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Point-of-Care Testing for Cardiac Markers: Has the Time Come?

Section Editor(s): Wu, Alan H. B. PhD

Focus on: Cardiac Markers

Symposium Editor

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About the Editor: Alan H.B. Wu, PhD is Director, Clinical Chemistry, Hartford Hospital, Hartford; and Professor of Laboratory Medicine, University of Connecticut, Farmington, Connecticut.

The incidence of coronary artery disease (CAD) has declined over the past two decades due to a more refined understanding of risk factors, improvements in diagnostic tools, and the development and use of better therapeutic agents and surgical interventions. However, heart disease is still the leading cause of morbidity and mortality in the western world. In the United States alone, about 8 million patients present to the emergency department (ED) each year with acute chest pain. Approximately 2 million patients will have a diagnosis of acute coronary syndromes (acute myocardial infarction (AMI) or unstable angina). The financial impact of this volume of patients on the nation's economy is enormous.

The diagnosis of AMI has been historically defined by the World Health Organization as requiring the presence of two of the following: a clinical history of chest pain, specific electrocardiographic (ECG) changes such as the presence of ST-segment elevations, and increased activities in cardiac enzymes.1 The development of new cardiac markers such as myoglobin, and in particular, cardiac troponin, has led to a redefinition of myocardial infarction. A joint committee of the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) concluded that in the context of cardiac ischemia, an AMI is defined by an increase in cardiac troponin or creatine kinase-MB (CK-MB) isoenzyme above the 99th percentile of the normal range, defined from blood collected from a healthy population. 2 Because most cardiac troponin assays do not have the sensitivity to detect troponin in normal blood, a more practical cutpoint has been suggested as the troponin concentration which exhibits a 10% within-run assay precision.3

As these markers are now the critical element for the diagnosis of the non-ST-segment AMI, the turnaround time (TAT) for reporting results of cardiac markers has become an increasingly important issue. The demand for shorter TATs is also the result of changing practices in the triaging of patients who present to the emergency department with chest pain. Due to cost constraints, EDs are under pressure to rapidly evaluate chest pain patients, to discharge those with noncardiac etiologies, and to triage others with acute cardiac problems to the appropriate level of care. Thus, many hospitals have created a rapid assessment area within the ED known as chest pain centers, where there is an accelerated protocol for the assessment of likelihood for cardiovascular risk. 4 Important diagnostic tools in these units include the continuous 12-lead ECG monitoring, and frequent collection and testing for serum cardiac markers to rule out AMI. Once an AMI is ruled out, the presence of active cardiac disease is evaluated with provocative procedures such as the stress test or nuclear imaging. Optimum use of ED bed space requires fast turnaround time for reporting of cardiac marker tests and a commitment of ED physicians to act on these results in real time.

Clinical practice guidelines have been published for the target turnaround time for results of biomarkers. The National Academy of Clinical Biochemistry (NACB) 5 and the International Federation of Clinical Chemistry (IFCC) 6 recommended a 60-minute TAT from the collection of blood to the reporting of results. The American Heart Association (AHA)/ACC also recommended a TAT of 60 minutes, but stated that a 30-minute TAT was preferable. 7 Although there are studies that demonstrate that implementation of point-of-care testing (POCT) can be successful in substantially reducing the TAT for results, these guidelines were prepared in the absence of evidence that lowering TATs improves clinical outcomes such as morbidity and mortality, and financial outcomes such as reductions in the ED, hospital length of stay, or overall hospital expenses. Nevertheless, physician attitudes are often the drivers for laboratory testing policies, and it is likely that the majority of ED physicians and cardiologists will continue to apply pressure to the clinical laboratory to reduce TATs. It is unlikely that the central laboratory can consistently deliver TATs for cardiac markers within the 30- to 60-minute time frame, even if the laboratory is connected to the ED with a pneumatic tube. Thus the NACB has recommended that for laboratories unable to meet TAT goals, POCT for cardiac markers is a more realistic option. Implementation of POCT within the central laboratory would obviate the need for sample centrifugation, as the specimens are tested in whole blood. Testing in the ED unit may be the most effective, as it also reduces the time and effort needed to transport the sample.

There are several remaining questions that must be addressed by each laboratory and ED before the implementation of POCT for cardiac markers. Currently, there is no assay standardization for myoglobin or cTnI, and no standardization between central laboratory platforms and POCT. Although a reference material for CK-MB mass has been validated, and is available, 8 it is not used by all manufacturers of CK-MB reagents. Thus if a cardiologist wishes to trend results of cardiac markers beginning with the ED sample, it will difficult, and in some cases impossible, to mix results of tests performed at the point of care (POC) versus the central laboratory. Due to cost constraints, it is unlikely that a laboratory will choose to perform all cardiac marker testing at the POC (including routine testing of admitted patients), unless the laboratory's cardiac marker testing volume is low. One way to overcome this problem; however, is to apply slope and intercept correction factors obtained from linear regression analysis between the two tests, to normalize results. This approach may be effective for CK-MB and myoglobin, as biases between commercial assays are largely due to the use of different reference standards. Unfortunately, this will not completely correct results for troponin I, as the discordant results are due to the absence of a uniform reference material and differences in specificities of commercial antibodies toward the different troponin forms that are released into blood (i.e., free, binary, and ternary complexes). 9 In this case, a better approach would be to repeat samples collected, and POC tested from the ED, and to report both under their respective methodologies (and reference intervals) in the final laboratory record. It is likely that ED samples, which are negative for troponin I, need not be repeated by the central laboratory. The lack of assay standardization is not an issue for troponin T, as there is only one manufacturer of POC and central laboratory assay tests. However, it would not be prudent to mix results of cardiac troponin T and I within the same patient, as this would add yet another variable to the biases of data.

A second question is whether quantitative testing is needed for POCT. If the central laboratory is to repeat POCT results at a later time in a central laboratory, as described above, a quantitative result at the POC may be unnecessary, and clinical decisions can be made on the basis of the qualitative result. A more important issue; however, is the sensitivity and precision at the cutoff concentration of qualitative versus quantitative assays. A qualitative test may not have the same degree of precision and discrimination between negative and positive result, and may be subject to visual endpoint biases versus an objective quantitative result. Similarly, a quantitative POCT assay may have lower precision than the corresponding automated central laboratory test. In light of new ESC/ACC guidelines emphasizing the need for detecting very minor myocardial damage, it is fair to state that all troponin assays (POC and laboratory-based) need improvements in analytical sensitivity and precision. This will especially pose a challenge for manufacturers of POC testing devices.

A third question is the frequency of blood collections. Most chest pain centers collect 2 to 3 blood samples beginning at patient presentation, and up to 6 to 8 hours after presentation. 10 Serial blood testing is a hallmark for diagnosis of AMI under any international criteria. Recent studies have suggested that AMI can be ruled out using a very aggressive strategy of testing at presentation and only 90 minutes after presentation.11 If fully implemented, this approach will lead to substantial reductions in ED operating expenses. However, the clinical trials are preliminary, and this triaging strategy has not been endorsed by cardiology societies yet.

The final question is the number of markers that is appropriate for testing ED patients with chest pain. As summarized in a recent editorial, 12 there is a consensus by the NACB, IFCC, ESC, ACC, and AHA that for institutions who have an aggressive early triaging strategy, at least two cardiac markers are needed; an early and a late marker. Myoglobin and troponin (T or I) are the best markers to date for these purposes, respectively. However, due to inherent specificity limitations, there is ongoing research to find a better early marker to replace myoglobin. The evidence that a multimarker strategy is superior to a single marker strategy with regards to early diagnosis and risk stratification of chest pain patients was provided by the CHECKMATE trial of 1005 patients from six chest pain units. 13 While there was substantial differences in the multimarker strategy versus single marker testing for these outcomes, there were minor differences between the 2- (cTnI and CK-MB) versus the 3-marker strategy (cTnI, CK-MB, and myoglobin).

The accompanying papers summarize the design and performance of commercial POCT assays, and address many of the continuing issues raised above.

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1. World Health Organization. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Nomenclature and criteria for diagnosis of ischemical heart disease. Circulation 1979;59:607-609.
2. The Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial infarction redefined - a consensus document of the joint ESC/ACC committee for the redefinition of myocardial infarction. J Am Col Card 2000;36:959-969.
3. Jaffe AS, Ravkilde J, Roberts R, et al. It's time for a change to a troponin standard. Circulation 2000; 102: 1216-1220.
4. Zalenski RJ, Selker HP, Cannon CP, et al. National heart attack alert program position paper: chest pain centers and programs for the evaluation of acute cardiac ischemia. Ann Emerg Med 2000; 35: 462-471.
5. Wu AH, Apple FS, Gibler WB, et al. National Academy of Clinical Biochemistry standards of laboratory practice: recommendations for the use of cardiac markers in coronary artery diseases. Clin Chem 1999; 45: 1104-1121.
6. Panteghini M, Apple FS, Christenson RH, et al. Proposals from IFCC committee on standardization of markers of cardiac damage (C-SMCD): recommendations on use of biochemical markers of cardiac damage in acute coronary syndromes. Scan J Clin Lab Invest 1999; 59 (suppl): 103-112.
7. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. 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 2000; 36: 970-1062.
8. Christenson RH, Vaidya H, Landt Y, et al. Standardization of creatine kinase-MB (CK-MB) mass assays: the use of recombinant CK-MB as a reference material. Clin Chem 1999; 45: 1414-1423.
9. Wu AHB, Feng YJ, Moore R, et al. Characterization of cardiac troponin subunit release into serum following acute myocardial infarction, and comparison of assays for troponin T and I. Clin Chem 1998; 44: 1198-1208.
10. Fesmire FM, Decker WW, Howell J, et al. Clinical policy: critical issues in the evaluation and management of adult patients presenting with suspected acute myocardial infarction or unstable angina. Ann Emerg Med 2000; 35: 521-544.
11. McCord J, Nowak RM, McCullough PA, 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.
12. Apple FS, Wu AHB. Myocardial infarction redefined: role of cardiac troponin testing. Clin Chem 2001; 47: 377-379.
13. Newby LK, Storrow AB, Gibler WB, et al. Bedside multimarker testing for risk stratification in chest pain units. The Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin, and Troponin I Study. Circulation 2001; 103: 1832-1837.
© 2002 Lippincott Williams & Wilkins, Inc.