Metabolic therapy for heart failure including diastolic heart failure

Cardiac energetic impairment is a feature of systolic heart failure irrespective of the underlying etiology, and the magnitude of this impairment is predictive of subsequent mortality. It is also a feature of other forms of heart muscle diseases including hypertrophic cardiomyopathy and heart failure with normal ejection fraction. While the adult heart normally uses predominantly free fatty acids to generate energy, this consumes more oxygen than the use of carbohydrate to generate energy. In the context of heart muscle disease the reduction in efficiency of fatty acid versus carbohydrate utilization may be substantial. This provides the rationale for the use of drugs that inhibit fatty acid utilization and increase carbohydrate utilization. These agents either prevent the uptake of long chain fatty acids into the mitochondria (eg, perhexiline) or inhibit fatty acid β-oxidation (eg, trimetazidine). Studies in patients with systolic heart failure have shown encouraging results with increased cardiac performance and exercise capacity with these agents.