Comparison of biomarker strategies for rapid rule out of myocardial infarction in the emergency department using ACC/ESC diagnostic criteria

Abstract

Objective: Creatine kinase MB isoenzyme (CK-MB) mass and rate of change of CK-MB have been proposed as superior to cardiac troponin measurement for very early exclusion of acute myocardial infarction (AMI). All three markers were examined prospectively in patients presenting to the Emergency Department (ED) for rule out of AMI. Methods: Consecutive admissions to the ED with undifferentiated chest pain were initially assessed clinically and by electrocardiography. A total of 786 patients (490 male, median age 52.5 years) considered at low risk of AMI had blood drawn on admission. If the first sample was less than 12 h from onset of chest pain, a second sample was then drawn at least 2 h later and at least 6 h from onset of chest pain. CK-MB mass was measured on the first sample and CK-MB mass and cardiac troponin T (cTnT) were measured on the second sample. Measurement of cTnT was using an Elecsys 2010 with the third generation assay (Roche Diagnostics, Lewes, UK). Assay coefficient of variation (CV) was 5.8% and 5.7% at 0.47 and 11.5 µg/L, respectively, with measuring range 0.01-25.0 µg/L; analytical sensitivity of 0.01 µg/L and functional sensitivity of 0.03 µg/L. CK-MB (mass) was measured by electrochemiluminesence using an Elecsys 2010 (Roche Diagnostics). The assay CV was 4.0% at 5.89 µg/L and 4.1% at 60.5 µg/L, with a detection limit of 0.1 µg/L and an upper measuring limit of 500 µg/L. Myocardial infarction was diagnosed if either sample had a CK-MB of more than 5 µg/L, if there was a change in CK-MB (∆CK-MB) of more than 1.5 µg/L or if the cTnT was more than 0.05 µg/L. When AMI was excluded, patients proceeded to stress electrocardiography and reattended 72 h from presentation for follow up phlebotomy for cTnT measurement. A final diagnosis of AMI was made according to American College of Cardiology/ European Society of Cardiology criteria using a cut-off of 0.05 μg/L cTnT in any of the samples. Diagnostic efficiency was compared by receiver operator characteristic (ROC) curve analysis with comparison of area under the curve (AUC) for four strategies: admission CK-MB measurement; 6-h post-pain CK-MB measurement; ∆CK-MB; and 6-h post-pain cTnT measurement. Results: On admission the AUC for CK-MB was 0.830 (95% confidence interval [CI] 0.757-0.904). At 6 h post pain the respective values were: CK-MB 0.939 (95% CI 0.889-0.988); -CK-MB 0.948 (95% CI 0.906-0.990); and cTnT 0.989 (95% CI 0.966-1.0). Conclusion: cTnT at 6 h has high diagnostic sensitivity for AMI and is superior to CK-MB mass and ∆CK-MB even using a low cut-off value.