Muthiah Vaduganathan MD, MPH , Brian L. Claggett PhD , Jacob A. Udell MD , Akshay S. Desai MD, MPH , Pardeep S. Jhund MD, PhD , Alasdair D. Henderson PhD , James Lay-Flurrie MSc , Flaviana Amarante MD , Andrea Glasauer PhD , Carolyn S.P. Lam MD, PhD , Michele Senni MD , Sanjiv J. Shah MD , Adriaan A. Voors MD, PhD , Faiez Zannad MD, PhD , Bertram Pitt MD , John J.V. McMurray MD , Scott D. Solomon MD
{"title":"Blinded Withdrawal of Finerenone After Long-Term Treatment in the FINEARTS-HF Trial","authors":"Muthiah Vaduganathan MD, MPH , Brian L. Claggett PhD , Jacob A. Udell MD , Akshay S. Desai MD, MPH , Pardeep S. Jhund MD, PhD , Alasdair D. Henderson PhD , James Lay-Flurrie MSc , Flaviana Amarante MD , Andrea Glasauer PhD , Carolyn S.P. Lam MD, PhD , Michele Senni MD , Sanjiv J. Shah MD , Adriaan A. Voors MD, PhD , Faiez Zannad MD, PhD , Bertram Pitt MD , John J.V. McMurray MD , Scott D. Solomon MD","doi":"10.1016/j.jacc.2025.05.038","DOIUrl":"10.1016/j.jacc.2025.05.038","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"86 5","pages":"Pages 396-399"},"PeriodicalIF":21.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713702","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":"Audio Summary","authors":"","doi":"10.1016/S0735-1097(25)06989-X","DOIUrl":"10.1016/S0735-1097(25)06989-X","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"86 5","pages":"Page e47"},"PeriodicalIF":21.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713837","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":"Mapping the Journeys to and From Improved Ejection Fraction","authors":"Andrew S. Perry MD, Lynne W. Stevenson MD","doi":"10.1016/j.jacc.2025.06.027","DOIUrl":"10.1016/j.jacc.2025.06.027","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"86 5","pages":"Pages 351-353"},"PeriodicalIF":21.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713843","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}
Nicolai Wallace MD , Karren Wong MD , Taylor Desmarais MD , Jin Joo Park MD, PhD , David Krummen MD , Woo-Hyun Lim MD , Claudio Campagnari PhD , Avi Yagil PhD , Barry Greenberg MD
{"title":"Optimizing the Primary Prevention of Sudden Cardiac Death in Patients With Heart Failure","authors":"Nicolai Wallace MD , Karren Wong MD , Taylor Desmarais MD , Jin Joo Park MD, PhD , David Krummen MD , Woo-Hyun Lim MD , Claudio Campagnari PhD , Avi Yagil PhD , Barry Greenberg MD","doi":"10.1016/j.jacc.2025.05.061","DOIUrl":"10.1016/j.jacc.2025.05.061","url":null,"abstract":"<div><div>Implantable cardioverter-defibrillators (ICDs) protect patients from sudden cardiac death (SCD). Landmark trials demonstrating their efficacy for primary prevention in patients with heart failure (HF) used reduced left ventricular ejection fraction (LVEF) as a major inclusion criterion and current recommendations for ICD implantation rely on this variable in patient selection. However, contemporary medical management has reduced the risk of SCD in patients with reduced LVEF so that an increasingly large proportion of this population never requires the protection offered by the device. Although SCD is the major cause of cardiovascular mortality in HF patients with preserved LVEF, ICDs are not recommended for primary prevention in this subset of the population. Advances in patient management, diagnostic testing, and data processing over the past 30 years have made it apparent that recommendations for ICD use for primary prevention of SCD are no longer optimal. This review summarizes the declining incidence of SCD and reasons for the widening gap between risk of SCD and current guideline recommendations for use of ICDs in the HF population. It discusses limitations in our ability to predict risk of SCD that need to be addressed and the potential impact of ongoing clinical trials on recommendations for ICD use for primary prevention of SCD. Patient-related variables including those available from diagnostic tests that could be used to generate prediction models that more accurately identify magnitude of risk of SCD in individual patients are identified. The use of artificial intelligence processing of data from diagnostic tests to facilitate and standardize extraction of predictive variables and the use of machine learning algorithms for developing risk prediction models are discussed. The review concludes by describing a dynamic approach for generating novel risk prediction models that could better align risk of SCD with the benefits of ICD implantation in patients with HF and that could evolve over time as additional treatment strategies that alter risk of SCD are introduced in the future.</div></div>","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"86 5","pages":"Pages 374-395"},"PeriodicalIF":21.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713701","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}
João Pedro Ferreira MD, PhD , Francisco Vasques-Nóvoa MD , Francisca Saraiva PhD , Ana C. Oliveira MSc , Jorge Almeida MD , Ana Beatriz Batista MSc , Arsénio Barbosa MD , Ana Filipa Ferreira PhD , Cátia Costa MSc , Silvia O. Diaz PhD , Diogo Santos-Ferreira MD , Fernando Friões MD, PhD , Cândida Goncalves MSc , João Tiago Guimarães MD, PhD , Marta Leite MD , Pedro Marques MD , Joana Mascarenhas MD , Maria Inês Matos MD , Catarina Pereira MD , Pedro Rodrigues MD , Adelino Leite-Moreira MD, PhD
{"title":"Sodium-Glucose Cotransporter 2 Inhibitor With and Without an Aldosterone Antagonist for Heart Failure With Preserved Ejection Fraction","authors":"João Pedro Ferreira MD, PhD , Francisco Vasques-Nóvoa MD , Francisca Saraiva PhD , Ana C. Oliveira MSc , Jorge Almeida MD , Ana Beatriz Batista MSc , Arsénio Barbosa MD , Ana Filipa Ferreira PhD , Cátia Costa MSc , Silvia O. Diaz PhD , Diogo Santos-Ferreira MD , Fernando Friões MD, PhD , Cândida Goncalves MSc , João Tiago Guimarães MD, PhD , Marta Leite MD , Pedro Marques MD , Joana Mascarenhas MD , Maria Inês Matos MD , Catarina Pereira MD , Pedro Rodrigues MD , Adelino Leite-Moreira MD, PhD","doi":"10.1016/j.jacc.2025.05.033","DOIUrl":"10.1016/j.jacc.2025.05.033","url":null,"abstract":"<div><h3>Background</h3><div>Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists improved heart failure outcomes in heart failure with mildly reduced ejection fraction or heart failure with preserved ejection fraction; however, their combination was not tested in a randomized manner. Whether the SGLT2i/mineralocorticoid receptor antagonist combination offers benefits compared to SGLT2i alone requires dedicated trials.</div></div><div><h3>Objectives</h3><div>This study aims to compare the efficacy and safety of dapagliflozin/spironolactone combination vs dapagliflozin alone in heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction.</div></div><div><h3>Methods</h3><div>This was a prospective randomized open, blinded endpoint crossover trial. A sample size of 108 patients was powered to detect 0.15 <em>Log</em> N-terminal pro–B-type natriuretic peptide (NT-proBNP) difference between the dapagliflozin/spironolactone combination and dapagliflozin alone sequences study primary outcome. Each treatment sequence was given for 12 weeks.</div></div><div><h3>Results</h3><div>One hundred eight patients were randomized. The median age was 76 years (Q1-Q3: 71-81 years), 57% were women, estimated glomerular filtration rate (eGFR) 72 mL/min/1.73 m<sup>2</sup> (Q1-Q3: 49-89 mL/min/1.73 m<sup>2</sup>), potassium 4.3 mmol/L (Q1-Q3: 4.0-4.6 mmol/L), and 45% had diabetes. The median NT-proBNP was 746 pg/mL (Q1-Q3: 401-1,493 pg/mL) and median LogNT-proBNP 6.6 Log-units (Q1-Q3: 6.0-7.3 Log-units). Compared to dapagliflozin, dapagliflozin/spironolactone combination reduced <em>Log</em>NT-proBNP levels: −0.11 (95% CI: −0.22 to −0.01) <em>Log</em>-units (<em>P</em> = 0.035) corresponding to an 11% relative reduction and increased the odds of reaching ≥20% NT-proBNP reduction (OR: 2.27; 95% CI: 1.16-4.44; <em>P</em> = 0.016). Compared to dapagliflozin, dapagliflozin/spironolactone combination reduced systolic blood pressure (−5.2 mm Hg; 95% CI: −8.4 to −2.0 mm Hg), reduced <em>Log</em>urinary-albumin-to-creatinine ratio (−0.32 <em>Log</em>; 95% CI: −0.54 to −0.11 <em>Log</em>) decreased eGFR (−6.4 mL/min/1.73 m<sup>2</sup>; 95% CI: −8.3 to −4.4 mL/min/1.73 m<sup>2</sup>), and increased serum potassium (+0.32 mmol/L; 95% CI: 0.23-0.41 mmol/L) and the frequency of serum potassium (>5.5 mmol/L: 5 [4.8%] vs 1 [0.9%]).</div></div><div><h3>Conclusions</h3><div>Dapagliflozin/spironolactone combination reduced NT-proBNP more than dapagliflozin. A greater eGFR decline and potassium increase was observed with dapagliflozin/spironolactone combination (SOGALDI-PEF [Dapagliflozin With or Without Spironolactone for HFpEF]; <span><span>NCT05676684</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"86 5","pages":"Pages 320-333"},"PeriodicalIF":21.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713840","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}
Harlan M. Krumholz MD, SM (Editor-in-Chief, JACC; Harold H. Hines, Jr Professor)
{"title":"Heart Failure in Practice","authors":"Harlan M. Krumholz MD, SM (Editor-in-Chief, JACC; Harold H. Hines, Jr Professor)","doi":"10.1016/j.jacc.2025.06.028","DOIUrl":"10.1016/j.jacc.2025.06.028","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"86 5","pages":"Pages 317-319"},"PeriodicalIF":21.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713839","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}
Muthiah Vaduganathan MD, MPH , Brendon L. Neuen MBBS(Hons), MSc(Oxon), PhD
{"title":"Combining SGLT2i and MRAs in Heart Failure","authors":"Muthiah Vaduganathan MD, MPH , Brendon L. Neuen MBBS(Hons), MSc(Oxon), PhD","doi":"10.1016/j.jacc.2025.06.029","DOIUrl":"10.1016/j.jacc.2025.06.029","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"86 5","pages":"Pages 334-337"},"PeriodicalIF":21.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713841","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}
Francesco Fioretti MD , Jeffrey M. Testani MD, MTR , Maria Clarissa Tio MD, MPH , Bertram Pitt MD , Javed Butler MD, MPH, MBA
{"title":"Aldosterone and Aldosterone Modulation in Cardio-Kidney Diseases","authors":"Francesco Fioretti MD , Jeffrey M. Testani MD, MTR , Maria Clarissa Tio MD, MPH , Bertram Pitt MD , Javed Butler MD, MPH, MBA","doi":"10.1016/j.jacc.2025.06.012","DOIUrl":"10.1016/j.jacc.2025.06.012","url":null,"abstract":"<div><div>Chronic renin-angiotensin-aldosterone system activation and excess aldosterone exert detrimental effects on the heart and the kidneys via contributing to inflammation, fibrosis, and dysfunction in the myocardium, vasculature, and the kidneys. These effects are purported to be through genomic mineralocorticoid receptor (MR)–mediated, nongenomic MR-dependent, and nongenomic non-MR dependent actions. Steroidal and nonsteroidal mineralocorticoid receptor antagonists (MRA) counteract the effects of aldosterone in heart failure (HF) and in chronic kidney disease (CKD), blocking, at least partially, both genomic and nongenomic MR-mediated effects. Because both hyperkalemia and excess aldosterone are associated with progression of CKD and HF, and MRA therapy is associated with elevations in aldosterone levels, patients on MRA therapy may remain at a high residual risk for poor outcomes even on MRA therapy. Although observational studies and trials suggest compensatory neurohormonal activation in patients treated with renin-angiotensin-aldosterone system inhibitors, its potential association with worse outcomes and clinical significance is complex and context-dependent. Further studies are needed to better clarify the clinical implications of these biological effects in patients with cardio-kidney diseases. Partial agonists of the MR and directly attenuating aldosterone production using selective aldosterone synthase inhibitors is an emerging approach for patients with HF, CKD, and uncontrolled and resistant arterial hypertension that requires prospective trials. This review sought to describe the role of aldosterone in HF and CKD and the role of steroidal and nonsteroidal MRA, partial agonists of the MR, and aldosterone synthase inhibitors in cardio-kidney diseases.</div></div>","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"86 5","pages":"Pages 354-373"},"PeriodicalIF":21.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713700","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}
Kyung H. Min MD , Alan S. Go MD , Keane Lee MD , Rishi V. Parikh MPH , Kate M. Horiuchi MPH , Andrew P. Ambrosy MD , Thida C. Tan MPH , Kishan Srikanth MD , Steven A. Hamilton MD , Jana Svetlichnaya MD , Scott D. Solomon MD , Riccardo M. Inciardi MD , Orly Vardeny PharmD, MS , Elena Vasti MD , Alexander T. Sandhu MD , Ivy A. Ku MD , Sirtaz Adatya MD , Ankeet S. Bhatt MD, MBA, ScM
{"title":"Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure With Improved Ejection Fraction","authors":"Kyung H. Min MD , Alan S. Go MD , Keane Lee MD , Rishi V. Parikh MPH , Kate M. Horiuchi MPH , Andrew P. Ambrosy MD , Thida C. Tan MPH , Kishan Srikanth MD , Steven A. Hamilton MD , Jana Svetlichnaya MD , Scott D. Solomon MD , Riccardo M. Inciardi MD , Orly Vardeny PharmD, MS , Elena Vasti MD , Alexander T. Sandhu MD , Ivy A. Ku MD , Sirtaz Adatya MD , Ankeet S. Bhatt MD, MBA, ScM","doi":"10.1016/j.jacc.2025.05.040","DOIUrl":"10.1016/j.jacc.2025.05.040","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of heart failure with improved ejection fraction (HFimpEF) is anticipated to increase with the availability and implementation of novel pharmacotherapy for heart failure with reduced ejection fraction (HFrEF). However, there are limited data on contemporary epidemiology, management, and outcomes for this clinical entity.</div></div><div><h3>Objectives</h3><div>The aim of this study was to describe epidemiology, guideline-directed medical therapy (GDMT), and outcomes among patients with HFimpEF across a large, diverse, multisite integrated health care delivery system.</div></div><div><h3>Methods</h3><div>Patients who were diagnosed with incident HFrEF between January 2013 and December 2022 across the Kaiser Permanente Northern California integrated health care delivery system were identified. Rates of incident HFimpEF, defined as HFrEF with a follow-up ejection fraction >40% and with >10% absolute left ventricular ejection fraction improvement within 12 months of incident HFrEF diagnosis, were identified. GDMT was examined at the time of incident HFrEF and HFimpEF and in the year following HFimpEF. Rates of worsening heart failure events and death were examined and compared among those with HFimpEF vs persistent HFrEF.</div></div><div><h3>Results</h3><div>In total, 28,292 patients with newly diagnosed HFrEF (mean left ventricular ejection fraction 31.1% ± 7.4%) were identified, of whom 8,656 (30.6%) experienced HFimpEF within 12 months. Use of GDMT marginally decreased in most medication categories after incident HFimpEF during the study period. Rates of worsening heart failure were 17.4 per 100 person-years (95% CI: 16.9-18.0 per 100 person-years) among patients with HFimpEF vs 34.1 per 100 person-years (95% CI: 33.5-34.6 per 100 person-years) among patients with persistent HFrEF (HR: 0.58; 95% CI: 0.55-0.61 per 100 person-years). Rates of death were 5.7 per 100 person-years (95% CI: 5.4-6.0 per 100 person-years) and 11.0 per 100 person-years (95% CI: 10.7-11.3 per 100 person-years) among patients with HFimpEF and those with persistent HFrEF, respectively (HR: 0.52; 95% CI: 0.49-0.56). Withdrawal of GDMT was modestly associated with greater clinical risk.</div></div><div><h3>Conclusions</h3><div>A significant percentage of patients with HFrEF experience improvement in ejection fraction, transitioning to HFimpEF, yet remain at significant clinical risk. Further research is needed to evaluate the impact of sustained GDMT adherence and therapeutic optimization on outcomes in patients with HFimpEF.</div></div>","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"86 5","pages":"Pages 338-350"},"PeriodicalIF":21.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713842","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}