Among patients with HFrEF who have initiated guideline-directed medical therapy, NT-proBNP may offer much greater prognostic value than LVEF, with even mildly to moderately elevated NT-proBNP levels portending meaningful incremental risk.
NT-proBNP had a much stronger association with composite outcome and greater discriminatory ability than LVEF in HFrEF patients on guideline-directed medical therapy.
Even mildly to moderately elevated NT-proBNP levels (125–1000 pg/mL) were associated with incremental risk of the composite outcome.
The study cohort consisted of 6168 patients with HFrEF who had both LVEF and NT-proBNP measurements approximately 9 months following diagnosis.
The median LVEF at study baseline was 36% and the median NT-proBNP was 2161 pg/mL among HFrEF patients approximately 9 months after diagnosis.
Few prior studies had directly compared the prognostic value of LVEF and NT-proBNP in HFrEF patients who have initiated guideline-directed medical therapy.
This research studied over 6,000 patients with heart failure with reduced ejection fraction (HFrEF) — a condition where the heart pumps less blood than normal — to understand which test better predicts serious outcomes like hospitalization or death. Two commonly used measurements were compared: the left ventricular ejection fraction (LVEF, a measure of how well the heart pumps, typically assessed by echocardiogram) and NT-proBNP (a blood protein released when the heart is under stress). Measurements were taken roughly 9 months after patients started standard heart failure medications. This research suggests that NT-proBNP was a far stronger predictor of hospitalization or death than LVEF in these patients. Specifically, NT-proBNP provided substantially better ability to distinguish between patients at high versus low risk, with a concordance index improvement of 0.129 over LVEF alone. Notably, even mildly to moderately elevated NT-proBNP levels (125–1000 pg/mL) were associated with meaningfully increased risk, suggesting that the threshold for concern may be lower than sometimes assumed. While both measurements provided some independent prognostic information, LVEF added only minimal value once NT-proBNP was already accounted for. These findings matter because they suggest that in patients already being treated for HFrEF, a blood test (NT-proBNP) may tell clinicians more about future risk than a cardiac imaging measurement (LVEF). This research suggests that ongoing monitoring of NT-proBNP levels — not just tracking whether the ejection fraction has improved — could be especially important for identifying patients who remain at high risk despite being on medications. This could potentially influence how clinicians prioritize follow-up testing and risk stratification in this patient population.
Kodur N, Gunsalus P, Milinovich A, Dalton J, Tang W. (2026). Combined Prognostic Value of Follow-Up Ejection Fraction and Natriuretic Peptide Measurements in Heart Failure With Reduced Ejection Fraction Following Initiation of Pharmacotherapy.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.125.047015