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

We 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

Over a median 2.7-year follow-up period, 1,343 cardiovascular deaths or first HF events occurred. At baseline, the participants who experienced a clinical event had higher NT-proBNP values, lower eGFR, higher NYHA functional class, lower KCCQ-TSS, and higher diuretic doses compared with the control population. The eGFR declined by about 5 mL/min/1.73 m² (from a mean of ∼57 to ∼52 mL/min/1.73 m²), 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)