Modification of myocardial substrate utilisation: a new therapeutic paradigm in cardiovascular disease

Therapies that aim to modify cardiac substrate utilisation are designed to increase metabolic efficiency. Although the main energy supply for the heart is generally provided by the oxidation of fatty acids, the heart is a metabolic omnivore and able to consume glucose as well as lactate and amino acids in varying proportions. A shift from fatty acid oxidation to glucose oxidation leads to lower oxygen consumption per unit of ATP produced. This concept of reduced oxygen utilisation underlies the use of metabolic modulating agents to treat chronic stable angina. Furthermore, the model of an energy-starved heart now forms the basis for our understanding of both ischaemic and non-ischaemic heart failure. Potential alterations in substrate utilisation and thus myocardial efficiency underlie the use of metabolic agents in heart failure. This is achieved by either promoting glucose or reducing the utilisation of fatty acids. Such a shift results in a relatively greater production of ATP per unit of oxygen consumed. With an ongoing demand for treatment options in ischaemic heart disease and a growing epidemic of heart failure, new treatment modalities beyond contemporary therapy need consideration.