Review article: Biomedical intelligence
Vol. 144 No. 3940 (2014)
Viral myocarditis
- Uwe Kühl
- Heinz-Peter Schultheiss
Summary
The term myocarditis describes inflammatory disorders of the heart muscle of varied infectious and non-infectious origins. It can be caused by any kind of infection, drugs, toxic substances, or be associated with autoimmune conditions. Viruses are the main causes at least in developed countries. Acute myocarditis most commonly results from an external inflammatory trigger inducing the host immune response, which may range from minimally transient response to fulminant overwhelming cellular infiltration. If the immune system does not eliminate the infectious pathogen early on, chronic infection develops with or without accompanying inflammation. Post-infectious autoimmunity may persist despite effective virus clearance.
Since the pathological conditions take place at the cellular level, viral myocarditis and postinfectious autoimmunity can be suggested but not diagnosed clinically. All clinical methods including imaging techniques are misleading if infectious agents are involved. Accurate diagnosis demands simultaneous histologic, immunohistochemical and molecular biological workup of the tissue. If the primary infectious or immune-mediated causes of the disease are carefully defined by clinical and biopsy based tools, specific antiviral treatment options in addition to basic symptomatic therapy are available under certain conditions. These may allow a tailored cause-specific treatment that improves symptoms and prognosis of patients with acute and chronic disease.
References
- Holzmann M, Nicko A, Kühl U, et al. Complication rate in right ventricular endomyocardial biopsy – A retro- and prospective study over a 11 year period analyzing 3048 diagnostic procedures. Circulation. 2008;2008:1722–8.
- Chimenti C, Frustaci A. Contribution and risks of left ventricular endomyocardial biopsy in patients with cardiomyopathies: retrospective study over a 28–year period. Circulation. 2013;128:1531–41.
- Caforio AL, Pankuweit S, Arbusti E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Europ Heart J. 2013;34:2636–48.
- Kuehl U, Schultheiss HP. Myocarditis in children. Heart Fail Clin. 2011;6:483–96.
- Frustaci A, Chimenti C, Calabrese F, et al. Immunosuppressive therapy for active lymphocytic myocarditis: virological and immunologic profile of responders versus nonresponders. Circulation. 2003;107:857–63.
- Schultheiss HP, Kuehl U, Cooper LT. The Management of Myocarditis. Eur Heart J. 2011;32:2616–65.
- Kuehl U, Lassner D, Dorner A, et al. A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression Basic Research Cardiology. 2013;108:372–82.
- Blauwet LA, Cooper LT. Myocarditis. Prog Cardiovasc Dis. 2010;52:274–88.
- Liu PP, Schultheiss HP. Myocarditis. In: Baunwald ed, Heart Disease. 8 ed. Philadelphia: W B Saunders co. 2008:1775–92.
- Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008;29:270–6.
- Dec GW, Jr., Palacios IF, Fallon JT, et al. Active myocarditis in the spectrum of acute dilated cardiomyopathies. Clinical features, histologic correlates, and clinical outcome. N Engl J Med. 1985;312:885–90.
- Pauschinger M, Bowles NE, Fuentes-Garcia FJ, et al. Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction. Circulation. 1999;99:1348–54.
- 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;42:466–72.
- Kühl 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;111:887–93.
- Breinholt JP, Moulik M, Dreyer WJ, et al. Viral epidemiologic shift in inflammatory heart disease: the increasing involvement of parvovirus B19 in the myocardium of pediatric cardiac transplant patients. J Heart Lung Transplant. 2010;29:739–46.
- Towbin JA, Ware SM, Jefferies JL. Heart transplants in pediatric patients: viral infection as a loss predictor. Future Cardiology. 2010;6:735–41.
- Kandolf R. Virus etiology of inflammatory cardiomyopathy. Dtsch Med Wochenschr 2004;129:2187–92.
- Norja P, Hokynar K, Aaltonen LM, et al. Bioportfolio: Lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue. Proc Natl Acad Sci U S A. 2006;103:7450–53.
- Pellett PE, Ablashi DV, Ambros PF, et al. Chromosomally integrated human herpesvirus 6: questions and answers. Rev Med Virol. 2012;22:144–55.
- Kereiakes DJ, Parmley WW. Myocarditis and cardiomyopathy. Am Heart J. 1984;108:1318–26.
- Mason JW. Myocarditis and dilated cardiomyopathy: an inflammatory link. Cardiovasc Res. 2003;60:5–10.
- Liu PP, Opavsky MA. Viral myocarditis: receptors that bridge the cardiovascular with the immune system? Circ Res. 2000;86:253–4.
- Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science. 1997;275:1320–3.
- Kandolf R, Ameis D, Kirschner P, Canu A, Hofschneider PH. 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 U S A. 1987;84:6272–6.
- Fairweather D, Frisancho-Kiss S, Rose NR. Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus-induced myocarditis. Rev Med Virol. 2005;15:17–27.
- Streitz M, Noutsias M, Volkmer R, et al. NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy. PLoS ONE. 2008;3:e2361.
- Mason JW. Immunopathogenesis and treatment of myocarditis: the United States Myocarditis Treatment Trial. J Card Fail. 1996;2:S173–77.
- Pauschinger M, Chandrasekharan K, Schultheiss HP. Myocardial remodeling in viral heart disease: possible interactions between inflammatory mediators and MMP-TIMP system. Heart Fail Rev. 2004;9:21–31.
- Heymans S, Pauschinger M, De Palma A, et al. Inhibition of urokinase-type plasminogen activator or matrix metalloproteinases prevents cardiac injury and dysfunction during viral myocarditis. Circulation. 2006;114:565–73.
- 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;28:1326–33.
- Baboonian C, Treasure T. Meta-analysis of the association of enteroviruses with human heart disease. Heart. 1997;78:539–43.
- D’Ambrosio A, Patti G, Manzoli A, et al. The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review. Heart. 2001;85:499–504.
- Towbin JA, Lowe AM, Colan SD, et al. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA. 2006;296:1867–76.
- Noutsias M, Fechner H, de Jonge H, et al. 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. 2001;104:275–80.
- Fujioka S, Kitaura Y, Ukimura A, et al. Evaluation of viral infection in the myocardium of patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2000;36:1920–6.
- Bultmann BD, Klingel K, Sotlar K, et al. Fatal parvovirus B19–associated myocarditis clinically mimicking ischemic heart disease: an endothelial cell-mediated disease. Hum Pathol. 2003;34:92–5.
- Bock CT, Klingel K, Aberle S, et al. Human Parvovirus B19: A new emerging pathogen of inflammatory cardiomyopathy. J Vet Med B. 2005;52:340–3.
- Klingel K, Sauter M, Bock CT, et al. Molecular pathology of inflammatory cardiomyopathy. Med Microbiol Immunol (Berl). 2004;193:101–7.
- Di Luca D, Mirandola P, Ravaioli T, Bigoni B, Cassai E. Distribution of HHV-6 variants in human tissues. Infect Agents Dis. 1996;5:203–14.
- Caruso A, Rotola A, Comar M, et al. HHV-6 infects human aortic and heart microvascular endothelial cells, increasing their ability to secrete proinflammatory chemokines. J Med Virol. 2002;67:528–33.
- Fotheringham J, Akhyani N, Vortmeyer A, et al. Detection of active human herpesvirus-6 infection in the brain: correlation with polymerase chain reaction detection in cerebrospinal fluid. J Infect Dis. 2007;195:450–4.
- Krueger GRF, Rojo J-, Buja LM, Lassner D, Kuehl U. Human herpesvirus-6 (HHV-6) is a possible cardiac pathogen: An immunihistological and ultrastructural study. Hospital General. 2008;71:187–91.
- Arbuckle JH, Medveczky MM, Luka J, et al. The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc Natl Acad Sci U S A. 2010;107:5563–8.
- Why HJ, Meany BT, Richardson PJ, et al. Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy. Circulation. 1994;89:2582–9.
- Kuehl U, Lassner D, von Schlippenbach J, Poller W, Schultheiss H-P. Interferon-beta- Improves Survival in Enterovirus-Associated Cardiomyopathy. J Am Coll Cardiol. 2012;60:1295–6.
- Kühl U, Pauschinger M, Seeberg B, et al. Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation. 2005;112:1965–70.
- Kühl 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;107:2793–8.
- Schmidt-Lucke C, Spillmann F, Bock T, et al. Interferon Beta Modulates Endothelial Damage in Patients with Cardiac Persistence of Human Parvovirus B19 Infection. J Infect Dis. 2010;201:6.
- Moulik M, Breinholt JP, Dreyer WJ, et al. Viral endomyocardial infection is an independent predictor and potentially treatable risk factor for graft loss and coronary vasculopathy in pediatric cardiac transplant recipients. J Am Coll Cardiol. 2010;56:582–92.
- Chen J, Kuhlencordt P, Urano F, et al. Effects of chronic treatment with L-arginine on atherosclerosis in apoE knockout and apoE/inducible NO synthase double-knockout mice. Arterioscler Thromb Vasc Biol. 2003;23:97–103.
- Kuehl U, Lassner D, Wallaschek N, Gross U, Krueger GRF, et al. Chromosomally integrated human herpesvirus 6 in heart failure – prevalence and treatment. Eur J Heart Failure. 2014; in press.