Requiem for a Heavyweight

T he development of rapid, automated, and accurate labo- ratory testing for creatine kinase MB (CK-MB) revolutionized the treatment of patients with acute cardiac events in the 1970s and 1980s. Elevations of CK-MB were never intended to be synonymous with myocardial infarction, only indicative of cardiac injury. 1 However, because of the relative insensitivity of measurements, increased concentrations occurred predominantly with larger insults such those associated with acute ischemic heart disease. For that reason, AMI was rarely diagnosed, assuming appropriate timing of the samples, in the absence of a CK-MB elevation. K-MB assays initially relied on the measurement of enzyme activity, but over time, improved accuracy and ease of use were established by the use of mass assays. Mass assays allowed earlier detection of abnormal values and improved both clinical sensitivity and specificity. However, mass assays unmasked an increased frequency of CK-MB elevations due primarily to skeletal muscle injury because of their increased sensitivity. 4 -6 Clinical use of the percent relative index was then initiated. This approach improved the specificity of elevations for cardiac muscle injury but was insensitive when concurrent cardiac injury and skeletal muscle injury were present because elevations from skeletal muscle often are of a large magnitude. 7-10 A large number of analytical confounds such as macrokinases and interfering substances also were substantial problems with these assays. Attempts to standardize assays 12 have been partially successful, but differences still exist between manufacturers and even between the same testing antibodies used on different analytical platforms (ie, small versus large automated instruments). A frequency of up to 20% "falsepositive" levels, thought to be due to skeletal muscle injury, was reported in patients with renal failure. This was only one of many conditions such as noncardiac surgery, chest trauma, asthma, pulmonary embolism, chronic and acute muscle disease, head trauma, hyperventilation, and hypothy-roidism in which CK-MB was elevated in the absence of cardiac injury. In some ways, analytical tribulations and the lack of cardiac specificity provided clinicians with more flexibility in their decision-making processes. Enough analytical and physiological reasons not related to cardiac injury were available that elevations of CK-MB in any given patient could be considered false positives if the physician did not believe the assay results fit the clinical presentation. It was clear that cardiac biomarkers with better specificity and sensitivity were needed.