) pattern (P<0.001).
CONCLUSIONS CMR Imaging-derived First-Pass Perfusion Parameters were sensitive for the diagnosis of cardiac amyloidosis and aid for further risk stratification in patients with advanced cardiac amyloidosis.
GW34-e0818
Shengsheng Zhuang1, Dong Chang1, Zhuang Tian2
1Department of Cardiology, The Xiamen Cardiovascular Hospital of Xiamen University, Xiamen, China
2Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
OBJECTIVES The flowchart to diagnose cardiac amyloidosis (CA) is well described. However, techniques such as bone scintigraphy or heart biopsy may not be available in primary hospitals, where the misdiagnosis and delay treatment could happen. Reliable and easy-used red flags are still needed. This study aimed to propose a novel computer simulation based electrocardiography (ECG) voltage index to screen cardiac amyloidosis patients with higher sensitivity and specificity than other voltage indexes.
METHODS We published a software (CPCC ID: 2021SR1488171) that uses ECG, chest CT and echocardiography as inputs and automatically calculates the novel ECG voltage index as outputs. The software integrates algorithms to generate patient-specific three-dimensional models of the thorax, heart and lungs with parameters of echocardiography and chest CT. Filling heart ventricles with healthy myocardium, forward simulation provides the theoretical ECG voltages of each patient. Then, a novel index can be calculated as the ratio of the real ECG voltages and theoretical ECG voltages, which indicates the deviation of the patient’s myocardium from the healthy myocardium. All process can be finished by a single doctor under the guiding of the software without knowing anything about the algorithms. To investigate the diagnosis power of the novel index, we recruited validation cohorts consisted of 101 consecutive CA patients, 125 disease controls and 89 healthy controls from Peking Union Medical College Hospital. Area under curve (AUC) analysis was used to compare the sensitivity and specificity of the novel index, Sokolow-lyon index and voltage to mass ratio.
RESULTS The novel indexes of CA patients were significantly lower than those of the controls (0.55±0.32). When used to differentiate CA patients from healthy controls, the AUC values of this novel index, Sokolow-Lyon voltage and voltage to mass ratio are 0.943, 0.714, and 0.912 respectively. When used to differentiate CA from hypertrophic cardiomyopathy, AUC values of these indexes are 0.831, 0.819 and 0.793. When used to differentiate CA from hypertension cardiomyopathy, the AUC values of these indexes are 0.916, 0.899 and 0.865. The ECG voltage index we proposed made the best index to screen CA patients with largest AUC.
CONCLUSIONS The novel index proposed in this study integrates the information of ECG, body geometry and heart geometry. It only requires the results of ECG, chest CT (no enhanced) and echocardiography. The index is convenient to be calculated in primary hospital with the help of our open-source software and has higher sensitivity and accuracy as a red flag sign to diagnose CA.
GW34-e1003
Wei Gao1,2, Wei Zhao1, Tianfu Qi1, Zhiming Li1, Jie Deng1, Wei Chen1
1The First Affiliated Hospital of Kunming Medical University
2The First People’s Hospital of Honghe State
OBJECTIVES Nonobstructive hypertrophic cardiomyopathy (NOHCM) should no longer be considered a low-risk condition. Coronary microvascular dysfunction (CMD) may mediate the development of adverse cardiovascular outcomes in patients with NOHCM, but there have been few investigations of CMD specifically in this population. This study aims to evaluate myocardial microvascular function in NOHCM using CMR first-pass perfusion imaging and determine significant risk factors contributing to CMD.
METHODS The study cohort consisted of 47 NOHCM and 18 obstructive hypertrophic cardiomyopathy (OHCM), and 28 healthy controls (HCs). Left ventricular outflow tract (LVOT) and aorta (AO) diameter ratio, Maximal wall thickness, LGE, and perfusion parameters, including time to peak (Tpeak), peak signal intensity (SIpeak), and upslope were calculated globally and segmentally. Univariable and multivariable linear regression analyses were performed to assess the potential risk factors for CMD.
RESULTS Globally, the OHCM group had significantly increased Tpeak and reduced upslope (both P<0.001) compared to the NOHCM group; the NOHCM group had significantly prolonged Tpeak and decreased upslope compared with HCs (Tpeak: 30.85±3.35 vs. 25.10±3.69 s; upslope: 18.36±4.73 vs. 23.62±4.84, both P<0.001). Myocardial segments with no hypertrophy and LGE (n=217) in NOHCM patients had a longer Tpeak and lower upslope compared with segments of HCs (n=448) (Tpeak: 29.98±3.64 vs. 25.11±4.11 s; upslope: 18.99±4.88 vs. 23.84±6.99, both P<0.001). In NOHCM patients, LVOT/AO diameter ratio was independently associated with Tpeak (adjusted β: −0.501, P<0.001) and upslope (adjusted β: −0.499, P=0.002).
CONCLUSIONS CMD can occur in NOHCM patients at rest, even in seemingly normal myocardial segments. The LVOT/AO diameter ratio was an independent risk factor of microvascular dysfunction, which implies it has potential added value in the management of NOHCM patients.
GW34-e1082
Fei Liu, Chenglin Li, Xiaolei Yang, Yunlong Xia
First Affiliated Hospital of Dalian Medical University
OBJECTIVES Data on the effect of atrial remodeling on cardiovascular diseases (CVD) are lacking. The objective of the present study is to investigate the predictive value of atrial cardiomyopathy (ACM) for hospitalization due to CVD in Type II diabetes mellitus (T2DM) patients.
METHODS This study is a cohort study that enrolled 10,751 hospitalized patients diagnosed with T2DM in First Affiliated Hospital of Dalian Medical University from January 2011 to July 2021. The primary endpoints were the first hospitalization due to any CVD-related events including myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), or ischemic stroke. P-wave terminal force in V1 (PTFV1) was derived from digital 12-lead ECGs on admission and was automatically measured using the GE Marquette 12-SL program (GE Marquette, Milwaukee, WI). We explored the association between quantitative measures of PTFV1 level and CVD-related hospitalization using restricted cubic spline analysis to stratify patients into low- and high-risk groups based on the new reference values of PTFV1. According to the new reference values of PTFV1 and LAD, ACM was defined as PTFV1 ≥3145 μV·ms or left atrial enlargement (LAD: male ≥40 mm; female ≥38 mm). Compared the prevalence of ACM between patients with CVD-related hospitalization and those without CVD-related hospitalization. Cox proportional model was used to demonstrate the association between ACM and the hospitalization due to CVD-related events in T2DM patients. We further performed a multivariate analysis by considering the significant variables based on clinical plausibility and P value <0.05 in the univariate Cox analysis. Cumulative incidence function (CIF) curves were established to compare the cumulative incidence of each type of CVD-related hospitalization among patients with and without ACM. Considering for the competing risks (MI, HF, AF), the competing risk model was used to verify the independent predictive effect of ACM on ischemic stroke-related hospitalization. To further examine the relationship between ACM and ischemic stroke-related hospitalization, subgroup analysis was performed according to the presence or absence of left ventricular hypertrophy (LVH).
RESULTS ACM occurred in 36.3% of the patients the prevalence of ACM in those with CVD-related hospitalization was relatively high compared to those without CVD-related hospitalization (P<0.001). After a average follow-up period of 42.33 months, a total of 1977 (18.4%) patients experienced hospitalization related to CVD-related events. The multivariate Cox regression analysis demonstrated that ACM was significantly associated with CVD-related hospitalization in T2DM patients (HR, 1.19 [95% CI, 1.05–1.34], P=0.006). The competing risk model showed the strong association between ACM and ischemic stroke-related hospitalization independent of AF with an adjusted sub-distribution hazard of 2.29 (95% CI, 1.63–3.25, P< 0.001). Similarly, subgroup analysis showed that ACM was associated with ischemic stroke-related hospitalization independent of AF in patients with and without LVH.
CONCLUSIONS ACM, a marker for evaluating early atrial remodeling in clinical practice, is significantly associated with CVD-related hospitalization in patients with T2DM and is an independent predictor of ischemic stroke-related hospitalization in patients with T2DM independent of AF. Thus, ACM may improve risk stratification in T2DM patients, which may lead to a significant reduction of the subsequent risk of CVD.
GW34-e1177
Zhu Li, Yunshu Li, Yuanjing Li, Yintao Chen
The First Affiliated Hospital of Chongqing Medical University
OBJECTIVES Hypertrophic cardiomyopathy (HCM) is the most common type of rare cardiomyopathy and is a leading cause of sudden cardiac death in adolescents and athletes. In its end-stage, it is characterized by heart failure and arrhythmias. Recent studies have suggested that the incidence of HCM may be underestimated in our country. There have been several deficiencies regarding the early diagnosis, standardized treatment, and management of HCM. The purpose of this study is to gain an understanding of the previous diagnostic and treatment practices of HCM and identify any deficiencies. By analyzing and summarizing this information, we aim to provide guidance and a basis for the next steps in precision screening and optimizing treatment for HCM.
METHODS This study included patients from the cardiology department of our center, who were diagnosed with ventricular septal hypertrophy (≥15 mm) based on echocardiography findings between January 2018 and June 2022. Patients with rheumatic heart disease (including valve replacement), moderate to severe aortic stenosis or regurgitation, congenital heart disease, aortic aneurysms or dissections, myocardial amyloidosis, or infective endocarditis were excluded. Relevant data including demographic characteristics, medical history, results of biochemical and physical examinations, as well as medication information, were collected.
RESULTS A total of 312 patients were included in the study, with a mean age of 60.3 years. Among them, 68.6% (n=214) were male. Of the participants, 54.2% (n=169) exhibited symptoms of heart failure (NYHA class II-IV). Additionally, 74% (n=231) of patients had a history of hypertension, 23.1% (n=72) had coronary artery disease, and 10.6% (n=33) presented with paroxysmal atrial fibrillation. The mean thickness of the interventricular septum in this population was 16.7 mm. Approximately 16.0% (n=50) of the patients had left ventricular outflow tract obstruction (LVOTG ≥30 mmHg), and another 9.6% (n=30) exhibited systolic anterior motion (SAM) phenomenon. As for treatment, approximately 64.7% (n=202) of patients were received beta-blockers, 1.6% (n=5) were using non-dihydropyridine calcium channel blockers, and around 57.7% (n=180) were taking renin-angiotensin-aldosterone system (RAAS) inhibitors. Furthermore, approximately 5.8% (n=18) of patients had pacemaker implantation, and 3.9% (n=12) underwent interventional reduction therapy.
CONCLUSIONS Currently, there are still deficiencies in the diagnosis and treatment of HCM. Early diagnosis based solely on ultrasound may have low sensitivity or potential for misdiagnosis. Recently, the integration of cardiac magnetic resonance imaging, nuclear imaging, metabolomics, and genetic testing has contributed to more accurate diagnosis and assessment of disease severity. Furthermore, there has been a lack of evidence-based medications with proven prognostic benefits in the past. Even recommended first-line medications have been underutilized or administered at suboptimal doses. However, with the emergence of targeted therapies such as Mavacamten, there are now more options available for optimizing HCM treatment. Additionally, when combined with cardiac rehabilitation programs and the establishment of effective long-term follow-up mechanisms, comprehensive management of HCM can be achieved, leading to greater benefits for patients.
GW34-e1238
Kai Kang, Hongzhuang Wang, Lishan Zeng, Dajun Chai
The First Affiliated Hospital, Fujian Medical University
OBJECTIVES Heterogeneous electrophysiologic activation in hypertrophic cardiomyopathy (HCM) causes abnormal 12-lead electrocardiogram (ECG) parameters. Conventional ECG indicators are not sufficient to specifically identify HCM. This study aimed to discover novel ECG parameters based on computer vision segmentation technology for the specific diagnosis of HCM.
METHODS Computer vision segmentation technology was used to automatically recognize ECG images and analyze 16 novel ECG parameters, such as R/S ratio, ventricular activation time (VAT), QRS complex area (QRS area), Q-wave amplitude in lead avR (Q (avR)), R-wave amplitude in lead V5 (RV5), and the sum of the R-wave amplitude in lead V5 and the S-wave amplitude in lead V1 (RV5+SV1). Receiver-operating-characteristic (ROC) curve analysis and consistency test were performed with echocardiography to extract novel specific diagnostic parameters.
RESULTS The values of R/S ratios in leads I, II, V1–V3, and V5–V6, QRS area in lead I, II, III, avR, avL, avF, and V1–V6, Q (avR), VAT, RV5, and RV5+SV1 were significantly higher in the HCM group than in the control group. ROC curve analysis and consistency test showed that the QRS areas in leads I (kappa coefficient of 0.898, sensitivity of 92.86% and specificity of 97.68%) and V5 (kappa coefficient of 0.777, sensitivity of 82.14% and specificity of 95.54%) could be used to diagnose HCM. The parallel test (kappa coefficient of 0.8571, sensitivity of 100% and specificity of 93.75% vs. kappa coefficient of 0.8438, sensitivity of 77.14% and specificity of 100%) had a higher diagnostic performance than the serial test.
CONCLUSIONS Based on the computer vision segmentation technology, the QRS areas in leads I and V5 become the valuable novel diagnostic markers for HCM, and parallel testing of them can be used to achieve high diagnostic performance in HCM.
GW34-e1275
Yunshu Li, Zhu Li, Yuanjing Li, Yintao Chen
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University
OBJECTIVES In the surgical treatment of hypertrophic obstructive cardiomyopathy, percutaneous transluminal septal myocardial ablation (PTSMA) involves the injection of chemical agents (such as absolute alcohol or gelatin sponge) into one or multiple septal branches of the left anterior descending coronary artery to induce myocardial infarction in the corresponding hypertrophic segments, thereby reducing left ventricular outflow tract gradient (LVOTG) and obstruction. In our center, we have adopted a physical occlusion method using absorbable gelatin sponge to occlude the target septal branches as an alternative to absolute alcohol, aiming to modify the conventional PTSMA procedure and reduce the occurrence of associated complications. This study aims to retrospectively summarize and analyze the differences in efficacy and safety between the ablation using these two different media in patients with hypertrophic cardiomyopathy (HCM) who underwent septal ablation in our center within the past five years.
METHODS This study included patients who underwent percutaneous transcatheter ventricular septal myocardial ablation in our center from January 2018 to June 2022. Patients were divided into two groups based on the use of chemical agents during the procedure: the “absolute alcohol” group and the “gelatin sponge” group. Clinical data, discharge diagnoses, medication information, and perioperative conditions were collected to compare the efficacy of ablation and the incidence of complications between the two groups. Statistical analysis was performed using Fisher’s exact test. A P-value of <0.05 was considered statistically significant.
RESULTS A total of 26 hospitalized patients were included in this study, with a mean age of 57.6 years. In terms of the application of chemical agents, 53.8% of patients used absolute alcohol. After the procedure, 28.6% of patients showed a reduction in left ventricular outflow tract pressure gradient exceeding 50% compared to baseline. Additionally, 28.5% of patients experienced complications, specifically atrioventricular conduction block. On the other hand, 46.2% of patients used gelatin sponge. After the procedure, 41.7% of patients demonstrated a reduction in left ventricular outflow tract pressure gradient exceeding 50% compared to baseline, and no complications were observed. Fisher’s exact test was used to calculate the significance between the two groups. In the absolute alcohol group, out of 14 individuals, 4 experienced complications, while in the gelatin sponge group, none of the 12 individuals experienced complications. The two-tailed P-value was 0.0297 (P<0.05).
CONCLUSIONS In this study, the use of gelatin sponge for ablation significantly reduced the occurrence of complications such as atrioventricular conduction block during the procedure, effectively reducing the risk of pacemaker dependency after ventricular septal ablation. Absolute alcohol has a higher incidence of complications due to its potential escape from the capillaries, which will lead to myocardial infarction in other regions. Unlike alcohol, gelatin sponge, due to its characteristic degradation and rapid aggregation in the body, prevents the medium from flowing to the left anterior descending coronary artery or other non-target areas through collateral circulation, resulting in a lower incidence of complications. In the future, larger-scale studies are needed to further clarify the advantages and safety of gelatin sponge as a medium for chemical ventricular septal ablation.
GW34-e1326
Xiaolei Li, Adi Dilare, Yitong Ma
First Affiliated Hospital of Xinjiang Medical University
OBJECTIVES Dilated cardiomyopathy (DCM) are frequently complicated by atrial fibrillation (AF) and leads to vascular embolism. The aim of this study was to develop and validate machine learning (ML) models for early screening of AF in DCM by using routine clinical indicators.
METHODS A total of 988 patients with DCM from the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed between 2016 and 2020 and 80% were assigned to the training set and 20% to the testing set. The least absolute shrinkage and selection operator (LASSO) was used in the selection of variables. Nine ML algorithms, including logistic regression (LR), decision tree (DT), K-nearest neighbors (KNN), random forest (RF), multiplayer perceptron (MLP), extreme gradient boosting machine (XGB), gradient boosting decision tree (GBDT), support vector machine (SVM), and Light Gradient Boosting Machine (LGBM), were used to construct AF screening models. The models were evaluated by combining several metrics, such as the area under the curve (AUC), accuracy score, sensitivity, specificity and F1 score. The SHapley Additive exPlanations (SHAP) method was used to demonstrate the interpretability of the optimal model.
RESULTS A total of 171 patients out of 988 DCM patients experienced AF, with an incidence of 17.31%. Six variables were eventually included in our model, namely age, ethnicity, left atrial internal diameter (LAd); left ventricular end-diastolic internal diameter (LVEDd), uric acid, and D-2 dimers. The AUC values of the nine prediction models ranged from 0.72 to 0.92. The XGB model showed the highest performance, with the following metrics: AUC (0.92, 95% CI: 0.88–0.93), accuracy (0.87), sensitivity (0.71), specificity (0.78) and F1 score (0.73). Each machine learning model also showed good calibration capability and clinical applicability. In the interpretability analysis, age was the most important factor influencing the performance of the XGB model, followed by LAd.
CONCLUSIONS The ML models developed could provide good performance for AF identification using routine clinical indicators. And XGB-based machine learning model could hopefully be applied in clinic for AF screening and prevention.
GW34-e1329
Lin Xie, Zedong He, Zhuheng Wu, Ke Lin
Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
OBJECTIVES Hypertrophic obstructive cardiomyopathy (HOCM) is a hereditary disease characterized by asymmetric myocardial hypertrophy and dynamic left ventricular outflow tract (LVOT) obstruction. Septal myectomy provides both LVOT obstruction elimination and symptom improvements, thus been recognized as the standard surgical treatment for HCOM. However, mitral valve abnormalities are also common in HOCM patients, and it is believed that these abnormalities contribute to systolic anterior motion (SAM) of the mitral leaflet and LVOT obstruction in some extent, but whether and how mitral valve procedures should be performed during surgical myectomy is still controversial. Previous studies have indicated that a relatively shallow myectomy combined with secondary chordal resection can provide better outcomes in HOCM patients with mild septal hypertrophy. We choose a combination of extended septal myectomy and secondary chordal resection in nonselective HOCM patients, and here we evaluate its effectiveness and potential advantages.
METHODS We retrospectively collected the data of patients with HOCM who underwent extended septal myectomy with secondary chordal resection at our center from 2014 to 2022. Patients’ echocardiographic data were collected preoperatively, before discharge and during follow-up, and the changes of atrial and ventricular diameter, septal thickness, LVOT gradient, degree of mitral regurgitation and cardiac function were analyzed. Besides, according to whether significant septal hypertrophy (septal thickness >18 mm) was present, patients were divided into two subgroups, and results between two groups were compared.
RESULTS A total number of 86 patients were included, and the mean follow-up time was 8.2 months (1–60 months), no death was observed perioperatively and during follow-up. Postoperative left atrium size reduced slightly, and left ventricular end diastolic volume (LVEDV) showed no significant change. Significant septal thickness reduction was revealed after surgery (21.79±5.76 mm vs 14.77±3.99 mm, t<0.01), and no recurrent septal hypertrophy had been observed during follow-up (14.71±4.22 mm at last follow-up). Postoperative LVOT gradient relief was also significant (75.28±32.09 mmHg vs 12.94±9.39 mmHg, t<0.01) and the relief maintained during follow-up (15.89±19.45 mmHg at last follow-up). Only 1 patient had residual SAM (Grade 2), and the MR degree reduction was also obvious, with less patients had moderate or higher degree of MR postoperatively (63.1 vs 11%, t<0.01). The ejection fraction (EF) decreased after surgery (71.82±6.62% vs 62.00±7.42%, t<0.01), and the trend didn’t reverse during follow-up, we speculated that it may be related to the overestimation of EF due to the presence of significant MR before surgery. In the subgroup analysis, there was significant difference in the postoperative septal thickness between groups, but the numerical valves were close (15.65±4.40 mm in patients with significant septal hypertrophy vs 13.09±2.18 mm in patients with mild septal hypertrophy, t<0.05), and no LVOT gradient difference had been revealed (3.73±9.94 mmHg vs 9.50±4.54 mmHg, t=0.130).
CONCLUSIONS Extended septal myectomy with secondary chordal resection in nonselective HOCM patients shows promising initial results, it can provide septal thickness decrease, LVOT gradient relief and MR improvements. Combine the results of this investigation and previous studies, Extended septal myectomy with secondary chordal resection may be a potentially better strategy, but further investigations with a larger sample size and longer follow-up period are needed to verify the safety and effectiveness of this strategy.
GW34-e1348
Xin Zhang1,2,3, Wenqian Wu1,2,3, Lingyun Fang1,2,3, He Li1,2,3, Manwei Liu1,2,3, Li Zhang1,2,3, Shu Chen4, Mingxing Xie1,2,3
1Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2Clinical Research Center for Medical Imaging in Hubei Province, Wuhan 430022, China
3Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
4Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
OBJECTIVES Myocardial work (MW) is a novel echocardiographic method that corrects speckle-tracking-derived global longitudinal strain (GLS) for afterload using non-invasive systolic blood pressure (SBP) as a surrogate for left ventricular systolic pressure (LVSP), which has potential value in hypertrophic obstructive cardiomyopathy (HOCM). However, the application of echocardiographic MW analysis in HOCM patients is challenging due to the inequality between SBP and LVSP caused by left ventricular outflow tract (LVOT) obstruction. This study sought to propose a corrected method for echocardiographic MW analysis in HOCM to evaluate LV function.
METHODS This study prospectively recruited a total of 31 HOCM patients who underwent septal myectomy (SM) from September 2021 to October 2022. All patients underwent echocardiography within 1 month before and 3–6 months after the surgery. To get our novel method of non-invasively estimated LVSP, 21 patients successfully underwent intraoperative direct pressure measurements to obtain invasive LVSP and SBP and simultaneous transesophageal echocardiography to calculate peak and mean LVOT gradients. Using the invasively measured LVSP as the gold standard, the accuracy of the direct addition of peak or mean LVOT gradient to SBP to estimate LVSP was compared. Non-invasive estimation of LVSP by correcting SBP with echocardiographic LVOT gradient solves the limitation of MW application in HOCM. A corrected method of MW analysis was thereby developed. Preoperative and postoperative global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) of 31 HOCM patients were analyzed to explore the characteristics of LV functional remodeling.
RESULTS Compared with the estimated LVSP corrected with mean LVOT gradient (mean LVOT gradient + SBP), the estimated LVSP corrected with peak LVOT gradient (peak LVOT gradient + SBP) had better correlation and agreement with invasively measured LVSP (r: 0.98 vs. 0.74; ICC: 0.96 vs. 0.51; mean difference: −7.1 vs. 34.0 mmHg; 95% limits of agreement: −28.95 to 14.76 vs. 17.9–85.9 mmHg). After SM, GWI (2174±599 vs. 1257±333 mmHg%, P<0.01), GCW [2271 (1877–2791) vs. 1373 (1204–1744) mmHg%, P<0.001] and GWE [92 (90–94) vs. 87 (83–90) %, P<0.01] were significantly decreased, while GWW [131 (101–156) vs. 153 (125–264) mmHg%, P<0.001] was increased.
CONCLUSIONS We propose a corrected method for echocardiographic MW analysis in HOCM. MW can be used to evaluate LV function in HOCM by adding the resting peak LVOT gradient to cuff arterial SBP to noninvasively estimate LVSP. HOCM patients showed decreased GWI, GCW, and GWE and increased GWW after SM.
GW34-e1353
Yajie Tang
Fuwai Hospital
OBJECTIVES The limited transaortic exposure and variable morphologic hypertrophic septum impede the generalization of extended myectomy for HOCM (hypertrophic obstructive cardiomyopathy). This study sought to conclude operative techniques and outcomes of mitral-spared extended myectomy for HOCM according to imaging-detected hypertrophic extent and anatomical abnormalities of mitral apparatus, trying to provide a useful imaging-guided resection protocol for further generalizing the myectomy procedure.
METHODS In this study, 431 consecutive HOCM patients without intrinsic mitral lesions underwent mitral-spared extended myectomy. A 17-segmentation-based hypertrophic distribution was performed for guidance of intraoperative resection extent.
RESULTS Patients associated with midventricular segment hypertrophy (72.4%) held a longer resection length than those without [45 mm (40, 50) vs 35 mm (33, 40); (P<0.001)], and so as those with concomitant hypertrophic anterior wall (58.3%) compared to ones without: [45 mm (40, 45) vs 35 mm (30, 38), (P<0.001)]. The follow-up LVOT (left ventricular outflow tract) gradients were significantly improved from 90 mmHg (74,108) to 9 mmHg (7, 14); P<0.001), which were found with weak negative correlation to resection length and thickness ((ρ=−0.186, P=0.0001 and ρ=−0.132, P=0.006, respectively)). Multivariate logistic analysis revealed that the unremoved abnormal mitral links (AMLs) (n=27, 6.3%) and the resection thickness was the independent risk and protective factor to the residual follow-up LVOT obstruction and systolic anterior motion, respectively (odds ratio (OR) 3.499, 95% confidence interval (95% CI) 1.358–9.018, P=0.010 and OR 0.763, 95% CI 0.661–0.881, P<0.001, respectively).
CONCLUSIONS The 17-segemtation protocol guided resection is a safe and accessible method for extended myectomy. Maximizing the resection extent remains the core issue for relieving LVOT obstruction, and the AMLs in HOCM should be further addressed in operation.
GW34-e1403
Yutong Sun, Qinghao Zhao, Yang Liu, Jin Lu, Lei Wen, Xuelin Dou, Ruxin Wen, Mei Bao, Cuncao Wu, Xiaoyu Wu, Jingyi Bi, Jian Liu
Peking University People’s Hospital
OBJECTIVES Given the widespread utility of anti-CD38 monoclonal antibodies in primary systemic light chain amyloidosis (AL amyloidosis), we have seen favorable hematologic CR rate, more organ responses especially cardiac in AL amyloidosis, and even a better 1-year overall survival (OS) in stage IIIB patients. We expect a better OS beyond 1 year of AL amyloidosis, which should be the focus of future research. In this context, our study aims to explore long-term (1 year after diagnosis) prognostic factors of Holter monitoring in AL amyloidosis patients.
METHODS One hundred and thirty-seven AL amyloidosis patients registered between December 28, 2011, and November 23, 2022, who underwent 24-hour Holter monitoring were included. The primary outcome was OS. Landmark analysis was taken at 1 year (long-term). Independent predictors were determined through the log-rank test and Cox proportional hazards model.
RESULTS 129 (94.2%) patients received chemotherapy as front-line treatment and 32 (23.4%) underwent daratumumab-based chemotherapy. Forty-seven deaths occurred during a median follow-up of 20.3 months. Atrial tachycardia (AT), conduction delay, and non-sustained ventricular tachycardia (NSVT) indicated inferior long-term outcomes in landmark analyses (for patients with vs without AT: 14.6 months (95% CI: 22.8–79.9) vs not reached (P=0.012); for patients with vs without conduction delay: 15.1 months (95% CI: 0–49.0) vs not reached (P=0.021); for patients with vs without NSVT: 25.5 months (95% CI: 0–91.6) vs not reached (P=0.029)). AT (HR: 2.7; 95% CI: 1.0–6.5; P=0.049) and conduction delay (HR: 4.3; 95% CI: 1.3–14.3; P=0.016) were independent long-term predictors after accounting for age and the 2012 Mayo stage.
CONCLUSIONS AT and conduction delay in Holter monitoring are associated with inferior long-term OS (1 year after diagnosis) in AL amyloidosis.
CARDIOVASCULAR SURGERY
GW34-e0057
Yuanrui Gu
Fuwai Hospital
OBJECTIVES The objective of this study was to introduce our institutional experience of treatment strategies (cervical subclavian artery reconstruction, thoracotomy subclavian artery reconstruction and endovascular treatment) for proximal isolated subclavian artery aneurysms (PISAAs).
METHODS We retrospectively analyzed 15 consecutive patients with PISAAs treated by different treatment strategies (cervical reconstruction, thoracotomy reconstruction and endovascular treatment) in our institution from May 2016 to May 2022. Baseline data, surgery-related data, postoperative information and long-term follow-up were assessed.
RESULTS A total of 17 PISAAs in 15 consecutive patients were treated in our institution. The success rates of subclavian artery reconstruction in the cervical reconstruction, the thoracotomy reconstruction and the endovascular treatment were 100,100 and 83.33%, respectively. About the involved vertebral artery, the reconstruction rates in the cervical reconstruction, the thoracotomy reconstruction, and the endovascular treatment were 80, 75, and 0%, respectively. The intraoperative blood loss in the thoracotomy reconstruction was significantly higher than that in the cervical reconstruction and the endovascular treatment (P<0.05). The total operation time of the thoracotomy reconstruction was significantly longer than that of the cervical reconstruction and the endovascular treatment (P<0.05). In terms of postoperative ventilator use time, total postoperative drainage fluid, total postoperative drainage time, and ICU duration, both the thoracotomy reconstruction and the cervical reconstruction were significantly more than the endovascular treatment (P<0.05). During the follow-up, one patient in the endovascular treatment underwent re-intervention 22 months after surgery due to in-stent occlusion.
CONCLUSIONS For patients with PISAAs, different treatment strategies are recommended depending on the size of the aneurysms and whether the involved vertebral arteries require reconstruction.
GW34-e0096
Hang Xu, Sheng Liu
Fuwai Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College
OBJECTIVES Postoperative atrial fibrillation (POAF) is a common complication that occurs after surgical repair of mitral valves for degenerative mitral regurgitation (DMR) and is associated with unfavorable outcomes. The objective of this study was to identify preoperative risk factors for acute POAF in patients with DMR undergoing mitral valve repair, with an emphasis on the role of preoperative echocardiography.
METHODS This retrospective study comprised 1127 patients with DMR who underwent mitral valve repair between 2017 and 2022. The primary endpoint was the incidence of acute POAF within 30 days postoperatively. Univariate and multivariate logistic regression analyses were executed to identify risk factors for POAF. Moreover, subgroup analyses were conducted to evaluate the predictive value of preoperative parameters for acute POAF.
RESULTS Acute POAF occurred in 152 patients (13.5%). Multivariate analysis unveiled that age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03–1.07; P<0.001), hypertension (OR, 1.50; 95% CI, 1.03–2.21; P=0.037), left ventricular ejection fraction (OR, 0.95; 95% CI, 0.92–0.98; P=0.004), and left atrial enlargement (OR, 1.03; 95% CI, 1.00–1.06; P=0.019) were independent predictors of acute POAF after adjustment of covariates. Of note, the thickness of the IVS was strongly associated with acute POAF (odds ratio 1.21, 95% confidence interval 1.06–1.38, P=0.005) among all echocardiographic parameters. Subgroup analyses exhibited that the IVS remained as a significant predictor of POAF in various subgroups.
CONCLUSIONS Preoperative assessment of clinical morbidity and echocardiographic parameters, particularly the interventricular septum, may be beneficial in identifying patients at a high risk of acute POAF and in the development of targeted strategies for its prevention and management.
GW34-e0119
Kun Fang1, Jiawei Zhao1, Mingyao Luo1, Chang Shu1,2
1Vascular Surgery Center, National Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
2Department of Vascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China
OBJECTIVES The indications for endovascular repair of abdominal aortic aneurysm (EVAR) have been rapidly expanded due to the improvement and innovation of devices and technology. However, the use of iodinated contrast agents limits its application in patients with severe contrast allergy or renal dysfunction. Our study reported a contrast free EVAR case through intraoperative cone-beam CT (CBCT) guidance and evaluation.
METHODS A 76 year-old female patient was diagnosed with abdominal aortic aneurysm by MRA. The patient had severe allergic history of iodine contrast medium. After general anesthesia, CBCT (syngo DynaCT 360) was acquired with projection angle range of 360 degrees around the abdomen. Based on the calcified plaques confirmed in MRA and CBCT, the orifice of each branching artery and its corresponding spinal position were marked on the sectional images. The stent-graft alignment was guided by the markers on the fluoroscopy screen. After deployment, another CBCT was acquired to evaluate the stent position and shape.
RESULTS No contrast medium was used during the whole procedure. The calcified plaques found in CBCT corresponded well with that in MRA. With the guidance of the anatomy markers on fluoroscopy screen, anchoring zones for stent-graft can be quickly localized. Two stent-grafts were deployed and the whole procedure took only 77 min. The postoperative CBCT images showed that all the stent-grafts were well aligned and attached to aorta wall. The patient recovered well and discharged after 7 days. A 3-month follow-up MRA demonstrated total thrombosis of the aneurysm with stent-grafts patent.
CONCLUSIONS The intraoperative CBCT guidance provides an alternative and effective option for contrast free EVAR. In this condition, intraoperative localization could be more accuracy without extra equipment, registration error or patient position variance during overlapping.
GW34-e0286
Chen Tao1, Li Lamei1, Yang Anni1, Huang Hui2, Shi Ganwei1, Li Feng1, Li Wenhua1, Lu Wei1, Xu Lingxia1, Li Li1, Cai Gaojun1
1Wujin Hospital Affiliated with Jiangsu University
2Jiangyin Hospital of Traditional Chinese Medicine
OBJECTIVES One of the important advantages of the distal radial artery (DRA) approach is the significant reduction in the incidence of radial artery occlusion (RAO). There are few reports on the influencing factors for distal radial artery occlusion (dRAO) after cardiovascular intervention via the DRA approach.
METHODS This retrospective analysis included patients who underwent cardiovascular intervention via the DRA approach. The dRAO and RAO were evaluated by ultrasound after 24 hours. Multivariate logistic analysis was used to explore the influencing factors for dRAO.
RESULTS The incidence of dRAO at 24 h after the operation was 3.6% (29 cases). In the comparison between the two groups, the preoperative DRA internal diameter in the dRAO group was significantly smaller than that in the non-dRAO group (P<0.001). The prevalence of DRA inner diameter/sheath outer diameter <1 was significantly higher in the dRAO group than in the non-dRAO group (P=0.041). The number of puncture attempts was significantly greater in the dRAO group than in the non-dRAO group (P=0.007). Multivariate logistic analysis showed that DRA inner diameter/sheath outer diameter <1 was an independent risk factor for dRAO (OR=4.827, 95% CI =1.087–21.441, P=0.039).
CONCLUSIONS The incidence of dRAO at 24 h after cardiovascular intervention via the DRA approach was 3.6%, and DRA inner diameter/sheath outer diameter <1 was an independent risk factor for dRAO. Preoperative ultrasound assessment of vessel inner diameter and selection of a sheath with a smaller outer diameter may reduce the risk of dRAO.
GW34-e0431
Songtao Liu
The People Hospital of JIANGXI Province
OBJECTIVES PAD is highly prevalent in whole world and a important predictor for death, myocardial infarction or stroke. However, most PAD patients are not be diagnosed because only 10%-20% of them have symptoms. At present, these patients are diagnosed by decreased ankle-brachial index (ABI of ≤0.90), a ratio of ankle systolic blood pressure (SBP) to brachial SBP. This paper is to evaluate the diagnostic value of systolic ankle-brachial index (ABI) and inter-ankle systolic blood pressure difference (sIAND) detected with oscillometric method for peripheral arterial disease in the leg.
METHODS This study included 206 patients underwent computed tomography angiography (CTA) to diagnosing leg artery disease. A stenosis ≥50% at least in one leg was used for diagnosis of PAD. Four limb blood pressure (BP) were measured by oscillometric method. The ABI were calculated with the following formula: ABI=ankle-SBP/brachial-SBP. Here, the brachial-SBP is the higher SBP value of two arms, and the ankle-SBP was the lower value. The absolute difference of SBP between two ankles was calculated as sIAND. ABI of ≤0.9 and sIAND of ≥15 mmHg were used as the cutoff values for diagnosis of PAD in leg.
RESULTS Among the 206 patients, 169 with ABI≤0.9 and 106 with sIAND≥15 mmHg. The sensitivity, specificity and accuracy of ABI≤0.9 for diagnosing 50% stenosis were 91.8, 91.7 and 91.7%. Those for the sIAND≥15 mmHg were 55.5, 79.2 and 58.3% respectively. When combination of OS-ABI≤0.9 and sIAND≥15 mmHg, those increased to 96.2, 70.8 and 93.2%.
CONCLUSIONS The ABI from oscillometric method is useful marker for diagnosis of PAD in leg, combination of sIAND≥15 mmHg could improve the diagnosis accuracy.
GW34-e0649
Shipan Wang, Yuan Xue, Haiyang Li, Wenjian Jiang, Hongjia Zhang
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Subclinical hypothyroidism can negatively affect the cardiovascular system and increase the risk of mortality, especially for individuals with thyroid-stimulating hormone (TSH) levels above 10 mU/L. We investigated the relationship between high-TSH subclinical hypothyroidism and postoperative mortality in acute type A aortic dissection (ATAAD) patients.
METHODS We enrolled 146 patients with ATAAD who underwent aortic surgery in Beijing Anzhen Hospital from July 2016 to November 2018. Thyroid hormone levels were obtained before surgery, and participants were divided into a ≥10 mU/L TSH level group and a <10 mU/L level group. Cox proportional hazard regression and subgroup analysis were conducted to examine the association of preoperative high-TSH subclinical hypothyroidism with postoperative mortality.
RESULTS Participants with preoperative high-TSH (≥10 mU/L) subclinical hypothyroidism tended to have longer hospitalization stays after surgery [16.0 (IQR 11.0–21.0) days vs 12.5 (IQR 8.0–16.0) days, P=0.001]. During the first 30 days after operation, 15 of 146 patients died (10.3%); during a median of 3.16 (IQR 1.76–4.56) years of follow-up, 24 patients died (16.4%). Cox proportional hazard regression showed that preoperative high-TSH subclinical hypothyroidism was independently associated with 30-day mortality (HR=6.2, 95% CI, 1.7–22.0, P=0.005) and postoperative mortality after adjusting for age, sex, BMI, hypertension, ejection fraction, diabetes and history of PCI (HR=3.4, 95% CI, 1.4–8.0, P=0.005).
CONCLUSIONS This study showed that preoperative high-TSH subclinical hypothyroidism was an independent predictor of postoperative mortality in ATAAD patients who underwent aortic surgery.
GW34-e0972
Zhou Liu, Jie Han, Wenjian Jiang, Yazhe Zhang, Hongjia Zhang
Beijing Anzhen Hospital
OBJECTIVES A significant proportion of patients undergoing valve surgery often have multiple valve lesions, and it has been shown in the past that excellent valve repair will bring a better prognosis for patients. It is frustrating for non-elderly patients with good mitral and tricuspid valve repair to undergo replacement surgery for severe aortic valve lesions at the same time. Aortic Valve Neo-cuspitization (AVNeo) is often considered a type of aortic valve repair surgery, and its efficacy and safety have been clinically proven. Based on good results of mitral and tricuspid valve repair, we tried to perform AVNeo for patients with severe aortic valve lesions simultaneously. Here we share our surgical experience and prognosis.
METHODS A total of 9 patients who underwent AVNeo combined valve repair surgery for multiple valve diseases from May 2016 to May 2023 were included in Beijing Anzhen Hospital. There were 6 males (66.6%) with a median age of 38 (31, 50) years. Rheumatic heart disease was found in 3 patients (33.3%) and non-rheumatic heart disease in 6 patients (66.6%).
RESULTS The median EuroSCORE II was 1.3 (1, 1.6). Six patients underwent AVNeo and mitral and tricuspid valve repair, and 3 patients underwent AVNeo and mitral valve repair. The median operative time was 329 (302.5, 394.5) min, and the median cardiopulmonary bypass time and aortic clamp time were 203 (165, 226.5) min and 168 (126.5, 185) min, respectively. In the early stage, 2 patients underwent combined valve repair surgery, and 1 patient underwent in-hospital reoperation for aortic valve replacement because of severe aortic regurgitation. There were 7 patients in the mature stage of AVNeo, and no perioperative adverse events or moderate or above residual valvular disease occurred. All patients recovered and were discharged from the hospital. The follow-up period was 2–98 months, and no reoperation, moderate and severe valve disease, bleeding, cerebral infarction, and other adverse events occurred in all patients.
CONCLUSIONS For non-elderly patients whose mitral and tricuspid valves can be repaired successfully with severe aortic valve lesions, AVNeo can be attempted after proficiency. But the operation time and cardiopulmonary bypass time will inevitably be prolonged, and the patient’s basic situation should be carefully evaluated before surgery.
GW34-e1179
Yanlin Yang1, Huolin Zeng2, Yajiao Li3, Zhuheng Wu1, Lin Xie1, Ke Lin1, Changping Gan1
1Department of Cardiovascular Surgery, West China Hospital, Sichuan University (SCU), Chengdu, Sichuan Province, China
2Department of Anesthesiology, West China Hospital, Sichuan University (SCU), Chengdu, Sichuan Province, China
3Department of Cardiology, West China Hospital, Sichuan University (SCU), Chengdu, Sichuan Province, China
OBJECTIVES Ventricular septal defect (VSD) is the most common congenital heart disease requiring surgical intervention in infants and small children. Tricuspid valvular detachment (TVD) technique is widely used in perimembranous VSD repair, which is made for better visualization of the margins of VSD to reduce the risk of residual shunt but may increases the incidence of new-onset or progressive tricuspid regurgitation (TR). No quantitative criteria for TVD have been established, and we aim to develop and deploy the prediction model of anatomical factors associated with TVD in VSD repair.
METHODS A total of 74 children with perimembranous VSD undergoing on-pump surgical repair from February 2022 to April 2023 were recruited in this prospective cohort, 38 of whom with selective strategy for TVD were enrolled for the construction of the nomogram model, in which the innovatively proposed subtricuspid chordal classification and membranous aneurysm formation degree, as well as high-level VSD and aortic valve prolapse were included as risk factors in multivariate logistic regression. The dataset was randomly divided into the training and testing parts (50–50) and tested by cross-validation before deployment. The cut-off value for TVD was determined by highest Youden’s index, according to which the whole cohort was separated into suggested-TVD and suggested-NTVD subgroups. Operating time, cardiopulmonary bypass (CPB) time, aortic clamp time, postoperative atrioventricular block, residual shunt, and TR progression at discharge were compared between patients actually undergoing TVD and NTVD procedures in each subgroup.
RESULTS The baseline characteristics and postoperative outcomes were comparable between TVD and non-TVD (NTVD) groups. Three transient AVB during surgery and intensive care unit stay in TVD group and three postoperative TR progressions (1 in NTVD group and 2 in TVD group) were observed but without statistical significance. The C-index of the nomogram prediction model was 0.98, and the Brier value was 0.059. Cross-validation showed the effectiveness of the model with area under curve of 0.742. The cut-off value of 65 was confirmed with sensitivity of 1.00 and specificity of 0.96. Among suggested-TVD subgroup (≥65), shorter duration of operation (181±40.3 min vs 226±26.4 min; P=0.003) and clamp (61.0±23.7 min vs 78.7±16.2 min; P=0.045) was found in actually TVD patients compared with those not receiving TVD procedure actually.
CONCLUSIONS Subtricuspid chordal type, membranous aneurysm formation degree, high-level VSD and combined aortic valve prolapse were leveraged to develop a feasible and effective model to predict the risk of TVD in VSD repair, which may confer a more precise VSD surgical strategy. The prognosis of participants in this cohort should be further verified by a larger sample and long-term follow-up.
GW34-e1276
Shuanglei Zhao1, Zhou Liu1, Mingxiu Wen1, Qianxian Li1, Bin Wang2, Zhaoqing Sun2, Ming Gong1
1Center of Valve Surgery, Beijing Anzhen Hospital, Capital Medical University
2Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Differences in adverse cardiac remodeling between patients who suffer multivalvular endocarditis (MVE) and single valvular endocarditis (SVE) and its prognostic impact after surgical valve replacement/repair remains unclear. We sought to investigate differences in preoperative diastolic and systolic function in patients with multivalvular endocarditis and patients with single valvular endocarditis (SVE) and the incidence of postoperative mortality.
METHODS Three hundred forty-four patients with MVE (n=143) or SVE (n=200), scheduled for valve surgery, were retrospectively included. Comprehensive preoperative echocardiographic assessment of left ventricular (LV) diastolic and systolic function was performed. The postoperative mortality were recorded during a mean follow-up of 47.93 months versus 69.98 months for patients with MVE or SVE, respectively.
RESULTS Patients with MVE had a more pronounced left ventricular dilatation with significantly higher left ventricular end-diastolic dimension (LVEDD) (61.03 mm versus 53.95 mm, P<0.001), higher Left ventricular end-systolic diameter (LVESD) (40.86 mm versus 35.58 mm, P<0.001). However, Patients with MVE had a similar left ventricular ejection fraction (LVEF) (60.57 versus 61.40%, P=0.332). Patients with MVE were older (46.55 versus 42.53, P=0.013). MVE was independently associated with significantly high risk of postoperative all-cause mortality (adjusted hazard ratio 2.64, 95% confidence interval 1.34–5.20, P=0.005). Results were similar in propensity matched MVE cohort (n=141) and SVE cohort (n=141) according to age.
CONCLUSIONS Patients with MVE had worse preoperative LV remodeling and an increased risk of postoperative all-cause mortality compared with patients with MVE. Our findings suggest that patients with MVE might benefit from closer surveillance and possibly earlier surgical intervention before the LV remodeling deteriorates.
GW34-e1299
Zhe Xu, Lijuan Liu, Banghuan Wei, Jian Ling, Song Yang, Jiajia Yan, Yongchao Wu, Baoling Yuan, Yingqi Xu, Xi Zhang, Zhongkai Wu
The First Affiliated Hospital of SunYat-sen University
OBJECTIVES To summarize the available data for the epidemiology of infective endocarditis (IE) in Asian low-income and middle-income countries (LMIC).
METHODS A systematic review and meta-analysis of relevant studies published before May 2022 were done according to PRISMA 2020. This study is registered with PROSPERO, CRD42022355488. Data were analyzed with the R software (version 4.1.3) and GraghPad Prism (version 9.0; GraphPad Software, Inc, La Jolla, CA).
RESULTS Sixty-five studies were included. Rheumatic heart disease [RHD, 32.74% (95% CI 22.71–43.61)] in South Asia, congenital heart disease [CHD, 25.80% (21.73–30.10)] in East Asia and prosthetic valves [21.58% (15.62–29.02)] in West Asia were the most common risk factors for IE in adults, whereas CHD was the most common risk factor for IE in children [83.13% (73.99–90.70)]. Healthcare-associated IE [17.65% (10.41–26.29)] was a significant IE type. Streptococci and staphylococci were the most commonly identified microorganisms. The pooled in-hospital mortality rate was 20.66% (17.57–23.93). Other frequent complications included heart failure [40.63% (33.28–48.18)] and embolic events [27.56% (21.44–34.12)].
CONCLUSIONS Apart from RHD and CHD, prosthetic valves and healthcare-associated procedures are the more prevalent IE risk factors and should be central in the management to reduce the burden of IE in Asian LMIC. Although the outcomes of IE seem similar to what has been reported in high-income countries, further efforts are needed to improve the care, especially in increasing the access to cardiac surgery, identifying the causative microorganism in cases of negative culture IE and obtaining multimodality imaging.
GW34-e1391
Fengqun Mao, Shoujun Li
Pediatric Cardiac Surgery Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing
OBJECTIVES Recurrence of mitral regurgitation after mitral valve repair or atrioventricular septal defect repair is common. While various techniques have been reported, the surgical management of recurrent mitral regurgitation remains technically demanding. In our institution, a leaflet augmentation technique has been applied since 2018. The efficacy of this technique and long-term result for the redo mitral repair is evaluated.
METHODS From January 2018 to December 2022, 24 pediatric patients who underwent reoperation for mitral regurgitation with leaflet augmentation after atrioventricular septal defect repair or mitral valve repair in Fuwai Hospital, including 6 males and 12 females with a median age of (49.1±29.1) months. The characteristics of mitral valve disease, key points of surgery and short and mid-term follow-up results were analyzed.
RESULTS The time span from the primary valve surgery to the reoperation was (24.9±17.0) months. The cardiopulmonary bypass time was (150.1±49.5) min and the aortic clamp time was (94.0±24.2) min. There was no early death. The average follow-up period was (20.3±9.1) months. During the follow-up period, the mortality rate was 4.2%, the rate of reoperation was 4.3%, and the rate of moderate or severe mitral regurgitation was 13.0%. The left ventricular ejection fraction was (62.6±6.7)%. In addition, the mean left ventricular end-diastolic dimension was (35.8±7.8) mm, which was significant smaller than that before the operation (t=4.858, P<0.000 1).
CONCLUSIONS The application of leaflet augmentation is a safe and effective treatment option with good results in the short and mid-term, which thus provides a good technical option for pediatric patients with recurrent mitral regurgitation.
CLINICAL DRUG RESEARCH AND DEVICE DEVELOPMENT药物研发与器械研发
GW34-e0126
Tian Zheng1, Qianwei Huang2, Xiao Huang2, Qianghui Huang2, Jianxin Hu2, Biming Zhan2
1Department of Radiology, The Second Affiliated Hospital of Nanchang University
2Department of Cardiology, The Second Affiliated Hospital of Nanchang University
OBJECTIVES With the application of contrast agents, contrast-induced nephropathy (CIN) is a growing concern. Most of the CIN data were collected from iodine-based contrast agents, while there are few studies on gadolinium-based contrast agents. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have strong cardioprotective and renal protective effects. In our study, we firstly investigated the potential effect of SGLT2 inhibitors on the prevalence of CIN caused by gadolinium-based contrast agents.
METHODS A total of 1204 diabetes patients who received gadolinium-based contrast agents in our hospital were included. The patients were divided into two groups: intervention group (n=602) and control group (n=602). Patients in the intervention group, patients were administered a dose of SGLT2i (10 mg, p.o.) before gadolinium contrast using, in the control group, patients did not use SGLT2 in the same period. The endpoints were development of CIN, which was determined by increased serum creatinine 48h following the intervention by at least 25% (or 44 μmol/L) of baseline value. The clinical characteristics before the use of contrast agents were compared between the two groups. The risk factors for contrast-induced nephropathy were analyzed by logistic regression.
RESULTS The groups were similar basic characteristics. The incidence of CIN caused by gadolinium-based contrast agents was 3.98% (48/1204). However, the development of CIN was observed to be significantly less in the group using SGLT2 inhibitor (17/602 vs 31/602, P=0.03). The multivariate analysis showed that sex, systolic pressure (SBP), fasting blood glucose level, and furosemide use were significant predictors of CIN, the use of SGLT2 inhibitors significantly reduced the risk of CIN (odds ratio [OR] 0.250, 95% confidence interval [CI] 0.092–0.677, P =0.006).
CONCLUSIONS The use of SGLT2i may be a promising option for the prevention of CIN caused by gadolinium-based contrast agents.
CARDIOVASCULAR DISEASES IN SPECIAL POPULATIONS (CHILDREN, WOMEN, ETC.)
GW34-e0019
Sulan Huang
The First People’s Hospital of Changde City
OBJECTIVES Previous studies have reported that serum uric acid (SUA) levels are associated with low birth weight (LBW) in children. However, the relationship between SUA and the risk of children born with LBW in advanced maternal-age patients with hypertensive diseases of pregnancy (HDP) remains unclear.
METHODS This was an observational study. A total of 346 advanced maternal age with hypertension were enrolled in our study. The data included demographic data, vital signs, laboratory test data, and pregnancy outcomes. The clinical endpoint was children born with LBW. Blood samples were obtained on admission, and women of advanced maternal age were classified into two groups according to SUA level. The logistic regression model was used to examine the associations between SUA and LBW. Residual unmeasured confounding was assessed through E-value analyses.
RESULTS The mean SUA level was increased in advanced maternal age patients with HDP. Of 346 newborns, 122 (35.26%) have LBW. After adjusting for potential confounders, high SUA level was an independent risk factor for the incidence of LBW (odds ratio [OR] 2.88, 95% confidence intervals [CI] 1.22–6.81), a pattern that was recapitulated by multivariate logistic regression analysis with SUA as a continuous variable (OR 1.01, 95% CI 1.00–1.01). Moreover, SUA levels in advanced maternal age with hypertension had a linear relationship with the incidence of LBW.
CONCLUSIONS This study suggests that SUA levels is associated with the incidence of LBW among patients of advanced maternal age with HDP.
GW34-e0022
Huai-Yu Wang1, Jinwei Wang2, Qin Wang3, Chao Yang2, Min Chen2
1National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Diseases, Beijing University of Chinese Medicine, Beijing, China
2Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China
3Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China
OBJECTIVES Management of blood pressure (BP) of the elderly has always been one of the focuses of clinical guidelines updating. The current clinical guidelines of BP management all pointed out the insufficiency of data and evidence of BP in the very old, especially those with frailty. Due to the rapid expansion of the oldest-old and the accompanied epidemic of frailty in the ageing society, it is urgent to increase the population-based evidence for the BP management of this population.
METHODS Adults ≥65 years in the Chinese Longitudinal Healthy Longevity Survey (2008–2018) were included. Frailty was identified by the Fried criteria. Hypertension was identified by self-report or SBP/DBP≥140/90 mmHg. The association between age and BP were investigated using linear regression models. Difference of BP was calculated by BP at the last interview minus BP at baseline. Annual change of BP (mmHg per year) was calculated dividing the difference of BP by the follow-up duration (year). Sharp variation of BP was defined if annual change of BP lower than quartile 1 or higher than quartile 3. The association between age and sharp variation of BP were investigated using multinominal logistic regression models. The association between BP and the risk of mortality was analyzed using Cox regression models. The age- and frailty status-stratified analyses were performed. To illustrate whether the results were influenced by the potential antihypertensive treatment, the analyses were repeated in the subgroup of participants with unaware hypertension.
RESULTS A total of 13,447 adults (octogenarian: 3,811[28.3%]; nonagenarian: 3,571[26.6%]; centenarian: 1,965[14.6%]) were included. In the cross-sectional analyses, age was positively associated with levels of SBP in the robust hypertensive elderly (β=1.64, 95% CI 0.60, 2.67) but negatively associated with it in the frail ones (β=−2.50, 95% CI −3.77, −1.23). No similar phenomenon existed among the normotensive elderly. Annual change of BP was increment among the normotensive elderly (e.g. SBP, Median [IQR]: Robust 1.33[−0.33, 3.67], Frailty 1.54[−1.40, 5.67]) but expanding reduction among the hypertensive elderly with severer frailty (e.g. SBP, Median [IQR]: Robust −1.40[−4.33, 1.00], Frailty −3.50[−8.33, 2.42]). Reference to those aged 65–79 years, age was associated with the increased risk of BP elevation but higher risk of BP drop. (e.g. 90–99 years, robust & normotension, sharp decrease of SBP vs. sharp increase of SBP: RRR=4.84 95% CI 2.21, 10.6 vs. RRR=2.88 95% CI 1.80, 4.62; 90–99 years, frailty & hypertension, sharp decrease of SBP vs. sharp increase of SBP: RRR=3.01 95% CI 1.52, 5.97 vs. RRR=1.42 95% CI 0.67, 3.03) Elderly with unaware hypertension showed similar results. SBP<120 mmHg was the risk predictor of mortality among the frail oldest-old (≥85 years) (HR=1.20, 95% CI 1.03, 1.39) while SBP≥150 mmHg was that among the robust young-old (65–84 years) (HR=1.68, 95% CI 1.25, 2.27).
CONCLUSIONS The different progression of BP with age among the elderly with different status of hypertension and frailty should be noted. Individualized goal of BP control should fully consider age and the status of frailty. Age and frailty might be the criteria to predict the progression of BP to guide the antihypertensive treatment of the very old.
GW34-e0028
Zhihua Huang, Zhihong Liu, Qin Luo, Zhihui Zhao, Qing Zhao, Yi Zhang, Xin Li, Anqi Duan, Sicheng Zhang, Meixi Hu, Luyang Gao
Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
OBJECTIVES Pulmonary arterial hypertension (PAH) is a progressive ailment that can result in right ventricular failure and premature death. Sleep-disordered breathing, particularly obstructive sleep apnea (OSA), is prevalent among PAH patients and has been correlated with unfavorable outcomes. Categorizing PAH patients into subgroups based on their sleep-disordered breathing patterns may assist in personalizing treatment approaches and enhancing clinical outcomes. This study aims to scrutinize the phenotypes of PAH patients by means of clustering overnight sleep signals and investigate their prognostic importance.
METHODS In this retrospective cohort study, we recruited consecutive patients who were diagnosed with PAH by means of right heart catheterization and underwent nocturnal cardiorespiratory polygraphy for evaluating sleep-disordered breathing. Cluster analysis was employed to classify patients based on their sleep-disordered breathing patterns. To assess the association between cluster membership and clinical outcomes, Cox regression analysis and Kaplan-Meier curves were utilized. Furthermore, we utilized logistic regression to identify the risk factors linked with cluster membership.
RESULTS The study comprised a cohort of 386 PAH patients, with a median follow-up period of 15 months and a mean age of 44.7±17.0, of which 46.6% were male. Three distinct clusters of PAH patients were identified based on their sleep-disordered breathing patterns: Cluster 1 (n=182) presented with minimal sleep-disordered breathing, Cluster 2 (n=125) displayed OSA without hypoxemia, and Cluster 3 (n=79) exhibited OSA with overt comorbid hypoxemia. Notably, patients in Cluster 3 had an independent association with an increased risk of clinical worsening (hazard ratio 1.96, 95% confidence interval 1.08–3.56, P=0.027) compared to those in Clusters 1 and 2, even after adjusting for common confounders. Additionally, the rate of hospitalization for PAH-related events and mortality was higher in Cluster 3 than in Clusters 1 and 2 (26.6 vs. 12.6 and 19.2%, respectively, log-rank P=0.024). Moreover, the left ventricular mass index was identified as an independent risk factor for Cluster 3 (odds ratios 1.01, 95% CI 1.00–1.02, P=0.004).
CONCLUSIONS Patients with PAH who also have OSA and hypoxemia had worse clinical outcomes compared to those with only minimal sleep-disordered breathing. Tailored management strategies that address both the PAH and nocturnal hypoxemia may be effective in improving clinical outcomes.
GW34-e0163
Sulan Huang
The First People’s Hospital of Changde City
OBJECTIVES Previous studies reported that hyperuricaemia is associated with hypertensive disorders of pregnancy (HDP), however, there are limited data on advanced maternal age pregnant women. We assessed the association of serum uric acid (SUA) with HDP in pregnant women of advanced maternal age.
METHODS This was a retrospective cohort study. Data was collected from January 2018 to May 2022. Using 1:2 PS matching (PSM), 780 advanced maternal age pregnant women were enrolled in this study.288 cases had HDP and 492 controls with normal blood pressure. A multivariate logistic regression model and three PS-based methods were applied to assess the actual association between HUA and HDP incidence. Stratified analyses and interactions were performed based on GDM, maternal age, platelets, RDW, BMI, blood pressure, gestational week, heart rate, anemia, and urine protein.
RESULTS The median age was 37 in interquartile 35–39 ranging from 35 to 50 years. 7.69% patients were in the second trimester and 92.31% participants were in the third trimester. The risk of HDP development increased with higher serum uric acid levels. After adjusting for confounders, the risk ratio for the development of HDP with HUA was 2.88(95% CI: 1.44–5.75) compared with the group with NUA in the PS-matched cohort. Also, HUA is substantially implicated in HDP incidence in the crude population (OR: 3.43, 95% CI: 2.01–5.84) and the weighted cohorts (OR: 3.62, 95% CI: 2.81–4.66). In the sensitivity analysis, similar conclusions were reached for both the original and weighted cohorts. Further interaction analysis revealed a clear BMI-based difference in the association between HUA and HDP incidence.
CONCLUSIONS SUA exhibited the great influence on HDP incidence in advanced maternal age pregnant women, supporting the necessity of early detection SUA in pregnant women with hyperuricemia. Additionally, this low-cost test would allow for better use of resources in developing countries.
GW34-e0192
Lan Mu
Department of Ultrasonography, Chongqing Health Center for Women and Children (CQHCWC)/Women and Children’s Hospital of Chongqing Medical University (CQMU-WCH), Chongqing, China
OBJECTIVES In clinical ultrasound screening, we often encounter the situation that aortic nature of the fetus has not yet reached the diagnostic standard of aortic stenosis. So we try to investigate the clinical features and postnatal outcome of fetal narrow Aorta.
METHODS Forty four cases of fetuses with postnatal follow-up and genetic detection were retrospectively analyzed by the parameter of Echocardiography and the follow-up before/after birth.
RESULTS There are 14 fetuses with isolated narrow Aorta, 28 fetuses with intracardiac malformation, 2 fetuses with both intracardiac and extracardiac anomaly, 1 fetus with chromosome aberrations of the 44 cases. A narrow of aortic annulus was shown in 43 cases, with the inner diameter of (0.34±0.08) cm, Z-S −1.54±0.95; a narrow of ascending aorta was shown in 39 cases, with the inner diameter of (0.32±0.09) cm, Z-S −2.46±0.99; the inner diameter of isthmus of aortic arch was 0.20±0.05 cm. The size and morphology of the Aorta became normal in 17 fetuses, while 6 of which ware still narrow. Four infant had an aortic coarctation diagnosed at birth. An increase in aorta Peak Doppler flow velocity was found in 2 case with normal size of the aorta after birth.
CONCLUSIONS The prognosis of the fetuses of narrow aorta are good when it is isolated or only associated with simple anomaly, while the size of aorta isthmus is bigger than the left subclavian artery. The frequency of chromosomal anomalies among fetuses with narrow aorta are rare, especially the aneuploid abnormality.
GW34-e0229
Yanping Ruan, Yihua He
Beijing Anzhen Hospital, Capital Medical University; Maternal-Fetal Medicine Center in Fetal Heart Disease, Beijing Anzhen Hospital
OBJECTIVES Evidence of maternal exposure to ambient air pollution on congenital heart defects (CHD) has been controversy and is still relatively limited in developing countries, especially the association of ozone with critical CHD, which is an important cause of neonatal mortality and morbidity. We aimed to investigate the association between maternal exposure to ozone and critical CHD in China.
METHODS Pregnant women who underwent fetal echocardiography were consecutively recruited in our hospital between Jan 2013 and Dec 2021. The maternal sociodemographic and lifestyle characteristics and some fetal factors were obtained. The critical CHD cases were prenatally diagnosed by fetal echocardiography. Address of hospitals for prenatal checkups during Pregnancy was linked to estimate maternal exposure to ambient ozone during the first trimester, during 3 months prior to last menstrual period (LMP) and during periconception period. Adjusted logistic regression models were used to assess the associations between per 10 μg/m3 or per quartile increase in ambient ozone exposure and critical CHD.
RESULTS A total of 24,767 subjects were enrolled, of whom 1558 (6.29%) had critical CHD fetuses. The multivariate logistic regression analysis has shown that positive associations were observed for the gestational exposures to ozone during embryonic period, during the preconception period, and during periconception period. For each 10 μg/m3 increase in ozone, the ORs (95% CI) were 1.130 (1.082, 1.179), 1.183 (1.121–1.248), and 1.306 (1.234–1.382), respectively, with higher risk of critical CHD during periconception period. Additionally, using the first quartile as a reference, the risk of the critical CHD increased progressively with each quartile increase in ozone during embryonic period and during the periconception period, with the most pronounced effect values during the periconceptional period (OR=2.11 for quartile 2, 2.414 for quartile 3, and 3.999 for quartile 4, all P<0.05). The trend was not significant during preconception period, but with higher risk for the fourth quartile level of ozone exposure (OR=3.343, 95% CI: 2.526, 4.424). Similar effect of maternal exposure to ozone on the critical CHD was observed in the stratified analyses, with more significant effect during periconception period. However, most of the differences were not statistically significant between the subgroups except the maternal age, the number of risk factors, and referral.
CONCLUSIONS Maternal exposure to greater levels of ozone during the pregnancy, especially during the periconception period, is associated with higher risk of fetal critical CHD. Further longitudinal well-designed studies are needed to confirm our findings.
GW34-e0281
Wei He, Pengyuan Zhang, Donghong Liu, Fengjuan Yao, Liuqin Liang
The First Affiliated Hospital, Sun Yat-sen University
OBJECTIVES Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease that primarily affects child-bearing period women, carries a higher risk of cardiovascular disease and is the primary cause of most cases of morbidity and mortality. The objective of this study was to assess left atrial (LA) strain values in SLE patients with preserved left ventricular ejection fraction by four-dimensional speckle-tracking imaging (4D-STI) to detect subclinical myocardial damage.
METHODS Forty-nine SLE patients (36.6±14.4 years, 81.6% women) without cardiac symptoms and 49 healthy subjects (39.7±12.2 years, 89.8% women) matched by age and sex were respectively enrolled. Firstly, patients were divided into normal LV diastolic function (n=38) and grade I diastolic dysfunction (n=11) subgroups. Secondly, the patients were divided into relatively low activity (SLE disease activity index 2000 (SLEDAI-2K)≤10, n=26) and high activity (SLEDAI-2K>10, n=23) subgroups. Standard transthoracic echocardiography was applied to evaluate the systolic myocardial function. The parameters of LA strain were calculated from 4D-STI.
RESULTS The value of LA peak longitudinal strain of reservoir function (LASr, 26.4±7.5% vs 32.2±8.8%, P=0.002) and LA peak longitudinal strain of conduit function (LAScd, −16.7±5.0% vs −19.9±6.3%, P=0.013) were impaired in SLE patients with normal LV diastolic function compared with the controls. SLE patients had a significantly lower LASr (26.5±8.2% vs 32.2±8.8%, P=0.007) in SLEDAI≤10 subgroup compared with the healthy controls. The LAScd value (−17.3±4.8% vs −13.6±5.4%, P=0.014) was damaged in SLEDAI>10 subgroup compared with the SLEDAI≤10 group. In separate multiple linear regression analyses, diastolic function pattern (B=2.459, P=0.044) and SLEDAI (B=0.303, P=0.044) were independently associated with LAScd, and SLEDAI (B=−4.627, P=0.021) were independently associated with LASr.
CONCLUSIONS LASr and LAScd could identified subclinical LA dysfunction early in SLE patients with normal LV diastolic function. LASr and LAScd are promising novel tools for distinguishing SLE patients with higher disease activity.
GW34-e0395
Yi Zhang
Dept. of Cardiovascular Medicine, The People’s Hospital of Danyang & Affiliated Danyang Hospital of Nantong University
OBJECTIVES DES gene mutations are often associated with cardiac involvement and skeletal muscle lesions. More than 70% of the mutations in the pathogenic DES gene show cardiac involvement, mainly manifested as arrhythmia, Dilated cardiomyopathy, and hypertrophic cardiomyopathy, often accompanied by conduction block, and even heart failure and cardiac Death during consensual sex in severe cases. Analyze the clinical phenotype and mutation sites of a DES gene mutation case in a 10 year old child characterized by atrioventricular block and Asperger’s syndrome.
METHODS The clinical data of a patient with severe arrhythmia and his family members who had been treated in our hospital and whose DES gene c. 1360C>T mutation was revealed by whole Exon sequencing (WES) were collected. Collect peripheral blood from the family, perform Sanger sequencing to identify potential pathogenic gene mutations, and predict the harmfulness of mutations through bioinformatics analysis.
RESULTS Sanger sequencing confirmed the WES results, and the child had a heterozygous mutation at this site, which was also carried by the mother. The mutation makes arginine at 406 of DES gene mutate into Tryptophan, and the database indicates that the mutation is harmful. Through phenotypic analysis, the patient had symptoms such as severe arrhythmia and muscle weakness, and received a lead free pacemaker implantation. The patient with atrioventricular block and Asperger’s syndrome is likely caused by a mutation in the DES gene.
CONCLUSIONS The mutation of c. 1216C>T in the DES gene is likely a pathogenic mutation in the patient. DES gene mutations often lead to severe cardiac phenotype, high mortality, and poor prognosis. For patients with atrioventricular block or muscle weakness, DES gene screening is helpful for diagnosis.
GW34-e0664
Wei Xiang, Ming-Huan Hong, Ling-Yun Kong, Ling-Ling Chen, Xiu-Juan Wang, Li Fu, Fang Liu
Beijing Tsinghua Changgung Hospital
OBJECTIVES Corynebacterium striatum (C. striatum) are often dismissed as contaminants in blood cultures, but it can also cause infective endocarditis (IE), which is a rare but potentially fatal condition. There is a lack of literature regarding the patterns and clinical course of IE development following C. striatum infection. We sought to pool the existing data in regards to defining characteristics, management options, and outcomes of C. striatum related IE (CSIE).
METHODS An electronic search of PubMed, China National Knowledge Network (CNKI), VIP Information Chinese periodical service platform, Wan fang data knowledge service platform were performed to identify all articles both in the English literature and in the Chinese literature that report IE caused by C. striatum in adult patients. Patient-level data were extracted and analyzed.
RESULTS Systematic search yielded 35 patients from 32 articles. Median patient age was 68 [IQR 53, 73] and 66% of patients (23/35) were male. 60.0% (21/35) patients had heart disease previously, 31.4% (11/35) had a history of cardiac device or intra cardiac catheter placement, and 25.7% (9/35) had chronic renal insufficiency. The most common symptome were fever 97.1% (34/35), dyspnea 42.9% (17/33), congestive heart failure and neurologic syndrome 34.3% (12/35), respectively. A heart murmur was recorded in 54.3% (19/35) patients. Vegetations was found in 94.3% (33/35) of patients. CSIE most often involves the left heart valve, the mitral valve was observed in 51.5% (17/33) of patients, followed by aortic valve SCIE in 33.3% (11/33), and the right heart valve were rare. Native valve involvement was 84.8% (28/33), while prosthetic valve involvement was 12.1% (4/33). 31.4% (11/35) of the patients were misdiagnosed, including being misdiagnosed as contaminated bacteria, not finding C. striatum in initial blood cultures, and being misdiagnosed as other bacteria. Drug susceptibility tests were performed in 62.9% (22/35) of the cases, 40.9% (9/22) were multi-antibiotic drugs resistant, and no resistance to vancomycin or dattomycin was reported. The most commonly used antibiotic was vancomycin (51.4%, 18/35) in clinic treatment. Surgical management of IE was observed in 54.3% (19/35) of cases. This included valve surgery for 28.6% (10/35), including the aortic valve in 20.0% (7/35) and mitral valve in 17.1% (6/35) of patients. Pacemakers were removed in 5 patients and central vein was removed in 2 patients. Overall case fatality was 35.3% (12/34). Of these, 26.5% (9/34) died during the hospitalization. Prosthetic valve CSIE was associated with a significantly higher case fatality 50% (2/4) than that of native CSIE 28.6% (8/28) (P=0.02).
CONCLUSIONS We report the first analysis of species-specific risk factors and outcomes in CSIE. This review highlights the seriousness of CSIE, On the one hand, although CSIE is rare, it is easily misdiagnosed and missed. On the other hand, as up to 40.9% of patients were multi-antibiotic drugs resistant and51.4% required surgical management. Overall CSIE patient survival is poor and may be worse if caused by prosthetic valve
GW34-e0738
Wei Sun1,2,3, Qing Lv1,2,3, Li Zhang1,2,3, Mingxing Xie1,2,3
1Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Clinical Research Center for Medical Imaging in Hubei Province, Wuhan 430022, China
3Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
OBJECTIVES Numerous right ventricular (RV) systolic function parameters have been recognized as an important predictor of outcomes in various cardiovascular diseases. However, it is not clear which one of the RV systolic function parameters is a truly strong and independent predictor of mortality after heart transplant (HT), or whether there is an incremental prognostic advantage in combining several RV function parameters. The study aimed to (1) explore the prognostic value of right ventricular (RV) systolic function; (2) further combine several RV function parameters to develop an RV function score (RVFS) of adverse clinical events post-heart transplant (HT) using echocardiography.
METHODS A total of 357 consecutive HT recipients were prospectively included. RV systolic function was evaluated by RV fractional area change (RV FAC), tricuspid annular plane systolic excursion (TAPSE), tricuspid lateral annular systolic velocity (S′), and RV free wall longitudinal strain (FWLS) using echocardiography. The multivariate Cox hazard model was performed to identify the independent predictors of RV function for adverse events. And receiver operating characteristic (ROC) curves were performed to identify their best cutoff values.
RESULTS A total of 357 patients post-HT were included, after a median follow-up period of 39 (29, 42) months, the adverse events occurred in 51 patients. The multivariate COX analysis showed that RV FAC, TAPSE, and RV FWLS were all the independent predictors of adverse events post-HT, and ROC curves were used to identify the optimal cutoff values. Then the RVFS was constructed by assigning the value of 1 to each independent predictor when it’s above the cutoff value, and 0 when it’s below the cutoff value, and then by summing the number, ranging from 0 to 3 points. And the ROC curves showed that the accuracy for predicting adverse events was greater for the RVFS than separate RV function parameters (area under the curve: 0.84 vs 0.64~0.78, P<0.05). Furthermore, adding the RVFS to the base clinical model improved the C index (from 0.74 to 0.81, P<0.0001), and yield an absolute IDI of 0.177 (P<0.001), and a continuous NRI of 0.462 (P<0.001).
CONCLUSIONS The RV FAC, TAPSE, and RV FWLS all were independent predictors of adverse events after HT. Furthermore, the RVFS, an easily obtainable echo score, which combined several RV function parameters, improved the predictive value over separate RV function parameters and baseline clinical predictors. Therefore, it is suggested that the RVFS may offer good discrimination of adverse outcomes after HT in clinical.
GW34-e0910
Shu-huai Hou1,2, Hong-gang Sui1,2, Tienan Zhou1,2, Lei Zhang1,2, Xiaozneg Wang1,2
1Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110016, China
2National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110012, China
OBJECTIVES To investigate the influencing factors and prognosis of bird-beak configuration formation after thoracic aortic endovascular repair (TEVAR) of Stanford type B aortic dissection.
METHODS From January 2010 to September 2021, 663 patients with Stanford type B aortic dissection with TEVAR were collected. The patients were divided into the bird-beak group (n=282) and the non-bird-beak group (n=381) according to whether the bird-beak configuration occurred after TEVAR. The clinical and surgical data of the two groups were compared, and the related factors affecting the formation of beak morphology and the prognosis of the patients after TEVAR were analyzed. A subgroup comparison was made on the occurrence of internal leakage in the bird-beak configuration group.
RESULTS In the bird-beak group the ratio of male, systolic blood pressure and diastolic blood pressure at admission and hemoglobin count were higher than those in the non-bird-beak group, with statistical significance (P<0.05). The proportion of cerebrovascular history in the bird-beak group was lower than that in the non-bird-beak group, with statistical significance (P<0.05). In the bird-beak group the ratio of the intimal rupture from the left subclavian artery opening <15 mm, the total length of the stent and stent implantation in aortic region 2 were higher than those in the non-bird-beak group, with statistical significance (P<0.05). The proportion of patients in the bird-beak group with proximal bare stent implantation, the mean diameter of distal stent implantation, and the proportion of type III aortic arch implantation were lower than those in the non-bird-beak group, with statistical significance (P<0.05). Multivariate logistic analysis showed that the stent implantation was located in aortic region 2 (OR=3.314, 95% CI: 1.795–6.119; P<0.001) was an independent risk factor for bird-beak configuration formation. Intraoperative implantation of proximal bare stents (OR=0.013, 95% CI: 0.006–0.026; P<0.001) was a protective factor for bird-beak configuration formation after surgery. The incidence of intraoperative immediate internal leakage was significantly higher in the bird-beak group than in the non-bird-beak group (27.3 vs. 17.6%, P=0.003). There were no significant differences in the incidence of all-cause death, new stroke, aortic related adverse events and overall clinical adverse events between the bird-beak group and non-bird-beak group at 30 days after surgery and at long-term follow-up (P>0.05). Rehairpin layer, internal leakage, aorta-related adverse events and overall clinical adverse events were higher than those in the non-immediate internal leakage group, and the difference was statistically significant (P<0.05).
CONCLUSIONS The placement of the proximal stent in area 2 was an independent risk factor for postoperative bird-beak configuration formation in Stanford type B AD patients treated with TEVAR, and implantation of the proximal nude stent was a protective factor for postoperative bird-beak configuration formation. The formation of bird-beak configuration after TEVAR significantly increased the occurrence of immediate postoperative internal leakage.
GW34-e0911
Tian-shu Xu1,2, Hong-gang Sui1,2, Xiao-zeng Wang1,2, Tie-nan Zhou1,2, Lei Zhang1,2
1Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110016, China
2National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110012, China
OBJECTIVES We aimed to analyze the risk factors for the deterioration after optimal medical therapy (OMT) in Stanford type B intramural hematoma (TBIMH) patients and the outcomes associated with the subsequent treatment options.
METHODS A total of 215 patients with TBIMH diagnosed by computed tomography angiography (CTA) were consecutively enrolled between January 2014 and June 2022 for this retrospective study. Among them, 98 patients showed stable OMT outcomes and 117 patients showed deteriorated OMT outcomes. Of the 117 patients who had a deterioration after OMT, 38 patients underwent further thoracic endovascular aortic repair (TEVAR) therapy (TEVAR group). Forty-five patients met TEVAR indications but refused intervention (TEVAR Rejection group). Thirty-four patients who did not meet the TEVAR indications continued to be treated with OMT (continued OMT group). Patient treatment outcomes were observed during the follow-up period. Multivariate Logistic regression was applied to analyze the risk factors for the deterioration after OMT. And the prognosis of patients receiving different treatments in the deteriorated group was compared.
RESULTS Multivariate analysis outcome showed that IMHT on initial CTA (OR=1.203, 95% CI: 1.085–1.333; P<0.001) and ΔIMHT (OR=1.231, 95% CI: 1.146–1.323; P<0.001) during follow-up were the risk factors for deterioration after OMT. The prognostic analysis of deteriorated patients after OMT was performed according to the subgroups of different treatments. The overall clinical adverse events were significantly greater in the TEVAR-rejection and continued OMT groups than in the TEVAR group, respectively (P=0.027, P=0.009). There was no significant difference in overall clinical adverse events was found between the TEVAR-rejection group and the continued OMT group (P=0.582). There was no statistically significant difference in the incidence of all-cause death and aortic-related death among the three subgroups of patients (all P values>0.050). The incidence of new-onset pleural effusion was substantially higher in the continued OMT group than in the TEVAR group (P=0.020). But no significant difference was found between the TEVAR group and the TEVAR-rejection group and the result was the same between the TEVAR-rejection group and the continued OMT group (All P values>0.050). Imaging outcomes during the follow-up period showed no significant difference in new-onset aortic-related adverse events among the three subgroups (P=0.494). The Kaplan-Meier curve analysis in three subgroups revealed a statistical difference in event-free survival rate (P=0.044). The TEVAR group had a significantly better survival rate than the TEVAR-rejection group and the continued OMT group in the mid-term (0–2 years) (TEVAR group vs. TEVAR-rejection group: P=0.019; TEVAR group vs. Continued OMT group: P=0.029). However, no significant difference in the long-term (2–5 years) survival rate between the TEVAR group and the other two groups was found (All P values> 0.050).
CONCLUSIONS IMHT on initial CTA and ΔIMHT during the follow-up period were the independent risk factors for deterioration after OMT. Patients who deteriorated after OMT had a better prognosis when treated with TEVAR.
GW34-e0914
Chun-liu Wu1,2, Hong-gang Sui1,2, Tie-nan Zhou1,2, Lei Zhang1,2, Xiao-zeng Wang1,2
1Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110016, China
2National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110012, China
OBJECTIVES To investigate the risk factors for false lumen extending beyond renal artery level in Stanford Type B aortic dissection (TBAD) patients, and observe the efficacy of thoracic endovascular aortic repair (TEVAR) and the influence of different renal artery involvement conditions on renal function and clinical prognosis in TBAD patients.
METHODS This study collected 797 patients with TBAD diagnosed by CT angiography from April 2002 to November 2022. All the patients were divided into the group that false lumen not extending beyond renal artery (FLNRA, n=243) and the group that false lumen extending beyond renal artery (FLRA, n=554), according to whether the scope of the false lumen extending in TBAD patients beyond renal artery. Multivariate Logistic regression was used to analyze the risk factors associated with false lumen extending beyond renal artery in TBAD patients, and its effect on the prognosis of patients after TEVAR. The patients with TBAD whose false lumen extended beyond the renal artery were divided into 3 groups according to the number of renal artery involved, and the prognosis of the three groups was observed.
RESULTS Univariate logistic regression analysis indicated that age, male, body mass index, hypertension history, abdominal pain, left ventricular end-diastolic diameter, white blood cell count, D-dimer and triglyceride were correlated with false lumen extending beyond renal artery level in TBAD (P<0.05). Multivariate Logistic regression analysis indicated that hypertension history, abdominal pain, D-dimer were independent risk factor for false lumen extending beyond renal artery level in TBAD, and age was a protective factor for false lumen extending beyond renal artery level in TBAD. Recent follow-up results showed that the incidence of postoperative AKI in the FLRA was significantly higher than the FLNRA (P<0.06). Long-term follow-up results showed that the incidence of aortic death, aorta-related adverse events, recurrent aortic dissection, total clinical adverse events, and reintervention in the FLRA were significantly higher than the FLNRA (P<0.05). Recent follow-up results of different renal artery involvement condition in TBAD patients whose false lumen extending beyond renal artery showed that there was statistically significant difference in postoperative acute kidney injury (AKI), incidence among the three groups (P<0.05), and the ilateral involvement group was significantly higher than non-involvement group (P<0.05). Compared with the group without renal artery involvement with the lowest incidence of AKI, and the risk of postoperative AKI was analyzed in the other two groups. The results indicated that the risk of postoperative AKI was increased in the bilateral renal artery involved group significantly (P<0.05). Long-term follow-up results showed that the incidence of long-term clinical adverse events were no significant differences among the 3 groups (P>0.05).
CONCLUSIONS History of hypertension, abdominal pain, D-dimer were independent risk factor for false lumen tear extending beyond renal artery level in TBAD, and age was a protective factor. Patients with false lumen extending beyond renal artery have a higher incidence of postoperative AKI and a poorer long-term prognosis.
GW34-e0923
Shuhui Wang, Haitao Lv
Children’s Hospital of Soochow University, Suzhou
OBJECTIVES Predicting intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) can aid early treatment and prevent coronary artery lesions. We established a clinically consistent model to predict IVIG resistance in KD.
METHODS In this retrospective cohort study of children diagnosed with KD from January 1, 2016 to December 31, 2021, a scoring system was constructed. A prospective model validation was performed using the dataset of children with KD diagnosed from January 1 to June 2022. The least absolute shrinkage and selection operator (LASSO) regression analysis optimally selected baseline variables. Predictors from the LASSO regression analysis were used to construct the prediction model using multivariate logistic regression. A nomogram was developed based on selected variables. The calibration plot, area under the receiver operating characteristic curve (AUC), and clinical impact curve (CIC) were used to evaluate model performance.
RESULTS Of 1 975, 1259 children (1177 IVIG-sensitive and 82 IVIG-resistant KD) were included in the training set. Lymphocyte percentage; C-reactive protein/albumin ratio (CAR); and aspartate aminotransferase, sodium, and total bilirubin levels, were risk factors for IVIG resistance. The training set AUC was 0.825 (sensitivity, 0.723; specificity, 0.744). CIC indicated good clinical application of the nomogram.
CONCLUSIONS A new prediction model was developed based on data from a large sample collected in a prospective manner, with improved modeling techniques and standardized methodological criteria. An emphasis on internal and external validation of models and model updates provides high-quality evidence for clinical practice. The nomogram can well predict IVIG resistance in KD. The C-reactive protein/albumin ratio was a novel biomarker in predicting IVIG resistance in Kawasaki disease.
GW34-e1002
Hongbiao Huang, Haitao Lv
Children’s Hospital of Soochow University
OBJECTIVES Kawasaki disease (KD) is an acute vasculitis that is self−limiting and affects children. In developed countries, KD represents the most common cause of childhood acquired heart disease. Serious complications include coronary artery disease and myocarditis. After COVID-19 pandemic, the incidence of KD has increased sharply in the world.
METHODS Phenotype in our research is KD vasculitis, we confirmed them by heart tissue sections pathology. The phenotype means different cells and genes change in inflamed tissues, we confirmed them by scRNA-seq+Spatial transciptomics (ST) and confirmed transcriptional regulation by scRNA-seq+scATAC-seq.
RESULTS
1. Firstly, we integrative scRNA-seq and ST. According to deconvolution results, we found that VSMC phenotypic switch in inflamed region (from original VSMC1 to fibroblast VSMC2), then we found that macrophages and neutrophils are increased gradually in inflamed region. Combine gene expression and its spatial location, we found T cell can interacts with VSMC.
2. Secondly, we download the coronary arteries bulk RNA-Seq data (GSE64486) from KD patients and non-KD controls. CIBERSORTS was used to analyze the cell proportion. We found that elevated T cell/macrophage infiltration in KD group & VSMCs switch into myofibroblast.
3. Thirdly, according to the HE staining section of myocarditis, we found that macrophage infiltrates into cardiomyocyte at the acute stage of KD in the mouse model.
4. Lastly, I further look into the potential transcription factor (TF) related transcriptional regulation. I observed AP-1 ranking on top in both the TF activity determined from scRNA-Seq data and the highest accessibility identified from scATAC-seq data in VSMC from KD14. AP-1 has been implicated as a key regulator in cell proliferation, differentiation, and transformation which may cause VSMC dedifferentiation in KD.
CONCLUSIONS By multi-omics analysis, we identify potential transcription factor AP-1 and its regulatory network changes associated with the progression of KD in different tissues, including vascular smooth muscle cells and immune cells, ultimately leading to the dedifferentiation of VSMC. We aim to reveal the underlying mechanisms of KD pathogenesis and identify potential therapeutic targets for this devastating disease.
GW34-e1187
Ziwei Wang, Juanjuan Qin
Department of Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
OBJECTIVES Our study targeted at explore metabolic feature of metabolically unhealthy normal weight (MUNW) of Chinese elderly persons and the association of metabolic subgroups of MUNW with cardiovascular disease and all-cause mortality.
METHODS Population were extracted from China Health and Retirement Longitudinal Study (CHARLS), a 7-year follow-up longitudinal population aged 45 years and above were included from China Health and Retirement Longitudinal Study (CHARLS). Body mass index (BMI) and five metabolic covariates, including lipid metabolism, glucose metabolism, high blood pressure, waist circumference (WC), and UA were utilized to classified MUNW. Latent class analysis (LCA) divided MUNW into metabolic subgroups. Cox proportional risk regression models was utilized to estimate the association between metabolic subgroups and new cardiovascular disease (CVD) including stroke and death, with the normal metabolic population serving as the reference. Two modes were estimated: sex (men or female) and age (in years) were adjusted in the mod-el1; age, sex, smoking (yes or no), drinking (yes or no), an education level (elementary school or below and college and above) and medicine use history were adjusted in model 2. Considering the influence of sex and age, we analyzed the population in separate clusters respectively.
RESULTS We found that MUNW accounted for nearly 40% in Chinese aged people, and almost 70% normal weight individuals had metabolic problems. Finally, 4001 individuals were filtered in baseline, and four metabolic categories were identified in MUNW: hypertension (N=433; 15.43%), glucose and lipid metabolism (N=808; 28.80%), dyslipidemia (N=464; 16.54%), and central obesity (1101; 39.24%), and the incidence of CVD was 18.01%, 17.57%, 15.51%, 19.44% respectively. We discovered that all four classes of metabolic disorders are risk factors for cardiovascular disease. The centrally obese group had a more prominent cardiovascular risk (HR=1.67, 95% CI: 1.35–2.07). And glucose and lipid metabolism group had a more significant all-cause of death (HR=2.5, 95% CI: 1.84–3.41). We found that men have a higher risk of incident cardiovascular disease, while female have a higher risk of all-cause mortality. In the 45–65 age group, central obesity and hypertension were high risk of CVD (HR=1.69; 95% CI: 1.3–2.19) and all cause of death (HR=3.25; 95% CI: 1.85–5.73) respectively. We did not discovered differences between metabolic subgroups in people over 75 years of age.
CONCLUSIONS This is the first study to investigate the metabolic patterns of MUNW, and we identified distinguishing features in each subgroup. Our study reveals that MUNW, which overlooked due to their healthy phenotype, are actually at high risk of developing cardiovascular disease in the future. Risk awareness should emerge in mind and early interventions could help decrease the risk of cardiovascular diseases.
GW34-e1417
Mengyuan Dai, Ping Du, Yanli Zhang, Zijie Ding, Xinxin Zhang, Ying Liu
First Affiliated Hospital of Dalian Medical University, Dalian 116011
OBJECTIVES The aim of this study is to explore the effects of early combination with soluble guanylate cyclase (sGC) stimulator vericiguat and Guideline-directed medical therapy (GDMT) on ventricular remodeling and cardiac function in patients with worsening heart failure in real-world.
METHODS This study retrospectively analyzed 135 patients with LVEF<45% HFrEF who were treated in the First Affiliated Hospital of Dalian Medical University from 1st Sep 2022 to 9th March 2023. During hospitalization, systematic etiological screening and standardized diagnosis and treatment were conducted, and strict outpatient follow-up was conducted after discharge. Patients were enrolled into two groups based on whether they were treated with vericiguat, vericiguat+GDMT group (57 cases) and GDMT group (78 cases). The changes in symptoms, signs, electrocardiogram, echocardiography, and NT-proBNP monitored during follow-up were examined in both groups of patients.
RESULTS 135 patients were enrolled, the mean age of the patients was 63.36±13.38 years, 87 (64.4%) were men. The median follow-up period was 3.5 months. Follow-up result shows that, compare with GDMT group, the increase of left ventricular Ejection fraction (LVEF) in the vericiguat+GDMT group was significantly higher (vericiguat combined with GDMT group 7.18±9.47 mm vs. GDMT group: 2.42±7.69 mm, P=0.002). The vericiguat+GDMT group was significant decrease in left ventricular diastolic diameter (LVEDD) compare with GDMT group. (vericiguat+GDMT group: −2.75±7.00 vs. GDMT group: −0.53±3.30–2.00 mm, P=0.021). The proportion of LVEF increased by more than 5%, vericiguat+GDMT group was significant higher than GDMT group (vericiguat+GDMT group: 47.36% vs. GDMT group: 25.64%, P=0.009). The proportion of LVEDD decreased by more than 10 mm, vericiguat+GDMT group was significant higher than GDMT group (vericiguat+GDMT group: 15.78% vs. GDMT group: 1.28%, P=0.001). Vericiguat+GDMT group have a higher proportion of patients with left ventricular reverse remodelling (vericiguat+GDMT group: 24.56% vs. GDMT group: 11.53%, P=0.047). The results of multivariate logistic regression analysis showed that early combination therapy with vericiguat was an independent predictor of LVEF increase>5% (OR=3.289, 95% CI 1.149–9.417, P=0.027), LVEDD decrease>10 mm (OR=9.926, 95% CI 1.021–96.474, P=0.048), and left ventricular reverse remodeling (OR=4.809, 95% CI 1.008–22.940, P=0.049).
CONCLUSIONS In real-world, patients with WHF can significantly reverse left ventricular remodeling by early combination with vericiguat on the GDMT during hospitalization. Early multi-pathway combination therapy can better improve heart function in patients with heart failure.
GW34-e1418
Daoyuan Si, Zihan Li, Yuquan He
China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun City, China
BACKGROUND Vericiguat has demonstrated efficacy and safety in clinical trials of patients reduced ejection fraction in heart failure (HFrEF), but real-world data are needed.
OBJECTIVE This study aimed to evaluate the efficacy and safety of vericiguat in HFrEF patients in a real-world setting.
METHODS Patients with HFrEF who were treated with vericiguat per the China approved indications at the third Bethune Hospital of Jilin University between Sep 2022 to June 2023 were enrolled. The primary endpoint was the change of LVEF from baseline to month 3.
RESULTS A total of 45 patients had at least one time echo test at 3 months were included in the study. Mean age was 59.5±13.6 years; 69% were men; 77.1% were ischemic cardiomyopathy, mean LVEF was 36.6±10.3%. LVEF significantly increased from baseline to month 3 (36.6±10.3–42.7±12.0%; P<0.05). NT-prBNP level significantly reduced from baseline to month 3 (6437.2±8235.9 pg/mL to 3150.4±3411.3 pg/mL; P<0.05). There were no significantly change on K+ level (4.2±0.5 mmol/L to 4.3±0.4 mmol/L) and eGFR (86.0±47.4–100±53.9).
CONCLUSIONS In this real-world study, significant improvements of vericiguat on LVEF and NT-proBNP were observed from baseline to month 3, and there is little impact on K+ level and eGFR.
OTHERS
GW34-e0035
Mengjun Wang, Hong Wang, Xiaotong Hou
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Cardiogenic shock (CS) has a high mortality rate and needs to be studied extensively to reduce this trend in future CS patients. Furthermore, there is a need to document the trends in CS research, and the contributions of different countries, institutions, journals, and authors over the past 10 years are not clear.
METHODS We searched the medical literature via the Web of Science and extracted all relevant publications about CS published between 2012 and 2021. The R package and VOSviewer software were used to analyze the publication trends in CS research.
RESULTS A total of 6007 publications were analyzed. The number of articles on CS has increased twofold in the past 10 years. The United States accounted for the largest number of articles (33.3%) and ranked first in the number of citations (30,043), followed by Germany in the number of articles (7.9%) and citations (13,435). The Journal of the American College of Cardiology had the highest number of publications (8.96%) in this field. Dr. H. Thiele has published the most papers (209) in this area, has attained the highest citation frequency (2189), and earned an h-index of 36. CS-related keywords were ranked according to their year of appearance in the selected time period (2012–2021). The keyword “venoarterial extracorporeal membrane oxygenation” (VA-ECMO) had the most recent time of appearance, with an average appearing year (AAY) value of 2018.96. Research related to mechanical support devices may become a hotspot in the coming years.
CONCLUSIONS CS-related research has increased twofold over the past 10 years. The United States contributed the highest number of CS research articles. The Journal of the American College of Cardiology published the highest number of CS research articles. Research related to mechanical support devices may become a hotspot in the coming years.
GW34-e0050
Wen Fuyuan1, Xie Yunyi1, Li Bingxiao1, Li Pandi1, Qi Han1,2, Zhang Fengxu1, Sun Yuan1, Zhang Ling1
1Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, and Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
2The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital and the Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
OBJECTIVES While growing evidence links long-term air pollution exposure with chronic kidney disease (CKD), combined effects of pollutants mixture and multiple mediation effects of metabolic risk factors were rarely discussed.
METHODS We included 8996 baseline CKD-free adults from the CHCN-BTH cohort study during 2017–2021. Three-year individual air pollutants exposure [particulate matter ≤2.5 μm (PM2.5), PM10, PM1, ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO)] and PM2.5 components [black carbon (BC), ammonium (NH4 +), nitrate (NO3 −), sulfate (SO4 2−) and organic matter (OM)] were assessed using well-validated machine learning methods. Generalized linear mixed models were applied to examine the associations between air pollutants and CKD progression. Quantile g-Computation was used to assess the combined effects of air pollutant mixtures. Causal mediation analysis and Bayesian mediation analysis were employed to estimate the univariate and multivariate mediation effects of metabolic risk factors.
RESULTS During the follow-up, 399 participants had an incident of CKD progression. Interquartile range (IQR) increases in BC [OR: 1.010 (95% CI: 1.008–1.012)], SO4 2− [1.024 (1.019–1.029)] and OM [1.028 (1.023–1.033)] were robustly associated with incident CKD progression, while a protective effect was observed for O3 [0.965 (0.957–0.974)]. Incident CKD progression was associated with PM2.5 components mixture [BC, SO4 2− and OM, 1.023 (1.017–1.29)]. OM was the major contributor to CKD progression (104.3%). Univariate mediation analysis showed that high-density lipoprotein (HDL) mediated 13.9% and 14.1% effects of O3 and SO4 2−. Fasting plasma glucose (FPG) also showed minor mediation effects of O3, BC, SO4 2− and OM (range: 2.142–3.459%). However, none of these mediation effects remained significant in Bayesian mediation analysis.
CONCLUSIONS The findings indicated the effect of PM2.5 component mixtures on CKD progression and the dominant contribution of OM over the other components. Metabolic risk factors might not mediate the effects of air pollutants. Further study is warranted to clarify the potential mechanism involved.
GW34-e0144
Xinyue Chen1,2, Chenxin Song1,2, Long Jiang1
1Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
2The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
OBJECTIVES Moyamoya disease (MMD) is an uncommon but important cerebrovascular disease. The factors associated with MMD are still unclear but may be related to various mechanisms such as genetics, inflammation, and immunity. This retrospective cohort study is aimed to investigate the potential association between lipoprotein(a) [Lp(a)] and MMD.
METHODS The data of inpatients with electronic health records were collected from the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The case and control groups were matched by the propensity score matching (PSM) method. Corrections between Lp(a) quantiles and MMD were analyzed by logistic regression and stratified analysis. The R and IBM SPSS software were used to perform statistical analyses.
RESULTS A total of 1012 MMD patients and 2024 control inpatients were matched at a 1:2 ratio by PSM methods. The median Lp(a) concentration was higher in MMD patients than in controls (18.45 vs. 14.92 mg/dL, P<0.001). Results of the Spearman correlation indicated that Lp(a) was significantly and positively correlated with MMD (r: 0.085, P<0.001). In addition, Lp(a) levels>32.56 mg/dL were associated with a significantly higher MMD risk in the unadjusted model [1.613 (1.299–2.002), P<0.001], model 1 [1.598 (1.286–1.986), P<0.001], and model 2 [1.661 (1.330–2.074), P<0.001]. Furthermore, this significant relationship was not impacted by age, sex, or hypertension in the stratified analysis.
CONCLUSIONS The high Lp(a) level (>32.56 mg/dL) was associated with MMD, suggesting that Lp(a) may be useful for risk stratification in MMD patients.
GW34-e0221
Chean Lin Chong1, Sok King Ong2
1RIPAS Hospital, Ministry of Health, Brunei
2NCD Prevention Unit, Ministry of Health, Brunei
OBJECTIVES Mobile health applications have been increasingly being adopted for use by healthcare sectors in the developed and also developing countries. The applications empower individuals to monitor, get updated, motivated and access accurate knowledge from different geographical locations in real time. The COVID-19 pandemic has accelerated the adoption of digital health in many areas including cardiovascular disease (CVD) prevention, screening and risk assessment. In Brunei, the national electronic medical system (BruHIMS) was established in 2013. In 2022, pilot programme of CVD screening and risk assessment was rolled out nationwide using Bruhealth mobile application which was initially developed for the use of contact tracing during the pandemic.
METHODS A literature review was conducted on the CVD risk scoring methods from the World Health Organisation (WHO) and other established scoring systems and screening guidelines. Local burden of CVDs and risk factors in Brunei were reviewed. Variable for WHO’s updated CVD risk laboratory based chart and additional variables relevant to the local populations were assessed for inclusion in the risk assessment algorithm. System testing was conducted and pilot rolled out to users aged 40 years or above from 21 November to 20 December 2022 with a target sample size of 3000.
RESULTS Additional variables for CVD risk assessment, in addition to the WHO chart, were included in the risk assessment algorithms. These are duration of smoking, year of diabetes diagnosis, year of other CVD diagnosis, family history, ethnicity, BMI, history of chronic kidney disease, atrial fibrillation, rheumatoid arthritis, systemic lupus erythematosus, steroid use, results of ECG, ECHO, CT angiogram, coronary artery calcium, creatinine and brain imaging. Data available from the participants’ BruHIMS records were linked for participants consented to participate in the risk assessment. In the initial phase (first 2-weeks) of pilot roll-out, low usage (about 1% of target sample size) was observed. With nudge strategy in the later phase of pilot, the usage rate was increased to 7% of the target sample.
CONCLUSIONS Mobile health application can be used to support disease prevention including screening and risk assessment of noncommunicable diseases such as CVDs, hypertension and diabetes. Challenges in the adoption of digital mobile application need to be addressed. Successful adoption requires multipronged public education to increase its usage, ensuring accessibility of technologies to target populations, and enhancing inter-operability between different digital and information system such as linking to the patient medical records.
GW34-e0243
Yan Chen
Wuhan Asian Heart Hospital
OBJECTIVES The incidence of Behcet’s disease involves various types of blood vessels, the most common being aneurysms. In our department, one patient with Behçet’s disease complicated by aortic root aneurysm and abdominal aortic aneurysm was treated with surgery, and the results were relatively satisfactory. The report is as follows.
METHODS The patient, male, 39 years old, was seen in our hospital on May 27, 2020 because of “intermittent chest tightness, chest pain and asthma for more than 3 years, which became worse in January”. After admission, CTA of large vessels and coronary arteries indicated: aortic atherosclerosis. The aortic sinus and ascending aorta widened. True aneurysm of the upper descending aorta and the transeptal segment of the abdominal aorta. Ask the rheumatology and immunology department for consultation and the final diagnosis is Serh’s disease. Begin to give prednisone 30 mg orally once a day; methotrexate tablets 4# orally once a week; folic acid tablets 10 mg orally once a week; thalidomide tablets 2# once a night. The above treatment plan was maintained during the perioperative period, and prednisone was changed to intravenous medication before the operation.
staging operation.
RESULTS After 14 days of hospitalization, one-stage surgical treatment assisted by cardiopulmonary bypass, (petticoat technique) aortic valve and ascending aorta replacement and coronary artery transplantation (Bentall surgery) + total aortic arch artificial blood vessel replacement + stent elephant nose surgery + intraoperative heart Pacemaker. Four months after the operation, he was hospitalized again for the second-stage operation. The abdominal aortic aneurysm was detected during the second-stage operation.
CONCLUSIONS The patient was discharged from the hospital 15 days after the operation (2020.10.23–2020.11.08), and the immunotherapy program was continued after discharge, while warfarin was treated with anticoagulation. Long-term follow-up observation in the Department of Rheumatology and Immunology after operation.
GW34-e0285
Xiang Li1, Heyi Zhang2, Juju Shang1, Hongxu Liu1, Qi Zhou1, Xiaolei Lai1
1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University
2Beijing University of Traditional Chinese Medicine
OBJECTIVES This study aimed to investigate the clinical characteristics of patients with unstable angina (UA) who received elective coronary interventional intervention (PCI) in a traditional Chinese medicine (TCM) hospital and to analyze the related risk factors of peri-procedure myocardial injury (PMI).
METHODS On the basis of cross-sectional investigation, case-control method was adopted. We retrospectively collected clinical data of patients with UA who successfully received elective PCI in Beijing Hospital of TCM from February 2017 to February 2019. Based on the occurrence of PMI, the case control was formed. The influence of related factors on PMI occurrence was analyzed by Logistic multiple regression equation based on the parameters between the comparison groups.
RESULTS 1) Incidence of PMI and related clinical features: Of the 265 UA patients, the incidence of PMI was 26.4%, nearly one quarter (23.4%) had old myocardial infarction, nearly half (45.3%) had previously received coronary intervention. The prevalence of patients with previous hypertension (75.8%), type 2 diabetes (57%), and high-low-density lipoprotein cholesterolemia (69.3%) exceeded 50%, more than 50% of patients have triple vessel disease (50.2%). 2) Features of TCM Syndrome Elements: The main TCM syndromes of the investigated patients are Blood stasis syndrome (81.1%) and Qi deficiency syndrome (77.3%), the others include Phlegm turbidity syndrome (53.2%), Yang deficiency syndrome (50.9%), Yin deficiency syndrome (50.1%), Qi stagnation syndrome (30.1%) and Coagulated cold syndrome (17.1%). 3) Factors of PMI occurrence: According to the occurrence of PMI, 265 patients were divided into PMI group (n=70) and non-PMI group (n=195). The comparison between groups shows that the preoperative Syntax score, the number of stents and the total length of stents of the patients in the PMI group were higher than those in the non-PMI group (P<0.05); the patients in PMI group treated by Shen-Yuan-Dan (SYD), a Chinese medicine prescription with Qi-Supplementing and Blood Stasis-Purging, was significantly lower than that of non-PMI group (P<0.05). Brought these four factors (preoperative Syntax score, number of stents implanted, total length of implanted stents, and treated by SYD) into the binary logistic regression equation, Only treated by SYD has statistical significant in the equation as a protective factor. (OR 0.327, 95% CI 0.117~0.916, P=0.033).
CONCLUSIONS Patients with UA who received elective PCI in TCM medical institutions may have clinical characteristics including multiple accompanying diseases and high stenosis coronary artery, in which the incidence of poor blood glucose control and high rate of three-vessel coronary disease are particularly significant. The TCM syndromes are mainly Qi deficiency and Blood stasis syndromes. The decrease of PMI may be attributed to the application of SYD in the real world.
GW34-e0366
Zhang Yingqian1, Hui Hui2, Chen Yundai1
1Chinese PLA General Hospital
2Beijing Key Laboratory of Molecular Imaging
OBJECTIVES Patients with diabetes mellitus (DM) have an increased risk of in stent restenosis (ISR). Neovascularization (NV) is considered as a unique phathophysiological factor of ISR in diabetic patients. However, the structures of in vivo human coronary NV and their relationship with ISR, especially in diabetic patients remain unclear. In this study, we aimed to investigate the NV structure differentiation between patients with and without DM after coronary stent implantation using optical coherence tomography (OCT).
METHODS We included 136 patients with ISR (70 patients in DM group and 66 patients in non-DM group) who underwent optical coherence tomography during coronary angiography follow-up. NVs were manually segmented and three-dimensional (3D) rendering of OCT images was performed. NVs >1 mm were classified into longitudinal running and coral tree types according to their 3D structures.
RESULTS The popularity of the coral tree pattern NV in the DM group was 2.14-fold higher than in the non-DM group (P=0.012). 47.14% of patients in the DM group and 51.51% of patients in the non-DM group presented longitudinal NV (P=0.610). The number of coral tree NV was relatively higher in DM patients than in the non-DM patients (P=0.019). However, the number of longitudinal NV showed no difference between the two group (P=0.872). The normalized NV volume of the DM group was significantly larger than the non-DM group (P=0.008). Normalized NV volume and DM were risk factors for coral tree NV formation in ISR lesions after adjustment for other factors.
CONCLUSIONS NV with particular restructuring patterns, including longitudinal running and coral tree patterns, could be found in ISR lesions. NV with a coral tree pattern, which is leakier and more immature, is more frequently found in patients with DM. Accurate and feasible imaging modalities for NV might offer promising opportunities to evaluate NV and prevent progression of ISR in diabetic patients.
GW34-e0417
Huang Kun1, Yue Wenheng1, Rao Jin2, Chen Yihong1, Liang Chun1
1Department of Cardiology, Second Affiliated Hospital of Naval Medical University
2Department of Cardiothoracic surgery, Second Affiliated Hospital of Naval Medical University
OBJECTIVES Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality in the world. Circulating endothelial cells (CECs), a mature cell population detached from the intimal monolayer in response to endothelial injury and stress, is reported to be associated with early stage of AMI. The specific aim of our study is to identify early diagnostic markers from CECs in circulation building on bioinformatics analysis.
METHODS Raw microarray data of GSE66360 was acquired from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by R software from the discovery cohort of GSE66360 (n=43). The weighted correlation network analysis (WGCNA) was performed to explore the key modules connected with AMI. Next, the main roles of pathological state in AMI were analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network. The selection and identification of diagnostic biomarkers were achieved with least absolute shrinkage and selection operator (LASSO) logistic regression, support vector machine-recursive feature elimination (SVM-RFE) and Random Forests (RF) algorithms. Additionally, the expression and the diagnostic efficiency of the 7 hub genes were proved in the validation cohort of GSE66360 (n=56).
RESULTS In samples of AMI group, we found 366 DEGs including 20 up-regulated genes and 306 down-regulated genes. 276 intersection genes were correlated with AMI significantly in pink and turquoise modules. Based on multiple machine learning algorithms, 7 genes (VCAM1, LILRA1, CCL20, IL1R2, TYROBP, CXCL16, NFKBIA) were identified as hub characteristic genes and showed the satisfactory diagnostic efficiency in the diagnostic cohort and validation cohort respectively.
CONCLUSIONS Our study identified 7 hub genes of circulating endothelial cells in AMI patients, providing novel targets for treatments. Also, we revealed that 7 identified genes in circulating endothelial cells may be early diagnosis markers of AMI.
GW34-e0421
Yuta Hirako1, Yoichi Sunagawa,1,2,3, Kana Shimizu1,3, Masafumi Funamoto1,3, Yasufumi Katanasaka1,2,3, Hiroyuki Shibata4, Koji Hasegawa1,2, Tatsuya Morimoto1,2,3
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
2Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan
3Shizuoka General Hospital, Shizuoka, Japan
4Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, Japan
OBJECTIVES The histone acetyltransferase (HAT) activity of the transcriptional co-activating protein p300 plays a crucial role in LV remodeling and the development of heart failure. We previously found that a natural p300 HAT inhibitor, curcumin (CUR), can inhibit cardiomyocyte hypertrophy and the development of heart failure in vivo. To enhance the therapeutic potency of CUR, many structural analogs of curcumin have been synthesized and investigated. In the present study, we focused on a CUR analog, GO-Y030, which shows stronger anti-cancer activity than CUR. The purpose of this study was to determine whether GO-Y030 inhibits p300-HAT activity and can be used as a therapeutic agent for heart failure.
METHODS First, in vitro HAT assay using recombinant p300-HAT domain showed that GO-Y030 inhibited p300-HAT activity more strongly than CUR. Next, primary cultured cardiomyocytes prepared from neonatal rats were treated with GO-Y030 or CUR and then stimulated with phenylephrine (PE). Finally, C57BL/6J male mice were subjected to transverse aortic constriction (TAC) or sham surgery. One day after surgery, the TAC mice were randomly assigned to one of five groups: vehicle, CUR at 1 or 50 mg/kg, or GO-Y030 at 0.1 or 0.5 mg/kg. The daily oral treatment was carried out for 6 weeks. After that we performed echocardiography, measurement of heart weight, histological analysis, reverse transcription polymerase chain reaction and western blotting.
RESULTS The p300-HAT inhibitory activity of GO-Y030 was stronger than that of CUR. The IC50 value of GO-Y030 was 1.1 μM and that of CUR was 9.4 μM. GO-Y030 suppressed PE-induced histone acetylation, hypertrophic response gene transcription, and cardiomyocyte hypertrophy to the same extent as 10 μM of CUR. Echocardiographic analysis showed that 0.5 mg/kg of GO-Y030 and 50 mg/kg of CUR significantly improved a TAC-induced increase in left ventricular posterior wall thickness and a decrease in fractional shortening. 0.5 mg/kg of GO-Y030 and 50 mg/kg of CUR also suppressed a TAC-induced increase in hypertrophic response gene transcription and HW/BW ratio to the same extent.
CONCLUSIONS These results indicate that the CUR analog GO-Y030 strongly inhibits PE-induced p300-HAT activity compared to CUR, and that a low dose of GO-Y030 prevented both PE-induced hypertrophic responses and pressure overload-induced development of heart failure. These findings suggest that GO-Y030 may be used for heart failure therapy at a lower concentration than CUR.
GW34-e0425
Hyuma Mogi1, Yasufumi Katanasaka1,2,3, Yoichi Sunagawa1,2,3, Toshihide Hamabe-Horiike1,2,3, Takehide Akimoto2, Chikara Ueki2, Mitsuru Kitano2, Koji Hasegawa1,3, Genichi Sakaguchi4, Tatsuya Morimoto1,3,5
1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka
2Department of Cardiovascular Surgery, Shizuoka General Hospital
3Division of Translational Research, National Hospital Organization Kyoto Medical Center
4Department of Cardiovascular Surgery, Kinki University Faculty of Medicine
5Laboratory of Clinical Cardiovascular Pharmacology, Shizuoka General Hospital
OBJECTIVES Adipose tissue is recognized to contribute to physiological regulation and pathological processes. Epicardial adipose tissue (EAT) is known to promote atherosclerosis and coronary artery disease (CAD) pathogenesis, persistently releasing pro-inflammatory adipokines that affect the myocardium and the coronary arteries. Angiopoietin-like 4 (ANGPTL4) is a multifunctional protein secreted from the adipose tissue and the liver. ANGPTL4 plays a critical role in the progression of atherosclerosis, but differences in its expression level in patients with or without CAD and the local effect of ANGPTL4 in the atherosclerotic region have not been clarified. We assessed the hypothesis that the expression of ANGPTL4 is increased in the EAT of patients with CAD compared to those with non-CAD.
METHODS A cross-sectional study approved by the ethics committee of Shizuoka General Hospital (Project identification code: 12-03-56) was carried out with 34 consecutive patients (13 patients with CAD; 21 patients without CAD) undergoing elective open-heart surgery. EAT and pericardial fluid were obtained at the time of surgery.
RESULTS mRNA expressions and protein levels in EAT were evaluated by qRT-PCR and ELISA. The expression levels of ANGPTL4 (P=0.0180) and IL-1β (P<0.0001) in EAT were significantly higher in the CAD group compared to the non-CAD group and were positively correlated with each other (P=0.004). Multiple regression analysis indicated that CAD is a contributing factor to ANGPTL4 expression in EAT. IL-1β level in the pericardial fluid was significantly increased in patients with CAD (P=0.020). Moreover, the expressions of ANGPTL4 (P=0.004) and IL-1β (P<0.001) in EAT were significantly increased in non-obese patients with CAD.
CONCLUSIONS ANGPTL4 expression was increased in the EAT of patients with CAD, and its expression level was positively correlated with that of IL-1β. This result significantly clarifies the mechanism by which EAT metabolism accelerates atherosclerosis and CAD development.
GW34-e0452
Dong Liu, Xiaomeng Zhang, Jingqing Wu, Qian Gao, Zhenguo Zhai
China-Japan Friendship Hospital
OBJECTIVES Therapeutic status and venous recanalization for peripherally inserted central catheter related upper extremity venous thrombosis (PICC-UEVT) were not clarified. The primary objective was to describe the anticoagulation regimen after the diagnosis of PICC-UEVT and to explore the reasons under different treatment regimens. The secondary objective was to explore the potential factors in recanalization of PICC-UEVT.
METHODS Adult patients diagnosed with PICC-UEVT by venous ultrasound in China-Japan Friendship Hospital from January 2018 to December 2020 were retrospectively included. Based on the anatomical location, they were divided into two groups, including isolated superficial venous thrombosis (SVT) and deep venous thrombosis (DVT) with or without SVT. Depending on the anticoagulation prescription, patients were divided into therapeutic dose group and adjusted dose group. Bleed risk assessment were conducted using VTE-BLEED, IMPROVE, RIETE and KUIGER. Meantime the repeated venous ultrasound results within three months after the diagnosis were recorded.
RESULTS Eighty-six patients diagnosed with PICC-UEVT were included and 3 patients were excluded due to the limited information in anticoagulation, comprising 46 males (53.49%) with mean age of (61.43±12.59) years. After the diagnosis, 75 (87.2%) patients have initiated anticoagulation therapy, and low molecular weight heparin was most common selection (60, 80.0%). Patients without anticoagulation had lower platelet level (140 vs 195, P=0.076), hemoglobin level (86 vs 99, P=0.146) compared with patients initiated anticoagulation therapy. Additionally, patients without anticoagulation all have concurrent lower extremity DVT (11,100%) compared with 16 (21.3%) compared with patients initiated anticoagulation therapy. In patients with isolated SVT, 18 (72.0%) patients received the adjusted dose anticoagulation and 7 (28.0%) patients received therapeutic dose anticoagulation. In patients with DVT (combined with SVT or not), 31 (68.9%) patients received the adjusted dose anticoagulation and 14 (31.1%) patients received therapeutic dose anticoagulation. No significant differences were in groups’ comparison in the percentage of dose usage. Besides, 53 (59.55%) patients had the records for the repeated venous ultrasound within three months. Venous recanalization were observed in 21 patients, of which 6 (33.3%) received therapeutic dose anticoagulation but 12 (66.7%) patients underwent adjusted dose anticoagulation.
CONCLUSIONS There exists a large heterogeneity in the management of PICC-UEVT. We observed that many patients underwent dose-adjusted anticoagulation due to bleeding risk but recanalization still exsits. We propose the hypothesis that dose-adjusted anticoagulation may be effective for the venous recanalization in upper extremity. Further prospective studies with regular follow-up strategy are still needed.
GW34-e0548
Li Ren, Chenghui Yan, Yaling Han
Department of Cardiology and Cardiovascular Research Institute of PLA, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES The WHO report indicates that the two most common causes of death are ischemic heart disease and stroke. Together, they account for 27% of the deaths, respectively, 16% and 11%. One of the main causes of CVD is arterial hypertension (AH), which is directly or indirectly responsible for 47% of myocardial ischemia and 54% of strokes. Hypertension is a serious medical problem not only in adults but also in children and adolescents. Many processes and systems are responsible for the efficient functioning of the cardiovascular system, which can be divided into hemodynamic, nervous, humoral, and renal. One of the most important humoral systems that regulate arterial blood pressure is the renin-angiotensin-aldosterone system (RAAS). RAAS is one of the most important mechanisms regulating blood pressure and the balance of water and electrolytes in the body by changing the sodium concentration in plasma and the volume of extracellular fluid. According to the latest reports, RAAS acts not only on endocrine but also on paracrine, autocrine, and intracrine.
METHODS The only precursor to all angiotensin peptides is angiotensinogen (AGT). Angiotensin II has been shown to increase the stability of AGT mRNA. This has positive feedback on AGT. Angiotensin II (Ang II), the major bioactive peptide of the renin/angiotensin system, plays a fundamental role in controlling cardiovascular homeostasis. It is also implicated in various cardiovascular diseases such as hypertension, atherosclerosis, restenosis after angioplasty and heart failure. Ang II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) has the strongest biological activity among the known hypertensive angiotensin-related peptides.
RESULTS Over the recent past, our views of Ang II have changed from being a simple vasoconstrictor to that of a complex growth factor that mediates effects through diverse signaling pathways involving PLC/PKC/Ca2+ mobilization, PLA2, PLD, MAP kinases, tyrosine kinases, proto-oncogene expression, RhoA/Rho kinase, and oxidative stress. Through increased Nox-derived ROS generation and activation of redoxsensitive transcription factors, Ang II promotes expression of cell adhesion molecules and induces synthesis of proinflammatory mediators and growth factors. These molecular and cellular processes facilitate increased vascular permeability, leukocyte recruitment, calcification and vascular fibrosis leading to vascular injury.
CONCLUSIONS Currently, at least five axes of the RAS have been described, with each having its key substrate, enzyme, effector peptide, receptor, and/or downstream signaling pathways. These include the classic angiotensinogen/renin/ACE/ANG II/AT1 receptor, the ANG II/APA/ANG III/AT2/NO/cGMP, theAngI/AngII/ACE2/ANG (1–7)/Mas receptor, the prorenin/renin/prorenin receptor (PRR or Atp6ap2)/M AP kinases ERK1/2/V-ATPase, and the ANG III/APN/ANG IV/IRAP/AT4 receptor axes. Since the roles and therapeutic implications of the classic angiotensinogen/renin/ACE/ANG II/AT1 receptor axis have been extensively reviewed. The major mechanisms of actions for these RAS inhibitors or receptor blockers are mediated primarily by blocking the detrimental effects of the classic angiotensinogen/renin/ACE/ANG II/AT1/aldosterone axis.
GW34-e0633
Zheming Yang1,2, Chenhui Yan1,2, Yaling Han1,2
1National Key Laboratory of Frigid Zone Cardiovascular Disease, 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 (GXST) capsule is a traditional Chinese medicine (TCM) used for treating cardiovascular disease in China. It has shown efficacy in improving symptoms and enhancing the quality of life in heart failure (HF) patients. However, the exact mechanism of action of GXST in HF treatment remains unclear. Therefore, this study aimed to investigate the active ingredients present in GXST and elucidate its mechanism of action in HF treatment using a combination of network pharmacology, molecular docking, molecular dynamics simulation approaches and experimental validation.
METHODS We utilized the SymMap database to identify the principal active ingredients in GXST. Additionally, TCMSP, SWISSTARGET PREDICTION, Pharmmapper, and SymMap databases were employed to obtain the key target genes related to HF. Then identified the overlapping genes between the target genes of GXST and Heart Failure using jvenn software. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed on the identified targets. Furthermore, we constructed a “Traditional Chinese Medicine-Active Ingredient-Target” network using Cytoscape 3.10.0 software, and protein-protein interaction (PPI) analyses on the intersection targets were carried out using the STRING platform. Molecular docking simulations of core protein-ligand interactions were conducted using AutoDock Vina software. Molecular dynamics simulations were performed on the optimal core protein-ligand complexes obtained from molecular docking using gromacs software. Finally, in vitro experimental verification was conducted using CCK8, western blotting, tunel assays, and other molecular biological methods.
RESULTS The constructed herbs-ingredients-target genes-disease network consisted of 72 active ingredients, 320 intersection genes, 399 nodes, and 1899 edges, as visualized in Cytoscape software. Key active ingredients identified included quercetin, kaempferol, beta-sitosterol, naringenin, and ZINC03860434. GO and KEGG pathway analyses demonstrated that the identified pathways were mainly associated with the PI3K-Akt signaling pathway, apoptosis, TNF signaling pathway, endocrine resistance, and HIF-1 signaling pathway. The PPI network revealed the involvement of key proteins such as AKT1, VEGFR2, and eNOS. Molecular docking results indicated that the identified compounds, including kaempferol, quercetin, (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl) chroman-4-one, and ellagic acid, formed stable complexes with their respective core proteins (VEGFR2, eNOS, and AKT). Molecular dynamics simulations further confirmed the stability of these complexes. In vitro experimental verification demonstrated the protective effects of GXST against H2O2-induced apoptosis in HUVECs cells and activation of the VEGFR2/AKT/eNOS signaling pathways.
CONCLUSIONS This study provides insights into the underlying mechanism of GXST’s therapeutic effects in heart failure. The mechanism of GXST in treating HF involves multiple active compounds acting on multiple targets, and multiple pathways, which provides an important reference for further elucidation the mechanism and clinical applications of GXST in the treatment of HF.
GW34-e0714
Yasong Wang1,2, Lin Yang1,2, Zhiqiang Zhang1,2, Tinghao Zhao1,2, Houlin He1,2, Tienan Zhou1,2, Quanyu Zhang1,2, Xiaozeng Wang1,2
1Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110016, China
2National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, Shenyang, Liaoning 110016, China
OBJECTIVES Acute aortic syndromes (AAS) represent a series of life-threatening conditions affecting the aorta. This study aimed to investigate the daily, weekly, monthly, and seasonal variations in the onset of type B AAS in NorthEastern China, and to assess the impact of chronobiological differences on prognosis.
METHODS We evaluated 1642 patients enrolled in the General Hospital of Northern Theater Command between June 2002 and February 2023, 74.6% (1212/1624) were male patients with a mean age of (57.4±12.0) years old. Patients are divided into the aortic dissection (AD) group (N=1055) and the Non-AD group (N=569, patients with intramural hematoma and penetrating aortic ulcer). The χ2 test was used to determine whether a specific period had significantly different distributions from other periods. Fourier models were used to analyse the rhythmicity in monthly distribution.
RESULTS The result of seasonal distribution showed significant differences in the seasonal distribution of overall AAS patients (P<0.001), the highest number of cases in autumn (28.6%, 459 cases), and the lowest number of cases in summer (18.8%, 306 cases). There are also significant seasonal differences in the distribution of AD patients (P<0.001). The fourier analysis confirmed this monthly variation with a peak in January. For patients with AAS and AD the number of cases mainly concentrated in the cooler months (November and December) and in the months of seasonal change (October and April), A peak was identified in October (AAS: 10.2%, 165 cases; AD: 11.2%, 118 cases). Non-AD patients with the highest number of cases in November (10.4%, 59 cases). No significant differences in weekly distribution were shown in all patients (P>0.05, respectively). A total of 1152 patients with a definable time of onset were included in the observation of the circadian distribution, with a significant difference in the circadian distribution of AAS patients (P<0.001), with the peak in the afternoon (12:00–17:59) (31.3%, 360 cases) and the lowest number of cases in the morning (17.3%, 199 cases). The number of AAS cases was negatively correlated with the mean monthly temperature (R2=0.3357, P=0.048), with the number of AAS cases decreasing by approximately 1.22 cases per month for every 1°C increase. Prognostic analysis showed that seasonal and circadian factors had no significant influence on prognosis, and there were no significant differences in adverse events such as all-cause death and aortogenic death (P>0.05, respectively). Kaplan-Meier survival analysis showed that AAS patients treated with Thoracic Endovascular Aortic Repair (TEVAR) had a significantly lower cumulative all-cause mortality rate than those in the drug-treated (logrank P<0.001) and surgical treatment groups (logrank P=0.003), and patients in the AD group treated with TEVAR had a lower cumulative all-cause death rate than those not treated with TEVAR (logrank P<0.001).
CONCLUSIONS The incidence of AAS exhibits significant seasonal, monthly, and circadian. The lowest average temperature (November and December) and seasonal temperature (October and April) transition may increase the incidence of AAS. Seasonal and circadian factors had no significant influence on the prognosis of type B AAS. Keeping warm during the cold months and the months of seasonal transition is of great importance in the management of type B AAS.
GW34-e0739
Zheming Yang1,2, Chenghui Yan2, Yaling Han1,2
1College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China
2National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
OBJECTIVES Nonalcoholic Steatohepatitis (NASH) is a chronic liver disease characterized by the accumulation of fat in the liver, inflammation, and fibrosis. If left untreated, NASH can progress to hepatocellular carcinoma (HCC) and liver failure, increasing the risk of cancer-related mortality. The polycyclic aromatic hydrocarbon carcinogen benzopyrene (B[a]P) has been implicated in the development of several cancers, including bladder, lung, liver, and skin cancers. To gain a better understanding of the relationship between B[a]P, NASH, and HCC, we conducted a comprehensive bioinformatics analysis.
METHODS Gene expression profiles related to B[a]P exposure, NASH, and liver cancer were obtained from the Gene Expression Omnibus (GEO) database. We performed differential gene expression analysis using the R software (version 4.2.1). Additionally, we employed various bioinformatics tools including the STRING database, CytoHubba, and Cytoscape software to identify key genes and their interactions. Moreover, we utilized the GSEA database to explore the signaling pathways associated with the observed gene expression changes.
RESULTS Our analysis of differential gene expression revealed a significant association between the set of differentially expressed genes involved in the B[a]P-NASH-HCC process and impaired cellular metabolic functions and DNA damage repair. This suggests that B[a]P exposure disrupts normal cellular metabolism and compromises DNA repair processes, contributing to the development of NASH and HCC. Furthermore, through four different algorithmic methods, we identified the top ten core genes that play essential roles in the B[a]P-NASH-liver cancer pathway. Notably, among these genes, HSPA1A and PPARGC1A emerged as particularly important candidates. Further investigation indicated their potential involvement in the molecular processes underlying benzopyrene-induced hepatotoxicity and the subsequent progression to NASH and HCC.
CONCLUSIONS Our comprehensive bioinformatics analysis provides insights into the potential regulatory mechanisms driving benzopyrene-induced hepatotoxicity and its association with the development of NASH and HCC. The identification of key genes, such as HSPA1A and PPARGC1A, highlights their potential as therapeutic targets for mitigating the effects of B[a]P-related NASH and HCC. These findings contribute to the advancement of precision medicine and the development of more effective treatments for patients affected by B[a]P-associated liver diseases.
GW34-e0755
Egor S. Chegodaev1,2,3,4,5, Alexander D. Zhuravlev1,2,3, Tatiana V. Kirichenko2,3, Nikita G. Nikiforov1,2,5, Alexander N. Orekhov2,3
1Petrovsky National Research Centre of Surgery, NRCS. The Federal Agency for Scientific Organizations, 119991 Moscow, Russia
2Avtsyn Science Research Institute of Human Morphology of FSBI “Petrovsky National Research Centre of Surgery”, 117418 Moscow, Russia
3Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russian Federation
5Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
OBJECTIVES The potential of the mitochondrial membrane is necessary for the synthesis of ATP, and its fall can be detected in violations of the respiratory chain. It was found that the pro-inflammatory activity of blood monocytes and pathogens of macrophages is covered by atherosclerosis in the carotid arteries. We decided to study whether there is a relationship between the mitochondrial membrane potential of circulating blood monocytes and stimulates the generation of a pro-inflammatory response.
METHODS CD14+ monocytes were isolated from the blood of 34 healthy individuals and stained with a potential-dependent Mitotracker Orange dye. Isolated cells were stimulated with 1 mcg/mL of LPS during the day. On day 6, LPS was added to unstimulated monocyte-macrophages during the day. The secretion of IL-1β, TNF-α, CCL2, IL-6, IL-8 and IL-10 was measured in the supernatants at each stage using ELISA.
RESULTS It turned out that there are individual differences in the level of mitochondrial membrane potential in circulating blood monocytes. The analysis showed direct correlations between the basal secretion of TNFα, IL-6, IL-10 by monocytes in culture with the mitochondrial potential of the cells. Moreover, inverse correlations were found between the secretion of TNFα and IL-6 by 7-day-old macrophages after LPS stimulation with the mitochondrial potential of the cells.
CONCLUSIONS A decrease in the potential of the mitochondrial membrane in monocytes is associated with a reduced basal secretory activity of monocytes and increased pro-inflammatory activation of monocytes-macrophages differentiated from them. However, the molecular mechanisms of this relationship have not yet been studied.
Supported by RSF (Grant No. 22-25-00650).
GW34-e0821
Alexander Zhuravlev1,2,3, Svetlana Verkhova1,2,3, Nikita Nikiforov1,2,3, Maria Marey4, Mikhail Vysokikh4, Alexander Orekhov5
1Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
2The Federal Agency for Scientific Organizations, Petrovsky National Research Centre of Surgery, NRCS, Moscow, Russian Federation
3Russian Academy of Sciences, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Moscow, Russian Federation
4Ministry of Healthcare of the Russian Federation, Laboratory of Mitochondrial Medicine, Federal State Budget Institution, “National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov”, Moscow, Russian Federation
5Laboratory of Atherosclerosis Research, Institute for Atherosclerosis Research, Moscow, Russian Federation
OBJECTIVES The functional activity of inflammatory cells depends on the work of mitochondria. Mitophagy is a cellular process by which damaged or dysfunctional mitochondria are selectively targeted for degradation. Arachidonic acid (AA) is an omega-6 fatty acid that is an important precursor to several inflammatory signaling molecules. Moreover, some studies have suggested that AA and its metabolites may play a role in regulating mitophagy. We hypothesized that AA may modulate cellular mitophagy, thereby affecting inflammation.
METHODS We studied the pro-inflammatory response of human macrophages after treatment with AA. The culture of human macrophages was treated with 20 μM AA for 24 h, after which the culture medium was changed. LPS was added at a concentration of 1 μg/mL for another 24 h. ELISA evaluated the secretion of pro-inflammatory cytokines (IL6, TNF-α and CCL2). In parallel, we measured mitophagy in human macrophages after treatment with 20 μM AA using confocal microscopy. The level of mitophagy was assessed by colocalization of the mitochondrial and lysosomal dye using CellProfiler.
RESULTS It turned out that AA reduced the secretion of cytokines IL6, TNF-α and CCL2 in response to LPS by macrophages. Quantitative image analysis showed that AA increased the percentage of mitochondria colocalized with lysosomes in macrophages.
CONCLUSIONS Perhaps this is a new mechanism of the anti-inflammatory action of AA due to the induction of mitophagy.
Supported by RSF (Grant No 23-25-00339).
GW34-e0825
Vasily Sukhorukov1, Maja Pučić-Baković2, Daria Borodko3, Alexander Orekhov1,3, Anatol Kontush4, Gordan Lauc2
1Petrovsky National Research Centre of Surgery, Moscow, Russia
2Genos Glycoscience Research Laboratory, Zagreb, Croatia
3Institute of General Pathology and Pathophysiology, Moscow, Russia
4Sorbonne Université, INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Paris, France
OBJECTIVES High-density lipoprotein (HDL) is a complex particle ensemble composed of proteins, lipids, and other molecules. HDL displays multiple anti-atherogenic activities which involve efflux of cellular cholesterol in the process of reverse cholesterol transport. HDL particles display considerable heterogeneity in their (glyco) protein and lipid composition, which directly influences their functional properties. Thus, HDL carries highly sialylated N-glycans, whose deficiency reduces the rate of cellular cholesterol efflux., Under pathological conditions, HDL N-glycosylation, in particular sialylation, can be altered in parallel to the immunomodulatory capacity of HDL. Analysis of HDL N-glycosylation in cardiovascular diseases can therefore provide both novel biomarkers and insights into biological role of HDL. The aim of this study was to evaluate alterations of the HDL N-glycome in patients with atherosclerosis relative to healthy controls.
METHODS HDL was isolated from human plasma of patients with atherosclerosis (defined as the increased carotid intima–media thickness relative to controls; n=20) and healthy controls (n=9) by density gradient ultracentrifugation. N-glycosylation profiles were obtained using HILIC-UPLC-FLD approach, which separated total HDL N-glycome into 22 N-glycan peaks.
RESULTS We found that relative abundance of high-mannose N-glycans in HDL of patients with atherosclerosis was significantly higher (by +25%) than in HDL of healthy subjects. Significant correlations were observed between HDL N-glycome composition and plasma total cholesterol level. The positive correlations were calculated for the total abundance of high-mannose and low branching N-glycans including those with one or two galactoses, as well as those without or with one or two sialic acids. Negative correlations with plasma total cholesterol level were observed for the total abundance of high branching N-glycans including those with three galactoses, three sialic acids, and with core or antennary fucose residues.
CONCLUSIONS HDL particles enriched in high-mannose N-glycans may represent a signature of atherosclerosis. The level of sialylation of HDL N-glycans is associated with plasma cholesterol levels.
This work was supported by Russian Science Foundation Grant # 22-25-00274, INSERM, Sorbonne University, and by the Croatian Science Foundation (Grant number UIP-2019-04-5692).
GW34-e0938
Svetlana Verkhova1,2, Alexander Zhuravlev1,2, Nirita Nikiforov2,3, Anton Postnov4, Yegor Yegorov5, Alexander Orekhov2,6
1FSBI “Petrovsky National Research Centre of Surgery”, Avtsyn Science Research Institute of Human Morphology of FSBI “Petrovsky National Research Centre of Surgery”, Moscow, Russian Federation
2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
3Russian Academy of Sciences, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Moscow, Russian Federation
4Laboratory of Cellular and Molecular Pathology of the Cardiovascular System, Federal State Budgetary Scientific Institution “Petrovsky National Research Centre of Surgery”, Moscow, Russian Federation
5Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, Moscow, Russian Federation
6Laboratory of Atherosclerosis Research, Institute for Atherosclerosis Research, Moscow, Russian Federation
OBJECTIVES It is well known that mitochondria play an important role in the immune response. Defects in the elimination of dysfunctional mitochondria may alter their inflammatory state. We decided to find out whether it is possible to modulate the immune response of inflammatory cells by influencing their mitophagy.
METHODS We screened fatty acids to evaluate their effect on mitophagy and pro-inflammatory response in THP 1 cells. First, we incubated THP-1 cells with arachidonic (at a concentration of 125 μM), linoleic (30 μM), linolenic (30 μM), oleic (30 μM) and palmitic (125 μM) for 24 h. Then the level of basal mitophagy was assessed by mitochondrial and lysosomal dye colocalization using confocal microscopy. In parallel, we stimulated cells with 1 μg/mL LPS for 24 h. The secretion of pro-inflammatory cytokines was assessed by ELISA (TNFa, IL-1β, IL-6, IL-8, CCL2).
RESULTS None of the fatty acids we used elicited a pro-inflammatory response in the THP1 cell line. It turned out that oleic and arachidonic acids increased the level of basal mitophagy in THP1 cells and reduced the secretion of pro-inflammatory cytokines (TNFa, IL-1β, IL-6, IL-8, CCL2) by LPS-stimulated cells. Palmitic acid, in contrast, reduced mitophagy in THP1 cells and increased secretion of IL-1β and CCL2 by LPS-stimulated cells.
CONCLUSIONS We suppose that the high pro-inflammatory activity of cells may be associated with the low efficiency of mitophagy. Increasing the intensity of mitophagy in inflammatory cells using natural lipid mediators may be a promising approach to target chronic inflammation.
GW34-e1192
Siyu Chen1,2, Pei Gao2,3, Yangfeng Wu2,3
1Peking University First Hospital
2Peking University Clinical Research Institute
3Peking University School of Public Health
OBJECTIVES To evaluate health interventions from population perspectives is a common interest of cardiovascular health researches. Cluster-randomized controlled design is a feasible choice; and sometimes to avoid selection bias, independent random samples at the baseline and follow-ups should be drawn to get an objective evaluation of the intervention effects. This particular approach is referred to as a cluster-randomized controlled trial design with repeated independent random samples (cRCT-IRS). cRCT-IRS design has some drawbacks concerning effect estimation. The individuals captured at follow-up visits are not guaranteed to actually have received the intervention because it is implemented on the group level, and therefore dilutes the observed effect. Moreover, the comparison of cross-sectional rather than cohort samples introduces extra inter-individual variance in the measurement of outcomes due to the existence of auto-correlation, thus could reduce the statistical power and result in a greater uncertainty in estimation and a failure to detect a real effect.
METHODS We transformed a cRCT-IRS into a cohort-based cRCT by predicting unobserved outcome measurements at different time points through multiple imputation (MI). MI is a reliable method to deal with missing values using information in the available data and it is widely adopted in clinical researches. We used data from the China Rural Health Initiative (CRHI) study, which is a good example of a cRCT-IRS. The intervention was training the primary care providers to screen and manage individuals with high risk of cardiovascular disease, and the outcome is systolic blood pressure (SBP) on individual level. We estimated the intervention effect on imputed datasets by linear mixed effects models and compared the combined results with the same analysis on the original dataset. We also further validated the difference of effect estimation through simulation studies that imitated the CRHI settings.
RESULTS The imputed values are analogous to the real data values both in distribution and intraclass correlation (ICC). The data records to be analyzed increased from 9937 to 17,888. The intervention effect estimated from imputations is −0.28 (95% CI: −3.173, 2.611). Compared to the original analysis where the effect was estimated as non-significantly positive, the transformed data arrived at a reasonable and consistent point estimate and a similar standard error. In addition, simulation studies also showed that the cRCT-IRS design resulted in weakened point estimates and larger standard errors than a cohort-based cRCT, and it is less powerful as well.
CONCLUSIONS The research supports that it is plausible to convert a cRCT-IRS to a cohort-based cRCT through MI for analysis. The imputations have concordant patterns with the real observed data, and are more efficient in intervention effect estimation.
GW34-e1208
Yating Liu1, Junyi Li2, Di Wang3, Juping Yu4, Mengqi Liu1, Dandan Tian1, Xinping Ouyang3, Pingping He3
1School of Nursing, Hengyang Medical School, University of South China
2Nursing Department, Chongqing Cancer Hospital
3Medical School, Medical College of Hunan Normal University
4Faculty of Life Sciences and Education, University of South Wales
OBJECTIVES The global population is steadily aging, with people aged 65 and older growing faster than those in lower age groups. According to a United Nations survey, one in six people on the planet will be 65 or older by 2050, and it is predicted that those aged 80 or older will be triple, from 143 million in 2019 to 426 million in 2050. Lower fertility and longer life expectancy as a result of global economic and social development have undoubtedly contributed to the aging population, which puts more demands on public infrastructure, healthcare systems, and smart technologies, such as artificial intelligence, machine learning, and mobile apps. The concept “Smart senior care” emerged in recent years. But there is no agreed definition of this concept. In general, it refers to a new care model that provides personalized care services for older adults by building a combined online and offline platform with the aid of smart products and intelligent technologies. It has been believed that this type of care model is effective in addressing the disparity between supply and demand for care services for older adults and provides new opportunities for the senior care industry.
METHODS The study was conducted between March and December 2021. In Phase 1, items of the scale were generated via a literature review and semi-structured interviews. In Phase 2, a 2-round Delphi expert consultation was conducted to test the content validity of the scale. Phase 3 involved a pilot study with community-dwelling older adults to test the readability and feasibility of the scale. In Phase 4, psychometric testing was carried out among older adults from four communities in three districts of Hengyang, China, to test the reliability and validity of the scale.
RESULTS The Knowledge, Attitudes, and Practices Scale of Smart Senior Care in community-dwelling older adults (SSC-KAP) consisted of three subscales: knowledge, attitude, and practice. The authority coefficients for the 2-round Delphi expert consultation were 0.84 and 0.91, and the Kendall’s coefficients were 0.17 and 0.26. The cumulative variance contribution of the total scale after factor rotation was 64.66%. The Cronbach’s α coefficient for the total scale was 0.931, and the Spearman-Brown coefficient for the total scale was 0.953, indicating good reliability.
CONCLUSIONS The 5-dimensional, 29-item SSC-KAP has showed satisfactory psychometric properties with good reliability and validity as tested with community-dwelling older adults.
GW34-e1211
Yichen Zhao, Junhui Sun, Jiang Wang
Beijing Anzhen Hospital, Capital Medical University
OBJECTIVES Delirium could be observed frequently after cardiac surgery. Psychological and social factors may have potential impacts on the occurrence of postoperative delirium (POD) but are rarely reported. This study made a comprehensive assessment of patient’s psychological and social status, trying to investigate whether such factors had relationships with POD in cardiac surgery.
METHODS This prospective cohort study was done between Sep 1, 2022 and Nov 33, 2022. Patients older than 18 years old who had planned cardiac surgeries in our center were recruited consecutively. A comprehensive assessment for cognitive function, anxiety, depression, and sleep quality was scheduled before surgery. The social and medical baseline information of patients was also recorded. The primary outcome was the occurrence of POD, which could be diagnosed according to the CAM-ICU method. A logistic regression model was used to identify the risk factors that may be associated with the primary outcome and establish a model for the prediction of POD. The nomogram was used to summarize the effect of each predictor on POD. The area under the curve (AUC) and the calibration of risk predictors were used to assess the discriminatory power of the predictive model. The bootstrap method was used for internal validation.
RESULTS A total of 218 cases were enrolled in this study. Patients who underwent surgeries with cardiopulmonary bypass (CPB) accounted for 68.9% of the whole population. POD was observed present among 44 patients (20.2%). The multivariate regression model showed that POD was more likely to be observed in patients who underwent surgeries with CPB supports and those who had abnormalities in cranial imaging before surgeries (P<0.05). The cognitive function (evaluated by Montreal Cognitive Assessment, MoCA) and the sleep quality (evaluated by Pittsburgh Sleep Quality Index, PSQI) before surgery were significantly associated with the occurrence of POD. Patients with a lower score in the MoCA (turning point=26) and a higher index of PSQI (turning point=5) may have a higher risk of POD. Additionally, a higher education level may be a protective factor for POD. The sensitivity and specialty of the predictive model were 81.8% and 83.9%, respectively. The AUC values indicated that the predictive model discriminates to a good extent (AUC=86.7, 95% CI (0.809–0.925)). The bias-corrected calibration intercepts indicated a reasonable estimation of the mean probability of POD for the predictive model (0.03).
CONCLUSIONS Cognitive function impairment and sleep disorders were associated with postoperative delirium in cardiac surgery. Preoperative assessments of cognitive function and sleep quality by using the MoCA test and PSQI were suggested in clinical practice. A lower level of education, abnormalities in the brain before surgery and CPB was also the risk factors for POD. The predictive model based on the above factors could predict POD effectively.
GW34-e1221
Yihong Chen1,2, Jan Nilsson3, Chun Liang1
1Department of Cardiology, Shanghai Changzheng Hospital, Shanghai 200003, China
2Department of Experimental Medical Science, Lund University, Lund 22184, Sweden
3Department of Clinical Sciences Malmö, Lund University, Malmö 20502, Sweden
OBJECTIVES Based on the evolving knowledge of injury and repair dysregulation in cardiovascular complications to diabetes, it’s important to perform preclinical testing of potential new therapies targeting these processes. In this study for approaches to stimulate tissue repair in diabetes, we tested a novel osteopontin-derived peptide FOL-005, which has been investigated in an animal model and two early clinical trials (NCT03467412 and NCT04774874) providing support for the presence of hair growth activation in both animals and humans, to identify possible drug candidate and underlying mechanism for vascular repair in diabetes with cardiovascular complications.
METHODS The cell viability, insulin secretion of β-cells and pancreatic islets, oral glucose tolerance test in mice were performed to evaluate the glucose-lowering effect of FOL-005. The ligand-receptor glycocapture technology, X-ray diffraction and microscale thermophoresis analysis were used to identify the receptor and binding site for FOL-005. To explore the FOL-005 effects on vascular repair responses and verify the receptor to which the FOL-005 bind and describe the intracellular signal pathways that become activated, FOL-005 stimulations and small interfering RNA (siRNA) were carried out to assess the role of FOL peptide in regulation of human endothelial cells (ECs) and smooth muscle cell (SMCs) proliferation, apoptosis, migration and viability. Tube formation and matrigel plug assay were used to test angiogenesis with FOL-005 in vitro and vivo. Peptide effects on vascular cells were also determined by RNA sequencing.
RESULTS FOL-005 peptide increased β-cell viability and stimulated the release of insulin from β-cells and pancreatic islets. It also lowered glucose levels in oral glucose tolerance test in mice and promoted β-cell survival in the BB-rat model of autoimmune type 1 diabetes. NRP-1, a co-receptor for vascular endothelial growth factor (VEGF) receptors, was identified as the most probable receptor for FOL-005. X-ray diffraction and microscale thermophoresis analysis revealed that the peptide shares binding site with VEGF in the NRP-1 b1-subdomain. Stimulation of ECs and SMCs with FOL-005 resulted in increased cell growth, migration, inhibition of apoptosis and oxidative stress. For ECs, FOL peptide induced an improvement of angiogenesis in vitro and vivo. For SMCs, FOL peptide activated collagen formation and VEGF transcription. Down-regulation of NRP-1 by specific siRNA blocked the stimulatory effects of FOL peptide on both two kinds of vascular cells. To better understand the protective effect of FOL-005 on vascular repair, a transcriptomic analysis revealed a dramatic activation of PI3K-Akt signaling pathway in vascular cells treated with FOL-005 peptide. Additionally, cyclin-dependent kinase 6 (CDK6) and BCL2 like 11 (BCL2L11) for ECs together with placental growth factor (PlGF) and VEGF receptor 2 (KDR) for SMCs were identified as hug genes for FOL-005 peptide effects through protein-protein interaction network analysis and gene set enrichment analysis.
CONCLUSIONS These findings identify NRP-1 as the receptor for osteopontin-derived peptide FOL-005 and show that its biological effects are similar to those of growth factors binding to the VEGF receptor family. They also suggest that FOL-005 peptide may have therapeutical potential in diabetes with cardiovascular complications that require vascular repair or enhanced angiogenesis.
GW34-e1234
Wenting Wang, Lulu Zhu, Qiongying Wang, Jing Yu
Center of Hypertension, Lanzhou University Secondary Hospital, Gansu, China
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 24 SHR were randomly divided into three groups: sham operation group (Sham group, n=8), bilateral ovariectomized group (OVX group, n=8) and testosterone propionate intervention group (OVX+T group, 2.85 mg/kg/Weekly, IM for 4 weeks, n=8). Western Blot was used to detect the protein expression of mTOR, p-mTOR, mTORC2 and its subunits Rictor. Moreover, the expression of autophagy-related proteins LC3 and P62 and Mitofusin2 (MFN2) and Dynamin related protein 1 (DRP1) in cardiac myocytes was observed.
RESULTS
1. Testosterone could activate the expression of mTORC2 in myocardial tissue: there was no significant difference in the expression of mTOR and p-mTOR in Sham group, OVX group and OVX+T group. However, the expression of p-mTOR/mTOR is significantly increased in OVX+T group. Although there was no significant difference in mTORC2 expression between Sham group and OVX group, testosterone could activate the expression of mTORC2 and the subunit Rictor in OVX+T group.
2. Testosterone could inhibit cardiomyocyte autophagy flux: Compared with the Sham and OVX group, it could be observed that the expression of LC3I is deceased in OVX+T group while the LC3II/LC3I ratio is increased in OVX+T group. It is interesting that with the testosterone intervention, the expression of both LC3 II/LC3I and P62 increases significantly in OVX+T group.
3. Testosterone could activate the mitochondrial cleavage of cardiomyocytes: there was no significant difference in the expression of MFN2 among Sham group, OVX group and OVX+T group, and there was no significant difference in the expression of DRP1 between Sham group and OVX group. However, the expression of DRP1 was increased in OVX+T group. Moreover, further detection of classical Parkin protein in activating mitochondrial autophagy, the result showed that there was no significant difference of Parkin expression among the three groups.
CONCLUSIONS In bilateral ovariectomized SHR, testosterone could activate the expression of mTORC2, which may block the autophagy flux at the later stage, ultimately resulting in insufficient autophagy. And in cardiomyocyte mitochondria, testosterone can promote mitochondrial cleavage through a pathway independent of Parkin pathway.
GW34-e1308
Wenli Gu1,2, Ronald Man3, Qing-Wen Ren1,2, Jiayi Huang1,2, Mei-Zhen Wu1,2, Kai-Hang Yiu1,2
1Cardiology Division, Department of Medicine, The University of Hong Kong Shen Zhen Hospital, No. 1 Haiyuan 1st Rd, Futian District, Shenzhen City, Guangdong Province 518009, China
2Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pok Fu Lam Rd 102. Hong Kong Island, Hong Kong 999077, China
3Department of Cardiology, National Heart Center, 5 Hospital Dr 169609, Singapore
OBJECTIVES Emerging evidence suggested osteoarthritis is associated with increasing risk of dementia possibly because of accumulative age-related comorbidity and physical inactivity. Our study investigated whether statin use could reduce risk of dementia in patients with osteoarthritis.
METHODS Using a territory-wide healthcare database, we identified all eligible patients with osteoarthritis (n=146,706) from 2000 to 2019. Inverse probability of treatment weighting was used to adjust demographics, lifestyles, comorbidities and concurrent medications between statin nonusers (n=58,178) and statin users (n=88,528). The adjusted hazard ratio was calculated using competing risk regression with Cox proportional-hazard model.
RESULTS Among all eligible patients, the mean age was 68.1±12.7 years. The median follow-up was 5.9 years (interquartile range: 1.7–10.6 years), and 8 169 (5.57%) patients developed dementia. Statin user (vs statin nonuser) was associated with a lower risk of dementia incidence [multivariable adjusted subdistribution hazard ratio (SHR)=0.56; 95% confidence interval (CI), 0.53–0.60]. Among the subtypes of dementia, statin user (vs statin nonuser) was associated with a lower risk of Alzheimer’s disease [multivariable adjusted SHR=0.50; 95% CI, 0.44–0.56] as well as vascular dementia [multivariable adjusted SHR=0.71; 95% CI, 0.62–0.81]. This observation remains consistent in patients across all time-weighted LDL-C levels.
CONCLUSIONS Our study suggested that statin use is associated with a lower risk of dementia in osteoarthritis patients, irrespective of time-weighted LDL-C levels. In particular, statin user has a lower risk of Alzheimer’s disease and vascular dementia when compared with statin nonusers.
GW34-e1341
Galina Kukharchik, Elena Parmon, Evgeny Shlyakhto
Almazov National Medical Research Centre
OBJECTIVES Interactive teaching methods is a fundamental approach in medical education, including the training of cardiologists. New interactive learning technologies are diverse and promising for use, but are not widely used. It is important to analyze the technologies used and evaluate their use by residents and teachers.
METHODS Analysis of interactive teaching methods for residents. 8 technologies have been developed: interactive clinical cases, interactive lectures, simulation training using robots and simulators, interdisciplinary clinical discussions, “cardio fights”, a flipped seminar, brainstorming, trainings. An analysis was made of the frequency of use of various technologies, an assessment of the effectiveness by residents and teachers were given, limitations of use and benefits were analyzed.
RESULTS Simulation training with the use of robots and simulators, interdisciplinary clinical discussions, “cardio fights” and trainings are of the greatest importance on the part of residents. Residents are involved in the process of preparing clinical cases and flipped seminars. Classical lectures have the lowest efficiency from the point of view of residents. During the creation of interactive modules, 48 interdisciplinary clinical cases were developed with the introduction of data on pathological anatomy, physiology, related fields of clinical medicine, pharmacology, bioethics, communication skills and others. More than 40% of residents and teachers noted the effectiveness of flipped seminars.
CONCLUSIONS It is necessary to include interactive technologies in the training program in residency in cardiology. The choice of technologies depends on the task and may vary depending on the level of training of students. Questioning of residents and teachers allows us to identify the most difficult issues in the development and implementation of interactive technologies and their limitations.
GW34-e1407
Liying Li1, Haiyan Ruan1,2, Muxin Zhang1,3, Sen He1
1Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China
2Department of Cardiology, Traditional Chinese Medicine Hospital of Shuangliu District, Chengdu, China
3Department of Cardiology, First People’s Hospital, Longquanyi District, Chengdu, China
OBJECTIVES Frailty and hypertension have a complex physiological link, and studies have shown that frailty and hypertension often coexist in the elderly. It is reported that frailty increased the risk of adverse health outcomes in older adults. However, there are few studies on the relationship between frailty and all-cause mortality (ACM) in older hypertensive patients. Therefore, the present study aims to investigate the association of frailty with the ACM in older people, using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).
METHODS A total of 2190 community-dwelling older hypertensive participants (aged ≥65 years) from two consecutive waves (2011 wave and 2014 wave) of the CLHLS were included for the present analysis. Frailty status was determined using the 38-item frailty index (FI) and participants were divided into three groups: “robust” (FI≤0.12), “pre-frail” (0.12<FI≤0.25), or “frail” (FI>0.25). Cox regression analysis was used to explore the association of frailty status and ACM.
RESULTS During a median follow-up of 3.87 years, ACM was observed in 1021 older hypertensive participants (46.6%). Kaplan-Meier analysis demonstrated that cumulative incidences of ACM was significantly higher in the frail participants (log-rank P<0.001). Compared with the robust participants, the unadjusted hazard ratios (HRs) for ACM were 2.00 (95% confidence interval [CI]: 1.62–2.46, P<0.001) for the pre-frail participants and 5.28 (95% CI: 4.26–6.55, P<0.001) for the frail participants. After adjusting for potentially confounding variables, the adjusted HRs for ACM for the pre-frail and frail participants were 1.58 (95% CI: 1.27–1.96, P<0.001) and 3.12 (95% CI: 2.45–3.97, P<0.001), respectively. For each standard deviation increment, the adjusted HRs of mortality risk was 1.51 (95% CI: 1.42–1.61, P<0.001). Stratified and sensitivity analyses suggested robustness of the results.
CONCLUSIONS Our results indicate that frailty status is associated with mortality in Chinese older people. Older hypertensive adults with frailty have higher risk of ACM.