Heart Failure With Preserved Ejection Fraction and Lower Natriuretic Peptide: Clinical Characteristics and Change in Natriuretic Peptide Levels

BACKGROUND: Recent heart failure (HF) guidelines emphasize the importance of recognizing patients with mild elevations in NT-proBNP (N-terminal pro-B-type natriuretic peptide). While NT-proBNP is a key biomarker for diagnosing HF and predicting outcomes, its levels are often lower than expected in HF with preserved ejection fraction. METHODS: Using data from the SUPPORT (Supplemental Benefit of an Angiotensin Receptor Blocker in Hypertensive Patients With Stable Heart Failure Using Olmesartan) trial, we examined the temporal changes in NT-proBNP and long-term outcomes in patients with HF with preserved ejection fraction (left ventricular ejection fraction ≥50%) categorized by NT-proBNP levels (≤55, 55-125, 125-300, and ≥300 pg/mL). RESULTS: Among 602 patients with HF with preserved ejection fraction, 335 (55.6%) had NT-proBNP <300 pg/mL (12.5% with ≤55, 18.1% with 55-125, and 25% with 125-300 pg/mL). Patients with NT-proBNP <300 pg/mL were younger and had higher body mass index, more ischemic heart disease, less cardiac remodeling, and lower risks of HF hospitalization or all-cause death compared with those with NT-proBNP ≥300 pg/mL. Over 3 years, 52 (15.5%) patients with NT-proBNP <300 pg/mL, including 40 with 125 to 300 pg/mL, experienced NT-proBNP increase to ≥300 pg/mL, accompanied by left ventricular end-systolic enlargement and left ventricular ejection fraction decline. Importantly, these patients had comparable risks of HF hospitalization or all-cause death as compared with those with persistently elevated NT-proBNP ≥300 pg/mL (adjusted hazard ratio, 1.08 [95% CI, 0.69-1.69]). CONCLUSIONS: More than half of patients with HF with preserved ejection fraction had NT-proBNP <300 pg/mL at baseline. Patients with mild elevations in NT-proBNP may progress to overt elevations over time, accompanied by cardiac deterioration and adverse outcomes.