A comprehensive review of the bioenergetics of fatty acid and glucose metabolism in the healthy and failing heart in nondiabetic condition.

The function of the heart is defined by its ability to deliver adequate cardiac output to meet the requirements of the body both at rest and with exertion. To fill this role, the heart demonstrates an impressive capacity to tightly regulate energy generation and consumption. Energy production and transfer within cardiac myocytes primarily relies on the process of oxidative phosphorylation. In the failing heart, there is an imbalance between the work of the cardiac system and the energy required to generate this work. This presence of this mismatch has given rise to the concept known as the energy starvation theory. This concept encapsulates observations such as perturbed substrate consumption, insufficient energy transfer and ingestion, reduced substrate and oxygen availability, and diminished energy production in the failing heart. Diminished available cellular energy may further result from a reduction in the biosynthesis of mitochondria and their protein synthesis and from global cellular architectural disarray. In essence, the energy starvation theory posits that cardiac pump function declines due to a reduction in oxygen and substrate availability, and thus leads to a total body starvation of systemic energy. This novel cognitive framework has led to encouraging new directions in a "metabolic therapeutic approach" for the failing heart.