Cardiac energy substrate utilization in heart failure with preserved ejection fraction: reconciling conflicting evidence on fatty acid and glucose metabolism

Abstract

Direct measurements reveal fatty acid oxidation remains active or increased in HFpEF hearts, whereas glucose oxidation becomes impaired, challenging previous assumptions. Apparent contradictions in HFpEF metabolism literature arise from methodological differences—studies using isolated mitochondria versus intact hearts. Evidence demonstrates fatty acid oxidation is maintained in HFpEF, with defects primarily in glucose oxidation. Successful therapeutic strategies should prioritize restoring metabolic flexibility rather than simply modulating fatty acid oxidation pathways.