In patients with heart failure with mildly reduced or preserved ejection fraction, sudden death was preceded by modest worsening in functional status, symptom burden, and natriuretic peptide levels—patterns that were also observed before other modes of death, limiting their specificity for sudden death risk.
In a post hoc analysis of the FINEARTS-HF randomized clinical trial, researchers evaluated longitudinal changes in functional status, patient-reported health status, and biomarker levels preceding different modes of death. The analysis included 6,001 patients with symptomatic heart failure and left ventricular ejection fraction of 40% or greater, followed for a median of 2.7 years, during which 215 sudden deaths occurred.
Trajectories were assessed using repeated measures of New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS), and N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels, modeled with linear mixed-effects methods.
In the 6 months preceding sudden death, NYHA class worsened slightly from approximately 2.3 to 2.4, patient-reported symptom scores declined by about eight points, and natriuretic peptide levels increased from roughly 1,800 to 2,000 pg/mL.
By contrast, patients who remained alive showed improvement across all domains, including NYHA class decreasing from approximately 2.3 to 2.1, symptom scores increasing from about 68 to 77, and natriuretic peptide levels declining from approximately 800 to 650 pg/mL over 18 months.
Patterns preceding other causes of death were similar and, in some cases, more pronounced. Patients who experienced heart failure–related death showed greater changes in functional status, with NYHA class increasing from approximately 2.4 to 2.8, KCCQ-TSS decreasing from approximately 70 to 50 over 18 months, and NT-proBNP levels increasing to approximately 3,000 pg/mL.
Patients who experienced nonsudden cardiovascular death showed progressive changes across these measures that were generally consistent with those observed before heart failure–related death. Patients who experienced noncardiovascular death showed smaller changes in functional status and symptom scores, and NT-proBNP levels remained largely unchanged.
Sudden death accounts for approximately 25% to 30% of deaths in heart failure with preserved ejection fraction, and current guidelines do not recommend implantable cardioverter-defibrillators for primary prevention because of limitations in risk stratification and lack of demonstrated benefit.
In an accompanying editorial, patients who experienced sudden death were described as having worsening functional class, declining health status, and increasing natriuretic peptide levels before death, while patients who died of other cardiovascular causes showed similar patterns. “However, the nonspecific nature of these changes limits their immediate clinical actionability, particularly in guiding decisions about preventive therapies,” wrote Gregg C. Fonarow, MD, of the Ahmanson-UCLA Cardiomyopathy Center in the David Geffen School of Medicine at the University of California.
Limitations included the post hoc design, potential misclassification of deaths, limited measurement of NT-proBNP levels, and analyses that provided estimates at the population level rather than the individual level.
“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,” wrote lead study researcher Henri Lu, MD, of the Division of Cardiology at Lausanne University Hospital of the University of Lausanne, and colleagues.
Full disclosures can be found in the study. The FINEARTS-HF trial received sponsorship from Bayer AG. Gregg C. Fonarow, MD, reported receiving personal fees from multiple pharmaceutical and medical device companies, including Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer, with no additional disclosures reported.
The findings were presented at the American College of Cardiology 75th Annual Scientific Session & Expo.
Source: JAMA Original Investigation, Editor’s Note
