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

Giancarlo Marenzi, Nicola Cosentino, Jasper Boeddinghaus, Mirella Trinei, Marco Giorgio, Valentina Milazzo, Marco Moltrasio, Daniela Cardinale, Maria Teresa Sandri, Fabrizio Veglia, Alice Bonomi, Max Kaech, Raphael Twerenbold, Thomas Nestelberger, Tobias Reichlin, Karin Wildi, Samyut Shrestha, Nikola Kohzuharov, Zaid Sabti, Carlo M. CipollaChristian Mueller, Antonio L. Bartorelli

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalCirculation Research
DOIs
Publication statusAccepted/In press - Nov 4 2016

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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