Point-of-care testing (POCT) exists for the purpose of expediting medical decisions not possible without this objective laboratory information. Responsibility for triage of patients suspected of experiencing myocardial ischemia, and the initiation of treatment of such patients, cannot be adequately discharged without the basic information of cardiac marker status. The reality of the delay in performance of testing by the central laboratory, in most settings, is not optimal for the task of supporting the emergency room needs.1 The process from request to result in hand is too long and inconsistent to meet the needs as defined by the American College of Cardiology/American Heart Association Guideline2 for these conditions. By contrast, the Cardiac Status (Spectral Diagnostics, Toronto, Ontario, Canada) tests have three simple qualities that justify their use in the emergency room environment. They are: 1) simple, 2) rapid, and 3) clinically proven to be accurate. All three are requirements for any laboratory supervisor or medical director who is diligent in overseeing POCT outside the central laboratory, while being sensitive to meeting the clinical needs for rapid test results.
Publication of similar, and almost simultaneous, guidelines of the American College of Cardiology (ACC)2 and the European Society of Cardiology,3 and the revised international consensus redefinition of myocardial infarction (MI),4 establishes the central role of cardiac markers, particularly troponin, in the early triage and treatment of patients with the acute coronary syndromes (ACS). Further, the quantity of troponin at the time of triage is not considered critical. The presence or absence of this protein establishes the risk stratification. As stated in the redefinition: “any amount of myocardial damage, as detected by cardiac troponins, implies an impaired clinical outcome for the patient.”4 Directly relevant to the same issue, the ACC Guideline states, “Elevated levels of cTnT and cTnI convey prognostic information beyond that supplied by the clinical characteristics of the patient, the electrocardiogram (ECG) at presentation, and a predischarge exercise test.” Laboratory data is rarely acknowledged to be of such premier importance by clinical authorities. Laboratorians can be proud of the role that testing plays. There is no reference specifying the level of troponin and the guideline proceeds to state, “… elevated (troponin) concentrations identify those at an increased risk of death.”2 Again, no quantitation is specified. Both guidelines stress the value of the newer antiplatelet blocking agents and the new, low molecular weight heparins in instituting early treatment of these patients. This echoes the explicit point made in a noted review of these syndromes, “Use of an early, reliable, risk-stratification process may permit the appropriate and economical allocation of medical resources and the optimal outcomes for patients.”5
Properties of the Cardiac Status Tests
The tests are small, hand-held, disposable plastic devices measuring 3.5 by 1.5 by .5 inches. There is no instrument required, no calibration and costly recalibration, nor instrument malfunction to deal with in an emergency room setting. There is no commitment to a capital investment and long-term contract. The reading is a simple visual one, with a control band indicating internal integrity of the test device and adequate flow of sufficient applied sample. The test predictably provides data 24 hours a day, 7 days per week, and is not affected by short staffing in the laboratory, nights, weekends, or holidays in accordance with clinical need.
The tests are performed on whole blood, typically obtained in a heparinized vacutainer at the time an intravenous line is initiated. Two hundred microliters of blood are deposited on the open window. The red cells separate, the serum migrates, and a positive visible red line develops often within five minutes, if positive. A negative reading requires 15 minutes before final reading and disposal. It is informative to contrast this reality with the recently confirmed reporting of the inadequacy of stat testing procedures in a study involving data from a sample of 690 American laboratories. Steindel and Howanitz1 reported, “Half of these laboratories responded that 90% of potassium tests were ordered and reported in 69 minutes or less, whereas the turnaround time (TAT) for 90% of hemoglobin tests was 55 minutes or less.” The authors summarized their findings as follows, “Laboratory emergency department (ED) TATs have remained unchanged for almost a decade. Emergency department physicians are not satisfied with laboratory services.” While this study of simple, very rapid assays confirms that only 50% of the laboratories could meet a 60 minutes standard for these simple tests, requests for cardiac markers can be expected to be, and are, less optimally fulfilled. In a detailed report from a heart-centered hospital where the original cardiac emergency room (ER) concept was developed, a recent study contrasted the rapid Cardiac Status tests with conventional testing after optimizing the TAT with a cooperative, dedicated laboratory support effort. The median TAT achieved by the central laboratory was 117 minutes with the 25th to 75th percentiles ranging from 85 to 147 minutes. The rapid bedside test was reported in 15 minutes.6 This device clearly helps the laboratory by removing the pressure for interruption of work flow to perform stat testing on an instrument platform. In fact, it is the partner of the responsible laboratory professional concerned with optimizing medical care.
The key to the accuracy of the cardiac markers, as applied to chest pain triage in the emergency setting, is the ability to distinguish those patients at high risk from those at low risk. The troponin test is the key indicator and the one test with the greatest emphasis. Hamm et al.7 provided testimony of the accuracy of the Cardiac Status Troponin I bedside test (Spectral Diagnostics, Toronto, Ontario, Canada). In this study, focused on sequential chest pain patients who did not have ST elevation on the ECG, patients were followed up for subsequent development of MI or death following discharge. As reported by Hamm et al., virtually 100% separation of those at risk was achieved using this device. In fact, in combination with the ECG, no patient with a negative bedside troponin and a negative ECG experienced a MI or death for the subsequent 30-day period. This outcome is the true test of accuracy of a troponin assay. A further elaboration on the technical aspects of the test was later published by the same group.8
Because the appearance curve of troponin follows the myoglobin and CK-MB, should one wait several hours after arrival for testing? If so, then why would one need a rapid test performed on arrival of the patient? Hamm and Heeschen provide data to answer this question. They demonstrated that the test is indeed informative at the time of presentation in the majority of patients who ultimately prove to be positive for troponin. Of those patients who were eventually positive for troponin I, the Cardiac Status test was positive for troponin at the time of presentation, in 64%7 and 60%8 of cases. This reflects the reality that many patients initially present well after the onset of symptoms, and that the evolution of infarction is often a stuttering, intermittent process leading eventually to necrosis. Symptom timing of the infarction is unreliable so patients should be tested at the time of presentation, possibly the most valuable contribution of rapid POC troponin testing.
Is the test sensitive enough to detect minor myocardial damage, as identified in the high-risk unstable angina patients? Again, Hamm and Heeschen addressed this question, reporting positives in unstable angina patients of 36% and 38% respectively. This exceeds the usually expected positive rate of 25% to 30% in this group. Finally, one can understand from the studies by Hamm et al., that if patients with even lower levels of troponin had been present in their study, the outcome might have been predicted to be different. That is, more patients would have been expected to have subsequent cardiac events; however, they did not.
The tests are available as a solitary troponin-I test device or as a combination test, with myoglobin and creatine kinase-MB (CK-MB) in a single device (Fig.). Myoglobin remains valued by some authorities in the field, particularly for chest pain triage as it provides a marker of earlier appearance than troponin. It is cited in the ACC/AHA Guideline2 as an option for early diagnosis. The well-known negative predictive value of myoglobin is held by many to be its most valued contribution, because in appropriate circumstances, it can rule out MI. Creatine kinase-MB, while clearly inferior to troponin I in terms of sensitivity for smaller myocardial insults, shorter half-life following an infarction, and less cardiospecificity, remains valued particularly for indicating reinfarction/extension of an existing ischemical episode because of its shorter half life and more rapid clearance from the blood than troponin. An ongoing debate exists as to whether the CK-MB positive is of value in differentiating the smaller infarction (formerly minimal myocardial damage) from the conventional infarction associated with a larger volume of necrosis. Finally, clinicians often wish to build their experience with troponin testing in relation to their long experience with CK-MB.
1. Steindel SJ, Howanitz PJ. Physician satisfaction and emergency department laboratory test turnaround time. Arch Pathol Lab Med
2. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation MI. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol
3. Bertrand ME, Simoons ML, Fox KA, et al. Management of acute coronary syndromes: acute coronary syndromes without persistent ST segment elevation; recommendations of the Task Force of the European Society of Cardiology. Eur Heart J
4. Thygesen K, Alpert JS. Myocardial infarction redefined: a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. JACC
5. Yeghiazarians Y, Braunstein JB, Askari A, et al. Unstable angina pectoris. N Engl J Med
6. Christenson RH. Related Articles Biochemical markers and the era of troponin. Md Med
7. Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med
8. Heeschen C, Goldmann BU, Moeller RH, et al. Analytical performance and clinical application of a new rapid bedside assay for the detection of serum cardiac troponin I. Clin Chem