In 231 heart failure patients with preserved or mildly reduced ejection fraction, a BNP level of 377 pg/mL or higher independently predicted worse outcomes regardless of how well the heart was pumping.
BNP ≥377 pg/mLThis cutoff significantly differentiated event-free survival (P<0.001) in heart failure patients with preserved ejection fraction, independent of LVEF and atrial fibrillation
What the researchers found
In 231 patients with heart failure and LVEF >40% (spanning HFmrEF and HFpEF categories), BNP levels were measured at hospital discharge:
- BNP levels were NOT significantly different across the three LVEF groups: HFmrEF median 195 pg/mL, HFpEF (LVEF 50-59%) median 242 pg/mL, and HFpEF (LVEF ≥60%) median 220 pg/mL (P=0.422)
- Despite similar BNP levels across groups, a BNP cutoff of ≥377 pg/mL significantly differentiated event-free survival (P<0.001)
- In multivariate Cox regression, BNP was independently associated with event-free survival after adjusting for LVEF, E/e' (a measure of heart stiffness), and concurrent atrial fibrillation
This means BNP provides prognostic information beyond what other standard heart failure measurements offer.
Why it matters
Heart failure with preserved ejection fraction (HFpEF) accounts for roughly half of all heart failure cases and is notoriously difficult to manage because the standard measure — how much blood the heart pumps per beat — looks relatively normal. This study confirms that BNP, a simple blood test, can identify which HFpEF patients are at highest risk for death or rehospitalization, even when other measurements look similar. This could help doctors make better treatment and follow-up decisions.
How the study worked
This was a multicenter, prospective, observational cohort study. Patients with heart failure and LVEF >40% at hospital discharge (n=231) had BNP levels, LVEF, E/e' (diastolic function marker), and atrial fibrillation status recorded. The composite endpoint was all-cause death and readmission due to heart failure. A BNP cutoff of 377 pg/mL was used for survival analysis. Multi-covariate Cox proportional hazards modeling assessed BNP's independent prognostic value after adjusting for LVEF, E/e', and atrial fibrillation.
What this study cannot tell us
The sample size of 231 is moderate for a prognostic study. The BNP cutoff of 377 pg/mL may not be generalizable to all populations — BNP levels are affected by age, sex, obesity, kidney function, and other factors. The study enrolled only patients with LVEF >40%, so findings do not apply to patients with severely reduced ejection fraction. BNP was measured once at discharge; serial measurements might provide additional prognostic value. The observational design cannot establish causation between BNP levels and outcomes.
How to read the evidence
This is a multicenter, prospective observational cohort study with 231 patients and a validated composite endpoint. The prospective design and multivariate adjustment strengthen the findings, but the moderate sample size and lack of external validation limit generalizability. Evidence level is moderate for a prognostic biomarker study.
When this study was published
Published in 2025, this study addresses the current clinical need for better prognostic tools in HFpEF, which remains one of the most challenging areas in cardiovascular medicine.
The bigger picture
BNP (B-type natriuretic peptide) is one of the most successful diagnostic peptides in all of medicine — it's already a cornerstone blood test for heart failure diagnosis and monitoring. This study extends its utility to prognostication in the challenging HFpEF population, where traditional measures like ejection fraction fail to adequately predict outcomes. As the heart failure population ages and HFpEF becomes more prevalent, having reliable prognostic tools becomes increasingly important for guiding therapy intensity and resource allocation.
Questions still open
- Would serial BNP measurements during outpatient follow-up provide even better prognostic information than a single discharge measurement?
- Should patients with HFpEF and BNP ≥377 pg/mL receive more aggressive treatment or closer follow-up?
- Does the 377 pg/mL cutoff hold across different racial, ethnic, and age groups?
Common questions
What is BNP and why is it important in heart failure?
What does 'preserved ejection fraction' mean, and why is it a problem?
Read the original research
Prognostic Value of B-Type Natriuretic Peptide Level in Patients With Heart Failure With a Higher Left Ventricular Ejection Fraction.
Circulation reports, 7(3), 191-197
Citation
Ohte, Nobuyuki; Kikuchi, Shohei; Iwahashi, Noriaki; Kinugasa, Yoshiharu; Dohi, Kaoru; Takase, Hiroyuki; Inoue, Katsuji; Okumura, Takahiro; Hachiya, Kenta; Sugiura, Emiyo; Kusunose, Kenya; Kitada, Shuichi; Seo, Yoshihiro. (2025). Prognostic Value of B-Type Natriuretic Peptide Level in Patients With Heart Failure With a Higher Left Ventricular Ejection Fraction.. Circulation reports, 7(3), 191-197. https://doi.org/10.1253/circrep.CR-24-0172