High incidence of discrepancies in new Siemens assay – a comparison of cardiac troponin I assays

Rasmus Bo Hasselbalch; Jonas Henrik Kristensen; Nicoline Jørgensen; Nina Strandkjær; Bashir Alaour; Shoaib Afzal; Michael Marber; Henning Bundgaard; Kasper Karmark Iversen

doi:10.1515/cclm-2022-0034

Article

High incidence of discrepancies in new Siemens assay – a comparison of cardiac troponin I assays

Rasmus Bo Hasselbalch , Jonas Henrik Kristensen , Nicoline Jørgensen , Nina Strandkjær , Bashir Alaour , Shoaib Afzal , Michael Marber , Henning Bundgaard and Kasper Karmark Iversen

Published/Copyright: April 12, 2022

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 60 Issue 6

Abstract

Objectives

Cardiac troponin (cTn) is the biochemical gold standard for diagnosing myocardial infarction (MI). We compared the Siemens ADVIA Centaur High-Sensitivity (hs-cTnI) assay with the Siemens Ultra assay (cTnI-U).

Methods

Over 3 months cTnI-U and hs-cTnI were measured simultaneously at Herlev-Gentofte Hospital. Acute myocardial injury was diagnosed using the 4th universal definition. Disputed cases were adjudicated using clinical data. We compared diagnostic accuracy using area under the curve (AUC) of the receiver operating characteristic. Outliers in between-assay differences were defined as a factor-5 difference and ≥1 measurement >40 ng/L. Patients with outlier differences were invited for re-sampling and tested with serial dilution and heterophilic blocking tubes.

Results

From the 18th January to the 20th April 2019, 4,369 samples on 2,658 patients were included. cTnI-U measured higher concentrations than hs-cTnI (mean 23%, −52–213%), resulting in a higher frequency of acute myocardial injury, 255 (9.6%) vs. 203 (7.6%), p<0.001. This remained significant after adjudication, 212 vs 197, p<0.001. AUC for the prediction of MI for was 0.963 for cTnI-U and 0.959 for hs-cTnI, p=0.001. Outlier differences were seen in 35 (1.2%) patients, primarily with elevated hs-cTnI (n=33, 94%). On two re-samplings (median 144 and 297 days since inclusion), 16 of 20 (80%) and 11 of 11 had sustained elevation of hs-cTnI. The samples showed no signs of heterophilic antibodies.

Conclusions

Using hs-cTnI resulted in a subset of patients with large, discrepant elevations in concentration. These patients still had elevated hs-cTnI 6–10 months post admission but no heterophilic antibodies.

Keywords: acute coronary syndrome; biomarkers; cardiovascular disease; troponin

Corresponding author: Rasmus Bo Hasselbalch, Department of Emergency Medicine and Department of Cardiology, Herlev and Gentofte Hospital, Borgmester Ib Juuls vej 1, 2730 Herlev, Denmark, E-mail: rasmus.bo.hasselbalch@regionh.dk

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Ethical approval: The use of blood samples and related clinical information was considered audit and quality assurance and was deemed exempt from formal approval by the Danish Scientific Ethical Committee. The study was approved by the Institutional Board at Herlev and Gentofte Hospital (19000557) as well as the Danish Data Protection Agency (VD-2019-172).

References

1. Thygesen, K, Alpert, JS, Jaffe, AS, Chaitman, BR, Bax, JJ, Morrow, DA, et al.. Fourth universal definition of myocardial infarction. Eur Heart J 2019;40:237–69. https://doi.org/10.1093/eurheartj/ehy462.Search in Google Scholar

2. Apple, FS, Sandoval, Y, Jaffe, AS, Ordonez-Llanos, J Cardiac troponin assays: Guide to understanding analytical characteristics and their impact on clinical care, 63. Clin Chem 2017. p. 73–81. https://doi.org/10.1373/clinchem.2016.255109.Search in Google Scholar

3. Cullen, L, Aldous, S, Than, M, Greenslade, JH, Tate, JR, George, PM, et al.. Comparison of high sensitivity troponin T and I assays in the diagnosis of non-ST elevation acute myocardial infarction in emergency patients with chest pain. Clin Biochem 2014;47:321–6. https://doi.org/10.1016/j.clinbiochem.2013.11.019.Search in Google Scholar

4. Rubini Gimenez, M, Twerenbold, R, Reichlin, T, Wildi, K, Haaf, P, Schaefer, M, et al.. Direct comparison of high-sensitivity-cardiac troponin I vs. T for the early diagnosis of acute myocardial infarction. Eur Hear J 2014;35:2303–11. https://doi.org/10.1093/eurheartj/ehu188.Search in Google Scholar

5. Apple, FS Standardization of cardiac troponin i assays will not occur in my lifetime, 58. Clin Chem 2012. p. 169–71. https://doi.org/10.1373/clinchem.2011.166165.Search in Google Scholar

6. Prince, AM, Brotman, B, Jass, D, Ikram, H. Specificity of the direct solid-phase radioimmunoassay for detection of hepatitis-B antigen. Lancet 1973;1:1346–50. https://doi.org/10.1016/s0140-6736(73)91674-7.Search in Google Scholar

7. Fitzmaurice, TF, Brown, C, Rifai, N, Wu, AH, Yeo, KT. False increase of cardiac troponin I with heterophilic antibodies. Clin Chem 1998;44:2212–4. https://doi.org/10.1093/clinchem/44.10.2212.Search in Google Scholar

8. Zhu, Y, Jenkins, MM, Brass, DA, Ravago, PG, Horne, BD, Dean, SB, et al.. Heterophilic antibody interference in an ultra-sensitive 3-site sandwich troponin I immunoassay. Clin Chim Acta 2008;395:181–2. https://doi.org/10.1016/j.cca.2008.04.027.Search in Google Scholar PubMed

9. Kavsak, PA, Worster, A, Hill, SA, Jaffe, AS. Evaluation of the Siemens ADVIA Centaur high-sensitivity cardiac troponin I assay in serum. Clin Chim Acta 2018;487:216–21. https://doi.org/10.1016/j.cca.2018.10.012.Search in Google Scholar PubMed

10. Lam, L, Aspin, L, Heron, RC, Ha, L, Kyle, C. Discrepancy between cardiac troponin assays due to endogenous antibodies. Clin Chem 2020;66:445–54. https://doi.org/10.1093/clinchem/hvz032.Search in Google Scholar PubMed

11. Collet, JP, Thiele, H, Barbato, E, Bauersachs, J, Dendale, P, Edvardsen, T, et al.. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021;42:1289–367. https://doi.org/10.1093/eurheartj/ehaa575.Search in Google Scholar PubMed

12. Robin, X, Turck, N, Hainard, A, Tiberti, N, Lisacek, F, Sanchez, J-C, et al.. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinf 2011;12:77. Available from: https://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-12-77. https://doi.org/10.1186/1471-2105-12-77.Search in Google Scholar PubMed PubMed Central

13. DeLong, ER, DeLong, DM, Clarke-Pearson, DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837–45. https://doi.org/10.2307/2531595.Search in Google Scholar

14. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing V; 2018. https://www.R-project.org/. AURL. No Title.Search in Google Scholar

15. Warner, JV, Marshall, GA. High incidence of macrotroponin I with a high-sensitivity troponin I assay. Clin Chem Lab Med 2016;54:1821–9. https://doi.org/10.1515/cclm-2015-1276.Search in Google Scholar PubMed

16. Yang, HS, Shemesh, A, Li, J, Xie, T, Apple, FS, Williams, JA, et al.. No increase in the incidence of cardiac troponin I concentration above the 99th percentile by Siemens Centaur high-sensitivity compared to the contemporary assay. Clin Biochem 2021;89:77–80. https://doi.org/10.1016/j.clinbiochem.2020.12.001.Search in Google Scholar PubMed

17. Kramer, CM Avoiding the imminent plague of troponinitis: The need for reference limits for high-sensitivity cardiac troponin T, 63. J Am Coll Cardiol. U S; 2014. p. 1449–50. https://doi.org/10.1016/j.jacc.2013.12.031.Search in Google Scholar PubMed

18. Árnadóttir, Á, Pedersen, S, Bo Hasselbalch, R, Goetze, JP, Friis-Hansen, LJ, Bloch-Münster, AM, et al.. Temporal release of high-sensitivity cardiac troponin T and I and copeptin after brief induced coronary artery balloon occlusion in humans. Circulation 2021:1095–104. https://doi.org/10.1161/CIRCULATIONAHA.120.046574.Search in Google Scholar PubMed

19. Gore, MO, Seliger, SL, Defilippi, CR, Nambi, V, Christenson, RH, Hashim, IA, et al.. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol 2014;63:1441–8. https://doi.org/10.1016/j.jacc.2013.12.032.Search in Google Scholar PubMed PubMed Central

20. Horn, PS, Feng, L, Li, Y, Pesce, AJ. Effect of outliers and nonhealthy individuals on reference interval estimation; 2001. https://doi.org/10.1093/clinchem/47.12.2137.Search in Google Scholar

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0034).

Received: 2021-10-12

Accepted: 2022-03-28

Published Online: 2022-04-12

Published in Print: 2022-05-25

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Supplementary Material

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https://doi.org/10.1515/cclm-2022-0034

Keywords for this article

acute coronary syndrome; biomarkers; cardiovascular disease; troponin