To the Editor:
A new common change criteria (3C) algorithm for high-sensitivity cardiac troponin (hs-cTn) yielded performance similar to that of European Society of Cardiology algorithms with serial sampling at < 3 hours.1 For the present analysis, we wanted to assess specificity of the 3C change for myocardial infarction (MI) in different emergency department (ED) populations with serial blood measurements ≥ 3 hours apart.
ED populations with serial testing for hs-cTn, namely at Strong Memorial Hospital, Rochester, NY2 (n = 18,022 patients with possible acute coronary syndrome, May 2018-October 2019, with 0 and 3 hours —Roche Diagnostics International AG Forrenstrasse 2 6343 [Rotkreuz Switzerland] hs-cTnT results) and Hamilton, Ontario, Canada3 (n = 2966 undifferentiated patients, November 2012-February 2013, with 0 and 8 hours—Abbott [Chicago, IL] ARCHITECT hs-cTnI results) were evaluated for 3C (change present if difference > 3 ng/L for initial concentrations < 10 ng/L, or > 30% if 10-100 ng/L, or > 15% above 100 ng/L) vs the 20% change criterion congruent with the Fourth Universal Definition of MI to identify stable levels and chronic injury. For Rochester, the index MI diagnosis was obtained from the Chest Pain–MI Registry for the ED visit, and for Hamilton, long-term health outcomes were obtained (30-day MI and 9-year composite of MI and heart failure [HF]) via provincial databases housed at ICES.4 In both populations for MI, we derived the specificity and sensitivity with 95% confidence intervals (CIs) for both the 3C and the 20% criteria. In the Hamilton cohort, we used a competing risks survival model for MI/HF (death as a competing risk). We adjusted models for age, sex, Charlson comorbidity index, and history (angina, arrhythmia, stroke, stress test, hypertension, diabetes, peripheral vascular disease, liver disease, and dementia).4 Statistical analyses were performed in SAS Enterprise Guide, version 8.3 (Cary, NC) and R, version 4.3 (R Foundation, Vienna, Austria).
The prevalence of MI was 2.95% (Rochester) and 9.5% (Hamilton). The specificity for MI using the 3C change was higher (Rochester: 90.9%; 95% CI: 90.5%-91.3%; Hamilton: 70.4%; 95% CI: 68.7%-72.1%) than the 20% criterion (Rochester: 79.5%; 95% CI:78.9%-80.1%; Hamilton: 44.8%; 95% CI: 42.9%-46.7%). All sensitivity estimates were < 81% (3C range: 69.1%-77.6%; 20% range: 69.8%-80.8%). In the Hamilton ED population, the adjusted sub-hazard ratio (aSHR) with death as a competing risk was 2-fold higher for 3C (aSHR = 2.29, 95% CI:1.95-2.68; P < 0.001) vs the 20% criterion (aSHR = 1.11; 95% CI: 1.02-1.21; P = 0.021).
Limitations include the different follow-up durations for MI—the Rochester cohort was only the index MI, whereas the Hamilton cohort included any MIs in the 30 days from and including presentation. Also, the 3C common algorithm was not assessed in this study, only the change criteria, and this could be the reason that the sensitivity was lower than that in the initial publication.1 However, employing the 3C change alone vs the 20% change criterion (used to identify stable unchanging patterns and not for ruling-in) for hs-cTn measurements ≥ 3 hours apart increased the specificity of a test for MI and identified patients at higher risk for future cardiovascular events. However, hs-cTn change alone yielded suboptimal sensitivity estimates to rule out MI.
Acknowledgements
This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care. This document used data adapted from the Statistics Canada Postal CodeOM Conversion File, which is based on data licensed from Canada Post Corporation, and/or data adapted from the Ontario MOH Postal Code Conversion File, which contains data copied under license from ©Canada Post Corporation and Statistics Canada. Parts of this material are based on data and/or information compiled and provided by Ontario Health, Canadian Institute for Health Information, and the Ontario MOH. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred.
Funding Sources
This work was supported by grants from the Canadian Institutes of Health Research (to P.A.K.). The funding organizations had no role in the design and conduct of the study, the collection, analysis, or interpretation of the data, or the final approval of the letter.
Disclosures
P.A.K. has received grants/reagents/consultant/advisor/ honoraria from Abbott Laboratories, Abbott Point of Care, Beckman Coulter, Ortho Clinical Diagnostics, Randox Laboratories, Roche Diagnostics, Siemens Healthcare Diagnostics, and Thermo Fisher Scientific. McMaster University has filed patents with P.A.K. listed as an inventor in the acute cardiovascular biomarker field. The other authors have no conflicts of interest to disclose.
References
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