Point-of-Care Cardiac Enzyme Testing: Pushing the Envelope?
Abstract & Commentary
Source: McCord J, et al. Ninety-minute exclusion of acute myocardial infarction by use of quantitative point-of-care testing of myoglobin and troponin I. Circulation 2001;104: 1483-1488.
The diagnosis of acute myocardial infarction (AMI) in the emergency department (ED) continues to be a challenge and remains a major source of malpractice occurrences in our specialty. Nearly half of all patients with AMI present with nondiagnostic electrocardiograms (ECGs), and anywhere from 2% to 5% are mistakenly discharged from the ED.1 Serial cardiac marker testing, primarily creatine kinase with muscle and brain subunits (CK-MB) and, more recently, cardiac troponin I (cTnI) and troponin T over a period of 6-18 hours, has been the primary means of excluding the diagnosis of AMI. However, this strategy leads to prolonged ED stays and unnecessary hospitalizations of large numbers of patients.
In this industry-sponsored study, investigators studied the utility of a point-of-care (POC) bedside assay (Biosite Diagnostics) for CK-MB, cTnI, and myoglobin, measured on initial presentation and at 90 minutes, three hours, and nine hours after ED arrival in patients evaluated for possible AMI. Results were compared against the final diagnosis of AMI as determined by agreement between two cardiologists reviewing the entire medical record and standard laboratory serial CK-MB levels over nine hours. Physicians caring for patients were blinded as to the bedside testing results.
Overall, 817 patients were enrolled in the study during the five-month period (excluding patients with ECG findings that led to reperfusion therapy and those in whom a full nine hours of serial CK-MB levels were not obtained). Of this group, 66% had nondiagnostic ST-T wave findings and 3% had normal ECGs. The majority of patients (78%) were admitted to either a telemetry bed or observation unit. Ultimately, 65 were diagnosed with AMI.
The investigators analyzed their results utilizing receiver-operating characteristic (ROC) curves to determine optimal cutoff values, which were: myoglobin greater than 200, CK-MB greater than 6.0, and cTnI greater than 0.4 ng/mL. The combination of abnormal myoglobin or cTnI at presentation or 90 minutes had the highest sensitivity (96.7%) and negative predictive value (99.6%) for AMI. Fifty-five of the 65 AMI patients had abnormal myoglobin or cTnI on presentation; an additional eight patients had elevations at 90 minutes. Two AMI patients were not identified until the nine-hour CK-MB marker was obtained. The investigators note that POC testing results were more rapidly available to physicians than standard laboratory results (24 minutes vs 71 minutes).
The investigators conclude that bedside testing for myoglobin and cTnI during the first 90 minutes can rapidly and accurately exclude AMI in patients presenting to the ED.
Commentary by Theodore C. Chan, MD, FACEP
In theory, the use of multiple cardiac markers for AMI is attractive in that it combines the strengths of each marker (myoglobin’s early rise, high sensitivity, and low cardiac specificity; cTnI’s high specificity, prolonged elevation, and superior prognostic value; and the traditional CK-MB). This work, along with another recent study,2 suggests that a combination of markers can safely exclude AMI within 90 minutes of presentation.
However, a number of points must be kept in mind when considering this accelerated "rule-out." First, not all assays for these markers are equal. For example, troponin assays can measure a variety of different complex and free forms, thus affecting standardization and applicability. Second, while POC testing will undoubtedly improve turnaround times, significant amounts of staff time, space, and money are required to maintain these resources in the ED.
In this study, markers were used to predict the diagnosis of AMI, rather than clinical outcome. In fact, 11% of patients were diagnosed with unstable angina (rather than AMI), and it is unknown whether the rapid markers had any utility in predicting subsequent short-term cardiac events. Methodologically, the strength of the study is limited because abnormal cut-off values were not determined until after the data was analyzed.
It is interesting that the investigators found excellent utility with myoglobin, which has been a source of controversy in the emergency medicine literature. As the investigators point out, such utility may have resulted from the later presentation (median 4.3 hours) of patients. It also is interesting to note that there was such little utility for POC CK-MB when laboratory CK-MB was one of the factors used for the diagnosis of AMI. This finding continues to affirm the utility of other, newer cardiac markers, particularly troponin, recently incorporated into the American College of Cardiology and American Heart Association guidelines on acute coronary syndromes.3
1. Pope JH, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000;342:1163.
2. Ng SM, et al. Ninety-minute accelerated critical pathway for chest pain evaluation. Am J Cardiol 2001;88:611.
3. Braunwald E, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: Executive summary and recommendations. Circulation 2000;102:1193.
(Dr. Chan, Associate Clinical Professor of Medicine, Emergency Medicine, University of California, San Diego, is on the Editorial Board of Emergency Medicine Alert.)