van Veldhuisen DJ, Linssen GC, Jaarsma T, et al.
J Am Coll Cardiol. 2013;61:1498-506. doi: 10.1016/j.jacc.2012.12.044.

Background

Heart failure with preserved ejection fraction (HFPEF) is a large medical and epidemiological problem [1–5]. Mortality in HFPEF patients is roughly similar to that in HF patients with a reduced left ventricular ejection fraction (LVEF) [3,4]. Although survival has improved over the last 10 to 20 years in HF patients with reduced LVEF, this was not observed in HFPEF patients.  Although a recent meta-analysis showed that medical treatment may improve exercise capacity [6], none of the treatments was convincingly shown to improve outcome, and therefore none of these drugs has received a
recommendation for HFPEF in current HF guidelines [1,5,7]. The presence of HF in patients with HFPEF can be defined by using natriuretic peptides: B-type natriuretic peptide (BNP); or N-terminal pro–B-type natriuretic peptide (NT-proBNP). These biomarkers have been proven to be of value in the management of HF patients with reduced LVEF. These natriuretic peptides may also be used in HFPEF, both for diagnostic and for prognostic purposes [8–11].
The aim of this study was to study the prognostic value of B-type natriuretic peptide (BNP) in patients with heart failure with preserved ejection fraction (HFPEF), in comparison to that in patients with reduced left ventricular (LV) EF (≤40%). This was an 18-month prospective cohort analysis of patients (n = 615) with New York Heart Association (NYHA) functional class II-IV heart failure participating in the COACH (Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) trial. COACH was a randomized trial to evaluate the effect of two levels of a disease management program versus usual care. In this trial, patients were randomized before discharge at the end of a hospitalization for HF. A single BNP measurement was taken at this time. The primary outcome was a composite of hospitalization for HF or all-cause mortality.

Main results

• BNP levels were significantly higher in patients with reduced LVEF than in those with HFPEF (p < 0.001).
• Among patients with an LVEF >50% (n = 74), the mean BNP level was 256 pg/ml (112-598 pg/ml), compared to 534 pg/ml (275-1130 pg/ml) in those with an LVEF ≤20%.
• BNP was a strong predictor for outcome, both in the whole population, as well as in the two subgroups of patients with LVEF ≤40% and in those with LVEF >40%.

Conclusions

BNP levels in patients with HFPEF are lower than in those with reduced LVEF, but are still predictive of prognosis. These findings may have important implications in the management of HFPEF patients in everyday clinical practice and in the design of trials in HFPEF.

Editorial comment [12]

While limited by a small size (especially in the subset of patients with an LVEF ≤40%, which the authors defined as PEF), the current analysis indicates that the prognosis in patients with HFPEF is similar as in those with reduced LVEF, for a given BNP level. Although future research is needed and there are still no proven therapies for the growing problem of HFPEF, this analysis would at least suggest that BNP can be used to guide prognosis in everyday clinical practice and in conduct of clinical trials, irrespective of LVEF.

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