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Elevated cardiac troponin concentration in the absence of an acute coronary syndrome

Authors
C Michael Gibson, MS, MD
David A Morrow, MD, MPH
Section Editor
Allan S Jaffe, MD
Deputy Editor
Gordon M Saperia, MD, FACC

INTRODUCTION

Cardiac troponin (cTn) is the standard serologic test to confirm the diagnosis of acute myocardial infarction. (See "Criteria for the diagnosis of acute myocardial infarction", section on 'Third universal definition of MI'.)

However, troponin is not specific for acute thrombotic occlusion of a coronary artery, the most common precursor to acute myocardial infarction. Increased blood concentrations of cTn can also be seen in a variety of other diseases, such as sepsis, atrial fibrillation, heart failure, pulmonary embolism, myocarditis, myocardial contusion, and renal failure. In addition, stable chronic elevation of cardiac troponin may be detectable with high-sensitivity assays in patients with underlying structural (muscle) heart disease.

Potential causes of troponin elevation unrelated to coronary thrombosis will be reviewed here. Other related topics include:

(See "Troponin testing: Clinical use".)

(See "Troponin testing: Analytical aspects".)

                       
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Literature review current through: Nov 2017. | This topic last updated: Aug 25, 2017.
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References
Top
  1. Jaffe AS, Vasile VC, Milone M, et al. Diseased skeletal muscle: a noncardiac source of increased circulating concentrations of cardiac troponin T. J Am Coll Cardiol 2011; 58:1819.
  2. 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.
  3. Higgins JP, Higgins JA. Elevation of cardiac troponin I indicates more than myocardial ischemia. Clin Invest Med 2003; 26:133.
  4. Wu AH. Increased troponin in patients with sepsis and septic shock: myocardial necrosis or reversible myocardial depression? Intensive Care Med 2001; 27:959.
  5. Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med 1993; 328:1471.
  6. Feng J, Schaus BJ, Fallavollita JA, et al. Preload induces troponin I degradation independently of myocardial ischemia. Circulation 2001; 103:2035.
  7. Weil BR, Shen Z, Suzuki G, et al. Brief Myocardial Ischemia Produces Cardiac Troponin I Release and Focal Myocyte Apoptosis in the Absence of Pathological Infarction in Swine. JACC Transitional Research 2017; 2:105.
  8. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Circulation 2012; 126:2020.
  9. Ammann P, Fehr T, Minder EI, et al. Elevation of troponin I in sepsis and septic shock. Intensive Care Med 2001; 27:965.
  10. Ammann P, Maggiorini M, Bertel O, et al. Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes. J Am Coll Cardiol 2003; 41:2004.
  11. Arlati S, Brenna S, Prencipe L, et al. Myocardial necrosis in ICU patients with acute non-cardiac disease: a prospective study. Intensive Care Med 2000; 26:31.
  12. Wright RS, Williams BA, Cramner H, et al. Elevations of cardiac troponin I are associated with increased short-term mortality in noncardiac critically ill emergency department patients. Am J Cardiol 2002; 90:634.
  13. Bakshi TK, Choo MK, Edwards CC, et al. Causes of elevated troponin I with a normal coronary angiogram. Intern Med J 2002; 32:520.
  14. Zellweger MJ, Schaer BA, Cron TA, et al. Elevated troponin levels in absence of coronary artery disease after supraventricular tachycardia. Swiss Med Wkly 2003; 133:439.
  15. Sandoval Y, Thygesen K. Myocardial Infarction Type 2 and Myocardial Injury. Clin Chem 2017; 63:101.
  16. 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.
  17. 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.
  18. Aw TC, van Wijk XM, Wu AH, Jaffe AS. Release of cardiac troponin using a high sensitivity assay after exercise: Type 2 acute myocardial infarction? Clin Chim Acta 2015; 446:6.
  19. White HD. Pathobiology of troponin elevations: do elevations occur with myocardial ischemia as well as necrosis? J Am Coll Cardiol 2011; 57:2406.
  20. Wu AH, Fukushima N, Puskas R, et al. Development and preliminary clinical validation of a high sensitivity assay for cardiac troponin using a capillary flow (single molecule) fluorescence detector. Clin Chem 2006; 52:2157.
  21. 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.
  22. Wilson SR, Sabatine MS, Braunwald E, et al. Detection of myocardial injury in patients with unstable angina using a novel nanoparticle cardiac troponin I assay: observations from the PROTECT-TIMI 30 Trial. Am Heart J 2009; 158:386.
  23. Venge P, Johnston N, Lindahl B, James S. Normal plasma levels of cardiac troponin I measured by the high-sensitivity cardiac troponin I access prototype assay and the impact on the diagnosis of myocardial ischemia. J Am Coll Cardiol 2009; 54:1165.
  24. Giannitsis E, Kurz K, Hallermayer K, et al. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem 2010; 56:254.
  25. Latini R, Masson S, Anand IS, et al. Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation 2007; 116:1242.
  26. Januzzi JL Jr, Bamberg F, Lee H, et al. High-sensitivity troponin T concentrations in acute chest pain patients evaluated with cardiac computed tomography. Circulation 2010; 121:1227.
  27. Diamond GA, Kaul S. How would the Reverend Bayes interpret high-sensitivity troponin? Circulation 2010; 121:1172.
  28. Sedaghat-Hamedani F, Kayvanpour E, Frankenstein L, et al. Biomarker changes after strenuous exercise can mimic pulmonary embolism and cardiac injury--a metaanalysis of 45 studies. Clin Chem 2015; 61:1246.
  29. Turer AT, Addo TA, Martin JL, et al. Myocardial ischemia induced by rapid atrial pacing causes troponin T release detectable by a highly sensitive assay: insights from a coronary sinus sampling study. J Am Coll Cardiol 2011; 57:2398.
  30. Lee G, Twerenbold R, Tanglay Y, et al. Clinical benefit of high-sensitivity cardiac troponin I in the detection of exercise-induced myocardial ischemia. Am Heart J 2016; 173:8.
  31. Collinson PO, Heung YM, Gaze D, et al. Influence of population selection on the 99th percentile reference value for cardiac troponin assays. Clin Chem 2012; 58:219.
  32. McKie PM, Heublein DM, Scott CG, et al. Defining high-sensitivity cardiac troponin concentrations in the community. Clin Chem 2013; 59:1099.
  33. Koerbin G, Abhayaratna WP, Potter JM, et al. Effect of population selection on 99th percentile values for a high sensitivity cardiac troponin I and T assays. Clin Biochem 2013; 46:1636.
  34. Ford I, Shah AS, Zhang R, et al. High-Sensitivity Cardiac Troponin, Statin Therapy, and Risk of Coronary Heart Disease. J Am Coll Cardiol 2016; 68:2719.
  35. Jaffe AS, Wright RS. High-Sensitivity Cardiac Troponin and Primary Prevention: An Important New Role. J Am Coll Cardiol 2016; 68:2729.
  36. Derdeyn CP. Moyamoya disease and moyamoya syndrome. N Engl J Med 2009; 361:97; author reply 98.
  37. Wu AH, Jaffe AS. The clinical need for high-sensitivity cardiac troponin assays for acute coronary syndromes and the role for serial testing. Am Heart J 2008; 155:208.
  38. Sabatine MS, Morrow DA, de Lemos JA, et al. 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 2009; 30:162.
  39. Kurz K, Giannitsis E, Zehelein J, Katus HA. Highly sensitive cardiac troponin T values remain constant after brief exercise- or pharmacologic-induced reversible myocardial ischemia. Clin Chem 2008; 54:1234.
  40. Everett BM, Brooks MM, Vlachos HE, et al. Troponin and Cardiac Events in Stable Ischemic Heart Disease and Diabetes. N Engl J Med 2015; 373:610.
  41. Eisen A, Bonaca MP, Jarolim P, et al. High-Sensitivity Troponin I in Stable Patients with Atherosclerotic Disease in the TRA 2°P - TIMI 50 Trial. Clin Chem 2017; 63:307.
  42. Bonaca MP, O'Malley RG, Jarolim P, et al. Serial Cardiac Troponin Measured Using a High-Sensitivity Assay in Stable Patients With Ischemic Heart Disease. J Am Coll Cardiol 2016; 68:322.
  43. Thygesen K, Mair J, Katus H, et al. Recommendations for the use of cardiac troponin measurement in acute cardiac care. Eur Heart J 2010; 31:2197.
  44. Lim W, Qushmaq I, Devereaux PJ, et al. Elevated cardiac troponin measurements in critically ill patients. Arch Intern Med 2006; 166:2446.
  45. Hamwi SM, Sharma AK, Weissman NJ, et al. Troponin-I elevation in patients with increased left ventricular mass. Am J Cardiol 2003; 92:88.
  46. Nunes JP, Mota Garcia JM, Farinha RM, et al. Cardiac troponin I in aortic valve disease. Int J Cardiol 2003; 89:281.
  47. Wang CH, Kuo LT, Hung MJ, Cherng WJ. Coronary vasospasm as a possible cause of elevated cardiac troponin I in patients with acute coronary syndrome and insignificant coronary artery disease. Am Heart J 2002; 144:275.
  48. Troøyen M, Indredavik B, Rossvoll O, Slørdahl SA. [Myocardial injury in acute stroke assessed by troponin I]. Tidsskr Nor Laegeforen 2001; 121:421.
  49. Tung P, Kopelnik A, Banki N, et al. Predictors of neurocardiogenic injury after subarachnoid hemorrhage. Stroke 2004; 35:548.
  50. Naidech AM, Kreiter KT, Janjua N, et al. Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation 2005; 112:2851.
  51. Homma S, Grahame-Clarke C. Editorial comment--myocardial damage in patients with subarachnoid hemorrhage. Stroke 2004; 35:552.
  52. Hijazi Z, Wallentin L, Siegbahn A, et al. High-sensitivity troponin T and risk stratification in patients with atrial fibrillation during treatment with apixaban or warfarin. J Am Coll Cardiol 2014; 63:52.
  53. Hijazi Z, Oldgren J, Andersson U, et al. Cardiac biomarkers are associated with an increased risk of stroke and death in patients with atrial fibrillation: a Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) substudy. Circulation 2012; 125:1605.
  54. Hijazi Z, Siegbahn A, Andersson U, et al. High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation 2014; 129:625.
  55. Velmahos GC, Karaiskakis M, Salim A, et al. Normal electrocardiography and serum troponin I levels preclude the presence of clinically significant blunt cardiac injury. J Trauma 2003; 54:45.
  56. Hasdemir C, Shah N, Rao AP, et al. Analysis of troponin I levels after spontaneous implantable cardioverter defibrillator shocks. J Cardiovasc Electrophysiol 2002; 13:144.
  57. Cantwell RV, Aviles RJ, Bjornsson J, et al. Cardiac amyloidosis presenting with elevations of cardiac troponin I and angina pectoris. Clin Cardiol 2002; 25:33.
  58. Cardinale D, Sandri MT, Martinoni A, et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol 2000; 36:517.
  59. Brandt RR, Filzmaier K, Hanrath P. Circulating cardiac troponin I in acute pericarditis. Am J Cardiol 2001; 87:1326.
  60. Smith SC, Ladenson JH, Mason JW, Jaffe AS. Elevations of cardiac troponin I associated with myocarditis. Experimental and clinical correlates. Circulation 1997; 95:163.
  61. Labarrere CA, Nelson DR, Cox CJ, et al. Cardiac-specific troponin I levels and risk of coronary artery disease and graft failure following heart transplantation. JAMA 2000; 284:457.
  62. Horwich TB, Patel J, MacLellan WR, Fonarow GC. Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 2003; 108:833.
  63. Logeart D, Beyne P, Cusson C, et al. Evidence of cardiac myolysis in severe nonischemic heart failure and the potential role of increased wall strain. Am Heart J 2001; 141:247.
  64. Rifai N, Douglas PS, O'Toole M, et al. Cardiac troponin T and I, echocardiographic [correction of electrocardiographic] wall motion analyses, and ejection fractions in athletes participating in the Hawaii Ironman Triathlon. Am J Cardiol 1999; 83:1085.
  65. Neumayr G, Gaenzer H, Pfister R, et al. Plasma levels of cardiac troponin I after prolonged strenuous endurance exercise. Am J Cardiol 2001; 87:369.
  66. Cheng W, Li B, Kajstura J, et al. Stretch-induced programmed myocyte cell death. J Clin Invest 1995; 96:2247.
  67. Torbicki A, Kurzyna M, Kuca P, et al. Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension. Circulation 2003; 108:844.
  68. Baillard C, Boussarsar M, Fosse JP, et al. Cardiac troponin I in patients with severe exacerbation of chronic obstructive pulmonary disease. Intensive Care Med 2003; 29:584.
  69. Hassan HC, Howlin K, Jefferys A, et al. High-sensitivity troponin as a predictor of cardiac events and mortality in the stable dialysis population. Clin Chem 2014; 60:389.
  70. Fridén V, Starnberg K, Muslimovic A, et al. Clearance of cardiac troponin T with and without kidney function. Clin Biochem 2017; 50:468.
  71. Sandoval Y, Herzog CA, Love SA, et al. Prognostic Value of Serial Changes in High-Sensitivity Cardiac Troponin I and T over 3 Months Using Reference Change Values in Hemodialysis Patients. Clin Chem 2016; 62:631.
  72. Murphy JT, Horton JW, Purdue GF, Hunt JL. Evaluation of troponin-I as an indicator of cardiac dysfunction after thermal injury. J Trauma 1998; 45:700.
  73. Kim M, Kim K. Elevation of cardiac troponin I in the acute stage of Kawasaki disease. Pediatr Cardiol 1999; 20:184.
  74. Checchia PA, Borensztajn J, Shulman ST. Circulating cardiac troponin I levels in Kawasaki disease. Pediatr Cardiol 2001; 22:102.
  75. Piechota W, Gielerak G, Ryczek R, et al. Cardiac troponin I after external electrical cardioversion for atrial fibrillation as a marker of myocardial injury--a preliminary report. Kardiol Pol 2007; 65:664.
  76. Willeit P, Welsh P, Evans JDW, et al. High-Sensitivity Cardiac Troponin Concentration and Risk of First-Ever Cardiovascular Outcomes in 154,052 Participants. J Am Coll Cardiol 2017; 70:558.
  77. Kavsak PA, Clark L, Jaffe AS. Effect of Repeat Measurements of High-Sensitivity Cardiac Troponin on the Same Sample Using the European Society of Cardiology 0-Hour/1-Hour or 2-Hour Algorithms for Early Rule-Out and Rule-In for Myocardial Infarction. Clin Chem 2017; 63:1163.
  78. McKie PM, AbouEzzeddine OF, Scott CG, et al. High-sensitivity troponin I and amino-terminal pro--B-type natriuretic peptide predict heart failure and mortality in the general population. Clin Chem 2014; 60:1225.
  79. Everett BM, Cook NR, Magnone MC, et al. Sensitive cardiac troponin T assay and the risk of incident cardiovascular disease in women with and without diabetes mellitus: the Women's Health Study. Circulation 2011; 123:2811.
  80. Omland T, Pfeffer MA, Solomon SD, et al. Prognostic value of cardiac troponin I measured with a highly sensitive assay in patients with stable coronary artery disease. J Am Coll Cardiol 2013; 61:1240.
  81. Kavsak PA, McQueen MJ. Sensitive and high sensitivity cardiac troponin I concentrations in the Heart Outcomes Prevention Evaluation (HOPE) study--a high risk population. Clin Chim Acta 2010; 411:1832.
  82. Omland T, de Lemos JA, Sabatine MS, et al. A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med 2009; 361:2538.
  83. White HD, Tonkin A, Simes J, et al. Association of contemporary sensitive troponin I levels at baseline and change at 1 year with long-term coronary events following myocardial infarction or unstable angina: results from the LIPID Study (Long-Term Intervention With Pravastatin in Ischaemic Disease). J Am Coll Cardiol 2014; 63:345.
  84. Beatty AL, Ku IA, Christenson RH, et al. High-sensitivity cardiac troponin T levels and secondary events in outpatients with coronary heart disease from the Heart and Soul Study. JAMA Intern Med 2013; 173:763.