The natriuretic peptide blind spot in obesity-related heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome in which obesity can influence both disease expression and diagnostic test performance. This editorial examines the clinical implications of low or apparently normal natriuretic peptide concentrations in obesity-related HFpEF. Published clinical and hemodynamic evidence indicates that some affected patients demonstrate pathological elevations in cardiac filling pressures, particularly during exercise, despite natriuretic peptide concentrations below conventional diagnostic thresholds. Although these patients may have less advanced structural disease and lower event rates than those with markedly elevated concentrations, they can still experience substantial functional limitation and worse outcomes than hemodynamically normal individuals. Reliance on fixed biomarker thresholds may therefore delay diagnosis and contribute to underrepresentation of this phenotype in clinical trials. Natriuretic peptides should remain central to HFpEF evaluation but should be interpreted in conjunction with the clinical phenotype, echocardiographic findings, validated probability scores, and selective exercise-based testing.