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Metabolic Reprogramming in Heart Failure: From Energy Starvation to Therapeutic Targets
Mariam Meddeb1, Joseph R Goldenberg1, Sydney C Jenkin1
1Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
Current Treatment Options in Cardiovascular Medicine
|October 10, 2025
Summary
Heart failure is linked to metabolic issues like reduced energy reserves and mitochondrial problems. Therapies targeting metabolic reprogramming show promise for improving heart function, but further research is needed.
Area of Science:
- Cardiology
- Metabolic research
- Biochemistry
Background:
- Heart failure (HF) is characterized by significant metabolic dysfunction in cardiac and skeletal muscle.
- Key abnormalities include diminished myocardial energy reserves (lower PCr/ATP ratio), altered substrate utilization, and mitochondrial dysfunction.
- Recent advancements in studying cardiac metabolism have provided critical insights into these changes.
Purpose of the Study:
- To review current literature on metabolic abnormalities in heart failure.
- To propose therapeutic strategies for metabolic reprogramming to benefit the failing heart.
- To highlight areas for future research in heart failure metabolism.
Main Methods:
- Literature review of cardiac and skeletal muscle metabolism in heart failure.
- Analysis of non-invasive and invasive methods for studying cardiac metabolism.
- Evaluation of existing and emerging therapeutic strategies for metabolic intervention.
Main Results:
- Heart failure involves reduced energy reserves, altered substrate use, and mitochondrial issues.
- Therapeutic strategies focus on ketone and fatty acid utilization, mitochondrial enhancement, and gene activation for metabolic remodeling.
- Existing therapies like cardiac resynchronization therapy (CRT) and left ventricular assist devices (LVADs) induce metabolic reprogramming.
Conclusions:
- Metabolic reprogramming strategies require further investigation in heart failure.
- Future research must differentiate metabolic abnormalities in HFrEF and HFpEF.
- Investigating methods to study metabolic responses to therapies and the clinical impact of reprogramming is crucial.
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