Pub Date : 2025-12-01Epub Date: 2025-08-17DOI: 10.1002/ejhf.70003
Guillaume Baudry, Maria Generosa Crespo-Leiro, Clément Delmas, Federica Guidetti, Marta Jimenez-Blanco Bravo, Federica Valente, Maja Cikes, Nicolas Girerd, Finn Gustafsson, Gianluigi Savarese, Linda W van Laake, Loreena Hill, Anne Kathrine Skibelund, Andreas Zuckermann, Marco Metra, Kevin Damman
The identification of patients with advanced heart failure (HF) remains challenging, often leading to delayed referrals and suboptimal use of advanced therapies such as long-term mechanical circulatory support (MCS) or heart transplantation (HT). This delay contributes to worse outcomes and missed opportunities for timely intervention. Many eligible patients are not recognized early enough in their clinical trajectory, either due to the complexity of the condition, overlapping HF phenotypes, or limited awareness of referral criteria among non-specialist clinicians. In this context, the aim of this scientific statement from the Heart Failure Association (HFA) of the ESC is to systematically identify and address the multifaceted barriers that hinder early recognition and referral for advanced HF care. These barriers span across different stakeholders-patients, caregivers, referring physicians, HF specialists, the academic community, and health authorities. The document proposes practical, stakeholder-specific solutions to improve awareness, standardize referral criteria, integrate digital decision-support tools, and structure care networks. Ultimately, the goal is to enable earlier access to specialized evaluation, ensure equitable use of HT and MCS when appropriate, and improve both survival and quality of life for patients living with advanced HF.
{"title":"Identifying and overcoming barriers to referral in advanced heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC.","authors":"Guillaume Baudry, Maria Generosa Crespo-Leiro, Clément Delmas, Federica Guidetti, Marta Jimenez-Blanco Bravo, Federica Valente, Maja Cikes, Nicolas Girerd, Finn Gustafsson, Gianluigi Savarese, Linda W van Laake, Loreena Hill, Anne Kathrine Skibelund, Andreas Zuckermann, Marco Metra, Kevin Damman","doi":"10.1002/ejhf.70003","DOIUrl":"10.1002/ejhf.70003","url":null,"abstract":"<p><p>The identification of patients with advanced heart failure (HF) remains challenging, often leading to delayed referrals and suboptimal use of advanced therapies such as long-term mechanical circulatory support (MCS) or heart transplantation (HT). This delay contributes to worse outcomes and missed opportunities for timely intervention. Many eligible patients are not recognized early enough in their clinical trajectory, either due to the complexity of the condition, overlapping HF phenotypes, or limited awareness of referral criteria among non-specialist clinicians. In this context, the aim of this scientific statement from the Heart Failure Association (HFA) of the ESC is to systematically identify and address the multifaceted barriers that hinder early recognition and referral for advanced HF care. These barriers span across different stakeholders-patients, caregivers, referring physicians, HF specialists, the academic community, and health authorities. The document proposes practical, stakeholder-specific solutions to improve awareness, standardize referral criteria, integrate digital decision-support tools, and structure care networks. Ultimately, the goal is to enable earlier access to specialized evaluation, ensure equitable use of HT and MCS when appropriate, and improve both survival and quality of life for patients living with advanced HF.</p>","PeriodicalId":164,"journal":{"name":"European Journal of Heart Failure","volume":" ","pages":"3312-3325"},"PeriodicalIF":10.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12803578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Why healthcare providers' adherence to guideline-directed medical therapy is only half the battle.","authors":"Martin Schulz,Felix Mahfoud,Ulrich Laufs","doi":"10.1002/ejhf.70092","DOIUrl":"https://doi.org/10.1002/ejhf.70092","url":null,"abstract":"","PeriodicalId":164,"journal":{"name":"European Journal of Heart Failure","volume":"151 1","pages":""},"PeriodicalIF":18.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2024-11-26DOI: 10.1002/ejhf.3522
Emerson C Perin, Kenneth M Borow, Timothy D Henry, Margaret Jenkins, Olga Rutman, Jack Hayes, Christopher W James, Eric Rose, Hicham Skali, Silviu Itescu, Barry Greenberg
Aims: Progressive heart failure with reduced ejection fraction (HFrEF) is adversely affected by alterations in the myocardial balance between bone marrow-derived pro-inflammatory cardiac macrophages and embryo-derived reparative cardiac resident macrophages. Mesenchymal precursor cells (MPCs) may restore this balance and improve clinical outcomes when inflammation is present. The purpose was to (i) identify risk factors for cardiovascular death (CVD) in control patients with HFrEF in the DREAM-HF trial, and (ii) determine if MPCs improve major clinical outcomes (CVD, myocardial infarction [MI], stroke) in high-risk patients with ischaemic HFrEF and inflammation.
Methods and results: Cause-specific regression analyses were used to identify CVD risk factors in DREAM-HF control patients. Aalen-Johansen cumulative incidence curves were used to examine CVD, 2-point major adverse cardiovascular events (MACE) (MI or stroke), and 3-point MACE (CVD or MI or stroke) by treatment group in ischaemic vs non-ischaemic HFrEF and in patients with or without baseline inflammation. In control DREAM-HF patients, factors portending the greatest risk for CVD were inflammation (baseline plasma high-sensitivity C-reactive protein ≥2 mg/L; p = 0.003) and ischaemic HFrEF aetiology (p = 0.097), with increased CVD risk of 61% and 38%, respectively. Over 30-month mean follow-up, MPCs reduced 2-point and 3-point MACE by 88% (p = 0.005) and 52% (p = 0.018), respectively, in patients with ischaemic HFrEF and inflammation compared to controls.
Conclusions: Ischaemic aetiology and inflammation were identified as major risk factors for MACE in control DREAM-HF patients. A single intramyocardial MPC administration produced the most significant, sustained reduction in 2-point and 3-point MACE in patients with ischaemic HFrEF and inflammation.
{"title":"Mesenchymal precursor cells reduce mortality and major morbidity in ischaemic heart failure with inflammation: DREAM-HF.","authors":"Emerson C Perin, Kenneth M Borow, Timothy D Henry, Margaret Jenkins, Olga Rutman, Jack Hayes, Christopher W James, Eric Rose, Hicham Skali, Silviu Itescu, Barry Greenberg","doi":"10.1002/ejhf.3522","DOIUrl":"10.1002/ejhf.3522","url":null,"abstract":"<p><strong>Aims: </strong>Progressive heart failure with reduced ejection fraction (HFrEF) is adversely affected by alterations in the myocardial balance between bone marrow-derived pro-inflammatory cardiac macrophages and embryo-derived reparative cardiac resident macrophages. Mesenchymal precursor cells (MPCs) may restore this balance and improve clinical outcomes when inflammation is present. The purpose was to (i) identify risk factors for cardiovascular death (CVD) in control patients with HFrEF in the DREAM-HF trial, and (ii) determine if MPCs improve major clinical outcomes (CVD, myocardial infarction [MI], stroke) in high-risk patients with ischaemic HFrEF and inflammation.</p><p><strong>Methods and results: </strong>Cause-specific regression analyses were used to identify CVD risk factors in DREAM-HF control patients. Aalen-Johansen cumulative incidence curves were used to examine CVD, 2-point major adverse cardiovascular events (MACE) (MI or stroke), and 3-point MACE (CVD or MI or stroke) by treatment group in ischaemic vs non-ischaemic HFrEF and in patients with or without baseline inflammation. In control DREAM-HF patients, factors portending the greatest risk for CVD were inflammation (baseline plasma high-sensitivity C-reactive protein ≥2 mg/L; p = 0.003) and ischaemic HFrEF aetiology (p = 0.097), with increased CVD risk of 61% and 38%, respectively. Over 30-month mean follow-up, MPCs reduced 2-point and 3-point MACE by 88% (p = 0.005) and 52% (p = 0.018), respectively, in patients with ischaemic HFrEF and inflammation compared to controls.</p><p><strong>Conclusions: </strong>Ischaemic aetiology and inflammation were identified as major risk factors for MACE in control DREAM-HF patients. A single intramyocardial MPC administration produced the most significant, sustained reduction in 2-point and 3-point MACE in patients with ischaemic HFrEF and inflammation.</p>","PeriodicalId":164,"journal":{"name":"European Journal of Heart Failure","volume":" ","pages":"3288-3296"},"PeriodicalIF":10.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-14DOI: 10.1002/ejhf.70006
Jishnu Malgie, Mariëlle I Wilde, Stefan Koudstaal, Robert Denham, Carlos A da Fonseca, Henk P Swart, Clara E E van Ofwegen, Ayten Yilmaz, Ron Pisters, Gerard C M Linssen, Nikola Faber, Loek van Heerebeek, Julio E C van de Swaluw, Rudolf A de Boer, Hans-Peter Brunner-La Rocca, Jasper J Brugts
Aims: Guideline-recommended medical therapy (GRMT) improves outcomes in heart failure (HF) with reduced ejection fraction (HFrEF), yet implementation remains suboptimal. TITRATE-HF prospectively evaluated GRMT implementation across different HFrEF stages, and its effect on 1-year prognosis and left ventricular ejection fraction (LVEF).
Methods and results: TITRATE-HF is an observational cohort study across 48 hospitals in the Netherlands (June 2022-February 2024). A total of 4288 patients were enrolled. This primary analysis includes 12-month follow-up data of all HFrEF patients (n = 3367), stratified into de novo, chronic, and worsening HF. Longitudinal trends in GRMT prescription rates and dosages were analysed. Serial echocardiographic data assessed changes in LVEF between baseline and 12 months. Kaplan-Meier analysis assessed the composite endpoint of all-cause death or HF hospitalization. Median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and 56% had non-ischaemic cardiomyopathy. In de novo HFrEF (n = 1353), quadruple therapy was 47.2% at 6 weeks, 64.7% at 3 months, 69.5% at 6 months, and 64.4% at 12 months. In chronic/worsening HFrEF (n = 1625), quadruple therapy increased from 44.6% at baseline to 54.6% at 12 months, primarily driven by greater sodium-glucose co-transporter 2 inhibitor uptake (66.0% to 78.5%). Among de novo HFrEF patients with serial echocardiograms (n = 752), median LVEF improved by 10% (IQR 3-17%) in ischaemic versus 15% (IQR 9-24%) in non-ischaemic cardiomyopathy (p < 0.001). Early quadruple GRMT initiation (within 6 weeks) and higher 6-month doses were associated with greater LVEF improvement. At 12 months, the composite endpoint occurred in 13.3%, 13.3%, and 43.8% of de novo, chronic, and worsening HFrEF patients, respectively.
Conclusions: These findings highlight the importance of early and intensive GRMT implementation, and emphasize the need for continuous dose titration beyond the initial phase to improve LVEF and clinical outcomes.
{"title":"Real-life implementation of guideline-recommended medical therapy in heart failure with reduced ejection fraction: Effects on prognosis and left ventricular ejection fraction. Primary results of TITRATE-HF.","authors":"Jishnu Malgie, Mariëlle I Wilde, Stefan Koudstaal, Robert Denham, Carlos A da Fonseca, Henk P Swart, Clara E E van Ofwegen, Ayten Yilmaz, Ron Pisters, Gerard C M Linssen, Nikola Faber, Loek van Heerebeek, Julio E C van de Swaluw, Rudolf A de Boer, Hans-Peter Brunner-La Rocca, Jasper J Brugts","doi":"10.1002/ejhf.70006","DOIUrl":"10.1002/ejhf.70006","url":null,"abstract":"<p><strong>Aims: </strong>Guideline-recommended medical therapy (GRMT) improves outcomes in heart failure (HF) with reduced ejection fraction (HFrEF), yet implementation remains suboptimal. TITRATE-HF prospectively evaluated GRMT implementation across different HFrEF stages, and its effect on 1-year prognosis and left ventricular ejection fraction (LVEF).</p><p><strong>Methods and results: </strong>TITRATE-HF is an observational cohort study across 48 hospitals in the Netherlands (June 2022-February 2024). A total of 4288 patients were enrolled. This primary analysis includes 12-month follow-up data of all HFrEF patients (n = 3367), stratified into de novo, chronic, and worsening HF. Longitudinal trends in GRMT prescription rates and dosages were analysed. Serial echocardiographic data assessed changes in LVEF between baseline and 12 months. Kaplan-Meier analysis assessed the composite endpoint of all-cause death or HF hospitalization. Median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and 56% had non-ischaemic cardiomyopathy. In de novo HFrEF (n = 1353), quadruple therapy was 47.2% at 6 weeks, 64.7% at 3 months, 69.5% at 6 months, and 64.4% at 12 months. In chronic/worsening HFrEF (n = 1625), quadruple therapy increased from 44.6% at baseline to 54.6% at 12 months, primarily driven by greater sodium-glucose co-transporter 2 inhibitor uptake (66.0% to 78.5%). Among de novo HFrEF patients with serial echocardiograms (n = 752), median LVEF improved by 10% (IQR 3-17%) in ischaemic versus 15% (IQR 9-24%) in non-ischaemic cardiomyopathy (p < 0.001). Early quadruple GRMT initiation (within 6 weeks) and higher 6-month doses were associated with greater LVEF improvement. At 12 months, the composite endpoint occurred in 13.3%, 13.3%, and 43.8% of de novo, chronic, and worsening HFrEF patients, respectively.</p><p><strong>Conclusions: </strong>These findings highlight the importance of early and intensive GRMT implementation, and emphasize the need for continuous dose titration beyond the initial phase to improve LVEF and clinical outcomes.</p>","PeriodicalId":164,"journal":{"name":"European Journal of Heart Failure","volume":" ","pages":"2735-2746"},"PeriodicalIF":10.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12803593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMSTafamidis reshaped the treatment paradigm in transthyretin amyloid cardiomyopathy (ATTR-CM) based on a phase-3 randomized controlled trial, but real-world data on its use remain limited. This study aimed to assess in a large, contemporary, real-world cohort of patients with wild-type ATTR-CM (ATTRwt-CM) (i) the clinical phenotype of patients receiving tafamidis, and (ii) the association of tafamidis with survival using propensity-matched observational data.METHODS AND RESULTSData of patients diagnosed with ATTRwt-CM (January 2017 to June 2023) from 19 Italian centres were analysed. A propensity score (PS) reflecting the likelihood of being treated with tafamidis for each patient was determined using four variables that were significantly different among the two groups: age, New York Heart Association (NYHA) class, National Amyloidosis Centre (NAC) stage and mineralocorticoid receptor antagonists (MRAs). The primary outcome was all-cause mortality. The study comprised 1556 ATTRwt-CM patients: 965 (62%) patients initiated on tafamidis by June 2023 and 591 (38%) patients never treated with disease-modifying therapy. Tafamidis-treated patients were older, exhibited a lower NYHA class and NAC stage, and were more often treated with MRAs compared to untreated patients. The PS-matched cohort comprised 426 patients treated with tafamidis and 426 PS-matched untreated patients (mean age 78.9 ± 5.0 years, 88.3% men, 12.9% in NYHA class III). Adequacy of matching was verified (standardized differences: <0.20 between groups). Over 25 months (interquartile range: 15-40), treatment with tafamidis was associated with lower rates of all-cause mortality (hazard ratio 0.55, 95% confidence interval 0.39-0.77, p = 0.001) across the spectrum of NAC disease stages (p-interaction = 0.94).CONCLUSIONSIn this large, contemporary, real-world cohort of patients with ATTRwt-CM, predominantly in NYHA class I or II, treatment with tafamidis was consistently associated with a significantly lower risk of all-cause mortality.
{"title":"Clinical phenotype and prognosis of real-world patients with wild-type transthyretin amyloid cardiomyopathy treated with tafamidis.","authors":"Aldostefano Porcari,Paolo Milani,Simone Longhi,Francesco Cappelli,Fabio Vagnarelli,Alberto Aimo,Alberto Cipriani,Elisa Gardini,Stefania Marazia,Emanuele Monda,Giacomo Tini,Beatrice Musumeci,Matteo Serenelli,Anna Cantone,Carla Lofiego,Marco Marini,Giuseppe Vergaro,Grazia Foti,Francesco Musca,Daniela Tomasoni,Giacomo Bonacchi,Federica Colio,Giulio Sinigiani,Laura De Michieli,Francesca Sturdà,Marco Pozzan,Piero Gentile,Samuela Carigi,Michela Bartolotti,Giuseppe Sena,Irene Ruotolo,Giuseppe Damiano Sanna,Margherita Zanoletti,Marco Canepa,Massimo Di Marco,Emilia D'Elia,Gianluca Di Bella,Mauro Driussi,Massimo Imazio,Federico Perfetto,Elena Biagini,Giuseppe Limongelli,Marco Metra,Michele Emdin,Giampaolo Merlini,Stefano Perlini,Marco Merlo,Giovanni Palladini,Gianfranco Sinagra","doi":"10.1002/ejhf.70071","DOIUrl":"https://doi.org/10.1002/ejhf.70071","url":null,"abstract":"AIMSTafamidis reshaped the treatment paradigm in transthyretin amyloid cardiomyopathy (ATTR-CM) based on a phase-3 randomized controlled trial, but real-world data on its use remain limited. This study aimed to assess in a large, contemporary, real-world cohort of patients with wild-type ATTR-CM (ATTRwt-CM) (i) the clinical phenotype of patients receiving tafamidis, and (ii) the association of tafamidis with survival using propensity-matched observational data.METHODS AND RESULTSData of patients diagnosed with ATTRwt-CM (January 2017 to June 2023) from 19 Italian centres were analysed. A propensity score (PS) reflecting the likelihood of being treated with tafamidis for each patient was determined using four variables that were significantly different among the two groups: age, New York Heart Association (NYHA) class, National Amyloidosis Centre (NAC) stage and mineralocorticoid receptor antagonists (MRAs). The primary outcome was all-cause mortality. The study comprised 1556 ATTRwt-CM patients: 965 (62%) patients initiated on tafamidis by June 2023 and 591 (38%) patients never treated with disease-modifying therapy. Tafamidis-treated patients were older, exhibited a lower NYHA class and NAC stage, and were more often treated with MRAs compared to untreated patients. The PS-matched cohort comprised 426 patients treated with tafamidis and 426 PS-matched untreated patients (mean age 78.9 ± 5.0 years, 88.3% men, 12.9% in NYHA class III). Adequacy of matching was verified (standardized differences: <0.20 between groups). Over 25 months (interquartile range: 15-40), treatment with tafamidis was associated with lower rates of all-cause mortality (hazard ratio 0.55, 95% confidence interval 0.39-0.77, p = 0.001) across the spectrum of NAC disease stages (p-interaction = 0.94).CONCLUSIONSIn this large, contemporary, real-world cohort of patients with ATTRwt-CM, predominantly in NYHA class I or II, treatment with tafamidis was consistently associated with a significantly lower risk of all-cause mortality.","PeriodicalId":164,"journal":{"name":"European Journal of Heart Failure","volume":"196 1","pages":""},"PeriodicalIF":18.2,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luca Monzo, Gianluigi Savarese, Wilfried Mullens, Amr Abdin, Biykem Bozkurt, Ovidiu Chioncel, Seif El Hadidi, Thomas M. Gorter, Riccardo M. Inciardi, Mark C. Petrie, Gabriele G. Schiattarella, Davide Stolfo, Marco Metra, Nicolas Girerd
There is growing clinical interest in strategies for improving clinical outcomes in patients with heart failure (HF) and obesity. The development of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and of the dual glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1 RA has expanded therapeutic options for this population. This expert consensus provides a comprehensive and pragmatic framework for the use of GLP‐1 RAs and GIP/GLP‐1 RA in patients with HF, focusing on clinical integration, patient selection, safety, and tolerability. We review the evidence supporting their use in patients with HF with preserved ejection fraction (HFpEF), where clinical trials have demonstrated meaningful reductions in body weight alongside improvements in health status and exercise capacity. Whether these effects translate into fewer HF events or lower cardiovascular mortality remains uncertain, as current evidence is limited to two small trials with few observed events. In contrast, data regarding the efficacy and safety of these drugs in HF with reduced ejection fraction are scarce, with dedicated outcome trials yet to be launched. Finally, this document highlights knowledge gaps and outlines future research directions in this field.
{"title":"Pharmacological treatment for patients with obesity and heart failure: Focus on glucagon‐like peptide‐1 receptor agonists. European Journal of Heart Failure expert consensus document","authors":"Luca Monzo, Gianluigi Savarese, Wilfried Mullens, Amr Abdin, Biykem Bozkurt, Ovidiu Chioncel, Seif El Hadidi, Thomas M. Gorter, Riccardo M. Inciardi, Mark C. Petrie, Gabriele G. Schiattarella, Davide Stolfo, Marco Metra, Nicolas Girerd","doi":"10.1002/ejhf.70082","DOIUrl":"https://doi.org/10.1002/ejhf.70082","url":null,"abstract":"There is growing clinical interest in strategies for improving clinical outcomes in patients with heart failure (HF) and obesity. The development of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and of the dual glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1 RA has expanded therapeutic options for this population. This expert consensus provides a comprehensive and pragmatic framework for the use of GLP‐1 RAs and GIP/GLP‐1 RA in patients with HF, focusing on clinical integration, patient selection, safety, and tolerability. We review the evidence supporting their use in patients with HF with preserved ejection fraction (HFpEF), where clinical trials have demonstrated meaningful reductions in body weight alongside improvements in health status and exercise capacity. Whether these effects translate into fewer HF events or lower cardiovascular mortality remains uncertain, as current evidence is limited to two small trials with few observed events. In contrast, data regarding the efficacy and safety of these drugs in HF with reduced ejection fraction are scarce, with dedicated outcome trials yet to be launched. Finally, this document highlights knowledge gaps and outlines future research directions in this field.","PeriodicalId":164,"journal":{"name":"European Journal of Heart Failure","volume":"5 1","pages":""},"PeriodicalIF":18.2,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ambarish Pandey, Michael Moroney, Subodh Verma, Barry A. Borlaug, Javed Butler, Melanie J. Davies, Dalane W. Kitzman, Sanjiv J. Shah, Mark C. Petrie, Cecilia Rönnbäck, Anne Domdey, Søren Rasmussen, Khaja M. Chinnakondepalli, Shachi Patel, Mikhail N. Kosiborod
Background The prevalence of heart failure with preserved ejection fraction (HFpEF) increases with age, and older adults with HFpEF have worse physical function, quality of life, and clinical outcomes. Semaglutide demonstrated efficacy in the treatment of obesity‐related HFpEF in the STEP‐HFpEF trials. Some have speculated that older patients may have less to gain from incretin therapies (and perhaps more to lose) than younger patients. Aims In this pre‐specified pooled subanalysis of the STEP‐HFpEF trials, we evaluated the efficacy of semaglutide across the age spectrum. Methods The STEP‐HFpEF and STEP‐HFpEF DM trials enrolled participants with obesity‐related HFpEF and randomized them to semaglutide 2.4 mg once weekly ( n = 573) or placebo ( n = 572) for 52 weeks. Dual primary outcomes (change in Kansas City Cardiomyopathy Questionnaire clinical summary score [KCCQ‐CSS] and change in body weight) and secondary outcome measures (6‐minute walk distance [6MWD], C‐reactive protein, hierarchical composite endpoint containing all‐cause death, heart failure events, changes in KCCQ‐CSS and 6MWD) were compared across specific age groups; <55 years, 55–64 years, 65–74 years and ≥75 years. Results Among 1145 randomized participants, 8.8% ( N = 101) were <55, 23.3% ( N = 267) were aged between 55–64, 42.4% ( N = 485) were between 65–74, and 25.5% ( N = 292) were 75 years or over. The efficacy of semaglutide on the dual primary endpoints was consistent across the age spectrum, KCCQ‐CSS ( p ‐interaction = 0.80), and body weight ( p ‐interaction = 0.41). Similar benefits were observed for the key secondary endpoints, with no treatment effect heterogeneity across age groups. Moreover, the safety of semaglutide was consistent across age groups. Conclusion In patients with HFpEF enrolled across the STEP‐HFpEF and STEP‐HFpEF DM trials, treatment with semaglutide improved disease‐specific symptoms, physical function and reduced body weight across the age spectrum. The safety profile of semaglutide was consistent in older and younger patients.
{"title":"Effects of semaglutide in obesity‐related heart failure with preserved ejection fraction across the age spectrum: Findings from the STEP ‐ HFpEF programme","authors":"Ambarish Pandey, Michael Moroney, Subodh Verma, Barry A. Borlaug, Javed Butler, Melanie J. Davies, Dalane W. Kitzman, Sanjiv J. Shah, Mark C. Petrie, Cecilia Rönnbäck, Anne Domdey, Søren Rasmussen, Khaja M. Chinnakondepalli, Shachi Patel, Mikhail N. Kosiborod","doi":"10.1002/ejhf.70049","DOIUrl":"https://doi.org/10.1002/ejhf.70049","url":null,"abstract":"Background The prevalence of heart failure with preserved ejection fraction (HFpEF) increases with age, and older adults with HFpEF have worse physical function, quality of life, and clinical outcomes. Semaglutide demonstrated efficacy in the treatment of obesity‐related HFpEF in the STEP‐HFpEF trials. Some have speculated that older patients may have less to gain from incretin therapies (and perhaps more to lose) than younger patients. Aims In this pre‐specified pooled subanalysis of the STEP‐HFpEF trials, we evaluated the efficacy of semaglutide across the age spectrum. Methods The STEP‐HFpEF and STEP‐HFpEF DM trials enrolled participants with obesity‐related HFpEF and randomized them to semaglutide 2.4 mg once weekly ( <jats:italic>n</jats:italic> = 573) or placebo ( <jats:italic>n</jats:italic> = 572) for 52 weeks. Dual primary outcomes (change in Kansas City Cardiomyopathy Questionnaire clinical summary score [KCCQ‐CSS] and change in body weight) and secondary outcome measures (6‐minute walk distance [6MWD], C‐reactive protein, hierarchical composite endpoint containing all‐cause death, heart failure events, changes in KCCQ‐CSS and 6MWD) were compared across specific age groups; <55 years, 55–64 years, 65–74 years and ≥75 years. Results Among 1145 randomized participants, 8.8% ( <jats:italic>N</jats:italic> = 101) were <55, 23.3% ( <jats:italic>N</jats:italic> = 267) were aged between 55–64, 42.4% ( <jats:italic>N</jats:italic> = 485) were between 65–74, and 25.5% ( <jats:italic>N</jats:italic> = 292) were 75 years or over. The efficacy of semaglutide on the dual primary endpoints was consistent across the age spectrum, KCCQ‐CSS ( <jats:italic>p</jats:italic> ‐interaction = 0.80), and body weight ( <jats:italic>p</jats:italic> ‐interaction = 0.41). Similar benefits were observed for the key secondary endpoints, with no treatment effect heterogeneity across age groups. Moreover, the safety of semaglutide was consistent across age groups. Conclusion In patients with HFpEF enrolled across the STEP‐HFpEF and STEP‐HFpEF DM trials, treatment with semaglutide improved disease‐specific symptoms, physical function and reduced body weight across the age spectrum. The safety profile of semaglutide was consistent in older and younger patients.","PeriodicalId":164,"journal":{"name":"European Journal of Heart Failure","volume":"18 1","pages":""},"PeriodicalIF":18.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daan C.H. Ceelen, Jozine M. ter Maaten, Geert H.D. Voordes, Gad Cotter, Beth A. Davison, Gerasimos Filippatos, Peter S. Pang, Claudio Gimpelewicz, John G.F. Cleland, G. Michael Felker, Barry Greenberg, Michael M. Givertz, Christopher M. O'Conner, John R. Teerlink, Marco Metra, Adriaan A. Voors
Aims Residual congestion (RC) is common at discharge after acute decompensated heart failure (ADHF) and is associated with early mortality and rehospitalization. The prognostic value of distinct RC phenotypes (i.e. intravascular and tissue congestion) remains unclear. This analysis investigated RC phenotypes and their outcomes. Methods and results Patients with congestion at admission from two large ADHF trials, PROTECT (rolofylline; index) and RELAX‐AHF‐2 (serelaxin; replication), were classified based on clinical signs at day 7/discharge as intravascular (jugular venous pressure) or tissue (pulmonary rales/peripheral oedema) congestion, each alone, combined or neither. Cox regression assessed 180‐day mortality after adjusting for risk factors. Overall, 1557 patients with predominantly combined (i.e. tissue and intravascular) congestion at admission were included, with a median age of 72 years. By day 7 or discharge, 580 (37%) patients had RC. In these patients, intravascular congestion ( n = 260; 45%) was most common, followed by combined ( n = 185; 32%) and tissue ( n = 135; 23%) congestion. During hospitalization, patients with solely intravascular RC had greater diuretic responses, shorter hospital stays and received lower doses of intravenous loop diuretics than those with tissue or combined congestion (all p < 0.05). Residual intravascular and tissue congestion were independently associated with increased 180‐day mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.15–2.49, and HR 2.07, 95% CI 1.25–3.41, respectively) compared to decongested patients. In the RELAX‐AHF‐2 substudy ( n = 476), similar findings were observed. Conclusions Patients with intravascular RC had better diuretic responses and shorter hospital stays than those with tissue/combined RC, but worse outcomes than decongested patients. This study highlights the importance of RC assessment to identify at‐risk patients. Future studies should evaluate phenotype‐guided treatments.
{"title":"Clinical profiles and prognostic impact of residual intravascular and tissue congestion in acute heart failure","authors":"Daan C.H. Ceelen, Jozine M. ter Maaten, Geert H.D. Voordes, Gad Cotter, Beth A. Davison, Gerasimos Filippatos, Peter S. Pang, Claudio Gimpelewicz, John G.F. Cleland, G. Michael Felker, Barry Greenberg, Michael M. Givertz, Christopher M. O'Conner, John R. Teerlink, Marco Metra, Adriaan A. Voors","doi":"10.1002/ejhf.70091","DOIUrl":"https://doi.org/10.1002/ejhf.70091","url":null,"abstract":"Aims Residual congestion (RC) is common at discharge after acute decompensated heart failure (ADHF) and is associated with early mortality and rehospitalization. The prognostic value of distinct RC phenotypes (i.e. intravascular and tissue congestion) remains unclear. This analysis investigated RC phenotypes and their outcomes. Methods and results Patients with congestion at admission from two large ADHF trials, PROTECT (rolofylline; index) and RELAX‐AHF‐2 (serelaxin; replication), were classified based on clinical signs at day 7/discharge as intravascular (jugular venous pressure) or tissue (pulmonary rales/peripheral oedema) congestion, each alone, combined or neither. Cox regression assessed 180‐day mortality after adjusting for risk factors. Overall, 1557 patients with predominantly combined (i.e. tissue and intravascular) congestion at admission were included, with a median age of 72 years. By day 7 or discharge, 580 (37%) patients had RC. In these patients, intravascular congestion ( <jats:italic>n</jats:italic> = 260; 45%) was most common, followed by combined ( <jats:italic>n</jats:italic> = 185; 32%) and tissue ( <jats:italic>n</jats:italic> = 135; 23%) congestion. During hospitalization, patients with solely intravascular RC had greater diuretic responses, shorter hospital stays and received lower doses of intravenous loop diuretics than those with tissue or combined congestion (all <jats:italic>p</jats:italic> < 0.05). Residual intravascular and tissue congestion were independently associated with increased 180‐day mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.15–2.49, and HR 2.07, 95% CI 1.25–3.41, respectively) compared to decongested patients. In the RELAX‐AHF‐2 substudy ( <jats:italic>n</jats:italic> = 476), similar findings were observed. Conclusions Patients with intravascular RC had better diuretic responses and shorter hospital stays than those with tissue/combined RC, but worse outcomes than decongested patients. This study highlights the importance of RC assessment to identify at‐risk patients. Future studies should evaluate phenotype‐guided treatments.","PeriodicalId":164,"journal":{"name":"European Journal of Heart Failure","volume":"22 1","pages":""},"PeriodicalIF":18.2,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rohanti Ravikulan, Sanjay Chavali, James E. Gunton, Carmine G. De Pasquale
Aims Atrial fibrillation (AF) is more prevalent in heart failure with preserved ejection fraction (HFpEF) than in other heart failure phenotypes and contributes to worse clinical outcomes. Despite structural and metabolic benefits observed with glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) in HFpEF and heart failure with mildly reduced ejection fraction (HFmrEF), their impact on AF incidence remains unclear. We conducted a meta‐analysis of randomized trials to evaluate whether GLP‐1 RA therapy reduces incident AF in patients with HFpEF and HFmrEF. Methods and results We systematically searched MEDLINE, Embase, and Cochrane databases (inception to 28 February 2025) for randomized controlled trials reporting incident AF in HFpEF populations treated with GLP‐1 RAs. Four eligible trials were identified (SELECT, FLOW, STEP‐HFpEF, STEP‐HFpEF DM), enrolling 3743participants with HFpEF or HFmrEF. The primary analysis used a fixed‐effect model. GLP‐1 RA therapy significantly reduced the risk of incident AF (risk ratio [RR] 0.54; 95% confidence interval [CI] 0.36–0.81; p = 0.003), with moderate heterogeneity ( I2 = 51%, τ 2 = 0.21). Secondary outcomes showed significantly greater reductions in body weight, systolic blood pressure, and left atrial volume in the treatment group. Conclusions Glucagon‐like peptide‐1 receptor agonist therapy is associated with a significant reduction in incident AF among patients with HFpEF and HFmrEF. These findings support the hypothesis that GLP‐1 RAs may offer rhythm‐modifying benefits in addition to weight and haemodynamic effects. Dedicated HFpEF trials with adjudicated AF outcomes are warranted.
{"title":"Glucagon‐like peptide‐1 receptor agonists reduce atrial fibrillation among patients with heart failure with preserved and mildly reduced ejection fraction – a meta‐analysis of randomized controlled trials","authors":"Rohanti Ravikulan, Sanjay Chavali, James E. Gunton, Carmine G. De Pasquale","doi":"10.1002/ejhf.70085","DOIUrl":"https://doi.org/10.1002/ejhf.70085","url":null,"abstract":"Aims Atrial fibrillation (AF) is more prevalent in heart failure with preserved ejection fraction (HFpEF) than in other heart failure phenotypes and contributes to worse clinical outcomes. Despite structural and metabolic benefits observed with glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) in HFpEF and heart failure with mildly reduced ejection fraction (HFmrEF), their impact on AF incidence remains unclear. We conducted a meta‐analysis of randomized trials to evaluate whether GLP‐1 RA therapy reduces incident AF in patients with HFpEF and HFmrEF. Methods and results We systematically searched MEDLINE, Embase, and Cochrane databases (inception to 28 February 2025) for randomized controlled trials reporting incident AF in HFpEF populations treated with GLP‐1 RAs. Four eligible trials were identified (SELECT, FLOW, STEP‐HFpEF, STEP‐HFpEF DM), enrolling 3743participants with HFpEF or HFmrEF. The primary analysis used a fixed‐effect model. GLP‐1 RA therapy significantly reduced the risk of incident AF (risk ratio [RR] 0.54; 95% confidence interval [CI] 0.36–0.81; <jats:italic>p</jats:italic> = 0.003), with moderate heterogeneity ( <jats:italic>I</jats:italic> <jats:sup>2</jats:sup> = 51%, τ <jats:sup>2</jats:sup> = 0.21). Secondary outcomes showed significantly greater reductions in body weight, systolic blood pressure, and left atrial volume in the treatment group. Conclusions Glucagon‐like peptide‐1 receptor agonist therapy is associated with a significant reduction in incident AF among patients with HFpEF and HFmrEF. These findings support the hypothesis that GLP‐1 RAs may offer rhythm‐modifying benefits in addition to weight and haemodynamic effects. Dedicated HFpEF trials with adjudicated AF outcomes are warranted.","PeriodicalId":164,"journal":{"name":"European Journal of Heart Failure","volume":"11 1","pages":""},"PeriodicalIF":18.2,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gianluigi Savarese,Felix Lindberg,Antonio Cannata,Marianna Adamo,Giuseppe Ambrosio,Pietro Ameri,Markus S Anker,Magnus Bäck,Antoni Bayes-Genis,Tuvia Ben Gal,Frieder Braunschweig,Ovidiu Chioncel,Emilia D'Elia,Hassan El-Tamimi,Gerasimos Filippatos,Nicolas Girerd,Loreena Hill,Ewa Jankowska,Kamlesh Khunti,Basil S Lewis,Brenda Moura,Offer Amir,Stefania Paolillo,Massimo Piepoli,Abdulla Shehab,Maggie Simpson,Hadi Skouri,Davide Stolfo,Carlo Gabriele Tocchetti,Cristiana Vitale,Maurizio Volterrani,Stephan von Haehling,Sven Wassmann,Mehmet Birhan Yilmaz,Juan Carlos Kaski,Dobromir Dobrev,Marco Metra,Giuseppe M C Rosano
Heart failure (HF) affects over 60 million individuals globally. Contemporary guideline-directed medical therapies (GDMT) reduce cardiovascular mortality and HF hospitalizations. However, medication non-adherence represents a critical barrier limiting real-world efficacy of GDMT. This scientific statement aims to provide a comprehensive framework for understanding, measuring, and addressing medication non-adherence in HF management across diverse healthcare settings. Addressing medication non-adherence requires systematic, multifaceted approaches targeting individual patient barriers while implementing system-level interventions. Polypills, digital monitoring platforms, enhanced patient education and empowerment, and multidisciplinary care models represent promising strategies to optimize therapeutic adherence and improve clinical outcomes in HF management.
{"title":"Adherence to guideline-directed medical treatments in heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Cardiovascular Pharmacotherapy.","authors":"Gianluigi Savarese,Felix Lindberg,Antonio Cannata,Marianna Adamo,Giuseppe Ambrosio,Pietro Ameri,Markus S Anker,Magnus Bäck,Antoni Bayes-Genis,Tuvia Ben Gal,Frieder Braunschweig,Ovidiu Chioncel,Emilia D'Elia,Hassan El-Tamimi,Gerasimos Filippatos,Nicolas Girerd,Loreena Hill,Ewa Jankowska,Kamlesh Khunti,Basil S Lewis,Brenda Moura,Offer Amir,Stefania Paolillo,Massimo Piepoli,Abdulla Shehab,Maggie Simpson,Hadi Skouri,Davide Stolfo,Carlo Gabriele Tocchetti,Cristiana Vitale,Maurizio Volterrani,Stephan von Haehling,Sven Wassmann,Mehmet Birhan Yilmaz,Juan Carlos Kaski,Dobromir Dobrev,Marco Metra,Giuseppe M C Rosano","doi":"10.1002/ejhf.70090","DOIUrl":"https://doi.org/10.1002/ejhf.70090","url":null,"abstract":"Heart failure (HF) affects over 60 million individuals globally. Contemporary guideline-directed medical therapies (GDMT) reduce cardiovascular mortality and HF hospitalizations. However, medication non-adherence represents a critical barrier limiting real-world efficacy of GDMT. This scientific statement aims to provide a comprehensive framework for understanding, measuring, and addressing medication non-adherence in HF management across diverse healthcare settings. Addressing medication non-adherence requires systematic, multifaceted approaches targeting individual patient barriers while implementing system-level interventions. Polypills, digital monitoring platforms, enhanced patient education and empowerment, and multidisciplinary care models represent promising strategies to optimize therapeutic adherence and improve clinical outcomes in HF management.","PeriodicalId":164,"journal":{"name":"European Journal of Heart Failure","volume":"4 1","pages":""},"PeriodicalIF":18.2,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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