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The Challenge of Evaluating the Patient With Chest Pain.

It is estimated that patients with complaints of chest pain comprise close to 6 million emergency department visits annually in the United States, resulting in 2 million hospital admissions at a cost of approximately $8 billion.[1] Proper evaluation of the patient with acute chest pain is a resource-intensive and expensive process. Physicians face enormous challenges in the management of these patients. The 2 major acute coronary syndromes (ACSs) that are encountered are acute myocardial infarction (AMI) and unstable angina pectoris. However, most chest pain patients do not have an ACS,[2] and most patients who do have an ACS have not had an AMI. Still, approximately 1.5 million patients experience an AMI each year, resulting in more than 500 000 deaths, with approximately one fourth of all deaths due to AMI.[3] The atypical presentation of many AMI patients can include symptoms such as nausea, shortness of breath, abdominal pain, syncope, and dizziness. Twenty-five percent of AMI patients may have no chest pain and are clinically silent. Because of missed diagnosis of at least 2% of AMI patients, inappropriate early discharge also results in significant morbidity and mortality.[1] Unstable angina pectoris is another major cause of chest pain and is responsible for more than 750 000 hospitalizations annually.[3]

Critical to the effective management of the chest pain patient is the early recognition of a cardiac ischemic event and the proper placement of the patient in the risk spectrum of ACS. To better achieve these goals, physicians and other health care professionals have created chest pain emergency centers at their institutions. Selected chest pain emergency centers place an emphasis on critical pathways or tracks, whereas other centers may use physically located chest pain evaluation units, which also incorporate the use of accelerated diagnostic protocols ("rapid ruleout" protocols) for use in the evaluation of patients with chest pain. Deservedly, management of the chest pain patient has been the subject of recent reviews,[4-6] a national US survey of emergency department chest pain centers,[7] and the National Heart Attack Alert Program Working Group.[8]

In this issue of the ARCHIVES, Caragher et al[9] report their experience in the use of an accelerated protocol for diagnosis of chest pain at a midsize community hospital in the western suburbs of Chicago, Ill. This study was conducted by a multidisciplinary team, a common characteristic of chest pain center working groups. Caragher et al first studied a preliminary control group of 100 successive chest pain patients diagnosed according to both their traditional chest pain protocol (TCPP) and the 9-hour accelerated chest pain protocol (ACPP) being considered. Key features of the TCPP included use of standard World Health Organization criteria and 8-hour total creatine kinase (CK) and creatine kinase MB (CK-MB) mass testing for up to 1 or 2 days at the physician's discretion. To accurately compare the ACPP with the TCPP, TCPP test results were only evaluated in the first 8 to 12 hours. In contrast, the ACPP incorporated 7 decision points during the 9-hour period, a more rigorous protocol for biomarker measurement and, generally, a more expeditious clinical assessment. The ACPP decision points included early assessment and triage of chest pain patients with initiation at TO of a 12-lead electrocardiogram and subsequent performance of any radiologic procedures.

In this reported study, once the final assigned diagnosis was made for the 100 control subjects using the appropriate criteria, diagnostic sensitivities and specificities of the TCPP and ACPP for ACS patients were compared. Considering ACS-positive control subjects, the authors found that the diagnostic sensitivity of the ACPP was superior to that of the TCPP. Key stakeholders at this clinical institution agreed that there was substantial improvement in the management of chest pain patients through the use of the ACPP, and the hospital subsequently opened a cardiovascular observation unit, where the ACPP was permanently implemented. Caragher et al then studied 2 groups of consecutively enrolled patients in the first (test group A) and 23rd (test group B) months of operation of the cardiovascular observation unit. Their findings indicated that there were significant reductions in length of stay (33%) and treatment costs (29%) when outcomes for test group B were compared with the control patients in this study.[9] Cost savings were calculated based on real savings achieved in reduced laboratory testing and potential savings achieved in the labor budget if unused labor flexed to other clinical service areas and if unused beds were filled with other non-ACS patients. The overall calculated reduction in treatment costs (as a percentage) from this study compared favorably with those from other literature reports addressing the benefits of establishing a chest pain program.

Another major difference between the 2 chest pain protocols reported by Caragher et al was that the ACPP incorporated serial biomarker measurements of cardiac troponin I (cTnI) and myoglobin in addition to total CK and CK-MB mass assays. These measurements started with a [T.sub.0] sample within 10 minutes of the patient's arrival at the emergency department and were generally consistent with the current guidelines of the National Academy of Clinical Biochemistry.[10] Caragher et al used an early marker, myoglobin, and a definitive specific marker of cardiac injury, cTnI. However, these investigators only used one (low) cutoff level for cTnI rather than the 2-level approach (a low level for risk stratification and a higher level for acute myocardial injury) recommended in the National Academy of Clinical Biochemistry's Standards of Laboratory Practice. Furthermore, Caragher et al chose to retain total CK testing and that for CK-MB mass and did not address the potential consideration of an accelerated diagnostic protocol, which only used cTnI and myoglobin measurements.

The issues regarding which (and when) biomarkers should be measured in the early evaluation and triage of chest pain patients demand a rigorous evidence-based assessment. Although CK-MB mass testing was once considered the "gold standard" of laboratory tests for this purpose, the use and advocation of cardiac troponins for this purpose have steadily grown throughout the past decade. This evolution was accelerated once the US Food and Drug Administration approved the use of cardiac troponin T and cTnI during the mid-1990s.

For clinicians and laboratorians interested in chest pain evaluation, the role of CK-MB mass still remains an unresolved issue. Some institutions have eliminated CK-MB mass for this purpose, and whether there is added benefit by incorporating CK-MB mass in chest pain treatment guidelines is controversial. Clearly, cardiac troponins have replaced CK-MB mass as the "gold standard." However, recently published clinical practice guidelines and selected literature reports still suggest a continued role for CK-MB mass testing. Standardization of cardiac marker assays has also received considerable attention, becoming key projects for the American Association for Clinical Chemistry and the International Federation of Clinical Chemistry. Although only one company markets a cTnT assay, approximately 10 manufacturers currently market cTnI assays. Considering the complexities of differently designed cTnI assays and the potential mechanisms for release of cardiac troponins into the bloodstream from damaged cardiac tissue, numerous clinical and analytical standardization issues persist in the measurement of cTnI.[11]

In the assessment of research on chest pain programs and in consideration of which (and how) biomarkers should be used, it is my belief that more results from solid evidence-based studies must be published. According to Sackett et al, evidence-based medicine is the integration of best research evidence with clinical expertise and patient values.[12] Evidence-based approaches for studies on chest pain treatment and cardiac biomarker strategies have been recently reported.[13,14] Relevant information is also available in electronic evidence-based medicine databases and the evidence-based medicine literature. Yet more evidence-based results from clinical studies is only one area of need for managing the chest pain patient. Broader standardization of diagnostic tests and a greater consensus on program and practice guidelines must be achieved if the millions of patients who present to emergency departments with complaints of chest pain are going to truly benefit from improved health care. However, as evidenced by the community hospital-based studies of Caragher and colleagues in this issue of the ARCHIVES, development of a chest pain program can both improve patient care and, at the same time, reduce treatment costs. These are highly desirable goals for any health care institution.


[1.] Hutter AM, Amsterdam EA, Jaffe AS. Task force 2: acute coronary syndromes: section 2 B--chest discomfort evaluation in the hospital. J Am Coll Cardiol. 2000;35:853-862.

2. Klootwijk P, Hamm C. Acute coronary syndromes: diagnosis. Lancet. 1999;353(suppl II):1015.

[3.] Yun DD, Alpert JS. Acute coronary syndromes. Cardiology. 1997;88:222-237.

[4.] Joseph AJ. Chest pain centers Clin Lab Med. 1997;1 7:685-699.

[5.] Ornato JO. Chest pain emergency centers: improving acute myocardial infarction care. Clin Cardiol. 1999;22(suppl IV):IV3-IV9.

[6.] deFilippi CP, Runge MS. Evaluating the chest pain patient--scope of the problem. Cardiol Clin. 1999;17:307-326.

[7.] Zalenski RJ, Rydman RJ, Ting S, Kampe L, Selker HP. A national survey of emergency department chest pain centers in the United States. Am J Cardiol. 1998;81:1305-1309.

[8.] National Heart Attack Alert Program Coordinating Committee Working Group. An evaluation of technologies for identifying acute cardiac ischemia in the emergency department: executive summary of a national heart attack alert program working group report. Ann Emerg Med. 1997;29:1-12.

[9.] Caragher TE, Fernandez BB, Bart LA. Long-term experience with an accelerated protocol for diagnosis of chest pain. Arch Pathol Lab Med. 2000; 124:1434-1439.

[10.] Wu AHB, Apple FS, Gibler WB, Jesse RL, Warshaw MM, Valdes RL. 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.

[11.] Apple FS. Clinical and analytical standardization issues confronting cardiac troponin I. Clin Chem. 1999;45:18-20.

[12.] Sackett DL, Straus SE, Richardson WS, Rosenberg W, Haynes RB. Introduction. In: Evidence-Based Medicine--How to Practice and Teach EBM. 2nd ed. Edinburgh, Scotland: Churchill Livingstone; 2000:1.

[13.] Christenson RH, Duh S-H. Evidence based approach to practice guidelines and decision thresholds for cardiac markers. Scand J Clin Lab Invest. 1999;59(suppl 230):90-102.

[14.] Husted SE. Targeting treatment for optimal outcome. Clin Cardiol. 2000;23(suppl I):118-122.

Accepted for publication May 22, 2000.

From the Departments of Pathology and Cell Biology, Loyola University Medical Center, Clinical Laboratories, Maywood, Ill.

Reprints: Stephen Kahn, PhD, Departments of Pathology and Cell Biology, Loyola University Medical Center, Room 0122, Clinical Laboratories, 2160 S First Ave, Maywood, IL 60153 (e-mail:
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Author:Kahn, Stephen E.
Publication:Archives of Pathology & Laboratory Medicine
Date:Oct 1, 2000
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