Metabolic Recovery of the Failing Heart: Emerging Therapeutic Options

Heart failure has mortality rates that parallel those of breast cancer. Current management strategies include neurohormonal blockade, rate control measures, natriuretic peptide preservation, implantation of mechanical assist devices, and heart transplantation. Despite these strategies, however, the failing myocardium remains energy depleted. New strategies to promote metabolic recovery are being developed to potentially augment current treatment guidelines. For example, an unexpected finding of our own studies showed that mechanical unloading with assist devices in advanced-stage heart failure restored metabolic flux. Unfortunately, at that point it is too late for myocardial recovery. Traditional metabolic therapies addressing hyperglycemia have had limited long-term outcome benefit. Now, new therapeutic options are emerging based on increased understanding of the molecular mechanisms underlying energy depletion. Metabolic cardiac imaging combined with laboratory diagnostics could guide the design of individual therapeutic strategies. To date, agents that show benefit in select individuals include mimetics that stimulate glucagon-like peptide-1, inhibitors of sodium-glucose cotransporter receptors, drugs that limit fatty acid oxidation, and hormonal therapy in select individuals. This review will summarize mechanisms and investigations related to these metabolic approaches to heart failure.