High-Sensitivity Troponin Assays in Clinical Diagnostics of Acute Coronary Syndrome

  • Danielle Hof
  • Arnold von EckardsteinEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1929)


Nowadays, measurement of cardiac troponins (cTn) in patient plasma is central for diagnosis of patients with acute coronary syndrome (ACS). High-sensitivity (hs) immunoassays have been developed that can very precisely record slightly elevated and rising plasma concentrations of cTn very early after onset of clinical symptoms. Algorithms integrate measurements of hs-cTn at onset of clinical symptoms of acute myocardial infarction (AMI), and 1 or 3 h after onset, to rule-in and rule-out AMI patients. More and more point-of-care (POC) cTn assays conquer the diagnostic market, but thorough clinical validation studies are required before potential implementation of such POC tests into hospital settings. This review provides an overview of the technical aspects, as well as diagnostic and prognostic use of cardiac troponins in AMI patients and in the healthy population.

Key words

Acute coronary syndrome Acute myocardial infarction Cardiac troponin High-sensitivity assay NSTEMI STEMI Laboratory medicine 


  1. 1.
    Ibanez B, James S, Agewall S et al (2018) 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 39:119–177. Scholar
  2. 2.
    Benjamin EJ, Blaha MJ, Chiuve SE (2017) Heart disease and stroke statistics—2017 update. A report from the American Heart Association. Circulation 135:e146–e603. Scholar
  3. 3.
    Muller JE, Tofler GH, Stone PH (1989) Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 79:733–743. Scholar
  4. 4.
    Davies MJ (2000) Coronary disease: the pathophysiology of acute coronary syndromes. Heart 83:361–366. Scholar
  5. 5.
    Bentzon JF, Otsuka F, Virmani R, Falk E (2014) Mechanisms of plaque formation and rupture. Circ Res 114:1852–1866. Scholar
  6. 6.
    Thygesen K, Alpert JS, White HD (2012) Expert consensus document. Third universal definition of myocardial infarction. Eur Heart J 33:2551–2567. Scholar
  7. 7.
    Ebashi S, Endo M (1968) Calcium ion and muscle contraction. Prog Biophys Mol Biol 18:123–183CrossRefGoogle Scholar
  8. 8.
    Perry SV (2008) Background to the discovery of troponin and Setsuro Ebashi’s contribution to our knowledge of the mechanism of relaxation in striated muscle. Biochem Biophys Res Commun 369:43–48. Scholar
  9. 9.
    Gordon AM, Homsher E, Regnier M (2000) Regulation of contraction in striated muscle. Physiol Rev 80:853–924. Scholar
  10. 10.
    Manning EP, Tardiff JC, Schwartz SD (2011) A model of calcium activation of the cardiac thin filament. Biochemistry (Mosc) 50:7405–7413. Scholar
  11. 11.
    Takeda S (2005) Crystal structure of troponin and the molecular mechanism of muscle regulation. J Electron Microsc 54. (Supplement 1:i35–i41CrossRefGoogle Scholar
  12. 12.
    Katrukha IA (2013) Human cardiac troponin complex. Structure and functions. Biochem Mosc 78:1447–1465. Scholar
  13. 13.
    Jaffe AS, Vasile VC, Milone M et al (2011) Diseased skeletal muscle. A noncardiac source of increased circulating concentrations of cardiac troponin T. J Am Coll Cardiol 58:1819–1824. Scholar
  14. 14.
    Hof D, Jung HH, Bloch KE (2013) Troponin T elevation in amyotrophic lateral sclerosis without cardiac damage. Amyotroph Lateral Scler Frontotemporal Degener 14:75–77. Scholar
  15. 15.
    Rittoo D, Jones A, Lecky B, Neithercut D (2014) Elevation of cardiac troponin T, but not cardiac troponin I, in patients with neuromuscular diseases. J Am Coll Cardiol 63:2411–2420. Scholar
  16. 16.
    Giannitsis E, Katus HA (2012) Challenging interpretation of elevated cardiac troponin T in complex case with rhabdomyolysis. J Am Coll Cardiol 60:1027–1028CrossRefGoogle Scholar
  17. 17.
    Hallén J (2012) Troponin for the estimation of infarct size: what have we learned. Cardiology 121:204–212. Scholar
  18. 18.
    Gerhardt W, Katus H, Ravkilde J et al (1991) S-Troponin T in suspected ischemic myocardial injury compared with mass and catalytic concentration of S-creatine kinase isoenzyme MB. Clin Chem 37:1405–1411PubMedGoogle Scholar
  19. 19.
    Bleier J, Vorderwinkler K-P, Falkensammer J et al (1998) Different intracellular compartmentations of cardiac troponins and myosin heavy chains: a casual connection to their different early release after myocardial damage. Clin Chem 44:1912–1918PubMedGoogle Scholar
  20. 20.
    Labugger R, Organ L, Collier C et al (2000) Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction. Circulation 102:1221–1226. Scholar
  21. 21.
    Peronnet E, Becquart L, Poirier F et al (2006) SELDI-TOF MS analysis of the cardiac troponin I forms present in plasma from patients with myocardial infarction. Proteomics 6:6288–6299. Scholar
  22. 22.
    Peronnet E, Becquart L, Martinez J et al (2007) Isoelectric point determination of cardiac troponin I forms present in plasma from patients with myocardial infarction. Clin Chim Acta 377:243–247. Scholar
  23. 23.
    Amsterdam EA, Wenger NK, Brindis RG et al (2014) 2014 AHA/ACC Guideline for the management of patients with non–ST-elevation acute coronary syndromes. J Am Coll Cardiol 64:e139–e228. Scholar
  24. 24.
    Roffi M, Patrono C, Collet J-P et al (2016) 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 37:267–315. Scholar
  25. 25.
    Alvin MD, Jaffe AS, Ziegelstein RC, Trost JC (2017) Eliminating creatine kinase–myocardial band testing in suspected acute coronary syndrome: a value-based quality improvement. JAMA Intern Med 177:1508. Scholar
  26. 26.
    Apple FS (2009) A new season for cardiac troponin assays: it’s time to keep a scorecard. Clin Chem 55:1303–1306. Scholar
  27. 27.
    IFCC task force on clinical applications of cardiac bio-markers (2018) Point of care cardiac troponin I and T assay analytical characteristics designated by manufacturer (v060617).
  28. 28.
    IFCC task force on clinical applications of cardiac bio-markers (2018) Contemporary cardiac troponin I and T assay analytical characteristic designated by manufacturer.
  29. 29.
    IFCC task force on clinical applications of cardiac bio-markers (2018) High sensitivity cardiac troponin I and T assay analytical characteristic designated by manufacturer.
  30. 30.
    Apple FS, Sandoval Y, Jaffe AS, Ordonez-Llanos J (2017) Cardiac troponin assays: guide to understanding analytical characteristics and their impact on clinical care. Clin Chem 63:73–81. Scholar
  31. 31.
    Apple FS, Collinson PO (2012) Analytical characteristics of high-sensitivity cardiac troponin assays. Clin Chem 58:54–61. Scholar
  32. 32.
    Apple FS, Ler R, Murakami MM (2012) Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem 58:1574–1581. Scholar
  33. 33.
    Apple FS, Jaffe AS, Collinson P et al (2015) IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin Biochem 48:201–203. Scholar
  34. 34.
    Singer AJ, Taylor M, LeBlanc D et al (2018) Early point-of-care testing at triage reduces care time in stable adult emergency department patients. J Emerg Med 55(2):172–178. Scholar
  35. 35.
    Suh D, Keller DI, Hof D et al (2018) Rule-out of non-ST elevation myocardial infarction by five point of care cardiac troponin assays according to the 0 h/3 h algorithm of the European Society of Cardiology. Clin Chem Lab Med 56:649–657. Scholar
  36. 36.
    Arshed S, Luo HX, Zafar S et al (2015) Elevated troponin I in the absence of coronary artery disease: a case report with review of literature. J Clin Med Res 7:820–824. Scholar
  37. 37.
    Sturgeon CM, Viljoen A (2011) Analytical error and interference in immunoassay: minimizing risk. Ann Clin Biochem 48:418–432. Scholar
  38. 38.
    Tate J, Ward G (2004) Interferences in Immunoassay. Clin Biochem Rev 25:105–120PubMedPubMedCentralGoogle Scholar
  39. 39.
    Ward G, Simpson A, Boscato L, Hickman PE (2017) The investigation of interferences in immunoassay. Clin Biochem 50:1306–1311. Scholar
  40. 40.
    Savukoski T, Ilva T, Lund J et al (2014) Autoantibody prevalence with an improved immunoassay for detecting cardiac troponin-specific autoantibodies. Clin Chem Lab Med 52:273–279. Scholar
  41. 41.
    Adamczyk M, Brashear RJ, Mattingly PG (2010) Coprevalence of autoantibodies to cardiac troponin I and T in normal blood donors. Clin Chem 56:676–677. Scholar
  42. 42.
    de Torbal A, Boersma E, Kors JA et al (2006) Incidence of recognized and unrecognized myocardial infarction in men and women aged 55 and older: the Rotterdam Study. Eur Heart J 27:729–736. Scholar
  43. 43.
    Diercks DB, Peacock WF, Hiestand BC et al (2006) Frequency and consequences of recording an electrocardiogram >10 minutes after arrival in an emergency room in non–ST-segment elevation acute coronary syndromes (from the CRUSADE Initiative). Am J Cardiol 97:437–442. Scholar
  44. 44.
    Zijlstra F, Hoorntje JCA, De Boer M-J et al (1999) Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. N Engl J Med 341:1413–1419CrossRefGoogle Scholar
  45. 45.
    Andersen HR, Nielsen TT, Rasmussen K et al (2003) A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med 349:733–742CrossRefGoogle Scholar
  46. 46.
    Chan AW, Kornder J, Elliott H et al (2012) Improved survival sssociated with pre-hospital triage strategy in a large regional ST-segment elevation myocardial infarction program. JACC Cardiovasc Interv 5:1239–1246. Scholar
  47. 47.
    Savonitto S, Ardissino D, Granger CB et al (1999) Prognostic value of the admission electrocardiogram in acute coronary syndromes. JAMA 281:707–713. Scholar
  48. 48.
    Keller T, Zeller T, Ojeda F et al (2011) Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction. JAMA 306:2684–2693. Scholar
  49. 49.
    Rubini Giménez M, Hoeller R, Reichlin T et al (2013) Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin. Int J Cardiol 168:3896–3901. Scholar
  50. 50.
    Thelin J, Melander O, Öhlin B (2015) Early rule-out of acute coronary syndrome using undetectable levels of high sensitivity troponin T. Eur Heart J Acute Cardiovasc Care 4:403–409. Scholar
  51. 51.
    Shah ASV, Anand A, Sandoval Y et al (2015) High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. Lancet 386:2481–2488. Scholar
  52. 52.
    Wildi K, Nelles B, Twerenbold R et al (2016) Safety and efficacy of the 0 h/3 h protocol for rapid rule out of myocardial infarction. Am Heart J 181:16–25. Scholar
  53. 53.
    Tang EW, Wong C-K, Herbison P (2007) Global Registry of Acute Coronary Events (GRACE) hospital discharge risk score accurately predicts long-term mortality post acute coronary syndrome. Am Heart J 153:29–35. Scholar
  54. 54.
    Reichlin T, Twerenbold R, Wildi K et al (2015) Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay. Can Med Assoc J 187:E243–E252. Scholar
  55. 55.
    Rubini Giménez M, Twerenbold R, Jaeger C et al (2015) One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I. Am J Med 128:861–870. Scholar
  56. 56.
    Jaeger C, Wildi K, Twerenbold R et al (2016) One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I. Am Heart J 171:92–102. Scholar
  57. 57.
    Mueller C, Giannitsis E, Christ M 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. Scholar
  58. 58.
    Neumann JT, Sörensen NA, Ojeda F et al (2017) Early diagnosis of acute myocardial infarction using high-sensitivity troponin I. PLoS One 12:e0174288. Scholar
  59. 59.
    Boeddinghaus J, Nestelberger T, Twerenbold R et al (2017) Direct comparison of 4 very early rule-out strategies for acute myocardial infarction using high-sensitivity cardiac troponin I. Circulation 135:1597–1611. Scholar
  60. 60.
    Westermann D, Neumann JT, Sörensen NA, Blankenberg S (2017) High-sensitivity assays for troponin in patients with cardiac disease. Nat Rev Cardiol 14:472–483. Scholar
  61. 61.
    Twerenbold R, Badertscher P, Boeddinghaus J et al (2018) 0/1-Hour triage algorithm for myocardial infarction in patients with renal dysfunction. Circulation 137:436–451. Scholar
  62. 62.
    Gunsolus I, Sandoval Y, Smith SW et al (2018) Renal dysfunction influences the diagnostic and prognostic performance of high-sensitivity cardiac troponin I. J Am Soc Nephrol 29:636–643. Scholar
  63. 63.
    Poldervaart JM, Langedijk M, Backus BE et al (2017) Comparison of the GRACE, HEART and TIMI score to predict major adverse cardiac events in chest pain patients at the emergency department. Int J Cardiol 227:656–661. Scholar
  64. 64.
    Bank IEM, de Hoog VC, de Kleijn DPV et al (2017) Sex-based differences in the performance of the HEART score in patients presenting to the emergency department with acute chest pain. J Am Heart Assoc 6:e005373. Scholar
  65. 65.
    Bonaca M, Scirica B, Sabatine M et al (2010) Prospective evaluation of the prognostic implications of improved assay performance with a sensitive assay for cardiac troponin I. J Am Coll Cardiol 55:2118–2124. Scholar
  66. 66.
    Scirica BM, Sabatine MS, Jarolim P et al (2011) Assessment of multiple cardiac biomarkers in non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 Trial. Eur Heart J 32:697–705. Scholar
  67. 67.
    Widera C, Pencina MJ, Bobadilla M et al (2013) Incremental prognostic value of biomarkers beyond the GRACE (Global Registry of Acute Coronary Events) score and high-sensitivity cardiac troponin T in non-ST-elevation acute coronary syndrome. Clin Chem 59:1497–1505. Scholar
  68. 68.
    O’Malley RG, Bonaca MP, Scirica BM et al (2014) Prognostic performance of multiple biomarkers in patients with non–ST-segment elevation acute coronary syndrome. J Am Coll Cardiol 63:1644–1653. Scholar
  69. 69.
    Klingenberg R, Aghlmandi S, Räber L et al (2018) Improved risk stratification of patients with acute coronary syndromes using a combination of hsTnT, NT-proBNP and hsCRP with the GRACE score. Eur Heart J Acute Cardiovasc Care 7:129–138. Scholar
  70. 70.
    Magnussen C, Blankenberg S (2018) Biomarkers for heart failure: small molecules with high clinical relevance. J Intern Med 283:530–543. Scholar
  71. 71.
    Januzzi JL, Filippatos G, Nieminen M, Gheorghiade M (2012) Troponin elevation in patients with heart failure: on behalf of the third Universal Definition of Myocardial Infarction Global Task Force: Heart Failure Section. Eur Heart J 33:2265–2271. Scholar
  72. 72.
    Wang J, Tan G-J, Han L-N et al (2017) Novel biomarkers for cardiovascular risk prediction. J Geriatr Cardiol 14:135–150. Scholar
  73. 73.
    Gordon T, Castelli WP, Hjortlnd MC et al (1977) High density lipoprotein as a protective factor against coronary heart disease—the Framingham study. Am J Med 62:707–714CrossRefGoogle Scholar
  74. 74.
    Assmann G, Schulte H, von Eckardstein A, Huang Y (1996) High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathphysiological implications for reverse cholesterol transport. Atherosclerosis 124(Suppl):S11–S20CrossRefGoogle Scholar
  75. 75.
    Stone NJ, Robinson JG, Lichtenstein AH et al (2014) 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. Circulation 129:S1–S45. Scholar
  76. 76.
    Catapano AL, Graham I, De Backer G et al (2016) 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 37:2999–3058. Scholar
  77. 77.
    Blankenberg S, Salomaa V, Makarova N et al (2016) Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium. Eur Heart J 37:2428–2437. Scholar
  78. 78.
    Apple FS, Steffen LM, Pearce LA et al (2012) Increased cardiac troponin I as measured by a high-sensitivity assay is associated with high odds of cardiovascular death: the Minnesota Heart Survey. Clin Chem 58:930–935. Scholar
  79. 79.
    Ford I, Shah ASV, Zhang R et al (2016) High-sensitivity cardiac troponin, statin therapy, and risk of coronary heart disease. J Am Coll Cardiol 68:2719–2728. Scholar
  80. 80.
    Xiao W, Cao R, Liu Y et al (2017) Association of high-sensitivity cardiac troponin T with mortality and cardiovascular events in a community-based prospective study in Beijing. BMJ Open 7:e013431. Scholar
  81. 81.
    Samman Tahhan A, Sandesara P, Hayek SS et al (2018) High-sensitivity troponin I levels and coronary artery disease severity, progression, and long-term outcomes. J Am Heart Assoc 7:e007914. Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Unilabs, DübendorfDübendorfSwitzerland
  2. 2.Institute for Clinical ChemistryUniversity Hospital ZurichZürichSwitzerland

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