Chest pain is a diagnostic dilemma for the emergency physician. Data from the United States suggest that 2.1% of patients with acute myocardial infarction and 2.3% of patients with unstable angina are misdiagnosed. Information obtained from the history, the initial 12-lead ECG, and a single set of cardiac markers does not have sufficient sensitivity to identify those patients who are safe for early discharge. The 2007 ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction do not identify a subset of patients at very low risk for acute coronary syndrome (ACS) who can be safely discharged from the ED without cardiac stress testing. As a result, many patients at low risk for ACS may undergo prolonged ED observation or extensive outpatient investigation, resulting in a greater likelihood of false positive cardiac stress testing and significant cost to the healthcare system.

Clinical prediction rules are clinical tools that are designed to be used at the bedside in order to assist physician decision-making. They are derived from original research and incorporate variables from the history, physical examination and basic laboratory tests. When evaluating patients with chest pain in the ED setting, clinicians rely on readily available information obtained from the history and physical examination, ECG and cardiac biomarkers. We conducted a systematic review of the literature to determine if any clinical decision rules for chest pain have been published that are ready for incorporation in clinical practice. We designed our inclusion criteria to reflect the current methodological standards for clinical decision rules, ensuring that high quality studies were identified in our search.

Our search identified 8 articles that met inclusion criteria. All 8 studies had methodological weaknesses that could have led to the introduction of bias. None of the studies verified the results of their index test (prediction rule) against a reference standard of diagnosis (cardiac stress testing or coronary angiography) on either the whole study population or random sample thereof. A proxy reference standard of close patient follow-up for the development of adverse events was used in 7 studies. The reference standard was not reported in one study. Of the 8 studies, 6 did not clearly specify that the index test (prediction rule) was interpreted without knowledge of results of the reference standard, nor did they specify that the reference standard was interpreted without knowledge of the results of the index test. Deficiencies in reference standard testing, follow-up, and blinding could have led to overestimation of sensitivity and specificity.

Clinical decision rules that have been derived only (Bassan 2004, Christenson 2006, Fernandez-Portales 2003) are considered level 4 evidence. These decision rules have been derived in only 1 setting and are not yet ready for incorporation in clinical practice. Studies that constitute level 3 evidence (Lyon 2007, Marsan 2005) have been validated in a single center. The generalizability of these rules has been demonstrated in a single setting and, as such, they can be considered for use in clinical practice. Lyon et al. validated the Global Registry of Acute Coronary Events (GRACE) risk score. Although they reported the sensitivity of the GRACE score to be 100%, data needed to calculate a complete GRACE score was missing in 24% of patients, suggesting that the score is as yet incompletely validated in the ED setting. The prediction rule published by Marsan et al. was restricted to young adults between 24 and 39 years of age, limiting its generalizability. In addition, the rule missed ACS cases when validated; the 98% sensitivity reported in our review represents the sensitivity of the rule after it was refined by adding “elevated initial cardiac marker” as an additional predictor variable. The Thrombolysis in Myocardial Infarction (TIMI) risk score has been validated broadly in 3 practice settings and thus constitutes level 2 evidence (Chase 2006, Conway-Morris 2006, Tong 2005). The sensitivity of the TIMI risk score varied between studies, ranging from 94-100%. When we pooled data from the three TIMI risk score studies, the sensitivity was 97% (95% CI 95-99%). In the US practice setting, missing 3% of adverse cardiac events is likely too high.

In summary, we did not identify a clinical decision rule fit for incorporation in clinical practice. Future studies in this area are needed to guide clinical practice and should be carefully designed to prevent intrusion of bias, take into account current AHA/ESC guidelines and standardized reporting guidelines for ED studies, and use the most sensitive cardiac troponin assays available. Clinical decision rule studies taking these factors into consideration are ongoing, and we look forward to the results.

Erik P. Hess, MD, is an assistant professor of emergency medicine at the
Mayo Clinic College of Medicine
All comments can be referenced upon request. Please contact me with commentary or questions about the sources of these statements.
Table.  Studies included in systematic review, arranged according to the hierarch of evidence for clinical decision rules.

Level of evidence                        Study
2                                                  Chase, 2006 (TIMI risk score)
                                                    Conway-Morris 2006 (TIMI risk score)
                                                    Tong, 2005 (TIMI risk score)
3                                                  Lyon, 2007 (GRACE risk score)
                                                    Marsan, 2005
4                                                  Bassan, 2004   
                                                    Christenson, 2006 (Vancouver rule)
                                                    Fernandez-Portales, 2003
1.  Pope, J. H., Aufderheide, T. P., Ruthazer, R., Woolard, R. H., Feldman, J. A., Beshansky, J. R., Griffith, J. L., et al., Missed diagnoses of acute cardiac ischemia in the emergency department., New England Journal of Medicine, 2000, 342(16):1163-1170.
2.  McGinn, T. G., Guyatt, G. H., Wyer, P. C., Naylor, C. D., Stiell, I. G., Richardson, W. S. and for the Evidence-Based Medicine Working Group, Users' Guides to the Medical Literature: XXII: How to Use Articles About Clinical Decision Rules, JAMA, 2000, 284(1):79-84.
3.  Hess, E. P., Thiruganasambandamoorthy, V., Wells, G. A., Erwin, P., Jaffe, A. S., Jaffe, A. S., Hollander, J. E., et al., Diagnostic accuracy of clinical prediction rules to exclude acute coronary syndrome in the emergency department setting: a systematic review, CJEM, 2008, 10(4):373-382.
4.  Stiell, I. G. and Wells, G. A., Methodologic standards for the development of clinical decision rules in emergency medicine, Annals of Emergency Medicine, 1999, 33(4):437-447.
5.  Hess, E. P., Wells, G. A., Jaffe, A. and Stiell, I. G., A study to derive a clinical decision rule for triage of emergency department patients with chest pain: design and methodology, BMC Emerg Med, 2008, 8:3.

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