Cardiac metabolism - A promising therapeutic target for heart failure

Abstract

Both heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) are associated with high morbidity and mortality. Although many established pharmacological interventions exist for HFrEF, hospitalization and death rates remain high, and for those with HFpEF (approximately half of all heart failure patients), there are no effective therapies. Recently, the role of impaired cardiac energetic status in heart failure has gained increasing recognition with the identification of reduced capacity for both fatty acid and carbohydrate oxidation, impaired function of the electron transport chain, reduced capacity to transfer ATP to the cytosol, and inefficient utilization of the energy produced. These nodes in the genesis of cardiac energetic impairment provide potential therapeutic targets, and there is promising data from recent experimental and early-phase clinical studies evaluating modulators such as carnitine palmitoyltransferase 1 inhibitors, partial fatty acid oxidation inhibitors and mitochondrial-targeted antioxidants. Metabolic modulation may provide significant symptomatic and prognostic benefit for patients suffering from heart failure above and beyond guideline-directed therapy, but further clinical trials are needed.

Keywords: Cardiac metabolism; Heart failure; Heart failure with preserved ejection fraction (HFpEF); Heart failure with reduced ejection fraction (HFrEF); Metabolic modulation.