Pub Date : 2026-02-01DOI: 10.1016/j.jchf.2025.102703
Henri Lu MD , Brian L. Claggett PhD , G. Michael Felker MD, MHS , John J.V. McMurray MD , John R. Teerlink MD , Riccardo M. Inciardi MD, PhD , Marco Metra MD , Stephen B. Heitner MD , Rafael Diaz MD , Fady Malik MD, PhD , Muthiah Vaduganathan MD, MPH , Scott D. Solomon MD
<div><h3>Background</h3><div>Older age is associated with a high prevalence of comorbidities and worse cardiovascular (CV) outcomes in patients with heart failure (HF) with reduced ejection fraction. Omecamtiv mecarbil, a selective cardiac myosin activator, exerts minimal effects on blood pressure and heart rate and has limited extracardiac activity, and thus it may be well-tolerated in older individuals. The safety profile and clinical benefits of omecamtiv mecarbil across the age spectrum remain uncertain.</div></div><div><h3>Objectives</h3><div>This study aims to assess CV outcomes, treatment response, and tolerability to omecamtiv mecarbil according to age in patients enrolled in the GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) trial.</div></div><div><h3>Methods</h3><div>GALACTIC-HF was a randomized, global, double-blind clinical trial testing omecamtiv mecarbil vs placebo in patients with symptomatic HF with reduced ejection fraction. Key eligibility criteria included an age between 18-85 years, elevated natriuretic peptides, and a left ventricular ejection fraction (LVEF) ≤35%. We examined the treatment effect of omecamtiv mecarbil vs placebo for the primary endpoint of CV death or first HF event (hospitalization or urgent visit for HF) in both the overall population and the severe HF subgroup (LVEF ≤30%, NYHA functional class III/IV, HF hospitalization within 6 months), as well as safety outcomes according to prespecified age groups (<65 or ≥65 years).</div></div><div><h3>Results</h3><div>A total of 8,232 patients (age 64.5 ± 11.4 years, 54.5% ≥65 years, 21% female) were included. The rate of the primary outcome was 21.4 per 100 patient years (py) in those <65 years of age and 28.8 per 100 py in those ≥65 years of age. The treatment effect of omecamtiv mecarbil for the primary outcome (HR: 0.92 [95% CI: 0.86-0.99]; <em>P =</em> 0.03) was consistent in age groups (<em>P</em><sub>interaction</sub> = 0.76) and irrespective of age as a continuous variable (<em>P</em><sub>interaction</sub> = 0.19, after adjusting for treatment interactions with known modifiers of the effects of omecamtiv mecarbil: LVEF and baseline atrial fibrillation status). In patients with severe HF, omecamtiv mecarbil significantly reduced the risk of the primary outcome in both patients <65 years of age (HR: 0.77 [95% CI: 0.64-0.92]) and those ≥65 years of age (HR: 0.83 [95% CI: 0.71-0.97]; <em>P</em><sub>interaction</sub> = 0.47). The safety profile of omecamtiv mecarbil was consistent irrespective of age (<em>P</em><sub>interaction</sub> > 0.05 for all).</div></div><div><h3>Conclusions</h3><div>In GALACTIC-HF, older individuals were well-represented and faced higher risks of CV events. Treatment with omecamtiv mecarbil was safe irrespective of age and reduced the risk of CV death or first HF event across the age spectrum, especially in those with severe HF. (Global Approach to Lowering Ad
{"title":"Efficacy and Safety of Omecamtiv Mecarbil in Heart Failure With Reduced Ejection Fraction According to Age","authors":"Henri Lu MD , Brian L. Claggett PhD , G. Michael Felker MD, MHS , John J.V. McMurray MD , John R. Teerlink MD , Riccardo M. Inciardi MD, PhD , Marco Metra MD , Stephen B. Heitner MD , Rafael Diaz MD , Fady Malik MD, PhD , Muthiah Vaduganathan MD, MPH , Scott D. Solomon MD","doi":"10.1016/j.jchf.2025.102703","DOIUrl":"10.1016/j.jchf.2025.102703","url":null,"abstract":"<div><h3>Background</h3><div>Older age is associated with a high prevalence of comorbidities and worse cardiovascular (CV) outcomes in patients with heart failure (HF) with reduced ejection fraction. Omecamtiv mecarbil, a selective cardiac myosin activator, exerts minimal effects on blood pressure and heart rate and has limited extracardiac activity, and thus it may be well-tolerated in older individuals. The safety profile and clinical benefits of omecamtiv mecarbil across the age spectrum remain uncertain.</div></div><div><h3>Objectives</h3><div>This study aims to assess CV outcomes, treatment response, and tolerability to omecamtiv mecarbil according to age in patients enrolled in the GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) trial.</div></div><div><h3>Methods</h3><div>GALACTIC-HF was a randomized, global, double-blind clinical trial testing omecamtiv mecarbil vs placebo in patients with symptomatic HF with reduced ejection fraction. Key eligibility criteria included an age between 18-85 years, elevated natriuretic peptides, and a left ventricular ejection fraction (LVEF) ≤35%. We examined the treatment effect of omecamtiv mecarbil vs placebo for the primary endpoint of CV death or first HF event (hospitalization or urgent visit for HF) in both the overall population and the severe HF subgroup (LVEF ≤30%, NYHA functional class III/IV, HF hospitalization within 6 months), as well as safety outcomes according to prespecified age groups (<65 or ≥65 years).</div></div><div><h3>Results</h3><div>A total of 8,232 patients (age 64.5 ± 11.4 years, 54.5% ≥65 years, 21% female) were included. The rate of the primary outcome was 21.4 per 100 patient years (py) in those <65 years of age and 28.8 per 100 py in those ≥65 years of age. The treatment effect of omecamtiv mecarbil for the primary outcome (HR: 0.92 [95% CI: 0.86-0.99]; <em>P =</em> 0.03) was consistent in age groups (<em>P</em><sub>interaction</sub> = 0.76) and irrespective of age as a continuous variable (<em>P</em><sub>interaction</sub> = 0.19, after adjusting for treatment interactions with known modifiers of the effects of omecamtiv mecarbil: LVEF and baseline atrial fibrillation status). In patients with severe HF, omecamtiv mecarbil significantly reduced the risk of the primary outcome in both patients <65 years of age (HR: 0.77 [95% CI: 0.64-0.92]) and those ≥65 years of age (HR: 0.83 [95% CI: 0.71-0.97]; <em>P</em><sub>interaction</sub> = 0.47). The safety profile of omecamtiv mecarbil was consistent irrespective of age (<em>P</em><sub>interaction</sub> > 0.05 for all).</div></div><div><h3>Conclusions</h3><div>In GALACTIC-HF, older individuals were well-represented and faced higher risks of CV events. Treatment with omecamtiv mecarbil was safe irrespective of age and reduced the risk of CV death or first HF event across the age spectrum, especially in those with severe HF. (Global Approach to Lowering Ad","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"14 2","pages":"Article 102703"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338757","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 : 2026-02-01DOI: 10.1016/j.jchf.2025.102680
Eiran Z. Gorodeski MD, MPH , Shashank Shekhar MD , Chantal ElAmm MD , Michelle M. Kittleson MD , Robert A. Montgomery MD
{"title":"The AHFTC Fellowship Match in an Era of Declining Interest","authors":"Eiran Z. Gorodeski MD, MPH , Shashank Shekhar MD , Chantal ElAmm MD , Michelle M. Kittleson MD , Robert A. Montgomery MD","doi":"10.1016/j.jchf.2025.102680","DOIUrl":"10.1016/j.jchf.2025.102680","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"14 2","pages":"Article 102680"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140319","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 : 2026-02-01DOI: 10.1016/j.jchf.2026.102936
Douglas L. Mann MD , Arthur M. Feldman MD, PhD , Mona Fiuzat PharmD , Chrisopher M. O’Connor MD , J. David Port PhD
{"title":"Michael R. Bristow, MD, PhD","authors":"Douglas L. Mann MD , Arthur M. Feldman MD, PhD , Mona Fiuzat PharmD , Chrisopher M. O’Connor MD , J. David Port PhD","doi":"10.1016/j.jchf.2026.102936","DOIUrl":"10.1016/j.jchf.2026.102936","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"14 2","pages":"Article 102936"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098684","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}
{"title":"Effects of GLP-1 RA Initiation in Patients With HFrEF and Implantable Cardiac Devices Divided for BMI Values","authors":"Celestino Sardu MD, MSc, PhD , Ferdinando Carlo Sasso MD , Raffaele Marfella MD, PhD","doi":"10.1016/j.jchf.2025.102839","DOIUrl":"10.1016/j.jchf.2025.102839","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"14 2","pages":"Article 102839"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098444","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 : 2026-01-29DOI: 10.1016/j.jchf.2026.102941
Wendy McCallum
{"title":"Navigating the Intersection of HFmrEF/HFpEF and CKD: High-Risk With Gaps in Evidence.","authors":"Wendy McCallum","doi":"10.1016/j.jchf.2026.102941","DOIUrl":"https://doi.org/10.1016/j.jchf.2026.102941","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"110 6 1","pages":"102941"},"PeriodicalIF":13.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073213","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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