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Diagnostic and Prognostic Utility of Circulating Cytochrome c in Acute Myocardial Infarction
Giancarlo Marenzi1, Nicola Cosentino2, Jasper Boeddinghaus2
1From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.). giancarlo.marenzi@ccfm.it.
Insights
Serum cytochrome c levels are not useful for diagnosing acute myocardial infarction (AMI). However, detectable cytochrome c in AMI patients indicates a higher risk of in-hospital mortality, serving as a significant prognostic marker.
Area of Science:
- Biochemistry
- Cardiology
- Clinical Medicine
Background:
- Cardiomyocyte necrosis in acute myocardial infarction (AMI) is measurable via cardiac troponin.
- Functional cardiomyocyte impairment, including mitochondrial dysfunction, remains clinically unassessed in AMI patients.
Purpose of the Study:
- To evaluate the diagnostic accuracy of serum cytochrome c for AMI.
- To determine the prognostic value of serum cytochrome c for predicting in-hospital mortality in AMI patients.
Main Methods:
- Prospective assessment of serum cytochrome c levels in two cohorts: suspected AMI and confirmed AMI patients.
- Analysis of diagnostic accuracy using receiver-operating characteristics curves.
- Evaluation of in-hospital mortality prediction in a cohort of 753 AMI patients.
Main Results:
- Serum cytochrome c showed no diagnostic utility for AMI (AUC 0.51, P=0.76).
- Detectable cytochrome c in 37% of AMI patients was associated with significantly higher in-hospital mortality (6% vs 1%, P<0.001).
- This association was particularly strong in ST-segment-elevation AMI patients (11% vs 1%, P<0.001) and remained an independent predictor of mortality (OR 3.0-4.0, P<0.001-0.02).
Conclusions:
- Serum cytochrome c lacks diagnostic value for acute myocardial infarction.
- Serum cytochrome c possesses substantial prognostic utility for predicting in-hospital mortality in AMI patients.
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.
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