Diagnostic and Prognostic Utility of Circulating Cytochrome c in Acute Myocardial Infarction. Issue 12 (9th December 2016)

• Record Type: Journal Article
• Authors: Marenzi, Giancarlo; Cosentino, Nicola; Boeddinghaus, Jasper; Trinei, Mirella; Giorgio, Marco; Milazzo, Valentina; Moltrasio, Marco; Cardinale, Daniela; Sandri, Maria Teresa; Veglia, Fabrizio; Bonomi, Alice; Kaech, Max; Twerenbold, Raphael; Nestelberger, Thomas; Reichlin, Tobias; Wildi, Karin; Shrestha, Samyut; Kohzuharov, Nikola; Sabti, Zaid; Cipolla, Carlo M.; Mueller, Christian; Bartorelli, Antonio L.
• Is Part Of: Circulation research. Volume 119:Issue 12(2016)
• Publication Date: 2016-12-09
• Subjects: acute myocardial infarction -- cardiac troponin -- cytochrome c -- mitochondrial dysfunction -- prognosis; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.116.309792
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : Rationale: : In contrast to cardiomyocyte necrosis, which can be quantified by cardiac troponin, 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 2 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 end point, and prognostic prediction of in-hospital mortality was the primary prognostic end point. Serum cytochrome c had no diagnostic utility for AMI (area under the receiver-operating characteristics curve 0.51; 95% confidence intervals 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 nondetectable cytochrome c (6% versus 1%; P <0.001). This result was mainly driven by the high mortality rate observed in ST-segment–elevation AMI patients with detectable cytochrome c, as compared with those with nondetectable cytochrome c (11% versus 1%; P <0.001). At multivariable analysis, cytochrome c remained a significant independent predictor of in-hospital mortality (odds ratio 3.0; 95% confidence interval 1.9–5.7; P <0.001), even after adjustment for major clinical confounders (odds ratio 4.01; 95% confidence interval 1.20–13.38; P =0.02). Conclusions: : Cytochrome c serum concentrations do not have diagnostic but substantial prognostic utility in AMI. Abstract : Supplemental Digital Content is available in the text.