Evidence based approach to practice guides and decision thresholds for cardiac markers

There is substantial evidence for use of CK-MB, myoglobin, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) for diagnosis of myocardial infarction (MI) and risk stratification of the acute coronary syndromes. Timing of specimen collection, patient population, and decision limits are important considerations. Serial CK-MB measurement must be considered a benchmark of cardiac markers. The National Heart Attack Alert Program (NHAAP) determined that high quality clinical trials show that serial CK-MB measurements are very accurate for diagnosis of MI and have large clinical impact. Meta-analysis of CK-MB mass for retrospective MI diagnosis yielded a clinical sensitivity of 96.8% and a specificity of 89.6% for sampling at 12-48 hours. Numerous studies of myoglobin have demonstrated a high negative predictive value and high sensitivity 2-6 hours after presentation. The NHAAP group, however, rated performance of myoglobin as modestly accurate with small clinical impact. cTnI has a clinical sensitivity and specificity for diagnosis of MI in the range of 90% and 97%, respectively. However decision limits for cTnI may differ by up to 10-fold for different assays, indicating need for standardization. Meta-analysis showed that cTnT had a sensitivity of 98.2% (CI: 97-99%) for diagnosis of MI with lower specificity due to detection of minor myocardial injury. Both cTnT and cTnI are more useful for stratifying risk in acute coronary syndrome patients than CK-MB mass. The predictive ability of both cTnT and cTnI is optimized by sampling > 6-12 hours after symptoms onset. But in unstable angina, the odds ratios for predicting outcomes of MI/short-term mortality with 12-24 hour sampling for cTnT was 2.7 the odds ratio for cTnI did not differ significantly at 4.2.