Assessing Analytical Performance and Correct Classification for Cardiac Troponin Deltas Across Diagnostic Pathways Used for Myocardial Infarction

<b>Background:</b> In the emergency setting, many diagnostic pathways incorporate change in high-sensitivity cardiac troponin (hs-cTn) concentrations (i.e., the delta) to classify patients as low-risk (rule-out) or high-risk (rule-in) for possible myocardial infarction (MI). However, the...

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Main Authors: Peter A. Kavsak, Sameer Sharif, Wael L. Demian, Won-Shik Choi, Emilie P. Belley-Cote, Jennifer Taher, Jennifer L. Shea, David W. Blank, Michael Knauer, Laurel Thorlacius, Joshua E. Raizman, Yun Huang, Daniel R. Beriault, Angela W. S. Fung, Paul M. Yip, Lorna Clark, Beth L. Abramson, Steven M. Friedman, Jesse McLaren, Paul Atkinson, Annabel Chen-Tournoux, Neville Suskin, Marco L. A. Sivilotti, Venkatesh Thiruganasambandamoorthy, Frank Scheuermeyer, Karin H. Humphries, Kristin M. Aakre, Shawn E. Mondoux, Craig Ainsworth, Flavia Borges, Andrew Worster, Andrew McRae, Allan S. Jaffe
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Language:English
Published: MDPI AG 2025-06-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/15/13/1652
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author Peter A. Kavsak
Sameer Sharif
Wael L. Demian
Won-Shik Choi
Emilie P. Belley-Cote
Jennifer Taher
Jennifer L. Shea
David W. Blank
Michael Knauer
Laurel Thorlacius
Joshua E. Raizman
Yun Huang
Daniel R. Beriault
Angela W. S. Fung
Paul M. Yip
Lorna Clark
Beth L. Abramson
Steven M. Friedman
Jesse McLaren
Paul Atkinson
Annabel Chen-Tournoux
Neville Suskin
Marco L. A. Sivilotti
Venkatesh Thiruganasambandamoorthy
Frank Scheuermeyer
Karin H. Humphries
Kristin M. Aakre
Shawn E. Mondoux
Craig Ainsworth
Flavia Borges
Andrew Worster
Andrew McRae
Allan S. Jaffe
author_facet Peter A. Kavsak
Sameer Sharif
Wael L. Demian
Won-Shik Choi
Emilie P. Belley-Cote
Jennifer Taher
Jennifer L. Shea
David W. Blank
Michael Knauer
Laurel Thorlacius
Joshua E. Raizman
Yun Huang
Daniel R. Beriault
Angela W. S. Fung
Paul M. Yip
Lorna Clark
Beth L. Abramson
Steven M. Friedman
Jesse McLaren
Paul Atkinson
Annabel Chen-Tournoux
Neville Suskin
Marco L. A. Sivilotti
Venkatesh Thiruganasambandamoorthy
Frank Scheuermeyer
Karin H. Humphries
Kristin M. Aakre
Shawn E. Mondoux
Craig Ainsworth
Flavia Borges
Andrew Worster
Andrew McRae
Allan S. Jaffe
author_sort Peter A. Kavsak
collection DOAJ
description <b>Background:</b> In the emergency setting, many diagnostic pathways incorporate change in high-sensitivity cardiac troponin (hs-cTn) concentrations (i.e., the delta) to classify patients as low-risk (rule-out) or high-risk (rule-in) for possible myocardial infarction (MI). However, the impact of analytical variation on the delta for correct classification is unknown, especially at concentrations below and around the 99th percentile. Our objective was to assess the impact of delta variation for correct risk classification across the European Society of Cardiology (ESC 0/1 h and 0/2 h), the High-STEACS, and the common change criteria (3C) pathways. <b>Methods</b>: A yearlong accuracy study for hs-cTnT was performed where laboratories across Canada tested three patient-based samples (level 1 target value = 6 ng/L, level 2 target value = 9 ng/L, level 3 target value = 12 ng/L) monthly across 41 different analyzers. The assigned low-delta between levels 1 and 2 was 3 ng/L (i.e., 9 − 6 = 3 ng/L) and the assigned high-delta between levels 1 and 3 was 6 ng/L (i.e., 12 − 6 = 6 ng/L). The low- and high-deltas for each analyzer were determined monthly from the measured values, with the difference calculated from the assigned deltas. The obtained deltas were then assessed via the different pathways on correct classification (i.e., percent correct with 95% confidence intervals, CI) and using non-parametric analyses. <b>Results</b>: The median (interquartile range) difference between the measured versus assigned low-delta (n = 436) and high-delta (n = 439) was −1 ng/L (−1 to 0). The correct classification differed among the pathways. The ESC 0/1 h pathway yielded the lowest percentage of correct classification at 35.3% (95% CI: 30.8 to 40.0) for the low-delta and 90.0% (95% CI: 86.8 to 92.6) for the high-delta. The 3C and ESC 0/2 h pathways yielded higher and equivalent estimates on correct classification: 95.2% (95% CI: 92.7 to 97.0) for the low-delta and 98.2% (95% CI: 96.4 to 99.2) for the high-delta. The High-STEACS pathway yielded 99.5% (95% CI: 98.4 to 99.9) of correct classifications for the high-delta but only 36.2% (95% CI: 31.7 to 40.9) for the low-delta. <b>Conclusions</b>: Analytical variation will impact risk classification for MI when using hs-cTn deltas alone per the pathways. The 3C and ESC 0/2 h pathways have <5% misclassification when using deltas for hs-cTnT in this dataset. Additional studies with different hs-cTnI assays at concentrations below and near the 99th percentile are warranted to confirm these findings.
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spelling doaj-art-6b3b8cbedf444b1b8a61cc2ba84875822025-08-20T03:16:47ZengMDPI AGDiagnostics2075-44182025-06-011513165210.3390/diagnostics15131652Assessing Analytical Performance and Correct Classification for Cardiac Troponin Deltas Across Diagnostic Pathways Used for Myocardial InfarctionPeter A. Kavsak0Sameer Sharif1Wael L. Demian2Won-Shik Choi3Emilie P. Belley-Cote4Jennifer Taher5Jennifer L. Shea6David W. Blank7Michael Knauer8Laurel Thorlacius9Joshua E. Raizman10Yun Huang11Daniel R. Beriault12Angela W. S. Fung13Paul M. Yip14Lorna Clark15Beth L. Abramson16Steven M. Friedman17Jesse McLaren18Paul Atkinson19Annabel Chen-Tournoux20Neville Suskin21Marco L. A. Sivilotti22Venkatesh Thiruganasambandamoorthy23Frank Scheuermeyer24Karin H. Humphries25Kristin M. Aakre26Shawn E. Mondoux27Craig Ainsworth28Flavia Borges29Andrew Worster30Andrew McRae31Allan S. Jaffe32Faculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, CanadaFaculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, CanadaFaculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, CanadaFaculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, CanadaPopulation Health Research Institute, Hamilton, ON L8L 2X2, CanadaUniversity of Toronto, Toronto, ON M5T 1R8, CanadaDepartment of Laboratory Medicine, Saint John Regional Hospital, Saint John, NB E2L 4L2, CanadaMcGill University, Montréal, QC H3A 0G4, CanadaWestern University, London, ON N6A 5B9, CanadaUniversity of Manitoba, Winnipeg, MB R2H 2A6, CanadaUniversity of Alberta, Edmonton, AB T6G 2G4, CanadaQueen’s University, Kingston, ON KL7 3N6, CanadaUniversity of Toronto, Toronto, ON M5T 1R8, CanadaUniversity of British Columbia, Vancouver, BC V6S 1Z2, CanadaUniversity of Toronto, Toronto, ON M5T 1R8, CanadaFaculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, CanadaUniversity of Toronto, Toronto, ON M5T 1R8, CanadaUniversity of Toronto, Toronto, ON M5T 1R8, CanadaUniversity of Toronto, Toronto, ON M5T 1R8, CanadaDalhousie Medicine, Saint John, NB E2K 5E2, CanadaMcGill University, Montréal, QC H3A 0G4, CanadaWestern University, London, ON N6A 5B9, CanadaQueen’s University, Kingston, ON KL7 3N6, CanadaUniversity of Ottawa, Ottawa, ON K1N 6N5, CanadaUniversity of British Columbia, Vancouver, BC V6S 1Z2, CanadaUniversity of British Columbia, Vancouver, BC V6S 1Z2, CanadaDepartment of Medical Biochemistry and Pharmacology & Department of Heart Disease, University Hospital, Haukeland, 5007 Bergen, NorwayFaculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, CanadaFaculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, CanadaFaculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, CanadaFaculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, CanadaUniversity of Calgary, Calgary, AB T2N1N4, CanadaMayo Clinic and Medical Center, Rochester, MN 55905, USA<b>Background:</b> In the emergency setting, many diagnostic pathways incorporate change in high-sensitivity cardiac troponin (hs-cTn) concentrations (i.e., the delta) to classify patients as low-risk (rule-out) or high-risk (rule-in) for possible myocardial infarction (MI). However, the impact of analytical variation on the delta for correct classification is unknown, especially at concentrations below and around the 99th percentile. Our objective was to assess the impact of delta variation for correct risk classification across the European Society of Cardiology (ESC 0/1 h and 0/2 h), the High-STEACS, and the common change criteria (3C) pathways. <b>Methods</b>: A yearlong accuracy study for hs-cTnT was performed where laboratories across Canada tested three patient-based samples (level 1 target value = 6 ng/L, level 2 target value = 9 ng/L, level 3 target value = 12 ng/L) monthly across 41 different analyzers. The assigned low-delta between levels 1 and 2 was 3 ng/L (i.e., 9 − 6 = 3 ng/L) and the assigned high-delta between levels 1 and 3 was 6 ng/L (i.e., 12 − 6 = 6 ng/L). The low- and high-deltas for each analyzer were determined monthly from the measured values, with the difference calculated from the assigned deltas. The obtained deltas were then assessed via the different pathways on correct classification (i.e., percent correct with 95% confidence intervals, CI) and using non-parametric analyses. <b>Results</b>: The median (interquartile range) difference between the measured versus assigned low-delta (n = 436) and high-delta (n = 439) was −1 ng/L (−1 to 0). The correct classification differed among the pathways. The ESC 0/1 h pathway yielded the lowest percentage of correct classification at 35.3% (95% CI: 30.8 to 40.0) for the low-delta and 90.0% (95% CI: 86.8 to 92.6) for the high-delta. The 3C and ESC 0/2 h pathways yielded higher and equivalent estimates on correct classification: 95.2% (95% CI: 92.7 to 97.0) for the low-delta and 98.2% (95% CI: 96.4 to 99.2) for the high-delta. The High-STEACS pathway yielded 99.5% (95% CI: 98.4 to 99.9) of correct classifications for the high-delta but only 36.2% (95% CI: 31.7 to 40.9) for the low-delta. <b>Conclusions</b>: Analytical variation will impact risk classification for MI when using hs-cTn deltas alone per the pathways. The 3C and ESC 0/2 h pathways have <5% misclassification when using deltas for hs-cTnT in this dataset. Additional studies with different hs-cTnI assays at concentrations below and near the 99th percentile are warranted to confirm these findings.https://www.mdpi.com/2075-4418/15/13/1652cardiac troponin deltahigh-sensitivity cardiac troponindiagnostic pathwaysEuropean Society of Cardiology (ESC)High-STEACSCommon Change Criteria (3C)
spellingShingle Peter A. Kavsak
Sameer Sharif
Wael L. Demian
Won-Shik Choi
Emilie P. Belley-Cote
Jennifer Taher
Jennifer L. Shea
David W. Blank
Michael Knauer
Laurel Thorlacius
Joshua E. Raizman
Yun Huang
Daniel R. Beriault
Angela W. S. Fung
Paul M. Yip
Lorna Clark
Beth L. Abramson
Steven M. Friedman
Jesse McLaren
Paul Atkinson
Annabel Chen-Tournoux
Neville Suskin
Marco L. A. Sivilotti
Venkatesh Thiruganasambandamoorthy
Frank Scheuermeyer
Karin H. Humphries
Kristin M. Aakre
Shawn E. Mondoux
Craig Ainsworth
Flavia Borges
Andrew Worster
Andrew McRae
Allan S. Jaffe
Assessing Analytical Performance and Correct Classification for Cardiac Troponin Deltas Across Diagnostic Pathways Used for Myocardial Infarction
Diagnostics
cardiac troponin delta
high-sensitivity cardiac troponin
diagnostic pathways
European Society of Cardiology (ESC)
High-STEACS
Common Change Criteria (3C)
title Assessing Analytical Performance and Correct Classification for Cardiac Troponin Deltas Across Diagnostic Pathways Used for Myocardial Infarction
title_full Assessing Analytical Performance and Correct Classification for Cardiac Troponin Deltas Across Diagnostic Pathways Used for Myocardial Infarction
title_fullStr Assessing Analytical Performance and Correct Classification for Cardiac Troponin Deltas Across Diagnostic Pathways Used for Myocardial Infarction
title_full_unstemmed Assessing Analytical Performance and Correct Classification for Cardiac Troponin Deltas Across Diagnostic Pathways Used for Myocardial Infarction
title_short Assessing Analytical Performance and Correct Classification for Cardiac Troponin Deltas Across Diagnostic Pathways Used for Myocardial Infarction
title_sort assessing analytical performance and correct classification for cardiac troponin deltas across diagnostic pathways used for myocardial infarction
topic cardiac troponin delta
high-sensitivity cardiac troponin
diagnostic pathways
European Society of Cardiology (ESC)
High-STEACS
Common Change Criteria (3C)
url https://www.mdpi.com/2075-4418/15/13/1652
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