Anna Kiepura, Maciej Suski, Kamila Stachyra, Katarzyna Kuś, Klaudia Czepiel, Anna Wiśniewska, Magdalena Ulatowska-Białas, Rafał Olszanecki
{"title":"The Influence of the FFAR4 Agonist TUG-891 on Liver Steatosis in ApoE-Knockout Mice.","authors":"Anna Kiepura, Maciej Suski, Kamila Stachyra, Katarzyna Kuś, Klaudia Czepiel, Anna Wiśniewska, Magdalena Ulatowska-Białas, Rafał Olszanecki","doi":"10.1007/s10557-023-07430-7","DOIUrl":"10.1007/s10557-023-07430-7","url":null,"abstract":"<p><strong>Background: </strong>Nonalcoholic fatty liver disease (NAFLD) constitutes an independent risk factor for the development of coronary heart disease. Low-grade inflammation has been shown to play an important role in the development of atherosclerosis and NAFLD. Free fatty acid receptor 4 (FFAR4/GPR120), which is involved in damping inflammatory reactions, may represent a promising target for the treatment of inflammatory diseases. Our objective was to evaluate the effect of TUG-891, the synthetic agonist of FFAR4/GPR120, on fatty liver in vivo.</p><p><strong>Methods: </strong>The effect of TUG-891 on fatty liver was investigated in apoE<sup>-/-</sup> mice fed a high-fat diet (HFD), using microscopic, biochemical, molecular, and proteomic methods.</p><p><strong>Results: </strong>Treatment with TUG-891 inhibited the progression of liver steatosis in apoE<sup>-/-</sup> mice, as evidenced by histological analysis, and reduced the accumulation of TG in the liver. This action was associated with a decrease in plasma AST levels. TUG-891 decreased the expression of liver genes and proteins involved in de novo lipogenesis (Srebp-1c, Fasn and Scd1) and decreased the expression of genes related to oxidation and uptake (Acox1, Ehhadh, Cd36, Fabp1). Furthermore, TUG-891 modified the levels of selected factors related to glucose metabolism (decreased Glut2, Pdk4 and Pklr, and increased G6pdx).</p><p><strong>Conclusion: </strong>Pharmacological stimulation of FFAR4 may represent a promising lead in the search for drugs that inhibit NAFLD.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10678129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Left Ventricular Thrombus After Myocardial Infarction: Opinions and Equipoise.","authors":"Shannon Clay, James C Blankenship","doi":"10.1007/s10557-024-07572-2","DOIUrl":"10.1007/s10557-024-07572-2","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lukasz Koltowski, Mariusz Tomaniak, Dorota Ochijewicz, Grzegorz Opolski, Janusz Kochman
{"title":"Third-Generation Sirolimus-Eluting Bioresorbable Tyrocore Scaffold Implantation in Patients with ST-Segment Elevation Myocardial Infarction: Baseline and 6-Month OCT and Clinical Outcomes-a FANTOM STEMI Pilot Study.","authors":"Lukasz Koltowski, Mariusz Tomaniak, Dorota Ochijewicz, Grzegorz Opolski, Janusz Kochman","doi":"10.1007/s10557-023-07429-0","DOIUrl":"10.1007/s10557-023-07429-0","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to evaluate the safety and efficacy of the Fantom BRS 6 months after implantation using the optical coherence tomography (OCT) imaging.</p><p><strong>Methods: </strong>Twenty STEMI patients treated with a sirolimus-eluting Fantom BRS were enrolled into a prospective, single-arm, serial observational study. The scaffold sizing, positioning and optimisation were guided by OCT imaging. The primary endpoint was device-orientated composite endpoints (DOCE), comprised of cardiac death, target-vessel-related myocardial infarction and target lesion failure. To evaluate the device performance at the scaffold level, we performed a quantitative coronary angiography (QCA) and OCT imaging at 6 months.</p><p><strong>Results: </strong>The primary endpoint did not occur in any patient within the 6-month follow-up. There were no major adverse cardiac events (MACEs) or DOCEs, no cases of scaffold thrombosis, target lesion revascularization and no deaths. In QCA, we observed a decrease in the minimum and mean lumen diameter in the in-scaffold region and in the proximal and distal peri-scaffold region. Similarly, the minimum lumen area and reference vessel diameter had decreased in both QCA and OCT. The OCT imaging showed improvement in the expansion index and malposition rate.</p><p><strong>Conclusion: </strong>A serial 6-month OCT imaging after implantation of a third-generation Tyrocore-based bioresorbable coronary scaffold indicated good coverage of the struts with excellent healing of the scaffold, low neointima growth and no signs of neoatherosclerosis.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9074261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander Lenard, Simon A Hermann, Felicitas Stoll, Juergen Burhenne, Kathrin I Foerster, Gerd Mikus, Andreas D Meid, Walter E Haefeli, Antje Blank
{"title":"Effect of Clarithromycin, a Strong CYP3A and P-glycoprotein Inhibitor, on the Pharmacokinetics of Edoxaban in Healthy Volunteers and the Evaluation of the Drug Interaction with Other Oral Factor Xa Inhibitors by a Microdose Cocktail Approach.","authors":"Alexander Lenard, Simon A Hermann, Felicitas Stoll, Juergen Burhenne, Kathrin I Foerster, Gerd Mikus, Andreas D Meid, Walter E Haefeli, Antje Blank","doi":"10.1007/s10557-023-07443-2","DOIUrl":"10.1007/s10557-023-07443-2","url":null,"abstract":"<p><strong>Purpose: </strong>We assessed the differential effect of clarithromycin, a strong inhibitor of cytochrome P450 (CYP) 3A4 and P-glycoprotein, on the pharmacokinetics of a regular dose of edoxaban and on a microdose cocktail of factor Xa inhibitors (FXaI). Concurrently, CYP3A activity was determined with a midazolam microdose.</p><p><strong>Methods: </strong>In an open-label fixed-sequence trial in 12 healthy volunteers, the pharmacokinetics of a microdosed FXaI cocktail (μ-FXaI; 25 μg apixaban, 50 μg edoxaban, and 25 μg rivaroxaban) and of 60 mg edoxaban before and during clarithromycin (2 x 500 mg/d) dosed to steady-state was evaluated. Plasma concentrations of study drugs were quantified using validated ultra-performance liquid chromatography-tandem mass spectrometry methods.</p><p><strong>Results: </strong>Therapeutic clarithromycin doses increased the exposure of a therapeutic 60 mg dose of edoxaban with a geometric mean ratio (GMR) of the area under the plasma concentration-time curve (AUC) of 1.53 (90 % CI: 1.37-1.70; p < 0.0001). Clarithromycin also increased the GMR (90% CI) of the exposure of microdosed FXaI apixaban to 1.38 (1.26-1.51), edoxaban to 2.03 (1.84-2.24), and rivaroxaban to 1.44 (1.27-1.63). AUC changes observed for the therapeutic edoxaban dose were significantly smaller than those observed with the microdose (p < 0.001).</p><p><strong>Conclusion: </strong>Clarithromycin increases FXaI exposure. However, the magnitude of this drug interaction is not expected to be clinically relevant. The edoxaban microdose overestimates the extent of the drug interaction with the therapeutic dose, whereas AUC ratios for apixaban and rivaroxaban were comparable to the interaction with therapeutic doses as reported in the literature.</p><p><strong>Trial registration: </strong>EudraCT Number: 2018-002490-22.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10827944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxidative Stress-Mediated Programmed Cell Death: a Potential Therapy Target for Atherosclerosis.","authors":"Yuwu Chen, Xing Luo, Biyi Xu, Xiaoyi Bao, Haibo Jia, Bo Yu","doi":"10.1007/s10557-022-07414-z","DOIUrl":"10.1007/s10557-022-07414-z","url":null,"abstract":"<p><p>Nowadays, as a type of orderly and active death determined by genes, programmed cell death (PCD), including apoptosis, pyroptosis, ferroptosis, and necroptosis, has attracted much attention owing to its participation in numerous chronic cardiovascular diseases, especially atherosclerosis (AS), a canonical chronic inflammatory disease featured by lipid metabolism disturbance. Abundant researches have reported that PCD under distinct internal conditions fulfills different roles of atherosclerotic pathological processes, including lipid core expansion, leukocyte adhesion, and infiltration. Noteworthy, emerging evidence recently has also suggested that oxidative stress (OS), an imbalance of antioxidants and oxygen free radicals, has the potential to mediate PCD occurrence via multiple ways, including oxidization and deubiquitination. Interestingly, more recently, several studies have proposed that the mediating mechanisms could effect on the atherosclerotic initiation and progression significantly from variable aspects, so it is of great clinical importance to clarify how OS-mediated PCD and AS interact. Herein, with the aim of summarizing potential and sufficient atherosclerotic therapy targets, we seek to provide extensive analysis of the specific regulatory mechanisms of PCD mediated by OS and their multifaceted effects on the entire pathological atherosclerotic progression.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10417581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jorik H Amesz, Sanne J J Langmuur, Nina Epskamp, Ad J J C Bogers, Natasja M S de Groot, Olivier C Manintveld, Yannick J H J Taverne
{"title":"Acute Biomechanical Effects of Empagliflozin on Living Isolated Human Heart Failure Myocardium.","authors":"Jorik H Amesz, Sanne J J Langmuur, Nina Epskamp, Ad J J C Bogers, Natasja M S de Groot, Olivier C Manintveld, Yannick J H J Taverne","doi":"10.1007/s10557-023-07434-3","DOIUrl":"10.1007/s10557-023-07434-3","url":null,"abstract":"<p><strong>Purpose: </strong>Multiple randomized controlled trials have presented SGLT2 inhibitors (SGLT2i) as novel pharmacological therapy for patients with heart failure, resulting in reductions in hospitalization for heart failure and mortality. Given the absence of SGLT2 receptors in the heart, mechanisms of direct cardioprotective effects of SGLT2i are complex and remain to be investigated. In this study, we evaluated the direct biomechanical effects of SGLT2i empagliflozin on isolated myocardium from end-stage heart failure patients.</p><p><strong>Methods: </strong>Ventricular tissue biopsies obtained from 7 patients undergoing heart transplantation or ventricular assist device implantation surgery were cut into 27 living myocardial slices (LMS) and mounted in custom-made cultivation chambers with mechanical preload and electrical stimulation, resulting in cardiac contractions. These 300 µm thick LMS were subjected to 10 µM empagliflozin and with continuous recording of biomechanical parameters.</p><p><strong>Results: </strong>Empagliflozin did not affect the maximum contraction force of the slices, however, increased total contraction duration by 13% (p = 0.002) which was determined by prolonged time to peak and time to relaxation (p = 0.009 and p = 0.003, respectively).</p><p><strong>Conclusion: </strong>The addition of empagliflozin to LMS from end-stage heart failure patients cultured in a biomimetic system improves contraction and relaxation kinetics by increasing total contraction duration without diminishing maximum force production. Therefore, we present convincing evidence that SGLT2i can directly act on the myocardium in absence of systemic influences from other organ systems.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10695780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of Heart Failure History at Baseline on Cardiovascular Effects of GLP-1 Receptor Agonists in Type 2 Diabetes: a Meta-analysis.","authors":"Mainak Banerjee, Indira Maisnam, Satinath Mukhopadhyay","doi":"10.1007/s10557-023-07432-5","DOIUrl":"10.1007/s10557-023-07432-5","url":null,"abstract":"<p><strong>Purpose: </strong>Effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type-2 diabetes mellitus (T2DM) with or without prior heart failure (HF) have been inconsistent across cardiovascular outcome trials. This study aimed to investigate the impact of HF history at baseline on cardiovascular effects of GLP-1 RAs in T2DM.</p><p><strong>Methods: </strong>PubMed, Embase, Web of Science, and clinical trial registries were searched for randomized controlled trials (RCTs) or post hoc analyses (≥ 24 weeks) reporting HF hospitalizations and/or cardiovascular death (HHF/CVD), major adverse cardiovascular events (MACE) comprising of cardiovascular death, myocardial infarction, and stroke in adults with T2DM with or without HF history (PROSPERO:CRD42022367633). Hazard ratios (HRs) in GLP-1RAs versus placebo arms were pooled together using the generic inverse variance method in fixed-effects model. Subgroup analysis was performed.</p><p><strong>Results: </strong>We identified 5 eligible studies, pooling data retrieved from six RCTs and 48,489 individuals with T2DM. On pooled analysis, GLP1RA treatment versus placebo significantly reduced risk of HHF/CVD in only T2DM without HF history (HR = 0.84; 95%CI, 0.77-0.91; I<sup>2</sup> = 14%; p < 0.001), but not in those with HF history (HR = 0.96; 95%CI, 0.85-1.08; I<sup>2</sup> = 14%; p = 0.4) (p-interaction < 0.1). GLP-1RAs reduced incident HHF in T2DM with or without HF history (HR = 0.89; 95%CI, 0.80-0.98; I<sup>2</sup> = 41%; p < 0.05) (p-interaction = 0.28). Sensitivity analysis excluding REWIND trial accentuated the impact of baseline HF history on both HHF/CVD and HHF (p-interaction < 0.05). Benefits on MACE with GLP-1RAs were consistently seen in T2DM regardless of HF history (p-interaction = 0.8).</p><p><strong>Conclusion: </strong>GLP-1RAs consistently prevented HF hospitalizations and MACE in T2DM regardless of baseline HF history, whereas significant attenuation of benefits on composite HHF/CV death were observed in those with HF history.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10619622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Iron Status Screening in Individuals with Heart Failure Before Initiating Sodium-Glucose Cotransporter 2 Inhibitor Therapy: Is It Necessary?","authors":"Ana Cirovic, Aleksandar Cirovic","doi":"10.1007/s10557-023-07498-1","DOIUrl":"10.1007/s10557-023-07498-1","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10303571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Zong, Xiaorui Wang, Yi Zhang, Na Tan, Yan Zhang, Li Li, Limei Liu
{"title":"Sitagliptin Ameliorates Creb5/lncRNA ENSMUST00000213271-Mediated Vascular Endothelial Dysfunction in Obese Mice.","authors":"Yi Zong, Xiaorui Wang, Yi Zhang, Na Tan, Yan Zhang, Li Li, Limei Liu","doi":"10.1007/s10557-023-07436-1","DOIUrl":"10.1007/s10557-023-07436-1","url":null,"abstract":"<p><strong>Purpose: </strong>Obesity is mediated by the changes in dyslipidemia, oxidative stress, and inflammation, leading to vascular endothelial dysfunction. Glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 inhibitors prevent the development of endothelial dysfunction. However, the underlying mechanism still remains largely unclear. Long non-coding RNAs (lncRNAs), one class of non-coding small RNAs, have been shown to exert a regulatory impact on the endothelial function in obesity. This study aimed to investigate whether the elevation of GLP-1 by a DPP-4 inhibitor sitagliptin improved vascular endothelial function by modulating lncRNAs in obese mice and to clarify the underlying molecular mechanism.</p><p><strong>Methods: </strong>Male C57BL/6J mice were fed a high-fat diet for 4 months to induce obesity and some obese mice were treated with sitagliptin for the last 1 month. Levels of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucagon-like peptide-1 (GLP-1) in plasma were detected by ELISA. LncRNA expression profile was analyzed via microarray. Aortic relaxations were examined by myograph. Protein expressions and phosphorylations were determined using western blot. The differentially expressed lncRNAs were validated using qRT-PCR.</p><p><strong>Results: </strong>Obese mice exhibited increased levels of TC and LDL, decreased concentrations of HDL and GLP-1 in plasma, and impaired aortic endothelium-dependent relaxations; such effects could be reversed by sitagliptin. Moreover, the altered expression profile of lncRNAs in the obese mouse aortae could be modulated by sitagliptin. Consistent with microarray analysis, qRT-PCR also revealed that lncRNA ENSMUST00000213271 was up-regulated in obese mouse aortae and aortic endothelial cells (ECs), which could be down-regulated by sitagliptin. Creb5 silencing reduced lncRNA ENSMUST00000213271 in obese mouse ECs. Knockdown of either Creb5 or lncRNA ENSMUST00000213271 restored the activation of AMPK/eNOS in obese mouse ECs. Furthermore, sitagliptin also suppressed Creb5 and lncRNA ENSMUST00000213271 and increased the phosphorylations of AMPK and eNOS in obese mice.</p><p><strong>Conclusion: </strong>Creb5/lncRNA ENSMUST00000213271 mediated vascular endothelial dysfunction through inhibiting AMPK/eNOS cascade in obesity. Elevation of GLP-1 by sitagliptin possibly improved endothelial function by suppressing Creb5/lncRNA ENSMUST00000213271 and subsequently restoring AMPK/eNOS activation in obese mice. This study will provide new evidence for the benefits of GLP-1 against vasculopathy in obesity.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10645779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J F Zhang, Y W Pan, J Li, X G Kong, M Wang, Z M Xue, J Gao, G S Fu
{"title":"Comparison of His-Purkinje Conduction System Pacing with Atrial-Ventricular Node Ablation and Pharmacotherapy in HFpEF Patients with Recurrent Persistent Atrial Fibrillation (HPP-AF study).","authors":"J F Zhang, Y W Pan, J Li, X G Kong, M Wang, Z M Xue, J Gao, G S Fu","doi":"10.1007/s10557-023-07435-2","DOIUrl":"10.1007/s10557-023-07435-2","url":null,"abstract":"<p><strong>Background: </strong>There is currently no particularly effective strategy for patients with persistent atrial fibrillation accompanying heart failure with preserved ejection fraction (HFpEF), especially with recurrent atrial fibrillation after ablation. In this study, we will evaluate a new treatment strategy for patients with persistent atrial fibrillation who had at least two attempts (≧2 times) of radio-frequency catheter ablation but experienced recurrence, and physiologic conduction was reconstructed after atrioventricular node ablation or drug therapy, to control the patient's ventricular rate to maintain a regular heart rhythm, which is called His-Purkinje conduction system pacing (HPCSP) with atrioventricular node ablation.</p><p><strong>Methods and results: </strong>This investigator-initiated, multicenter prospective randomized controlled trial aimed to recruit 296 randomized HFpEF patients with recurrent atrial fibrillation. All the enrolled patients were randomly assigned to the pacing group or the drug treatment group. The primary endpoint is differences in cardiovascular events and clinical composite endpoints (all-cause mortality) between patients in the HPCSP and drug-treated groups. Secondary endpoints included heart failure hospitalization, exercise capacity assessed by cardiopulmonary exercise tests, quality of life, echocardiogram parameters, 6-minute walk distance, NT-ProBNP, daily patient activity levels, and heart failure management report recorded by the CIED. It is planned to compete recruitment by the end of 2023 and report in 2025.</p><p><strong>Conclusions: </strong>The study aims to determine whether His-Purkinje conduction system pacing with atrioventricular node ablation can better improve patients' symptoms and quality of life, postpone the progression of heart failure, and reduce the rate of rehospitalization and mortality of patients with heart failure.</p><p><strong>Clinical trial registration number: </strong>ChiCTR1900027723, URL: http://www.chictr.org.cn/edit.aspx?pid=46128&htm=4.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9231780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}