Rapid rule-out of suspected acute coronary syndrome in the Emergency Department by high-sensitivity cardiac troponin T levels at presentation

  • Andrea Fabbri
  • Cristina Bachetti
  • Filippo Ottani
  • Alice Morelli
  • Barbara Benazzi
  • Sergio Spiezia
  • Marco Cortigiani
  • Romolo Dorizzi
  • Allan S. Jaffe
  • Marcello Galvani


The reliability of initial high-sensitivity cardiac troponin T (hs-cTnT) under limit-of-detection in ruling-out short- and long-term acute coronary events in subjects for suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is not definitely settled. In a retrospective chart review analysis, 1001 subjects with hs-cTnT ≤ 14 ng/L out of 4053 subjects with hs-cTnT measured at Emergency Department (ED) presentation were recruited. The main outcome measure is fatal or non-fatal myocardial infarction (MI) within 30 days; secondary outcomes are MI or major acute coronary events (MACE) as a combination of MI or re-hospitalization for unstable angina within 1 year. In subjects with hs-cTnT < 5 ng/L [32.6% of cases, mean age 63 years (interquartile range 23)], no cases (0%, NPV 100%) had MI within 30 days, 2 cases (0.6%, NPV 99.4%) MI at 1-year, and 11 cases (3.4%, NPV 96.6%) MACE at 1-year. Patients with hs-cTnT < 5 ng/L would have benefited from a shortened decision (9.30 h and 53% overnight ED stay saved). Hs-cTnT < 5 ng/L is confirmed as safe for patients and comfortable for physicians in ruling out MI or MACE both at short and long term, suggesting that a sizable number of patients can be rapidly discharged without unnecessary diagnostic tests and ED observation.


Undetectable high-sensitivity cardiac troponin T Suspected non-ST-segment elevation acute coronary syndrome Emergency department Myocardial infarction 



We are grateful to Daniela Bellavista, Medical Project Manager, Roche Diagnostics Italy for helpful support.

Author contributions

AF and MG had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the results. All authors were involved in the study concept and design and statistical analyses. MC, BB, AM, SS and BC were responsible for collection, management, analyses and interpretation of the data. AF and MG conducted the statistical analyses and drafted the manuscript. All authors contributed substantially to its revision and agree to be accountable for all the aspects of the work. FO, ASJ and RD supervised the study. AF takes responsibility for the paper as a whole.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to disclose.

Statement of human and animal rights

The authors declare that all contents in this study are in accordance with ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

This is a retrospective study and for this type of study formal consent is not required.


  1. 1.
    Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F et al (2016) 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 37:267–315CrossRefGoogle Scholar
  2. 2.
    Body R, Carley S, McDowell G, Jaffe AS, France M, Cruickshank K et al (2011) Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivity assay. J Am Coll Cardiol 58:1332–1339CrossRefGoogle Scholar
  3. 3.
    Reichlin T, Hochholzer W, Stelzig C, Laule K, Freidank H, Morgenthaler NG et al (2009) Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol 54:60–68CrossRefGoogle Scholar
  4. 4.
    Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S et al (2009) Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 361:858–867CrossRefGoogle Scholar
  5. 5.
    Than M, Cullen L, Aldous S, Parsonage WA, Reid CM, Greenslade J et al (2012) 2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial. J Am Coll Cardiol 59:2091–2098CrossRefGoogle Scholar
  6. 6.
    Goodacre SW, Bradburn M, Cross E, Collinson P, Gray A, Hall AS et al (2011) The randomised assessment of treatment using panel assay of cardiac markers (RATPAC) trial: a randomised controlled trial of point-of-care cardiac markers in the emergency department. Heart 97:190–196CrossRefGoogle Scholar
  7. 7.
    Munro AR, Jerram T, Morton T, Hamilton S (2015) Use of an accelerated diagnostic pathway allows rapid and safe discharge of 70% of chest pain patients from the emergency department. N Z Med J 128:62–71PubMedGoogle Scholar
  8. 8.
    Sebbane M, Lefebvre S, Kuster N, Jreige R, Jacques E, Badiou S et al (2013) Early rule out of acute myocardial infarction in ED patients: value of combined high-sensitivity cardiac troponin T and ultrasensitive copeptin assays at admission. Am J Emerg Med 31:1302–1308CrossRefGoogle Scholar
  9. 9.
    Biener M, Mueller M, Vafaie M, Katus HA, Giannitsis E (2015) Impact of leading presenting symptoms on the diagnostic performance of high-sensitivity cardiac troponin T and on outcomes in patients with suspected acute coronary syndrome. Clin Chem 61:744–751CrossRefGoogle Scholar
  10. 10.
    Freund Y, Chenevier-Gobeaux C, Bonnet P, Claessens YE, Allo JC, Doumenc B et al (2011) High-sensitivity versus conventional troponin in the emergency department for the diagnosis of acute myocardial infarction. Crit Care 15:R147CrossRefGoogle Scholar
  11. 11.
    Ter Avest E, Visser A, Reitsma B, Breedveld R, Wolthuis A (2016) Point-of-care troponin T is inferior to high-sensitivity troponin T for ruling out acute myocardial infarction in the emergency department. Eur J Emerg Med 23:95–101CrossRefGoogle Scholar
  12. 12.
    Mokhtari A, Lindahl B, Smith JG, Holzmann MJ, Khoshnood A, Ekelund U (2016) Diagnostic accuracy of high-sensitivity cardiac troponin T at presentation combined with history and ECG for ruling out major adverse cardiac events. Ann Emerg Med 68(649–658):e643Google Scholar
  13. 13.
    Body R, Mueller C, Giannitsis E, Christ M, Ordonez-Llanos J, de Filippi CR et al (2016) The use of very low concentrations of high-sensitivity troponin t to rule out acute myocardial infarction using a single blood test. Acad Emerg Med 23:1004–1013CrossRefGoogle Scholar
  14. 14.
    Bandstein N, Ljung R, Johansson M, Holzmann MJ (2014) Undetectable high-sensitivity cardiac troponin T level in the emergency department and risk of myocardial infarction. J Am Coll Cardiol 63:2569–2578CrossRefGoogle Scholar
  15. 15.
    Chapman AR, Anand A, Boeddinghaus J, Ferry AV, Sandeman D, Adamson PD et al (2017) Comparison of the efficacy and safety of early rule-out pathways for acute myocardial infarction. Circulation 135:1586–1596CrossRefGoogle Scholar
  16. 16.
    Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP et al (2003) Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med 163:2345–2353CrossRefGoogle Scholar
  17. 17.
    Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD et al (2012) Third universal definition of myocardial infarction. J Am Coll Cardiol 60:1581–1598CrossRefGoogle Scholar
  18. 18.
    Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA (2010) Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem 56:254–261CrossRefGoogle Scholar
  19. 19.
    Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K (2012) Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med 156:785–795 (W-270–W-278) CrossRefGoogle Scholar
  20. 20.
    Thygesen K, Mair J, Giannitsis E, Mueller C, Lindahl B, Blankenberg S et al (2012) How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 33:2252–2257CrossRefGoogle Scholar
  21. 21.
    Sanchis J, Garcia-Blas S, Carratala A, Valero E, Mollar A, Minana G et al (2016) Clinical evaluation versus undetectable high-sensitivity troponin for assessment of patients with acute chest pain. Am J Cardiol 118:1631–1635CrossRefGoogle Scholar
  22. 22.
    Shah AS, Anand A, Sandoval Y, Lee KK, Smith SW, Adamson PD et al (2015) High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. Lancet 386:2481–2488CrossRefGoogle Scholar
  23. 23.
    Body R, Burrows G, Carley S, Cullen L, Than M, Jaffe AS et al (2015) High-sensitivity cardiac troponin t concentrations below the limit of detection to exclude acute myocardial infarction: a prospective evaluation. Clin Chem 61:983–989CrossRefGoogle Scholar
  24. 24.
    Love SA, Sandoval Y, Smith SW, Nicholson J, Cao J, Ler R et al (2016) Incidence of undetectable, measurable, and increased cardiac troponin I concentrations above the 99th percentile using a high-sensitivity vs a contemporary assay in patients presenting to the emergency Department. Clin Chem 62:1115–1119CrossRefGoogle Scholar
  25. 25.
    Chenevier-Gobeaux C, Lefevre G, Bonnefoy-Cudraz E, Charpentier S, Dehoux M, Meune C et al (2016) Why a new algorithm using high-sensitivity cardiac troponins for the rapid rule-out of NSTEMI is not adapted to routine practice. Clin Chem Lab Med 54:e279–e280CrossRefGoogle Scholar
  26. 26.
    Than M, Herbert M, Flaws D, Cullen L, Hess E, Hollander JE et al (2013) What is an acceptable risk of major adverse cardiac event in chest pain patients soon after discharge from the Emergency Department?: a clinical survey. Int J Cardiol 166:752–754CrossRefGoogle Scholar
  27. 27.
    Carlton E, Greenslade J, Cullen L, Body R, Than M, Pickering JW et al (2016) Evaluation of high-sensitivity cardiac troponin I levels in patients with suspected acute coronary syndrome. JAMA Cardiol 1:405–412CrossRefGoogle Scholar
  28. 28.
    Pickering JW, Greenslade JH, Cullen L, Flaws D, Parsonage W, Aldous S et al (2016) Assessment of the European Society of Cardiology 0-Hour/1-hour algorithm to rule-out and rule-in acute myocardial infarction. Circulation 134:1532–1541CrossRefGoogle Scholar
  29. 29.
    Than M, Aldous S, Lord SJ, Goodacre S, Frampton CM, Troughton R et al (2014) A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial. JAMA Intern Med 174:51–58CrossRefGoogle Scholar
  30. 30.
    McRae AD, Innes G, Graham M, Lang E, Andruchow JE, Ji Y et al (2017) Undetectable concentrations of a food and drug administration-approved high-sensitivity cardiac troponin T assay to rule out acute myocardial infarction at emergency department arrival. Acad Emerg Med 24:1267–1277CrossRefGoogle Scholar
  31. 31.
    Julicher P, Greenslade JH, Parsonage WA, Cullen L (2017) The organisational value of diagnostic strategies using high-sensitivity troponin for patients with possible acute coronary syndromes: a trial-based cost-effectiveness analysis. BMJ Open 7:e013653CrossRefGoogle Scholar
  32. 32.
    Mueller C, Giannitsis E, Christ M, Ordonez-Llanos J, deFilippi C, McCord J et al (2016) Multicenter evaluation of a 0-hour/1-hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin T. Ann Emerg Med 68(76–87):e74Google Scholar
  33. 33.
    MacGougan CK, Christenson JM, Innes GD, Raboud J (2001) Emergency physicians’ attitudes toward a clinical prediction rule for the identification and early discharge of low risk patients with chest discomfort. CJEM 3:89–94CrossRefGoogle Scholar
  34. 34.
    Mausner JSKS, Bahn AK (1985) Epidemiology: an introductory text, 6th edn. American Public Health Association, PhiladelphiaGoogle Scholar

Copyright information

© Società Italiana di Medicina Interna (SIMI) 2018

Authors and Affiliations

  • Andrea Fabbri
    • 1
  • Cristina Bachetti
    • 2
  • Filippo Ottani
    • 2
    • 5
  • Alice Morelli
    • 1
  • Barbara Benazzi
    • 1
  • Sergio Spiezia
    • 1
  • Marco Cortigiani
    • 1
  • Romolo Dorizzi
    • 3
  • Allan S. Jaffe
    • 4
  • Marcello Galvani
    • 2
    • 5
  1. 1.Dipartimento EmergenzaPresidio Ospedaliero Morgagni-Pierantoni, Azienda USL della RomagnaForlìItaly
  2. 2.Dipartimento Cardio-vascolare, Presidio Ospedaliero Morgagni-Pierantoni, AUSL della RomagnaForlìItaly
  3. 3.Laboratorio Unico AUSL della RomagnaPievesestina di CesenaItaly
  4. 4.Cardiovascular Department and Department of Laboratory Medicine and PathologyMayo Clinic and Medical SchoolRochesterUSA
  5. 5.Cardiovascular Research UnitFondazione Cardiologica SaccoForlìItaly

Personalised recommendations