Do we really need high-sensitivity troponin immunoassays in the emergency department? Maybe not
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Giuseppe Lippi
und
Gianfranco Cervellin
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”.
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-2013-0210Suche 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.2011.91Suche 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/S148180350001335XSuche 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)00804-4Suche 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/ehm355Suche 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.107.182881Suche 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.Suche 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-2012-0572Suche 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.Suche 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.0b013e31826e1058Suche 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/ehs154Suche 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.2013.203307Suche 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.2012.192716Suche 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-2011-0895Suche 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.2012.05.016Suche 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.2013.01.019Suche 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.2013.01.018Suche 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.2011.692Suche 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.2008.116020Suche 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.2011.171082Suche 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-2013-0021Suche 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.2012.198614Suche 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.2011.011211Suche 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.2013.03.056Suche 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.113.000204Suche 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-2013-303643Suche 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.2013.01.002Suche 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).Suche 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.2011.1896Suche 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.2013.03.044Suche 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.112.128603Suche 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.2013.05.043Suche 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/B978-0-12-394383-5.00007-2Suche 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-2013-0023Suche 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.2012.194928Suche 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-2012-0449Suche 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.2011.165795Suche 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/hta17010Suche in Google Scholar PubMed PubMed Central
©2014 by Walter de Gruyter Berlin Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- The ten commandments of laboratory testing for emergency physicians
- Review
- Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?
- Opinion Papers
- Do we really need high-sensitive troponin immunoassays in the emergency department? Definitely, yes!
- Do we really need high-sensitivity troponin immunoassays in the emergency department? Maybe not
- General Clinical Chemistry and Laboratory Medicine
- Cortisol and cortisone ratio in urine: LC-MS/MS method validation and preliminary clinical application
- Urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion increases in normal pregnancy but not in preeclampsia
- Influence of urine volume on the assessment of intestinal permeability in affected children by multiple sugar probes
- Measurement of amino terminal propeptide of type III procollagen (PIIINP) employing the ADVIA Centaur platform. Validation, reference interval and comparison to UniQ RIA
- Cancer Diagnostics
- Enrichment and enumeration of circulating tumor cells by efficient depletion of leukocyte fractions
- Immunological screening for tumor cells in serous body fluids has added value with the CELL-DYN Sapphire
- Cardiovascular Diseases
- The value of clinical and laboratory diagnostics for chest pain patients at the emergency department
- The concentration of high-sensitivity troponin I, galectin-3 and NT-proBNP substantially increase after a 60-km ultramarathon
- Autoantibody prevalence with an improved immunoassay for detecting cardiac troponin-specific autoantibodies
- Increased B-type natriuretic peptide levels in early-onset versus late-onset preeclampsia
- Association of the GCKR rs780094 polymorphism with metabolic traits including carotid intima-media thickness in Japanese community-dwelling men, but not in women
- Infectious Diseases
- Analysis of antibody response (IgM, IgG, IgG3) to Chikungunya virus using panel of peptides derived from envelope protein for serodiagnosis
- Letters to the Editor
- A short story on how the H-index may change the fate of scientists and scientific publishing
- A new and effective way for preventing pre-analytical laboratory errors
- Digital immunofluorescence enables automated detection of antinuclear antibody endpoint titers avoiding serial dilution
- Multicenter method evaluation of the ARK™ Methotrexate Immunoassay
- Haemoglobinopathies in nonendemic areas in recent years
- Clinical implications of a recent adjustment to the high-sensitivity cardiac troponin T assay: some results
- Effect of recalibration of the hs-TnT assay on diagnostic performance
Artikel in diesem Heft
- Frontmatter
- Editorial
- The ten commandments of laboratory testing for emergency physicians
- Review
- Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?
- Opinion Papers
- Do we really need high-sensitive troponin immunoassays in the emergency department? Definitely, yes!
- Do we really need high-sensitivity troponin immunoassays in the emergency department? Maybe not
- General Clinical Chemistry and Laboratory Medicine
- Cortisol and cortisone ratio in urine: LC-MS/MS method validation and preliminary clinical application
- Urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion increases in normal pregnancy but not in preeclampsia
- Influence of urine volume on the assessment of intestinal permeability in affected children by multiple sugar probes
- Measurement of amino terminal propeptide of type III procollagen (PIIINP) employing the ADVIA Centaur platform. Validation, reference interval and comparison to UniQ RIA
- Cancer Diagnostics
- Enrichment and enumeration of circulating tumor cells by efficient depletion of leukocyte fractions
- Immunological screening for tumor cells in serous body fluids has added value with the CELL-DYN Sapphire
- Cardiovascular Diseases
- The value of clinical and laboratory diagnostics for chest pain patients at the emergency department
- The concentration of high-sensitivity troponin I, galectin-3 and NT-proBNP substantially increase after a 60-km ultramarathon
- Autoantibody prevalence with an improved immunoassay for detecting cardiac troponin-specific autoantibodies
- Increased B-type natriuretic peptide levels in early-onset versus late-onset preeclampsia
- Association of the GCKR rs780094 polymorphism with metabolic traits including carotid intima-media thickness in Japanese community-dwelling men, but not in women
- Infectious Diseases
- Analysis of antibody response (IgM, IgG, IgG3) to Chikungunya virus using panel of peptides derived from envelope protein for serodiagnosis
- Letters to the Editor
- A short story on how the H-index may change the fate of scientists and scientific publishing
- A new and effective way for preventing pre-analytical laboratory errors
- Digital immunofluorescence enables automated detection of antinuclear antibody endpoint titers avoiding serial dilution
- Multicenter method evaluation of the ARK™ Methotrexate Immunoassay
- Haemoglobinopathies in nonendemic areas in recent years
- Clinical implications of a recent adjustment to the high-sensitivity cardiac troponin T assay: some results
- Effect of recalibration of the hs-TnT assay on diagnostic performance
