Abstract 1755: Metabolic Changes in Plasma Revealed by Planned Heart Attacks
Background: An emerging set of metabolic profiling tools enable the monitoring of hundreds of analytes in biological samples, and have raised the possibility of establishing metabolic signatures of myocardial injury.
Methods: We applied metabolic profiling to 36 patients undergoing alcohol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of “planned” myocardial infarction (MI). Serial samples of peripheral blood were obtained before and at 10, 60, 120, and 240 minutes and 24 hours after induced MI. In a subset of 13 patients, samples were obtained simultaneously from the coronary sinus. Patients undergoing elective diagnostic coronary angiography and patients with spontaneous MI served as negative and positive controls, respectively. Plasma was fractionated by liquid chromatography and measurement of metabolites was performed using a high-sensitivity electrospray triple quadrupole mass spectrometer under selected reaction monitoring conditions.
Results: We identified novel changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream contributors, as well as the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes following myocardial injury in an initial derivation group (n=20 patients, 7 metabolites with P<0.005 vs. baseline), and were validated in a second independent group of 16 planned MI patients (P<0.05 for 6 out of 7 metabolites). A metabolic signature derived from the PMI cohort, consisting of aconitic acid, carnitine, glyceraldehyde, hypoxanthine, metanephrine, trimethylamine-N-oxide and threonine, differentiated cases of spontaneous MI from controls with high accuracy (P=0.0002, C-statistic 0.84). Coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes.
Conclusion: This study identifies changes in circulating metabolites as soon as 10 minutes after myocardial injury, a time frame in which no currently used plasma biomarkers are elevated. Ultimately, metabolic markers may help early detection of disease and suggest measures designed to redress metabolic derangements.