Abstract
Despite advances in treatment, chronic heart failure is still associated with significant morbidity and a poor prognosis. The scope for further advances based on additional neurohumoral blockade is small. Effective adjunctive therapies acting via a different cellular mechanism would, therefore, be attractive. Energetic impairment seems to contribute to the pathogenesis of heart failure. The findings from several studies have shown that the so-called metabolic agents could have potential as adjunctive therapies in heart failure. These agents cause a shift in the substrate used by the heart away from free fatty acids, the oxidation of which normally provides around 70% of the energy needed, towards glucose. The oxygen cost of energy generation is lessened when glucose is used as the substrate. In this review we aim to draw attention to the metabolic alteration in heart failure and we present evidence supporting the use of metabolic therapy in heart failure.
Key Points
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Emerging evidence shows that, irrespective of the etiology, an energetic impairment contributes to the pathogenesis of heart failure
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Patterns of substrate use in heart failure are complex and depend on species, cause, duration, underlying coronary artery disease, endothelial dysfunction, and the presence of genetic and other comorbidities
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Myocardial use of fatty acids costs more oxygen per unit of ATP generated than glucose
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Animal models and small-scale human studies suggest benefits with the use of agents that shift myocardial substrate use from free fatty acids towards glucose, but larger human studies are needed
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Michael Frenneaux has applied for a patent for the use of perhexiline therapy in chronic heart failure patients. The other authors declared they have no competing interests.
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Abozguia, K., Clarke, K., Lee, L. et al. Modification of myocardial substrate use as a therapy for heart failure. Nat Rev Cardiol 3, 490–498 (2006). https://doi.org/10.1038/ncpcardio0583
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DOI: https://doi.org/10.1038/ncpcardio0583
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