Use of high‐sensitivity cardiac troponin in the emergency department: A policy resource and education paper (PREP) from the American College of Emergency Physicians

Abstract

This Policy Resource and Education Paper (PREP) from the American College of Emergency Physicians (ACEP) discusses the use of high‐sensitivity cardiac troponin (hs‐cTn) in the emergency department setting. This brief review discusses types of hs‐cTn assays as well as the interpretation of hs‐cTn in the setting of various clinical factors such as renal dysfunction, sex, and the important distinction between myocardial injury versus myocardial infarction. In addition, the PREP provides one possible example of an algorithm for the use of a hs‐cTn assay in patients in whom the treating clinician is concerned about potential acute coronary syndrome.

1. INTRODUCTION

Chest pain is a common emergency department (ED) complaint with heart disease being a leading cause of death in the United States. ¹ Myocardial infarction (MI) is a diagnosis with significant morbidity and mortality that has many atypical presentations such that it may be misdiagnosed. Criteria for diagnosing an acute MI include detection of a rise and/or fall of cardiac biomarkers with at least 1 value above the 99th percentile of the upper reference limit (URL) and at least 1 of the following: symptoms of myocardial ischemia, electrocardiogram (ECG) changes indicative of new ischemia, development of pathological Q waves, imaging evidence of new loss of viable myocardium (eg, new regional wall motion abnormality) or coronary thrombus. ² Over the years, various biomarkers, each with their own unique profiles (eg, creatine kinase, myoglobin, troponin), have been used to establish the diagnosis of acute MI. Cardiac troponin is currently considered the industry standard biomarker.

The latest generation of troponin is a high‐sensitivity troponin (hs‐cTnT or hs‐cTnI), which can detect very small levels of troponin in the bloodstream. Given an increase in the detectability of hs‐cTn, it is important for emergency physicians to understand that a detectable level does not mean a patient is necessarily having an acute MI. There are multiple other conditions that can result in an elevated hs‐cTn result other than acute coronary syndrome (ACS) such as renal failure, chronic heart failure, sepsis, pulmonary embolism, myocarditis, or aortic dissection (Table 1). ³ Therefore, emergency physicians must interpret the hs‐cTn results in the context of the patient's history and clinical presentation. A diagnostic algorithm is useful to inform the clinical decision‐making for patients who present to the ED with suspected ACS. As with any diagnostic workup, engaging patients in shared decision‐making, taking into account their values and preferences is prudent. The objective of this paper is to discuss interpretation of high‐sensitivity troponin and present a sample algorithm for patients undergoing evaluation for potential ACS.

TABLE 1.

Etiologies of elevation of coronary troponin unrelated to acute coronary syndrome.

	Acute	Chronic
Supply and demand mismatch	Arrhythmias
	Coronary spasm
	Endothelial dysfunction
	Aortic dissection	Severe aortic valve disease
	Shock (cardiogenic, hypovolemic, septic)	Hypertrophic cardiomyopathy
	Respiratory failure	Left ventricular hypertrophy
	Cocaine use	Hypertension
	Coronary embolism or vasculitis	Anemia
Non‐ischemic myocardial damage	Myopericarditis
	Pacing or defibrillation shocks
	Cardiotoxic agents
	Cardiac contusion
	Cardiac surgery
	Radiofrequency or cryoablation
	Carbon monoxide poisoning
Multifactorial causes of myocardial damage	Heart failure
	Renal failure
	Sepsis	Sarcoidosis
	Pulmonary embolism	Amyloidosis
	Takotsubo cardiomyopathy
	Extreme exertion
	Gastrointestinal bleeding
	Rhabdomyolysis
	Stroke
	Skeletal myopathy

2. INTERPRETATIONS

2.1. Types of high‐sensitivity troponin

Both hs‐cTnI and hs‐cTnT assays are approved for use. In the United States, available hs‐cTnI assays include Abbott Architect Stat and the Siemens HsVista; and only 1 hs‐cTnT assay, the Roche Elecsys Troponin T STAT. Each assay has different analytic characteristics including different sensitivities (limit of detection) and 99th percentile cutoffs) and, as a result, their values cannot be compared interchangeably. ⁴ , ⁵ Although few studies directly compare these assays, most evidence evaluating hs‐cTn assays show similar clinical performance. ⁶ One meta‐analysis evaluating the performance of a 0‐ and‐1‐hour rule‐in/rule‐out algorithm in detecting acute MI, found all 3 assays had similar diagnostic characteristics, with negative predictive values >99% and sensitivities of ≈98%. ⁷ Some hs‐cTn manufacturers provide conversion factors to aid in comparing a patient's baseline conventional troponin with hs‐cTn measurements, which may be useful in trending troponin levels during transitions to hs‐cTn assays at individual institutions.

2.2. Myocardial injury versus infarction

One concern with high‐sensitivity troponin assays is an increase in the number of patients with abnormal troponin levels and the assumption that the abnormal troponin levels indicate acute MI rather than myocardial injury. Several clinical entities aside from ACS can cause elevations in troponin, which are more detectable with hs‐cTn assays. According to the fourth universal definition of MI, myocardial injury can be associated with either stable troponin levels or rise and fall in troponin. However, myocardial injury is not always associated with signs and/or symptoms of MI. ² Examples of myocardial injury include acute heart failure, chronic kidney disease, sepsis, and myocarditis. In 1 trial of 48,282 patients with suspected ACS in Scotland, 21% had hs‐cTnI concentrations above the 99th percentile, which would be considered abnormal. Of those cases that were adjudicated with a final diagnosis, 67% were classified as having MIs and 33% as having myocardial injury. A higher proportion of patients were reclassified as having myocardial injury by the hs‐cTnI compared with conventional troponin. Although 7% more of these patients underwent angiography, MI and cardiovascular death remained unchanged, introducing some concern for overdiagnosis leading to increased unnecessary testing and potential for iatrogenic complications. ⁸ Similarly, a prospective observational study in the United States found that when hs‐cTnT assay was used, 16% of patients were classified as myocardial injury. ⁹ These studies demonstrate that, compared with conventional troponin assays, a significantly higher proportion of patients undergoing testing with hs‐cTn assays will have elevated baseline troponin values, but this should not necessarily be mistaken for ACS. Although abnormal hs‐cTn levels do not necessarily indicate the presence of ACS, abnormal troponin levels are associated with increased morbidity and mortality. ¹⁰ , ¹¹

2.3. Sex‐specific cutoffs

Sex‐specific differences in pathophysiology and clinical presentation of cardiovascular diseases have been well described. Additionally, the 99th percentile URL of hs‐cTnI assays in healthy adults is consistently higher for men than women. ¹² There is considerable debate regarding the clinical utility of these cutoffs. ² A study of over 1600 patients presenting to US EDs with suspected ACS found that the use of sex‐specific cutoffs did not significantly change test characteristics. ¹³ Another observational study in the United States found that the use of sex‐specific cutoffs with hs‐cTnT increased the number of patients diagnosed with myocardial injury but not with MI. ⁹ Both of these studies used serial troponin testing and the value of sex‐specific cutoffs may depend on the use of serial testing.

2.4. Delta troponin

When hs‐cTn is undetectable, ACS is extremely unlikely, although most patients in these studies had an initial troponin drawn at least 2–3 hours after chest pain onset. ¹⁴ , ¹⁵ , ¹⁶ However, few patients presenting with suspicion of ACS will have undetectable hs‐cTn. Most patients will have low hs‐cTn levels that are below the abnormal threshold. In cases of low but detectable hs‐cTn levels, serial troponin testing can help exclude ACS. ² One widely used and well‐studied algorithm uses the change (delta) in troponin in either a positive or negative direction between 0 and 1 hour. ¹⁷ , ¹⁸ For patients with a low but detectable level of hs‐cTn, the algorithm recommends that MI can be safely excluded if the delta hs‐cTn value is <3 ng/L. However, if the patient has a delta troponin of ≥5 ng/L, then the patient meets the diagnostic criteria for an acute MI. ¹⁷ , ¹⁸ In a recent meta‐analysis, an algorithm using delta troponins with any hs‐cTn had a pooled sensitivity of 98.7% (95% confidence interval 97.3%–99.3%) across diverse cohorts. ⁷

2.5. Renal dysfunction

The diagnosis of MI in patients with renal insufficiency can be difficult as many patients with chronic kidney disease have elevated troponin values and the majority of patients with end‐stage renal disease (ESRD) have elevated hs‐cTn values. As might be expected, the specificity of troponin for MI is reduced at lower levels of renal function. ¹⁹ , ²⁰ , ²¹ , ²² One meta‐analysis found that hs‐cTnT may be less specific compared to hs‐cTnI assays; however, the studies included in this analysis were heterogeneous making definitive conclusions difficult. ²³ Some authors have proposed alternative cutoff values in patients with ESRD, but none have been externally validated. ²⁴ Therefore, clinicians should continue to integrate a patient's pretest probability, based on clinical history and exam, with the hs‐cTn lab results and use serial troponin measurements as appropriate.

3. ALGORITHMS

There have been several proposed algorithms reported in the literature using hs‐cTn in the evaluation of patients presenting to the ED with chest pain and suspected ACS. Most early algorithms developed and validated in Europe incorporated clinical gestalt, patient risk, and serial troponin measurement either at time 0 and 1 hour, 0 and 2 hour, and/or 0 and 3 hours from presentation to the ED. ²⁵ These algorithms were found to perform similarly in the United States even in the absence of incorporating ECG changes and clinical risk stratification tools. ²⁶

The successful development and adoption of a hs‐cTn clinical algorithm for suspected ACS require addressing inevitable challenges in adoption while involving appropriate stakeholders within individual health care organizations including cardiology, emergency medicine, internal medicine, and clinical laboratory technicians. All users of the algorithm must be educated on the nuances of hs‐cTn and how it differs compared to prior conventional troponin use. ²⁷ Furthermore, there is not 1 universally accepted clinical algorithm as each institution will have unique characteristics that need to be addressed such as patient population, practice environment, physician and non‐physician healthcare practitioner risk tolerance, and the type of hs‐cTn assay used. In addition, the role for point‐of‐care troponin testing as well as use of coronary computed tomography angiography for risk stratification are evolving.

Figure 1 is an example of one algorithm for the evaluation and management of patients presenting to the ED with chest pain using hs‐cTn. The assay‐specific values are included in the table to help with interpretation. It is important to note that this approach is exclusive to patients with signs and symptoms concerning for ACS. High‐sensitivity troponin values require interpretation based on clinical context in conjunction with a clinical algorithm. It is impossible to show one universal algorithm due to the different assays available and nuances at individual institutions. The algorithm depicted in Figure 1 has both the 0‐ and 1‐hour, 0‐ and 2‐hour, or 0‐ and 3‐hour options overlaid in a single algorithm. In particular, an institution may choose not to implement the 1‐hour component and use a 2‐ or 3‐hour interval due to logistical challenges in getting the repeat hs‐cTn drawn that quickly.

FIGURE 1.

Example of one possible algorithm for patients undergoing evaluation for acute coronary syndrome using high‐sensitivity cardiac troponin. Abbreviations: ACS, acute coronary syndrome; FDA, Food and Drug Administration; hs‐CTn, high‐sensitivity cardiac troponin; hs‐CTnI, high‐sensitivity cardiac troponin I. ²⁸ , ²⁹ , ³⁰ , ³¹

4. CONCLUSION

The growing use of hs‐cTn in clinical practice requires understanding the particular assay and the factors that influence the interpretation of a specific value in the context of the patient's clinical presentation. Future research is necessary to delineate meaningful cutoff values in patients with renal dysfunction and baseline elevated values and to understand the clinical impact of various diagnostic strategies.

Promes SB, Gemme S, Westafer L, Wolf SJ, Diercks DB. Use of high‐sensitivity cardiac troponin in the emergency department: A policy resource and education paper (PREP) from the American College of Emergency Physicians. JACEP Open. 2023;4:e12999. 10.1002/emp2.12999