Temporal Changes in Biomarkers, Functional Status, and Quality of Life Prior to Adverse Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction

BACKGROUND: Mapping clinical, biomarker, and diuretic dosing trajectories before adverse clinical outcomes in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) may inform population monitoring approaches. OBJECTIVES: The authors assessed temporal patterns of 2 biomarkers (N-terminal pro-B-type natriuretic peptide NT-proBNP and estimated glomerular filtration rate eGFR), physician assigned functional status (NYHA functional class), a patient-reported outcome (Kansas City Cardiomyopathy Questionnaire-Total Symptom Score KCCQ-TSS), and diuretic dosing leading up to a clinical event. METHODS: FINEARTS-HF was a double-blind, randomized clinical trial testing finerenone vs placebo in 6,001 patients with symptomatic HF and a left ventricular ejection fraction of ≥40%. Key variables including NT-proBNP, eGFR, NYHA functional class, KCCQ-TSS, and diuretic dosing (expressed as furosemide equivalents) were serially assessed until the occurrence of cardiovascular death, first HF event, or the end of the follow-up period. Each variable was plotted relative to the number of months before an event or the end of follow-up. Patients who experienced a clinical event were compared with a control population who remained alive and free of hospitalization during follow-up. RESULTS: ), and the NT-proBNP level increased by approximately 70% to 80%, in the 12 to 18 months leading up to an event; these markers remained relatively stable in the control group. NYHA functional class showed a sharp deterioration in the 6 to 9 months before an event, and KCCQ-TSS declined by approximately 6 points (from a mean of ∼68 to ∼62) during this period, reflecting worsening functional class and patient-reported symptoms, respectively. Finally, diuretic doses increased in the 6 months preceding the event, from ∼50 to ∼60 mg/day of furosemide equivalents. CONCLUSIONS: In a large HFmrEF/HFpEF trial population, clinically meaningful changes in readily available biomarkers, functional status, and patient-reported health status were observed in the months leading up to a clinical event. Monitoring these parameters may help identify patients at high risk for near-term adverse clinical events. (Finerenone Trial to Investigate the Efficacy and Safety Superior to Placebo in Patients With Heart Failure FINEARTS-HF; NCT04435626).