Abstract
Background: The time required for patients with acute chest pain to reach a hospital emergency department varies, possibly lowering the diagnostic performance of a general cut-off value for high-sensitivity cardiac troponin T (hs-cTnT) in diagnosing acute myocardial infarction (AMI). The aim of this study was to determine the cut-off values as calculated by receiver operating characteristic (ROC) of hs-cTnT at different times from onset of symptoms to admission, and to evaluate their diagnostic performance.
Methods: Our study included 3096 patients with symptoms suggestive of AMI. These patients were classified according to time from onset of symptoms to admission. The diagnostic accuracy was quantified by the area under the ROC curve (AUC).
Results: Of the patients, 1082 (49.3%) were diagnosed as having AMI (317 were non-ST segment elevation myocardial infarction [NSTEMI]). The AUC for hs-cTnT to diagnose AMI was 0.881 at <3 h after symptom onset, 0.940 at 3–6 h after symptom onset, 0.966 at 6–12 h after symptom onset, and 0.974 at >12 h after symptom onset. The threshold as determined by ROC of hs-cTnT was 13.5 ng/L to diagnose AMI at ≤3 h after symptom onset with a sensitivity of 81.8% and a specificity of 80.1%, 17.8 ng/L at 3–6 h after symptom onset with a sensitivity of 94.6% and a specificity of 84.3%, 30.0 ng/L at 6–12 h after symptom onset with a sensitivity of 95.9% and a specificity of 85.5%, and 58.0 ng/L at >12 h after symptom onset with a sensitivity of 92.7% and a specificity of 93.3%. The same observations were performed for the diagnosis of NSTEMI.
Conclusions: The ROC-determined cut-off value of hs-cTnT for AMI or NSTEMI diagnosis gradually increased with time from onset of symptoms to presentation. Using a higher cut-off value by ROC for hs-cTnT will improve its accuracy in diagnosing AMI or NSTEMI patients in late presenters. The higher value will enable physicians to more quickly rule in patients compared to the 99th percentile cut-off, and can rule out patients safely.
Acknowledgments
We are indebted to the patients who participated in this study, and to the ED staff as well as the laboratory technicians for their most valuable efforts. This study was supported by Roche Diagnostics GmbH in Shanghai (H1311115).
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Pope JH, Aufderheide TP, Ruthazer R, Woolard RH, Feldman JA, Beshansky JR, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000;342:1163–70.10.1056/NEJM200004203421603Search in Google Scholar PubMed
2. Tiemann O. Variations in hospitalisation costs for acute myocardial infarction – a comparison across Europe. Health Econ 2008;17:S33–45.10.1002/hec.1322Search in Google Scholar PubMed
3. Forberg JL, Henriksen LS, Edenbrandt L, Ekelund U. Direct hospital costs of chest pain patients attending the emergency department: a retrospective study. BMC Emerg Med 2006;6:6.10.1186/1471-227X-6-6Search in Google Scholar PubMed PubMed Central
4. Apple FS, Smith SW, Pearce LA, Ler R, Murakami MM. Use of the Centaur TnI-Ultra assay for detection of myocardial infarction and adverse events in patients presenting with symptoms suggestive of acute coronary syndrome. Clin Chem 2008;54:723–8.10.1373/clinchem.2007.097162Search in Google Scholar PubMed
5. Keller T, Zeller T, Peetz D, Tzikas S, Roth A, Czyz E, et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 2009;361:868–77.10.1056/NEJMoa0903515Search in Google Scholar PubMed
6. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837–45.10.2307/2531595Search in Google Scholar
7. Wildi K, Reichlin T, Twerenbold R, Mader F, Zellweger C, Moehring B, et al. Serial changes in high-sensitivity cardiac troponin I in the early diagnosis of acute myocardial infarction. Int J Cardiol 2013;168:4103–10.10.1016/j.ijcard.2013.07.078Search in Google Scholar PubMed
8. 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
9. Razzouk L, Fusaro M, Esquitin R. Novel biomarkers for risk stratification and identification of life-threatening cardiovascular disease: troponin and beyond. Curr Cardiol Rev 2012;8:109–15.10.2174/157340312801784943Search in Google Scholar PubMed PubMed Central
10. Aldous SJ, Richards M, Cullen L, Troughton R, Than M. Diagnostic and prognostic utility of early measurement with high-sensitivity troponin T assay in patients presenting with chest pain. Can Med Assoc J 2012;184:E260–8.10.1503/cmaj.110773Search in Google Scholar PubMed PubMed Central
11. Aldous S, Pemberton C, Richards AM, Troughton R, Than M. High-sensitivity troponin T for early rule-out of myocardial infarction in recent onset chest pain. Emerg Med J 2012;29:805–10.10.1136/emermed-2011-200222Search in Google Scholar PubMed
12. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461–70.10.7326/0003-4819-130-6-199903160-00002Search in Google Scholar PubMed
13. White H. Avatar of the universal definition of periprocedural myocardial infarction. J Am Coll Cardiol 2013;62:1571–4.10.1016/j.jacc.2013.08.721Search in Google Scholar PubMed
14. Muller-Bardorff M, Hallermayer K, Schroder A, Ebert C, Borgya A, Gerhardt W, et al. Improved troponin T ELISA specific for cardiac troponin T isoform: assay development and analytical and clinical validation. Clin Chem 1997;43:458–66.10.1093/clinchem/43.3.458Search in Google Scholar
15. Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem 2010;56:254–61.10.1373/clinchem.2009.132654Search in Google Scholar PubMed
16. Mueller C, Laule-Kilian K, Schindler C, Klima T, Frana B, Rodriguez D, et al. Cost-effectiveness of B-type natriuretic peptide testing in patients with acute dyspnea. Arch Intern Med 2006;166:1081–7.10.1001/archinte.166.10.1081Search in Google Scholar PubMed
17. Eggers KM, Lind L, Ahlstrom H, Bjerner T, Ebeling BC, Larsson A, et al. Prevalence and pathophysiological mechanisms of elevated cardiac troponin I levels in a population-based sample of elderly subjects. Eur Heart J 2008;29:2252–8.10.1093/eurheartj/ehn327Search in Google Scholar PubMed
18. Meune C, Balmelli C, Vogler E, Twerenbold R, Reiter M, Reichlin T, et al. Consideration of high-sensitivity troponin values below the 99th percentile at presentation: does it improve diagnostic accuracy? Int J Cardiol 2013;168:3752–7.10.1016/j.ijcard.2013.06.011Search in Google Scholar PubMed
19. Reichlin T, Schindler C, Drexler B, Twerenbold R, Reiter M, Zellweger C, et al. One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Arch Intern Med 2012;172:1211–8.10.1001/archinternmed.2012.3698Search in Google Scholar PubMed
20. Meune C, Balmelli C, Twerenbold R, Reichlin T, Reiter M, Haaf P, et al. Patients with acute coronary syndrome and normal high-sensitivity troponin. Am J Med 2011;124:1151–7.10.1016/j.amjmed.2011.07.032Search in Google Scholar PubMed
21. Tsutamoto T, Kawahara C, Yamaji M, Nishiyama K, Fujii M, Yamamoto T, et al. Relationship between renal function and serum cardiac troponin T in patients with chronic heart failure. Eur J Heart Fail 2009;11:653–8.10.1093/eurjhf/hfp072Search in Google Scholar PubMed
22. Chen S, Huang C, Wu B, Lian X, Mei X, Wan J. Cardiac troponin I in non- acute coronary syndrome patients with chronic kidney disease. PLoS One 2013;8:e82752.10.1371/journal.pone.0082752Search in Google Scholar PubMed PubMed Central
23. Mueller M, Celik S, Biener M, Vafaie M, Schwoebel K, Wollert KC, et al. Diagnostic and prognostic performance of a novel high-sensitivity cardiac troponin T assay compared to a contemporary sensitive cardiac troponin I assay in patients with acute coronary syndrome. Clin Res Cardiol 2012;101:837–45.10.1007/s00392-012-0469-6Search in Google Scholar PubMed
24. Lotze U, Lemm H, Heyer A, Muller K. Combined determination of highly sensitive troponin T and copeptin for early exclusion of acute myocardial infarction: first experience in an emergency department of a general hospital. Vasc Health Risk Manag 2011;7:509–15.10.2147/VHRM.S21753Search in Google Scholar PubMed PubMed Central
25. Amsterdam EA, Kirk JD, Bluemke DA, Diercks D, Farkouh ME, Garvey JL, et al. Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association. Circulation 2010;122:1756–76.10.1161/CIR.0b013e3181ec61dfSearch in Google Scholar PubMed PubMed Central
26. Dehghan A, Leening MJ, Solouki AM, Boersma E, Deckers JW, van Herpen G, et al. Comparison of prognosis in unrecognized versus recognized myocardial infarction in men versus women >55 years of age (from the Rotterdam Study). Am J Cardiol 2014;113:1–6.10.1016/j.amjcard.2013.09.005Search in Google Scholar PubMed
27. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. Circulation 2012;126:2020–35.10.1161/CIR.0b013e31826e1058Search in Google Scholar PubMed
28. Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009;361:858–67.10.1056/NEJMoa0900428Search in Google Scholar PubMed
29. Giannitsis E, Becker M, Kurz K, Hess G, Zdunek D, Katus HA. High-sensitivity cardiac troponin T for early prediction of evolving non-ST-segment elevation myocardial infarction in patients with suspected acute coronary syndrome and negative troponin results on admission. Clin Chem 2010;56:642–50.10.1373/clinchem.2009.134460Search in Google Scholar PubMed
©2016 by De Gruyter
