Heart failure with preserved ejection fraction in patients with normal natriuretic peptide levels is associated with increased morbidity and mortality

Heart failure (HF) with preserved ejection fraction (HFpEF) afflicts over half of all patients with HF, and there are few effective treatments. Patients with HFpEF share common haemodynamic abnormalities, defined by an elevated pulmonary arterial wedge pressure (PAWP).1–4 While many patients with HFpEF display an elevation in PAWP that is present at rest, a substantial proportion of patients has evidence of circulatory congestion exclusively during exercise. Such patients frequently exhibit normal or near-normal plasma natriuretic peptide (NP) levels.

A recent consensus document has proposed a new universal definition of HF, which requires elevation in NP levels or objective evidence of pulmonary or systemic congestion to meet diagnostic criteria for HF.5 This definition conflicts with prior studies showing that a substantial proportion of patients with HFpEF display unequivocal haemodynamic evidence of HF when evaluated invasively, despite the presence of normal NP levels.1,2,6 Multiple studies have shown that patients with HFpEF and elevated NP levels have an increased risk of adverse events, indicating its role in risk stratification.6–8 Although the presence of normal NP levels in some patients with HFpEF is recognized in the new European HF guidelines, no study has yet compared event rates in patients with HFpEF and normal NP levels to patients without HFpEF