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The Role of Viral Infections in the Development of Dilated Cardiomyopathy

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Pathology & Oncology 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.

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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

References

  1. Goodwin JF, Oakley CM (1972) The cardiomyopathies. Br Heart J 34(6):545–552

    Article  PubMed  CAS  Google Scholar 

  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):672–673

    Article  Google Scholar 

  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):841–842

    PubMed  CAS  Google Scholar 

  4. Mason JW (2003) Myocarditis and dilated cardiomyopathy: an inflammatory link. Cardiovasc Res 60(1):5–10

    Article  PubMed  CAS  Google Scholar 

  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):466–472

    Article  PubMed  Google Scholar 

  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):290–300

    Article  PubMed  CAS  Google Scholar 

  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):1046–1052

    Article  PubMed  Google Scholar 

  8. Woodruff JF (1980) Viral myocarditis. A review. Am J Pathol 101(2):425–484

    PubMed  CAS  Google Scholar 

  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):80–83

    Article  PubMed  CAS  Google Scholar 

  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):632–636

    Article  PubMed  CAS  Google Scholar 

  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):4585–4587

    Article  PubMed  CAS  Google Scholar 

  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):792–795

    Article  PubMed  CAS  Google Scholar 

  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):152–157

    Article  PubMed  Google Scholar 

  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):416–420

    Article  PubMed  Google Scholar 

  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):274–276

    PubMed  CAS  Google Scholar 

  16. Dennert R, Crijns HJ, Heymans S (2008) Acute viral myocarditis. Eur Heart J 29:2073–2082

    Article  PubMed  Google Scholar 

  17. Caforio AL (1994) Role of autoimmunity in dilated cardiomyopathy. Br Heart J 72(6 Suppl):S30–34

    Article  PubMed  CAS  Google Scholar 

  18. Martin AB, Webber S, Fricker FJ et al (1994) Acute myocarditis. Rapid diagnosis by PCR in children. Circulation 90(1):330–339

    PubMed  CAS  Google Scholar 

  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):857–865

    Article  PubMed  CAS  Google Scholar 

  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):1348–1354

    PubMed  CAS  Google Scholar 

  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):133–140

    Article  PubMed  CAS  Google Scholar 

  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):32–39

    Article  PubMed  CAS  Google Scholar 

  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):269–272

    Article  PubMed  CAS  Google Scholar 

  24. Tátrai E, Hartyánszky I, Lászik A et al (2007) Molecular biological virus identification in dilated cardiomyopathy. Orvosi Hetilap 148(48):2275–2278

    Article  PubMed  Google Scholar 

  25. Mahrholdt H, Wagner A, Deluigi CC et al (2006) Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation 114(15):1581–1590

    Article  PubMed  Google Scholar 

  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):1235–1245

    PubMed  CAS  Google Scholar 

  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):887–893

    Article  PubMed  Google Scholar 

  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):2793–2798

    Article  PubMed  Google Scholar 

  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):5–8

    Article  PubMed  Google Scholar 

  30. Lawson CM (2000) Evidence for mimicry by viral antigens in animal models of autoimmune disease including myocarditis. Cell Mol Life Sci 57(4):552–560

    Article  PubMed  CAS  Google Scholar 

  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):565–573

    Article  PubMed  CAS  Google Scholar 

  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):1734–1742

    PubMed  CAS  Google Scholar 

  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):528–533

    Article  PubMed  CAS  Google Scholar 

  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):17–24

    Article  PubMed  CAS  Google Scholar 

  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):233–240

    PubMed  CAS  Google Scholar 

  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):53–59

    Article  PubMed  CAS  Google Scholar 

  37. Petitjean J, Kopecka H, Freymuth F et al (1992) Detection of enteroviruses in endomyocardial biopsy by molecular approach. J Med Virol 37(1):76–82

    Article  PubMed  CAS  Google Scholar 

  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):256–259

    Article  PubMed  Google Scholar 

  39. Mahon NG, Zal B, Arno G et al (2001) Absence of viral nucleic acids in early and late dilated cardiomyopathy. Heart 86(6):687–692

    Article  PubMed  CAS  Google Scholar 

  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):156–159

    Article  PubMed  CAS  Google Scholar 

  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):1807–1816

    Article  PubMed  Google Scholar 

  42. Osterziel KJ, Scheffold T, Perrot A et al (2001) Genetics of dilated cardiomyopathy. Z Kardiol 90(7):461–469

    Article  PubMed  CAS  Google Scholar 

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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.

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Authors and Affiliations

  1. Department of Forensic & Insurance Medicine, Semmelweis University, Budapest, 93 Ulloi str., 1091, Budapest, Hungary

    Enikő Tátrai, András Lászik, Péter Sótonyi & Márta Hubay

  2. Vascular- and Cardiac Surgery Clinic, Semmelweis University, Budapest, 68 Varosmajor str., 1122, Budapest, Hungary

    István Hartyánszky Jr. & György Acsády

Authors
  1. Enikő Tátrai
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  2. István Hartyánszky Jr.
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  3. András Lászik
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Correspondence to Enikő Tátrai.

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Tátrai, E., Hartyánszky, I., Lászik, A. et al. The Role of Viral Infections in the Development of Dilated Cardiomyopathy. Pathol. Oncol. Res. 17, 229–235 (2011). https://doi.org/10.1007/s12253-010-9302-6

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  • DOI: https://doi.org/10.1007/s12253-010-9302-6

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