Written by Jason Lesnick
High sensitivity cardiac troponins (hs-cTn) can be more complex to interpret than our usual diagnostics and are worth a deep dive to understand. This article does an incredible job summarizing existing guidelines and data about how to utilize hs-cTn clinically.
Why does this matter?
hs-cTn assays have been used outside of the U.S. for over a decade and were approved for use in the U.S. by the FDA in 2017. AHA/ACC guidelines recommend hs-cTn as the preferred biomarker for myocardial injury.
My heart can’t take it.. The troponins are just.. too sensitive!
The fourth Universal Definition of Myocardial Infarction recommends using the 99th percentile of the upper reference limits as the threshold for myocardial injury. That sounds simple enough, but there are many caveats. First, the 99th percentile varies by sex – women have lower 99th percentiles than men; thus, there need to be sex-specific 99th percentiles. Second, the 99th percentile upper reference limits are assay-specific and can vary from 11.6/19.8 ng/L for women/men in one assay, respectively, up to 53.7/78.5 ng/L for another. This means you must know what specific hs-cTn assay your facility uses.
The authors share that a single low hs-cTn can sufficiently identify patients at low risk for acute MI based on existing data in patients who present >2 hours from chest pain onset. The 2021 AHA/ACC guidelines state that, “for patients with acute chest pain, a normal ECG, and symptoms suggestive of ACS that began at least 3 hours before ED arrival, a single hs-cTn concentration that is below the limit of detection (LoD) on initial measurement (time zero) is reasonable to exclude myocardial injury.” That sounds great, right? Except that none of the FDA approved hs-cTn assays are allowed to report the LoD; instead, they can only report the limit of limit of quantitation (LoQ), which is the lowest concentration with a 20% coefficient of variation. The LoQ is higher than the LoD and varies by assay, and the existing recommendation then doesn’t apply in the US. There is, however, some data that LoQ is safe for a single-sample rule out.
Utilizing a delta troponin can help increase specificity of hs-cTn, because hs-cTns detect more chronic myocardial injury. Some patient populations where this results in a lack of specificity for MI include: elderly, critically ill, and those with ESRD. The benefit of hs-cTn to us in the ED is that this can expedite early discharge in low risk patients and reduce overcrowding.
Notably, the European Society of Cardiology 2020 guidelines recommend using 0/1 hour and 0/2 hour early rule-out algorithms with class IB recommendations. They downgraded the recommendation for using a 0/3 hour rule out given that the data points to the 0/1 and 0/2 hour early rule outs being safer than the 0/3 hour algorithm.
The entire article is a fascinating read, and the authors have done an excellent job reviewing the current guidelines and evidence regarding hs-cTn. It’s a must-read if you use – or will soon use – hs-cTn in your shop!
High-Sensitivity Cardiac Troponin and the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guidelines for the Evaluation and Diagnosis of Acute Chest Pain. Circulation vol. 146,7 (2022): 569-581. doi:10.1161/CIRCULATIONAHA.122.059678.