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[Cardiotropic DNA viruses and bacteria in the pathogenesis of dilated cardiomyopathy with or without inflammation]
S Pankuweit1, G Hufnagel, H Eckhardt
1Abteilung Innere Medizin-Schwerpunkt Kardiologie, Philipps-Universität Marburg. pankuwei@mailer.uni-marburg.de
Insights
Inflammatory cardiomyopathy, defined as myocarditis with cardiac dysfunction, is increasingly recognized. Viral persistence, particularly enteroviruses, adenoviruses, and cytomegaloviruses, plays a key role in its development and dilated cardiomyopathy.
Area of Science:
- Cardiology
- Infectious Diseases
- Pathology
Context:
- The 1995 WHO/ISFC task force defined inflammatory cardiomyopathy as myocarditis associated with cardiac dysfunction.
- Dilated cardiomyopathy with inflammation (DCMi) is characterized by over 14 lymphocytes/macrophages/mm³.
- Enteroviruses, adenoviruses, and cytomegaloviruses are implicated in the pathogenesis of inflammatory heart disease.
Purpose:
- To define inflammatory cardiomyopathy and its subtypes (idiopathic, autoimmune, infectious).
- To investigate the role of viral persistence and immunopathogenesis in dilated cardiomyopathy.
- To standardize diagnostic criteria for virally induced inflammatory cardiomyopathy using endomyocardial biopsies.
Summary:
- Endomyocardial biopsies analyzed by PCR and Southern blot are crucial for detecting viral persistence in cardiomyopathy.
- Cytomegalovirus-DNA was found in 10% of inflammatory cardiomyopathy cases, adenovirus-DNA in 17%, and Borreliosis in <1%.
- Viral DNA incidence in dilated cardiomyopathy without inflammation was similar for cytomegalovirus (12%) and adenovirus (15%), with Borreliosis at 0.5%.
Impact:
- Diagnostic criteria for virally induced inflammatory cardiomyopathy can be standardized.
- Immunohistochemical and molecular analyses of biopsies inform future therapeutic strategies.
- Treatment approaches vary: immunosuppression for virus-negative cases, immunomodulation for viral persistence, and antibiotics for Borreliosis.
Abstract:
In the report of the 1995 WHO/ISFC task force on the definition and classification of cardiomyopathies a new entity within the dilated cardiomyopathies was introduced as "inflammatory cardiomyopathy". It is defined as myocarditis associated with cardiac dysfunction. Idiopathic, autoimmune and infectious forms of inflammatory cardiomyopathy are now recognized through this definition. Dilated cardiomyopathy with inflammation (DCMi, chronic myocarditis) was also defined by a recent ISFC task force as > 14 lymphocytes/macrophages/mm3. Enteroviruses, adenoviruses and cytomegaloviruses are considered as main etiopathogenetic factors in the pathogenesis of inflammatory heart disease and have been demonstrated as important trigger for inflammatory cardiac disease. They may also cause dilated cardiomyopathy by viral persistence or secondary immunopathogenesis due to antigenic or molecular mimicry. For the detection of viral persistence the investigation of endomyocardial biopsies in patients with cardiomyopathy by the use of polymerase chain reaction and southern blot analysis is an important step for the standardization of diagnostic criteria on virally induced inflammatory cardiomyopathy. Present studies indicate an incidence of cytomegalovirus-DNA in patients with inflammatory cardiomyopathy in 10%, adenoviral-DNA in 17% and borreliosis only in rare cases (< 1%). In dilated cardiomyopathy without inflammation the respective incidences were for cytomegalovirus 12%, 15% for adenovirus and only 0.5% of cases for borreliosis. In addition the results of immunohistochemical analysis and molecular biological investigations of endomyocardial biopsies may have implications for future therapeutic studies. Depending on the etiology of the disease, immunosuppression may have benefit for patients with virus-negative cardiomyopathy with inflammation in contrast to patients with cytomegalo-, adenovirus-DNA or enteroviral persistence, in whom immunomodulation with hyperimmunoglobulins or immunoglobulins may be a feasible therapeutic option. Patients with a positive PCR for Borrelia burgdorferi should be treated with 3rd generation cephalosporines and/or sublactam.