Algorithms based on high-sensitivity assays of cardiac troponins may potentially facilitate the effective triage of emergency medicine department patients with suspected myocardial infarction (MI) to more timely and effective intervention.¹⁰

The patients presenting with complaints suggestive of myocardial infarction comprised 5 to 10% of pre-pandemic emergency medicine department (ED) consults,^1,2 approximately 7 million in the US annually.¹ Being able to rapidly identify the 5 to 20% of those patients who are experiencing acute myocardial infarction (AMI) ³ increases their chance of survival.⁴

Gesa Ines Albert, PhD, senior international medical affairs manager, cardiac, of Roche Diagnostics International, Rotkreuz, Switzerland, described how the use of algorithms based on the high-sensitivity assays can improve patient outcomes as well as the efficiency of EDs.

"Rapid identification of MI as a life-threatening disorder is important for the early initiation of appropriate, evidence-based and effective therapy," Albert said. "In addition, rapid and safe rule-out of MI is of major medical and economic importance because it allows the timely detection and treatment of alternative causes of acute chest pain.

"Many of the alternative causes of acute chest pain are benign, so that rule-out of MI allows patient reassurance and often consideration of discharge from the ED and outpatient management," she explained.

The US lagged behind Europe, Australia, Asia and Canada in not approving the first high-sensitivity assay of cardiac troponins (hs-cTn) until 2017.⁵ Prior to availability of the assays and validated algorithms to interpret changes in levels, the target in EDs to safely "rule out" myocardial infarction with less than a 1% "miss" rate was, itself, often missed.⁶

The hs-cTn assay, specific to myocardial injury, and the European Society of Cardiology (ESC) algorithms to interpret change in serial measurements, have improved the disposition and outcome for these patients; this, by aiding in differentiating between chronic and acute myocardial injury, and rapidly revealing non-ST segment elevation (NSTEMI) myocardial infarction which cannot be diagnosed or excluded by electrocardiogram (ECG) alone.⁹

"ECG and serial sampling of cardiac troponin complement clinical assessment and form the diagnostic cornerstones for MI in the ED," Albert emphasized.

Considering Available Algorithms

The ESC 0/1h and 0/3h algorithms have been validated, and both are recommended by the ESC to interpret changes in troponin level between presentation (0 time) and at a 1- or 3-hour interval, respectively, for presence of AMI.^7,8The 0/3h algorithm has been recommended by the ESC since 2011 and remains commonly used in Europe. The 0/1h algorithm was subsequently developed and has proven useful for very early triage to rule-out or rule-in AMI.⁹

Besides different time intervals, the algorithms employ different protocols. While the results of the 0/1h are available as soon as the second hs-cTn level, the 0/3h algorithm is interpreted on a fixed threshold in conjunction with a Global Registry of Acute Coronary Events (GRACE) score.

To investigate whether either is superior in safety, measured with negative predictive value (NPV) and negative likelihood ratio (LR), and efficacy for the proportion of patients triaged toward ruled-out, Patrick Badertscher, MD, at CRIB in Basel, Switzerland, and colleagues conducted a retrospective analysis of populations receiving either an hs-cTnT or hs-cTnI assay, across multiple EMDs, excluding patients with STEMI.¹⁰ The triage toward rule-in/rule-out with each algorithm was adjudicated by 2 independent cardiologists.

In a cohort of 2,547 patients receiving cTnT-hs measurement, the investigators found the algorithms were comparably safe, but that the 0/1h allowed rule-out of significantly more patients than the 0/3h (60% vs 44%; P = .001).

Badertscher and colleagues declared that both algorithms demonstrate excellent safety in documenting the suitability of most of these patients for early discharge and outpatient management. They concluded, however, that the 0/1h algorithm is superior to the 0/3h, using either hs-cTnT or hs-cTnI, "because it more favorably combines safety and efficacy."

Albert remarked that the data from the large population studies have been convincing.

"Supported by evidence from large diagnostic studies, the latest guidelines of the ESC for the first time recommended the use of a 0/1h algorithm to rapidly rule-out or rule-in NSTEMI, based on high-sensitivity troponin concentrations at presentation and their absolute 1 hour changes," she said.

In an editorial published shortly after the first hs-cTn was approved in the United States, Marc Bonaca, MD, MPH, TIMI Study Group, Brigham and Women's Hospital, Cardiovascular Division, Harvard Medical School, Boston, MA, also commented on the hesitancy to adopt the new tools.¹²

"The broader clinical utility for hs-cTn as a prognostic marker, however, has not been routinely adopted in practice as clinicians struggle to understand how to respond in terms of additional testing and changes in treatment," Bonaca wrote. "In addition, the dramatically increasing frequency of stable, low-level cTn elevations detected with high-sensitivity assays in patients without ACS may lead clinicians to disregard results and be falsely reassured."

Adopting Assay and Algorithm

New methods for rule-out/rule-in of suspected AMI in emergency medicine are necessarily adopted with careful consideration, following validation studies and examination of the context for their development and optimal application.

Raphael Twerenbold, MD, Cardiovascular Research Institute Basel (CRIB), Department of Cardiology, University Hospital Basel, Basel, Switzerland, and colleagues recommend 5 corollaries for incorporating an hs-cTn and ESC algorithm into ED practice:¹³

Use only in conjunction with full clinical assessment: This includes pre-test probability assessment to identify patients at high risk who may not be suitable for early discharge.
Consider it a strategy for triage rather than fully diagnostic: Additional imaging tests such as invasive coronary or CT angiography may be necessary for a definite diagnosis.
Recognize that the percentage of patients meeting criteria for rule-in/rule-out can vary depending on the algorithm, the particular hs-cTn assay, and the clinical setting, including the prevalence of NSTEMI.
Use only after the initial ECG has excluded ST-segment elevation myocardial infarction (STEMI). These high-risk patients need immediate reperfusion therapy based on the ECG without hs-cTn testing.
Incorporate guidance on utilizing hs-cTn assay and algorithm into standard operating procedures of the ED.

"To maximally profit from hs-cTn assays in clinical practice, they should best be used embedded in an institutional standard operating procedure of the ED and in conjunction with a rapid triage algorithm enabling rapid decision-making within a few hours," Twerenbold and colleagues urge in their article. "Such an approach will allow not only to increase patients' safety as compared with conventional, less sensitive cTn assays, but also to substantially reduce duration of stay (in) the ED and costs."

Albert concurred with this assessment of benefit to both patients and the healthcare system. "Particularly overcrowded EDs are likely to benefit most from fast rule-out protocols in order to discharge a substantial proportion of low-risk patients," she said.

References

1. Centers for Disease Control and Prevention. National Hospital Ambulatory Medical Care Survey: 2017 Emergency Department Summary Tables. 2017. https://www.cdc.gov/nchs/data/nhamcs/web_tables/2017_ed_web_tables-508.pdf. Accessed May 29, 2020.

2. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST elevation acute coronary syndromes: executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 64: e139-228.

3. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016; 37:267-315.

4. Twerenbold R, Costabel JP, Nestelberger T, et al. Outcome of applying the ESC 0/1-hour algorithm in patients with suspected myocardial infarction. J Am Col Cardiol. 2019; 74: 483-494.

5. Roche. Breakthrough development for Americans with suspected heart attack--Next generation Troponin T test from Roche cleared by FDA. January 19, 2017. https://www.prnewswire.com/news-releases/breakthrough-development-for-americans-with-suspected-heart-attack--next-generation-troponin-t-test-from-roche-cleared-by-fda-300393665.html. Accessed May 29, 2020.

6. Hollander JE. High-sensitivity troponin: Time to implement. Ann Emerg Med. 2018; 72: 665-667.

7. Twerenbold R, Neumann JT, Sörensen NA, et al. Prospective validation of the 0/1-h algorithm for early diagnosis of myocardial infarction. J Am Coll Cardiol. 2018; 72:620-632.

8. Thygesen K, Mair J, Giannitsis E, Mueller C, et al. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J. 2012; 33:2252-2257.

9. Roffi M, Patrono C, Collet JP, et al. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Hear J. 2016; 37:267-315.

10. Badertscher P, Boeddinghaus J, Twerenbold R, et al. Direct comparison of the 0/1h and 0/3h algorithms for early rule-out of acute myocardial infarction. Circulation. 2018; 137:2536-2538.

11. Nowak RM, Christenson RH, Jacobsen G, et al. Performance of novel high-sensitivity cardiac troponin I assays for 0/1-hour and 0/2- to 3-hour evaluations for acute myocardial infarction: Results form the HIGH-US study. Ann Emerg Med. February 8, 2020. DOI:https://doi.org/10.1016/j.annemergmed.2019.12.008. Accessed May 30, 2020.

12. Bonaca M. Time for a new strategy for high-sensitivity troponin in the emergency department. J Am Coll Cardiol. 2017; 2237-2239.

13. Twerenbold R, Boeddinghaus J, Mueller C. Update on high-sensitivity cardiac troponin in patients with suspected myocardial infarction. Eur Heart J. 2018; 20 (supplement G): G2-G10.

14. Twerenbold R, Rubini GM, Nestelberger T, et al. Optimising the early rule-out and rule-in of myocardial infarction using biomarkers. Cardiovasc Med. 2019;22:w02010.

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