1932

Abstract

Rapid and accurate triage of patients presenting with chest pain to an emergency department (ED) is critical to prevent ED overcrowding and unnecessary resource use in individuals at low risk of acute myocardial infarction (AMI) and to efficiently and effectively guide patients at high risk to definite therapy. The use of biomarkers for rule-out or rule-in of suspected AMI has evolved substantially over the last several decades. Previously well-established biomarkers have been replaced by cardiac troponin (cTn). High-sensitivity cTn (hs-cTn) assays represent the newest generation of cTn assays and offer tremendous advantages, including improved sensitivity and precision. Still, implementation of these assays in the United States lags behind several other areas of the world. Within this educational review, we discuss the evolution of biomarker testing for detection of myocardial injury, address the specifics of hs-cTn assays and their recommended use within triage algorithms, and highlight potential challenges in their use. Ultimately, we focus on implementation strategies for hs-cTn assays, as they are now clearly ready for prime time.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-051022-113931
2024-01-29
2024-06-17
Loading full text...

Full text loading...

/deliver/fulltext/med/75/1/annurev-med-051022-113931.html?itemId=/content/journals/10.1146/annurev-med-051022-113931&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Apple FS, Mills NL, Mueller C. 2022. The origin and future of cardiac troponin testing. Eur. Heart J. Acute Cardiovasc. Care 11:e1e2
    [Google Scholar]
  2. 2.
    Garg P, Morris P, Fazlanie AL et al. 2017. Cardiac biomarkers of acute coronary syndrome: from history to high-sensitivity cardiac troponin. Intern. Emerg. Med. 12:14755
    [Google Scholar]
  3. 3.
    Danese E, Montagnana M. 2016. An historical approach to the diagnostic biomarkers of acute coronary syndrome. Ann. Transl. Med. 4:194
    [Google Scholar]
  4. 4.
    Ebashi S, Ebashi F, Kodama A. 1967. Troponin as the Ca++-receptive protein in the contractile system. J. Biochem. 62:13738
    [Google Scholar]
  5. 5.
    Cummins B, Auckland ML, Cummins P. 1987. Cardiac-specific troponin-I radioimmunoassay in the diagnosis of acute myocardial infarction. Am. Heart J. 113:133344
    [Google Scholar]
  6. 6.
    Larue C, Defacque-Lacquement H, Calzolari C et al. 1992. New monoclonal antibodies as probes for human cardiac troponin I: epitopic analysis with synthetic peptides. Mol. Immunol. 29:27178
    [Google Scholar]
  7. 7.
    Katus HA, Remppis A, Looser S et al. 1989. Enzyme linked immuno assay of cardiac troponin T for the detection of acute myocardial infarction in patients. J. Mol. Cell Cardiol. 21:134953
    [Google Scholar]
  8. 8.
    Jarolim P. 2015. High sensitivity cardiac troponin assays in the clinical laboratories. Clin. Chem. Lab. Med. 53:63552
    [Google Scholar]
  9. 9.
    Apple FS, Sandoval Y, Jaffe AS et al. 2017. Cardiac troponin assays: guide to understanding analytical characteristics and their impact on clinical care. Clin. Chem. 63:7381
    [Google Scholar]
  10. 10.
    Clerico A, Zaninotto M, Aimo A et al. 2023. Variability of cardiac troponin levels in normal subjects and in patients with cardiovascular diseases: analytical considerations and clinical relevance. Clin. Chem. Lab. Med. 61:120929
    [Google Scholar]
  11. 11.
    Thygesen K, Alpert JS, Jaffe AS et al. 2018. Fourth universal definition of myocardial infarction 2018. Circulation 138:e618e51
    [Google Scholar]
  12. 12.
    Chapman AR, Lee KK, McAllister DA et al. 2017. Association of high-sensitivity cardiac troponin I concentration with cardiac outcomes in patients with suspected acute coronary syndrome. JAMA 318:191324
    [Google Scholar]
  13. 13.
    Westwood ME, Armstrong N, Worthy G et al. 2021. Optimizing the use of high-sensitivity troponin assays for the early rule-out of myocardial infarction in patients presenting with chest pain: a systematic review. Clin. Chem. 67:23744
    [Google Scholar]
  14. 14.
    Sandoval Y, Smith SW, Apple FS. 2016. Present and future of cardiac troponin in clinical practice: a paradigm shift to high-sensitivity assays. Am. J. Med. 129:35465
    [Google Scholar]
  15. 15.
    Reichlin T, Hochholzer W, Bassetti S et al. 2009. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N. Engl. J. Med. 361:85867
    [Google Scholar]
  16. 16.
    Reichlin T, Twerenbold R, Reiter M et al. 2012. Introduction of high-sensitivity troponin assays: impact on myocardial infarction incidence and prognosis. Am. J. Med. 125:120513.e1
    [Google Scholar]
  17. 17.
    Bohula May EA, Bonaca MP, Jarolim P et al. 2014. Prognostic performance of a high-sensitivity cardiac troponin I assay in patients with non-ST-elevation acute coronary syndrome. Clin. Chem. 60:15864
    [Google Scholar]
  18. 18.
    Collet JP, Thiele H, Barbato E et al. 2021. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur. Heart J. 42:1289367
    [Google Scholar]
  19. 19.
    Twerenbold R, Neumann JT, Sorensen NA et al. 2018. Prospective validation of the 0/1-h algorithm for early diagnosis of myocardial infarction. J. Am. Coll. Cardiol. 72:62032
    [Google Scholar]
  20. 20.
    Gulati M, Levy PD, Mukherjee D et al. 2021. AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J. Am. Coll. Cardiol 78:e187e285
    [Google Scholar]
  21. 21.
    McCarthy CP, Raber I, Chapman AR et al. 2019. Myocardial injury in the era of high-sensitivity cardiac troponin assays: a practical approach for clinicians. JAMA Cardiol 4:103442
    [Google Scholar]
  22. 22.
    Mair J, Lindahl B, Hammarsten O et al. 2018. How is cardiac troponin released from injured myocardium?. Eur. Heart J. Acute Cardiovasc. Care 7:55360
    [Google Scholar]
  23. 23.
    Aengevaeren VL, Baggish AL, Chung EH et al. 2021. Exercise-induced cardiac troponin elevations: from underlying mechanisms to clinical relevance. Circulation 144:195572
    [Google Scholar]
  24. 24.
    Sabatine MS, Morrow DA, de Lemos JA et al. 2009. Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischaemia using an ultrasensitive assay: results from TIMI 35. Eur. Heart J. 30:16269
    [Google Scholar]
  25. 25.
    Arnadottir A, Pedersen S, Bo Hasselbalch R et al. 2021. Temporal release of high-sensitivity cardiac troponin T and I and copeptin after brief induced coronary artery balloon occlusion in humans. Circulation 143:1095104
    [Google Scholar]
  26. 26.
    van den Berg VJ, Oemrawsingh RM, Umans V et al. 2021. Temporal evolution of serum concentrations of high-sensitivity cardiac troponin during 1 year after acute coronary syndrome admission. J. Am. Heart Assoc. 10:e017393
    [Google Scholar]
  27. 27.
    Hartikainen TS, Gossling A, Sorensen NA et al. 2021. Prognostic implications of a second peak of high-sensitivity troponin T after myocardial infarction. Front. Cardiovasc. Med. 8:780198
    [Google Scholar]
  28. 28.
    Laugaudin G, Kuster N, Petiton A et al. 2016. Kinetics of high-sensitivity cardiac troponin T and I differ in patients with ST-segment elevation myocardial infarction treated by primary coronary intervention. Eur. Heart J. Acute Cardiovasc. Care 5:35463
    [Google Scholar]
  29. 29.
    Solecki K, Dupuy AM, Kuster N et al. 2015. Kinetics of high-sensitivity cardiac troponin T or troponin I compared to creatine kinase in patients with revascularized acute myocardial infarction. Clin. Chem. Lab. Med. 53:70714
    [Google Scholar]
  30. 30.
    Stoyanov KM, Hund H, Biener M et al. 2020. RAPID-CPU: a prospective study on implementation of the ESC 0/1-hour algorithm and safety of discharge after rule-out of myocardial infarction. Eur. Heart J. Acute Cardiovasc. Care 9:3951
    [Google Scholar]
  31. 31.
    Chew DP, Lambrakis K, Blyth A et al. 2019. A randomized trial of a 1-hour troponin T protocol in suspected acute coronary syndromes: the Rapid Assessment of Possible Acute Coronary Syndrome in the Emergency Department with High-Sensitivity Troponin T Study (RAPID-TnT). Circulation 140:154356
    [Google Scholar]
  32. 32.
    Badertscher P, Boeddinghaus J, Twerenbold R et al. 2018. Direct Comparison of the 0/1h and 0/3h algorithms for early rule-out of acute myocardial infarction. Circulation 137:253638
    [Google Scholar]
  33. 33.
    Neumann JT, Sorensen NA, Schwemer T et al. 2016. Diagnosis of myocardial infarction using a high-sensitivity troponin I 1-hour algorithm. JAMA Cardiol 1:397404
    [Google Scholar]
  34. 34.
    Nestelberger T, Wildi K, Boeddinghaus J et al. 2016. Characterization of the observe zone of the ESC 2015 high-sensitivity cardiac troponin 0h/1h-algorithm for the early diagnosis of acute myocardial infarction. Int. J. Cardiol. 207:23845
    [Google Scholar]
  35. 35.
    Lopez-Ayala P, Nestelberger T, Boeddinghaus J et al. 2021. Novel criteria for the observe-zone of the ESC 0/1h-hs-cTnT algorithm. Circulation 144:77387
    [Google Scholar]
  36. 36.
    Mair J, Giannitsis E, Mills NL et al. 2022. How to deal with unexpected cardiac troponin results. Eur. Heart J. Acute Cardiovasc. Care 11:e1e3
    [Google Scholar]
  37. 37.
    Ola O, Akula A, De Michieli L et al. 2021. Clinical impact of high-sensitivity cardiac troponin T implementation in the community. J. Am. Coll. Cardiol. 77:316070
    [Google Scholar]
  38. 38.
    Mariathas M, Allan R, Ramamoorthy S et al. 2019. True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study. BMJ 364:l729
    [Google Scholar]
  39. 39.
    Gallacher PJ, Miller-Hodges E, Shah ASV et al. 2021. Use of high-sensitivity cardiac troponin in patients with kidney impairment: a randomized clinical trial. JAMA Intern. Med. 181:123739
    [Google Scholar]
  40. 40.
    Lee KK, Ferry AV, Anand A et al. 2019. Sex-specific thresholds of high-sensitivity troponin in patients with suspected acute coronary syndrome. J. Am. Coll. Cardiol. 74:203243
    [Google Scholar]
  41. 41.
    Doudesis D, Lee KK, Boeddinghaus J et al. 2023. Machine learning for diagnosis of myocardial infarction using cardiac troponin concentrations. Nat. Med. 29:120110
    [Google Scholar]
  42. 42.
    Jaffe AS, Lindahl B, Giannitsis E et al. 2021. ESC study group on cardiac biomarkers of the association for acute cardiovascular care: a fond farewell at the retirement of CKMB. Eur. Heart J. 42:226064
    [Google Scholar]
  43. 43.
    Mueller C, Mockel M, Giannitsis E et al. 2018. Use of copeptin for rapid rule-out of acute myocardial infarction. Eur. Heart J. Acute Cardiovasc. Care 7:57076
    [Google Scholar]
  44. 44.
    Mockel M, Searle J, Hamm C et al. 2015. Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study. Eur. Heart J. 36:36976
    [Google Scholar]
  45. 45.
    Keller T, Tzikas S, Zeller T et al. 2010. Copeptin improves early diagnosis of acute myocardial infarction. J. Am. Coll. Cardiol. 55:2096106
    [Google Scholar]
  46. 46.
    Collinson PO, Saenger AK, Apple FS. 2019. High sensitivity, contemporary and point-of-care cardiac troponin assays: educational aids developed by the IFCC Committee on Clinical Application of Cardiac Bio-Markers. Clin. Chem. Lab. Med. 57:62332
    [Google Scholar]
  47. 47.
    Cullen L, Collinson PO, Giannitsis E. 2022. Point-of-care testing with high-sensitivity cardiac troponin assays: the challenges and opportunities. Emerg. Med. J. 39:86166
    [Google Scholar]
  48. 48.
    Miller R, Nixon G, Pickering JW et al. 2022. A prospective multi-centre study assessing the safety and effectiveness following the implementation of an accelerated chest pain pathway using point-of-care troponin for use in New Zealand rural hospital and primary care settings. Eur. Heart J. Acute Cardiovasc. Care 11:41827
    [Google Scholar]
  49. 49.
    Ezekowitz JA, Welsh RC, Weiss D et al. 2015. Providing rapid out of hospital acute cardiovascular treatment 4 (PROACT-4). J. Am. Heart Assoc. 4:e002859
    [Google Scholar]
  50. 50.
    Pickering JW, Young JM, George PM et al. 2018. Validity of a novel point-of-care troponin assay for single-test rule-out of acute myocardial infarction. JAMA Cardiol 3:110812
    [Google Scholar]
  51. 51.
    Boeddinghaus J, Nestelberger T, Koechlin L et al. 2020. Early diagnosis of myocardial infarction with point-of-care high-sensitivity cardiac troponin I. J. Am. Coll. Cardiol. 75:111124
    [Google Scholar]
  52. 52.
    Apple FS, Smith SW, Greenslade JH et al. 2022. Single high-sensitivity point-of-care whole-blood cardiac troponin I measurement to rule out acute myocardial infarction at low risk. Circulation 146:191829
    [Google Scholar]
  53. 53.
    Alghamdi A, Cook E, Carlton E et al. 2019. PRe-hospital Evaluation of Sensitive TrOponin (PRESTO) Study: multicentre prospective diagnostic accuracy study protocol. BMJ Open 9:e032834
    [Google Scholar]
  54. 54.
    Aarts GWA, Camaro C, van Geuns RJ et al. 2020. Acute rule-out of non-ST-segment elevation acute coronary syndrome in the (pre)hospital setting by HEART score assessment and a single point-of-care troponin: rationale and design of the ARTICA randomised trial. BMJ Open 10:e034403
    [Google Scholar]
  55. 55.
    Dolci A, Braga F, Valente C et al. 2011. Impact of implementation of the high-sensitivity cardiac troponin T assay in a university hospital setting. Clin. Chem. 57:121112
    [Google Scholar]
  56. 56.
    Eggers KM, Lindahl B, Melki D, Jernberg T. 2016. Consequences of implementing a cardiac troponin assay with improved sensitivity at Swedish coronary care units: an analysis from the SWEDEHEART registry. Eur. Heart J. 37:241724
    [Google Scholar]
  57. 57.
    Odqvist M, Andersson PO, Tygesen H et al. 2018. High-sensitivity troponins and outcomes after myocardial infarction. J. Am. Coll. Cardiol. 71:261624
    [Google Scholar]
  58. 58.
    Newby LK, Lowenstern A. 2018. Implications of high-sensitivity troponin testing: learning from those who came before us. J. Am. Coll. Cardiol. 71:262527
    [Google Scholar]
  59. 59.
    Sandoval Y, Chapman AR, Mills NL et al. 2021. Sex-specific kinetics of high-sensitivity cardiac troponin I and T following symptom onset and early presentation in non-ST-segment elevation myocardial infarction. Clin. Chem. 67:32124
    [Google Scholar]
  60. 60.
    Mills NL, Churchhouse AM, Lee KK et al. 2011. Implementation of a sensitive troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome. JAMA 305:121016
    [Google Scholar]
  61. 61.
    Shah ASV, Anand A, Strachan FE et al. 2018. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial. Lancet 392:91928
    [Google Scholar]
  62. 62.
    Twerenbold R, Jaeger C, Rubini Gimenez M et al. 2016. Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. Eur. Heart J. 37:332432
    [Google Scholar]
  63. 63.
    McCord J, Newby LK, deFilippi CR. 2018. Designing a better mousetrap: reflections on the November 28, 2017, US Food and Drug Administration meeting on next-generation “high-sensitivity” cardiac troponin assays to diagnose myocardial infarction. Circulation 138:31618
    [Google Scholar]
  64. 64.
    McCarthy C, Li S, Wang TY et al. 2023. Implementation of high-sensitivity cardiac troponin assays in the United States. J. Am. Coll. Cardiol. 81:20719
    [Google Scholar]
  65. 65.
    Gulati M, Berg DD. 2023. High-sensitivity cardiac troponin assays in U.S. hospitals: a report card. J. Am. Coll. Cardiol. 81:22023
    [Google Scholar]
  66. 66.
    Ford JS, Chaco E, Tancredi DJ, Mumma BE. 2021. Impact of high-sensitivity cardiac troponin implementation on emergency department length of stay, testing, admissions, and diagnoses. Am. J. Emerg. Med. 45:5460
    [Google Scholar]
  67. 67.
    Ganguli I, Cui J, Thakore N et al. 2021. Downstream cascades of care following high-sensitivity troponin test implementation. J. Am. Coll. Cardiol. 77:317179
    [Google Scholar]
  68. 68.
    Sandoval Y, Askew JW 3rd, Newman JS et al. 2020. Implementing high-sensitivity cardiac troponin T in a US regional healthcare system. Circulation 141:193739
    [Google Scholar]
  69. 69.
    Vigen R, Diercks DB, Hashim IA et al. 2020. Association of a novel protocol for rapid exclusion of myocardial infarction with resource use in a US safety net hospital. JAMA Netw. Open 3:e203359
    [Google Scholar]
  70. 70.
    Januzzi JL Jr., Mahler SA, Christenson RH et al. 2019. Recommendations for institutions transitioning to high-sensitivity troponin testing: JACC scientific expert panel. J. Am. Coll. Cardiol. 73:105977
    [Google Scholar]
  71. 71.
    Kavsak PA, Beattie J, Pickersgill R et al. 2015. A practical approach for the validation and clinical implementation of a high-sensitivity cardiac troponin I assay across a North American city. Pract. Lab. Med. 1:2834
    [Google Scholar]
  72. 72.
    Lyon AR, Lopez-Fernandez T, Couch LS et al. 2022. ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur. Heart J. 43:4229361
    [Google Scholar]
  73. 73.
    Devereaux PJ, Chan MTV, Alonso-Coello P et al. 2012. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA 307:2295304
    [Google Scholar]
  74. 74.
    Puelacher C, Lurati Buse G, Seeberger D et al. 2018. Perioperative myocardial injury after noncardiac surgery: incidence, mortality, and characterization. Circulation 137:122132
    [Google Scholar]
  75. 75.
    Halvorsen S, Mehilli J, Cassese S et al. 2022. 2022 ESC guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur. Heart J. 43:3826924
    [Google Scholar]
  76. 76.
    de Lemos JA, Drazner MH, Omland T et al. 2010. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA 304:250312
    [Google Scholar]
  77. 77.
    deFilippi CR, de Lemos JA, Christenson RH et al. 2010. Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. JAMA 304:2494502
    [Google Scholar]
  78. 78.
    Willeit P, Welsh P, Evans JDW et al. 2017. High-sensitivity cardiac troponin concentration and risk of first-ever cardiovascular outcomes in 154,052 participants. J. Am. Coll. Cardiol. 70:55868
    [Google Scholar]
  79. 79.
    Patel SM, Qamar A, Giugliano RP et al. 2022. Association of serial high-sensitivity cardiac troponin T with subsequent cardiovascular events in patients stabilized after acute coronary syndrome: a secondary analysis from IMPROVE-IT. JAMA Cardiol 7:1199206
    [Google Scholar]
  80. 80.
    Omland T, de Lemos JA, Sabatine MS et al. 2009. A sensitive cardiac troponin T assay in stable coronary artery disease. N. Engl. J. Med. 361:253847
    [Google Scholar]
  81. 81.
    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. 37:242837
    [Google Scholar]
  82. 82.
    Visseren FLJ, Mach F, Smulders YM et al. 2021. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur. Heart J. 42:3227337
    [Google Scholar]
  83. 83.
    Neumann JT, Sorensen NA, Rubsamen N et al. 2019. Evaluation of a new ultra-sensitivity troponin I assay in patients with suspected myocardial infarction. Int. J. Cardiol. 283:3540
    [Google Scholar]
  84. 84.
    Baker JO, Tyther R, Liebetrau C et al. 2015. Cardiac myosin-binding protein C: a potential early biomarker of myocardial injury. Basic Res. Cardiol. 110:23
    [Google Scholar]
  85. 85.
    Kaier TE, Twerenbold R, Puelacher C et al. 2017. Direct comparison of cardiac myosin-binding protein C with cardiac troponins for the early diagnosis of acute myocardial infarction. Circulation 136:1495508
    [Google Scholar]
/content/journals/10.1146/annurev-med-051022-113931
Loading
/content/journals/10.1146/annurev-med-051022-113931
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error