Myocardial metabolic abnormalities and cardiac dysfunction

To sustain contractile function, the myocardium has a very high and continuous demand for ATP, which it generates from a variety of carbon sources, including fatty acids, glucose, ketone bodies, pyruvate, and lactate. In the healthy adult heart, most of the ATP is generated via mitochondrial oxidation of fatty acids (50-70 %), and the balance between fatty acid oxidation and other forms of ATP production, such as glucose oxidation and glycolysis, is tightly regulated. In fact, dysregulation or inflexibility of myocardial energy metabolism has been linked to a number of major cardiac diseases including myocardial hypertrophy, heart failure, ischemic heart disease, and obesity and diabetes mellitus-associated cardiomyopathy. Deranged cardiac energy metabolism and impaired cardiac energetics have been suggested to contribute to these pathophysiological states, rendering metabolic modulators an attractive option for the management of various forms of heart disease. This chapter summarizes our current understanding of the role of cardiac energy metabolism in the development and progression of heart failure, pressure overload-induced hypertrophy, and obesity-related cardiomyopathy. In addition, potential therapies to restore metabolic balance and efficiency in the heart and ameliorate cardiac dysfunction are outlined.