HFA-PEFF, BREATH2, and the challenges of HFpEF classification

The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains strongly dependent on contemporary diagnostic algorithms, which are largely consensus-based and heavily influenced by natriuretic peptide thresholds originally developed primarily for acute heart failure rule-out. In the analyzed study, patients were clinically stable, with normal ventricular filling pressures. These observations may suggest that contemporary HFpEF screening strategies predominantly identify a syndrome of exertional and mild biomarker abnormalities rather than a condition intrinsically prone to spontaneous episodes of acute decompensation with overt fluid overload. Importantly, recent evidence suggests patients hospitalized with preserved ejection fraction exhibit alternative identifiable causes of congestion. In this context, hospitalization-based HFpEF outcomes may themselves remain strongly influenced by natriuretic peptide-driven diagnosis rather than by presence of congestion, potentially complicating interpretation of the true prognostic significance of contemporary HFpEF scores.