Progress in Cardiovascular Diseases
Volume 52, Issue 4 , Pages 274-288 , January 2010

Myocarditis

  • Lori A. Blauwet
    • ,
  • Leslie T. Cooper

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Leslie T. Cooper, Jr, MD, Consultant, Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW Rochester, MN 55905.

References 

  1. Chow LH, Radio SJ, Sears TD, et al. Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. J Am Coll Cardiol. 1989;14:915–920
  2. Baughman KL. Diagnosis of myocarditis: death of Dallas criteria. Circulation. 2006;113:593–595
  3. Herskowitz A, Ahmed-Ansari A, Neumann DA, et al. Induction of major histocompatibility complex antigens within the myocardium of patients with active myocarditis: a nonhistologic marker of myocarditis. J Am Coll Cardiol. 1990;15:624–632
  4. Maisch B, Portig I, Ristic A, et al. Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus. A status report. Herz. 2000;25:200–209
  5. Kindermann I, Kindermann M, Kandolf R, et al. Predictors of outcome in patients with suspected myocarditis. Circulation. 2008;118:639–648
  6. Friedrich MG, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009;53:1475–1487
  7. Mahrholdt H, Goedecke C, Wagner A, et al. Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology. Circulation. 2004;109:1250–1258
  8. Gutberlet M, Spors B, Thoma T, et al. Suspected chronic myocarditis at cardiac MR: diagnostic accuracy and association with immunohistologically detected inflammation and viral persistence. Radiology. 2008;246:401–409
  9. Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation. 2007;116:2216–2233
  10. Wakafuji S, Okada R. Twenty year autopsy statistics of myocarditis incidence in Japan. Jpn Circ J. 1986;50:1288–1293
  11. Carniel E, Sinagra G, Bussani R, et al. Fatal myocarditis: morphologic and clinical features. Ital Heart J. 2004;5:702–706
  12. Kyto V, Saraste A, Voipio-Pulkki LM, et al. Incidence of fatal myocarditis: a population-based study in Finland. Am J Epidemiol. 2007;165:570–574
  13. Gravanis MB, Sternby NH. Incidence of myocarditis. A 10-year autopsy study from Malmo, Sweden. Arch Pathol Lab Med. 1991;115:390–392
  14. Doolan A, Langlois N, Semsarian C. Causes of sudden cardiac death in young Australians. Med J Aust. 2004;180:110–112
  15. Hahn EA, Hartz VL, Moon TE, et al. The Myocarditis Treatment Trial: design, methods and patients enrollment. Eur Heart J. 1995;16(Suppl O):162–167
  16. Kuhl 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;111:887–893
  17. 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;333:269–275
  18. 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;28:1326–1333
  19. Magnani JW, Danik HJ, Dec GW, et al. Survival in biopsy-proven myocarditis: a long-term retrospective analysis of the histopathologic, clinical, and hemodynamic predictors. Am Heart J. 2006;151:463–470
  20. Lyden DC, Olszewski J, Feran M, et al. Coxsackievirus B-3-induced myocarditis. Effect of sex steroids on viremia and infectivity of cardiocytes. Am J Pathol. 1987;126:432–438
  21. Schwartz J, Sartini D, Huber S. Myocarditis susceptibility in female mice depends upon ovarian cycle phase at infection. Virology. 2004;330:16–23
  22. Frisancho-Kiss S, Coronado MJ, Frisancho JA, et al. Gonadectomy of male BALB/c mice increases Tim-3(+) alternatively activated M2 macrophages, Tim-3(+) T cells, Th2 cells and Treg in the heart during acute coxsackievirus-induced myocarditis. Brain Behav Immun. 2009;23:649–657
  23. Cooper LT, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis—natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med. 1997;336:1860–1866
  24. Fenoglio JJ, Ursell PC, Kellogg CF, et al. Diagnosis and classification of myocarditis by endomyocardial biopsy. N Engl J Med. 1983;308:12–18
  25. Kyto V, Saukko P, Lignitz E, et al. Diagnosis and presentation of fatal myocarditis. Hum Pathol. 2005;36:1003–1007
  26. Shen WK, Edwards WD, Hammill SC, et al. Sudden unexpected nontraumatic death in 54 young adults: a 30-year population-based study. Am J Cardiol. 1995;76:148–152
  27. Passarino G, Burlo P, Ciccone G, et al. Prevalence of myocarditis at autopsy in Turin. Italy. Arch Pathol Lab Med. 1997;121:619–622
  28. Eckart RE, Scoville SL, Campbell CL, et al. Sudden death in young adults: a 25-year review of autopsies in military recruits. Ann Intern Med. 2004;141:829–834
  29. 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;119:1085–1092
  30. Rasten-Almqvist P, Eksborg S, Rajs J. Myocarditis and sudden infant death syndrome. Apmis. 2002;110:469–480
  31. Topaz O, Edwards JE. Pathologic features of sudden death in children, adolescents, and young adults. Chest. 1985;87:476–482
  32. Neuspiel DR, Kuller LH. Sudden and unexpected natural death in childhood and adolescence. JAMA. 1985;254:1321–1325
  33. Nugent AW, Daubeney PE, Chondros P, et al. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med. 2003;348:1639–1646
  34. Weber MA, Ashworth MT, Risdon RA, et al. Clinicopathological features of paediatric deaths due to myocarditis: an autopsy series. Arch Dis Child. 2008;93:594–598
  35. Towbin JA, Lowe AM, Colan SD, et al. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA. 2006;296:1867–1876
  36. Rahman JE, Helou EF, Gelzer-Bell R, et al. Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. J Am Coll Cardiol. 2004;43:410–415
  37. Frustaci A, Verardo R, Caldarulo M, et al. Myocarditis in hypertrophic cardiomyopathy patients presenting acute clinical deterioration. Eur Heart J. 2007;28:733–740
  38. Pieroni M, Dello Russo A, Marzo F, et al. High prevalence of myocarditis mimicking arrhythmogenic right ventricular cardiomyopathy differential diagnosis by electroanatomic mapping-guided endomyocardial biopsy. J Am Coll Cardiol. 2009;53:681–689
  39. Basso C, Corrado D, Marcus FI, et al. Arrhythmogenic right ventricular cardiomyopathy. Lancet. 2009;373:1289–1300
  40. McCully RB, Cooper LT, Schreiter S. Coronary artery spasm in lymphocytic myocarditis: a rare cause of acute myocardial infarction. Heart (British Cardiac Society). 2005;91:202
  41. Hufnagel G, Pankuweit S, Richter A, et al. The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID). First epidemiological results. Herz. 2000;25:279–285
  42. Freedman SB, Haladyn JK, Floh A, et al. Pediatric myocarditis: emergency department clinical findings and diagnostic evaluation. Pediatrics. 2007;120:1278–1285
  43. Amabile N, Fraisse A, Bouvenot J, et al. Outcome of acute fulminant myocarditis in children. Heart (British Cardiac Society). 2006;92:1269–1273
  44. Morgera T, Di Lenarda A, Dreas L, et al. Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes. Am Heart J. 1992;124:455–467
  45. Vignola PA, Aonuma K, Swaye PS, et al. Lymphocytic myocarditis presenting as unexplained ventricular arrhythmias: diagnosis with endomyocardial biopsy and response to immunosuppression. J Am Coll Cardiol. 1984;4:812–819
  46. Dec GW, Waldman H, Southern J, et al. Viral myocarditis mimicking acute myocardial infarction. J Am Coll Cardiol. 1992;20:85–89
  47. Kuhl U, Pauschinger M, Seeberg B, et al. Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation. 2005;112:1965–1970
  48. Nakashima H, Katayama T, Ishizaki M, et al. Q wave and non-Q wave myocarditis with special reference to clinical significance. Jpn Heart J. 1998;39:763–774
  49. Greenwood RD, Nadas AS, Fyler DC. The clinical course of primary myocardial disease in infants and children. Am Heart J. 1976;92:549–560
  50. Fuse K, Kodama M, Okura Y, et al. Predictors of disease course in patients with acute myocarditis. Circulation. 2000;102:2829–2835
  51. 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;44:1292–1297
  52. Smith SC, Ladenson JH, Mason JW, et al. Elevations of cardiac troponin I associated with myocarditis. Experimental and clinical correlates. Circulation. 1997;95:163–168
  53. Franz WM, Remppis A, Kandolf R, et al. Serum troponin T: diagnostic marker for acute myocarditis. Clin Chem. 1996;42:340–341
  54. Lauer B, Niederau C, Kuhl U, et al. Cardiac troponin T in patients with clinically suspected myocarditis. J Am Coll Cardiol. 1997;30:1354–1359
  55. Soongswang J, Durongpisitkul K, Nana A, et al. Cardiac troponin T: a marker in the diagnosis of acute myocarditis in children. Pediatr Cardiol. 2005;26:45–49
  56. Pinamonti B, Alberti E, Cigalotto A, et al. Echocardiographic findings in myocarditis. Am J Cardiol. 1988;62:285–291
  57. Nieminen MS, Heikkila J, Karjalainen J. Echocardiography in acute infectious myocarditis: relation to clinical and electrocardiographic findings. Am J Cardiol. 1984;53:1331–1337
  58. Mendes LA, Dec GW, Picard MH, et al. Right ventricular dysfunction: an independent predictor of adverse outcome in patients with myocarditis. Am Heart J. 1994;128:301–307
  59. Angelini A, Calzolari V, Calabrese F, et al. Myocarditis mimicking acute myocardial infarction: role of endomyocardial biopsy in the differential diagnosis. Heart (British Cardiac Society). 2000;84:245–250
  60. James KB, Lee K, Thomas JD, et al. Left ventricular diastolic dysfunction in lymphocytic myocarditis as assessed by Doppler echocardiography. Am J Cardiol. 1994;73:282–285
  61. Daly K, Monaghan M, Richardson P, et al. Significant incidence of mural thrombi in acute myocarditis—indications for early anticoagulation (abstract). J Am Coll Cardiol. 1983;1:584
  62. Felker GM, Boehmer JP, Hruban RH, et al. Echocardiographic findings in fulminant and acute myocarditis. J Am Coll Cardiol. 2000;36:227–232
  63. Friedrich MG, Strohm O, Schulz-Menger J, et al. Contrast media-enhanced magnetic resonance imaging visualizes myocardial changes in the course of viral myocarditis. Circulation. 1998;97:1802–1809
  64. Laissy JP, Messin B, Varenne O, et al. MRI of acute myocarditis: a comprehensive approach based on various imaging sequences. Chest. 2002;122:1638–1648
  65. Laissy JP, Hyafil F, Feldman LJ, et al. Differentiating acute myocardial infarction from myocarditis: diagnostic value of early- and delayed-perfusion cardiac MR imaging. Radiology. 2005;237:75–82
  66. Abdel-Aty H, Boye P, Zagrosek A, et al. Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches. J Am Coll Cardiol. 2005;45:1815–1822
  67. Mahrholdt H, Wagner A, Deluigi CC, et al. Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation. 2006;114:1581–1590
  68. Yilmaz A, Mahrholdt H, Athanasiadis A, et al. Coronary vasospasm as the underlying cause for chest pain in patients with PVB19 myocarditis. Heart (British Cardiac Society). 2008;94:1456–1463
  69. Asimaki A, Tandri H, Huang H, et al. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy. N Engl J Med. 2009;360:1075–1084
  70. Holzmann M, Nicko A, Kuhl U, et al. Complication rate of right ventricular endomyocardial biopsy via the femoral approach: a retrospective and prospective study analyzing 3048 diagnostic procedures over an 11-year period. Circulation. 2008;118:1722–1728
  71. Matsumori A, Shimada T, Chapman NM, et al. Myocarditis and heart failure associated with hepatitis C virus infection. J Card Fail. 2006;12:293–298
  72. Matsumori A. Hepatitis C virus infection and cardiomyopathies. Circ Res. 2005;96:144–147
  73. 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;24:1025–1032
  74. Breuckmann F, Neumann T, Kondratieva J, et al. Dilated cardiomyopathy in two adult human immunodeficiency positive (HIV+) patients possibly related to highly active antiretroviral therapy (HAART). Eur J Med Res. 2005;10:395–399
  75. Chen F, Shannon K, Ding S, et al. HIV type 1 glycoprotein 120 inhibits cardiac myocyte contraction. AIDS Res Hum Retrovir. 2002;18:777–784
  76. Lanjewar DN, Katdare GA, Jain PP, et al. Pathology of the heart in acquired immunodeficiency syndrome. Indian Heart J. 1998;50:321–325
  77. Hofman P, Drici MD, Gibelin P, et al. Prevalence of toxoplasma myocarditis in patients with the acquired immunodeficiency syndrome. Br Heart J. 1993;70:376–381
  78. Pugliese A, Isnardi D, Saini A, et al. Impact of highly active antiretroviral therapy in HIV-positive patients with cardiac involvement. J Infect. 2000;40:282–284
  79. Barbaro G. Reviewing the cardiovascular complications of HIV infection after the introduction of highly active antiretroviral therapy. Curr Drug Targets. 2005;5:337–343
  80. Costello JM, Alexander ME, Greco KM, et al. Lyme carditis in children: presentation, predictive factors, and clinical course. Pediatrics. 2009;123:e835–e841
  81. Stanek G, Klein J, Bittner R, et al. Borrelia burgdorferi as an etiologic agent in chronic heart failure. Scand J Infect Dis. 1991;77:85–87
  82. Higuchi MD, Ries MM, Aiello VD, et al. Association of an increase in CD8+ T cells with the presence of Trypanosoma cruzi antigens in chronic, human, chagasic myocarditis. Am J Trop Med Hyg. 1997;56:485–489
  83. Acquatella H. Echocardiography in Chagas heart disease. Circulation. 2007;115:1124–1131
  84. Maguire JH, Hoff R, Sherlock I, et al. Cardiac morbidity and mortality due to Chagas' disease: prospective electrocardiographic study of a Brazilian community. Circulation. 1987;75:1140–1145
  85. Simmons A, Vacek JL, Meyers D. Anthracycline-induced cardiomyopathy. Postgraduate medicine. 2008;120:67–72
  86. Phillips K, Luk A, Soor GS, et al. Cocaine cardiotoxicity: a review of the pathophysiology, pathology, and treatment options. Am J Cardiovasc Drugs. 2009;9:177–196
  87. Taliercio CP, Olney BA, Lie JT. Myocarditis related to drug hypersensitivity. Mayo Clin Proc. 1985;60:463–468
  88. Hervier B, Masseau A, Bossard C, et al. Vasa-vasoritis of the aorta and fatal myocarditis in fulminant Churg-Strauss syndrome. Rheumatology (Oxford). 2008;47:1728–1729
  89. Frustaci A, Cuoco L, Chimenti C, et al. Celiac disease associated with autoimmune myocarditis. Circulation. 2002;105:2611–2618
  90. Corssmit EP, Trip MD, Durrer JD. Loffler's endomyocarditis in the idiopathic hypereosinophilic syndrome. Cardiology. 1999;91:272–276
  91. Kirchhoff LV, Weiss LM, Wittner M, et al. Parasitic diseases of the heart. Front Biosci. 2004;9:706–723
  92. Dilber E, Karagoz T, Aytemir K, et al. Acute myocarditis associated with tetanus vaccination. Mayo Clin Proc. 2003;78:1431–1433
  93. Cassimatis DC, Atwood JE, Engler RM, et al. Smallpox vaccination and myopericarditis: a clinical review. J Am Coll Cardiol. 2004;43:1503–1510
  94. Davies MJ, Pomerance A, Teare RD. Idiopathic giant cell myocarditis—a distinctive clinico-pathological entity. Br Heart J. 1975;37:192–195
  95. Kilgallen CM, Jackson E, Bankoff M, et al. A case of giant cell myocarditis and malignant thymoma: a postmortem diagnosis by needle biopsy. Clin Cardiol. 1998;21:48–51
  96. Daniels PR, Berry GJ, Tazelaar HD, et al. Giant cell myocarditis as a manifestation of drug hypersensitivity. Cardiovasc Pathol. 2000;9:287–291
  97. Litovsky SH, Burke AP, Virmani R. Giant cell myocarditis: an entity distinct from sarcoidosis characterized by multiphasic myocyte destruction by cytotoxic T cells and histiocytic giant cells. Mod Pathol. 1996;9:1126–1134
  98. Okura Y, Dec GW, Hare JM, et al. A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis. J Am Coll Cardiol. 2003;41:322–329
  99. Yazaki Y, Isobe M, Hiramitsu S, et al. Comparison of clinical features and prognosis of cardiac sarcoidosis and idiopathic dilated cardiomyopathy. Am J Cardiol. 1998;82:537–540
  100. Badorff C, Lee GH, Lamphear BJ, et al. Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat Med. 1999;5:320–326
  101. Lozano MD, Rubocki RJ, Wilson JE, et al. Human leukocyte antigen class II associations in patients with idiopathic dilated cardiomyopathy. Myocarditis Treatment Trial Investigators. J Card Fail. 1997;3:97–103
  102. Tchilian EZ, Gil J, Navarro ML, et al. Unusual case presentations associated with the CD45 C77G polymorphism. Clin Exp Immunol. 2006;146:448–454
  103. Beck MA, Levander OA, Handy J. Selenium deficiency and viral infection. J Nutr. 2003;133(5 Suppl 1):1463S–1467S
  104. Ilback NG, Wesslen L, Fohlman J, et al. Effects of methyl mercury on cytokines, inflammation and virus clearance in a common infection (coxsackie B3 myocarditis). Toxicol Lett. 1996;89:19–28
  105. Cooper LT, Rader V, Ralston NV. The roles of selenium and mercury in the pathogenesis of viral cardiomyopathy. Congest Heart Fail (Greenwich, Conn). 2007;13:193–199
  106. Tracy S, Hofling K, Pirruccello S, et al. Group B coxsackievirus myocarditis and pancreatitis: connection between viral virulence phenotypes in mice. Journal of medical virology. 2000;62:70–81
  107. Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science (New York, NY). 1997;275:1320–1323
  108. Shafren DR, Bates RC, Agrez MV, et al. Coxsackieviruses B1, B3, and B5 use decay accelerating factor as a receptor for cell attachment. J Virol. 1995;69:3873–3877
  109. Wickham TJ, Filardo EJ, Cheresh DA, et al. Integrin alpha v beta 5 selectively promotes adenovirus mediated cell membrane permeabilization. J Cell Biol. 1994;127:257–264
  110. Wickham TJ, Mathias P, Cheresh DA, et al. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell. 1993;73:309–319
  111. Salone B, Martina Y, Piersanti S, et al. Integrin alpha3beta1 is an alternative cellular receptor for adenovirus serotype 5. J Virol. 2003;77:13448–13454
  112. Martino TA, Petric M, Brown M, et al. Cardiovirulent coxsackieviruses and the decay-accelerating factor (CD55) receptor. Virology. 1998;244:302–314
  113. Fechner H, Noutsias M, Tschoepe C, et al. Induction of coxsackievirus-adenovirus-receptor expression during myocardial tissue formation and remodeling: identification of a cell-to-cell contact-dependent regulatory mechanism. Circulation. 2003;107:876–882
  114. Kashimura T, Kodama M, Hotta Y, et al. Spatiotemporal changes of coxsackievirus and adenovirus receptor in rat hearts during postnatal development and in cultured cardiomyocytes of neonatal rat. Virchows Arch. 2004;444:283–292
  115. Shi Y, Chen C, Lisewski U, et al. Cardiac deletion of the Coxsackievirus-adenovirus receptor abolishes Coxsackievirus B3 infection and prevents myocarditis in vivo. J Am Coll Cardiol. 2009;53:1219–1226
  116. Huber SA. Autoimmunity in coxsackievirus B3 induced myocarditis. Autoimmunity. 2006;39:55–61
  117. Huang CH, Vallejo JG, Kollias G, et al. Role of the innate immune system in acute viral myocarditis. Basic Res Cardiol. 2009;104:228–237
  118. Lowenstein CJ, Hill SL, Lafond-Walker A, et al. Nitric oxide inhibits viral replication in murine myocarditis. J Clin Invest. 1996;97:1837–1843
  119. Szalay G, Sauter M, Hald J, et al. Sustained nitric oxide synthesis contributes to immunopathology in ongoing myocarditis attributable to interleukin-10 disorders. Am J Pathol. 2006;169:2085–2093
  120. Hardarson HS, Baker JS, Yang Z, et al. Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury. Am J Physiol. 2007;292:H251–H258
  121. Fuse K, Chan G, Liu Y, et al. Myeloid differentiation factor-88 plays a crucial role in the pathogenesis of Coxsackievirus B3-induced myocarditis and influences type I interferon production. Circulation. 2005;112:2276–2285
  122. Fairweather D, Frisancho-Kiss S, Njoku DB, et al. Complement receptor 1 and 2 deficiency increases coxsackievirus B3-induced myocarditis, dilated cardiomyopathy, and heart failure by increasing macrophages, IL-1beta, and immune complex deposition in the heart. J Immunol. 2006;176:3516–3524
  123. 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;66:24–31
  124. Lamphear BJ, Yan R, Yang F, et al. Mapping the cleavage site in protein synthesis initiation factor eIF-4 gamma of the 2A proteases from human Coxsackievirus and rhinovirus. J Biol Chem. 1993;268:19200–19203
  125. Xiong D, Yajima T, Lim BK, et al. Inducible cardiac-restricted expression of enteroviral protease 2A is sufficient to induce dilated cardiomyopathy. Circulation. 2007;115:94–102
  126. Chau DH, Yuan J, Zhang H, et al. Coxsackievirus B3 proteases 2A and 3C induce apoptotic cell death through mitochondrial injury and cleavage of eIF4GI but not DAP5/p97/NAT1. Apoptosis. 2007;12:513–524
  127. Pummerer C, Berger P, Fruhwirth M, et al. Cellular infiltrate, major histocompatibility antigen expression and immunopathogenic mechanisms in cardiac myosin-induced myocarditis. Lab Invest. 1991;65:538–547
  128. Goser S, Ottl R, Brodner A, et al. Critical role for monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha in induction of experimental autoimmune myocarditis and effective anti-monocyte chemoattractant protein-1 gene therapy. Circulation. 2005;112:3400–3407
  129. Rangachari M, Mauermann N, Marty RR, et al. T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17. J Exp Med. 2006;203:2009–2019
  130. Haga T, Suzuki J, Kosuge H, et al. Attenuation of experimental autoimmune myocarditis by blocking T cell activation through 4-1BB pathway. J Mol Cell Cardiol. 2009;46:719–727
  131. Afanasyeva M, Wang Y, Kaya Z, et al. Experimental autoimmune myocarditis in A/J mice is an interleukin-4-dependent disease with a Th2 phenotype. Autoimmunity. 2001;159:193–203
  132. Eriksson U, Ricci R, Hunziker L, et al. Dendritic cell-induced autoimmune heart failure requires cooperation between adaptive and innate immunity. Nat Med. 2003;9:1484–1490
  133. Hayward SL, Bautista-Lopez N, Suzuki K, et al. CD4 T cells play major effector role and CD8 T cells initiating role in spontaneous autoimmune myocarditis of HLA-DQ8 transgenic IAb knockout nonobese diabetic mice. J Immunol. 2006;176:7715–7725
  134. Neumann DA, Rose NR, Ansari AA, et al. Induction of multiple heart autoantibodies in mice with coxsackievirus B3- and cardiac myosin-induced autoimmune myocarditis. J Immunol. 1994;152:343–350
  135. Caforio AL, Mahon NJ, Tona F, et al. Circulating cardiac autoantibodies in dilated cardiomyopathy and myocarditis: pathogenetic and clinical significance. Eur J Heart Fail. 2002;4:411–417
  136. Neumann DA, Burek CL, Baughman KL, et al. Circulating heart-reactive antibodies in patients with myocarditis or cardiomyopathy. J Am Coll Cardiol. 1990;16:839–846
  137. Caforio AL, Mahon NJ, McKenna WJ. Cardiac autoantibodies to myosin and other heart-specific autoantigens in myocarditis and dilated cardiomyopathy. Autoimmunity. 2001;34:199–204
  138. Wallukat G, Morwinski M, Kowal K, et al. Autoantibodies against the beta-adrenergic receptor in human myocarditis and dilated cardiomyopathy: beta-adrenergic agonism without desensitization. Eur Heart J. 1991;12(Suppl D):178–181
  139. Staudt A, Dorr M, Staudt Y, et al. Role of immunoglobulin G3 subclass in dilated cardiomyopathy: results from protein A immunoadsorption. Am Heart J. 2005;150:729–736
  140. 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;143:1076–1084
  141. Latva-Hirvela J, Kyto V, Saraste A, et al. Development of troponin autoantibodies in experimental coxsackievirus B3 myocarditis. Eur J Clin Invest. 2009;39:457–462
  142. Kaya Z, Katus HA, Rose NR. Cardiac troponins and autoimmunity: Their role in the pathogenesis of myocarditis and of heart failure. Clin Immunol (Orlando, Fla). 2009;
  143. Goser S, Andrassy M, Buss SJ, et al. Cardiac troponin I but not cardiac troponin T induces severe autoimmune inflammation in the myocardium. Circulation. 2006;114:1693–1702
  144. Matsumori A, Igata H, Ono K, et al. High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myocarditis: a possible mechanism of digitalis toxicity. Jpn Circ J. 1999;63:934–940
  145. Wang WZ, Matsumori A, Yamada T, et al. Beneficial effects of amlodipine in a murine model of Congest Heart Fail induced by viral myocarditis. A possible mechanism through inhibition of nitric oxide production. Circulation. 1997;95:245–251
  146. Liu W, Shimada M, Xiao J, et al. Nifedipine inhibits the activation of inflammatory and immune reactions in viral myocarditis. Life Sci. 2009;85:235–240
  147. Khatib R, Reyes MP, Smith FE. Enhancement of Coxsackievirus B3 replication in Vero cells by indomethacin. J Infect Dis. 1990;162:997–998
  148. Khatib R, Reyes MP, Smith F, et al. Enhancement of coxsackievirus B4 virulence by indomethacin. J Lab Clin Med. 1990;116:116–120
  149. Costanzo-Nordin MR, Reap EA, O'Connell JB, et al. A nonsteroid anti-inflammatory drug exacerbates Coxsackie B3 murine myocarditis. J Am Coll Cardiol. 1985;6:1078–1082
  150. Pages ON, Aubert S, Combes A, et al. Paracorporeal pulsatile biventricular assist device versus extracorporal membrane oxygenation-extracorporal life support in adult fulminant myocarditis. J Thorac Cardiovasc Surg. 2009;137:194–197
  151. Duncan BW, Bohn DJ, Atz AM, et al. Mechanical circulatory support for the treatment of children with acute fulminant myocarditis. J Thorac Cardiovasc Surg. 2001;122:440–448
  152. Reinhartz O, Hill JD, Al-Khaldi A, et al. Thoratec ventricular assist devices in pediatric patients: update on clinical results. Asaio J. 2005;51:501–503
  153. Topkara VK, Dang NC, Barili F, et al. Ventricular assist device use for the treatment of acute viral myocarditis. J Thorac Cardiovasc Surg. 2006;131:1190–1191
  154. 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;42:466–472
  155. Wang YX, da Cunha V, Vincelette J, et al. Antiviral and myocyte protective effects of murine interferon-beta and -{alpha}2 in coxsackievirus B3-induced myocarditis and epicarditis in Balb/c mice. Am J Physiol. 2007;293:H69–H76
  156. 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;6:693–697
  157. Okada I, Matsumori A, Matoba Y, et al. Combination treatment with ribavirin and interferon for coxsackievirus B3 replication. J Lab Clin Med. 1992;120:569–573
  158. Matsumori A, Crumpacker CS, Abelmann WH. Prevention of viral myocarditis with recombinant human leukocyte interferon alpha A/D in a murine model. J Am Coll Cardiol. 1987;9:1320–1325
  159. Ray CG, Icenogle TB, Minnich LL, et al. The use of intravenous ribavirin to treat influenza virus-associated acute myocarditis. J Infect Dis. 1989;159:829–836
  160. Kuhl U, Pauschinger M, Schwimmbeck PL, et al. Interferon-beta treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction. Circulation. 2003;107:2793–2798
  161. Jones SR, Herskowitz A, Hutchins GM, et al. Effects of immunosuppressive therapy in biopsy-proved myocarditis and borderline myocarditis on left ventricular function. Am J Cardiol. 1991;68:370–376
  162. Maisch B, Camerini F, Schultheiss HP. Immunosuppressive therapy for myocarditis. N Engl J Med. 1995;333:1713;[author reply 4]
  163. McNamara DM, Rosenblum WD, Janosko KM, et al. Intravenous immune globulin in the therapy of myocarditis and acute cardiomyopathy. Circulation. 1997;95:2476–2478
  164. McNamara DM, Starling RC, Dec GW. Intervention in myocarditis and acute cardiomyopathy with immune globulin: results from the randomized placebo controlled IMAC trial. Circulation. 1999;100(Suppl I):I–21[Abstract]
  165. Cooper LT, Hare JM, Tazelaar HD, et al. Usefulness of immunosuppression for giant cell myocarditis. Am J Cardiol. 2008;102:1535–1539
  166. Chan KY, Iwahara M, Benson LN, et al. Immunosuppressive therapy in the management of acute myocarditis in children: a clinical trial. J Am Coll Cardiol. 1991;17:458–460
  167. Drucker NA, Colan SD, Lewis AB, et al. Gamma-globulin treatment of acute myocarditis in the pediatric population. Circulation. 1994;89:252–257
  168. Parrillo JE, Cunnion RE, Epstein SE, et al. A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy. N Engl J Med. 1989;321:1061–1068
  169. Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, et al. Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: two-year follow-up results. Circulation. 2001;104:39–45
  170. Frustaci A, Chimenti C, Calabrese F, et al. Immunosuppressive therapy for active lymphocytic myocarditis: virological and immunologic profile of responders versus nonresponders. Circulation. 2003;107:857–863
  171. Gullestad L, Aass H, Fjeld JG, et al. Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. Circulation. 2001;103:220–225
  172. Frustaci A, Russo MA, Chimenti C. Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study. Eur Heart J. 2009;
  173. Camargo PR, Snitcowsky R, da Luz PL, et al. Favorable effects of immunosuppressive therapy in children with dilated cardiomyopathy and active myocarditis. Pediatr Cardiol. 1995;16:61–68
  174. Balaji S, Wiles HB, Sens MA, et al. Immunosuppressive treatment for myocarditis and borderline myocarditis in children with ventricular ectopic rhythm. Br Heart J. 1994;72:354–359
  175. McNamara DM, Holubkov R, Starling RC, et al. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation. 2001;103:2254–2259
  176. Cabinian AE, Kiel RJ, Smith F, et al. Modification of exercise-aggravated coxsackievirus B3 murine myocarditis by T lymphocyte suppression in an inbred model. J Lab Clin Med. 1990;115:454–462
  177. Maron BJ. Sudden death in young athletes. N Engl J Med. 2003;349:1064–1075
  178. Maron BJ, Ackerman MJ, Nishimura RA, et al. Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol. 2005;45:1340–1345
  179. Magnani JW, Dec GW. Myocarditis: current trends in diagnosis and treatment. Circulation. 2006;113:876–890
  180. McCarthy RE, Boehmer JP, Hruban RH, et al. Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. N Engl J Med. 2000;342:690–695
  181. Sheppard R, Bedi M, Kubota T, et al. Myocardial expression of fas and recovery of left ventricular function in patients with recent-onset cardiomyopathy. J Am Coll Cardiol. 2005;46:1036–1042
  182. Fuse K, Kodama M, Okura Y, et al. Short-term prognostic value of initial serum levels of interleukin-10 in patients with acute myocarditis. Eur J Heart Fail. 2005;7:109–112
  183. Gagliardi MG, Bevilacqua M, Bassano C, et al. Long term follow up of children with myocarditis treated by immunosuppression and of children with dilated cardiomyopathy. Heart (British Cardiac Society). 2004;90:1167–1171
  184. Cooper DK, Schlesinger RG, Shrago S, et al. Heart transplantation for giant cell myocarditis. J Heart Lung Transplant. 1994;13:555
  185. Singh TP, Rabah R, Cooper LT, et al. Total lymphoid irradiation: new therapeutic option for refractory giant cell myocarditis. J Heart Lung Transplant. 2004;23:492–495
  186. Fontanella GH, De Vusser K, Laroy W, et al. Immunization with an engineered mutant trans-sialidase highly protects mice from experimental Trypanosoma cruzi infection: a vaccine candidate. Vaccine. 2008;26:2322–2334
  187. Fohlman J, Ilback NG, Friman G, et al. Vaccination of Balb/c mice against enteroviral mediated myocarditis. Vaccine. 1990;8:381–384
  188. Oberg AL, Mahoney DW, Eckel-Passow JE, et al. Statistical analysis of relative labeled mass spectrometry data from complex samples using ANOVA. J Proteome Res. 2008;7:225–233

 Statement of Conflict of Interest: see page 284.

⁎ Author's note: Substantial content in this review article is drawn from Cooper LT Jr. Myocarditis. N Engl J Med 2009;9;360(15):1526-38.

PII: S0033-0620(09)00096-6

doi: 10.1016/j.pcad.2009.11.006

Progress in Cardiovascular Diseases
Volume 52, Issue 4 , Pages 274-288 , January 2010

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