Metabolic Reprogramming in Heart Failure: From Energy Starvation to Therapeutic Targets.

Purpose of review: The goals of this review are to summarize the current literature regarding metabolic abnormalities in heart failure and propose therapies that can induce metabolic reprogramming to benefit the diseased heart.

Recent findings: Analysis of cardiac and skeletal muscle metabolism in heart failure has revealed several abnormalities including lower PCr/ATP ratio (indicating diminished myocardial energy reserves), altered substrate utilization, and mitochondrial abnormalities. Several advances in both non-invasive and invasive methods to studying cardiac metabolism have allowed recent key contributions to the field. Promising therapeutic strategies include shifting towards increased utilization of ketones and fatty acids, targeting mitochondrial biogenesis and function, and activation of genes that promote metabolic remodeling. Several current therapies lead to metabolic reprogramming, including both drug and device-based therapies such as cardiac resynchronization therapy (CRT) and left ventricular assist devices (LVADs).

Summary: Strategies to induce metabolic reprogramming in the diseased heart need further study. Future research should address differences in metabolic abnormalities in HFrEF and HFpEF, methods to study metabolic responses to therapies, and impact of metabolic reprogramming on clinical outcomes in heart failure.