{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T03:31:37Z","timestamp":1783999897829,"version":"3.55.0"},"reference-count":19,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Sudden death remains a leading cause of mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HF with preserved ejection fraction (HFpEF), but whether these events are preceded by clinical deterioration remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize clinical trajectories preceding sudden death in patients with HFmrEF or HFpEF and compare them with trajectories before other modes of death and survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This was a post hoc analysis of the Finerenone Trial to Investigate the Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) randomized clinical trial evaluating trajectories of functional status, patient-reported health status, and natriuretic peptide levels preceding adjudicated modes of death. This was a global, event-driven clinical trial. Patients with symptomatic HF, left ventricular EF of 40% or greater, New York Heart Association class (NYHA) II to IV, and elevated N-terminal pro\u2013B-type natriuretic peptide (NT-proBNP) were enrolled between September 14, 2020, and January 10, 2023. Data analysis was conducted in December 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Finerenone vs placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Longitudinal trajectories of NYHA class, Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS), and NT-proBNP levels preceding sudden death were compared with trajectories in survivors and those who died of HF-related, nonsudden cardiovascular, or noncardiovascular causes, using linear mixed-effects models with restricted cubic splines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Included in this analysis were 6001 patients (mean [SD] age, 72.0 [9.6] years; 3269 male [54%]). Over a median (IQR) follow-up of 2.7 (1.9-3.0) years, 215 sudden deaths occurred. In the 6 months before death, sudden death was preceded by a slight worsening in physician-assigned NYHA class (from\u2009approximately\u20092.3 to 2.4), worsening self-reported health status (an approximately\u20098-point decline in KCCQ-TSS), and a gradual rise in NT-proBNP levels (from\u2009approximately\u20091800 to 2000 pg\/mL). In contrast, among patients who survived, NYHA class improved (from\u2009approximately\u20092.3 to 2.1), KCCQ-TSS increased (from\u2009approximately\u200968 to 77), and NT-proBNP levels declined (from\u2009approximately\u2009800 to 650 pg\/mL) over the 18 months before the end of follow-up. Comparable patterns of deterioration to those preceding sudden death, often more pronounced, were observed before other modes of death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Results of this post hoc analysis of the FINEARTS-HF randomized clinical trial reveal that in this contemporary HFmrEF or HFpEF cohort, sudden death was preceded by modest worsening of symptoms, declining quality of life, and rising natriuretic peptide levels, suggesting many of these events may not have been entirely sudden. However, similar deterioration preceding other modes of death suggests limited specificity for sudden death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04435626?id=NCT04435626&amp;amp;amp;rank=1\">NCT04435626<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamacardio.2026.0682","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T19:30:18Z","timestamp":1774726218000},"page":"574","source":"Crossref","is-referenced-by-count":3,"title":["Biomarker, Functional Status, and Quality-of-Life Trajectories Before Modes of Death in Heart Failure"],"prefix":"10.1001","volume":"11","author":[{"given":"Henri","family":"Lu","sequence":"first","affiliation":[{"name":"Division of Cardiology, Lausanne University Hospital, University of Lausanne, Lausanne, Vaud, Switzerland"},{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Kosztin","sequence":"additional","affiliation":[{"name":"Semmelweis University, Heart and Vascular Center, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Fo\u00e0","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Heart Failure and Transplant Unit - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Pab\u00f3n","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay S.","family":"Desai","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pardeep S.","family":"Jhund","sequence":"additional","affiliation":[{"name":"University of Glasgow, Glasgow, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alasdair D.","family":"Henderson","sequence":"additional","affiliation":[{"name":"University of Glasgow, Glasgow, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela","family":"Merkely","sequence":"additional","affiliation":[{"name":"Semmelweis University, Heart and Vascular Center, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn S. P.","family":"Lam","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore & Duke-National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Senni","sequence":"additional","affiliation":[{"name":"University of Milano-Bicocca ASST Papa Giovanni XXIII Hospital, Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"University of Lorraine, Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaviana","family":"Amarante","sequence":"additional","affiliation":[{"name":"Cardiology and Nephrology Clinical Development, Bayer SA, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riitta","family":"Saarinen","sequence":"additional","affiliation":[{"name":"Bayer AG, Global Medical Affairs, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoriko","family":"De Sanctis","sequence":"additional","affiliation":[{"name":"Bayer U.S. LLC, Research & Development, Pharmaceuticals, Whippany, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Glasauer","sequence":"additional","affiliation":[{"name":"Bayer AG, Global Medical Affairs, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J. V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"University of Glasgow, Glasgow, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"16","key":"hoi260014r1","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1056\/NEJMoa2407107","article-title":"Finerenone in heart failure with mildly reduced or preserved ejection fraction.","volume":"391","author":"Solomon","year":"2024","journal-title":"N Engl J Med"},{"issue":"16","key":"hoi260014r2","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1056\/NEJMoa2107038","article-title":"Empagliflozin in heart failure with a preserved ejection fraction.","volume":"385","author":"Anker","year":"2021","journal-title":"N Engl J Med"},{"issue":"12","key":"hoi260014r3","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1056\/NEJMoa2306963","article-title":"Semaglutide in patients with heart failure with preserved ejection fraction and obesity.","volume":"389","author":"Kosiborod","year":"2023","journal-title":"N Engl J Med"},{"issue":"5","key":"hoi260014r4","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1056\/NEJMoa2410027","article-title":"Tirzepatide for heart failure with preserved ejection fraction and obesity.","volume":"392","author":"Packer","year":"2025","journal-title":"N Engl J Med"},{"issue":"7","key":"hoi260014r5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.123.012724","article-title":"Sudden cardiac death in patients with advanced heart failure and preserved ejection fraction.","volume":"17","author":"Suen","year":"2024","journal-title":"Circ Arrhythm Electrophysiol"},{"issue":"5","key":"hoi260014r6","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.jacc.2016.10.078","article-title":"Mode of death in heart failure with preserved ejection fraction.","volume":"69","author":"Vaduganathan","year":"2017","journal-title":"J Am Coll Cardiol"},{"issue":"5","key":"hoi260014r7","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.jacc.2025.05.061","article-title":"Optimizing the primary prevention of sudden cardiac death in patients with heart failure.","volume":"86","author":"Wallace","year":"2025","journal-title":"J Am Coll Cardiol"},{"issue":"5","key":"hoi260014r8","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.jchf.2020.03.002","article-title":"Effects of sacubitril\/valsartan on N-terminal pro-B-type natriuretic peptide in heart failure with preserved ejection fraction.","volume":"8","author":"Cunningham","year":"2020","journal-title":"JACC Heart Fail"},{"issue":"10","key":"hoi260014r9","doi-asserted-by":"publisher","first-page":"1892","DOI":"10.1002\/ejhf.2652","article-title":"Dapagliflozin and New York Heart Association functional class in heart failure with mildly reduced or preserved ejection fraction: the DELIVER trial.","volume":"24","author":"Ostrominski","year":"2022","journal-title":"Eur J Heart Fail"},{"issue":"2","key":"hoi260014r10","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.jacc.2024.09.023","article-title":"Effect of finerenone on the KCCQ in patients with HFmrEF\/HFpEF: a prespecified analysis of FINEARTS-HF.","volume":"85","author":"Yang","year":"2025","journal-title":"J Am Coll Cardiol"},{"issue":"7","key":"hoi260014r11","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1001\/jamacardio.2025.0860","article-title":"Mode of death in patients with heart failure with mildly reduced or preserved ejection fraction: the FINEARTS-HF randomized clinical trial.","volume":"10","author":"Desai","year":"2025","journal-title":"JAMA Cardiol"},{"issue":"6","key":"hoi260014r12","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1093\/eurjhf\/hft062","article-title":"How do patients with heart failure with preserved ejection fraction die?","volume":"15","author":"Chan","year":"2013","journal-title":"Eur J Heart Fail"},{"issue":"5","key":"hoi260014r13","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1002\/ejhf.3230","article-title":"Cause-specific death in heart failure across the ejection fraction spectrum: a comprehensive assessment of over 100?000 patients in the Swedish Heart Failure Registry.","volume":"26","author":"Settergren","year":"2024","journal-title":"Eur J Heart Fail"},{"issue":"11","key":"hoi260014r14","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1002\/ejhf.172","article-title":"A prediction model for sudden cardiac death in patients with heart failure and preserved ejection fraction.","volume":"16","author":"Adabag","year":"2014","journal-title":"Eur J Heart Fail"},{"issue":"8","key":"hoi260014r15","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1007\/s00392-020-01786-8","article-title":"Developing and validating models to predict sudden death and pump failure death in patients with heart failure and preserved ejection fraction.","volume":"110","author":"Shen","year":"2021","journal-title":"Clin Res Cardiol"},{"issue":"8","key":"hoi260014r16","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.jchf.2018.02.014","article-title":"Sudden death in heart failure with preserved ejection fraction: a competing risks analysis from the TOPCAT trial.","volume":"6","author":"Vaduganathan","year":"2018","journal-title":"JACC Heart Fail"},{"issue":"1","key":"hoi260014r17","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41572-024-00540-y","article-title":"Heart failure with preserved ejection fraction.","volume":"10","author":"Hamo","year":"2024","journal-title":"Nat Rev Dis Primers"},{"issue":"10","key":"hoi260014r18","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1002\/ejhf.1970","article-title":"Ventricular tachyarrhythmia detection by implantable loop recording in patients with heart failure and preserved ejection fraction: the VIP-HF study.","volume":"22","author":"van Veldhuisen","year":"2020","journal-title":"Eur J Heart Fail"},{"issue":"6","key":"hoi260014r19","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1007\/s10741-019-09804-2","article-title":"Sudden death in heart failure with preserved ejection fraction and beyond: an elusive target.","volume":"24","author":"Manolis","year":"2019","journal-title":"Heart Fail Rev"}],"container-title":["JAMA Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/articlepdf\/2847051\/jamacardiology_lu_2026_oi_260014_1780929858.4128.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:00:56Z","timestamp":1781103656000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/fullarticle\/2847051"}},"subtitle":["Post Hoc Analysis of the FINEARTS-HF Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamacardio.2026.0682","relation":{},"ISSN":["2380-6583"],"issn-type":[{"value":"2380-6583","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6,1]]}}}