Vaishnavi Aradhyula, Sareeta Manandhar, Alborz Sherafati, Alex Kloster, Anas Fares, Prabhatchandra Dube, Pamela S. Brewster, George V. Moukarbel, Krishna Rao Maddipati, Steven T. Haller, David J. Kennedy, Rajesh Gupta, Samer J. Khouri
Aims
Heart failure with preserved ejection fraction (HFpEF) poses significant diagnostic, prognostic and therapeutic challenges, with high morbidity and mortality rates. Currently, there are limited predictors of outcomes in HFpEF patients. Circulating oxidized polyunsaturated fatty acyl lipids, or oxylipins, are known to initiate and resolve inflammation in cardiovascular diseases. However, their ability to predict mortality in HFpEF has not been established. We hypothesize that a panel of oxylipins can predict and stratify mortality risk in HFpEF patients.
Methods and results
Venous and arterial blood samples were collected during right heart catheterization from 90 HFpEF patients at a single institution. Patients were followed for 5 years to determine morbidity and mortality rates. We measured 143 arterial and 143 venous oxylipins in all study participants using liquid chromatography-mass spectrometry. Volcano plots were used to visualize differences in oxylipins between survived and deceased groups. Receiver operator characteristic (ROC) curves were used to determine optimal biomarker cut-points, and the relationship between the most significant oxylipins and mortality was assessed with Kaplan–Meier (KM) curves. HFpEF patients with 5-year mortality had increased age, decreased body mass index, decreased diastolic blood pressure and worse renal function at baseline. They also had more severe pulmonary hypertension (PH) and right heart dysfunction. Volcano plot analysis revealed that arterial oxylipin 15-keto prostaglandin F2a (PGF2a) was significantly associated with 5-year mortality. ROC curve analysis identified an optimal cut-point for 15-keto PGF2a, and participants with elevated arterial 15-keto PGF2a had significantly increased 5-year mortality on KM curves. Multivariable adjusted analysis identified 15-keto PGF2a as a significant predictor of 5-year mortality (OR 1.82; CI 1.03, 3.5).
Conclusions
In this cohort of patients with HFpEF, arterial 15-keto PGF2a, a stable metabolite of PGF2a, significantly predicted 5-year mortality.
目的：保留射血分数的心力衰竭（HFpEF）具有很高的发病率和死亡率，对诊断、预后和治疗提出了重大挑战。目前，HFpEF患者预后的预测指标有限。循环氧化的多不饱和脂肪酸酰基脂，或氧脂类，已知可以引发和解决心血管疾病中的炎症。然而，它们预测HFpEF死亡率的能力尚未得到证实。我们假设一组氧脂素可以预测和分层HFpEF患者的死亡风险。方法和结果：在同一医院对90例HFpEF患者进行右心导管置管时采集静脉和动脉血样。患者随访5年以确定发病率和死亡率。我们使用液相色谱-质谱法测量了所有研究参与者的143个动脉和143个静脉氧脂素。火山图用于可视化幸存和死亡群体之间的氧化脂质差异。采用受试者操作特征（ROC）曲线确定最佳生物标志物切点，并采用Kaplan-Meier （KM）曲线评估最显著的氧化脂素与死亡率之间的关系。HFpEF患者的5年死亡率在基线时年龄增加，体重指数下降，舒张压下降，肾功能恶化。他们也有更严重的肺动脉高压（PH）和右心功能障碍。火山图分析显示，动脉氧脂素15-酮前列腺素F2a （PGF2a）与5年死亡率显著相关。ROC曲线分析确定了15-酮PGF2a的最佳切割点，动脉15-酮PGF2a升高的参与者在KM曲线上的5年死亡率显着增加。多变量调整分析发现15-酮PGF2a是5年死亡率的重要预测因子（OR 1.82; CI 1.03, 3.5）。结论：在该HFpEF患者队列中，动脉15-酮PGF2a （PGF2a的稳定代谢物）显著预测5年死亡率。
{"title":"Circulating oxylipins predict mortality in heart failure with preserved ejection fraction","authors":"Vaishnavi Aradhyula, Sareeta Manandhar, Alborz Sherafati, Alex Kloster, Anas Fares, Prabhatchandra Dube, Pamela S. Brewster, George V. Moukarbel, Krishna Rao Maddipati, Steven T. Haller, David J. Kennedy, Rajesh Gupta, Samer J. Khouri","doi":"10.1002/ehf2.15425","DOIUrl":"10.1002/ehf2.15425","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Heart failure with preserved ejection fraction (HFpEF) poses significant diagnostic, prognostic and therapeutic challenges, with high morbidity and mortality rates. Currently, there are limited predictors of outcomes in HFpEF patients. Circulating oxidized polyunsaturated fatty acyl lipids, or oxylipins, are known to initiate and resolve inflammation in cardiovascular diseases. However, their ability to predict mortality in HFpEF has not been established. We hypothesize that a panel of oxylipins can predict and stratify mortality risk in HFpEF patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Venous and arterial blood samples were collected during right heart catheterization from 90 HFpEF patients at a single institution. Patients were followed for 5 years to determine morbidity and mortality rates. We measured 143 arterial and 143 venous oxylipins in all study participants using liquid chromatography-mass spectrometry. Volcano plots were used to visualize differences in oxylipins between survived and deceased groups. Receiver operator characteristic (ROC) curves were used to determine optimal biomarker cut-points, and the relationship between the most significant oxylipins and mortality was assessed with Kaplan–Meier (KM) curves. HFpEF patients with 5-year mortality had increased age, decreased body mass index, decreased diastolic blood pressure and worse renal function at baseline. They also had more severe pulmonary hypertension (PH) and right heart dysfunction. Volcano plot analysis revealed that arterial oxylipin 15-keto prostaglandin F2a (PGF2a) was significantly associated with 5-year mortality. ROC curve analysis identified an optimal cut-point for 15-keto PGF2a, and participants with elevated arterial 15-keto PGF2a had significantly increased 5-year mortality on KM curves. Multivariable adjusted analysis identified 15-keto PGF2a as a significant predictor of 5-year mortality (OR 1.82; CI 1.03, 3.5).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this cohort of patients with HFpEF, arterial 15-keto PGF2a, a stable metabolite of PGF2a, significantly predicted 5-year mortality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4255-4265"},"PeriodicalIF":3.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tania Pastrana, Matthew Grant, Paula Hidalgo Andrade, Daniele Marelli, Klaus Witte, Geert-Jan Geersing, Carla Ripamonti, Roman Rolke, Marco Metra, Matteo Pagnesi, Everlien De Graaf, Cosimo Chelazzi, RAPHAEL consortium
Heart failure (HF) is a growing health and societal challenge in Europe, due to an increasingly elderly, frail and multimorbid population. Many patients with HF experience a high burden of complex and multidimensional symptoms leading to a reduced quality of life and significant socioeconomic impact. Despite proven benefits, the integration of palliative care into HF management pathways remains inconsistent and underutilized. We aim to map how current national and international guidelines recommend integrating palliative care into HF management across the 10 countries represented by the EU-funded RAPHAEL consortium (Horizon Europe programme, No 101137170): Belgium, Germany, Lithuania, the Netherlands, Spain, Italy, Poland, Sweden, Switzerland and the United Kingdom. A systematic search was conducted across six databases (EMBASE, Global Health, MEDLINE, PsycINFO, The Cochrane Library and Web of Science) for publications from 1 January 2000 to 25 May 2024. Eligible publications focused on adults with HF and models of palliative care integration. Data were synthesized using content analysis. Of 1543 records screened, 13 publications were included. Most studies were guidelines, consensus or position papers; only one was qualitative research. The definition of the population with HF eligible for palliative care was heterogeneous and inconsistently defined, mostly by symptoms (4/13 publications; 31%) and pathophysiology (2/13; 15%). The most frequent triggers for palliative care referral were clinical features and symptoms (8/13; 62%), patients approaching the end of life (8/13; 62%), and symptomatic deterioration despite optimal therapy (7/13; 54%). Additional triggers included multiple (>1) unplanned hospitalizations (6/13; 46%) and spiritual, emotional or social issues (7/13; 54%). Outcomes of palliative care referral for HF patients focused on quality of life (9/13; 69%) and symptom control (9/13; 69%). Multiprofessional involvement was emphasized with cardiologists (12/13; 92%), nurses (10/12; 77%), palliative care specialists (9/13; 69%) and primary care physicians (4/13; 31%). Publications generally noted that despite increased awareness and recommendations, referrals remain low and mostly late stages. This review underscores the need for structured, early integration of palliative care in HF management across Europe with clear triggers for palliative care referral, application of standardized pathways and fostering of multiprofessional collaboration. Developing these, while simultaneously addressing implementation challenges through policy development, could improve patient outcomes and quality of life.
心力衰竭（HF）在欧洲是一个日益严重的健康和社会挑战，原因是老年、体弱和多病人群日益增多。许多心衰患者经历复杂和多方面症状的沉重负担，导致生活质量下降和显著的社会经济影响。尽管证明了益处，但将姑息治疗纳入心衰管理途径仍然不一致且未得到充分利用。我们的目标是绘制当前国家和国际指南如何建议在欧盟资助的RAPHAEL联盟（Horizon Europe项目，No . 101137170）所代表的10个国家将姑息治疗纳入心衰管理的地图：比利时、德国、立陶宛、荷兰、西班牙、意大利、波兰、瑞典、瑞士和英国。系统检索了六个数据库（EMBASE、Global Health、MEDLINE、PsycINFO、Cochrane图书馆和Web of Science） 2000年1月1日至2024年5月25日的出版物。合格的出版物集中于HF成人和姑息治疗整合模型。采用内容分析法对数据进行综合。在筛选的1543份记录中，包括13份出版物。大多数研究是指导方针、共识或立场文件；只有一个是定性研究。有资格接受姑息治疗的心衰人群的定义是异质且不一致的，主要是通过症状（4/13篇，31%）和病理生理学（2/13篇，15%）来定义。姑息治疗转诊最常见的触发因素是临床特征和症状（8/13;62%），患者接近生命终点（8/13;62%），以及最佳治疗后症状恶化（7/13;54%）。其他触发因素包括多次计划外住院（6/13;46%）和精神、情感或社会问题（7/13;54%）。心衰患者姑息治疗转诊的结果主要集中在生活质量（9/13;69%）和症状控制（9/13;69%）。强调多专业参与，包括心脏病专家（12/13;92%）、护士（10/12;77%）、姑息治疗专家（9/13;69%）和初级保健医生（4/13;31%）。出版物普遍指出，尽管提高了认识并提出了建议，但转诊仍然很低，而且大多处于后期阶段。这篇综述强调了在欧洲HF管理中需要结构化的、早期整合姑息治疗，明确姑息治疗转诊的触发因素，应用标准化途径和促进多专业合作。制定这些措施，同时通过制定政策解决实施方面的挑战，可以改善患者的治疗效果和生活质量。
{"title":"Mapping of current practices of palliative care for patients with heart failure throughout Europe: A scoping review","authors":"Tania Pastrana, Matthew Grant, Paula Hidalgo Andrade, Daniele Marelli, Klaus Witte, Geert-Jan Geersing, Carla Ripamonti, Roman Rolke, Marco Metra, Matteo Pagnesi, Everlien De Graaf, Cosimo Chelazzi, RAPHAEL consortium","doi":"10.1002/ehf2.15431","DOIUrl":"10.1002/ehf2.15431","url":null,"abstract":"<p>Heart failure (HF) is a growing health and societal challenge in Europe, due to an increasingly elderly, frail and multimorbid population. Many patients with HF experience a high burden of complex and multidimensional symptoms leading to a reduced quality of life and significant socioeconomic impact. Despite proven benefits, the integration of palliative care into HF management pathways remains inconsistent and underutilized. We aim to map how current national and international guidelines recommend integrating palliative care into HF management across the 10 countries represented by the EU-funded RAPHAEL consortium (Horizon Europe programme, No 101137170): Belgium, Germany, Lithuania, the Netherlands, Spain, Italy, Poland, Sweden, Switzerland and the United Kingdom. A systematic search was conducted across six databases (EMBASE, Global Health, MEDLINE, PsycINFO, The Cochrane Library and Web of Science) for publications from 1 January 2000 to 25 May 2024. Eligible publications focused on adults with HF and models of palliative care integration. Data were synthesized using content analysis. Of 1543 records screened, 13 publications were included. Most studies were guidelines, consensus or position papers; only one was qualitative research. The definition of the population with HF eligible for palliative care was heterogeneous and inconsistently defined, mostly by symptoms (4/13 publications; 31%) and pathophysiology (2/13; 15%). The most frequent triggers for palliative care referral were clinical features and symptoms (8/13; 62%), patients approaching the end of life (8/13; 62%), and symptomatic deterioration despite optimal therapy (7/13; 54%). Additional triggers included multiple (>1) unplanned hospitalizations (6/13; 46%) and spiritual, emotional or social issues (7/13; 54%). Outcomes of palliative care referral for HF patients focused on quality of life (9/13; 69%) and symptom control (9/13; 69%). Multiprofessional involvement was emphasized with cardiologists (12/13; 92%), nurses (10/12; 77%), palliative care specialists (9/13; 69%) and primary care physicians (4/13; 31%). Publications generally noted that despite increased awareness and recommendations, referrals remain low and mostly late stages. This review underscores the need for structured, early integration of palliative care in HF management across Europe with clear triggers for palliative care referral, application of standardized pathways and fostering of multiprofessional collaboration. Developing these, while simultaneously addressing implementation challenges through policy development, could improve patient outcomes and quality of life.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4021-4032"},"PeriodicalIF":3.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anika S. Naidu, Andrew P. Ambrosy, Gad Cotter, Edimar A. Bocchi, Javed Butler, Ovidiu Chioncel, Beth Davison, Anastase Dzudie, Yonathan Freund, Marat Fudim, Sivadasanpillai Harikrishnan, Ivna G. Cunha, Alexandre Mebazaa, Robert J. Mentz, Òscar Miró, Siti E. Nauli, Mateo Pagnesi, Naoki Sato, Gianluigi Savarese, Karen Sliwa-Hahnle, Yuhui Zhang, Jingmin Zhou, Jan Biegus
Acute heart failure (AHF) remains a major global health challenge, contributing significantly to morbidity, mortality and healthcare resource utilization. It is one of the leading causes of hospitalization, with persistently high readmission rates underscoring the need for improved early management strategies. Despite its prevalence, clear and evidence-based guidance for the early evaluation and treatment of AHF is limited. Congestion is the primary reason for emergency admission, making rapid and effective decongestion a top priority, but diuretics are often underdosed in AHF patients. Medications proven to improve mortality are often not started. In this state-of-the-art review, we address this critical gap by outlining a practical, evidence-based framework for the early management of AHF. Key components include early identification of co-existing conditions, bedside haemodynamic profiling, a structured diagnostic approach incorporating both standard and individualized assessments, a stepwise pharmacologic diuretic strategy beginning with high-dose intravenous loop diuretics, and early in-hospital initiation of guideline-directed medical therapy.
{"title":"Early in-hospital treatment of acute heart failure. Part 2 of the international expert opinion series on AHF management","authors":"Anika S. Naidu, Andrew P. Ambrosy, Gad Cotter, Edimar A. Bocchi, Javed Butler, Ovidiu Chioncel, Beth Davison, Anastase Dzudie, Yonathan Freund, Marat Fudim, Sivadasanpillai Harikrishnan, Ivna G. Cunha, Alexandre Mebazaa, Robert J. Mentz, Òscar Miró, Siti E. Nauli, Mateo Pagnesi, Naoki Sato, Gianluigi Savarese, Karen Sliwa-Hahnle, Yuhui Zhang, Jingmin Zhou, Jan Biegus","doi":"10.1002/ehf2.15389","DOIUrl":"10.1002/ehf2.15389","url":null,"abstract":"<p>Acute heart failure (AHF) remains a major global health challenge, contributing significantly to morbidity, mortality and healthcare resource utilization. It is one of the leading causes of hospitalization, with persistently high readmission rates underscoring the need for improved early management strategies. Despite its prevalence, clear and evidence-based guidance for the early evaluation and treatment of AHF is limited. Congestion is the primary reason for emergency admission, making rapid and effective decongestion a top priority, but diuretics are often underdosed in AHF patients. Medications proven to improve mortality are often not started. In this state-of-the-art review, we address this critical gap by outlining a practical, evidence-based framework for the early management of AHF. Key components include early identification of co-existing conditions, bedside haemodynamic profiling, a structured diagnostic approach incorporating both standard and individualized assessments, a stepwise pharmacologic diuretic strategy beginning with high-dose intravenous loop diuretics, and early in-hospital initiation of guideline-directed medical therapy.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"3826-3843"},"PeriodicalIF":3.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joongmin Kim, Sungyoun Chun, Jong-Kwan Park, Hancheol Lee, Ji-Yong Jang, Hyeongsoo Kim, Geunhee Park, Seung-Jin Oh, Se-Jung Yoon
Aims
Body mass index (BMI) has been widely used as a simple tool for predicting cardiovascular risk. Here we aimed to analyse the distribution and cardiovascular outcomes according to BMI and waist circumference (WC) of the newly diagnosed heart failure (HF) patients in the entire population of the Republic of Korea for 10 years.
Methods
A total of 999 127 patients newly diagnosed with HF between 2012 and 2021 among the entire population were included. The epidemiologic data of each subgroup according to BMI and WC were analysed, and cardiovascular outcomes were evaluated.
Results
Over the decade from 2012 to 2021, the obese group accounted for 47.1% of the newly diagnosed HF population. Kaplan–Meier curve and hazard ratio of cardiovascular events in each subgroup revealed significantly increased rates of hospitalization, death from all causes, cardiovascular death, acute myocardial infarction, atrial fibrillation and composite cardiac events in the underweight group compared with other groups (P value < 0.05). The subgroups of abdominal obesity in normal, overweight and obese patients revealed significantly high hazard ratio in almost all cardiovascular events (P value < 0.05).
Conversely, the overweight and obese groups without abdominal obesity showed the best cardiovascular outcomes. Increased cardiovascular risk was shown in groups with abdominal obesity even at the same BMI.
Conclusion
The cardiovascular prognosis was significantly worse in the underweight group than in the obese group, especially in the underweight abdominal obesity group. Even in the same BMI group, the prognosis is worse in the group with abdominal obesity. For a more accurate cardiovascular prognosis analysis, it is necessary to use WC along with BMI.
{"title":"Poor cardiovascular outcomes of underweight abdominal obesity in the entire population of newly diagnosed heart failure","authors":"Joongmin Kim, Sungyoun Chun, Jong-Kwan Park, Hancheol Lee, Ji-Yong Jang, Hyeongsoo Kim, Geunhee Park, Seung-Jin Oh, Se-Jung Yoon","doi":"10.1002/ehf2.15413","DOIUrl":"10.1002/ehf2.15413","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Body mass index (BMI) has been widely used as a simple tool for predicting cardiovascular risk. Here we aimed to analyse the distribution and cardiovascular outcomes according to BMI and waist circumference (WC) of the newly diagnosed heart failure (HF) patients in the entire population of the Republic of Korea for 10 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 999 127 patients newly diagnosed with HF between 2012 and 2021 among the entire population were included. The epidemiologic data of each subgroup according to BMI and WC were analysed, and cardiovascular outcomes were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over the decade from 2012 to 2021, the obese group accounted for 47.1% of the newly diagnosed HF population. Kaplan–Meier curve and hazard ratio of cardiovascular events in each subgroup revealed significantly increased rates of hospitalization, death from all causes, cardiovascular death, acute myocardial infarction, atrial fibrillation and composite cardiac events in the underweight group compared with other groups (<i>P</i> value < 0.05). The subgroups of abdominal obesity in normal, overweight and obese patients revealed significantly high hazard ratio in almost all cardiovascular events (<i>P</i> value < 0.05).</p>\u0000 \u0000 <p>Conversely, the overweight and obese groups without abdominal obesity showed the best cardiovascular outcomes. Increased cardiovascular risk was shown in groups with abdominal obesity even at the same BMI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The cardiovascular prognosis was significantly worse in the underweight group than in the obese group, especially in the underweight abdominal obesity group. Even in the same BMI group, the prognosis is worse in the group with abdominal obesity. For a more accurate cardiovascular prognosis analysis, it is necessary to use WC along with BMI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4242-4254"},"PeriodicalIF":3.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Judith Gronwald, Torben Lange, Sören J. Backhaus, Bo E. Beuthner, Ruben Evertz, Miriam Puls, Johannes T. Kowallick, Karl Toischer, Gerd Hasenfuß, Andreas Schuster, Alexander Schulz
Aims
Epicardial adipose tissue (EAT) is closely associated with the development of heart failure and adverse myocardial remodelling. In patients with severe aortic valve stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), increased EAT has been identified as a predictor of adverse outcomes; however, the underlying pathophysiological mechanisms remain unclear. This study aims to explore the effects of increased EAT volumes on myocardial remodelling and dysfunction in patients with severe AS.
Methods and results
One hundred thirty-seven patients with severe AS (median age 80 years, 62% male) underwent cardiac magnetic resonance imaging (CMR) prior to TAVR. Myocardial volumes and function as well as EAT volumes were quantified from CMR acquisitions. The cohort was dichotomised at the median EAT volume. Patients with increased EAT volumes above the median (≥46.5 mL/m2) showed impaired left atrial (LA) reservoir strain (Es) as a distinct functional feature compared with patients with lower EAT volumes (11.8% [7.6–16.7] vs. 15.0% [10.9–19.1], P = 0.011), while left ventricular (LV) morphology and function (all P ≥ 0.216), right atrial and ventricular morphology and function (all P ≥ 0.090), as well as tissue characteristics (all ≥ 0.229) were similar between both groups. In a subgroup analysis of the four types of severe AS, the difference was most prominent in patients with low ejection fraction high-gradient AS. In multivariable regression analyses, EAT was independently associated with impaired LA Es, irrespective of co-morbidities, ventricular function, tissue characteristics and functional characteristics of AS.
Conclusions
In patients with severe AS, increased EAT volume is independently associated with impaired LA function but not with other features of biventricular morphology, function or tissue composition. The incremental deterioration of LA function, in addition to the afterload imposed by AS in these patients, could increase vulnerability to heart failure and may require consideration as a therapeutic target beyond TAVR.
目的：心外膜脂肪组织（EAT）与心力衰竭和不良心肌重构的发展密切相关。在接受经导管主动脉瓣置换术（TAVR）的严重主动脉瓣狭窄（AS）患者中，增加的EAT已被确定为不良结局的预测因子；然而，潜在的病理生理机制尚不清楚。本研究旨在探讨进食量增加对严重AS患者心肌重构和功能障碍的影响。方法和结果：137例严重AS患者（中位年龄80岁，男性62%）在TAVR之前接受了心脏磁共振成像（CMR）。心肌体积和功能以及EAT体积通过CMR采集进行量化。按中位进食容积对队列进行二分。EAT容积高于中位数（≥46.5 mL/m2）的患者与EAT容积较低的患者相比（11.8% [7.6-16.7]vs. 15.0% [10.9-19.1], P = 0.011），左心室（LV）形态和功能（均P≥0.216）、右心房和心室形态和功能（均P≥0.090）以及组织特征（均≥0.229）在两组之间相似。在四种类型严重AS的亚组分析中，低射血分数高梯度AS患者的差异最为突出。在多变量回归分析中，与AS的合并症、心室功能、组织特征和功能特征无关，EAT与LA Es受损独立相关。结论：在严重AS患者中，EAT体积增加与LA功能受损独立相关，但与双心室形态、功能或组织组成的其他特征无关。在这些患者中，LA功能的逐渐恶化，加上AS带来的后负荷，可能增加心力衰竭的易损性，可能需要考虑将其作为TAVR以外的治疗靶点。
{"title":"Impact of epicardial adipose tissue on myocardial function and structure in patients with severe aortic valve stenosis","authors":"Judith Gronwald, Torben Lange, Sören J. Backhaus, Bo E. Beuthner, Ruben Evertz, Miriam Puls, Johannes T. Kowallick, Karl Toischer, Gerd Hasenfuß, Andreas Schuster, Alexander Schulz","doi":"10.1002/ehf2.15422","DOIUrl":"10.1002/ehf2.15422","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Epicardial adipose tissue (EAT) is closely associated with the development of heart failure and adverse myocardial remodelling. In patients with severe aortic valve stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), increased EAT has been identified as a predictor of adverse outcomes; however, the underlying pathophysiological mechanisms remain unclear. This study aims to explore the effects of increased EAT volumes on myocardial remodelling and dysfunction in patients with severe AS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>One hundred thirty-seven patients with severe AS (median age 80 years, 62% male) underwent cardiac magnetic resonance imaging (CMR) prior to TAVR. Myocardial volumes and function as well as EAT volumes were quantified from CMR acquisitions. The cohort was dichotomised at the median EAT volume. Patients with increased EAT volumes above the median (≥46.5 mL/m<sup>2</sup>) showed impaired left atrial (LA) reservoir strain (Es) as a distinct functional feature compared with patients with lower EAT volumes (11.8% [7.6–16.7] vs. 15.0% [10.9–19.1], <i>P</i> = 0.011), while left ventricular (LV) morphology and function (all <i>P</i> ≥ 0.216), right atrial and ventricular morphology and function (all <i>P</i> ≥ 0.090), as well as tissue characteristics (all ≥ 0.229) were similar between both groups. In a subgroup analysis of the four types of severe AS, the difference was most prominent in patients with low ejection fraction high-gradient AS. In multivariable regression analyses, EAT was independently associated with impaired LA Es, irrespective of co-morbidities, ventricular function, tissue characteristics and functional characteristics of AS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with severe AS, increased EAT volume is independently associated with impaired LA function but not with other features of biventricular morphology, function or tissue composition. The incremental deterioration of LA function, in addition to the afterload imposed by AS in these patients, could increase vulnerability to heart failure and may require consideration as a therapeutic target beyond TAVR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4230-4241"},"PeriodicalIF":3.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jan Biegus, Leszek Szenborn, Michał Tkaczyszyn, Robert Zymlinski, Gad Cotter, Michał Zakliczynski, Krzysztof Reczuch, Mateusz Guzik, Szymon Urban, Marta Rosiek-Biegus, Berenika Jankowiak, Gracjan Iwanek, Marta Wleklik, Marat Fudim, Piotr Ponikowski
Background
There is a scarcity of prospective data on the impact of available vaccinations against respiratory viruses on hard clinical endpoints in patients with heart failure (HF).
Aims
We investigated whether, in the population of high-risk HF patients, simultaneous vaccination against influenza and respiratory syncytial virus (RSV) improves outcomes during the subsequent infection season.
Methods
We conducted a prospective, randomized, single-centre, open-label study in which patients with high-risk HF were randomized 1:1 to simultaneous influenza and RSV vaccination or standard of care (SOC). The primary composite endpoint comprised all-cause death, HF hospitalization (HFH) or clinical signs/symptoms of infection within a 6 month follow-up period (regular structured telephone interview). Secondary endpoints were components of the composite primary endpoint.
Results
Two hundred twenty patients were randomized. During the follow-up period, the primary endpoint occurred in 59% of patients in the vaccination group versus 75% in the SOC group [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.48–0.92, P = 0.01]. Regarding the secondary endpoint analyses, during 6 month follow-up, 3% in the vaccination group died compared with 5% of patients in the SOC arm (HR 0.50, 95% CI 0.12 1.99, P = 0.32), and 18% versus 16% of study participants were hospitalized for HF in the two study arms, respectively (HR 0.86, 95% CI 0.45–1.62, P = 0.64). Infection occurred in 53% of vaccinated patients compared with 68% in SOC (HR 0.68, 95% CI 0.48–0.96, P = 0.03).
Conclusions
In the population of high-risk HF, simultaneous vaccination against influenza and RSV reduced the incidence of the primary outcome. The effect was driven by a significant reduction in infections.
背景：目前缺乏关于呼吸道病毒疫苗接种对心力衰竭（HF）患者硬临床终点影响的前瞻性数据。目的：我们调查在高危HF患者人群中，同时接种流感和呼吸道合胞病毒（RSV）疫苗是否能改善随后感染季节的预后。方法：我们进行了一项前瞻性、随机、单中心、开放标签的研究，在该研究中，高危HF患者以1:1的比例随机分组，同时接种流感和RSV疫苗或接受标准治疗（SOC）。主要复合终点包括6个月随访期内的全因死亡、心衰住院（HFH）或感染的临床体征/症状（定期结构化电话访谈）。次要终点是复合主要终点的组成部分。结果：随机选取220例患者。在随访期间，接种组59%的患者出现主要终点，而SOC组为75%[风险比（HR） 0.66, 95%可信区间（CI） 0.48-0.92, P = 0.01]。关于次要终点分析，在6个月的随访期间，接种组中有3%的患者死亡，而SOC组中有5%的患者死亡（HR 0.50, 95% CI 0.12 1.99, P = 0.32），两个研究组中分别有18%和16%的研究参与者因HF住院（HR 0.86, 95% CI 0.45-1.62, P = 0.64）。接种疫苗的患者感染发生率为53%，而SOC组为68% （HR 0.68, 95% CI 0.48-0.96, P = 0.03）。结论：在高危HF人群中，同时接种流感和RSV疫苗可降低主要结局的发生率。这种效果是由感染的显著减少所驱动的。
{"title":"Simultaneous vaccination against influenza and respiratory syncytial virus in high-risk heart failure patients","authors":"Jan Biegus, Leszek Szenborn, Michał Tkaczyszyn, Robert Zymlinski, Gad Cotter, Michał Zakliczynski, Krzysztof Reczuch, Mateusz Guzik, Szymon Urban, Marta Rosiek-Biegus, Berenika Jankowiak, Gracjan Iwanek, Marta Wleklik, Marat Fudim, Piotr Ponikowski","doi":"10.1002/ehf2.15432","DOIUrl":"10.1002/ehf2.15432","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is a scarcity of prospective data on the impact of available vaccinations against respiratory viruses on hard clinical endpoints in patients with heart failure (HF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We investigated whether, in the population of high-risk HF patients, simultaneous vaccination against influenza and respiratory syncytial virus (RSV) improves outcomes during the subsequent infection season.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a prospective, randomized, single-centre, open-label study in which patients with high-risk HF were randomized 1:1 to simultaneous influenza and RSV vaccination or standard of care (SOC). The primary composite endpoint comprised all-cause death, HF hospitalization (HFH) or clinical signs/symptoms of infection within a 6 month follow-up period (regular structured telephone interview). Secondary endpoints were components of the composite primary endpoint.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two hundred twenty patients were randomized. During the follow-up period, the primary endpoint occurred in 59% of patients in the vaccination group versus 75% in the SOC group [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.48–0.92, <i>P</i> = 0.01]. Regarding the secondary endpoint analyses, during 6 month follow-up, 3% in the vaccination group died compared with 5% of patients in the SOC arm (HR 0.50, 95% CI 0.12 1.99, <i>P</i> = 0.32), and 18% versus 16% of study participants were hospitalized for HF in the two study arms, respectively (HR 0.86, 95% CI 0.45–1.62, <i>P</i> = 0.64). Infection occurred in 53% of vaccinated patients compared with 68% in SOC (HR 0.68, 95% CI 0.48–0.96, <i>P</i> = 0.03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In the population of high-risk HF, simultaneous vaccination against influenza and RSV reduced the incidence of the primary outcome. The effect was driven by a significant reduction in infections.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"3869-3877"},"PeriodicalIF":3.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>We read with great interest the prospective analysis by McCambridge et al. on the management and outcomes of worsening heart failure (WHF) in the outpatient setting (ESC Heart Fail. 2025; doi: 10.1002/ehf2.15400). The authors should be commended for addressing an important and timely topic. However, I would like to highlight several issues that may limit the interpretation and generalizability of the findings.</p><p>First, the study applied two different definitions of WHF: (a) a prespecified, objective definition requiring symptoms of worsening together with clinical signs of congestion and/or supportive biomarker or imaging evidence, and (b) a broader, subjective definition based solely on senior physician judgment when the objective criteria were not met. Notably, about 16% of patients were included under this discretionary pathway. Such heterogeneity increases the risk of misclassification and makes it difficult to compare results with other registries and trials. Recent international consensus statements have underlined the need for a single, standardized definition of WHF to ensure comparability and external validity across studies.<span><sup>1, 2</sup></span></p><p>Second, the investigation was monocentric and included 234 patients over 19 months. While the prospective design is a strength, the limited sample size and the setting in a specialized heart failure clinic restrict broader applicability, particularly in health systems without comparable ambulatory infrastructure. Moreover, patients managed in emergency departments without hospitalization were excluded, potentially omitting a clinically relevant subset.</p><p>Third, the finding that fewer than half of patients with reduced ejection fraction were on optimal guideline-directed medical therapy (GDMT) at baseline is striking. Underuse of foundational therapies—angiotensin receptor–neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors—likely contributed to the high recurrence rate (24.5% at 3 months). Contemporary data demonstrate that full implementation of GDMT significantly reduces adverse outcomes in HFrEF, underscoring the need for rigorous therapeutic optimization.<span><sup>3</sup></span></p><p>Another point concerns the definition of ‘clinical stability’, which relied largely on symptom resolution and physical examination. Despite treatment, natriuretic peptide values remained markedly elevated at ‘stability’, suggesting persistent subclinical congestion. This highlights the limitations of purely clinical assessment and supports the integration of objective tools such as natriuretic peptide–guided strategies, echocardiographic congestion indices, or novel remote haemodynamic monitoring technologies to more accurately define stability and prevent early relapse.<span><sup>4, 5</sup></span></p><p>In conclusion, while this prospective study contributes valuable insight into the management of outpatient WHF, i
{"title":"Methodological issues in outpatient worsening heart failure research","authors":"Karim Hnid","doi":"10.1002/ehf2.15438","DOIUrl":"10.1002/ehf2.15438","url":null,"abstract":"<p>We read with great interest the prospective analysis by McCambridge et al. on the management and outcomes of worsening heart failure (WHF) in the outpatient setting (ESC Heart Fail. 2025; doi: 10.1002/ehf2.15400). The authors should be commended for addressing an important and timely topic. However, I would like to highlight several issues that may limit the interpretation and generalizability of the findings.</p><p>First, the study applied two different definitions of WHF: (a) a prespecified, objective definition requiring symptoms of worsening together with clinical signs of congestion and/or supportive biomarker or imaging evidence, and (b) a broader, subjective definition based solely on senior physician judgment when the objective criteria were not met. Notably, about 16% of patients were included under this discretionary pathway. Such heterogeneity increases the risk of misclassification and makes it difficult to compare results with other registries and trials. Recent international consensus statements have underlined the need for a single, standardized definition of WHF to ensure comparability and external validity across studies.<span><sup>1, 2</sup></span></p><p>Second, the investigation was monocentric and included 234 patients over 19 months. While the prospective design is a strength, the limited sample size and the setting in a specialized heart failure clinic restrict broader applicability, particularly in health systems without comparable ambulatory infrastructure. Moreover, patients managed in emergency departments without hospitalization were excluded, potentially omitting a clinically relevant subset.</p><p>Third, the finding that fewer than half of patients with reduced ejection fraction were on optimal guideline-directed medical therapy (GDMT) at baseline is striking. Underuse of foundational therapies—angiotensin receptor–neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors—likely contributed to the high recurrence rate (24.5% at 3 months). Contemporary data demonstrate that full implementation of GDMT significantly reduces adverse outcomes in HFrEF, underscoring the need for rigorous therapeutic optimization.<span><sup>3</sup></span></p><p>Another point concerns the definition of ‘clinical stability’, which relied largely on symptom resolution and physical examination. Despite treatment, natriuretic peptide values remained markedly elevated at ‘stability’, suggesting persistent subclinical congestion. This highlights the limitations of purely clinical assessment and supports the integration of objective tools such as natriuretic peptide–guided strategies, echocardiographic congestion indices, or novel remote haemodynamic monitoring technologies to more accurately define stability and prevent early relapse.<span><sup>4, 5</sup></span></p><p>In conclusion, while this prospective study contributes valuable insight into the management of outpatient WHF, i","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4531-4532"},"PeriodicalIF":3.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>We read with great interest the article by Lobeek et al.,<span><sup>1</sup></span> which offers valuable insights into the distribution of adipose tissue depot in heart failure with preserved ejection fraction (HFpEF) and highlights important sex-specific differences in epicardial, visceral, and subcutaneous fat. The authors are to be commended for addressing this clinically relevant and underexplored area, as understanding adipose distribution in HFpEF has the potential to improve risk stratification and guide personalized management. Their use of multimodality imaging represents a noteworthy methodological strength and adds depth to the field. We sincerely appreciate their contribution in advancing this important topic; however, the study has the following limitations that merit further discussion.</p><p>First, the study used cardiac magnetic resonance (CMR) for epicardial adipose tissue (EAT) and computed tomography (CT) for visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT), which introduces measurement bias since different imaging modalities have variable reproducibility and sensitivity for adipose tissue quantification. This could partly explain the only ‘modest’ association found between VAT and EAT. For instance, Shuster et al.<span><sup>2</sup></span> highlighted that CT and Magnetic Resonance imaging (MRI) provide differing estimates of visceral and subcutaneous adiposity, which may affect cross-modality comparability. Second, the study focused only on volumetric quantification (EAT, VAT and SAT), ignoring functional aspects like adipose tissue inflammation, fibrosis, or metabolic activity, which are increasingly recognized as critical determinants of cardiovascular risk in HFpEF. This omission may underestimate the pathophysiological impact of adipose depots. For instance, Dronkers et al.<span><sup>3</sup></span> reviewed how molecular mechanisms (inflammation and adipokine secretion) in adipose depots influence HFpEF beyond fat volume. Third, the study provides a snapshot of fat distribution but cannot establish causality or predict clinical outcomes such as hospitalization, arrhythmias, or mortality. This weakens the translational impact of findings for clinical practice. For instance, van Woerden et al.<span><sup>4</sup></span> showed that longitudinal changes in EAT are associated with outcomes in HFpEF, underlining the need for follow-up data. Fourth, the study enrolled patients from the Netherlands only, which limits external validity to diverse ethnic populations where adipose distribution and HFpEF phenotypes differ. For instance, South Asian patients have more VAT at lower body mass index (BMI), altering risk. Pandey et al.<span><sup>5</sup></span> demonstrated race-specific associations between adipose distribution and Heart failure (HF) risk.</p><p>Thus, the future studies should aim to harmonize imaging, preferably using a single modality for all adipose depots or cross-calibrated approaches, while integrati
{"title":"‘Letter to the editor: Epicardial, visceral and subcutaneous adipose tissue in heart failure with preserved ejection fraction’","authors":"Ahmed Raza, Ahmad Furqan Anjum","doi":"10.1002/ehf2.15433","DOIUrl":"10.1002/ehf2.15433","url":null,"abstract":"<p>We read with great interest the article by Lobeek et al.,<span><sup>1</sup></span> which offers valuable insights into the distribution of adipose tissue depot in heart failure with preserved ejection fraction (HFpEF) and highlights important sex-specific differences in epicardial, visceral, and subcutaneous fat. The authors are to be commended for addressing this clinically relevant and underexplored area, as understanding adipose distribution in HFpEF has the potential to improve risk stratification and guide personalized management. Their use of multimodality imaging represents a noteworthy methodological strength and adds depth to the field. We sincerely appreciate their contribution in advancing this important topic; however, the study has the following limitations that merit further discussion.</p><p>First, the study used cardiac magnetic resonance (CMR) for epicardial adipose tissue (EAT) and computed tomography (CT) for visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT), which introduces measurement bias since different imaging modalities have variable reproducibility and sensitivity for adipose tissue quantification. This could partly explain the only ‘modest’ association found between VAT and EAT. For instance, Shuster et al.<span><sup>2</sup></span> highlighted that CT and Magnetic Resonance imaging (MRI) provide differing estimates of visceral and subcutaneous adiposity, which may affect cross-modality comparability. Second, the study focused only on volumetric quantification (EAT, VAT and SAT), ignoring functional aspects like adipose tissue inflammation, fibrosis, or metabolic activity, which are increasingly recognized as critical determinants of cardiovascular risk in HFpEF. This omission may underestimate the pathophysiological impact of adipose depots. For instance, Dronkers et al.<span><sup>3</sup></span> reviewed how molecular mechanisms (inflammation and adipokine secretion) in adipose depots influence HFpEF beyond fat volume. Third, the study provides a snapshot of fat distribution but cannot establish causality or predict clinical outcomes such as hospitalization, arrhythmias, or mortality. This weakens the translational impact of findings for clinical practice. For instance, van Woerden et al.<span><sup>4</sup></span> showed that longitudinal changes in EAT are associated with outcomes in HFpEF, underlining the need for follow-up data. Fourth, the study enrolled patients from the Netherlands only, which limits external validity to diverse ethnic populations where adipose distribution and HFpEF phenotypes differ. For instance, South Asian patients have more VAT at lower body mass index (BMI), altering risk. Pandey et al.<span><sup>5</sup></span> demonstrated race-specific associations between adipose distribution and Heart failure (HF) risk.</p><p>Thus, the future studies should aim to harmonize imaging, preferably using a single modality for all adipose depots or cross-calibrated approaches, while integrati","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4529-4530"},"PeriodicalIF":3.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristian Hellenkamp, Sophia Kaebe, Miroslava Valentova, Stephan von Haehling, Fani Delistefani, Katja Gollisch, Dirk Raddatz, Ann-Kathrin Schäfer, Michael J. Koziolek, Manuel Wallbach
<div> <section> <h3> Purpose</h3> <p>Finerenone, a highly selective non-steroidal mineralocorticoid receptor antagonist, was approved for the treatment of patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (diabetic kidney disease, DKD). Finerenone reduced the composite endpoint of heart failure events and cardiovascular death in patients with heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). This study aimed to investigate the safety and cardiac effects of finerenone in patients with DKD with or without HFpEF/HFmrEF in a real-world setting.</p> </section> <section> <h3> Methods</h3> <p>Patients with DKD were prospectively enrolled and were treated with finerenone according to best clinical practice. Clinical, laboratory and echocardiographic assessments were performed before, 4 weeks and 6 months after starting finerenone.</p> </section> <section> <h3> Results</h3> <p>Thirty-one patients with DKD were included. At baseline, patients had a typical risk profile with arterial hypertension (90.3%) and hyperlipoproteinemia (87.1%). Most patients were treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (93.5%). Treatment with finerenone was safe and well tolerated: after 4 weeks, the glomerular filtration rate decreased slightly from 52 (43–78) mL/min/1.73 m<sup>2</sup> to 48.0 (39.0–71.0) mL/min/1.73 m<sup>2</sup> (<i>P</i> = 0.002 vs. baseline), but stabilized thereafter. Similarly, the median potassium value increased from 4.2 (3.8–4.5) mmol/L to 4.4 (4.2–4.8) mmol/L (<i>P</i> = 0.017) after 4 weeks, but remained stable thereafter [4.4 (4.1–4.6) mmol/L (<i>P</i> = 0.079)]. Only one patient (3.2%) had an unplanned hospitalization and concomitant hyperkalaemia up to 6.0 mmol/L. HFpEF/HFmrEF was frequently found in patients with DKD (71.0%), although most patients had a rather early stage with only mild symptoms and a median N-terminal pro B-type natriuretic peptide (NT-proBNP) value of 150.8 (54.5–325.7) ng/L. During treatment with finerenone, NT-proBNP and left ventricular mass index (LVMI) remained stable. In contrast, left atrial volume index (LAVI) decreased from baseline [31.2 (26.8–39.7) mL/m<sup>2</sup>] to 4 weeks follow-up [29.7 (20.8–33.6) mL/m<sup>2</sup>, <i>P</i> = 0.027] and decreased further after 6 months [26.6 (20.8–34.9) mL/m<sup>2</sup>, <i>P</i> = 0.029]. In the subgroup of patients with HFpEF/HFmrEF, E/e′ decreased from 11.9 (8.7–14.5) at baseline to 9.9 (8.0–12.4) after 6 months (<i>P</i> = 0.043).</p> </section> <section> <h3> Conclusions</h3> <p>In a real-world sett
{"title":"Finerenone in diabetic chronic kidney disease—Real-world insights including patients with HFpEF or HFmrEF","authors":"Kristian Hellenkamp, Sophia Kaebe, Miroslava Valentova, Stephan von Haehling, Fani Delistefani, Katja Gollisch, Dirk Raddatz, Ann-Kathrin Schäfer, Michael J. Koziolek, Manuel Wallbach","doi":"10.1002/ehf2.15424","DOIUrl":"10.1002/ehf2.15424","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Finerenone, a highly selective non-steroidal mineralocorticoid receptor antagonist, was approved for the treatment of patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (diabetic kidney disease, DKD). Finerenone reduced the composite endpoint of heart failure events and cardiovascular death in patients with heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). This study aimed to investigate the safety and cardiac effects of finerenone in patients with DKD with or without HFpEF/HFmrEF in a real-world setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with DKD were prospectively enrolled and were treated with finerenone according to best clinical practice. Clinical, laboratory and echocardiographic assessments were performed before, 4 weeks and 6 months after starting finerenone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-one patients with DKD were included. At baseline, patients had a typical risk profile with arterial hypertension (90.3%) and hyperlipoproteinemia (87.1%). Most patients were treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (93.5%). Treatment with finerenone was safe and well tolerated: after 4 weeks, the glomerular filtration rate decreased slightly from 52 (43–78) mL/min/1.73 m<sup>2</sup> to 48.0 (39.0–71.0) mL/min/1.73 m<sup>2</sup> (<i>P</i> = 0.002 vs. baseline), but stabilized thereafter. Similarly, the median potassium value increased from 4.2 (3.8–4.5) mmol/L to 4.4 (4.2–4.8) mmol/L (<i>P</i> = 0.017) after 4 weeks, but remained stable thereafter [4.4 (4.1–4.6) mmol/L (<i>P</i> = 0.079)]. Only one patient (3.2%) had an unplanned hospitalization and concomitant hyperkalaemia up to 6.0 mmol/L. HFpEF/HFmrEF was frequently found in patients with DKD (71.0%), although most patients had a rather early stage with only mild symptoms and a median N-terminal pro B-type natriuretic peptide (NT-proBNP) value of 150.8 (54.5–325.7) ng/L. During treatment with finerenone, NT-proBNP and left ventricular mass index (LVMI) remained stable. In contrast, left atrial volume index (LAVI) decreased from baseline [31.2 (26.8–39.7) mL/m<sup>2</sup>] to 4 weeks follow-up [29.7 (20.8–33.6) mL/m<sup>2</sup>, <i>P</i> = 0.027] and decreased further after 6 months [26.6 (20.8–34.9) mL/m<sup>2</sup>, <i>P</i> = 0.029]. In the subgroup of patients with HFpEF/HFmrEF, E/e′ decreased from 11.9 (8.7–14.5) at baseline to 9.9 (8.0–12.4) after 6 months (<i>P</i> = 0.043).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In a real-world sett","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4219-4229"},"PeriodicalIF":3.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cynthia M. Westerhout, Wendimagegn Alemayehu, Alain Cohen-Solal, Carolyn S. P. Lam, Justin A. Ezekowitz, Stefano Corda, Ciaran J. McMullan, Christopher M. O'Connor, Paul W. Armstrong, for the VICTORIA Study Group
Aims
Heterogeneity in demographics, aetiology, healthcare access and guideline-directed medical therapy (GDMT), and survival bias of patients with heart failure with reduced ejection fraction (HFrEF) is evident from international trials and registries. The current study examines conventional geographic variation in participants' phenotypes, standard of care, clinical outcomes and treatment effects of vericiguat versus placebo within the VICTORIA trial. We then evaluate an alternative approach to assessing the relationship between geographic variation in the efficacy of new therapeutics.
Methods and results
Characteristics, standard of care and outcomes (time to first HF hospitalization (HFH) or cardiovascular death (CVD), time to first HFH and to CVD) of the 5050 participants from 42 countries and the effect of vericiguat versus placebo were analysed according to five prespecified geographic regions. Further examination of the study treatment effect according to country-level human development index (HDI) was undertaken to evaluate intra-regional variation. Notable inter-region differences existed in participant characteristics, standard of care at randomization and clinical outcomes. There was no modification of vericiguat's treatment benefit across geographic regions for the primary composite endpoint or its components. When examined by HDI, vericiguat's benefit on HFH and the primary composite was retained overall but attenuated as HDI rose (Pinteraction = 0.009, 0.088, respectively). There was no apparent treatment effect modification due to HDI on cardiovascular death (Pinteraction = 0.623).
Conclusions
Geographic variation in the phenotype of patients with HFrEF, standard of care, and clinical outcomes was observed, while there was no intra-regional heterogeneity in vericiguat's treatment effect. However, when considering contextual/systemic measures via country-level HDI, further insights into treatment effect were revealed. Country-level measures may be helpful in the planning of future trials and in the translation of evidence into practice.
{"title":"Geographic region variation in patient characteristics, clinical outcomes and treatment of HFrEF in the VICTORIA trial","authors":"Cynthia M. Westerhout, Wendimagegn Alemayehu, Alain Cohen-Solal, Carolyn S. P. Lam, Justin A. Ezekowitz, Stefano Corda, Ciaran J. McMullan, Christopher M. O'Connor, Paul W. Armstrong, for the VICTORIA Study Group","doi":"10.1002/ehf2.15416","DOIUrl":"10.1002/ehf2.15416","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Heterogeneity in demographics, aetiology, healthcare access and guideline-directed medical therapy (GDMT), and survival bias of patients with heart failure with reduced ejection fraction (HFrEF) is evident from international trials and registries. The current study examines conventional geographic variation in participants' phenotypes, standard of care, clinical outcomes and treatment effects of vericiguat versus placebo within the VICTORIA trial. We then evaluate an alternative approach to assessing the relationship between geographic variation in the efficacy of new therapeutics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Characteristics, standard of care and outcomes (time to first HF hospitalization (HFH) or cardiovascular death (CVD), time to first HFH and to CVD) of the 5050 participants from 42 countries and the effect of vericiguat versus placebo were analysed according to five prespecified geographic regions. Further examination of the study treatment effect according to country-level human development index (HDI) was undertaken to evaluate intra-regional variation. Notable inter-region differences existed in participant characteristics, standard of care at randomization and clinical outcomes. There was no modification of vericiguat's treatment benefit across geographic regions for the primary composite endpoint or its components. When examined by HDI, vericiguat's benefit on HFH and the primary composite was retained overall but attenuated as HDI rose (<i>P</i><sub>interaction</sub> = 0.009, 0.088, respectively). There was no apparent treatment effect modification due to HDI on cardiovascular death (<i>P</i><sub>interaction</sub> = 0.623).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Geographic variation in the phenotype of patients with HFrEF, standard of care, and clinical outcomes was observed, while there was no intra-regional heterogeneity in vericiguat's treatment effect. However, when considering contextual/systemic measures via country-level HDI, further insights into treatment effect were revealed. Country-level measures may be helpful in the planning of future trials and in the translation of evidence into practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"3910-3919"},"PeriodicalIF":3.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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