Sudden death in patients with HFmrEF or HFpEF was preceded by worsening NYHA class, an 8-point decline in KCCQ-TSS, and rising NT-proBNP levels (1800 to 2000 pg/mL) in the 6 months prior.
RCT (n=6,001)
Yes
Are sudden deaths in patients with HFmrEF or HFpEF preceded by clinical deterioration in functional status, quality of life, and natriuretic peptide levels?
Sudden death in HFmrEF and HFpEF is preceded by modest worsening of symptoms, quality of life, and natriuretic peptides, indicating these events may not be entirely sudden.
Importance 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. Objective 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. Design, Setting, and Participants 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–B-type natriuretic peptide (NT-proBNP) were enrolled between September 14, 2020, and January 10, 2023. Data analysis was conducted in December 2025. Interventions Finerenone vs placebo. Main Outcomes and Measures 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. Results 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 approximately 2.3 to 2.4), worsening self-reported health status (an approximately 8-point decline in KCCQ-TSS), and a gradual rise in NT-proBNP levels (from approximately 1800 to 2000 pg/mL). In contrast, among patients who survived, NYHA class improved (from approximately 2.3 to 2.1), KCCQ-TSS increased (from approximately 68 to 77), and NT-proBNP levels declined (from approximately 800 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. Conclusions and Relevance 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. Trial Registration ClinicalTrials.gov Identifier: NCT04435626
“These trajectories may reflect heightened near-term vulnerability to death more broadly, which may help identify patients at increased overall risk rather than guide sudden death–specific preventive strategies.”
This post hoc analysis from a major clinical trial, published in JAMA Cardiology, provides insights into the clinical course of heart failure patients leading up to different modes of death. Understanding these trajectories can help in prognosticating and managing end-of-life care.
Lu et al. (2026) conducted an RCT in Heart failure with mildly reduced or preserved ejection fraction (HFmrEF or HFpEF) (n=6,001). Finerenone vs. Placebo was evaluated on Longitudinal trajectories of NYHA class, KCCQ-TSS, and NT-proBNP levels preceding sudden death. Sudden death in patients with HFmrEF or HFpEF was preceded by worsening NYHA class, an 8-point decline in KCCQ-TSS, and rising NT-proBNP levels (1800 to 2000 pg/mL) in the 6 months prior.