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

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.

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).

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]).

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.