Laboratory assessment of myocardial damage: which test is best?

For many years , the test pane l for d i agnos ing myocardial infarction was easy to remember: creatine kinase (CK), lactate dehydrogenase (LD), and their respect ive i soenzymes . A combina t ion of total enzyme activity plus fractionation by electrophoresis provided the physician everything needed to make the diagnosis in most cases. Even as LD came under assault and was relegated to the cases in which CK and its MB isoenzyme (CK-MB) were nondiagnostic, this test panel retained its supremacy, with sensitivity and specificity well above 90% in most published reports. CK-MB mass is now routinely measured by immunoassay, which further has improved the availability, accuracy, and precision of this test. The impressive performance of CK, LD, and their isoenzymes did not stop investigators from searching for even better markers of myocardia l damage . Ischemic heart cells release a variety of enzymes and proteins that can be measured in peripheral blood. During the past decade, a number of new analytes have been studied, and their performance has been documented in laboratory and clinical journals. The list includes myoglobin, CK isoforms, myosin light chains, troponin T, and troponin I. Most of these are now marketed commercially. Before offering one or more of the new tests as a clinical service, the obvious question to ask is, "Does it outperform CK-MB? " The ideal marker of cardiac damage should have very high diagnost ic sensit ivity and specificity. Sensitivity is not a major concern, because virtually all episodes of myocardial necrosis can be detected by serial sampling of venous blood and measurement of an appropriate enzyme or protein. However, specificity is a problem, because the standard markers are not restricted to the heart. CK-MB is present at a low concentration in skeletal muscle, and rhabdomyolysis can elevate CK-MB into the abnormal range. A CK-MB index (CK-MB activity or mass divided by total CK activity) has been introduced to correct for skeletal muscle injury, but its value can be misleading in cases in which heart and skeletal muscle damage coexist (eg, cardiac surgery). An increase in serum LD isoenzyme 1 or the LD1:2 ratio is characteristic of myocardial damage, but hemolysis and renal cortical necrosis also can generate this result. The most exciting development in the field of cardiac markers has been the introduction of the troponins, T and I. The troponin complex consists of three subunits, troponin T (TnT), troponin I (Tnl), and troponin C (TnC), that regulate the interaction of actin and myosin filaments during muscular contraction. Both TnT and Tnl have three isoforms, one of which is specific to the heart. Immunoassays for both cardiac-specific isoforms have been developed and tested in a variety of clinical situations. Under normal conditions, these proteins are present at very low concentrations in the circulation. Following myocardial damage, TnT and Tnl are elevated within 3 to 12 hours and achieve concentrations of 5to 50-fold above the upper reference limit. Their values may remain elevated for a week or more, and their cardiospecificity ensures that skeletal muscle damage will not interfere with interpretation of the results. At last, the perfect diagnostic test for a heart attack.