Skip to main content

Advertisement

Log in

Viral heart disease: molecular diagnosis, clinical prognosis, and treatment strategies

  • Review
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

Myocarditis is considered as a potent predisposing factor for dilated cardiomyopathy (DCM). Molecular biological proof of viral genome and immunohistochemical evaluation of intramyocardial inflammation are substantial in the identification and diagnosis of this pathological condition. Viruses are generally thought to be the common causative agents that trigger myocarditis and, therefore, several investigations are indispensable for the detection of viral genome in the myocardium in diagnosing viral myocarditis. The era of molecular diagnosis for viral myocarditis began with the establishment of the slot blot hybridization technique for the detection of viral genome in endomyocardial biopsy specimens. Due to inherent technical inadequacies, this method soon was replaced by in situ hybridization and polymerase chain reaction (PCR). Although in situ hybridization combines both morphological and molecular diagnosis, difficulty in standardization, possibility of nonspecific hybridization, and focal viral infection have led PCR to be an ideal molecular diagnostic strategy for the detection of viral myocarditis. Despite controversies over the specificity of this technique, several studies have substantiated the use of PCR in virological diagnosis. The ability to detect the state of viral replicative activity by demonstrating the presence of enteroviral minus-strand RNA has added a new dimension to studies on viral etiology of myocarditis and DCM. Advances in molecular diagnosis have indicated beyond doubt that persistence of viral infection is associated with disease deterioration and poor prognosis. Viral etiology of myocarditis and its contribution to the development of DCM have suggested antiviral therapy for myocarditis and DCM patients with proven viral infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Abelmann WH (1973) Viral myocarditis and its sequelae. Annu Rev Med 24:145–152

    Google Scholar 

  2. Baboonian C, Treasure T (1997) Meta-analysis of the association of enteroviruses with human heart disease. Heart 78:539–543

    CAS  PubMed  Google Scholar 

  3. Baykurt C, Caglar K, Ceviz N, et al (1999) Successful treatment of Epstein-Barr virus infection associated with myocarditis. Pediatr Int 41:389–391

    Article  PubMed  Google Scholar 

  4. Bowles NE, Vallejo J (2003) Viral causes of cardiac inflammation. Curr Opin Cardiol 18:182–188

    Article  PubMed  Google Scholar 

  5. Bowles NE, Richardson PJ, Olsen EG, Archard LC (1986) Detection of Coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet I:1120–1123

    Article  Google Scholar 

  6. Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R, Hare J, Bricker JT, Bowles KR, Towbin JA (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 42:466–472

    Article  PubMed  Google Scholar 

  7. Braimbridge MV, Darracott S, Chayen J, Bitensky L, Poulter LW (1967) Possibility of a new infective etiological agent in congestive cardiomyopathy. Lancet I:171–176

    Google Scholar 

  8. Calabrese F, Rigo E, Milanesi O, Boffa GM, Angelini A, Valente M, Thiene G (2002) Molecular diagnosis of myocarditis and dilated cardiomyopathy in children: clinicopathologic features and prognostic implications. Diagn Mol Pathol 11:212–221

    Article  PubMed  Google Scholar 

  9. Dec GW Jr, Palacios IF, Fallon JT, et al (1985) Active myocarditis in the spectrum of acute dilated cardiomyopathies. Clinical features, histologic correlates, and clinical outcome. N Engl J Med 312:885–890

    PubMed  Google Scholar 

  10. Elliot P (2000) Diagnosis and management of dilated cardiomyopathy. Eur Heart J 84:106–112

    Google Scholar 

  11. Feldmann AM, McNamara D (2000) Myocarditis. N Engl J Med 343:1388–1398

    Article  CAS  PubMed  Google Scholar 

  12. Fujioka S, Kitaura Y, Ukimura A, Deguchi H, Kawamura K, Isomura T, Suma H, Shimizu A (2000) Evaluation of viral infection in the myocardium of patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 36:1920–1926

    CAS  Google Scholar 

  13. Grasso M, Arbustini E, Silini E, Diegoli M, Percivalle E, Ratti G, Bramerio M, Gavazzi A, Vigano M, Milanesi G (1992) Search for coxsackievirus B3 RNA in idiopathic dilated cardiomyopathy using gene amplification by polymerase chain reaction. Am J Cardiol 69:658–664

    PubMed  Google Scholar 

  14. Grogan M, Redfield MM, Bailey KR, et al (1995) Long-term outcome of patients with biopsy-proved myocarditis: comparison with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 26:80–84

    Article  PubMed  Google Scholar 

  15. Grumbach IM, Heim A, Pring-Akerblom P, Vonhof S, Hein WJ, Muller G, Figulla HR (1999) Adenoviruses and enteroviruses as pathogens in myocarditis and dilated cardiomyopathy. Acta Cardiol 54:83–88

    CAS  PubMed  Google Scholar 

  16. Heim A, Canu A, Kirschner P, et al (1992) Synergistic interaction of interferon-beta and interferon-gamma in coxsackievirus B3-infected carrier cultures of human myocardial fibroblasts. J Infect Dis 166:958–965

    CAS  PubMed  Google Scholar 

  17. Hohenadl C, Klingel K, Mertsching J, Hofschneider PH, Kandolf R (1991) Strand-specific detection of enteroviral RNA in myocardial tissue by in situ hybridization. Mol Cell Probes 5:11–20

    PubMed  Google Scholar 

  18. Jin O, Sole MJ, Butany JW, Chia WK, McLaughlin PR, Liu P, Liew CC (1990) Detection of enterovirus RNA in myocardial biopsies from patients with myocarditis and cardiomyopathy using gene amplification by polymerase chain reaction. Circulation 82:8–16

    PubMed  Google Scholar 

  19. Kandolf R, Hofshneider PH (1989) Viral heart disease. Springer Semin Immunopathol 11:1–13

    CAS  Google Scholar 

  20. Kandolf R, Ameis D, Kirschner P, Canu A, Hofschnieder PH (1987) In situ detection of enteroviral genomes in myocardial cells by nucleic acid hybridization: an approach to the diagnosis of viral heart disease. Proc Natl Acad Sci USA 84:6272–6276

    CAS  PubMed  Google Scholar 

  21. Kühl U, Pauschinger M, Bock T, Klingel K, Schwimmbeck CP, Seeberg B, Krautwurm L, Poller W, Schultheiss HP, Kandolf R (2003) Parvovirus B19 infection mimicking acute myocardial infarction. Circulation 108:945–950

    Article  PubMed  Google Scholar 

  22. Kühl U, Pauschinger M, Schwimmbeck PL, Seeberg B, Lober C, Noutsias M, Poller W, Schultheiss H-P (2003) Interferon-β treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction. Circulation 107:2793–2798

    Article  PubMed  Google Scholar 

  23. Martin AB, Webber S, Fricker FJ, Jaffe R, Demmler G, Kearney D, Zhang Y-H, Bodurtha J, Gelb B, Ni J, Bricker T, Towbin JA (1994) Acute myocarditis: rapid diagnosis by PCR in children. Circulation 90:330–339

    CAS  PubMed  Google Scholar 

  24. Matsumori A, Tomioka N, Kawai C (1988) Protective effect of recombinant alpha interferon on coxsackievirus B3 myocarditis in mice. Am Heart J 115:1229–1232

    CAS  PubMed  Google Scholar 

  25. McCarthy RE, Boehmer JP, hruban RH, et al (2000) Long-terme outcome of fulminant myocarditis as compared with acute (non-fulminant) myocarditis. N Engl J Med 342:734–735

    Article  PubMed  Google Scholar 

  26. Miric M, Vasiljevic J, Bojic M, Popovic Z, Keserovic N, Pesic M (1996) Long-term follow up of patients with dilated heart muscle disease treated with human leucocytic interferon alpha or thymic hormones initial results. Heart 75:596–601

    PubMed  Google Scholar 

  27. Pankuweit S, Moll R, Baandrup U, Portig I, Hufnagel G, Maisch B (2003) Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens. Hum Pathol 34:497–503

    Article  PubMed  Google Scholar 

  28. Pauschinger M, Doerner A, Remppis A, Tannhauser R, Kühl U, Schultheiss HP (1998) Differential myocardial abundance of collagen type I and type III mRNA in dilated cardiomyopathy: effects of myocardial inflammation. Cardiovasc Res 37:123–129

    CAS  PubMed  Google Scholar 

  29. Pauschinger M, Kühl U, Dörner A, Schieferecke K, Petschauer S, Rauch U, Schwimmbeck PL, Kandolf R, Schultheiss HP (1998) Nachweis enteroviraler RNA in endomyokardialen Biopsien bei inflammatorischer Kardiomyopathie und idiopathischer dilatativer Kardiomyopathie. Z Kardiol 87:443–452

    CAS  PubMed  Google Scholar 

  30. Pauschinger M, Bowles NE, Fuentes-Garcia FJ, Pham V, Kuhl U, Schwimmbeck PL, Schultheiss HP, Towbin JA (1999) Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction. Circulation 99:1348–1354

    CAS  PubMed  Google Scholar 

  31. Pauschinger M, Doerner A, Kuehl U, Schwimmbeck PL, Poller W, Kandolf R, Schultheiss HP (1999) Enteroviral RNA replication in the myocardium of patients with left ventricular dysfunction and clinically suspected myocarditis. Circulation 99:889–895

    CAS  PubMed  Google Scholar 

  32. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connel J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P (1996) Report of the 1995 world health organization/international society and federation of cardiology task force on the definition and classification of cardiomyopathies. Circulation 93:841–842

    PubMed  Google Scholar 

  33. Schonian U, Crombach M, Maser S, Maisch B (1995) Cytomegalovirus-associated heart muscle disease. Eur Heart J 16(Suppl O):46–49

    Google Scholar 

  34. Schowengerdt KO, Ni J, Denfield SW, Gajarski RJ, Bowles NE, Rosenthal G, Kearney DL, Price JK, Rogers BB, Schauer GM, Chinnock RE,Towbin JA (1997) Association of parvovirus B19 genome in children with myocarditis and cardiac allograft rejection: diagnosis using the polymerase chain reaction. Circulation 96:3549–3554

    CAS  PubMed  Google Scholar 

  35. Tracy S, Wiegand V, McManus B, et al (1990) Molecular approaches to enteroviral diagnosis in idiopathic cardiomyopathy and myocarditis. J Am Coll Cardiol 15:1688–1694

    CAS  PubMed  Google Scholar 

  36. Why HJ, Meany BT, Richardson PJ, Olsen EG, Bowles NE, Cunningham L, Freeke CA, Archard LC (1994) Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy. Circulation 89:2582–2589

    CAS  PubMed  Google Scholar 

  37. Woodruff JF (1980) Viral myocarditis: a review. Am J Pathol 101:425–484

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matthias Pauschinger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pauschinger, M., Chandrasekharan, K., Noutsias, M. et al. Viral heart disease: molecular diagnosis, clinical prognosis, and treatment strategies. Med Microbiol Immunol 193, 65–69 (2004). https://doi.org/10.1007/s00430-003-0213-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-003-0213-y

Keywords

Navigation