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

Giancarlo Silvio Marenzi, Nicola Cosentino, Jasper Boeddinghaus, Mirella Trinei, Marco Giorgio, Valentina Milazzo, Marco Moltrasio, Daniela Maria 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 CipollaChristian Mueller, Antonio Bartorelli

Research output: Contribution to journalArticle

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

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Cytochromes c
Myocardial Infarction
Hospital Mortality
Confidence Intervals
Cardiac Myocytes
Serum
Odds Ratio
Troponin
ROC Curve
Necrosis
Mortality

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Diagnostic and Prognostic Utility of Circulating Cytochrome c in Acute Myocardial Infarction. / Marenzi, Giancarlo Silvio; Cosentino, Nicola; Boeddinghaus, Jasper; Trinei, Mirella; Giorgio, Marco; Milazzo, Valentina; Moltrasio, Marco; Cardinale, Daniela Maria; 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; Mueller, Christian; Bartorelli, Antonio.

In: Circulation Research, 04.11.2016.

Research output: Contribution to journalArticle

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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.",
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T1 - Diagnostic and Prognostic Utility of Circulating Cytochrome c in Acute Myocardial Infarction

AU - Marenzi, Giancarlo Silvio

AU - Cosentino, Nicola

AU - Boeddinghaus, Jasper

AU - Trinei, Mirella

AU - Giorgio, Marco

AU - Milazzo, Valentina

AU - Moltrasio, Marco

AU - Cardinale, Daniela Maria

AU - Sandri, Maria Teresa

AU - Veglia, Fabrizio

AU - Bonomi, Alice

AU - Kaech, Max

AU - Twerenbold, Raphael

AU - Nestelberger, Thomas

AU - Reichlin, Tobias

AU - Wildi, Karin

AU - Shrestha, Samyut

AU - Kohzuharov, Nikola

AU - Sabti, Zaid

AU - Cipolla, Carlo

AU - Mueller, Christian

AU - Bartorelli, Antonio

PY - 2016/11/4

Y1 - 2016/11/4

N2 - 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.

AB - 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.

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