Metabolomic Profiling of Cardiac Substrate Utilization

T he astonishing observation that the human heart beats Ϸ100 000 times a day and cycles through up to 30 kg of ATP daily (the energy required to climb a Ϸ100-story building) vividly illustrates the pertinence of energy metabolism to both cardiac health and disease.1,2 A key determinant of the efficient energy generation capacity of the heart is the pattern of cardiac substrate utilization.3,4 Although studies, such as the seminal coronary sinus sampling observations made by Richard Bing and colleagues 5 that delineated the patterns of cardiac substrate metabolism, have informed our understanding of cardiac biology, 3,4 their greatest limitation derives from the small number of "biased" candidate metabolites they have surveyed.Metabolomics, which seeks to comprehensively analyze and dynamically quantify many of the metabolites in biological samples, may thus be regarded as the logical sequitur to traditional substrate studies.6 Metabolomic studies, ranging from the assessment of atrial tissue in atrial fibrillation 7 to peripheral blood and coronary sinus sampling in stress-induced cardiac ischemia 8 and myocardial infarction, 9 have accordingly already yielded insights into the metabolic sequelae of these disorders.10