What does this research mean for the field?

In heart failure with preserved ejection fraction (HFpEF), fatty acid oxidation remains active or increased while glucose oxidation is impaired, indicating that therapies should focus on restoring metabolic flexibility rather than simply modulating fatty acid oxidation. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

April 19, 2025Open Access

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

Structured PICO

Population

44 studies identified from MEDLINE, Embase, and Web of Science databases examining cardiac energy metabolism in heart failure with preserved ejection fraction (HFpEF).

Intervention

Systematic review of experimental approaches and metabolic markers assessing fatty acid oxidation and glucose oxidation.

Outcome

Direction and role of fatty acid oxidation (FAO) and glucose oxidation in HFpEF disease progression.

This systematic review clarifies that in HFpEF, fatty acid oxidation is maintained or increased while glucose oxidation is impaired, suggesting therapeutic strategies should focus on restoring metabolic flexibility.

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.

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