Deprivation of available energy has been postulated to play a major role in the genesis of heart failure,1–3 and accumulating evidence points to the premise that changes in gene expression that alter energy metabolism weaken the heart muscle,4,5 reinforcing the logic of ameliorating energy substrates, and/or metabolism as a heart failure therapeutic. Reduced cardiac energy levels, in turn, influence a plethora of cardiac events, including free radical defense mechanisms which lower cardiomyocyte survivability,6 cardiac contractility,7 adverse remodelling and arrhythmogenic susceptibility.8 The heart is able to produce energy from a wide range of substrates and shifts continuously between sources, according to supply availability as controlled by exercise, nutritional status, or pathophysiological conditions. Therefore, the immediate cardiac capacity to produce energy and to adapt its metabolism to requirement changes is a crucial cardiac functional parameter. ATP is the direct source of energy for all energy-consuming reactions in the heart (pump function, Ca2+ re-uptake into the sarcoplasmic reticulum and maintenance of the sarcolemmal ion gradients). In the healthy adult heart, more than 70% of the energy required is covered by fatty acid oxidation in mitochondria, with the remaining 30% being accounted for by carbohydrate oxidation, mainly using glucose and ketone bodies as exogenous substrates.9–11 Under conditions of high ATP demand relative to ATP availability, the myocyte is able to recruit additional pathways or depend more heavily on alternative pathways for … *Corresponding author. Tel: +31 30 253 8900; fax: +31 30 253 9036. E-mail address : p.a.dacostamartins{at}umcutrecht.nl