Do we really need high-sensitivity troponin immunoassays in the emergency department? Maybe not

Giuseppe Lippi; Gianfranco Cervellin

doi:10.1515/cclm-2013-0524

Article

Do we really need high-sensitivity troponin immunoassays in the emergency department? Maybe not

Giuseppe Lippi and Gianfranco Cervellin

Published/Copyright: July 30, 2013

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 52 Issue 2

Abstract

The diagnosis of acute coronary syndrome (ACS) has challenged the minds of cardiologists, emergency physicians and laboratorists for decades. A major breakthrough has, however, occurred at the dawn of the third millennium, with development, commercialization and introduction into clinical practice of troponin immunoassays. A novel generation of these methods, conventionally defined as “high-sensitivity” (HS), has more recently emerged. These latest generation assays are characterized by improved analytical sensitivity, which would theoretically allow earlier and more efficient diagnosis of ACS. Despite the considerable amount of information gathered over the past few years about the clinical use of conventional and HS immunoassays, several doubts persist and – according to our personal perspective – the evidence that the latest generation methods would represent a real breakthrough in management of patients in short-stay units such as the emergency department is still an unresolved issue. Beside the mystifying nomenclature that characterizes several commercial tests, recent evidence suggests that the diagnostic performance of some contemporary sensitive methods would equal those of HS immunoassays for early diagnosis, serial assessment and even prognostication of patients. Conversely, the better diagnostic specificity of conventional methods may represent an advantage for triaging patients in overcrowded emergency departments. There is hence a tangible threat that the measurement of troponin with HS methods would become more or less an “expensive cholesterol of the third millennium”, and this risk must be carefully considered in a world of limited resources. So, our answer to the question if we do really need HS troponin immunoassays in the emergency department is “maybe not”.

Keywords: acute coronary syndrome; high-sensitivity; myocardial infarction; troponin

Corresponding author: Prof. Giuseppe Lippi, Unità Operativa Diagnostica Ematochimica, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126 Parma, Italy, Phone: +39 0521 703050, Fax: +39 0521 703791, E-mail: glippi@ao.pr.it; ulippi@tin.it

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Lippi G, Plebani M. Biomarker research and leading causes of death worldwide: a rather feeble relationship. Clin Chem Lab Med 2013;51:1695–7.10.1515/cclm-2013-0210Search in Google Scholar

2. Lippi G, Franchini M, Targher G. Arterial thrombus formation in cardiovascular disease. Nat Rev Cardiol 2011;8:502–12.10.1038/nrcardio.2011.91Search in Google Scholar

3. Lippi G, Montagnana M, Salvagno GL, Guidi GC. Potential value for new diagnostic markers in the early recognition of acute coronary syndromes. Can J Emerg Med 2006;8:27–31.10.1017/S148180350001335XSearch in Google Scholar

4. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined – a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959–69.10.1016/S0735-1097(00)00804-4Search in Google Scholar

5. Thygesen K, Alpert JS, White HD; Joint ESC/ACCF/AHA/WHF task force for the redefinition of myocardial infarction. Universal definition of myocardial infarction. Eur Heart J 2007;28:2525–38.10.1093/eurheartj/ehm355Search in Google Scholar PubMed

6. Apple FS, Jesse RL, Newby LK, Wu AH, Christenson RH; National Academy of Clinical Biochemistry; IFCC Committee for Standardization of Markers of Cardiac Damage. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical issues for biochemical markers of acute coronary syndromes. Circulation 2007;115:e352–5.10.1161/CIRCULATIONAHA.107.182881Search in Google Scholar PubMed

7. Armbruster DA, Pry T. Limit of blank, limit of detection and limit of quantitation. Clin Biochem Rev 2008;29(Suppl 1):S49–52.Search in Google Scholar

8. Lackner KJ. Laboratory diagnostics of myocardial infarction – troponins and beyond. Clin Chem Lab Med 2013;51:83–9.10.1515/cclm-2012-0572Search in Google Scholar PubMed

9. Lindahl B. Acute coronary syndrome – the present and future role of biomarkers. Clin Chem Lab Med 2013;23:1–8.Search in Google Scholar

10. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF task force for the universal definition of myocardial infarction. Third universal definition of myocardial infarction. Circulation 2012;126:2020–35.10.1161/CIR.0b013e31826e1058Search in Google Scholar PubMed

11. Thygesen K, Mair J, Mueller C, Huber K, Weber M, Plebani M, 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;33:2252–7.10.1093/eurheartj/ehs154Search in Google Scholar PubMed

12. Apple FS, Saenger AK. The state of cardiac troponin assays: looking bright and moving in the right direction. Clin Chem 2013;59:1014–6.10.1373/clinchem.2013.203307Search in Google Scholar PubMed

13. Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem 2012;58:1574–81.10.1373/clinchem.2012.192716Search in Google Scholar PubMed

14. Cardinaels EP, Mingels AM, Jacobs LH, Meex SJ, Bekers O, van Dieijen-Visser MP. A comprehensive review of upper reference limits reported for (high-)sensitivity cardiac troponin assays: the challenges that lie ahead. Clin Chem Lab Med 2012;50: 791–806.10.1515/cclm-2011-0895Search in Google Scholar PubMed

15. Lippi G, Cervellin G. Identification of troponin determinants for improving its diagnostic performance in the emergency department. J Emerg Med 2012;43:e487–8.10.1016/j.jemermed.2012.05.016Search in Google Scholar PubMed

16. Lippi G, Margapoti R, Aloe R, Cervellin G. Highly-sensitive troponin I in patients admitted to the emergency room with acute infections. Eur J Intern Med 2013;24:e57–8.10.1016/j.ejim.2013.01.019Search in Google Scholar PubMed

17. Lippi G, Dipalo M, Carbucicchio A, Aloe R, Benatti M, Cervellin G. The concentration of highly-sensitive troponin I is increased in patients with brain injury after mild head trauma. Int J Cardiol 2013 Feb 7. [Epub ahead of print].10.1016/j.ijcard.2013.01.018Search in Google Scholar PubMed

18. Cardinale D, Salvatici M, Sandri MT. Role of biomarkers in cardioncology. Clin Chem Lab Med 2011;49:1937–48.10.1515/CCLM.2011.692Search in Google Scholar PubMed

19. Kavsak PA, MacRae AR, Yerna MJ, Jaffe AS. Analytic and clinical utility of a next-generation, highly sensitive cardiac troponin I assay for early detection of myocardial injury. Clin Chem 2009;55:573–7.10.1373/clinchem.2008.116020Search in Google Scholar PubMed

20. Collinson PO, Heung YM, Gaze D, Boa F, Senior R, Christenson R, et al. Influence of population selection on the 99th percentile reference value for cardiac troponin assays. Clin Chem 2012;58:219–25.10.1373/clinchem.2011.171082Search in Google Scholar PubMed

21. Plebani M, Lippi G. Personalized (laboratory) medicine: a bridge to the future. Clin Chem Lab Med 2013;51:703–6.10.1515/cclm-2013-0021Search in Google Scholar PubMed

22. McKie PM, Heublein DM, Scott CG, Gantzer ML, Mehta RA, Rodeheffer RJ, et al. Defining high-sensitivity cardiac troponin concentrations in the community. Clin Chem 2013;59:1099–107.10.1373/clinchem.2012.198614Search in Google Scholar PubMed

23. Lippi G, Cervellin G, Robuschi E, Salvagno GL, Montagnana M, Aloe R, et al. Comparison of high sensitivity and contemporary troponin I immunoassays for the early detection of acute myocardial infarction in the emergency department. Ann Clin Biochem 2012;49:205–6.10.1258/acb.2011.011211Search in Google Scholar PubMed

24. Conde D, Costabel JP, Lambardi F. Chest pain unit: 4th generation troponin T versus high sensitivity troponin T. Int J Cardiol 2013 Apr 10. [Epub ahead of print].10.1016/j.ijcard.2013.03.056Search in Google Scholar PubMed

25. Hammerer-Lercher A, Ploner T, Neururer S, Schratzberger P, Griesmacher A, Pachinger O, et al. High-sensitivity cardiac troponin T compared with standard troponin T testing on emergency department admission: how much does it add in everyday clinical practice? J Am Heart Assoc 2013;2:e000204.10.1161/JAHA.113.000204Search in Google Scholar PubMed PubMed Central

26. Hoeller R, Rubini Giménez M, Reichlin T, Twerenbold R, Zellweger C, Moehring B, et al. Normal presenting levels of high-sensitivity troponin and myocardial infarction. Heart 2013 Apr 19. [Epub ahead of print].10.1136/heartjnl-2013-303643Search in Google Scholar PubMed

27. Mion MM, Bragato G, Zaninotto M, Vettore G, Tosato F, Babuin L, et al. Effect of a last generation cardiac troponin assay on patients’ management: a real world emergency department experience. Clin Chim Acta 2013;418:77–8.10.1016/j.cca.2013.01.002Search in Google Scholar PubMed

28. Lippi G, Cervellin G. Assay characteristics and diagnostic improvement from contemporary to high-sensitivity troponin I immunoassays. Am J Med (in press).Search in Google Scholar

29. Keller T, Zeller T, Ojeda F, Tzikas S, Lillpopp L, Sinning C, et al. Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction. J Am Med Assoc 2011;306:2684–93.10.1001/jama.2011.1896Search in Google Scholar PubMed

30. Cullen L, Parsonage WA, Greenslade J, Lamanna A, Hammett CJ, Than M, et al. Delta troponin for the early diagnosis of AMI in emergency patients with chest pain. Int J Cardiol 2013 Apr 10. [Epub ahead of print].10.1016/j.ijcard.2013.03.044Search in Google Scholar PubMed

31. Lippi G, Cervellin G. Letter by Lippi and Cervellin regarding article, “High-sensitivity cardiac troponin in the distinction of acute myocardial infarction from acute cardiac noncoronary artery disease”. Circulation 2013;127:e353.10.1161/CIRCULATIONAHA.112.128603Search in Google Scholar PubMed

32. Lippi G, Cervellin G. Challenges of serial troponin testing: an unfinished symphony. Int J Cardiol 2013 May 22. [Epub ahead of print]. No abstract available.10.1016/j.ijcard.2013.05.043Search in Google Scholar PubMed

33. Lippi G, Montagnana M, Aloe R, Cervellin G. Highly sensitive troponin immunoassays: navigating between the scylla and charybdis. Adv Clin Chem 2012;58:1–29.10.1016/B978-0-12-394383-5.00007-2Search in Google Scholar

34. Lindahl B, Eggers KM, Venge P, James S. Evaluation of four sensitive troponin assays for risk assessment in acute coronary syndromes using a new clinically oriented approach for comparison of assays. Clin Chem Lab Med 2013;51:1859–64.10.1515/cclm-2013-0023Search in Google Scholar PubMed

35. Venge P, Lindahl B. Cardiac troponin assay classification by both clinical and analytical performance characteristics: a study on outcome prediction. Clin Chem 2013;59:976–81.10.1373/clinchem.2012.194928Search in Google Scholar PubMed

36. Lippi G, Gillery P, Kazmierczak S, Lackner KJ, Melichar B, Siest G, et al. Clinical Chemistry and Laboratory Medicine: progress and new challenges for our 50-year-old journal. Clin Chem Lab Med 2013;51:5–7.10.1515/cclm-2012-0449Search in Google Scholar PubMed

37. Apple FS, Collinson PO; IFCC task force on clinical applications of cardiac biomarkers. Analytical characteristics of high-sensitivity cardiac troponin assays. Clin Chem 2012;58:54–61.10.1373/clinchem.2011.165795Search in Google Scholar PubMed

38. Goodacre S, Thokala P, Carroll C, Stevens JW, Leaviss J, Al Khalaf M, et al. Systematic review, meta-analysis and economic modelling of diagnostic strategies for suspected acute coronary syndrome. Health Technol Assess 2013;17:v-vi,1–188.10.3310/hta17010Search in Google Scholar PubMed PubMed Central

Received: 2013-7-5

Accepted: 2013-7-10

Published Online: 2013-7-30

Published in Print: 2014-2-1

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Articles in the same Issue

https://doi.org/10.1515/cclm-2013-0524

Keywords for this article

acute coronary syndrome; high-sensitivity; myocardial infarction; troponin