Myocardial Infarction The Prognostic Value of Serum Myoglobin in Patients With Non – ST-Segment Elevation Acute Coronary Syndromes Results From the TIMI 11 B and TACTICS-TIMI 18 Studies

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 g/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 g/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. (J Am Coll Cardiol 2002;40:238–44) © 2002 by the American College of Cardiology Foundation

[1]  C. Vassanelli,et al.  [Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban]. , 2001, Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology.

[2]  E. Antman,et al.  Myoglobin levels at 12 hours identify patients at low risk for 30-day mortality after thrombolysis in acute myocardial infarction: a Thrombolysis in Myocardial Infarction 10B substudy. , 2001, American heart journal.

[3]  V. Hasselblad,et al.  Benefit of Glycoprotein IIb/IIIa Inhibition in Patients With Acute Coronary Syndromes and Troponin T–Positive Status: The PARAGON-B Troponin T Substudy , 2001, Circulation.

[4]  L. Newby,et al.  Bedside Multimarker Testing for Risk Stratification in Chest Pain Units: The Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin, and Troponin I (CHECKMATE) Study , 2001, Circulation.

[5]  L. Wallentin,et al.  Comparison between strategies using creatine kinase-MB(mass), myoglobin, and troponin T in the early detection or exclusion of acute myocardial infarction in patients with chest pain and a nondiagnostic electrocardiogram. , 2000, The American journal of cardiology.

[6]  V. Hombach,et al.  Diagnostic and prognostic role of myoglobin in patients with suspected acute coronary syndrome. North-Württemberg Infarction Study (NOWIS) Group. , 2000, The American journal of cardiology.

[7]  E. Antman,et al.  Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy. , 2000, Journal of the American College of Cardiology.

[8]  R. Wilensky,et al.  Prospective Study Correlating Fibrinopeptide A, Troponin I, Myoglobin, and Myosin Light Chain Levels With Early and Late Ischemic Events in Consecutive Patients Presenting to the Emergency Department With Chest Pain , 2000, Circulation.

[9]  E. Antman,et al.  Very early risk stratification after thrombolytic therapy with a bedside myoglobin assay and the 12-lead electrocardiogram. , 2000, American heart journal.

[10]  J. W. Schaeffer,et al.  ACC/AHA guidelines for the management of patients with unstable angina and non–st-segment elevation myocardial infarction: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on the management of patients with unstable angina) , 2000 .

[11]  E. Antman,et al.  Clinical efficacy of three assays for cardiac troponin I for risk stratification in acute coronary syndromes: a Thrombolysis In Myocardial Infarction (TIMI) 11B Substudy. , 2000, Clinical chemistry.

[12]  G. Wagner,et al.  Very early diagnosis and risk stratification of patients admitted with suspected acute myocardial infarction by the combined evaluation of a single serum value of cardiac troponin-T, myoglobin, and creatine kinase MB(mass) , 2000, European heart journal.

[13]  E. Antman,et al.  Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial. , 1999, Circulation.

[14]  C. Heeschen,et al.  Angiographic findings in patients with refractory unstable angina according to troponin T status. , 1999, Circulation.

[15]  J. Zimmerman,et al.  Diagnostic marker cooperative study for the diagnosis of myocardial infarction. , 1999, Circulation.

[16]  E. Cook,et al.  Value of additional two-hour myoglobin for the diagnosis of myocardial infarction in the emergency department. , 1999, The American journal of cardiology.

[17]  K. Thygesen,et al.  Very early risk stratification using combined ECG and biochemical assessment in patients with unstable coronary artery disease (A thrombin inhibition in myocardial ischemia [TRIM] substudy). The TRIM Study Group. , 1998, Circulation.

[18]  R. Jesse,et al.  Use of the combination of myoglobin and CK-MB mass for the rapid diagnosis of acute myocardial infarction. , 1997, The American journal of emergency medicine.

[19]  R. D. de Winter,et al.  Value of myoglobin, troponin T, and CK-MBmass in ruling out an acute myocardial infarction in the emergency room. , 1995, Circulation.

[20]  A. Ellis,et al.  Cardiac and skeletal muscle myoglobin release after reperfusion of injured myocardium in dogs with systemic hypotension. , 1995, Circulation.

[21]  J. Mair,et al.  Different time courses of cardiac contractile proteins after acute myocardial infarction. , 1994, Clinica chimica acta; international journal of clinical chemistry.

[22]  A. R. Zaki Masud,et al.  Patterns of myoglobin release after reperfusion of injured myocardium. , 1985, Circulation.