Prognostic Value of Natriuretic Peptide Levels in Heart Failure With Recovered Ejection Fraction

BACKGROUND: There are currently no robust clinical markers for assessing prognosis in patients with heart failure (HF) with recovered left ventricular ejection fraction (LVEF). This study sought to investigate whether NT-proBNP (N-terminal pro-B-type natriuretic peptide) measured at the time of LVEF recovery is an independent predictor of prognosis among patients with HF with recovered LVEF. METHODS: This retrospective cohort study (2009–2024) included 3935 patients with HF with recovered LVEF (previous LVEF of ≤40% with subsequent improvement to ≥50%) and available NT-proBNP data at the time of LVEF recovery. Patients were categorized into 7 different NT-proBNP groups, which were compared using Kaplan-Meier analysis and multivariable Cox regression to evaluate the outcome of LVEF relapse (decrease in LVEF by ≥10% to <50%) and the composite outcome of HF hospitalization or all-cause death. RESULTS: The median value of NT-proBNP at the time of LVEF recovery was 1341 pg/mL (interquartile range, 400–4207). The probability of remaining free from LVEF relapse and the composite outcome decreased across NT-proBNP groups. After multivariable adjustment, NT-proBNP was an independent predictor of both LVEF relapse and the composite outcome, with higher NT-proBNP levels associated with higher risk of both outcomes in a dose-response manner. Even near-normal NT-proBNP levels (125–299 pg/mL) were associated with poorer prognosis relative to normal levels (<125 pg/mL), with a 46% higher risk of LVEF relapse and 82% higher risk of the composite outcome. This relationship was consistent and similar across age, sex, atrial fibrillation status, and renal function, but was modified by body mass index, with higher body mass index associated with higher risk. Notably, NT-proBNP was predictive of the composite outcome even when patients sustained LVEF recovery without experiencing LVEF relapse. CONCLUSIONS: NT-proBNP is an independent and robust predictor of prognosis in patients with HF with recovered LVEF and may therefore be used to guide further optimization of pharmacotherapy.