Abstract 16632: Metabolomic Profiling in a Human Model of Myocardial Infarction Identifies Novel Early Biomarkers of Cellular Damage
Background: Clinical biomarkers for myocardial injury reflect enzyme or protein release from irreversibly damaged myocytes and are not reliably detected in blood until four hours after injury. We hypothesized that peripheral blood small molecules report on myocardial cellular damage prior to leak of these macromolecules.
Methods: From a study of 36 patients undergoing planned myocardial infarction (PMI) with alcohol septal ablation for hypertrophic cardiomyopathy, 15 were selected for this study. Extending prior studies with this model, quantitative mass spectrometry profiling of 15 amino acids and 45 acylcarnitines was performed on frozen plasma at baseline (immediately before PMI), 1 hour (1h) and 24 hours (24h) after onset of injury. Repeated measures analysis of variance of log transformed metabolites with Bonferroni correction (≤0.0008) was used.
Results: Metabolites showing the greatest changes were alanine, C2, C3 and C10:1 acylcarnitines (all p<0.0001), with different patterns of change. Alanine levels decreased at 1h, increasing to baseline after 24h (mean [SD] 464.2 μM [141.3], 340.2 μM [81.7], 469.4 μM [62.3], respectively). C2 levels did not change acutely but decreased after 24h (7.94 [3.13], 8.84 [3.98], 5.26 [1.96] μM). C3 decreased acutely, returning to baseline after 24h (0.39 [0.17], 0.25 [0.12], 0.42 [0.13] μM). C10:1 decreased linearly (0.15 [0.04], 0.14 [0.04], 0.09 [0.04] μM). Tyrosine, proline, histidine, phenylalanine, serine, C4/Ci4, C4-OH and C14:1-OH/C12:1-DC acylcarnitines (p=0.0008-0.0001) were also significant. Dicarboxylacylcarnitines (shown to predict cardiovascular events) did not change.
Conclusions: Using a unique human model of PMI, we have identified novel metabolic markers reporting on early myocardial injury in the blood. Alanine changes may represent glycolytic flux over the course of MI. C2 (acetyl carnitine) may reflect changes in fatty acid β-oxidation and substrate utilization and remodeling. C3 (propionyl carnitine) changes may reflect acute compensatory responses with increased myocardial utilization and anaplerotic shuttling to the TCA cycle. These markers could enable earlier detection of spontaneous MI, and merit further investigation in heterogeneous “real world” cohorts.
- © 2013 by American Heart Association, Inc.