Pub Date : 2024-09-17DOI: 10.1093/eurheartj/ehae571
Alessio Gasperetti, Richard T Carrick, Alexandros Protonotarios, Brittney Murray, Mikael Laredo, Iris van der Schaaf, Ronald H Lekanne, Petros Syrris, Douglas Cannie, Crystal Tichnell, Chiara Cappelletto, Marta Gigli, Kristen Medo, Ardan M Saguner, Firat Duru, Nisha A Gilotra, Stefan Zimmerman, Robyn Hylind, Dominic J Abrams, Neal K Lakdawala, Julia Cadrin-Tourigny, Mattia Targetti, Iacopo Olivotto, Maddalena Graziosi, Moniek Cox, Elena Biagini, Philippe Charron, Michela Casella, Claudio Tondo, Momina Yazdani, James S Ware, Sanjay K Prasad, Leonardo Calò, Eric D Smith, Adam S Helms, Sophie Hespe, Jodie Ingles, Harikrishna Tandri, Flavie Ader, Giovanni Peretto, Stacey Peters, Ari Horton, Jess Yao, Sven Dittmann, Eric Schulze-Bahr, Maria Qureshi, Katelyn Young, Eric D Carruth, Chris Haggerty, Victoria N Parikh, Matthew Taylor, Luisa Mestroni, Arthur Wilde, Gianfranco Sinagra, Marco Merlo, Estelle Gandjbakhch, J Peter van Tintelen, Anneline S J M te Riele, Perry M Elliott, Hugh Calkins, Cynthia A James
Background and Aims Pathogenic variants in the desmoplakin (DSP) gene are associated with the development of a distinct arrhythmogenic cardiomyopathy phenotype not fully captured by either dilated cardiomyopathy (DCM), non-dilated left ventricular cardiomyopathy (NDLVC), or arrhythmogenic right ventricular cardiomyopathy (ARVC). Prior studies have described baseline DSP cardiomyopathy genetic, inflammatory, and structural characteristics. However, cohort sizes have limited full clinical characterization and identification of clinical and demographic predictors of sustained ventricular arrhythmias (VAs), heart failure (HF) hospitalizations, and transplant/death. In particular, the relevance of acute myocarditis-like episodes for subsequent disease course is largely unknown. Methods All patients with pathogenic/likely pathogenic (P/LP) DSP variants in the worldwide DSP-ERADOS Network (26 academic institutions across nine countries) were included. The primary outcomes were the development of sustained VA and HF hospitalizations during follow-up. Fine–Gray regressions were used to test association between clinical and instrumental parameters and the development of outcomes. Results Eight hundred patients [40.3 ± 17.5 years, 47.5% probands, left ventricular ejection fraction (LVEF) 49.5 ± 13.9%] were included. Over 3.7 [1.4–7.1] years, 139 (17.4%, 3.9%/year) and 72 (9.0%, 1.8%/year) patients experienced sustained VA and HF episodes, respectively. A total of 32.5% of individuals did not fulfil diagnostic criteria for ARVC, DCM, or NDLVC; their VA incidence was 0.5%/year. In multivariable regression, risk features associated with the development of VA were female sex [adjusted hazard ratio (aHR) 1.547; P = .025], prior non-sustained ventricular tachycardia (aHR 1.721; P = .009), prior sustained VA (aHR 1.923; P = .006), and LVEF ≤ 50% (aHR: 1.645; P = .032), while for HF, they were the presence of T-wave inversion in 3+ electrocardiogram leads (aHR 2.036, P = .007) and LVEF ≤ 50% (aHR 3.879; P < .001). Additionally, 70 (8.8%) patients experienced a myocardial injury episode at presentation or during follow-up. These episodes were associated with an increased risk of VA and HF thereafter (HR 2.394; P < .001, and HR 5.064, P < .001, respectively). Conclusions Patients with P/LP DSP variants experience high rates of sustained VA and HF hospitalizations. These patients demonstrate a distinct clinical phenotype (DSP cardiomyopathy), whose most prominent risk features associated with adverse clinical outcomes are the presence of prior non-sustained ventricular tachycardia or sustained VA, T-wave inversion in 3+ leads on electrocardiogram, LVEF ≤ 50%, and myocardial injury events.
背景和目的 去鳞片蛋白（DSP）基因中的致病变体与独特的致心律失常性心肌病表型的发生有关，而扩张型心肌病（DCM）、非扩张型左室心肌病（NDLVC）或致心律失常性右室心肌病（ARVC）并不能完全反映这种表型。先前的研究描述了 DSP 心肌病的遗传、炎症和结构基线特征。然而，队列规模限制了全面的临床特征描述以及持续室性心律失常（VAs）、心力衰竭（HF）住院和移植/死亡的临床和人口学预测因素的识别。特别是，急性心肌炎样发作与后续病程的相关性在很大程度上尚属未知。方法 纳入全球 DSP-ERADOS 网络（9 个国家的 26 家学术机构）中所有致病性/可能致病性（P/LP）DSP 变体患者。主要研究结果是随访期间出现持续的退行性变异和心房颤动住院。采用精细格雷回归法检验临床和工具参数与结局发展之间的关联。结果 共纳入 800 名患者[40.3 ± 17.5 岁，47.5% 为原发性，左心室射血分数（LVEF）49.5 ± 13.9%]。在 3.7 [1.4-7.1] 年的时间里，分别有 139 名（17.4%，3.9%/年）和 72 名（9.0%，1.8%/年）患者经历了持续的 VA 和 HF 发作。共有32.5%的患者不符合ARVC、DCM或NDLVC的诊断标准；他们的VA发生率为0.5%/年。在多变量回归中，与 VA 发生相关的风险特征为女性[调整后危险比 (aHR) 1.547; P = .025]、既往非持续性室速（aHR 1.721; P = .009）、既往持续性 VA（aHR 1.923；P = .006）和 LVEF ≤ 50%（aHR：1.645；P = .032），而对于 HF，则是 3+ 个心电图导联出现 T 波倒置（aHR 2.036，P = .007）和 LVEF ≤ 50%（aHR 3.879；P <.001）。此外，70 例（8.8%）患者在发病时或随访期间发生过心肌损伤。这些损伤事件与此后发生 VA 和 HF 的风险增加有关（分别为 HR 2.394; P < .001 和 HR 5.064, P < .001）。结论 P/LP DSP 变体患者的持续 VA 和 HF 住院率很高。这些患者表现出一种独特的临床表型（DSP 心肌病），其与不良临床结局相关的最显著的风险特征是既往存在非持续性室速或持续性 VA、心电图 3+ 导联 T 波倒置、LVEF ≤ 50%，以及心肌损伤事件。
{"title":"Clinical features and outcomes in carriers of pathogenic desmoplakin variants","authors":"Alessio Gasperetti, Richard T Carrick, Alexandros Protonotarios, Brittney Murray, Mikael Laredo, Iris van der Schaaf, Ronald H Lekanne, Petros Syrris, Douglas Cannie, Crystal Tichnell, Chiara Cappelletto, Marta Gigli, Kristen Medo, Ardan M Saguner, Firat Duru, Nisha A Gilotra, Stefan Zimmerman, Robyn Hylind, Dominic J Abrams, Neal K Lakdawala, Julia Cadrin-Tourigny, Mattia Targetti, Iacopo Olivotto, Maddalena Graziosi, Moniek Cox, Elena Biagini, Philippe Charron, Michela Casella, Claudio Tondo, Momina Yazdani, James S Ware, Sanjay K Prasad, Leonardo Calò, Eric D Smith, Adam S Helms, Sophie Hespe, Jodie Ingles, Harikrishna Tandri, Flavie Ader, Giovanni Peretto, Stacey Peters, Ari Horton, Jess Yao, Sven Dittmann, Eric Schulze-Bahr, Maria Qureshi, Katelyn Young, Eric D Carruth, Chris Haggerty, Victoria N Parikh, Matthew Taylor, Luisa Mestroni, Arthur Wilde, Gianfranco Sinagra, Marco Merlo, Estelle Gandjbakhch, J Peter van Tintelen, Anneline S J M te Riele, Perry M Elliott, Hugh Calkins, Cynthia A James","doi":"10.1093/eurheartj/ehae571","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae571","url":null,"abstract":"Background and Aims Pathogenic variants in the desmoplakin (DSP) gene are associated with the development of a distinct arrhythmogenic cardiomyopathy phenotype not fully captured by either dilated cardiomyopathy (DCM), non-dilated left ventricular cardiomyopathy (NDLVC), or arrhythmogenic right ventricular cardiomyopathy (ARVC). Prior studies have described baseline DSP cardiomyopathy genetic, inflammatory, and structural characteristics. However, cohort sizes have limited full clinical characterization and identification of clinical and demographic predictors of sustained ventricular arrhythmias (VAs), heart failure (HF) hospitalizations, and transplant/death. In particular, the relevance of acute myocarditis-like episodes for subsequent disease course is largely unknown. Methods All patients with pathogenic/likely pathogenic (P/LP) DSP variants in the worldwide DSP-ERADOS Network (26 academic institutions across nine countries) were included. The primary outcomes were the development of sustained VA and HF hospitalizations during follow-up. Fine–Gray regressions were used to test association between clinical and instrumental parameters and the development of outcomes. Results Eight hundred patients [40.3 ± 17.5 years, 47.5% probands, left ventricular ejection fraction (LVEF) 49.5 ± 13.9%] were included. Over 3.7 [1.4–7.1] years, 139 (17.4%, 3.9%/year) and 72 (9.0%, 1.8%/year) patients experienced sustained VA and HF episodes, respectively. A total of 32.5% of individuals did not fulfil diagnostic criteria for ARVC, DCM, or NDLVC; their VA incidence was 0.5%/year. In multivariable regression, risk features associated with the development of VA were female sex [adjusted hazard ratio (aHR) 1.547; P = .025], prior non-sustained ventricular tachycardia (aHR 1.721; P = .009), prior sustained VA (aHR 1.923; P = .006), and LVEF ≤ 50% (aHR: 1.645; P = .032), while for HF, they were the presence of T-wave inversion in 3+ electrocardiogram leads (aHR 2.036, P = .007) and LVEF ≤ 50% (aHR 3.879; P &lt; .001). Additionally, 70 (8.8%) patients experienced a myocardial injury episode at presentation or during follow-up. These episodes were associated with an increased risk of VA and HF thereafter (HR 2.394; P &lt; .001, and HR 5.064, P &lt; .001, respectively). Conclusions Patients with P/LP DSP variants experience high rates of sustained VA and HF hospitalizations. These patients demonstrate a distinct clinical phenotype (DSP cardiomyopathy), whose most prominent risk features associated with adverse clinical outcomes are the presence of prior non-sustained ventricular tachycardia or sustained VA, T-wave inversion in 3+ leads on electrocardiogram, LVEF ≤ 50%, and myocardial injury events.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1093/eurheartj/ehae551
Monika Gawałko, Melissa E Middeldorp, Arnela Saljic, John Penders, Thomas Jespersen, Christine M Albert, Gregory M Marcus, Christopher X Wong, Prashanthan Sanders, Dominik Linz
Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. Comprehensive modification of established AF risk factors combined with dietary interventions and breaking deleterious habits has been shown to reduce AF burden and recurrence. Numerous AF risk factors, such as diabetes, obesity or hypertension can be partially related to dietary and lifestyle choices. Therefore, dietary interventions may have potential as a therapeutic approach in AF. Based on available data, current guidelines recommend alcohol abstinence or reduction to decrease AF symptoms, burden, and progression, and do not indicate the need for caffeine abstention to prevent AF episodes (unless it is a trigger for AF symptoms). Uncertainty persists regarding harms or benefits of other dietary factors including chocolate, fish, salt, polyunsaturated and monounsaturated fatty acids, vitamins, and micronutrients. This article provides a systematic review of the association between AF and both dietary patterns and components. Additionally, it discusses potentially related mechanisms and introduces different strategies to assess patients’ nutrition patterns, including mobile health solutions and diet indices. Finally, it highlights the gaps in knowledge requiring future investigation.
{"title":"Diet and risk of atrial fibrillation: a systematic review","authors":"Monika Gawałko, Melissa E Middeldorp, Arnela Saljic, John Penders, Thomas Jespersen, Christine M Albert, Gregory M Marcus, Christopher X Wong, Prashanthan Sanders, Dominik Linz","doi":"10.1093/eurheartj/ehae551","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae551","url":null,"abstract":"Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. Comprehensive modification of established AF risk factors combined with dietary interventions and breaking deleterious habits has been shown to reduce AF burden and recurrence. Numerous AF risk factors, such as diabetes, obesity or hypertension can be partially related to dietary and lifestyle choices. Therefore, dietary interventions may have potential as a therapeutic approach in AF. Based on available data, current guidelines recommend alcohol abstinence or reduction to decrease AF symptoms, burden, and progression, and do not indicate the need for caffeine abstention to prevent AF episodes (unless it is a trigger for AF symptoms). Uncertainty persists regarding harms or benefits of other dietary factors including chocolate, fish, salt, polyunsaturated and monounsaturated fatty acids, vitamins, and micronutrients. This article provides a systematic review of the association between AF and both dietary patterns and components. Additionally, it discusses potentially related mechanisms and introduces different strategies to assess patients’ nutrition patterns, including mobile health solutions and diet indices. Finally, it highlights the gaps in knowledge requiring future investigation.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1093/eurheartj/ehae625
Milton Packer
{"title":"Traditional Chinese medicine: cardiovascular drug development through a holistic framework.","authors":"Milton Packer","doi":"10.1093/eurheartj/ehae625","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae625","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1093/eurheartj/ehae631
{"title":"Correction to: Electrical storm treatment by percutaneous stellate ganglion block: the STAR study.","authors":"","doi":"10.1093/eurheartj/ehae631","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae631","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1093/eurheartj/ehae416
Mario Gaudino, Allan S Jaffe, Milan Milojevic, Yader Sandoval, Philip J Deveraux, Kristian Thygesen, Patrick O Myers, Jolanda Kluin
{"title":"Great debate: myocardial infarction after cardiac surgery must be redefined.","authors":"Mario Gaudino, Allan S Jaffe, Milan Milojevic, Yader Sandoval, Philip J Deveraux, Kristian Thygesen, Patrick O Myers, Jolanda Kluin","doi":"10.1093/eurheartj/ehae416","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae416","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":null,"pages":null},"PeriodicalIF":37.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1093/eurheartj/ehae461
Chisom Obiezu-Umeh, Mark D Huffman, Dike Ojji
{"title":"Multi-stakeholder workshop on reducing population-wide dietary sodium intake in Nigeria.","authors":"Chisom Obiezu-Umeh, Mark D Huffman, Dike Ojji","doi":"10.1093/eurheartj/ehae461","DOIUrl":"10.1093/eurheartj/ehae461","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":null,"pages":null},"PeriodicalIF":37.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11400797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1093/eurheartj/ehae322
Sanjiv J Shah, Kavita Sharma, Barry A Borlaug, Javed Butler, Melanie Davies, Dalane W Kitzman, Mark C Petrie, Subodh Verma, Shachi Patel, Khaja M Chinnakondepalli, Mette N Einfeldt, Thomas J Jensen, Søren Rasmussen, Rabea Asleh, Tuvia Ben-Gal, Mikhail N Kosiborod
Background and aims: In the STEP-HFpEF trial programme, treatment with semaglutide resulted in multiple beneficial effects in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Efficacy may vary according to baseline diuretic use, and semaglutide treatment could modify diuretic dose.
Methods: In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks, we examined whether efficacy and safety endpoints differed by baseline diuretic use, as well as the effect of semaglutide on loop diuretic use and dose changes over the 52-week treatment period.
Results: At baseline, across no diuretic (n = 220), non-loop diuretic only (n = 223), and loop diuretic [<40 (n = 219), 40 (n = 309), and >40 (n = 174) mg/day furosemide equivalents] groups, there was progressively higher prevalence of hypertension and atrial fibrillation; and greater severity of obesity and heart failure. Over 52 weeks of treatment, semaglutide had a consistent beneficial effect on change in body weight across diuretic use categories (adjusted mean difference vs. placebo ranged from -8.8% [95% confidence interval (CI) -10.3, -6.3] to -6.9% [95% CI -9.1, -4.7] from no diuretics to the highest loop diuretic dose category; interaction P = .39). Kansas City Cardiomyopathy Questionnaire clinical summary score improvement was greater in patients on loop diuretics compared to those not on loop diuretics (adjusted mean difference vs. placebo: +9.3 [6.5; 12.1] vs. +4.7 points [1.3, 8.2]; P = .042). Semaglutide had consistent beneficial effects on all secondary efficacy endpoints (including 6 min walk distance) across diuretic subgroups (interaction P = .24-.92). Safety also favoured semaglutide vs. placebo across the diuretic subgroups. From baseline to 52 weeks, loop diuretic dose decreased by 17% in the semaglutide group vs. a 2.4% increase in the placebo group (P < .0001). Semaglutide (vs. placebo) was more likely to result in loop diuretic dose reduction (odds ratio [OR] 2.67 [95% CI 1.70, 4.18]) and less likely dose increase (OR 0.35 [95% CI 0.23, 0.53]; P < .001 for both) from baseline to 52 weeks.
Conclusions: In patients with obesity-related HFpEF, semaglutide improved heart failure-related symptoms and physical limitations across diuretic use subgroups, with more pronounced benefits among patients receiving loop diuretics at baseline. Reductions in weight and improvements in exercise function with semaglutide vs. placebo were consistent in all diuretic use categories. Semaglutide also led to a reduction in loop diuretic use and dose between baseline and 52 weeks.
Clinical trial registration: NCT04788511 and NCT04916470.
背景与目的：在STEP-HFpEF试验项目中，使用semaglutide治疗肥胖相关性射血分数保留型心力衰竭（HFpEF）患者可获得多种益处。疗效可能因基线利尿剂使用情况而异，而塞马鲁肽治疗可改变利尿剂剂量：在这项对STEP-HFpEF和STEP-HFpEF-DM试验（n=1145）的汇总数据进行的预先指定分析中，我们考察了疗效和安全性终点是否因基线利尿剂使用情况而不同，以及在52周的治疗期间内，塞马鲁肽对襻利尿剂使用和剂量变化的影响：基线时，在不使用利尿剂组（220人）、仅使用非襻利尿剂组（223人）和襻利尿剂组（40 [n=174]毫克/天呋塞米当量）中，高血压和心房颤动的发病率以及肥胖和心力衰竭的严重程度逐渐升高。在52周的治疗中，塞马鲁肽对不同利尿剂使用类别的体重变化具有一致的有利影响（与安慰剂相比，调整后的平均差异从-8.8% [95% CI -10.3，-6.3]到-6.9% [95% CI -9.1，-4.7]不使用利尿剂到最高襻利尿剂剂量类别；交互作用P=0.39）。与未使用襻利尿剂的患者相比，使用襻利尿剂的患者的堪萨斯城心肌病问卷临床总分改善幅度更大（与安慰剂相比，调整后的平均差异为 +9.3 [6.5.5] ：+9.3 [6.5; 12.1] vs. +4.7 分 [1.3, 8.2]; P=0.042）。在不同的利尿剂亚组中，塞马鲁肽对所有次要疗效终点（包括6分钟步行距离）都有一致的有利影响（交互作用P=0.24-0.92）。在所有利尿剂亚组中，塞马鲁肽对安慰剂的安全性也更有利。从基线到52周，塞马鲁肽组的襻利尿剂剂量减少了17%，而安慰剂组则增加了2.4%（PC结论：塞马鲁肽组的襻利尿剂剂量减少了17%，而安慰剂组则增加了2.4%）：在肥胖相关的高频心衰患者中，各利尿剂使用亚组的心衰相关症状和身体限制均有所改善，基线接受襻利尿剂治疗的患者获益更明显。与安慰剂相比，使用塞马鲁肽后体重减轻、运动功能改善的情况在所有使用利尿剂的类别中都是一致的。在基线至52周期间，塞马鲁肽还能减少襻利尿剂的使用和剂量：NCT04788511和NCT04916470。
{"title":"Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials.","authors":"Sanjiv J Shah, Kavita Sharma, Barry A Borlaug, Javed Butler, Melanie Davies, Dalane W Kitzman, Mark C Petrie, Subodh Verma, Shachi Patel, Khaja M Chinnakondepalli, Mette N Einfeldt, Thomas J Jensen, Søren Rasmussen, Rabea Asleh, Tuvia Ben-Gal, Mikhail N Kosiborod","doi":"10.1093/eurheartj/ehae322","DOIUrl":"10.1093/eurheartj/ehae322","url":null,"abstract":"<p><strong>Background and aims: </strong>In the STEP-HFpEF trial programme, treatment with semaglutide resulted in multiple beneficial effects in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Efficacy may vary according to baseline diuretic use, and semaglutide treatment could modify diuretic dose.</p><p><strong>Methods: </strong>In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks, we examined whether efficacy and safety endpoints differed by baseline diuretic use, as well as the effect of semaglutide on loop diuretic use and dose changes over the 52-week treatment period.</p><p><strong>Results: </strong>At baseline, across no diuretic (n = 220), non-loop diuretic only (n = 223), and loop diuretic [<40 (n = 219), 40 (n = 309), and >40 (n = 174) mg/day furosemide equivalents] groups, there was progressively higher prevalence of hypertension and atrial fibrillation; and greater severity of obesity and heart failure. Over 52 weeks of treatment, semaglutide had a consistent beneficial effect on change in body weight across diuretic use categories (adjusted mean difference vs. placebo ranged from -8.8% [95% confidence interval (CI) -10.3, -6.3] to -6.9% [95% CI -9.1, -4.7] from no diuretics to the highest loop diuretic dose category; interaction P = .39). Kansas City Cardiomyopathy Questionnaire clinical summary score improvement was greater in patients on loop diuretics compared to those not on loop diuretics (adjusted mean difference vs. placebo: +9.3 [6.5; 12.1] vs. +4.7 points [1.3, 8.2]; P = .042). Semaglutide had consistent beneficial effects on all secondary efficacy endpoints (including 6 min walk distance) across diuretic subgroups (interaction P = .24-.92). Safety also favoured semaglutide vs. placebo across the diuretic subgroups. From baseline to 52 weeks, loop diuretic dose decreased by 17% in the semaglutide group vs. a 2.4% increase in the placebo group (P < .0001). Semaglutide (vs. placebo) was more likely to result in loop diuretic dose reduction (odds ratio [OR] 2.67 [95% CI 1.70, 4.18]) and less likely dose increase (OR 0.35 [95% CI 0.23, 0.53]; P < .001 for both) from baseline to 52 weeks.</p><p><strong>Conclusions: </strong>In patients with obesity-related HFpEF, semaglutide improved heart failure-related symptoms and physical limitations across diuretic use subgroups, with more pronounced benefits among patients receiving loop diuretics at baseline. Reductions in weight and improvements in exercise function with semaglutide vs. placebo were consistent in all diuretic use categories. Semaglutide also led to a reduction in loop diuretic use and dose between baseline and 52 weeks.</p><p><strong>Clinical trial registration: </strong>NCT04788511 and NCT04916470.</p>","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":null,"pages":null},"PeriodicalIF":37.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11400859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1093/eurheartj/ehae586
Filippo Crea
{"title":"The fascinating story of lipid-lowering drugs, sodium-glucose co-transporter 2 inhibitors and GLP1-R agonists: new light shed on their beneficial effects.","authors":"Filippo Crea","doi":"10.1093/eurheartj/ehae586","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae586","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1093/eurheartj/ehae492
Stephan Nopp, Cihan Ay, Ingrid Pabinger
{"title":"From arteries to veins: the expanding role of lipid-lowering drugs in preventing thrombosis.","authors":"Stephan Nopp, Cihan Ay, Ingrid Pabinger","doi":"10.1093/eurheartj/ehae492","DOIUrl":"10.1093/eurheartj/ehae492","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":null,"pages":null},"PeriodicalIF":37.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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