Table of Contents

 

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

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

Abstract

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.

Introduction

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 (www.guideline.gov) 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

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

References

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.

• For the evaluation of suspected acute coronary syndromes (ACS) in the ED, consensus guidelines recommend obtaining basic history, physical examination, electrocardiogram (ECG), cardiac biomarkers, and chest radiography. If these tests are unremarkable, confirmatory tests can be performed, with a focus on diagnosis of atherosclerotic coronary artery disease (CAD).
• History cannot reliably rule in or rule out ACS.

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Identifying Emergency Department Patients With Chest Pain who are at Low Risk for Acute Coronary Syndromes  - Calculated Decisions

The EDACS identifies patients with chest pain who are at low risk for a major adverse cardiac event. The HEART Pathway was designed to aid in efficiently evaluating patients with acute chest pain, using the previously validated HEART Score. The HEART Score predicts 6-week risk of major adverse cardiac events, including all-cause mortality, myocardial infarction, or coronary revascularization, and can be used to identify patients who are safe for discharge. The TIMI risk score for UA/NSTEMI estimates mortality in patients with unstable angina and non-ST-segment elevation myocardial infarction. The Vancouver Chest Pain Rule identifies low-risk chest pain patients who are safe for early discharge from the emergency department.

1. Emergency Department Assessment of Chest Pain Score (EDACS)
2. HEART Pathway for Early Discharge in Acute Chest Pain
3. HEART Score for Major Cardiac Events
4. TIMI Risk Score for UA/NSTEMI
5. Vancouver Chest Pain Rule

Emergency Department Assessment of Chest Pain Score (EDACS)

• Introduction
• Points & Pearls
• Why and When to Use, and Next Steps
• Calculator Review Author
• Advice
• Critical Actions
• Evidence Appraisal
• Selected Abbreviations
• Calculator Creator
• References
• Related Calculator

Introduction

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Points & Pearls

• The EDACS accelerated diagnostic protocol (EDACS-ADP) study included any symptoms lasting longer than 5 minutes that the attending physician thought were worth working up for possible acute coronary syndromes (ACS). This is a broader definition than other studies, such as the Vancouver Chest Pain Score, which only included chest pain patients.
• Like other chest pain evaluation studies, the primary outcome for the EDACS-ADP study was a major adverse cardiac event (MACE), as defined by any of the following:
  • ST-elevation or non-ST-elevation myocardial infarction
  • Requiring an emergency revascularization procedure
  • Death from cardiovascular causes
  • Ventricular arrhythmia
  • Cardiac arrest
  • Cardiogenic shock
  • High atrioventricular block
• The goal of these rules is to identify a low-risk population of patients who need less testing than other, higher-risk patients. As a rule-out calculator, the EDACS is good at identifying who is relatively safe to go home (highly sensitive), but not good at identifying who does have the disease (not terribly specific). The fairly extreme goal of ≥ 99% sensitivity was achieved in the study (see the Evidence Appraisal section below).
• The score was initially created without electrocardiogram (ECG) or biomarkers. These were added into the EDACS ADP, which includes an ECG and troponin at 0 hours and at 2 hours.
• The score was internally validated in the original paper, but has not yet been externally validated.

Why and When to Use, and Next Steps 

Calculator Review Author

Graham Walker, MD

Department of Emergency Medicine

Kaiser Permanente San Francisco, San Francisco, CA

Joseph Habboushe, MD, MBA

Department of Emergency Medicine

NYU Langone / Bellevue Medical Center, New York, NY

Advice

Barring other concerning features for ACS or other life-threatening causes of chest pain (pneumothorax, pulmonary embolism, cardiac tamponade, aortic dissection, esophageal rupture, etc), patients who meet the low-risk criteria can be considered for discharge after negative 0-hour and 2-hour troponin testing, with close follow-up by a primary care physician.

Patients who do not meet the low-risk criteria cannot be ruled out using the EDACS or EDACS-ADP. As a rule-out calculator, the EDACS does not provide definitive guidance for treatment of patients who fail the rule, so physicians should use best judgment and follow other evidence-based chest pain guidelines.

Critical Actions

Patients deemed to be at low risk are safe for discharge to early outpatient follow-up investigation, or to proceed to earlier inpatient testing. For patients who are not at low risk, physicians should use best judgment, as this rule-out calculator was not designed to “rule in” patients with ACS. Physicians cannot use the EDACS to rule out ACS.

Evidence Appraisal

The EDACS-ADP was prospectively validated in the original paper (Than et al, 2014), but would be strengthened by an external validation as well. The EDACS-ADP was 99% to 100% sensitive for correctly identifying patients as low-risk and identified 45% of its cohort as low-risk. This is much higher than other emergency department-based risk scores such as the HEART Score (history, ECG, age, risk factors, troponin), the Vancouver Chest Pain Score, ADAPT (Two-hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker), the Marberg Score, and the GRACE (Global Registry of Acute Coronary Events ) ACS Risk Score.

In the EDACS-ADP cohorts, SelectedAbbreviations1the prevalence of MACE in the study overall was 13% to 15%.

EDACS may help rule out ACS in patients with chest pain, but still requires strong external validation before widespread use.

Selected Abbreviations

Calculator Creator

Martin Than, MD

References

Original/Primary Reference

• Than M, Flaws D, Sanders S, et al. Development and validation of the Emergency Department Assessment of Chest pain Score and 2 h accelerated diagnostic protocol. Emerg Med Australas. 2014;26(1):34-44.

Related Calculator

• Access the ADAPT Protocol for Cardiac Event Risk.
• Access the GRACE ACS Risk and Mortality Calculator.

HEART Pathway for Early Discharge in Acute Chest Pain

• Introduction
• Points & Pearls
• Why and When to Use, and Next Steps
• Calculator Review Author
• Advice
• Critical Actions
• Evidence Appraisal
• Calculator Creator
• References

Introduction

The HEART Pathway was designed to aid in efficiently evaluating patients with acute chest pain, using the previously validated HEART Score.

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Points & Pearls

• The HEART Pathway identifies patients who are safe for early discharge versus those who need observation, admission, and potentially emergent cardiology assessment.
• While patients with ischemic changes on electrocardiogram (ECG) or elevated troponin may be classified as low-risk using the HEART Pathway, the creators recommend against relying on the HEART Pathway in such cases.
• New elevations in troponin or ECG changes require further workup and these patients should not be deemed to be low-risk.
• The creators of the HEART Pathway recommend against using this clinical decision tool in patients with known coronary artery disease, a disease state that puts patients at significant increased risk of acute coronary syndromes (ACS).
• The HEART Pathway was designed for patients presenting to the emergency department (ED) with chest pain, and was not tested in patients with chest pain who are already hospitalized.

Why and When to Use, and Next Steps

Calculator Review Author

Cullen Clark, MD

Department of Emergency Medicine

Louisiana State University School of Medicine, New Orleans, LA

Advice

The HEART Pathway is an accelerated diagnostic pathway. It is not designed to replace clinical judgment. Any patient with a concerning presentation or clinical progression should receive workup and treatment based on the clinician’s discretion, regardless of the HEART Pathway’s predicted risk.

Shared decision-making is a crucial part of further management after ACS risk has been determined, especially in patients with moderate risk who are recommended for observation and comprehensive cardiac evaluation. There is notable risk involved with hospitalization as well as risk of false-positive or nondiagnostic testing that would result in invasive procedures such as cardiac catheterization. The patient should be presented with the risk of both missed ACS and hospitalization for further workup.

Any patient presenting with chest pain and subsequently discharged should be informed that even with a negative workup, there is still a small risk of ACS. Patients should have close follow-up arranged and be given extensive return precautions prior to discharge.

Critical Actions

Clinician judgment should prevail, even if patients are deemed to be at low risk by the HEART Pathway. If there is some other cause for concern for an acute cardiac event, workup should be individualized to the patient.

All patients presenting to the ED with chest pain concerning for ACS should receive aspirin unless there is an absolute contraindication, such as known allergy, active bleeding, or if the patient has received a therapeutic aspirin dose prior to arrival. 

Evidence Appraisal

The HEART Pathway was developed by Mahler et al in 2015 in a randomized controlled single-center trial. The control arm was managed at the discretion of care providers encouraged to follow American College of Cardiology/American Heart Association guidelines for acute chest pain.

The use of the HEART Pathway in this study was designed to mimic the real world in that it was used as an accelerated diagnostic pathway. Patient care was at the discretion of the healthcare provider and not mandated by the outcome of the HEART Pathway.

There were 282 patients studied, with 141 patients in each treatment group. The primary outcome was the rate of objective cardiac testing (stress test, coronary computed tomography angiogram, or invasive coronary angiography) within 30 days of presentation. Secondary outcomes were early discharge rate, index length of stay, cardiac-related recurrent ED visits, and nonindex hospitalization at 30 days.

The rate of objective cardiac testing in the HEART Pathway group was 12% less than the usual care group. The rate of early discharge in the HEART Pathway was 21% higher than the usual care group. The index length of stay was 12 hours shorter using the HEART Pathway. There was no significant difference between the 2 groups for cardiac-related recurrent ED visits or nonindex hospitalization at 30 days. No patients identified for early discharge in either group had missed a missed major adverse cardiac event (MACE) during the first 30-day follow-up period. The study was not powered to adequately detect differences in MACE between the 2 study groups.

Riley et al in 2017 published a cost analysis of the HEART Pathway compared to usual care, using the same dataset as the original HEART Pathway trial. There were 270 patients studied. Billing data were missing for 12 patients from the original study. Cost metrics considered in each group were index visit cost, total cost at 30 days, cardiac-related healthcare cost at 30 days, cardiac and noncardiac diagnostic testing cost, ED cost, inpatient cost for index visit, and outpatient cost. HEART Pathway patients had a significantly lower mean and median cost for both index visit and 30-day follow-up. There was no significant difference between the median and mean costs of the other metrics. Average savings per patient was $216, using the HEART Pathway. On a larger scale, this would mean approximately $2 billion in savings per year for undifferentiated chest pain.

Mahler et al in 2017 also published a secondary analysis looking at high-sensitivity cardiac troponin I and high-sensitivity cardiac troponin T. The study compared risk stratification using cardiac troponin I versus high-sensitivity cardiac troponin I and high-sensitivity cardiac troponin T in calculating the HEART Pathway score. Blood samples were sent for troponin I, high-sensitivity troponin I, and high-sensitivity troponin T for 133 patients.

All of the troponin assays had poor sensitivity for predicting MACE when used separately from the HEART score. There was no difference in the predicted risk of MACE between the use of serial troponin I and 3-hour high-sensitivity troponin I in the HEART Pathway. Using high-sensitivity troponin T in the HEART Pathway led to 1 patient with a non-ST-segment elevation myocardial infarction being misclassified as low-risk. The study found the HEART Pathway using serial troponin I or 3-hour high-sensitivity troponin I to have sensitivity and negative predictive value of 100% for 30-day MACE. Although hs-cTnT use in the HEART Pathway caused a non-ST-segment elevation myocardial infarction to be misclassified as low risk, the reduction in sensitivity was not statistically significant, given the small study population. The authors recommend further appropriately powered studies to determine small differences in the accuracy of the high-sensitivity troponin assays.

Calculator Creator

Simon A. Mahler, MD

References

Original/Primary Reference

• Mahler SA, Riley RF, Hiestand BC, et al. The HEART Pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge. Circ Cardiovasc Qual Outcomes. 2015;8(2):195-203.

Other References

• Poldervaart JM, Reitsma JB, Backus BE, et al. Effect of using the HEART score in patients with chest pain in the emergency department: a stepped-wedge, cluster randomized trial. Ann Intern Med. 2017;166(10):689-697.
• Riley RF, Miller CD, Russell GB, et al. Cost analysis of the History, ECG, Age, Risk factors, and initial Troponin (HEART) Pathway randomized control trial. Am J Emerg Med. 2017;35(1):77-81.
• Mahler SA, Stopyra JP, Apple FS, et al. Use of the HEART Pathway with high sensitivity cardiac troponins: a secondary analysis. Clin Biochem. 2017;50(7-8):401-407.

HEART Score for Major Cardiac Events

• Introduction
• Points & Pearls
• Why and When to Use, and Next Steps
• Calculator Review Author
• Critical Actions
• Evidence Appraisal
• Selected Abbreviations
• Calculator Creator
• References
• Related Calculator

Introduction

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Points & Pearls

• The HEART Score helps emergency department (ED) providers risk stratify patients with chest pain into low-, moderate-, and high-risk groups.
• HEART is an acronym of its components: history, ECG, age, risk factors, and troponin. Each of these components is scored with 0, 1, or 2 points.
• It was designed to risk stratify patients with un-differentiated chest pain, not those already diagnosed with acute coronary syndromes (ACS).
• The HEART Score helps identify patients with higher risk of having a major adverse cardiac event (MACE) within the following 6 weeks. MACE is defined as all-cause mortality, myocardial infarction, or coronary revascularization.
• The user needs some experience taking a detailed chest pain history and reading electrocardiograms (ECGs) to adequately apply these 2 components of the score.
• The HEART Score is sometimes compared to the TIMI (Thrombolysis in Myocardial Infarction) Risk Score for UA (unstable angina) / NSTEMI (non-ST-segment elevation myocardial infarction) and the GRACE (Global Registry of Acute Coronary Events) ACS Risk Score, which are older ACS scores; however, the latter 2 scores are different from the HEART Score in that they measure risk of death for patients with ACS.
• The HEART Score outperforms the TIMI Risk Score for UA/NSTEMI, safely identifying more low-risk patients.

Why and When to Use, and Next Steps

Calculator Review Author

Hyunjoo Lee, MD

Department of Emergency Medicine

Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA

Carlos Rodriguez, MD

Department of Emergency Medicine

Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA

Critical Actions

Do not use if the ECG shows new ST-segment elevation requiring immediate intervention or with clinically unstable patients.

Evidence Appraisal

The HEART Score was originally developed by Backus et al (2008) in a cohort of 122 patients with chest pain in an ED setting. The study included any patients admitted to the ED due to chest pain, irrespective of age, prehospital assumptions, and previous medical treatments. It excluded patients with chest pain and significant ST segment elevations. End points in this study were acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, and death. HEART scores of 0-3 points confer a risk of 2.5% for any end point, and therefore were used to support discharge from the ED. Conversely, HEART scores of 4-6 points confer a risk of 20.3% for any end point, implying admission for clinical observation is necessary. HEART scores of ≥ 7 points have a risk of 72.7% for any end point, and support early invasive strategies.

In a retrospective multicenter validation study also by Backus et al (2010), 880 patients presenting with chest pain were evaluated. The primary end points studied were the same as in the original study. In this study, 158 patients (17.95%) reached a primary end point. Of the 303 patients with HEART scores of 0-3 points, 3 (0.99%) had a MACE. Among 413 patients with HEART scores of 4-6 points, 48 cases (11.6%) resulted in a MACE, and among patients with HEART scores of 7-10 points, a MACE was identified in 107 of 164 cases (65.2%).

Backus et al (2013) externally validated the HEART Score with a prospective multicenter study. The study evaluated 2440 patients presenting with chest pain to 10 EDs in the Netherlands. The primary end point was the occurrence of any MACE within 6 weeks. The performance of the HEART Score was also compared to that of the TIMI Risk Score for UA/ NSTEMI and the GRACE ACS Risk Score. In the low-risk group (HEART scores of 0-3 points), 15 of 870 patients (1.7%) were found to have a MACE. In the group with HEART scores of 4-6 points, 183 of 1101 patients (16.6%) were diagnosed with a MACE. A MACE occurred in 50.1% of patients with HEART scores of 7-10 points. The C statistic of the HEART score (0.83) was significantly higher than the C statistic of the TIMI Risk Score (0.75) and the GRACE ACS Risk Score (0.70), respectively (P < .0001).

Poldervaart et al (2017) studied the HEART Score in a stepped-wedge, cluster-randomized trial, with the objective of measuring both outcomes and use of healthcare resources. The 9 Dutch hospitals included in the study were instructed to start usual care when assessing patients with chest pain. Every 6 weeks, 1 hospital was randomly assigned to use the HEART Score to assess patients with chest pain. A total of 3648 patients were included (1827 receiving usual care and 1821 receiving HEART care). The study found that the 6-week MACE incidence while using the HEART Score was 1.3% lower than with usual care, but there were no statistically significant differences in early discharge, readmissions, recurrent ED visits, outpatient visits, or visits to general practitioners.

Recent studies have compared the HEART Score head-to-head with other clinical decision rules for the ability to safely identify low-risk patients. A study by Poldervaart et al (2017) comparing the HEART Score to the TIMI Score and GRACE Score showed that the HEART Score outperformed the others when identifying low-risk patients, with only 0.8% incidence of MACE in the low-risk group.

In addition, Nieuwets et al (2016) compared the HEART Score with the TIMI Score for identifying low-risk patients without compromising safety, while also evaluating expected cost reductions. They found that the HEART Score identified more patients as low-risk than the TIMI Score did, which would have led to potential cost savings of €64,107 (~USD $76,000) by using the HEART Score cutoffs versus cost savings of €14,670 (~USD $17,000) using the TIMI Score cutoffs.

The HEART Pathway developed by Mahler et al (2015) combined the HEART Score with 0- and 3-hour cardiac troponin tests in a decision aid designed to identify ED patients who are safe for early discharge. The study found that the HEART Pathway decreased length of stay by 12 hours, decreased objective cardiac testing by 12%, and increased early discharges by 21%. No MACE was seen within 30 days in patients who were identified for early discharge. Of note, this study (and the original HEART Score studies) used regular-sensitivity cardiac troponin testing.

Selected Abbreviations

Calculator Creator

Barbra Backus, MD

References

Original/Primary Reference

• Six AJ, Backus BE, Kelder JC. Chest pain in the emergency room: value of the HEART score. Neth Heart J. 2008;16(6):191-196.

Validation

• Backus BE, Six AJ, Kelder JC, et al. A prospective validation of the HEART score for chest pain patients at the emergency department. Int J Cardiol. 2013;168(3):2153-8.
• Backus BE, Six AJ, Kelder JC, et al. Chest pain in the emer-gency room: a multicenter validation of the HEART Score. Crit Pathw Cardiol. 2010;9(3):164-169.

Additional References

• Poldervaart JM, Langedijk M, Backus BE, et al. Comparison of the GRACE, HEART and TIMI score to predict major adverse cardiac events in chest pain patients at the emergency department. Int J Cardiol. 2017;227:656-661.
• Nieuwets A, Poldervaart JM, Reitsma JB, et al. Medical consumption compared for TIMI and HEART score in chest pain patients at the emergency department: a retrospective cost analysis. BMJ Open. 2016;6(6):e010694.
• Poldervaart JM, Reitsma JB, Backus BE, et al. Effect of using the HEART score in patients with chest pain in the emergency department: a stepped-wedge, cluster randomized trial. Ann Intern Med. 2017;166(10):689-697.
• Mahler SA, Riley RF, Hiestand BC, et al. The HEART Pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge. Circ Cardiovasc Qual Outcomes. 2015;8(2):195-203.

Related Calculator

• Access the GRACE ACS Risk and Mortality Calculator.

TIMI Risk Score for UA/NSTEMI

• Introduction
• Points & Pearls
• Why and When to Use, and Next Steps
• Calculator Review Author
• Advice
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Introduction

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Points & Pearls

• The TIMI (Thrombolysis in Myocardial Infarction) Risk Score for UA (unstable angina) / NSTEMI (non-ST-segment elevation myocardial infarction) has historical significance as one of the earliest chest pain decision rules that was widely implemented.
• A TIMI Risk Index and TIMI Risk Score for STEMI (ST-segment elevation myocardial infarction) also exist; however, in this review, “TIMI Risk Score” refers only to the TIMI Risk Score for UA/NSTEMI.
• The TIMI Risk Score was originally derived with patients with known UA or NSTEMI.
• A TIMI Risk Score of 0 or 1 point does not equal zero risk of adverse outcome. The original study showed 4.7% of patients with a score of 0 or 1 point had adverse outcomes within 14 days.
• Validation studies showed 1.7% to 2.1% of patients with a score of 0 still had adverse outcomes within 30 days.
• It is unclear whether this risk score can be used in patients with chest pain in the setting of cocaine use.
• The TIMI Risk Score was further studied as part of an accelerated diagnostic protocol in the ADAPT (Two-hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker) trial, which included estimation of pretest probability using TIMI, plus abnormal electrocardiogram (ECG) and troponin (high-sensitivity cardiac troponin I).

Why and When to Use, and Next Steps

Calculator Review Author

Hyunjoo Lee, MD

Department of Emergency Medicine

Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA

Carlos Rodriguez, MD

Department of Emergency Medicine

Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA

Advice

Patients in the 0-1 point group should be further risk stratified using another risk score or institutional practices, as risk is not low enough to safely discharge these patients from the hospital. Many guidelines recommend aggressive medical intervention and/or early invasive management for higher-risk patients.

Critical Actions

A TIMI Risk Score of 0 does not equate to zero risk of adverse outcome.

Evidence Appraisal

Antman et al (2000) used a merged database of 7081 UA/NSTEMI patients in the TIMI 11B and ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events) trials for the original derivation and validation of this TIMI Risk Score. The risk score was originally derived from 1957 UA/NSTEMI patients receiving unfractionated heparin in the TIMI 11B trial, and was internally validated in 3 cohorts of patients from the rest of the merged data: 1953 patients receiving enoxaparin in the TIMI 11B trial; 1564 patient receiving unfractionated heparin in the ESSENCE Trial; and 1607 patients receiving enoxaparin in the ESSENCE Trial. The study included UA/NSTEMI patients with chest pain at rest who presented within 24 hours of symptoms, and who had ST-segment deviation on their presenting ECG, history of coronary artery disease, and a measured cardiac enzyme that was elevated. Patients were excluded if revascularization was within 24 hours or if the patient had a contraindication to anticoagulation. The primary end points were composite all-cause mortality, myocardial infarction, or urgent revascularization within 14 days.

By the end of the 14 days, 16.7% of the derivation group had died, had a myocardial infarction, or needed urgent revascularization. An increase of the TIMI Risk Score correlated with an increase in all-cause mortality, myocardial infarction, or urgent revascularization. The same pattern was seen in the internally validated groups. There have been many external validation studies since the original derivation.

Scirica et al (2002) externally validated the TIMI Risk Score in patients from 9 sites in the TIMI III Registry. This study included UA/NSTEMI patients with ischemic chest pain lasting more than 5 minutes, presenting within 96 hours of symptom onset. Patients were excluded if they had a STEMI, chest pain of other origin, planned revascularization, or if the patient was in a prior TIMI trial. Primary end points were death, myocardial infarction, and recurrent ischemia within 6 weeks and at 1 year. As in the original derivation study and internal validation studies, there was an increase in mortality, myocardial infarction, and recurrent ischemia with each increase in the TIMI Risk Score. However, this study modified the TIMI Risk Score definitions to some degree by substituting a patient’s history of myocardial infarction or revascularization history for “known coronary artery stenosis > 50%,” and assigning 1 point for aspirin use in the past 24 hours, not the past 7 days as in the original trial by Antman et al. Still, this population was in a registry for patients with known UA/NSTEMI. Thus, this validation is less useful for patients with undifferentiated chest pain seen in the acute care setting of the emergency department (ED).

Pollack et al (2006) externally validated the TIMI Risk Score in a prospective observational cohort study of 3929 adult patients with chest pain in the ED. The study included adult chest pain patients aged > 24 years who were evaluated with ECG. Adults aged < 24 years were included if the chest pain was preceded by cocaine use within the previous week. Patients were excluded if they had a STEMI. Whereas the original derivation study looked at adverse outcomes within 14 days, and Scirica et al (2002) validated the risk score looking up to 6 weeks and even 1 year, Pollack et al followed up with patients for up to 30 days from presentation for adverse outcomes of death, myocardial infarction, or revascularization. As in prior studies, the higher the TIMI Risk Score, the higher the likelihood of adverse outcome within the measured time period, which was 30 days in this study. However, the patient population was different in that there were more black patients and more female patients. Also, if no cardiac markers were ordered, a score of 0 was assumed and assigned to the category of cardiac enzymes.

Chase et al (2006) externally validated the TIMI Risk Score in a prospective observational study of 1458 patient visits in the ED. The study included patients aged > 30 years with nontraumatic chest pain who had an ECG performed in the ED. Whereas Pollack et al included patients with cocaine use, Chase et al excluded patients if cocaine was used in the 7 days prior to presentation. Like Pollack et al, Chase et al assigned a score of 0 to cardiac enzymes if they were not drawn. Chase et al also followed patients for up to 30 days. Within 30 days, 12.8% of patients had an adverse outcome of death, myocardial infarction, or revascularization. In patients with a TIMI Risk Score of 0, 1.7% had an adverse outcome. Although there was a general correlation of an increase in adverse outcome with higher TIMI Risk Score, this study did not show a similar stepwise increase. This is likely secondary to having a study population that was dissimilar to the original derivation group or other validation studies, as this study had patients with mostly low TIMI scores and included STEMI patients in the study population.

Selected Abbreviations

Calculator Creator

Elliot M. Antman, MD

References

Original/Primary Reference

• Antman EM, Cohen M, Bernink PJLM, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835-842

Validation

• Scirica BM, Cannon CP, Antman EM, et al. Validation of the thrombolysis in myocardial infarction (TIMI) risk score for unstable angina pectoris and non-ST-elevation myo-cardial infarction in the TIMI III registry. Am J Cardiol. 2002;90(3):303-305.
• Chase M, Robey JL, Zogby KE, et al. Prospective validation of the thrombolysis in myocardial infarction risk score in the emergency department chest pain population. Ann Emerg Med. 2006;48(3):252-259.
• Pollack CV, Sites FD, Shofer FS, et al. Application of the TIMI risk score for unstable angina and non-ST elevation acute coronary syndrome to an unselected emergency department chest pain population. Acad Emerg Med. 2006;13(1):13-18.

Additional References

• Than M, Cullen L, Aldous S, et al. 2-Hour accelerated diag-nostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial. J Am Coll Cardiol. 2012;59(23):2091-2098.

Related Calculator

• Access the ADAPT Protocol for Cardiac Event Risk.
• Access the TIMI Risk Index.
• Access the TIMI Risk Score for STEMI.

Vancouver Chest Pain Rule

• Introduction
• Points & Pearls
• Why and When to Use, and Next Steps
• Calculator Review Author
• Advice
• Critical Actions
• Evidence Appraisal
• Selected Abbreviations
• Calculator Creator
• References

Introduction

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Points & Pearls

• The goal of the original derivation study was to have a prediction rule that allowed for the safe discharge of emergency department (ED) chest pain patients within 2 hours and without the need for further provocative testing.
• The original derivation study tested with troponin T, but an external validation study showed no difference in the performance of the rule with high-sensitivity troponin.
• The incidence of disease may be higher in the countries where the rule was developed and tested (Canada, Australia, New Zealand) than in the United States.
• The primary outcome was the diagnosis of acute coronary syndromes (ACS), defined as an acute myocardial infarction or unstable angina, within 30 days. Acute myocardial infarction was defined as positive troponin, electrocradiogram (ECG) consistent with acute myocardial infarction, or death without any other cause or event; unstable angina was defined as coronary angiogram showing 70% lesion or revascularization, with either percutaneous coronary intervention or coronary artery bypass grafting.
• Adverse events were broadly defined and included the following: tachycardia or bradycardia requiring medical intervention; respiratory failure requiring assisted ventilation; pulmonary embolism; aortic dissection or aneurysm; new congestive heart failure requiring intravenous medications; hypotension requiring vasoactive agents or an intra-aortic balloon pump; chest compressions; percutaneous coronary intervention; or coronary artery bypass grafting.

Why and When to Use, and Next Steps

Calculator Review Author

Hyunjoo Lee, MD

Department of Emergency Medicine

Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA

Carlos Rodriguez, MD

Department of Emergency Medicine

Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA

Advice

Patients who meet the low-risk criteria can be considered for discharge from the ED without further provocative testing. Otherwise, patients should be ruled out for ACS per normal chest pain protocols utilizing serial ECGs, cardiac biomarkers, and risk stratification. These patients may require additional provocative testing.

Critical Actions

Patients who meet low-risk criteria can be consid-ered for discharge from the ED without further provocative testing for ACS. Other etiologies of chest pain should be considered, including aortic, esophageal, pulmonary, cardiac, abdominal, and musculoskeletal sources. On the other hand, patients who do not meet the low-risk criteria should be managed as per usual chest pain protocols, including but not limited to consideration of aspirin, nitroglycerin, and serial ECGs and biomarkers.

Evidence Appraisal

Scheuermeyer et al (2014) derived the Vancouver Chest Pain Rule in a prospective cohort study of 763 ED patients at St. Paul’s Hospital, an urban tertiary care center, and internally validated the rule in a prospective cohort of 906 ED patients at the same hospital. The study included ED patients complaining of anterior or lateral chest pain who were suspected of having possible ischemic chest pain. Patients were excluded for any of the following: aged < 25 years, traumatic etiology, radiologically evident alternate cause of chest pain, previous study enrollment in the past 30 days, terminal illness, or communication barriers. The primary outcome was the diagnosis of ACS, defined as an acute myocardial infarction or unstable angina within 30 days.

ECGs were labeled as having ischemic factors if there were any of the following: ST elevation > 2 mm in 2 consecutive precordial leads or > 1 mm in 2 consecutive limb leads; ST depression > 2 mm in V1/V2; ST depression > 0.5 mm or Q waves or T-wave inversions in 2 contiguous leads; left bundle branch block; left ventricular hypertrophy; or a paced rhythm. Of note, “ischemic ECG changes” in this study are not the same as those in the American Heart Association (AHA) guidelines. The AHA uses 1 mm as the measurement cutoff for significant ST elevation, except in the anterior leads, which are age- and sex-dependent. Also, the AHA does not consider a paced rhythm or the existence of a left bundle branch block or left ventricular hypertrophy as signs of acute ischemia.

In the derivation cohort, 10.1% had an acute myocardial infarction and 11.5% had unstable angina. Based on the Vancouver Chest Pain Rule, no cases of ACS were missed, and 18.6% of patients without ACS would have been able to be discharged within 2 hours without the need for additional provocative testing, resulting in 100% sensitivity, 18.6% specificity, 100% negative predictive value (NPV), and 25.3% positive predictive value (PPV).

In the internal validation cohort, 4.3% had an acute myocardial infarction and 8.8% had unstable angina. The Vancouver Chest Pain Rule missed 1 case of unstable angina: a 48-year-old male who screened as low-risk but was taken to the catheterization lab because of documented prehospital hypotension, and was found to have a 50% lesion to the left anterior descending coronary artery. Based on the validation cohort, the Vancouver Chest Pain Rule had 99.2% sensitivity, 23.4% specificity, 99.5% NPV, and 16.4% PPV.

Cullen et al (2014) externally validated the Vancouver Chest Pain Rule in a prospective cohort of 1635 ED patients in Brisbane, Australia, and Christchurch, New Zealand, comparing sensitive and highly sensitive troponin assays. The study included ED patients with ≥ 5 minutes of suspected ischemic chest pain. Patients were excluded if there was a clear non-ACS etiology of chest pain, previous study enrollment in the past 45 days, terminal illness, inability or unwillingness to consent, or pregnancy. All patients had troponins drawn on presentation and at ≥ 6 hours. Blood was also drawn at 2 hours for the highly sensitive troponin assay. Cullen et al looked at the same primary outcome of ACS, defined as acute myocardial infarction or unstable angina within 30 days. With the usual-sensitivity troponin assay, 20.4% of patients had ACS, resulting in 98.8% sensitivity, 15.8% specificity, 98.1% NPV, and 23.2% PPV. The Vancouver Chest Pain Rule, using the usual-sensitivity troponin assay, missed 4 cases of unstable angina. When the highly sensitive troponin assay was used, 20.2% of patients were identified with ACS, resulting in 99.1% sensitivity, 16.1% specificity, 98.6% NPV, and 23.3% PPV. The Vancouver Chest Pain Rule using the highly sensitive troponin assay missed 3 cases of unstable angina. There was no statistically significant difference in the function of the Vancouver Chest Pain Rule using the usual-sensitivity troponin versus the highly sensitive troponin assay.

Selected Abbreviations

Calculator Creator

Frank X. Scheuermeyer, MD

References

Original/Primary Reference

• Scheuermeyer FX, Wong H, Yu E, et al. Development and validation of a prediction rule for early discharge of low-risk emergency department patients with potential ischemic chest pain. CJEM. 2014;16(2):106-119.

Validation

• Cullen L, Greenslade JH, Than M, et al. The new Vancouver Chest Pain Rule using troponin as the only biomarker: an external validation study. Am J Emerg Med. 2014;32(2):129- 134.

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