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Editor's Correspondence
Mar 25, 2013

High-Five for High-Sensitivity Cardiac Troponin T: Depends on the Precision and Analytical Platform

Author Affiliations
Author Affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
JAMA Intern Med. 2013;173(6):477. doi:10.1001/jamainternmed.2013.2270

Reichlin and colleagues1 have developed an algorithm for ruling-in or ruling-out myocardial infarction (MI) within 1 hour after presentation using high-sensitivity cardiac troponin T (hs-cTnT) for patients within the Advantageous Predictors of Acute Coronary Syndrome Evaluation study. The data analyses using classification and regression tree analysis for ruling-in via a training and validation set are powerful for supporting a 1-hour sampling/testing algorithm, albeit there is a major limitation in that both groups are from the same study population.2 Most strikingly, however, is the analytical criteria that was developed in this study to rule-in an MI, specifically, that either a hs-cTnT concentration of 52 ng/L or greater (to convert to micrograms per liter, multiply by 0.001) or a change (delta) in hs-cTnT concentrations of 5 ng/L or greater within 1 hour was used to rule-in.1 The absolute concentration of 52 ng/L is not the published 99th percentile for this assay3 and is in fact similar to the fourth generation's troponin T 10% coefficient of variation (CV) concentration of 0.03 ng/L, which has been shown in a large prospective study to predict death within 30 days.4 More intriguing is the 5-ng/L absolute change in hs-cTnT concentrations. On the basis of reported precision data, the 10% CV for the hs-cTnT is 13 ng/L1; using established laboratory medicine practices, acceptable variation would permit concentrations ranging from 15.6 ng/L to 10.4 ng/L around this point estimate. Thus, the imprecision of the assay alone could result in a change of 5 ng/L or greater in absence of any clinical change.

To avoid this assay imprecision trap, one may wish to (1) incorporate a longer time between samples to rule-in (ie, 3 hours; as was recently suggested for high-sensitivity assays)5 or (2) use a more precise platform to measure hs-cTnT.3 For the first point, the longer the time between blood sampling, the more likely that the troponin concentration will increase with the difference (delta) exceeding the analytical imprecision. For the second point, there are analytical platforms that have different precision profiles. The E-modular platform is more precise than the Elecsys 2010 platform, with the latter often yielding imprecision that would result in 5 ng/L or greater difference in concentrations.3 Finally, prospective studies assessing this algorithm should compare this shorter interval (ie, 1 hour) to a longer time interval (ie, 3 hours) for measurements and should also report on the platform and precision data for the hs-cTnT testing during the study. These are important points that should be addressed before considering adopting this algorithm for clinical care.

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Article Information

Correspondence: Dr Kavsak, Juravinski Hospital and Cancer Centre, 711 Concession Street Hamilton, ON L8V 1C3, Canada (kavsakp@mcmaster.ca).

Conflict of Interest Disclosures: Dr Kavsak has received grants/consultant/honorariums from Abbott Diagnostics, Beckman Coulter, Randox Laboratories, and Roche Diagnostics. He is listed as an inventor on patents filed by McMaster University related to laboratory testing in acute cardiac care.

References
1.
Reichlin T, Schindler C, Drexler B,  et al.  One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T.  Arch Intern Med. 2012;172(16):1211-121822892889PubMedGoogle ScholarCrossref
2.
Henderson MP, Pond GR, Kavsak PA. Statistical and analytical approaches for assessing biomarkers: new approaches, new technologies, with the same-old rigor for evaluation.  Clin Biochem. 2012;45(3):187-18822300592PubMedGoogle ScholarCrossref
3.
Saenger AK, Beyrau R, Braun S,  et al.  Multicenter analytical evaluation of a high-sensitivity troponin T assay.  Clin Chim Acta. 2011;412(9-10):748-75421219893PubMedGoogle ScholarCrossref
4.
Devereaux PJ, Chan MT, Alonso-Coello P,  et al; Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators.  Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery.  JAMA. 2012;307(21):2295-230422706835PubMedGoogle ScholarCrossref
5.
Thygesen K, Mair J, Giannitsis E,  et al; Study Group on Biomarkers in Cardiology of ESC Working Group on Acute Cardiac Care.  How to use high-sensitivity cardiac troponins in acute cardiac care.  Eur Heart J. 2012;33(18):2252-225722723599PubMedGoogle ScholarCrossref
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