Key result
Both HFpEF and HFrEF share impaired metabolic flexibility and mitochondrial dysfunction driving cardiac energy deficits.
Why the study?
To review current concepts regarding bioenergetic decline and mitochondrial dysfunction in heart failure.
This narrative review highlights how loss of cardiac metabolic flexibility and mitochondrial bioenergetic decline drive both HFpEF and HFrEF, outlining emerging metabolically targeted therapeutic strategies.
Answers are grounded in this paper and cite their sources.
Metabolic therapies in HF should not yet change practice; leaves open whether phenotype-specific bioenergetic targeting improves clinical outcomes in prospective trials.
Objectives We will review current concepts regarding bioenergetic decline in heart failure (HF). In the heart, the high energy demand must be met by continuous ATP generation. Cardiac energetic machinery orchestrates the ATP production by using oxidation of multiple energetic substrates including fatty acids (FA), glucose, amino acids and ketone bodies. The normal heart is metabolically flexible and able to use different energetic fuels during physiologic or pathologic circumstances to better match the energy demand. Mitochondria have critical role in maintaining cardiac metabolic flexibility. Methods We analyzed the scientific literature pertinent to HF and mitochondrial dysfunction. Results The general consent is that metabolic flexibility is lost in HF with either preserved or reduced ejection fraction (HFpEF and HFrEF, respectively). The prototype of HFpEF is the metabolic heart disease that is characterized by increased reliance on FA oxidation for ATP production and decreased glucose oxidation, while HFrEF presents a decreased FA oxidation. Both types of HF are associated with a decline in mitochondrial function leading to increased oxidative stress, abnormalities in the redox status and energy deficit. Conclusion Current research is committed to find novel metabolically targeted therapeutic approaches to improve energetic metabolism and alleviate HF progression.
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M. Rosca (2021) conducted a review in Heart Failure (HFpEF and HFrEF). Metabolically and mitochondrially targeted therapeutic approaches (e.g., methylene blue, coenzyme Q10, idebenone, substrate preference modulators) was evaluated. Both HFpEF and HFrEF exhibit loss of cardiac metabolic flexibility and mitochondrial dysfunction leading to oxidative stress, redox abnormalities, and energy deficit.
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