Advertisement

Possible Causative or Contributing Role of Viruses

  • Fiorella Calabrese
  • Elisa Carturan
  • Gaetano Thiene
  • Jeffrey A. Towbin

Abstract

Arrhthmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a primary heart muscle disease characterized by transmural fibrofatty replacement of the right ventricle and clinically by life-threatening ventricular arrhythmias in apparently healthy people [1]. The disease results in a high risk of sudden death, particularly in young people [2] and athletes [3]. Over the past several years, the genetic basis of this disease has been unraveled and shown to be a disease of the desmosome [4]. Mutations in desmoplakin, plakoglobin, plakophilin, desmoglein, and desmocollin have been identified, along with the desmosome modifying gene TGF-β3 [5, 6, 7, 8, 9, 10].

Keywords

Right Ventricle Polymerase Chain Reac Ventricular Cardiomyopathy Arrhythmogenic Right Ventricular Dysplasia Endocardial Fibroelastosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Nava A, Rossi L, Thiene G (eds) (1997) Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Elsevier, AmsterdamGoogle Scholar
  2. 2.
    Thiene G, Nava A, Corrado D et al (1988) Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med 318:129–133PubMedCrossRefGoogle Scholar
  3. 3.
    Corrado D, Thiene G, Nava A et al (1990) Sudden death in young competitive athletes: Clinicopathologic correlation in 22 cases. Am J Med 89:588–596PubMedCrossRefGoogle Scholar
  4. 4.
    Towbin JA, Bowles NE (2002) The failing heart. Nature 415: 227–233PubMedCrossRefGoogle Scholar
  5. 5.
    McKoy G, Protonotarios N, Crosby A et al (2000) Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 355:2119–2124PubMedCrossRefGoogle Scholar
  6. 6.
    Rampazzo A, Nava A, Malacrida S et al (2002) Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 71:1200–1206PubMedCrossRefGoogle Scholar
  7. 7.
    Gerull B, Heuser A, Wichter T et al (2004) Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet 36:1162–1164PubMedCrossRefGoogle Scholar
  8. 8.
    Beffagna G, Occhi G, Nava A et al (2005) Regulatory mutations in transforming growth factor-β3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res 65:366–373PubMedCrossRefGoogle Scholar
  9. 9.
    Pilichou K, Nava A, Basso C et al (2006) Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy. Circulation 113:1171–1179PubMedCrossRefGoogle Scholar
  10. 10.
    Syrris P, Ward D, Evans S et al (2006) Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am J Hum Genet 79:978–984PubMedCrossRefGoogle Scholar
  11. 11.
    Ananthasubramaniam K, Khaja F (1998) Arrhythmogenic right ventricular dysplasia/cardiomyopathy: Review for the clinician. Prog Cardiovasc Dis 41:237–246PubMedCrossRefGoogle Scholar
  12. 12.
    Basso C, Thiene G, Corrado D et al (1996) Arrhythmogenic right ventricular cardiomyopathy. Dysplasia, dystrophy or myocarditis? Circulation 94:983–991PubMedGoogle Scholar
  13. 13.
    Miani D, Pinamonti B, Bussani R et al (1993) Right ventricular dysplasia: A clinical and pathological study of two families with left ventricular involvement. Br Heart J 69:151–157PubMedCrossRefGoogle Scholar
  14. 14.
    Fontaine G, Fontaliran F, Lascault G et al (1990) Congenital and acquired right ventricular dysplasia. Arch Mal Coeur Vaiss 83:915–290PubMedGoogle Scholar
  15. 15.
    Thiene G, Corrado D, Nava A et al (1991) Right ventricular cardiomyopathy: Is there evidence of an inflammatory aetiology? Eur Heart J 12:22–25PubMedGoogle Scholar
  16. 16.
    Pinamonti B, Miani D, Sinagra G et al (1996) Familial right ventricular dysplasia with biventricular involvement and inflammatory infiltration. Heart 76:66–69PubMedCrossRefGoogle Scholar
  17. 17.
    Grumbach IM, Heim A, Vonhof S et al (1998) Coxsackievirus genome in myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Cardiology 89:241–245PubMedCrossRefGoogle Scholar
  18. 18.
    Williams GT, Smith CA (1993) Molecular regulation of apoptosis: Genetic controls on cell death. Cell 74:777–779PubMedCrossRefGoogle Scholar
  19. 19.
    Mallat Z, Tedgui A, Fontaliran F et al (1996) Evidence of apoptosis in arrhythmogenic right ventricular dysplasia. N Engl J Med 335:1190–1196PubMedCrossRefGoogle Scholar
  20. 20.
    Valente M, Calabrese F, Thiene G et al (1998) In vivo evidence of apoptosis in arrhythmogenic right ventricular cardiomyopathy. Am J Pathol 152:479–484PubMedGoogle Scholar
  21. 21.
    D’Amati G, di Gioia CR, Giordano C et al (2000). Myocyte transdifferentiation: A possible pathogenetic mechanism for arrhythmogenic right ventricular cardiomyopathy. Arch Pathol Lab Med 124:287–290PubMedGoogle Scholar
  22. 22.
    Corrado D, Basso C, Thiene G et al (1997) Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: A multicenter study. J Am Coll Cardiol 30:1512–1520PubMedCrossRefGoogle Scholar
  23. 23.
    Orth T, Herr W, Spahn T et al (1997) Human parvovirus B19 infection associated with severe acute perimyocarditis in a 34-year-old man. Eur Heart J 18:524–525PubMedGoogle Scholar
  24. 24.
    Nilsson K, Lindquist O, Påhlson C (1999) Association of Rickettsia helvetica with chronic perimyocarditis in sudden cardiac death. Lancet 354:1169–1173PubMedCrossRefGoogle Scholar
  25. 25.
    Ristic AD, Maisch B, Hufnagel G et al (2000) Arrhythmias in acute pericarditis. An endomyocardial biopsy study. Herz 25:729–733PubMedCrossRefGoogle Scholar
  26. 26.
    Pankuweit S, Moll R, Baandrup U et al (2003) Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens. Hum Pathol 34:497–503PubMedCrossRefGoogle Scholar
  27. 27.
    Lobo FV, Heggtveit HA, Butany J et al (1992) Right ventricular dysplasia: Morphological findings in 13 cases. Can J Card 8:261–268Google Scholar
  28. 28.
    Fornes P, Ratel S, Lecomte D (1998) Pathology of arrhythmogenic right ventricular cardiomyopathy/dysplasia — An autopsy study of 20 forensic cases. J Forensic Sci 43:777–783PubMedGoogle Scholar
  29. 29.
    Burke AP, Farb A, Tashko G et al (1998) Arrhythmogenic right ventricular cardiomyopathy and fatty replacement of the right ventricular myocardium: Are they different diseases? Circulation 97:1571–1580PubMedGoogle Scholar
  30. 30.
    Fox PR, Maron BJ, Basso C et al (2000) Spontaneously occurring arrhythmogenic right ventricular cardiomyopathy in the domestic cat: A new animal model similar to the human disease. Circulation 102:1863–1870PubMedGoogle Scholar
  31. 31.
    Harvey AM, Battersby IA, Faena M et al (2005) Arrhythmogenic right ventricular cardiomyopathy in two cats. J Small Anim Pract 46:151–156PubMedCrossRefGoogle Scholar
  32. 32.
    Basso C, Fox PR, Meurs KM et al (2004) Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death in boxer dogs: A new animal model of human disease. Circulation 109:1180–1185PubMedCrossRefGoogle Scholar
  33. 33.
    Calabrese F, Basso C, Carturan E et al (2006) Arrhythmogenic right ventricular cardiomyopathy/dysplasia: Is there a role for viruses? Cardiovasc Pathol 15:11–17PubMedCrossRefGoogle Scholar
  34. 34.
    Matsumori A, Kawai C. (1980) Coxsackie virus B3 perimyocarditis in BALB/c mice: Experimental model of chronic perimyocarditis in the right ventricle. J Pathol l131:97–106CrossRefGoogle Scholar
  35. 35.
    Kearney DL, Towbin JA, Bricker JT et al (1995) Familial right ventricular dysplasia (cardiomyopathy). Pediatr Pathol Lab Med 15:181–189PubMedGoogle Scholar
  36. 36.
    Heim A, Grumbach I, Hake S et al (1997) Enterovirus heart disease of adults: A persistent, limited organ infection in the presence of neutralizing antibodies. J Med Virol 53:196–204PubMedCrossRefGoogle Scholar
  37. 37.
    Heim A, Grumbach I, Stille-Siegener M et al (1997) Detection of enterovirus RNA in the myocardium of a patient with arrhythmogenic right ventricular cardiomyopathy by in situ hybridization. Clin Infect Dis 25:1471–1472PubMedCrossRefGoogle Scholar
  38. 38.
    Calabrese F, Angelini A, Thiene G et al (2000) No detection of enteroviral genome in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy. J Clin Pathol 53:382–387PubMedCrossRefGoogle Scholar
  39. 39.
    Bowles NE, Ni J, Marcus F et al (2002) The detection of cardiotropic viruses in the myocardium of patients with arrhythmogenic right ventriculardysplasia/cardiomyopathy. J Am Coll Cardiol 39:892–895PubMedCrossRefGoogle Scholar
  40. 40.
    Chimenti C, Pieroni M, Maseri A et al (2004) Histologic findings in patients with clinical and instrumental diagnosis of sporadic arrhythmogenic right ventricular dysplasia. J Am Coll Cardiol 43:2305–2313PubMedCrossRefGoogle Scholar
  41. 41.
    McKenna WJ, Thiene G, Nava A et al (1994) Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology. Br Heart J 71:215–218PubMedCrossRefGoogle Scholar
  42. 42.
    Bowles NE, Richardson PJ, Olsen EG et al (1986) Detection of Coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet 1:1120–1123PubMedCrossRefGoogle Scholar
  43. 43.
    Bowles NE, Rose ML, Taylor P et al (1989) End-stage dilated cardiomyopathy: Persistence of enterovirus RNA in myocardium at cardiac transplantation. Circulation 80:1128–1136PubMedGoogle Scholar
  44. 44.
    Towbin JA, Griffin LD, Martin AB et al (1994) Intrauterine adenoviral myocarditis presenting a nonimmune hydrops fetalis: Diagnosis by polymerase chain reaction. Ped Inf Dis 13:144–150CrossRefGoogle Scholar
  45. 45.
    Martin AB, Webber S, Fricker FJ et al (1994) Acute myocarditis: Rapid diagnosis by polymerase chain reaction (PCR) in children. Circulation 90:330–339PubMedGoogle Scholar
  46. 46.
    Griffin L, Kearney D, Ni J et al (1995) Analysis of formalin-fixed and frozen myocardial autopsy samples for viral genome in childhood myocarditis and dilated cardiomyopathy with endocardial fibroelastosis using polymerse chain reaction (PCR). Cardiovasc Pathol 4:3–11CrossRefGoogle Scholar
  47. 47.
    Bowles NE, Ni J, Kearney DL et al (2003) 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 42:466–472PubMedCrossRefGoogle Scholar
  48. 48.
    Pauschinger M, Bowles NE, Fuentes-Garcia FJ et al (1999) Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction. Circulation 99:1348–1354PubMedGoogle Scholar
  49. 49.
    Schowengerdt KO, Ni J, Denfield SW et al (1996) Diagnosis, surveillance, and epidemiologic evaluation of viral infection in pediatric cardiac transplant recipients using the polymerase chain reaction (PCR). J Heart Lung Transplant 15:111–123PubMedGoogle Scholar
  50. 50.
    Teodoro JG, Branton PE (1997) Regulation of apoptosis by viral gene products. J Virol 71:1739–1746PubMedGoogle Scholar
  51. 51.
    Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257PubMedGoogle Scholar
  52. 52.
    Talanian RV, Yang X, Turbov J et al (1997) Granule-mediated killing: Pathways for granzyme B-initiated apoptosis. J Exp Med 186:1323–1331PubMedCrossRefGoogle Scholar
  53. 53.
    Seko Y, Shinkai Y, Kawasaki A et al (1991) Expression of perforin in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3. Circulation 84:788–795PubMedGoogle Scholar
  54. 54.
    Seko Y, Shinkai Y, Kawasaki A et al (1993) Evidence of perforin-mediated cardiac myocyte injury in acute murine myocarditis caused by Coxsackie virus B3. J Pathol 170:53–58PubMedCrossRefGoogle Scholar
  55. 55.
    Badorff C, Berkely N, Mehrotra S et al (2000) Enteroviral protease 2A directly cleaves dystrophin and is inhibited by a dystrophin-based substrate analogue. J Biol Chem 275:11191–11197PubMedCrossRefGoogle Scholar
  56. 56.
    Sabel KG, Blomstrom-Lundqvist C, Olsson SB et al (1990) Arrhythmogenic right ventricular dysplasia in brother and sister: Is it related to myocarditis? Pediatr Cardiol 11:113–116PubMedCrossRefGoogle Scholar
  57. 57.
    Hisaoka T, Kawai S, Ohi H et al (1990) Two cases of chronic myocarditis mimicking arrhythmogenic right ventricular dysplasia. Heart Vessels 5:51–54Google Scholar
  58. 58.
    D’Amati G, Fiore F, Giordano C et al (1998) Pathologic evidence of arrhythmogenic cardiomyopathy and myocarditis in two sibilings. Cardiovasc Pathol 7:39–46CrossRefGoogle Scholar
  59. 59.
    Kasai Y, Takeda S, Takagi H (1996) Pathogenesis of hepatocellular carcinoma: A review from the viewpoint of molecular analysis. Semin Surg Oncol 12:155–159PubMedCrossRefGoogle Scholar
  60. 60.
    Wentzensen N, Vinokurova S, von Knebel Doeberitz M (2004) Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res 64:3878–3884Google Scholar
  61. 61.
    Calabrese F, Thiene G (2003) Myocarditis and inflammatory cardiomyopathy: Microbiological and molecular biological aspects. Cardiovasc Res 60:11–25PubMedCrossRefGoogle Scholar
  62. 62.
    Noutsias M, Fechner H, de Jonge H et al (2001) Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulated in dilated cardiomyopathy: Implications for cardiotropic viral infections. Circulation 104:275–280PubMedGoogle Scholar
  63. 63.
    Fechner H, Noutsias M, Tschoepe C et al (2003) Induction of coxsackievirus-adenovirus-receptor expression during myocardial tissue formation and remodeling: Identification of a cell-to-cell contact-dependent regulatory mechanism. Circulation 107:876–882PubMedCrossRefGoogle Scholar
  64. 64.
    Liu P, Aitken K, Kong YY et al (2000) The tyrosine kinase p56lck is essential in coxsackievirus B3-mediated heart disease. Nat Med 6:429–434PubMedCrossRefGoogle Scholar
  65. 65.
    Deonarain R, Cerullo D, Fuse K et al (2004) Protective role for interferon-beta in coxsackievirus B3 infection. Circulation 110:3540–3543PubMedCrossRefGoogle Scholar
  66. 66.
    Xiong D, Lee GH, Bardoff C et al (2002) Dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy: A genetic predisposition to viral heart disease. Nat Med 8:872–877PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2007

Authors and Affiliations

  • Fiorella Calabrese
    • 1
  • Elisa Carturan
    • 1
  • Gaetano Thiene
    • 1
  • Jeffrey A. Towbin
    • 2
  1. 1.Department of Medical Diagnostic SciencesUniversity of PaduaItaly
  2. 2.Pediatric Cardiology, Texas Children’s HospitalBaylor College of MedicineHoustonUSA

Personalised recommendations