Low Risk Chest Pain and Clinically Relevant Adverse Cardiac Events (CRACE)

Background: In 2010, 5.4% of all emergency department (ED) visits in the United States were for chest pain. Admission or observation of such patients cost about $11 billion dollars in the United States in 2006. The majority of these admissions are commonly determined to be non-cardiac in etiology. Many physicians and patients believe that a hospital admission or extended observation after a “negative” ED workup has a safety benefit for patients. Previous studies have looked at 30-day mortality, but no current large trials have looked the short-term risk for clinically relevant adverse cardiac events, including inpatient STEMI, life-threatening arrhythmias, cardiac or respiratory arrest, or death. Other things to keep in mind is that one of the pitfalls of hospitalization of chest pain patients can lead to false-positive testing, hospital-acquired infections, venous thromboembolism, and other iatrogenic events, and can have greater than a 2% rate of adverse events at 30 days often cited as the upper boundary estimate for low-risk chest pain patients.

The purpose of the current study was to quantify the incidence of short-term clinically relevant adverse cardiac events (CRACE), or more simply put, life-threatening events  in patients admitted to the hospital after a “negative” ED evaluation of ischemia. The definition of “negative” was negative serial cardiac biomarkers, normal vital signs, and non-ischemic electrocardiograms (ECGs).

And by the way, checkout the authors: Scott Weingart and David Neman….

What They Did:

Blinded, Multicenter (3 hospitals in the US Midwest) retrospective chart review of 45,416 patient encounters that were admitted or observed with:

  1. Primary chief complaint of chest pain, chest tightness, chest burning, or chest pressure and
  2. Negative serial cardiac biomarkers performed at 60 – 420 minutes after initial cardiac biomarkers


Clinically Relevant Adverse Cardiac Events (CRACE):

  1. Life-threatening arrhythmia (i.e Ventricular fibrillation, sustained ventricular tachycardia requiring treatment, symptomatic bradycardia or bradyasystole requiring emergent intervention, and any tachydysrhuthmia treated with cardioversion);
  2. Inpatient STEMI;
  3. Cardiac or respiratory arrest; and
  4. Death



  • 45,416 patients reviewed –> 22,457 were admitted –> 11,230 (24.72%) had 2 troponin negative results between 60 – 420 minutes apart
  • 20/11,230 (0.18%) patients had CRACE
  • Instead of reviewing all >11k charts, 561 charts were randomly sampled of which 363 (64.7%) met inclusion criteria (i.e. Chest pain + 2 negative troponins) –> This estimate was applied to the total (i.e. 0.647 x 11,230) –> 7,266 medical records (estimate of all charts)
  • If you excluded patients with abnormal vitals signs (VS) and/or ischemic ECG findings, LBBB or Paced Rhythms, only 4 patients had CRACE (i.e. 4/7266 or 0.06%)
  • 62/11230 (0.55%) patients had possible or definite MI –> After exclusion of patients with abnormal VS and non-ischemic ECGs, 28 patients remained –> none suffered CRACE
    • 26 Patients had heart catheterization
    • 18 Percutaneous Coronary Intervention (PCI)
    • 5 Coronary Artery Bypass Graft (CABG)
    • 4 Optimized medical management


  • This is a chart review, therefore if something was not documented in the chart, this could underestimate the incidence of clinically relevant events
  • Only hospitalized patients with events were evaluated, therefore patients who were discharged didn’t have follow-up or outcome data reported
  • Even though this is a multicenter study, all three hospitals were from a single city in the US Midwest, and the patient population may not be generalized to other settings
  • The primary outcome was based on an estimate of a 5% sample of 11,230 patients (i.e. 7266 patients), which means the exact rate of CRACE may be slightly higher or lower, but with such a small number of CRACE events, this alteration of rate would be minimal
  • Small number of events prevents meaningful analysis of risk factors that could be associated with adverse outcomes
  • 26 patients underwent invasive testing with 22 undergoing subsequent coronary revascularization, which raises the possibility that adverse outcomes may have been prevented by revascularization
  • This study was not able to capture the incidence of iatrogenic harm owing to hospitalization, therefore a true risk-benefit analysis of admission compared with expedited outpatient follow-up could not be determined



  • Summary of 4 CRACE events (2 non-cardiac chest pain & 2 possible iatrogenic etiologies):
  1. 80s year old with PMH of CAD s/p stent, HTN, DM, obesity CHF, CKD on Coumadin who died from massive GI hemorrhage secondary to Coumadin coagulopathy.
  2. 60s year old with PMH of HTN, DM, and MI with 2 troponins 130 minutes apart negative. Patient had angiography showing triple-vessel disease and suffered STEMI (99% LAD occlusion) in recovery unit s/p angiography. Patient had emergent IABP and CABG and ultimately discharged to skilled nursing facility.
  3. 40s year old PMH of HTN, T2DM with 2 troponins 97 minutes apart negative. Patient had stress test and developed STEMI during provocative test. He ultimately had angiography with stent in RCA with subsequent VFib and successful defibrillation and ultimately discharge home
  4. 60s year old PMH of HTN, CAD s/p CABG with 2 troponins 315 minutes apart negative. Patient had bradyasystole cardiac arrest after being given nitroglycerine which resulted with chest compressions and successful pacemaker placement. Final diagnosis was sinus node dysfunction and ultimately patient was discharged home.
  • NSTEMI patients were excluded from the primary outcome, but included in the secondary outcomes. The reason is an elevated troponin in the absence of morbidity, mortality, or a life-threatening cardiac event was not deemed to be a clinically relevant endpoint. Also routine invasive intervention does not appear to affect mortality in patients with NSTEMI and associated with small, equivocal benefits on nonfatal MI.
  • Adverse iatrogenic events as a result of admission may eclipse potential benefits in low-risk chest pain patients. This study quotes that current estimates are 1 in 164 hospitalized patients have a preventable adverse event that contributes to their death with serious harm 10 to 20 fold more common. When compared to the cohort in this study the risk of CRACE after negative ED workup was 1 in 1817, suggesting that we are more likely to do harm than benefit in these already low risk patients by admission.
  • This study is not concluding that no benefit is derived from further management or diagnostic workup of these low risk chest pain patients, but instead maybe further evaluation performed in the outpatient rather than inpatient setting after shared decision making discussions about risks/benefits of admission should be considered.

Study Conclusion: The risk of clinically relevant adverse cardiac events in patients treated in the ED with chest pain, serial troponin-negative findings, no concerning vital signs, and interpretable non-ischemic ECG findings is exceedingly low and may inform physicians and patients decisions about the utility and potential benefits of hospitalization compared with outpatient evaluation.

Clinical Take Home Point: In patients presenting to the ED with chest pain, normal VS, non-ischemic ECG, negative serial cardiac enzymes 3 hours apart, a shared decision making approach should be taken discussing the risks and benefits of inpatient vs outpatient diagnostic workups.


  1. Weinstock MB et al. Risk For Clinically Relevant Adverse Cardiac Events in Patients With Chest Pain at Hospital Admission. JAMA Intern Med 2015. [Epub ahead of print] PMID: 25985100

For More on this Topic Checkout:

Post Peer Reviewed By: Matt Astin (Twitter: @mastinmd)

Cite this article as: Salim Rezaie, "Low Risk Chest Pain and Clinically Relevant Adverse Cardiac Events (CRACE)", REBEL EM blog, June 4, 2015. Available at: https://rebelem.com/low-risk-chest-pain-and-clinically-relevant-adverse-cardiac-events-crace/.

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