Numerous high-sensitivity cardiac troponin (hs-cTn) assays for acute myocardial infarction (MI) are available.^1,2 These assays differ in their limits of detection, precision, and repeatability.³ The American College of Cardiology and American Heart Association guidelines endorse the 99th percentile upper reference limit for detecting myocardial injury to diagnose acute MI using hs-cTn.⁴ Evidence of myocardial injury with cardiac symptoms, new electrocardiogram changes, loss of viable myocardium per imaging, or evidence of coronary thrombus on angiography meets diagnostic criteria for acute MI.⁵ There is no standard cutoff value for hs-cTn. Abnormal values are based on a reference population for individual assays.

ACCURACY

There is little evidence comparing the diagnostic accuracy between conventional and hs-cTn assays. One study of 440 emergency department patients with chest pain found no statistically significant difference in acute MI diagnosis when comparing conventional troponin assay and hs-cTn testing.⁶

A prospective meta-analysis of 22,457 emergency department patients studied the use of hs-cTn assays for risk stratification with a primary outcome of acute MI or cardiac death at 30 days.⁷ In patients with hs-cTn I concentrations less than 5 ng per L (5 μg per L) on presentation, the negative predictive value was 99.5%.⁷ Similarly, a prospective, multicenter, observational study of 2,212 adult patients identified a negative predictive value of 99.6% (95% CI, 99.2% to 99.9%) for acute MI or death at 30 days if a single hs-cTn was less than 5 ng per L.⁸ A positive predictive value of at least 70% for acute MI was identified with hs-cTn of 120 ng per L (120 μg per L) or greater.⁸

A series of prospective studies of emergency department patients found that the positive predictive value of hs-cTn I and troponin assays for acute MI varies depending on timing and cutoff concentration.⁹ At presentation, lower hs-cTn concentrations and smaller absolute changes during serial sampling were associated with a lower likelihood of acute MI. From these data, risk calculator tools have been developed to determine negative predictive value, positive predictive value, sensitivity, specificity, and 30-day risk of death or MI.⁹

BENEFIT

The hs-cTn assay detects positive values at a much lower concentration than a conventional assay.¹ Variables such as age, sex, time of day, and underlying medical conditions can lead to inaccurate diagnosis of myocardial damage in conventional troponin testing. The hs-cTn assays do not vary as much with these variables.¹

The potential for early discharge from the emergency department without invasive testing is a benefit of hs-cTn testing (Figure 1¹⁰). The American College of Emergency Physicians developed a clinical policy supported by a systematic review recommending that patients be eligible for early discharge with a non-ischemic electrocardiography finding and negative hs-cTn results tested serially over 2 hours.^4,11 In a retrospective observational study involving 18,025 medical and surgical patients who underwent hs-cTn testing, there was a decrease in the number of patients diagnosed with MI, although there was no change in use of resources or in-hospital mortality.¹²

HARMS

With a lower limit of detection compared with a conventional assay, hs-cTn assays may overdiagnose MI and result in more false-positive results.¹³ A retrospective study across five emergency departments showed that hs-cTn assays increased initial blood testing and electrocardiography.¹⁴ They did not decrease the number of computed tomography scans, stress tests, and percutaneous cardiac interventions.¹⁴ However, a European prospective study of 2,544 patients showed similar rates of coronary angiography with lower rates of stress testing and shorter time to emergency department discharge.¹⁵

Like conventional assays, the hs-cTn assay may be elevated in conditions other than acute coronary syndrome (e.g., sepsis, myocarditis, pericarditis).¹ Further, subsequent blood measurements can be invasive for patients.¹

COST

Medicare recognizes hs-cTn testing and reimburses $390.75 per blood draw (Healthcare Common Procedure Coding System [HCPCS] code 0308U; analysis of three proteins [high-sensitivity troponin, adiponectin, and kidney]).¹⁶ This is significantly more costly than quantitative troponin analysis (HCPCS 84484) and qualitative troponin analysis (HCPCS 84512), for which Medicare reimburses $12.47 and $10.09, respectively, per blood draw.¹⁶

A 2021 economic analysis found no differences in costs and outcomes between high-sensitivity and conventional troponin protocols in patients presenting to the emergency department with suspected acute coronary syndrome.¹⁷ Despite improved emergency department efficiency, the associated cost savings were offset by higher inpatient costs.¹⁷

BOTTOM LINE

Compared with conventional assays, hs-cTn assays have a lower limit of detection and a good overall negative predictive value at certain levels in diagnosing acute MI in patients presenting with cardiac symptoms. Despite guidelines to define the criteria for “high sensitivity,” the heterogeneity between assays and institutional protocols makes universal adoption of the hs-cTn assay challenging. Evidence is limited in the primary care setting, and further research is needed.