Igor F. Palacios, Michael A. Fifer, Xu Shi, Laurie A. Farrell, Hasmik Keshishian, Anthony Rosenzweig, Elaine Yang, Emerson Liu, Steven A. Carr, Murat Tasan, Robert E. Gerszten, Ru Wei, Vamsi K. Mootha, Gregory D. Lewis, Gabriel F. Berriz, Jiangyong Min, Oded Shaham, Terri Addona, Arvind Ramanathan, Aarti Asnani, Christian Baumgartner, Marcoli Cyrille, Patricia A. Lowry, Maryann E. Martinovic, Frederick P. Roth, and Marc S. Sabatine
Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We applied a mass spectrometry–based metabolite profiling platform to 36 patients undergoing alco-hol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned myo-cardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with spontaneous myocardial infarction (SMI) serving as negative and positive controls, respectively. We identified changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream con-tributors, and the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes after PMI in an initial derivation group and were validated in a second, independent group of PMI patients. A PMI-derived metabolic signature consisting of aconitic acid, hypoxanthine, trimethylamine N-oxide, and threonine differentiated patients with SMI from those undergoing diagnostic coronary angiogra-phy with high accuracy, and coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes. Our results identify a role for metabolic profiling in the early detection of myocardial injury and sug-gest that similar approaches may be used for detection or prediction of other disease states.