The management of emergency department patients with chest pain continues to evolve. There was a time when  everyone with nary but a thoracic twinge got admitted. Even many low-risk patients were admitted (either to an observation unit or an inpatient bed) for noninvasive cardiac testing. Others would get testing within 24 to 72 hours. However, this approach was and remains inefficient and costly. Most important, it has never been shown to definitively improve patient-oriented outcomes.

We tend to underestimate the risks of admitting patients to the hospital as well as the risks of overdiagnosis (ie, false positives associated with noninvasive cardiac tests). With the recent introduction and use of sixth-generation high-sensitivity (hs) troponins, validation of the HEART Pathway (a clinical decision tool with an acronym that includes physician gestalt based on History, ECG features, Age of patient, traditional Risk factors for ACS, and initial Troponin) for both diagnosis and prognostication, and an ACEP clinical policy suggesting that stress testing should not be routinely done, the emergency management of the low-risk chest pain patient is undergoing a paradigm shift—for the better.^1–3

Patients at low risk for acute coronary syndromes (ACS) are those who are hemodynamically stable, have no concerning features on history or examination, and do not have objective evidence of myocardial ischemia on initial ECGs and biomarker testing. Consensus guidelines further define the low-risk patient as having a less than 1 percent risk of a major adverse cardiac event (MACE) or death at 30 days’ follow-up, a threshold below which the harms inherent in further testing appear to outweigh any clinical benefit.^4,5

Conventional Versus hs-Troponin

Conventional troponin assays use a reference limit at or near the 99th percentile of normal value, so any elevation above the reference level is, supposedly, consistent with myocardial injury. However, because these are binary assays (a test that gives a yes-or-no answer), some clinically important myocardial injury may not be initially detected at normal levels, thus necessitating serial troponin testing over 6 to 12 hours to achieve sufficient sensitivity.

In contrast, hs-troponin assays should not be considered binary tests. In fact, by definition, 50 percent of healthy individuals have detectable hs-troponin concentrations at baseline. Hs-troponin assays detect much lower concentrations of serum troponin and with much greater precision. This means that hs-troponin assays can detect clinically significant (but also some tiny insignificant) rises and falls in troponin concentrations much sooner in an ED evaluation. Moreover, the accuracy of diagnosing myocardial injury more than merely increases with hs-troponin; the Fourth Universal Definition of Myocardial Infarction is met specifically by the presence of a value above the 99th percentile and a rise or fall in that value (in order to be considered acute).⁶ The key in utilizing the hs-troponin is both recognizing elevated values and observing a rising and falling pattern of hs-troponin (the “delta troponin”), rather than relying on a binary cutoff.

The “delta troponin” is defined as the change in troponin concentration between two assays performed a prespecified time interval apart. The National Academy of Clinical Biochemistry recommends using a dynamic change of 20 percent or more to define myocardial infarction in patients with baseline elevations in troponin.⁷ Note that this change can be an increase or a decrease, in which increasing troponin suggests an evolving myocardial infarction while decreasing troponin suggests a resolving one. However, the bulk of the literature suggests that an absolute delta (eg, 10 ng/L troponin T) rather than a relative change (eg, 20 percent) generally performs better.

Several rapid testing algorithms have been developed with very high sensitivity for ruling out myocardial infarction, in some cases with a single troponin at the time of ED arrival. A normal ECG and a single undetectable hs-troponin drawn three hours or more after the onset of symptoms rules out myocardial infarction at ED arrival in a third of patients.⁸ The ability to detect lower concentrations of troponin also enables rapid serial testing protocols that are independent of the timing of the patient’s symptoms. For example, two-hour serial testing algorithms have been derived and validated for hs-troponin T and hs-troponin I assays (which are similar molecules made by different manufacturers and with different reference ranges) that rule out myocardial infarction in 60 percent of patients and rule in myocardial infarction in 15 percent of patients, leaving only 25 percent of patients undifferentiated after a two-hour ED evaluation.⁹

Utilizing the HEART score with hs-troponins also lowers the number of patients considered low risk from 40 percent to 10 percent.¹

While theoretically the higher sensitivity of these troponin assays is expected to result in lower specificity and overdiagnosis of ACS, based on experience in Canada, where hs-troponins have been widely adapted, the use of hs-troponins compared to conventional assays decreases length of stay and admissions without missing any additional myocardial infarctions.¹⁰

Which Patients Are Safe to Discharge?

Using a single undetectable hs-troponin after three hours of symptom onset or a negative delta two-hour hs-troponin regardless of symptom onset, in combination with normal serial ECGs, not only rules out myocardial infarction in the vast majority of patients but also lowers the posttest probability of 30-day MACE to below 2 percent, a level below which ancillary testing may cause more harm than the risk of ACS itself.⁵

The addition of the HEART score to the pathway lowers the predicted 30-day MACE rate to less than 1 percent.¹¹ Using this decision tool identifies patients considered safe for early discharge. While the HEART score was initially designed to predict the likelihood of ACS in ED patients presenting with acute chest pain, it has now been robustly validated using both conventional and hs-troponin to predict 30-day MACE, leading to a 2018 ACEP Level B recommendation for its use in patients being evaluated for non–ST-elevation acute coronary syndrome or suspected ACS.³

Which Delta HS-Troponin Is Best?

The one-hour delta troponin algorithms perform well; however, the rule-out delta and rule-in delta are often different by only a few nanograms, which may be within the variation of the assay itself.¹² Consequently, misclassification on the basis of assay variation alone may occur. The studies validating one-hour algorithms were done in ideal conditions with samples being batch-tested on a single analyzer with the same lot of reagents. In the real world with multiple analyzers testing samples over time, assay variation is likely to be higher than observed in published studies. With two-hour delta troponins, there is less risk of misclassification from assay variation. Three-hour algorithms have not been shown to be any more accurate than two-hour algorithms.¹³

Is Ancillary Testing After the Initial ED Visit Necessary?

With such a highly sensitive pathway using hs-troponins and HEART score, ancillary testing after the initial ED workup has come under scrutiny. Exercise treadmill stress tests have a false-positive rate as high as 80 percent, leading to unnecessary angiograms, cardiac stents, and even bypass surgery.¹⁴ In ED patients with chest pain and no evidence of acute myocardial infarction, stress testing is associated with higher rates of invasive procedures without reductions in death or myocardial infarction.¹⁵

The 2018 ACEP clinical policy recommends against routine use of ancillary testing prior to discharge in low-risk patients in whom myocardial infarction has been ruled out.³ It argues that limiting complex, expensive, and time-consuming testing can reduce patient cost, emergency department and hospital length of stay, and patient anxiety caused by unnecessary stress testing and potentially false-positive results, once adequate acute myocardial infarction rule-out and risk stratification have occurred.

The American Heart Association guideline recommends that hospital systems establish an agreed-on standard approach to minimize medicolegal risk.¹⁶ Sit down with your cardiologists and hash this out so there is an agreed-upon algorithm that makes sense based on the literature. An algorithm for low-risk chest pain patients that includes hs-troponin and does not include routine ancillary testing is the most reasonable approach based on the current body of literature. Efforts should also be focused on patient education so they understand their incredibly low risk of MACE as well as the significant risks of ancillary testing.

What’s the bottom line? A single undetectable hs-troponin after three hours of symptom onset or a delta two-hour hs-troponin T less than 4 ng/L plus normal serial ECGs and a HEART score of 0–3 rules out acute myocardial infarction and lowers the predicted 30-day MACE to well below 1 percent, a threshold below which ancillary testing may lead to more harm than benefit.

Does clinician judgment (ie, gestalt) matter anymore? On one hand, gestalt is inherent in part of the HEART score (“suspicious” history). However, data on how gestalt performs out of the context of clinical decision tools are emerging, so this remains an open question.

References

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2. Laureano-Phillips J, Robinson RD, Aryal S, et al. HEART score risk stratification of low-risk chest pain patients in the emergency department: a systematic review and meta-analysis. Ann Emerg Med. 2019;74(2):187-203.
3. Tomaszewski CA, Nestler D, Shah KH, et al. Clinical policy: critical issues in the evaluation and management of emergency department patients with suspected non-ST-elevation acute coronary syndromes. Ann Emerg Med. 2018;72(5):e65-e106.
4. Amsterdam EA, Kirk JD, Bluemke DA, et al. Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association. Circulation. 2010;122(17):1756-1776.
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8. Pickering JW, Than MP, Cullen L, et al. Rapid rule-out of acute myocardial infarction with a single high-sensitivity cardiac troponin T measurement below the limit of detection: a collaborative meta-analysis. Ann Intern Med. 2017;166(10):715-724.
9. Reichlin T, Cullen L, Parsonage WA, et al. Two-hour algorithm for triage toward rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Am J Med. 2015;128(4):369-379.e4.
10. Crowder K, Jones T, Wang D, et al. Operational impact and patient outcomes following implementation of high–sensitivity troponin testing in three urban emergency departments. Ann Emerg Med. 2014;64(4 Suppl.):S110.
11. Rezaie S. Management and disposition of low risk chest pain. REBEL EM blog website. Accessed Aug. 13, 2019.
12. Reichlin T, Twerenbold R, Wildi K, et al. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay. CMAJ. 2015;187(8):E243-E252.
13. Fox WR, Diercks DB. Troponin assay use in the emergency department for management of patients with potential acute coronary syndrome: current use and future directions. Clin Exp Emerg Med. 2016;3(1):1-8.
14. Arbab-Zadeh A. Stress testing and non-invasive coronary angiography in patients with suspected coronary artery disease: time for a new paradigm. Heart Int. 2012;7(1):e2.
15. Foy AJ, Liu G, Davidson WR Jr, et al. Comparative effectiveness of diagnostic testing strategies in emergency department patients with chest pain: an analysis of downstream testing, interventions, and outcomes. JAMA Intern Med. 2015;175(3):428-436.
16. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130(25):e344-426.