Diagnostic and Prognostic Utility of Circulating Cytochrome c in Acute Myocardial Infarction

RATIONALE:: In contrast to cardiomyocyte necrosis, which can be quantified by cardiac troponin (cTn), functional cardiomyocyte impairment, including mitochondrial dysfunction, has escaped clinical recognition in acute myocardial infarction (AMI) patients. OBJECTIVE:: To investigate the diagnostic accuracy for AMI and prognostic prediction of in-hospital mortality of cytochrome c. METHODS AND RESULTS:: We prospectively assessed cytochrome c serum levels at hospital presentation in two cohorts: a diagnostic cohort of patients presenting with suspected AMI, and a prognostic cohort of definite AMI patients. Diagnostic accuracy for AMI was the primary diagnostic endpoint, and prognostic prediction of in-hospital mortality was the primary prognostic endpoint. Serum cytochrome c had no diagnostic utility for AMI (area under the receiver-operating characteristics curve 0.51; 95% confidence intervals [CI] 0.44-0.58; P=0.76). Among 753 AMI patients in the prognostic cohort, cytochrome c was detectable in 280 (37%) patients. These patients had higher in-hospital mortality than patients with non-detectable cytochrome c (6% vs. 1%; P<0.001). This result was mainly driven by the high mortality rate observed in ST-elevation AMI patients with detectable cytochrome c, as compared to those with non-detectable cytochrome c (11% vs. 1%; P<0.001). At multivariable analysis, cytochrome c remained a significant independent predictor of in-hospital mortality (odds ratio 3.0; 95% CI 1.9-5.7; P<0.001), even after adjustment for major clinical confounders (odds ratio 4.01; 95% CI 1.20-13.38; P=0.02). CONCLUSIONS:: Cytochrome c serum concentrations do not have diagnostic, but substantial prognostic utility in AMI.