Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in Acute Coronary Syndrome: Expert Opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine

Abstract

This document is an essential companion to the third iteration of the National Academy of Clinical Biochemistry [NACB, now the American Association for Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG) on cardiac markers. The expert consensus recommendations were drafted in collaboration with the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF-CB). We determined that there is sufficient clinical guidance on the use of cardiac troponin (cTn) testing from clinical practice groups. Thus, in this expert consensus document, we focused on clinical laboratory practice recommendations for high-sensitivity (hs)-cTn assays. This document utilized the expert opinion class of evidence to focus on the following 10 topics: () quality control (QC) utilization, () validation of the lower reportable analytical limits, () units to be used in reporting measurable concentrations for patients and QC materials, () 99th percentile sex-specific upper reference limits to define the reference interval; () criteria required to define hs-cTn assays, () communication with clinicians and the laboratory's role in educating clinicians regarding the influence of preanalytic and analytic problems that can confound assay results, () studies on hs-cTn assays and how authors need to document preanalytical and analytical variables, () harmonizing and standardizing assay results and the role of commutable materials, () time to reporting of results from sample receipt and sample collection, and () changes in hs-cTn concentrations over time and the role of both analytical and biological variabilities in interpreting results of serial blood collections.

Clinical chemistry score versus high-sensitivity cardiac troponin I and T tests alone to identify patients at low or high risk for myocardial infarction or death at presentation to the emergency department

“…A CCS of 4 points or more yielded a specificity of 85% with hs-cTnI and 76% with hs-cTnT, whereas a CCS of 5 points yielded a specificity of 96% with hscTnI and 90% with hs-cTnT. Participants with a CCS of 5 points, reflecting abnormal results for all laboratory tests, represented a high-risk group, with an adjusted HR for patients with a CCS of 5 points versus those with a CCS of less than 5 points of 4.63 The analytical performances of the hs-cTn assays in the 4 cohorts were in agreement with laboratory recommendations for hs-cTn assays (i.e., > 50% above the limit of detection); 6 the range of detectable hs-cTnI concentrations was 84%-94% and that for hs-cTnT concentrations was 64%-84% (Table 1). And across all 4 cohorts, the higher the CCS, the older the participant's age, the higher the hs-cTn level, the higher the glucose level and the lower the eGFR ( Table 2).…”

“…[4][5][6] In practice, different lots of reagents for both hs-cTnI and hs-cTnT have already been observed to yield variation that exceeds 3 ng/L. 7,8 In addition, there are several interferences that affect hs-cTn measurements.…”

“…Algorithms that use the lower limit of reporting, such as the limit of detection, for hs-cTn assays are approaches that pose a safety risk for patients, because this metric is not monitored by clinical laboratories and is subject to analytical bias, with wide variation on repeat measurements on different instruments and different lots of reagents; all of which may lead to patient misclassification. 4,[6][7][8]36 Just as important is that there is no standardization on reporting at the low end: in a 2018 quality survey, undetectable ranges were reported from clinical laboratories that ranged from less than 1 to less than 10 ng/L for the Abbott hs-cTnI assay and less than 3 to less than 13 ng/L for the Roche hs-cTnT assay. 37 In this regard, physicians using "undetectable concentrations" will misclassify patients depending on how the clinical laboratory reports their results, if they use results from hs-cTn testing alone.…”

“…5,38 The CCS was reproducible across different sample types (ethylenediaminetetraacetic acid plasma, lithium heparin plasma and serum), and under different storage and preanalytical conditions, which should be reassuring to physicians and clinical laboratories, because hs-cTn measurements alone can be affected by different blood collection tubes and preanalytical interferences. 6,39 Some of these preanalytical sources of variation easily exceed the analytical imprecision benchmark of 10% for hs-cTn assays, and despite attempts to sensitize the clinical community to the importance of this matter, it still represents a substantial gap in optimizing patient care. 6,39 Adoption of the CCS algorithm would standardize reporting of hs-cTn test results, how the tests are interpreted in the normal range, and represent an option less susceptible to both analytical and preanalytical errors.…”

“…Both the Roche Elecsys Troponin T hs and Abbott ARCHITECT High Sensitive Troponin-I assays used in these studies met the most recent laboratory recommendations for total analytic error for hs-cTn assays 6 (Appendix 2). The approach to developing the CCS was pragmatic, using equal weighting for eGFR and glucose, and using established and recognized cut-offs for normality for these tests.…”