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Pathology & Oncology Research

, Volume 17, Issue 2, pp 229–235 | Cite as

The Role of Viral Infections in the Development of Dilated Cardiomyopathy

  • Enikő TátraiEmail author
  • István HartyánszkyJr.
  • András Lászik
  • György Acsády
  • Péter Sótonyi
  • Márta Hubay
Research

Abstract

Enteroviruses (EVs) are the most frequent pathogens in myocarditis and in the subsequently developing dilated cardiomyopathy as well. Furthermore, persistence of other viruses might play a pathogenic role in the evolution from myocarditis to dilated cardiomyopathy. Explanted heart of 28 patients, who underwent heart transplantation were screened for EV, AdV3 and HHV6 sequences in order to assess the incidence of cardiac viral infection that may be implicated in the pathogenesis of cardiomyopathy, and estimate viral distribution in the myocardium. Viral sequences were extracted from five different regions of the hearts. Nested PCR was used to amplify conservative regions of AdV3, HHV6 and EVs. Histological examination was performed on routinely processed myocardial samples. AdV3 was verified in one fourth of the patients. ADV3 and HHV6 sequences coexisted in one case with inflammatory cardiomyopathy. Some patients had more than one positive area of their heart. AdV3 positive right ventricular samples were double in amount compared to the left ones. None of the patients had positive result for EV. This is the first occasion to identify AdV3 (a mainly respiratory infective virus) sequence in explanted hearts of cardiomyopathy patients. Though the clinical importance of our results is still unclear, AdV3 could be a new member of the viral group with possible pathogenic effect on the myocardium. Regional distribution of viral sequence location confirmed that the right ventricular wall as a biopsy sampling site might be adequate for endomyocardial biopsy pro diagnostic purposes.

Keywords

Cardiomyopathy Endomyocardial biopsy Myocardium Polymerase chain reaction Viruses 

Abbreviations

AdV2

Adenovirus type 2

AdV3

Adenovirus type 3

AdV5

Adenovirus type 5

CM

Cardiomyopathy

DCM

Dilated cardiomyopathy

DNA

Deoxyribonucleic acid

EMB

Endomyocardial biopsy

EV

Enterovirus

HHV6

Human Herpes Virus type 6

MC

Myocarditis

NCBI

National Centre for Biotechnology Information

neg.

negative result

PCR

Polymerase chain reaction

PTAH

Phosphotungstic acid-haematoxylin

PVB19

Parvovirus B19

RNA

Ribonucleic acid

WHO

World Health Organization

Notes

Acknowledgements

This study was supported by grant No. ETT 165/2006. We express our gratitude to Ilona Kovalszky and Katalin Bedi at the 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest.

References

  1. 1.
    Goodwin JF, Oakley CM (1972) The cardiomyopathies. Br Heart J 34(6):545–552PubMedCrossRefGoogle Scholar
  2. 2.
    Brandenburg RO, Chazov E, Cherian G et al (1980) Report of the WHO/ISFC task force on the definition and classification of cardiomyopathies. Br Heart J 44(6):672–673CrossRefGoogle Scholar
  3. 3.
    Richardson P, McKenna W, Bristow M et al (1996) Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 93(5):841–842PubMedGoogle Scholar
  4. 4.
    Mason JW (2003) Myocarditis and dilated cardiomyopathy: an inflammatory link. Cardiovasc Res 60(1):5–10PubMedCrossRefGoogle Scholar
  5. 5.
    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(3):466–472PubMedCrossRefGoogle Scholar
  6. 6.
    Basso C, Calabrese F, Corrado D et al (2001) Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings. Cardiovasc Res 50(2):290–300PubMedCrossRefGoogle Scholar
  7. 7.
    Francalanci P, Chance JL, Vatta M et al (2004) Cardiotropic viruses in the myocardium of children with end-stage heart disease. J Heart Lung Transplant 23(9):1046–1052PubMedCrossRefGoogle Scholar
  8. 8.
    Woodruff JF (1980) Viral myocarditis. A review. Am J Pathol 101(2):425–484PubMedGoogle Scholar
  9. 9.
    Comar M, D'Agaro P, Campello C et al (2009) Human herpes virus 6 in archival cardiac tissues from children with idiopathic dilated cardiomyopathy or congenital heart disease. J Clin Pathol 62(1):80–83PubMedCrossRefGoogle Scholar
  10. 10.
    Fukae S, Ashizawa N, Morikawa S et al (2000) A fatal case of fulminant myocarditis with human herpesvirus-6 infection. Intern Med 39(8):632–636PubMedCrossRefGoogle Scholar
  11. 11.
    Rohayem J, Dinger J, Fischer R et al (2001) Fatal myocarditis associated with acute parvovirus B19 and human herpesvirus 6 coinfection. J Clin Microbiol 39(12):4585–4587PubMedCrossRefGoogle Scholar
  12. 12.
    Yoshikawa T, Ihira M, Suzuki K et al (2001) Fatal acute myocarditis in an infant with human herpesvirus 6 infection. J Clin Pathol 54(10):792–795PubMedCrossRefGoogle Scholar
  13. 13.
    Savon C, Acosta B, Valdes O et al (2008) A myocarditis outbreak with fatal cases associated with adenovirus subgenera C among children from Havana City in 2005. J Clin Virol 43(2):152–157PubMedCrossRefGoogle Scholar
  14. 14.
    James L, Vernon MO, Jones RC et al (2007) Outbreak of human adenovirus type 3 infection in a pediatric long-term care facility–Illinois, 2005. Clin Infect Dis 45(4):416–420PubMedCrossRefGoogle Scholar
  15. 15.
    Herbert FA, Wilkinson D, Burchak E et al (1977) Adenovirus type 3 pneumonia causing lung damage in childhood. Can Med Assoc J 116(3):274–276PubMedGoogle Scholar
  16. 16.
    Dennert R, Crijns HJ, Heymans S (2008) Acute viral myocarditis. Eur Heart J 29:2073–2082PubMedCrossRefGoogle Scholar
  17. 17.
    Caforio AL (1994) Role of autoimmunity in dilated cardiomyopathy. Br Heart J 72(6 Suppl):S30–34PubMedCrossRefGoogle Scholar
  18. 18.
    Martin AB, Webber S, Fricker FJ et al (1994) Acute myocarditis. Rapid diagnosis by PCR in children. Circulation 90(1):330–339PubMedGoogle Scholar
  19. 19.
    Bowles NE, Kearney DL, Ni J et al (1999) The detection of viral genomes by polymerase chain reaction in the myocardium of pediatric patients with advanced HIV disease. J Am Coll Cardiol 34(3):857–865PubMedCrossRefGoogle Scholar
  20. 20.
    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(10):1348–1354PubMedGoogle Scholar
  21. 21.
    Rey L, Lambert V, Wattre P et al (2001) Detection of enteroviruses ribonucleic acid sequences in endomyocardial tissue from adult patients with chronic dilated cardiomyopathy by a rapid RT-PCR and hybridization assay. J Med Virol 64(2):133–140PubMedCrossRefGoogle Scholar
  22. 22.
    Donoso Mantke O, Nitsche A, Meyer R et al (2004) Analysing myocardial tissue from explanted hearts of heart transplant recipients and multi-organ donors for the presence of parvovirus B19 DNA. J Clin Virol 31(1):32–39PubMedCrossRefGoogle Scholar
  23. 23.
    Suedkamp M, Lissel C, Eiffert H et al (1999) Cardiac myocytes of hearts from patients with end-stage dilated cardiomyopathy do not contain Borrelia burgdorferi DNA. Am Heart J 138(2 Pt 1):269–272PubMedCrossRefGoogle Scholar
  24. 24.
    Tátrai E, Hartyánszky I, Lászik A et al (2007) Molecular biological virus identification in dilated cardiomyopathy. Orvosi Hetilap 148(48):2275–2278PubMedCrossRefGoogle Scholar
  25. 25.
    Mahrholdt H, Wagner A, Deluigi CC et al (2006) Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation 114(15):1581–1590PubMedCrossRefGoogle Scholar
  26. 26.
    Hauck AJ, Kearney DL, Edwards WD (1989) Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error. Mayo Clin Proc 64(10):1235–1245PubMedGoogle Scholar
  27. 27.
    Kuhl U, Pauschinger M, Noutsias M et al (2005) High prevalence of viral genomes and multiple viral infections in the myocardium of adults with “idiopathic” left ventricular dysfunction. Circulation 111(7):887–893PubMedCrossRefGoogle Scholar
  28. 28.
    Kuhl U, Pauschinger M, Schwimmbeck PL et al (2003) Interferon-beta treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction. Circulation 107(22):2793–2798PubMedCrossRefGoogle Scholar
  29. 29.
    Maekawa Y, Ouzounian M, Opavsky MA et al (2007) Connecting the missing link between dilated cardiomyopathy and viral myocarditis: virus, cytoskeleton, and innate immunity. Circulation 115(1):5–8PubMedCrossRefGoogle Scholar
  30. 30.
    Lawson CM (2000) Evidence for mimicry by viral antigens in animal models of autoimmune disease including myocarditis. Cell Mol Life Sci 57(4):552–560PubMedCrossRefGoogle Scholar
  31. 31.
    Heymans S, Pauschinger M, De Palma A et al (2006) Inhibition of urokinase-type plasminogen activator or matrix metalloproteinases prevents cardiac injury and dysfunction during viral myocarditis. Circulation 114(6):565–573PubMedCrossRefGoogle Scholar
  32. 32.
    Caforio AL, Grazzini M, Mann JM et al (1992) Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. Circulation 85(5):1734–1742PubMedGoogle Scholar
  33. 33.
    Caruso A, Rotola A, Comar M et al (2002) HHV-6 infects human aortic and heart microvascular endothelial cells, increasing their ability to secrete proinflammatory chemokines. J Med Virol 67(4):528–533PubMedCrossRefGoogle Scholar
  34. 34.
    Horvath R, Cerny J, Benedik J et al (2000) The possible role of human cytomegalovirus (HCMV) in the origin of atherosclerosis. J Clin Virol 16(1):17–24PubMedCrossRefGoogle Scholar
  35. 35.
    Ismail A, Khosravi H, Olson H (1999) The role of infection in atherosclerosis and coronary artery disease: a new therapeutic target. Heart Dis 1(4):233–240PubMedGoogle Scholar
  36. 36.
    Andreoletti L, Hober D, Decoene C et al (1996) Detection of enteroviral RNA by polymerase chain reaction in endomyocardial tissue of patients with chronic cardiac diseases. J Med Virol 48(1):53–59PubMedCrossRefGoogle Scholar
  37. 37.
    Petitjean J, Kopecka H, Freymuth F et al (1992) Detection of enteroviruses in endomyocardial biopsy by molecular approach. J Med Virol 37(1):76–82PubMedCrossRefGoogle Scholar
  38. 38.
    de Leeuw N, Melchers WJ, Balk AH et al (1998) No evidence for persistent enterovirus infection in patients with end-stage idiopathic dilated cardiomyopathy. J Infect Dis 178(1):256–259PubMedCrossRefGoogle Scholar
  39. 39.
    Mahon NG, Zal B, Arno G et al (2001) Absence of viral nucleic acids in early and late dilated cardiomyopathy. Heart 86(6):687–692PubMedCrossRefGoogle Scholar
  40. 40.
    Weiss LM, Liu XF, Chang KL et al (1992) Detection of enteroviral RNA in idiopathic dilated cardiomyopathy and other human cardiac tissues. J Clin Invest 90(1):156–159PubMedCrossRefGoogle Scholar
  41. 41.
    Maron BJ, Towbin JA, Thiene G et al (2006) Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 113(14):1807–1816PubMedCrossRefGoogle Scholar
  42. 42.
    Osterziel KJ, Scheffold T, Perrot A et al (2001) Genetics of dilated cardiomyopathy. Z Kardiol 90(7):461–469PubMedCrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2010

Authors and Affiliations

  • Enikő Tátrai
    • 1
    Email author
  • István HartyánszkyJr.
    • 2
  • András Lászik
    • 1
  • György Acsády
    • 2
  • Péter Sótonyi
    • 1
  • Márta Hubay
    • 1
  1. 1.Department of Forensic & Insurance MedicineSemmelweis UniversityBudapestHungary
  2. 2.Vascular- and Cardiac Surgery ClinicSemmelweis UniversityBudapestHungary

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