Alexios S. Antonopoulos, Theodoros Tsampras, Dimitrios Terentes-Printzios, George Lazaros, Konstantinos Tsioufis, Charalambos Vlachopoulos
Aims
The aim of this meta-analysis was to evaluate the effects of targeted treatments for transthyretin amyloid cardiomyopathy (ATTR-CM) on clinical outcomes by integrating clinical trial and real-world data.
Methods and results
A systematic literature search of PubMed was conducted up to 30 June 2025. A total of 714 relevant records were identified; out of 51 potentially eligible studies, 10 randomized placebo-controlled and non-randomized control comparison studies were selected, with available outcome data on all-cause mortality and cardiovascular hospitalizations. The estimates were extrapolated to real-world outcome data of untreated ATTR-CM patients to estimate absolute risk reduction (ARR) and number needed to treat (NNT). Ten studies comprising 5203 patients were included. ATTR-targeted treatments reduced mortality by 39% [risk ratio (RR) 0.61, 95% confidence interval (CI): 0.52 to 0.70, I2 = 35%, P = 0.13]. A sensitivity subgroup analysis for RCT only confirmed a 28% reduction in all-cause mortality (RR 0.72, 95% CI: 0.60 to 0.86, I2 = 0%, P = 0.56). The random effects model for cardiovascular hospitalizations demonstrated a 31% reduction in the ATTR-targeted treatment group compared with control (RR: 0.69, 95% CI: 0.53 to 0.89, I2 = 68%, P = 0.01). By applying these estimates to published large-scale epidemiological data on the natural disease course from 18238 untreated patients, the estimated NNT of ATTR-CM therapeutics to prevent one death is an NNT of 10 at 2 years and an NNT of 5 at 5 years.
Conclusions
Targeted treatments for ATTR-CM significantly reduce mortality and cardiovascular hospitalizations. When extrapolated to population-level data, these treatments show clinical benefits, emphasizing the importance of early diagnosis and therapeutic intervention.
{"title":"Real-world effectiveness of targeted therapies in ATTR cardiomyopathy: A meta-analysis integrating population-based data","authors":"Alexios S. Antonopoulos, Theodoros Tsampras, Dimitrios Terentes-Printzios, George Lazaros, Konstantinos Tsioufis, Charalambos Vlachopoulos","doi":"10.1002/ehf2.70011","DOIUrl":"10.1002/ehf2.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aim of this meta-analysis was to evaluate the effects of targeted treatments for transthyretin amyloid cardiomyopathy (ATTR-CM) on clinical outcomes by integrating clinical trial and real-world data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>A systematic literature search of PubMed was conducted up to 30 June 2025. A total of 714 relevant records were identified; out of 51 potentially eligible studies, 10 randomized placebo-controlled and non-randomized control comparison studies were selected, with available outcome data on all-cause mortality and cardiovascular hospitalizations. The estimates were extrapolated to real-world outcome data of untreated ATTR-CM patients to estimate absolute risk reduction (ARR) and number needed to treat (NNT). Ten studies comprising 5203 patients were included. ATTR-targeted treatments reduced mortality by 39% [risk ratio (RR) 0.61, 95% confidence interval (CI): 0.52 to 0.70, <i>I</i><sup>2</sup> = 35%, <i>P</i> = 0.13]. A sensitivity subgroup analysis for RCT only confirmed a 28% reduction in all-cause mortality (RR 0.72, 95% CI: 0.60 to 0.86, <i>I</i><sup>2</sup> = 0%, <i>P</i> = 0.56). The random effects model for cardiovascular hospitalizations demonstrated a 31% reduction in the ATTR-targeted treatment group compared with control (RR: 0.69, 95% CI: 0.53 to 0.89, <i>I</i><sup>2</sup> = 68%, <i>P</i> = 0.01). By applying these estimates to published large-scale epidemiological data on the natural disease course from 18238 untreated patients, the estimated NNT of ATTR-CM therapeutics to prevent one death is an NNT of 10 at 2 years and an NNT of 5 at 5 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Targeted treatments for ATTR-CM significantly reduce mortality and cardiovascular hospitalizations. When extrapolated to population-level data, these treatments show clinical benefits, emphasizing the importance of early diagnosis and therapeutic intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4475-4485"},"PeriodicalIF":3.7,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631437","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}
Marco Merlo, Giulia Bassetto, Antonio Cannatà, Alberto Aimo, Camillo Autore, Barbara Bauce, Elena Biagini, Francesco Cappelli, Silvia Castelletti, Flavio D'Ascenzi, Cesare de Gregorio, Giuseppe Limongelli, Francesca Marzo, Beatrice Musumeci, Giacomo Tini, Roberto Pedrinelli, Pasquale Perrone Filardi, Gianfranco Sinagra, Massimo Imazio
In the past decade, advancements in knowledge on the immune system have partially unveiled the complex interplay between the heart and the immune system. This new branch of cardiology is now called cardio-immunology. It encompasses different areas from preclinical to translational and purely clinical research aiming to identify the relationship between the immune system and different cardiovascular diseases. Inflammatory cardiomyopathies are a heterogeneous subgroup of non-ischaemic cardiomyopathies characterized by left ventricular, or biventricular, dysfunction after an inflammatory insult. Recently, genetic testing allowed to identify specific genotype–phenotype correlation in the diagnosis and, mostly, in the prognosis of different cardiomyopathies. Some pathogenic variants might lead to a clinical phenotype in overlap with inflammatory myocardial diseases and inflammation can be found in cardiac magnetic resonance or endomyocardial biopsies of different cardiomyopathies. Although prognostic predictors of adverse events and indication to immunosuppressive therapies have been identified in myocarditis, data are lacking in the context of genetic cardiomyopathies presenting myocardial inflammation. As for pericardial diseases, genetic variants in immune-related genes, such as IL1B have been described, specifically in recurrent pericarditis. A growing body of evidence starting form genetics and cardio-immunology are trying to elucidate the basic mechanisms of the disease and may play a significant role in the understanding the pathophysiology and potentially the treatment of patients. Some examples are represented by arrhythmogenic cardiomyopathy presenting with hot-phases or biopsy-proven myocarditis presenting genetic mutations in specific genes as TTN or DSP. The aim of this review paper is to highlight the current knowledge and the unmet clinical needs, providing a practical and concise guidance for specific areas of research and management of patients affected by myo-pericardial diseases with overlap between genetics and inflammation, ranging from genetic testing to medical and device therapy.
{"title":"Inflammation and genetics in myo-pericardial diseases: Insights from the Italian Study Group on Cardiomyopathies and Pericardial Diseases","authors":"Marco Merlo, Giulia Bassetto, Antonio Cannatà, Alberto Aimo, Camillo Autore, Barbara Bauce, Elena Biagini, Francesco Cappelli, Silvia Castelletti, Flavio D'Ascenzi, Cesare de Gregorio, Giuseppe Limongelli, Francesca Marzo, Beatrice Musumeci, Giacomo Tini, Roberto Pedrinelli, Pasquale Perrone Filardi, Gianfranco Sinagra, Massimo Imazio","doi":"10.1002/ehf2.15231","DOIUrl":"10.1002/ehf2.15231","url":null,"abstract":"<p>In the past decade, advancements in knowledge on the immune system have partially unveiled the complex interplay between the heart and the immune system. This new branch of cardiology is now called cardio-immunology. It encompasses different areas from preclinical to translational and purely clinical research aiming to identify the relationship between the immune system and different cardiovascular diseases. Inflammatory cardiomyopathies are a heterogeneous subgroup of non-ischaemic cardiomyopathies characterized by left ventricular, or biventricular, dysfunction after an inflammatory insult. Recently, genetic testing allowed to identify specific genotype–phenotype correlation in the diagnosis and, mostly, in the prognosis of different cardiomyopathies. Some pathogenic variants might lead to a clinical phenotype in overlap with inflammatory myocardial diseases and inflammation can be found in cardiac magnetic resonance or endomyocardial biopsies of different cardiomyopathies. Although prognostic predictors of adverse events and indication to immunosuppressive therapies have been identified in myocarditis, data are lacking in the context of genetic cardiomyopathies presenting myocardial inflammation. As for pericardial diseases, genetic variants in immune-related genes, such as <i>IL1B</i> have been described, specifically in recurrent pericarditis. A growing body of evidence starting form genetics and cardio-immunology are trying to elucidate the basic mechanisms of the disease and may play a significant role in the understanding the pathophysiology and potentially the treatment of patients. Some examples are represented by arrhythmogenic cardiomyopathy presenting with hot-phases or biopsy-proven myocarditis presenting genetic mutations in specific genes as <i>TTN</i> or <i>DSP</i>. The aim of this review paper is to highlight the current knowledge and the unmet clinical needs, providing a practical and concise guidance for specific areas of research and management of patients affected by myo-pericardial diseases with overlap between genetics and inflammation, ranging from genetic testing to medical and device therapy.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"3987-3999"},"PeriodicalIF":3.7,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631407","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}
Josep Darbà, Meritxell Ascanio, Antonio Rodríguez, Sarah J. Charman, Nduka C. Okwose, Renae J. Stefanetti, Amy Groenewegen, Annamaria Del Franco, Maria Tafelmeier, Andrej Preveden, Amy S. Fuller, Fatima Bano, David R. Sinclair, Duncan Edwards, Anne P. Nelissen, Petros N. Malitas, Aikaterini Zisaki, Zoran Bosnić, Petar Vračar, Alessandra Fornaro, Fausto Barlocco, Dimitris Fotiadis, Prithwish Banerjee, Guy A. MacGowan, Oscar Fernandez, José Luis Zamorano, Marta Jimenez-Blanco Bravo, Lars S. Maier, Iacopo Olivotto, Massimo Milli, Frans H. Rutten, Jonathan Mant, Lazar Velicki, Petar M. Seferovic, Nenad Filipovic, Djordje G. Jakovljevic
Heart failure (HF) affects over 64 million individuals worldwide and is a major cause of hospitalization and mortality, particularly among older adults. In Europe, HF imposes a significant and growing economic burden. This systematic review aimed to evaluate the economic impact of HF diagnosis, treatment and management across European healthcare systems. A systematic literature search was conducted using PubMed, Cochrane Library and Econlit databases including the terms ‘heart failure’ AND ‘costs’ OR ‘cost of illness’ OR ‘cost analysis’ OR ‘economic burden’ OR ‘cost effectiveness’ OR ‘primary care’ OR ‘secondary care’. Studies published between January 2000 and January 2024 were included. A total of 49 studies were included: 17 on resource use, 11 on costs, 15 on resource use and costs, 1 on costs and cost-effectiveness, and 5 on resource use, costs and cost-effectiveness. Hospitalizations and medication use were the most frequently reported resource parameters. Annual HF-related costs varied widely across countries, ranging from €613 to €22,647 per patient. Hospitalizations represented the primary cost driver, accounting for 15% to 92% of total HF costs. Cost-reduction strategies included multidisciplinary care, telemonitoring and pharmacologic interventions. Several disease management programmes reduced hospital admissions and emergency visits. Cost-effectiveness analyses supported the use of certain HF therapies, with incremental cost-effectiveness ratios ranging from €1490 to €9406 per QALY gained. F imposes a substantial economic burden in Europe, largely driven by hospitalizations. Cost-effective interventions such as remote monitoring and integrated care programmes can reduce this burden. Broader adoption of these strategies may improve outcomes and optimize resource allocation across healthcare systems.
{"title":"Economic burden of heart failure in Europe: A systematic review of costs and cost-effectiveness","authors":"Josep Darbà, Meritxell Ascanio, Antonio Rodríguez, Sarah J. Charman, Nduka C. Okwose, Renae J. Stefanetti, Amy Groenewegen, Annamaria Del Franco, Maria Tafelmeier, Andrej Preveden, Amy S. Fuller, Fatima Bano, David R. Sinclair, Duncan Edwards, Anne P. Nelissen, Petros N. Malitas, Aikaterini Zisaki, Zoran Bosnić, Petar Vračar, Alessandra Fornaro, Fausto Barlocco, Dimitris Fotiadis, Prithwish Banerjee, Guy A. MacGowan, Oscar Fernandez, José Luis Zamorano, Marta Jimenez-Blanco Bravo, Lars S. Maier, Iacopo Olivotto, Massimo Milli, Frans H. Rutten, Jonathan Mant, Lazar Velicki, Petar M. Seferovic, Nenad Filipovic, Djordje G. Jakovljevic","doi":"10.1002/ehf2.70017","DOIUrl":"10.1002/ehf2.70017","url":null,"abstract":"<p>Heart failure (HF) affects over 64 million individuals worldwide and is a major cause of hospitalization and mortality, particularly among older adults. In Europe, HF imposes a significant and growing economic burden. This systematic review aimed to evaluate the economic impact of HF diagnosis, treatment and management across European healthcare systems. A systematic literature search was conducted using PubMed, Cochrane Library and Econlit databases including the terms ‘heart failure’ AND ‘costs’ OR ‘cost of illness’ OR ‘cost analysis’ OR ‘economic burden’ OR ‘cost effectiveness’ OR ‘primary care’ OR ‘secondary care’. Studies published between January 2000 and January 2024 were included. A total of 49 studies were included: 17 on resource use, 11 on costs, 15 on resource use and costs, 1 on costs and cost-effectiveness, and 5 on resource use, costs and cost-effectiveness. Hospitalizations and medication use were the most frequently reported resource parameters. Annual HF-related costs varied widely across countries, ranging from €613 to €22,647 per patient. Hospitalizations represented the primary cost driver, accounting for 15% to 92% of total HF costs. Cost-reduction strategies included multidisciplinary care, telemonitoring and pharmacologic interventions. Several disease management programmes reduced hospital admissions and emergency visits. Cost-effectiveness analyses supported the use of certain HF therapies, with incremental cost-effectiveness ratios ranging from €1490 to €9406 per QALY gained. F imposes a substantial economic burden in Europe, largely driven by hospitalizations. Cost-effective interventions such as remote monitoring and integrated care programmes can reduce this burden. Broader adoption of these strategies may improve outcomes and optimize resource allocation across healthcare systems.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4055-4068"},"PeriodicalIF":3.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603166","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}
Holger Priebe-Brämer, Firas Jaly, Nithusa Rahunathan, Mark Luedde, Alexander Albert, Klaus K. Witte, Hans-Joerg Hippe
Aims
We aim to evaluate the real-world effectiveness and safety of the Carillon Mitral Contour System (CMCS) for indirect annuloplasty in patients with heart failure (HF) and secondary mitral regurgitation (SMR).
Methods and results
This was a single-centre retrospective study of 204 consecutive patients (age 83 ± 6 years, 68% female, 72% HFrEF) with NYHA class II-IV HF and moderate and moderate-to-severe (grade 2 + or 3+) SMR planned for CMCS implantation between 2021 and 2024. Echocardiographic variables, B-type natriuretic peptide (BNP) and NYHA functional class were routinely assessed prior to the procedure and, in those with a successful implantation, after 3 months. The device was successfully implanted in 201 (98.5%) patients; the remaining 3 had unsuitable coronary sinus anatomy. Procedural complications occurred in 10.4% and included circumflex artery compression requiring percutaneous coronary intervention (9.5%); coronary sinus injury (1.5%); procedural mortality (0%). At 3 months, NYHA class improved by ≥1 category in 94% of patients and 98% achieved NYHA class I or II. MR decreased by ≥1 grade in 91% of patients, with all patients classified as grade 1+ or 2+ post-procedure. Vena contracta width decreased (6.43 ± 0.84 to 3.85 ± 1.19 mm; P < 0.001), and there was a reduction of LA area from 44.4 ± 6.0 to 35.4 ± 5.1 cm2 (P < 0.001). Diastolic filling was improved (change in E/E′ ratio from 20.1 ± 5.5 to 14.0 ± 3.8; P < 0.001), systolic pulmonary artery pressure was lower in follow-up (44 ± 11 to 35 ± 9 mm; P < 0.001), and there was also a clinically relevant reduction in median BNP levels from 2849 to 1390 pg/mL (P < 0.001). These changes were not different between HFrEF and HFpEF.
Conclusions
In this single-centre observational cohort study, CMCS implantation success was high, and associated with low complication rates, improvements in symptoms and echocardiographic variables, and clinically relevant reductions in BNP levels.
{"title":"Indirect mitral annuloplasty in patients with reduced or preserved ejection fraction: A real-world, single-centre experience","authors":"Holger Priebe-Brämer, Firas Jaly, Nithusa Rahunathan, Mark Luedde, Alexander Albert, Klaus K. Witte, Hans-Joerg Hippe","doi":"10.1002/ehf2.70016","DOIUrl":"10.1002/ehf2.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We aim to evaluate the real-world effectiveness and safety of the Carillon Mitral Contour System (CMCS) for indirect annuloplasty in patients with heart failure (HF) and secondary mitral regurgitation (SMR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>This was a single-centre retrospective study of 204 consecutive patients (age 83 ± 6 years, 68% female, 72% HFrEF) with NYHA class II-IV HF and moderate and moderate-to-severe (grade 2 + or 3+) SMR planned for CMCS implantation between 2021 and 2024. Echocardiographic variables, B-type natriuretic peptide (BNP) and NYHA functional class were routinely assessed prior to the procedure and, in those with a successful implantation, after 3 months. The device was successfully implanted in 201 (98.5%) patients; the remaining 3 had unsuitable coronary sinus anatomy. Procedural complications occurred in 10.4% and included circumflex artery compression requiring percutaneous coronary intervention (9.5%); coronary sinus injury (1.5%); procedural mortality (0%). At 3 months, NYHA class improved by ≥1 category in 94% of patients and 98% achieved NYHA class I or II. MR decreased by ≥1 grade in 91% of patients, with all patients classified as grade 1+ or 2+ post-procedure. <i>Vena contracta</i> width decreased (6.43 ± 0.84 to 3.85 ± 1.19 mm; <i>P</i> < 0.001), and there was a reduction of LA area from 44.4 ± 6.0 to 35.4 ± 5.1 cm<sup>2</sup> (<i>P</i> < 0.001). Diastolic filling was improved (change in E/E′ ratio from 20.1 ± 5.5 to 14.0 ± 3.8; <i>P</i> < 0.001), systolic pulmonary artery pressure was lower in follow-up (44 ± 11 to 35 ± 9 mm; <i>P</i> < 0.001), and there was also a clinically relevant reduction in median BNP levels from 2849 to 1390 pg/mL (<i>P</i> < 0.001). These changes were not different between HFrEF and HFpEF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this single-centre observational cohort study, CMCS implantation success was high, and associated with low complication rates, improvements in symptoms and echocardiographic variables, and clinically relevant reductions in BNP levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4410-4418"},"PeriodicalIF":3.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548806","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}
Carlos Moliner-Abós, Maria Calvo-Barceló, Eduard Solé-Gonzalez, Andrea Borrellas Martín, Paula Fluvià Brugués, Jesus Sánchez Vega, Joan Vime Jubany, Maria Ferré Vallverdú, Manel Taurón Ferrer, Pablo Eduardo Tobias Castillo, Juan Carlos de la Fuente Mancera, Pau Vilardell Rigau, Rosa Vila Olives, Carles Diez López, Antoni Bayés-Genís, Dabit Arzamendi Aizpurua, Ignacio Ferreira González, Sònia Mirabet Pérez
Aims
Guideline-directed medical therapy (GDMT) remains the cornerstone for treating patients with heart failure (HF) and reduced ejection fraction (HFrEF) and coronary artery disease (CAD). However, real-world implementation of GDMT (GDMTi) is suboptimal. This subanalysis of the RevascHeart study evaluates the impact of GDMTi on long-term mortality in patients with de novo ischaemic heart failure (HF) undergoing revascularization.
Methods
Among 409 patients with HFrEF (left ventricular ejection fraction ≤40%) and CAD, 275 one-year survivors who underwent revascularisation shortly after index HF admission were included in this landmark analysis (LA). GDMTi at 12 months was defined as initiation of each recommended drug class, regardless of dose. Primary endpoints were all-cause and cardiovascular mortality by GDMTi. Secondary endpoints included outcomes by revascularisation strategy and temporal trends in GDMTi.
Results
Over a median follow-up of 41.6 months, all-cause mortality occurred in 29 GDMTi patients (18%) versus 47 non-GDMTi (42%) and cardiovascular mortality in 10% versus 24%, respectively. After adjustment, GDMTi was not significantly associated with lower all-cause [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.39–1.02; P = 0.06] or cardiovascular mortality (HR 0.62, 95% CI 0.33–1.18; P = 0.14). GDMTi/coronary artery bypass grafting (CABG) was associated with lower all-cause (HR 0.42, 95% CI 0.20–0.87; P = 0.02) and cardiovascular mortality (HR 0.40, 95% CI 0.16–0.99; P = 0.05). GDMTi use increased progressively over the study period.
Conclusions
GDMTi was associated with lower unadjusted mortality, though not significant after adjustment. GDMTi combined with CABG showed the best outcomes. The use of GDMTi improved over time.
目的：指南导向的药物治疗（GDMT）仍然是治疗心力衰竭（HF）、射血分数降低（HFrEF）和冠状动脉疾病（CAD）患者的基石。然而，实际实现的GDMT （GDMTi）并不是最优的。这项revasheart研究的亚分析评估了GDMTi对接受血运重建术的新发缺血性心力衰竭（HF）患者长期死亡率的影响。方法：在409例HFrEF（左室射血分数≤40%）和CAD患者中，275例在指数HF入院后不久接受血运重建术的1年存活患者被纳入这项里程碑式分析（LA）。12个月时的GDMTi定义为每个推荐药物类别的起始，无论剂量如何。主要终点是GDMTi的全因死亡率和心血管死亡率。次要终点包括血运重建策略和GDMTi的时间趋势。结果：在中位41.6个月的随访中，GDMTi患者的全因死亡率分别为29例（18%）和47例（42%），心血管死亡率分别为10%和24%。调整后，GDMTi与低全因风险比（HR） 0.63, 95%可信区间（CI） 0.39-1.02无显著相关；P = 0.06]或心血管死亡率（HR 0.62, 95% CI 0.33-1.18; P = 0.14）。GDMTi/冠状动脉旁路移植术（CABG）与较低的全因死亡率（HR 0.42, 95% CI 0.20-0.87; P = 0.02）和心血管死亡率（HR 0.40, 95% CI 0.16-0.99; P = 0.05）相关。GDMTi的使用在研究期间逐渐增加。结论：GDMTi与较低的未调整死亡率相关，但调整后不显著。GDMTi联合CABG治疗效果最好。随着时间的推移，GDMTi的使用得到了改善。
{"title":"Guideline-directed medical therapy after revascularization and outcomes in ischaemic cardiomyopathy","authors":"Carlos Moliner-Abós, Maria Calvo-Barceló, Eduard Solé-Gonzalez, Andrea Borrellas Martín, Paula Fluvià Brugués, Jesus Sánchez Vega, Joan Vime Jubany, Maria Ferré Vallverdú, Manel Taurón Ferrer, Pablo Eduardo Tobias Castillo, Juan Carlos de la Fuente Mancera, Pau Vilardell Rigau, Rosa Vila Olives, Carles Diez López, Antoni Bayés-Genís, Dabit Arzamendi Aizpurua, Ignacio Ferreira González, Sònia Mirabet Pérez","doi":"10.1002/ehf2.70014","DOIUrl":"10.1002/ehf2.70014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Guideline-directed medical therapy (GDMT) remains the cornerstone for treating patients with heart failure (HF) and reduced ejection fraction (HFrEF) and coronary artery disease (CAD). However, real-world implementation of GDMT (GDMTi) is suboptimal. This subanalysis of the RevascHeart study evaluates the impact of GDMTi on long-term mortality in patients with de novo ischaemic heart failure (HF) undergoing revascularization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Among 409 patients with HFrEF (left ventricular ejection fraction ≤40%) and CAD, 275 one-year survivors who underwent revascularisation shortly after index HF admission were included in this landmark analysis (LA). GDMTi at 12 months was defined as initiation of each recommended drug class, regardless of dose. Primary endpoints were all-cause and cardiovascular mortality by GDMTi. Secondary endpoints included outcomes by revascularisation strategy and temporal trends in GDMTi.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over a median follow-up of 41.6 months, all-cause mortality occurred in 29 GDMTi patients (18%) versus 47 non-GDMTi (42%) and cardiovascular mortality in 10% versus 24%, respectively. After adjustment, GDMTi was not significantly associated with lower all-cause [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.39–1.02; <i>P</i> = 0.06] or cardiovascular mortality (HR 0.62, 95% CI 0.33–1.18; <i>P</i> = 0.14). GDMTi/coronary artery bypass grafting (CABG) was associated with lower all-cause (HR 0.42, 95% CI 0.20–0.87; <i>P</i> = 0.02) and cardiovascular mortality (HR 0.40, 95% CI 0.16–0.99; <i>P</i> = 0.05). GDMTi use increased progressively over the study period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>GDMTi was associated with lower unadjusted mortality, though not significant after adjustment. GDMTi combined with CABG showed the best outcomes. The use of GDMTi improved over time.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4442-4450"},"PeriodicalIF":3.7,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534565","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}
Chen Hsiang Ma, Arthur Qi, Luke Gagnon, Kaiming Wang, Chandu Sadasivan, Anukul Ghimire, Matthew Cooper, Somkanya Tungsanga, Bonaventure Oguaju, Ben Vandermeer, Finlay A. McAlister, Aminu K. Bello, Gavin Y. Oudit
Aims
Despite emerging evidence for new pharmacotherapies to improve outcomes in patients with heart failure (HF) and kidney dysfunction, data on contemporary HF therapy use in this population are lacking. This study evaluated contemporary longitudinal treatment patterns in patients with HF across the spectrum of kidney function and left ventricular ejection fraction (LVEF).
Methods
In a prospective, observational cohort of 1401 HF patients, we examined HF therapy use over 2 years and dose intensity stratified by ambulatory estimated glomerular filtration rate (eGFR ≥60, 30 to <60 and <30 mL/min/1.73 m2) and HF with reduced (HFrEF), mildly reduced (HFmrEF) and preserved (HFpEF) ejection fraction. Clinical outcomes, incidence of hyperkalaemia (serum potassium > 5.5 mmol/L) and clinician-reported reasons for underutilizing HF therapies were examined.
Results
Median age was 68 (58 to 76) years; 29% were female; 54%, 37% and 9% had an eGFR of ≥60, 30 to <60 and <30, respectively. Among patients with eGFR ≥60, 95%, 94%, 75% and 15% were on a beta-blocker (BB), renin–angiotensin system inhibitor (RASi), mineralocorticoid receptor antagonist (MRA) and sodium glucose cotransporter-2 inhibitor, respectively. In patients with eGFR <30, corresponding baseline rates were 88%, 68%, 35% and 7%. Utilization rates were similar in patients with eGFR 30 to <60 compared with eGFR ≥60; however, fewer patients were on guideline-directed dose intensities with 44% versus 57% for RASi and 19% versus 26% for MRA. However, >90% of patients were on a BB, with similar utilization rates across HF and eGFR categories. Baseline ARNI use was 29%, 24% and 11% in eGFR ≥60, 30 to <60 and <30, respectively. Trends in HF therapy use persisted over 2 years. Among patients with eGFR <30, kidney dysfunction was the most frequently cited reason for underutilizing RASi. Patients with eGFR <60 experienced higher all-cause mortality, hospitalization and higher rates of hyperkalaemia.
Conclusion
Gaps in HF therapy use persist in patients with comorbid kidney dysfunction. Targeted strategies to implement new therapies and improve adherence to HF treatments are necessary to improve outcomes in a highly comorbid and at-risk population.
{"title":"Therapy gaps for patients with heart failure and reduced kidney function: A prospective cohort study","authors":"Chen Hsiang Ma, Arthur Qi, Luke Gagnon, Kaiming Wang, Chandu Sadasivan, Anukul Ghimire, Matthew Cooper, Somkanya Tungsanga, Bonaventure Oguaju, Ben Vandermeer, Finlay A. McAlister, Aminu K. Bello, Gavin Y. Oudit","doi":"10.1002/ehf2.70008","DOIUrl":"10.1002/ehf2.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Despite emerging evidence for new pharmacotherapies to improve outcomes in patients with heart failure (HF) and kidney dysfunction, data on contemporary HF therapy use in this population are lacking. This study evaluated contemporary longitudinal treatment patterns in patients with HF across the spectrum of kidney function and left ventricular ejection fraction (LVEF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a prospective, observational cohort of 1401 HF patients, we examined HF therapy use over 2 years and dose intensity stratified by ambulatory estimated glomerular filtration rate (eGFR ≥60, 30 to <60 and <30 mL/min/1.73 m<sup>2</sup>) and HF with reduced (HFrEF), mildly reduced (HFmrEF) and preserved (HFpEF) ejection fraction. Clinical outcomes, incidence of hyperkalaemia (serum potassium > 5.5 mmol/L) and clinician-reported reasons for underutilizing HF therapies were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Median age was 68 (58 to 76) years; 29% were female; 54%, 37% and 9% had an eGFR of ≥60, 30 to <60 and <30, respectively. Among patients with eGFR ≥60, 95%, 94%, 75% and 15% were on a beta-blocker (BB), renin–angiotensin system inhibitor (RASi), mineralocorticoid receptor antagonist (MRA) and sodium glucose cotransporter-2 inhibitor, respectively. In patients with eGFR <30, corresponding baseline rates were 88%, 68%, 35% and 7%. Utilization rates were similar in patients with eGFR 30 to <60 compared with eGFR ≥60; however, fewer patients were on guideline-directed dose intensities with 44% versus 57% for RASi and 19% versus 26% for MRA. However, >90% of patients were on a BB, with similar utilization rates across HF and eGFR categories. Baseline ARNI use was 29%, 24% and 11% in eGFR ≥60, 30 to <60 and <30, respectively. Trends in HF therapy use persisted over 2 years. Among patients with eGFR <30, kidney dysfunction was the most frequently cited reason for underutilizing RASi. Patients with eGFR <60 experienced higher all-cause mortality, hospitalization and higher rates of hyperkalaemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Gaps in HF therapy use persist in patients with comorbid kidney dysfunction. Targeted strategies to implement new therapies and improve adherence to HF treatments are necessary to improve outcomes in a highly comorbid and at-risk population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4431-4441"},"PeriodicalIF":3.7,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534514","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}
Hinojar, R., Moreno-Gómez-Toledano, R., Conde, E., Gonzalez-Gomez, A., García-Martin, A., González-Portilla, P., Fernández-Golfín, C., García-Bermejo, M. L., Zaragoza, C., and Zamorano, J. L. (2024) Circulating miRNA in functional tricuspid regurgitation. Unveiling novel links to heart failure: A pilot study. ESC Heart Failure, 11: 2272–2286. 10.1002/ehf2.14765.
In the Funding section, the current text states: “This study was supported by the Instituto de Salud Carlos III, PI20/01206.”
However, it should read: “This study was supported by the Instituto de Salud Carlos III, PI20/01206, and co-funded by the European Union.”
We apologize for this error.
Hinojar， R. Moreno-Gómez-Toledano， R., Conde， E., Gonzalez-Gomez， A., García-Martin， A., González-Portilla， P., Fernández-Golfín， C., García-Bermejo, m.l, Zaragoza， C.和Zamorano， J. L.（2024）功能性三尖瓣反流的循环miRNA。揭示与心力衰竭的新联系：一项初步研究。心衰学报，11:2272-2286。10.1002 / ehf2.14765。在资金部分，目前的案文指出：“这项研究得到了Salud Carlos III研究所的支持，PI20/01206。”然而，它应该是这样写的：“这项研究得到了卡洛斯三世研究所（PI20/01206）的支持，并由欧盟共同资助。”我们为这个错误道歉。
{"title":"Correction to ‘Circulating miRNA in functional tricuspid regurgitation. Unveiling novel links to heart failure: A pilot study’","authors":"","doi":"10.1002/ehf2.70018","DOIUrl":"10.1002/ehf2.70018","url":null,"abstract":"<p>\u0000 <span>Hinojar, R.</span>, <span>Moreno-Gómez-Toledano, R.</span>, <span>Conde, E.</span>, <span>Gonzalez-Gomez, A.</span>, <span>García-Martin, A.</span>, <span>González-Portilla, P.</span>, <span>Fernández-Golfín, C.</span>, <span>García-Bermejo, M. L.</span>, <span>Zaragoza, C.</span>, and <span>Zamorano, J. L.</span> (<span>2024</span>) <span>Circulating miRNA in functional tricuspid regurgitation. Unveiling novel links to heart failure: A pilot study</span>. <i>ESC Heart Failure</i>, <span>11</span>: <span>2272</span>–<span>2286</span>. 10.1002/ehf2.14765.</p><p>In the Funding section, the current text states: <i>“This study was supported by the Instituto de Salud Carlos III, PI20/01206.”</i></p><p>However, it should read: <i>“This study was supported by the Instituto de Salud Carlos III, PI20/01206, and co-funded by the European Union.”</i></p><p>We apologize for this error.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534509","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}
Michael Massin, Guillaume Baudry, Kevin Duarte, Luca Monzo, Nicolas Sadoul, Oren Caspi, Wilfried Mullens, Olivier Huttin, Nicolas Girerd
Background
The use of intravenous (IV) diuretics in an outpatient setting may represent an alternative to conventional hospitalization. Our objective was to identify factors associated with diuretic response during ambulatory IV diuretic sessions in a population of advanced heart failure with no therapeutic project and a frequent flyer profile.
Method
All patients with 4-h IV diuretic sessions were analysed. An initial bolus followed a tailored protocol for continuous infusion based on the patient's baseline diuretic dose. Variables associated with diuresis and natriuresis following furosemide infusion were evaluated using mixed linear models.
Results
Seventy-six patients (mean age 75.4 years; LVEF 42.7%; eGFR 40.7 mL/min/1.73 m2) totalling 175 IV diuretic sessions were included. Mean diuresis was 1.0 L, natriuresis 92.6 mmol/L, and weight loss 610 grams. Baseline use of ACE inhibitors (+302 mL, P = 0.0005), eGFR (+160 mL per 10 mL/min/1.73 m2 increase, P < 0.0001), and addition of thiazide during the diuretic session (+238 mL, P = 0.0001) were associated with higher diuresis. Prior percutaneous mitral valve repair or chronic thiazide treatment was associated with lower diuresis. Baseline use of ACE inhibitors (+10.83 mmol/L, P = 0.018) was associated with higher natriuresis. Worsening renal function (>3 mg/L increase from baseline) and dyskalaemia 48 h after these sessions were uncommon (respectively 11% and 15%).
Conclusions
Ambulatory 4-h IV loop diuretic sessions induced a diuresis of approximately 1000 mL with a substantial sodium content, without causing significant complications. Addition of thiazide during the session increased diuresis and/or natriuresis, and could potentially be implemented to maximize the efficacy of ambulatory IV diuretic therapy.
{"title":"Determinants of diuresis/natriuresis following ambulatory intravenous loop diuretics for worsening heart failure","authors":"Michael Massin, Guillaume Baudry, Kevin Duarte, Luca Monzo, Nicolas Sadoul, Oren Caspi, Wilfried Mullens, Olivier Huttin, Nicolas Girerd","doi":"10.1002/ehf2.15439","DOIUrl":"10.1002/ehf2.15439","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The use of intravenous (IV) diuretics in an outpatient setting may represent an alternative to conventional hospitalization. Our objective was to identify factors associated with diuretic response during ambulatory IV diuretic sessions in a population of advanced heart failure with no therapeutic project and a frequent flyer profile.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>All patients with 4-h IV diuretic sessions were analysed. An initial bolus followed a tailored protocol for continuous infusion based on the patient's baseline diuretic dose. Variables associated with diuresis and natriuresis following furosemide infusion were evaluated using mixed linear models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-six patients (mean age 75.4 years; LVEF 42.7%; eGFR 40.7 mL/min/1.73 m<sup>2</sup>) totalling 175 IV diuretic sessions were included. Mean diuresis was 1.0 L, natriuresis 92.6 mmol/L, and weight loss 610 grams. Baseline use of ACE inhibitors (+302 mL, <i>P</i> = 0.0005), eGFR (+160 mL per 10 mL/min/1.73 m<sup>2</sup> increase, <i>P</i> < 0.0001), and addition of thiazide during the diuretic session (+238 mL, <i>P</i> = 0.0001) were associated with higher diuresis. Prior percutaneous mitral valve repair or chronic thiazide treatment was associated with lower diuresis. Baseline use of ACE inhibitors (+10.83 mmol/L, <i>P</i> = 0.018) was associated with higher natriuresis. Worsening renal function (>3 mg/L increase from baseline) and dyskalaemia 48 h after these sessions were uncommon (respectively 11% and 15%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Ambulatory 4-h IV loop diuretic sessions induced a diuresis of approximately 1000 mL with a substantial sodium content, without causing significant complications. Addition of thiazide during the session increased diuresis and/or natriuresis, and could potentially be implemented to maximize the efficacy of ambulatory IV diuretic therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"3976-3980"},"PeriodicalIF":3.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502884","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}
Yoshimitsu Takaoka, Yu Horiuchi, Michael Strader, Patrick Murray, Nicholas Wettersten
Aims
Chronic kidney disease (CKD) increases the risk of morbidity and mortality in patients with heart failure (HF). Guidelines recommend assessing CKD using the urinary albumin-to-creatinine ratio (UACR), as albuminuria is strongly associated with the risk of incident HF and outcomes in chronic HF; however, its prognostic role in acute HF (AHF) remains unclear. We evaluated if albuminuria was associated with adverse outcomes in individuals hospitalized with AHF in Renal Optimization Strategies Evaluation-Acute Heart Failure (ROSE-AHF).
Methods
There were 339 participants with baseline UACR, 248 with UACR at Day 7 and 237 with both measurements for assessing change in UACR. Associations of baseline, Day 7 and change in UACR with all-cause mortality at 6 months and the composite of first HF hospitalization or cardiovascular mortality at 2 months were assessed with Cox proportional hazards models. We assessed for effect modification by treatment arm and diabetes status.
Results
The mean age was 70 years, 73.2% were male, 55.8% had diabetes mellitus, the mean estimated glomerular filtration rate was 45 mL/min/1.73 m2 and mean UACR was 208 mg/g. There were 65 deaths and 82 HF hospitalizations or cardiovascular deaths. Baseline UACR was not associated with either outcome; however, there was a significant interaction by diabetes status for all-cause mortality (P = 0.022) such that baseline UACR was associated with the risk of death in non-diabetics [hazard ratio (HR) 2.58, 95% CI 1.00, 6.66, P = 0.050 third tertile versus first tertile], but not diabetics. Neither Day 7 UACR nor the change in UACR were associated with outcomes.
Conclusions
Albuminuria is largely not associated with the risk of death, cardiovascular death, or HF hospitalization in AHF, except admission UACR is associated with the risk of death in non-diabetics.
目的：慢性肾脏疾病（CKD）增加心力衰竭（HF）患者发病率和死亡率的风险。指南建议使用尿白蛋白与肌酐比值（UACR）来评估CKD，因为蛋白尿与慢性HF的发生风险和结局密切相关；然而，其在急性心衰（AHF）中的预后作用尚不清楚。我们在肾优化策略评估-急性心力衰竭（ROSE-AHF）中评估了蛋白尿是否与AHF住院患者的不良结局相关。方法：339名参与者基线UACR， 248名参与者第7天UACR， 237名参与者采用两种测量方法来评估UACR的变化。采用Cox比例风险模型评估基线、第7天和UACR变化与6个月时全因死亡率以及2个月时首次HF住院或心血管死亡率的相关性。我们通过治疗组和糖尿病状态来评估效果的改变。结果：平均年龄70岁，男性占73.2%，糖尿病占55.8%，平均肾小球滤过率45 mL/min/1.73 m2，平均UACR为208 mg/g。65例死亡，82例心衰住院或心血管死亡。基线UACR与两种结果均无相关性；然而，糖尿病状况与全因死亡率之间存在显著的相互作用（P = 0.022），因此基线UACR与非糖尿病患者的死亡风险相关[风险比（HR） 2.58, 95% CI 1.00, 6.66, P = 0.050]，但与糖尿病患者无关。第7天的UACR和UACR的变化都与结果无关。结论：除了入院UACR与非糖尿病患者的死亡风险相关外，蛋白尿在很大程度上与AHF患者的死亡、心血管死亡或HF住院风险无关。
{"title":"Albuminuria is associated with worse outcomes in non-diabetics hospitalized with acute heart failure","authors":"Yoshimitsu Takaoka, Yu Horiuchi, Michael Strader, Patrick Murray, Nicholas Wettersten","doi":"10.1002/ehf2.70006","DOIUrl":"10.1002/ehf2.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Chronic kidney disease (CKD) increases the risk of morbidity and mortality in patients with heart failure (HF). Guidelines recommend assessing CKD using the urinary albumin-to-creatinine ratio (UACR), as albuminuria is strongly associated with the risk of incident HF and outcomes in chronic HF; however, its prognostic role in acute HF (AHF) remains unclear. We evaluated if albuminuria was associated with adverse outcomes in individuals hospitalized with AHF in Renal Optimization Strategies Evaluation-Acute Heart Failure (ROSE-AHF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>There were 339 participants with baseline UACR, 248 with UACR at Day 7 and 237 with both measurements for assessing change in UACR. Associations of baseline, Day 7 and change in UACR with all-cause mortality at 6 months and the composite of first HF hospitalization or cardiovascular mortality at 2 months were assessed with Cox proportional hazards models. We assessed for effect modification by treatment arm and diabetes status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean age was 70 years, 73.2% were male, 55.8% had diabetes mellitus, the mean estimated glomerular filtration rate was 45 mL/min/1.73 m<sup>2</sup> and mean UACR was 208 mg/g. There were 65 deaths and 82 HF hospitalizations or cardiovascular deaths. Baseline UACR was not associated with either outcome; however, there was a significant interaction by diabetes status for all-cause mortality (<i>P</i> = 0.022) such that baseline UACR was associated with the risk of death in non-diabetics [hazard ratio (HR) 2.58, 95% CI 1.00, 6.66, <i>P</i> = 0.050 third tertile versus first tertile], but not diabetics. Neither Day 7 UACR nor the change in UACR were associated with outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Albuminuria is largely not associated with the risk of death, cardiovascular death, or HF hospitalization in AHF, except admission UACR is associated with the risk of death in non-diabetics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4369-4378"},"PeriodicalIF":3.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502962","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}
Deniz Akdis, Lukas Weidmann, Paolo Nanni, Anna Gaertner, Hendrik Milting, Peter Bode, Corinna Brunckhorst, Liang Chen, Felix C. Tanner, Frank Ruschitzka, Ardan M. Saguner, Firat Duru
Aims
Arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease characterized by fibrofatty myocardial replacement and a predisposition to malignant ventricular arrhythmias. The underlying pathomechanisms remain incompletely understood, and specific disease markers are sparse. This study aimed to characterize the myocardial transcriptome and proteome in ACM patients and assess whether key identified molecules were also detectable in plasma and tissue samples.
Methods and results
Myocardial tissues were obtained from ACM and dilated cardiomyopathy (DCM) patients as well as healthy controls (n = 10/group). Transcriptomic profiling was performed by RNA sequencing and proteomic profiling by label-free liquid chromatography–tandem mass spectrometry. Differential expression and pathway enrichment analyses were performed to identify key biological processes. Selected targets were validated by tissue immunofluorescence and plasma ELISA. Transcriptomic analysis revealed 3030 dysregulated mRNAs in ACM versus healthy controls and 120 versus DCM. Enriched clusters in ACM versus healthy controls were related to immune activation, inflammation, extracellular matrix remodelling and mitochondrial stress; redox and metabolic processes, cell junction regulation and immune responses were enriched clusters in ACM versus DCM. Proteomics identified 206 and 65 differentially expressed proteins, respectively. Three novel proteins, UCHL1, OCIAD1 and desmoyokin, were consistently up-regulated at transcript and protein levels. The latter two were confirmed in myocardial tissue staining and showed elevated plasma levels in ACM compared with DCM and controls.
Conclusion
This integrated transcriptomic and proteomic study of myocardial tissue and plasma from patients with ACM compared with those with DCM and healthy controls, identified key dysregulated pathways, involving immune response, inflammation and oxidative and mitochondrial stress. Desmoyokin and OCIAD1, in particular, may represent specific candidate biomarkers for ACM.
{"title":"Transcriptomic and proteomic profiling shows dysregulated immune and metabolic pathways in arrhythmogenic cardiomyopathy","authors":"Deniz Akdis, Lukas Weidmann, Paolo Nanni, Anna Gaertner, Hendrik Milting, Peter Bode, Corinna Brunckhorst, Liang Chen, Felix C. Tanner, Frank Ruschitzka, Ardan M. Saguner, Firat Duru","doi":"10.1002/ehf2.70013","DOIUrl":"10.1002/ehf2.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease characterized by fibrofatty myocardial replacement and a predisposition to malignant ventricular arrhythmias. The underlying pathomechanisms remain incompletely understood, and specific disease markers are sparse. This study aimed to characterize the myocardial transcriptome and proteome in ACM patients and assess whether key identified molecules were also detectable in plasma and tissue samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Myocardial tissues were obtained from ACM and dilated cardiomyopathy (DCM) patients as well as healthy controls (<i>n</i> = 10/group). Transcriptomic profiling was performed by RNA sequencing and proteomic profiling by label-free liquid chromatography–tandem mass spectrometry. Differential expression and pathway enrichment analyses were performed to identify key biological processes. Selected targets were validated by tissue immunofluorescence and plasma ELISA. Transcriptomic analysis revealed 3030 dysregulated mRNAs in ACM versus healthy controls and 120 versus DCM. Enriched clusters in ACM versus healthy controls were related to immune activation, inflammation, extracellular matrix remodelling and mitochondrial stress; redox and metabolic processes, cell junction regulation and immune responses were enriched clusters in ACM versus DCM. Proteomics identified 206 and 65 differentially expressed proteins, respectively. Three novel proteins, UCHL1, OCIAD1 and desmoyokin, were consistently up-regulated at transcript and protein levels. The latter two were confirmed in myocardial tissue staining and showed elevated plasma levels in ACM compared with DCM and controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This integrated transcriptomic and proteomic study of myocardial tissue and plasma from patients with ACM compared with those with DCM and healthy controls, identified key dysregulated pathways, involving immune response, inflammation and oxidative and mitochondrial stress. Desmoyokin and OCIAD1, in particular, may represent specific candidate biomarkers for ACM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4419-4430"},"PeriodicalIF":3.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502903","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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