Chest Pain - Acute Coronary Syndromes - EB Medicine
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Identifying Emergency Department Patients With Chest Pain Who Are at Low Risk for Acute Coronary Syndromes

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Table of Contents
About This Issue

A missed diagnosis of acute coronary syndromes can be life threatening, but what about patients who appear to be at low risk of ACS? What are the best ways to make sure those at risk are flagged without ordering unnecessary testing? In this issue, you will learn to:

Order, manage, and evaluate ECG and biomarker testing, the first line of risk stratification

Identify the differences in the most-used clinical risk scores: TIMI, HEART, Vancouver, and EDACS

Assess the consensus guidelines on the value of confirmatory testing for low-risk patients

Discuss the latest evidence on high-sensitivity troponin testing and the accelerated diagnostic protocol

Manage the special diagnostic challenges with women, the young, the old, and those with previously treated CAD

Table of Contents
  1. Abstract
  2. Case Presentations
  3. Introduction
  4. Critical Appraisal of the Literature
  5. Selected Abbreviations
  6. Etiology And Pathophysiology
  7. Differential Diagnosis
  8. Prehospital Care
  9. Emergency Department Evaluation
    1. History
    2. Physical Examination
  10. Diagnostic Studies
    1. Electrocardiogram
    2. Biomarkers
    3. Early Risk Stratification and Clinical Risk Scores
      1. The TIMI Score
      2. The HEART Score
      3. The Vancouver Chest Pain Rule
      4. The North American Chest Pain Rule
      5. Summary
    4. Chest Radiography
    5. Confirmatory Testing
      1. Summary
  11. Treatment
  12. Special Populations
    1. Chest Pain in Women
    2. Younger Patients
    3. Elderly Patients
    4. Patients With Known Coronary Artery Disease or Previous Cardiac Testing
  13. Controversies and Cutting Edge
    1. High-Sensitivity Troponin Testing
    2. Triple-Rule-Out Computed Tomography
  14. Disposition
  15. Summary
  16. Risk Management Pitfalls in Managing Patients at Low Risk for Acute Coronary Syndromes
  17. Time- and Cost-Effective Strategies
  18. Case Conclusions
  19. Clinical Pathway for Emergency Department Testing of Patients With Signs or Symptoms of Acute Coronary Syndromes
  20. Tables and Figures
    1. Table 1. Differential Diagnosis of Chest Pain
    2. Table 2. Electrocardiographic Classification and Likelihood of 30-day Major Adverse Cardiac Event
    3. Table 3. Summary of the TIMI Score and HEART Score
    4. Table 4. Estimated Diagnostic Accuracy of Confirmatory Testing for Detection of Coronary Artery Disease With ≥ 50% Stenosis
    5. Figure 1. Serial Electrocardiograms in a Patient With Acute Left Anterior Descending Artery Occlusion
    6. Appendix 1. Summary of Major Clinical Risk Scores (Derivation Studies Only) (Continued on page 15)
    7. Appendix 1. Summary of Major Clinical Risk Scores (Derivation Studies Only) (Continued from page 14)
  21. References


Though a minority of patients presenting to the emergency department with chest pain have acute coronary syndromes, identifying the patients who may be safely discharged and determining whether further testing is needed remains challenging. From the prehospital care setting to disposition and follow-up, this systematic review addresses the fundamentals of the emergency department evaluation of patients determined to be at low risk for acute coronary syndromes or adverse outcomes. Clinical risk scores are discussed, as well as the evidence and indications for confirmatory testing. The emerging role of new technologies, such as high-sensitivity troponin assays and advanced imaging techniques, are also presented.

Case Presentation

A 65-year-old man with a history of hypertension, diabetes, and prior myocardial infarction presents to the ED after he experienced a 20-minute episode of dull, aching, left-sided chest discomfort while doing yard work an hour ago. His wife tells you that he’s been having similar episodes on and off for the past 2 weeks. He is pain-free on arrival, and his vital signs are unremarkable. His ECG, chest x-ray, and troponin are all normal. When you go back into the room to reassess him, he says he feels fine and asks if he can go home. You hesitate and wonder if it would be safe to send him home without further testing.

A 22-year-old college student presents with sharp, left-sided chest pain and shortness of breath. He recently returned from a spring break trip to Mexico and reports symptoms of an upper respiratory infection. He feels that his chest pain is worse when lying flat, and is concerned he’s having a heart attack. His vital signs and physical examination are normal. He has no past medical history, no cardiac risk factors, and no family history of heart disease. His triage ECG is normal. ACS seems unlikely, but as you’re thinking through your differential diagnosis, you wonder if you need to do any other tests to rule it out definitively.

A 46-year-old woman with end-stage renal disease, hypertension, diabetes, and tobacco use presents with dull, aching, substernal chest pain radiating to her arms and shortness of breath that began shortly after completing dialysis. She is hypertensive, but her vital signs are otherwise normal. She has soft, bibasilar inspiratory crackles on pulmonary examination. Her initial ECG shows nonspecific T-wave changes and left ventricular hypertrophy, but it is otherwise unremarkable. Her troponin is elevated at 0.098 ng/mL (conventional sensitive troponin I assay, reference range 0-0.04 ng/mL), but when you review her records, you see it is similar to baseline from previous testing. She is treated with aspirin and nitroglycerin, and her chest pain improves. On review of her records, you note that she had an unremarkable stress test (pharmacologic myocardial perfusion imaging) about 6 months ago. Your partner says, “Oh, she’s here all the time with chest pain. There’s never anything wrong with her.” You wonder what other tests should be done, and how to interpret her elevated troponin.


Every year in the United States, there are approximately 8 million emergency department (ED) visits for chest pain, but only 13% to 25% lead to a diagnosis of acute coronary syndromes (ACS).1,2 ACS is a group of potentially life-threatening conditions comprised of ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation mycocardial infarction (NSTEMI), and unstable angina. For the evaluation of suspected ACS in the ED, consensus guidelines recommend obtaining electrocardiogram (ECG) and cardiac biomarker testing in addition to the basic history, physical examination, and chest radiography.2-8 If these tests are unremarkable, guidelines then recommend further confirmatory testing. Despite the extensive testing typically performed for patients with chest pain from suspected ACS, a landmark study by Pope et al estimated that more than 2% of patients with ACS are mistakenly discharged from the ED, potentially leading to increased risk of harm.9 Although this study is nearly 20 years old, more-recent research has shown similar miss rates, suggesting that the ED evaluation of chest pain for suspected ACS remains challenging despite advances in knowledge and technology.10-12

The term low-risk patient is inherently unclear and can mean different things among providers. In most literature, patients with chest pain who are described as being at low risk for ACS are those who: (1) are hemodynamically stable, (2) are without concerning features on history or examination, and (3) do not have immediate objective evidence of myocardial ischemia on initial ECGs and biomarker testing.2 Current consensus guidelines further define the low-risk patient as one who has a < 1% risk of a major adverse cardiac event (MACE) or death at ≥ 30-days' follow-up.3 For the purposes of this article, we define the low-risk patient more broadly as one who may be safely discharged home with little, if any, further testing. This issue of Emergency Medicine Practice reviews the current evidence regarding ED evaluation and risk stratification strategies for patients presenting with chest pain from suspected ACS.

Critical Appraisal Of The Literature

There is a large body of research on the evaluation and management of undifferentiated chest pain in the ED. Narrowing this work to chest pain only from presumed ACS yielded 1145 articles (using the search terms chest pain, acute coronary syndrome, and emergency department). Among these, articles from the following categories were reviewed: low risk (169 articles), risk stratification (168 articles), clinical decision rules (35 articles), stress testing (91 articles), cardiac imaging (128 articles), and disposition (31 articles). The Cochrane Library was searched using the term chest pain (77 articles) and acute coronary syndrome (16 articles), but none were directly applicable to this topic. A National Guideline Clearinghouse search ( using the terms low-risk, chest pain, and acute coronary syndrome yielded 104 articles, 8 of which were applicable. Additional references were gathered by reviewing the bibliographies of selected articles generated from these searches.

Relevant guidelines and statements from various professional groups were reviewed. Guidelines and statements that have superseded older versions were emphasized.

Selected Abbreviations

ACI-TIPI Acute Cardiac Ischemia Time-Intensive Predictive Instrument
ACS Acute coronary syndromes
ADAPT  Two-hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker
ASPECT Asia-Pacific Evaluation of Chest Pain Trial
CAD Coronary artery disease
CATCH  Cardiac CT in the Treatment of Acute Chest Pain Trial
CCTA Coronary computed tomography angiography
CI Confidence interval
CK-MB Creatinine kinase-MB isoenzyme
CT Computed tomography
ECG Electrocardiogram
EDACS Emergency Department Assessment of Chest Pain Score
GRACE Global Registry of Acute Coronary Events
HEART History, ECG, Age, Risk Factors, Troponin [Score]
MACE Major adverse cardiac event
mSv Millisievert
mV Millivolt
NACPR North American Chest Pain Rule
NPV Negative predictive value
NSTEMI Non-ST-segment elevation myocardial infarction
PROMISE Prospective Multicenter Imaging Study for Evaluation of Chest Pain
PROSPECT Prospective Randomized Outcome Trial Comparing Radionuclide Stress Myocardial Perfusion Imaging and ECG-gated CCTA
PURSUIT Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy
STEMI ST-segment elevation myocardial infarction
TIMI Thrombolysis in Myocardial Infarction [Score]
TRO CT Triple-rule-out computed tomography

Risk Management Pitfalls in Managing Patients at Low Risk for Acute Coronary Syndromes

1. “My patient was young and healthy, so I didn’t suspect ACS.”

Younger patients are at lower risk of ACS, but 4% to 8% of myocardial infarctions still occur in patients < 40 years old. While traditional cardiac risk factors are generally not useful in the management of undifferentiated chest pain, a high risk-factor burden is more predictive of ACS in younger patients. Validated clinical risk scores can identify very-low-risk patients in this age group with excellent accuracy.

2. “Her symptoms didn’t sound like angina, so ACS wasn’t even in my differential diagnosis.”

A patient's history cannot reliably exclude ACS. Atypical symptoms are often present and are more common in women, the elderly, and diabetics. Additional testing, especially in these population groups, should be considered to reliably rule out ACS.

3. “The pain was reproducible on palpation, so I ruled out ACS.”

Pain that is reproducible on palpation lowers the risk of ACS, but does not exclude it.

4. “The ECG was normal, so I didn’t think further testing was indicated.”

A normal ECG lowers the risk of ACS but does not adequately exclude it, and nearly 8% of patients with myocardial infarction have a normal ECG. Misinterpretation of the ECG is also a factor associated with missed diagnosis of ACS. Accuracy is increased by obtaining serial ECGs.

5. "His chest pain began 6 hours prior, so I thought 1 troponin would be sufficient.”

Troponin will be detectable within 6 hours in nearly all patients with myocardial infarction. However, if the history is inexact, if the patient has a moderate to high pretest probability of ACS, or if the troponin assay is older or less-sensitive, additional

6. “The patient had negative serial troponins, so I thought that ruled out ACS.”

Currently, unstable angina is a purely clinical diagnosis, and biomarkers will be negative in this condition. Negative biomarkers should be used in conjunction with validated clinical risk scores for optimal risk stratification.

7. “He had chest pain and an elevated troponin, so I diagnosed him as having a myocardial infarction.”

The specificity of troponin for myocardial infarction is less than its sensitivity, and troponin can be elevated in many other conditions that cause nonischemic myocardial injury (eg, heart failure, pulmonary embolism, chronic kidney disease, sepsis).

8. “My patient had a TIMI score of 0, so I excluded ACS and discharged him without further testing.”

A TIMI score of 0 confers a 1.8% risk of 30-day MACE, which may be unacceptably high. Using TIMI in conjunction with serial biomarkers improves its prognostic ability.

9. “My patient had normal serial ECGs and negative serial troponins, so I told him that ACS was ruled out and he didn't need any further testing.”

There is strong evidence to suggest that confirmatory testing does not add any incremental benefit in low-risk patients. However, this approach has not been tested in randomized trials, and is not yet endorsed by consensus guidelines. Furthermore, patients who are at intermediate or high risk of ACS or MACE as determined by a validated clinical risk score should undergo further testing, even with normal ECGs and negative troponins.

10. “She had a negative stress test 6 months prior and the ECG was normal, so I thought it was safe to send her home without any further testing.”

The annual event rate (myocardial infarction or cardiac death) is about 1% after any stress test. Any patient presenting to the ED with chest pain should be evaluated with ECG and biomarkers, and risk stratified using a validated clinical risk score, despite the recent negative stress test.

Tables and Figures

Table 1. Differential Diagnosis of Chest Pain


Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the author, are noted by an asterisk (*) next to the number of the reference.

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David Markel, MD

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July 1, 2017

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