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CLINICAL STUDY: MYOCARDIAL INFARCTION

The prognostic value of serum myoglobin in patients with non–ST-segment elevation acute coronary syndromes

Results from the TIMI 11B and TACTICS-TIMI 18 studies

James A. de Lemos, MD^*,*, David A. Morrow, MD, MPH^*, C. Michael Gibson, MD, MS, FACC^*, Sabina A. Murphy, MPH^*, Marc S. Sabatine, MD^*, Nader Rifai, PhD^||, Carolyn H. McCabe, BS^*, Elliott M. Antman, MD, FACC^*, Christopher P. Cannon, MD, FACC^* and Eugene Braunwald, MD, FACC^*

^* Thrombolysis In Myocardial Infarction (TIMI) Study Group, Boston, Massachusetts, USA
Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical School, Dallas, Texas, USA
Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Harvard Clinical Research Institute, Boston, Massachusetts, USA
^|| Children’s Hospital, Boston, Massachusetts, USA

Manuscript received December 17, 2001; revised manuscript received March 7, 2002, accepted April 18, 2002.

^* Reprint requests and correspondence: Dr. James A. de Lemos, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Room CS7.142, Dallas, Texas 75390-9047, USA.
james.delemos{at}utsouthwestern.edu

OBJECTIVES: The goal of this study was to define the prognostic value of serum myoglobin in patients with non–ST-elevation acute coronary syndromes (ACS).

BACKGROUND: While myoglobin is useful for the early diagnosis of myocardial infarction (MI), its role in the early risk-stratification of patients with ACS has not been established.

METHODS: Myoglobin, creatine kinase-MB subfraction (CK-MB) and troponin I (cTnI) were measured at randomization in 616 patients from the Thrombolysis In Myocardial Ischemia/Infarction (TIMI) 11B study and 1,841 patients from the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Therapy-Thrombolysis In Myocardial Ischemia/Infarction (TACTICS-TIMI) 18 study. The risks for death and nonfatal MI through six months of follow-up were compared between patients with and without myoglobin elevation (>110 µg/l) in each study and in a dataset combining all eligible patients from both studies (n = 2,457).

RESULTS: In a multivariate model adjusting for baseline characteristics, ST changes and CK-MB and cTnI levels, an elevated baseline myoglobin was associated with increased six-month mortality in TIMI 11B (adjusted odds ratio [OR] 2.9 [95% confidence interval {CI} 1.2 to 7.1]), TACTICS-TIMI 18 (adjusted OR 3.0 [95% CI 1.5 to 5.9]) and the combined dataset (adjusted OR 3.0 [95% CI 1.8 to 5.0]). In contrast, there was no significant association between myoglobin elevation and nonfatal MI (combined dataset adjusted OR 1.55, 95% CI 0.9 to 2.6). In TACTICS-TIMI 18, patients with versus those without myoglobin elevation were more likely to have an occluded culprit artery (28% vs. 10%; p < 0.0001) and visible thrombus (49% vs. 34%; p = 0.006) and less likely to have TIMI 3 flow (53% vs. 68%; p = 0.009).

CONCLUSIONS: A serum concentration of myoglobin above the MI detection threshold (>110 µg/l) is associated with an increased risk of six-month mortality, independent of baseline clinical characteristics, electrocardiographic changes and elevation in CK-MB and cTnI. These findings suggest that myoglobin may be a useful addition to cardiac biomarker panels for early risk-stratification in ACS.

Abbreviations and Acronyms   ACS   acute coronary syndrome   CHECKMATE   Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin and Troponin I study   CI   confidence interval   CK-MB   creatine kinase-MB subfraction   cTnI   cardiac troponin I   cTnT   cardiac troponin T   ECG   electrocardiogram/electrocardiographic   MI   myocardial infarction   OR   odds ratio   RR   relative risk   TACTICS-TIMI   Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Therapy-Thrombolysis In Myocardial Ischemia/Infarction   TIMI   Thrombolysis In Myocardial Ischemia/Infarction

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