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Etiology and pathogenesis of myocarditis

Leslie T Cooper, Jr, MD
Section Editor
William J McKenna, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


Myocarditis is an inflammatory disease of cardiac muscle, diagnosed on endomyocardial biopsy (EMB) by established histological, immunological, and immunohistochemical criteria [1]. It can be acute, subacute, or chronic, and there may be either focal or diffuse involvement of the myocardium. In symptomatic patients, the cardiac presentation is frequently one of acute heart failure (HF), although a syndrome mimicking acute myocardial infarction or a tachyarrhythmia, including sudden death, or high-grade heart block may occur. If the epicardium is involved, pericarditis may be associated with pleuritic chest pain and pericardial effusion. Isolated endomyocardial inflammation and fibrosis is seen in Löffler's cardiomyopathy, tropical endomyocarditis, hypereosinophilic syndrome, and some adverse drug reactions.

The etiology and pathogenesis of myocarditis will be reviewed here. Issues related to the clinical manifestations, diagnosis, natural history, and treatment of myocarditis are discussed separately. (See "Clinical manifestations and diagnosis of myocarditis in adults" and "Treatment and prognosis of myocarditis in adults".)


Myocarditis can be caused by a variety of infectious and noninfectious illnesses (table 1). Among the infectious etiologies, viruses are the presumed most frequent pathogens, but bacteria, fungi, protozoa, and helminths have also been implicated [2,3]. In North America and Western Europe, the most frequently identified viruses were enteroviruses (including coxsackievirus) until the 1990s. Parvovirus B-19 and human herpes virus 6 are the viruses most frequently found.

This topic review will focus on viral and hypersensitivity myocarditis. Many of the other causes of myocarditis are discussed in detail elsewhere in UpToDate. These include:

Infections such as acute rheumatic fever due to group A streptococci and Chagas disease. (See "Acute rheumatic fever: Epidemiology and pathogenesis" and "Chagas heart disease: Clinical manifestations and diagnosis".)


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  1. Caforio AL, Pankuweit S, Arbustini E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013; 34:2636.
  2. Cooper LT Jr. Myocarditis. N Engl J Med 2009; 360:1526.
  3. Walsh TJ, Hutchins GM, Bulkley BH, Mendelsohn G. Fungal infections of the heart: analysis of 51 autopsy cases. Am J Cardiol 1980; 45:357.
  4. Wijetunga M, Rockson S. Myocarditis in systemic lupus erythematosus. Am J Med 2002; 113:419.
  5. Zawadowski GM, Klarich KW, Moder KG, et al. A contemporary case series of lupus myocarditis. Lupus 2012; 21:1378.
  6. Pfizenmaier DH, Al Atawi FO, Castillo Y, et al. Predictors of left ventricular dysfunction in patients with Takayasu's or giant cell aortitis. Clin Exp Rheumatol 2004; 22:S41.
  7. Virmani R, Robinowitz M, Smialek JE, Smyth DF. Cardiovascular effects of cocaine: an autopsy study of 40 patients. Am Heart J 1988; 115:1068.
  8. Kloner RA, Hale S, Alker K, Rezkalla S. The effects of acute and chronic cocaine use on the heart. Circulation 1992; 85:407.
  9. O'Connell, JB. Diagnosis and medical treatment of inflammatory cardiomyopathy. In: Cardiovascular Medicine, Topol, E, Nissen, J (Eds), Lippincott-Raven, Philadelphia 1998.
  10. Rose NR, Neumann DA, Herskowitz A. Coxsackievirus myocarditis. Adv Intern Med 1992; 37:411.
  11. Burch GE, Sun SC, Colcolough HL, et al. Coxsackie B viral myocarditis and valvulitis identified in routine autopsy specimens by immunofluorescent techniques. Am Heart J 1967; 74:13.
  12. Bowles NE, Ni J, Kearney DL, et al. Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol 2003; 42:466.
  13. Kindermann I, Kindermann M, Kandolf R, et al. Predictors of outcome in patients with suspected myocarditis. Circulation 2008; 118:639.
  14. Grist NR, Bell EJ. Coxsackie viruses and the heart. Am Heart J 1969; 77:295.
  15. Cambridge G, MacArthur CG, Waterson AP, et al. Antibodies to Coxsackie B viruses in congestive cardiomyopathy. Br Heart J 1979; 41:692.
  16. Kühl U, Pauschinger M, Seeberg B, et al. Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation 2005; 112:1965.
  17. Matsumori A, Yutani C, Ikeda Y, et al. Hepatitis C virus from the hearts of patients with myocarditis and cardiomyopathy. Lab Invest 2000; 80:1137.
  18. Schönian U, Crombach M, Maser S, Maisch B. Cytomegalovirus-associated heart muscle disease. Eur Heart J 1995; 16 Suppl O:46.
  19. Cohen JI, Corey GR. Cytomegalovirus infection in the normal host. Medicine (Baltimore) 1985; 64:100.
  20. Chimenti C, Russo A, Pieroni M, et al. Intramyocyte detection of Epstein-Barr virus genome by laser capture microdissection in patients with inflammatory cardiomyopathy. Circulation 2004; 110:3534.
  21. Breinholt JP, Moulik M, Dreyer WJ, et al. Viral epidemiologic shift in inflammatory heart disease: the increasing involvement of parvovirus B19 in the myocardium of pediatric cardiac transplant patients. J Heart Lung Transplant 2010; 29:739.
  22. Lamparter S, Schoppet M, Pankuweit S, Maisch B. Acute parvovirus B19 infection associated with myocarditis in an immunocompetent adult. Hum Pathol 2003; 34:725.
  23. Pankuweit S, Moll R, Baandrup U, et al. Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens. Hum Pathol 2003; 34:497.
  24. Mahrholdt H, Goedecke C, Wagner A, et al. Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology. Circulation 2004; 109:1250.
  25. Schultheiss, H-P. The effect of subcutaneous treatment with interferon-beta-1b over 24 weeks on safety, virus elimination, and clinical outcome in patients with chronic viral cardiomyopathy. Presented November 11th, 2008. AHA Annual Scientific Sessions Late Breaking Clinical Trials III. http://americanheart.mediaroom.com/index.php?s=43&item=590 (Accessed 4-29-09).
  26. Baruteau AE, Boimond N, Ramful D. Myocarditis associated with 2009 influenza A (H1N1) virus in children. Cardiol Young 2010; 20:351.
  27. Engler RJ, Nelson MR, Collins LC Jr, et al. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination. PLoS One 2015; 10:e0118283.
  28. From the Centers for Disease Control and Prevention. Update: cardiac-related events during the civilian smallpox vaccination program-- United States, 2003. JAMA 2003; 290:31.
  29. Casey CG, Iskander JK, Roper MH, et al. Adverse events associated with smallpox vaccination in the United States, January-October 2003. JAMA 2005; 294:2734.
  30. Caforio AL, Calabrese F, Angelini A, et al. A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J 2007; 28:1326.
  31. Gerzen P, Granath A, Holmgren B, Zetterquist S. Acute myocarditis. A follow-up study. Br Heart J 1972; 34:575.
  32. Cooper LT Jr, Keren A, Sliwa K, et al. The global burden of myocarditis: part 1: a systematic literature review for the Global Burden of Diseases, Injuries, and Risk Factors 2010 study. Glob Heart 2014; 9:121.
  33. Maron BJ, Doerer JJ, Haas TS, et al. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006. Circulation 2009; 119:1085.
  34. Lambert EC, Menon VA, Wagner HR, Vlad P. Sudden unexpected death from cardiovascular disease in children. A cooperative international study. Am J Cardiol 1974; 34:89.
  35. Maron BJ, Udelson JE, Bonow RO, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 3: Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy and Other Cardiomyopathies, and Myocarditis: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation 2015; 132:e273.
  36. Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med 2000; 342:1077.
  37. Mason JW, O'Connell JB, Herskowitz A, et al. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med 1995; 333:269.
  38. Nugent AW, Daubeney PE, Chondros P, et al. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med 2003; 348:1639.
  39. Gauntt CJ. Roles of the humoral response in coxsackievirus B-induced disease. Curr Top Microbiol Immunol 1997; 223:259.
  40. Grist NR, Bell EJ, Assaad F. Enteroviruses in human disease. Prog Med Virol 1978; 24:114.
  41. Lau RC. Coxsackie B virus infections in New Zealand patients with cardiac and non-cardiac diseases. J Med Virol 1983; 11:131.
  42. Chow LH, Beisel KW, McManus BM. Enteroviral infection of mice with severe combined immunodeficiency. Evidence for direct viral pathogenesis of myocardial injury. Lab Invest 1992; 66:24.
  43. Huber SA, Feldman AM, Sartini D. Coxsackievirus B3 induces T regulatory cells, which inhibit cardiomyopathy in tumor necrosis factor-alpha transgenic mice. Circ Res 2006; 99:1109.
  44. Godeny EK, Gauntt CJ. Murine natural killer cells limit coxsackievirus B3 replication. J Immunol 1987; 139:913.
  45. Lowenstein CJ, Hill SL, Lafond-Walker A, et al. Nitric oxide inhibits viral replication in murine myocarditis. J Clin Invest 1996; 97:1837.
  46. Horwitz MS, La Cava A, Fine C, et al. Pancreatic expression of interferon-gamma protects mice from lethal coxsackievirus B3 infection and subsequent myocarditis. Nat Med 2000; 6:693.
  47. Deonarain R, Cerullo D, Fuse K, et al. Protective role for interferon-beta in coxsackievirus B3 infection. Circulation 2004; 110:3540.
  48. Kandolf R, Canu A, Hofschneider PH. Coxsackie B3 virus can replicate in cultured human foetal heart cells and is inhibited by interferon. J Mol Cell Cardiol 1985; 17:167.
  49. Cooper LT Jr, Hare JM, Tazelaar HD, et al. Usefulness of immunosuppression for giant cell myocarditis. Am J Cardiol 2008; 102:1535.
  50. Cooper LT Jr, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis--natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med 1997; 336:1860.
  51. Rosenstein ED, Zucker MJ, Kramer N. Giant cell myocarditis: most fatal of autoimmune diseases. Semin Arthritis Rheum 2000; 30:1.
  52. Kandolin R, Lehtonen J, Salmenkivi K, et al. Diagnosis, treatment, and outcome of giant-cell myocarditis in the era of combined immunosuppression. Circ Heart Fail 2013; 6:15.
  53. Kodama M, Matsumoto Y, Fujiwara M, et al. A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction. Clin Immunol Immunopathol 1990; 57:250.
  54. Maleszewski JJ, Orellana VM, Hodge DO, et al. Long-term risk of recurrence, morbidity and mortality in giant cell myocarditis. Am J Cardiol 2015; 115:1733.
  55. Burke AP, Saenger J, Mullick F, Virmani R. Hypersensitivity myocarditis. Arch Pathol Lab Med 1991; 115:764.
  56. Fenoglio JJ Jr, McAllister HA Jr, Mullick FG. Drug related myocarditis. I. Hypersensitivity myocarditis. Hum Pathol 1981; 12:900.
  57. Wu L, Cooper LT, Kephart G, Gleich GJ. The Eosinophil in Cardiac Disease. In: Myocarditis: From Bench to Bedside, Cooper L (Ed), Humana Press, Totowa 2002. p.437.
  58. Taliercio CP, Olney BA, Lie JT. Myocarditis related to drug hypersensitivity. Mayo Clin Proc 1985; 60:463.
  59. Pursnani A, Yee H, Slater W, Sarswat N. Hypersensitivity myocarditis associated with azithromycin exposure. Ann Intern Med 2009; 150:225.
  60. Ben m'rad M, Leclerc-Mercier S, Blanche P, et al. Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients. Medicine (Baltimore) 2009; 88:131.
  61. Haas SJ, Hill R, Krum H, et al. Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis associated with the use of clozapine in Australia during 1993-2003. Drug Saf 2007; 30:47.
  62. Johnson MR. Eosinophilic myocarditis in the explanted hearts of cardiac transplant recipients: Interesting pathologic finding or pathophysiologic entity of clinical significance? Crit Care Med 2004; 32:888.
  63. Spear GS. Eosinophilic explant carditis with eosinophilia: ?Hypersensitivity to dobutamine infusion. J Heart Lung Transplant 1995; 14:755.
  64. Takkenberg JJ, Czer LS, Fishbein MC, et al. Eosinophilic myocarditis in patients awaiting heart transplantation. Crit Care Med 2004; 32:714.
  65. Gravanis MB, Hertzler GL, Franch RH, et al. Hypersensitivity myocarditis in heart transplant candidates. J Heart Lung Transplant 1991; 10:688.
  66. Hawkins ET, Levine TB, Goss SJ, et al. Hypersensitivity myocarditis in the explanted hearts of transplant recipients. Reappraisal of pathologic criteria and their clinical implications. Pathol Annu 1995; 30 ( Pt 1):287.
  67. Daniels PR, Berry GJ, Tazelaar HD, Cooper LT. Giant cell myocarditis as a manifestation of drug hypersensitivity. Cardiovasc Pathol 2000; 9:287.
  68. Billingham M. Morphologic changes in drug-induced heart disease. In: Drug-induced Heart Disease, Bristow M (Ed), 1980. p.127.
  69. Frustaci A, Cuoco L, Chimenti C, et al. Celiac disease associated with autoimmune myocarditis. Circulation 2002; 105:2611.
  70. Curione M, Barbato M, De Biase L, et al. Prevalence of coeliac disease in idiopathic dilated cardiomyopathy. Lancet 1999; 354:222.
  71. Polat TB, Urganci N, Yalcin Y, et al. Cardiac functions in children with coeliac disease during follow-up: insights from tissue Doppler imaging. Dig Liver Dis 2008; 40:182.
  72. Chimenti C, Pieroni M, Maseri A, Frustaci A. Histologic findings in patients with clinical and instrumental diagnosis of sporadic arrhythmogenic right ventricular dysplasia. J Am Coll Cardiol 2004; 43:2305.
  73. Frustaci A, Verardo R, Caldarulo M, et al. Myocarditis in hypertrophic cardiomyopathy patients presenting acute clinical deterioration. Eur Heart J 2007; 28:733.
  74. Chow LH, Gauntt CJ, McManus BM. Differential effects of myocarditic variants of Coxsackievirus B3 in inbred mice. A pathologic characterization of heart tissue damage. Lab Invest 1991; 64:55.
  75. Esfandiarei M, McManus BM. Molecular biology and pathogenesis of viral myocarditis. Annu Rev Pathol 2008; 3:127.
  76. Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 1997; 275:1320.
  77. Carson SD, Chapman NN, Tracy SM. Purification of the putative coxsackievirus B receptor from HeLa cells. Biochem Biophys Res Commun 1997; 233:325.
  78. Tomko RP, Xu R, Philipson L. HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. Proc Natl Acad Sci U S A 1997; 94:3352.
  79. Bowles KR, Gibson J, Wu J, et al. Genomic organization and chromosomal localization of the human Coxsackievirus B-adenovirus receptor gene. Hum Genet 1999; 105:354.
  80. Barnabei MS, Sjaastad FV, Townsend D, et al. Severe dystrophic cardiomyopathy caused by the enteroviral protease 2A-mediated C-terminal dystrophin cleavage fragment. Sci Transl Med 2015; 7:294ra106.
  81. Shafren DR, Williams DT, Barry RD. A decay-accelerating factor-binding strain of coxsackievirus B3 requires the coxsackievirus-adenovirus receptor protein to mediate lytic infection of rhabdomyosarcoma cells. J Virol 1997; 71:9844.
  82. Clapham PR, Weiss RA. Immunodeficiency viruses. Spoilt for choice of co-receptors. Nature 1997; 388:230.
  83. Martino TA, Petric M, Brown M, et al. Cardiovirulent coxsackieviruses and the decay-accelerating factor (CD55) receptor. Virology 1998; 244:302.
  84. Opavsky MA, Martino T, Rabinovitch M, et al. Enhanced ERK-1/2 activation in mice susceptible to coxsackievirus-induced myocarditis. J Clin Invest 2002; 109:1561.
  85. Xiong D, Yajima T, Lim BK, et al. Inducible cardiac-restricted expression of enteroviral protease 2A is sufficient to induce dilated cardiomyopathy. Circulation 2007; 115:94.
  86. Badorff C, Lee GH, Lamphear BJ, et al. Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat Med 1999; 5:320.
  87. Grady RM, Teng H, Nichol MC, et al. Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy. Cell 1997; 90:729.
  88. Knowlton KU. CVB infection and mechanisms of viral cardiomyopathy. Curr Top Microbiol Immunol 2008; 323:315.
  89. Klingel K, Hohenadl C, Canu A, et al. Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation. Proc Natl Acad Sci U S A 1992; 89:314.
  90. Wessely R, Henke A, Zell R, et al. Low-level expression of a mutant coxsackieviral cDNA induces a myocytopathic effect in culture: an approach to the study of enteroviral persistence in cardiac myocytes. Circulation 1998; 98:450.
  91. Wessely R, Klingel K, Santana LF, et al. Transgenic expression of replication-restricted enteroviral genomes in heart muscle induces defective excitation-contraction coupling and dilated cardiomyopathy. J Clin Invest 1998; 102:1444.
  92. Martino TA, Liu P, Sole MJ. Viral infection and the pathogenesis of dilated cardiomyopathy. Circ Res 1994; 74:182.
  93. Keeling PJ, Tracy S. Link between enteroviruses and dilated cardiomyopathy: serological and molecular data. Br Heart J 1994; 72:S25.
  94. Pauschinger M, Bowles NE, Fuentes-Garcia FJ, et al. Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction. Circulation 1999; 99:1348.
  95. Akhtar N, Ni J, Stromberg D, et al. Tracheal aspirate as a substrate for polymerase chain reaction detection of viral genome in childhood pneumonia and myocarditis. Circulation 1999; 99:2011.
  96. Pauschinger M, Phan MD, Doerner A, et al. Enteroviral RNA replication in the myocardium of patients with left ventricular dysfunction and clinically suspected myocarditis. Circulation 1999; 99:889.
  97. Why HJ, Meany BT, Richardson PJ, et al. Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy. Circulation 1994; 89:2582.
  98. Mahrholdt H, Wagner A, Deluigi CC, et al. Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation 2006; 114:1581.
  99. Chen F, Shannon K, Ding S, et al. HIV type 1 glycoprotein 120 inhibits cardiac myocyte contraction. AIDS Res Hum Retroviruses 2002; 18:777.
  100. De Castro S, d'Amati G, Gallo P, et al. Frequency of development of acute global left ventricular dysfunction in human immunodeficiency virus infection. J Am Coll Cardiol 1994; 24:1018.
  101. Matsumori A, Ohashi N, Hasegawa K, et al. Hepatitis C virus infection and heart diseases: a multicenter study in Japan. Jpn Circ J 1998; 62:389.
  102. Tsintsof A, Delprado WJ, Keogh AM. Varicella zoster myocarditis progressing to cardiomyopathy and cardiac transplantation. Br Heart J 1993; 70:93.
  103. Figulla HR, Stille-Siegener M, Mall G, et al. Myocardial enterovirus infection with left ventricular dysfunction: a benign disease compared with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 1995; 25:1170.
  104. Martin AB, Webber S, Fricker FJ, et al. Acute myocarditis. Rapid diagnosis by PCR in children. Circulation 1994; 90:330.
  105. Herskowitz A, Wu TC, Willoughby SB, et al. Myocarditis and cardiotropic viral infection associated with severe left ventricular dysfunction in late-stage infection with human immunodeficiency virus. J Am Coll Cardiol 1994; 24:1025.
  106. Shaboodien G, Maske C, Wainwright H, et al. Prevalence of myocarditis and cardiotropic virus infection in Africans with HIV-associated cardiomyopathy, idiopathic dilated cardiomyopathy and heart transplant recipients: a pilot study: cardiovascular topic. Cardiovasc J Afr 2013; 24:218.
  107. Omura T, Yoshiyama M, Hayashi T, et al. Core protein of hepatitis C virus induces cardiomyopathy. Circ Res 2005; 96:148.
  108. Kühl U, Pauschinger M, Noutsias M, et al. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with "idiopathic" left ventricular dysfunction. Circulation 2005; 111:887.
  109. Tschöpe C, Bock CT, Kasner M, et al. High prevalence of cardiac parvovirus B19 infection in patients with isolated left ventricular diastolic dysfunction. Circulation 2005; 111:879.
  110. Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 1996; 93:841.
  111. Nakamura H, Yamamura T, Umemoto S, et al. Autoimmune response in chronic ongoing myocarditis demonstrated by heterotopic cardiac transplantation in mice. Circulation 1996; 94:3348.
  112. Schultheiss HP. The significance of autoantibodies against the ADP/ATP carrier for the pathogenesis of myocarditis and dilated cardiomyopathy--clinical and experimental data. Springer Semin Immunopathol 1989; 11:15.
  113. Caforio AL, Goldman JH, Haven AJ, et al. Circulating cardiac-specific autoantibodies as markers of autoimmunity in clinical and biopsy-proven myocarditis. The Myocarditis Treatment Trial Investigators. Eur Heart J 1997; 18:270.
  114. Lauer B, Schannwell M, Kühl U, et al. Antimyosin autoantibodies are associated with deterioration of systolic and diastolic left ventricular function in patients with chronic myocarditis. J Am Coll Cardiol 2000; 35:11.
  115. Iwata M, Yoshikawa T, Baba A, et al. Autoantibodies against the second extracellular loop of beta1-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 2001; 37:418.
  116. Münch G, Boivin-Jahns V, Holthoff HP, et al. Administration of the cyclic peptide COR-1 in humans (phase I study): ex vivo measurements of anti-β1-adrenergic receptor antibody neutralization and of immune parameters. Eur J Heart Fail 2012; 14:1230.
  117. Maisch B. Autoreactivity to the cardiac myocyte, connective tissue and the extracellular matrix in heart disease and postcardiac injury. Springer Semin Immunopathol 1989; 11:369.
  118. Wolff PG, Kühl U, Schultheiss HP. Laminin distribution and autoantibodies to laminin in dilated cardiomyopathy and myocarditis. Am Heart J 1989; 117:1303.
  119. Caforio AL, Mahon NG, Baig MK, et al. Prospective familial assessment in dilated cardiomyopathy: cardiac autoantibodies predict disease development in asymptomatic relatives. Circulation 2007; 115:76.
  120. Warraich RS, Dunn MJ, Yacoub MH. Subclass specificity of autoantibodies against myosin in patients with idiopathic dilated cardiomyopathy: pro-inflammatory antibodies in DCM patients. Biochem Biophys Res Commun 1999; 259:255.
  121. Warraich RS, Noutsias M, Kazak I, et al. Immunoglobulin G3 cardiac myosin autoantibodies correlate with left ventricular dysfunction in patients with dilated cardiomyopathy: immunoglobulin G3 and clinical correlates. Am Heart J 2002; 143:1076.
  122. Staudt A, Böhm M, Knebel F, et al. Potential role of autoantibodies belonging to the immunoglobulin G-3 subclass in cardiac dysfunction among patients with dilated cardiomyopathy. Circulation 2002; 106:2448.
  123. Staudt A, Dörr M, Staudt Y, et al. Role of immunoglobulin G3 subclass in dilated cardiomyopathy: results from protein A immunoadsorption. Am Heart J 2005; 150:729.
  124. Matsui S, Fu ML, Katsuda S, et al. Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits. J Mol Cell Cardiol 1997; 29:641.
  125. Luppi P, Rudert WA, Zanone MM, et al. Idiopathic dilated cardiomyopathy: a superantigen-driven autoimmune disease. Circulation 1998; 98:777.
  126. Opavsky MA, Penninger J, Aitken K, et al. Susceptibility to myocarditis is dependent on the response of alphabeta T lymphocytes to coxsackieviral infection. Circ Res 1999; 85:551.
  127. Henke A, Huber S, Stelzner A, Whitton JL. The role of CD8+ T lymphocytes in coxsackievirus B3-induced myocarditis. J Virol 1995; 69:6720.
  128. Cruz-Adalia A, Jiménez-Borreguero LJ, Ramírez-Huesca M, et al. CD69 limits the severity of cardiomyopathy after autoimmune myocarditis. Circulation 2010; 122:1396.
  129. Zhou L, Chong MM, Littman DR. Plasticity of CD4+ T cell lineage differentiation. Immunity 2009; 30:646.
  130. Matsumori A. Cytokines in myocarditis and cardiomyopathies. Curr Opin Cardiol 1996; 11:302.
  131. Okura Y, Yamamoto T, Goto S, et al. Characterization of cytokine and iNOS mRNA expression in situ during the course of experimental autoimmune myocarditis in rats. J Mol Cell Cardiol 1997; 29:491.
  132. Watanabe K, Nakazawa M, Fuse K, et al. Protection against autoimmune myocarditis by gene transfer of interleukin-10 by electroporation. Circulation 2001; 104:1098.
  133. Nishii M, Inomata T, Takehana H, et al. Serum levels of interleukin-10 on admission as a prognostic predictor of human fulminant myocarditis. J Am Coll Cardiol 2004; 44:1292.
  134. Bowles NE, Towbin JA. Molecular aspects of myocarditis. Curr Opin Cardiol 1998; 13:179.
  135. Bryant D, Becker L, Richardson J, et al. Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha. Circulation 1998; 97:1375.
  136. Shioi T, Matsumori A, Sasayama S. Persistent expression of cytokine in the chronic stage of viral myocarditis in mice. Circulation 1996; 94:2930.
  137. Satoh M, Nakamura M, Satoh H, et al. Expression of tumor necrosis factor-alpha--converting enzyme and tumor necrosis factor-alpha in human myocarditis. J Am Coll Cardiol 2000; 36:1288.
  138. Caforio AL, Baboonian C, McKenna WJ. Postviral autoimmune heart disease--fact or fiction? Eur Heart J 1997; 18:1051.
  139. Caforio AL, Grazzini M, Mann JM, et al. Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. Circulation 1992; 85:1734.