Discordance of High-Sensitivity Troponin Assays in Patients With Suspected Acute Coronary Syndromes

Abstract

Background: High-sensitivity cardiac troponin (hs-cTn) assays have different analytic characteristics.

Objectives: The goal of this study was to quantify differences between assays for common analytical benchmarks and to determine whether they may result in differences in the management of patients with suspected acute coronary syndrome (ACS).

Methods: The authors included patients with suspected ACS enrolled in the ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography) I and II trials, with blood samples taken at emergency department presentation (ROMICAT-I and -II) or at 2 and 4 h thereafter (ROMICAT-II). hs-cTn concentrations were measured using 3 assays (Roche Diagnostics, Elecsys 2010 platform; Abbott Diagnostics, ARCHITECT i2000SR; Siemens Diagnostics, HsVista). Per blood sample, we determined concordance across analytic benchmarks (<limit of detection [<LOD]/LOD-99th percentile/>99th percentile). Per-patient, the authors determined concordance of management recommendations (rule-out/observe/rule-in) per the 0/2-h algorithm, and their association with diagnostic test findings (coronary artery stenosis >50% on coronary computed tomography angiography or inducible ischemia on perfusion imaging) and ACS.

Results: Among 1,027 samples from 624 patients (52.8 ± 10.0 years; 39.4% women), samples were classified as <LOD (56.3% vs. 10.4% vs. 41.2%; p < 0.001), LOD-99th percentile (36.5% vs. 83.5% vs. 52.6; p < 0.001), >99th percentile (7.2% vs. 6.0% vs. 6.2%) by Roche, Abbott, and Siemens, respectively. A total of 37.4% (n = 384 of 1,027) of blood samples were classified into the same analytical benchmark category, with low concordance across benchmarks (<LOD 11.1%; LOD-99th percentile 29.3%; >99th percentile 43.6%). Serial samples were available in 242 patients (40.1% women; mean age: 52.8 ± 8.0 years). The concordance of management recommendations across assays was 74.8% (n = 181 of 242) considering serial hs-cTn measurements. Of patients who were recommended to discharge, 19.6% to 21.1% had positive diagnostic test findings and 2.8% to 4.3% had ACS at presentation.

Conclusions: Caregivers should be aware that there are significant differences between hs-cTn assays in stratifying individual samples and patients with intermediate likelihood of ACS according to analytical benchmarks that may result in different management recommendations. (Rule Out Myocardial Infarction by Computer Assisted Tomography [ROMICAT]; NCT00990262) (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239).

Keywords: acute coronary syndrome; concordance; high-sensitivity cardiac troponin; high-sensitivity cardiac troponin assays.

Conflict of interest statement

Funding Support and Author Disclosures Dr. Karády has received grant support from the Fulbright Visiting Researcher Grant (E0583118), and the Rosztoczy Foundation. Dr. Ferencik has been supported by a grant from the American Heart Association (Fellow to Faculty Award #13FTF16450001). Dr. Peacock has received grant support from Abbott, Boehringer Ingelheim, Braincheck, CSL Behring, Daiichi-Sankyo, Immunarray, Janssen, Ortho Clinical Diagnostics, Portola, Relypsa, Roche, Salix, and Siemens; has received consulting income from Abbott, AstraZeneca, Bayer, Beckman, Boehrhinger Ingelheim, Ischemia Care, Dx, Immunarray, Instrument Labs, Janssen, Nabriva, Ortho Clinical Diagnostics, Relypsa, Roche, Quidel, Salix, and Siemens; has provided expert testimony for Johnson and Johnson; and has stock/ownership interest in AseptiScope Inc., Brainbox Inc., Comprehensive Research Associates LLC, Emergencies in Medicine LLC, and Ischemia DX LLC. Dr. Nagurney has received research funds from Roche Diagnostics, Ortho Diagnostics, and Alere/Biosite to the Massachusetts General Hospital. Dr. Januzzi has been a Trustee of the American College of Cardiology, and a board member of Imbria Pharmaceuticals; has received grant support from Novartis Pharmaceuticals, Roche Diagnostics, Abbott, Singulex, and Prevencio; has received consulting income from Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Boehringer Ingelheim, Janssen, and Takeda. Dr. Koenig has received personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, DalCor, Kowa, Amgen, Corvidia, Berlin-Chemie, and Sanofi; and has received grants and nonfinancial support from Beckmann, Singulex, Abbott, and Roche Diagnostics, outside the submitted work. Dr. Hoffmann has received research support on behalf of his institution from Duke University (Abbott), HeartFlow, Kowa Company Limited, and MedImmune/AstraZeneca; and has received consulting fees from Duke University (NIH), and Recor Medical, unrelated to this research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.. Study Population enrollment, exclusion, and inclusion.

The flow chart summarizes the selection of the patient population included in the per-sample and per-patient analyses. ED=emergency department; Hs-cTn=High-sensitivity cardiac troponin; R-I=ROMICAT-I; R-II=ROMICAT-II; ROMICAT=Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography II.

Figure 2.

Agreement between assays in classifying blood samples along analytic benchmarks using non-sex specific 99th percentile. Concordant is defined as agreement between all three assays, anything else is considered as discordant*. LOD=Limit of detection; 99th%tile=99th percentile.*Discordant cases are classified to more than one analytic benchmark, therefore the overall sum of the columns is not equal to the overall sum of studied blood samples (n=1,027), but it is higher because of the redundancy.

Figure 3.

Agreement between assays in patient management recommendations based on the 0/2 hour algorithm. Concordant is defined as agreement between all three assays, anything else is considered as discordant*. *Discordant cases are stratified to more than one analytic benchmark, therefore the overall sum of the columns is not equal to the overall sum of studied patients (n=242), but it is higher because of the redundancy.

Central illustration:. Study design.

Outline of the per-sample and per-patient analysis to assess the concordance between the three assays. Hs-cTn=High-Sensitivity Cardiac Troponin; LOD=Limit of Detection; %tile=Percentile.