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Current insights into the pathogenesis, diagnosis and therapy of inflammatory cardiomyopathy
Michel Noutsias1, Matthias Pauschinger, Wolfgang-Christian Poller
1Department of Cardiology and Pneumonology, University Hospital, Benjamin Franklin Free University of Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany. noutsias@zedat.fu-berlin.de
Insights
Dilated cardiomyopathy (DCM) is often caused by viral infections or autoimmunity. Differentiating these causes allows for targeted treatments, improving heart function and reducing inflammation.
Area of Science:
- Cardiology
- Virology
- Immunology
Background:
- Dilated cardiomyopathy (DCM) pathogenesis involves cardiotropic viruses and autoimmunity.
- Current diagnostic criteria for inflammatory cardiomyopathy (InfCM) lack sensitivity and specificity.
- InfCM is recognized by the WHO as a secondary cardiomyopathy in about 50% of DCM cases.
Purpose of the Study:
- To differentiate etiopathogenic pathways in DCM.
- To evaluate diagnostic and therapeutic strategies for InfCM.
- To investigate the role of viral persistence and autoimmunity in DCM.
Main Methods:
- Immunohistological analysis of immunocompetent infiltrates and cell adhesion molecules (CAMs).
- Detection of enteroviral and adenoviral genomes.
- Assessment of coxsackie-adenovirus receptor (CAR) expression.
- Evaluation of treatment responses to immunosuppression and interferon-beta.
Main Results:
- InfCM, characterized by specific infiltrates and CAM expression, is identified in 50% of DCM patients.
- Viral genomes (enterovirus, adenovirus) are detected in a significant proportion of DCM patients.
- Enteroviral persistence correlates with a worse prognosis.
- CAR induction is specific to 63% of DCM patients, suggesting a role in viral susceptibility.
- Interferon-beta therapy in viral persistence cases led to viral elimination, reduced inflammation, and improved cardiac function.
- Immunosuppressive treatment benefited autoimmune InfCM patients.
Conclusions:
- Biopsy-guided differentiation of DCM etiologies enables tailored treatments.
- Immunosuppression is effective for autoimmune InfCM.
- Antiviral immunomodulation, like interferon-beta, benefits DCM patients with viral persistence.
- Accurate diagnosis of InfCM is crucial for effective therapeutic strategies in DCM.
Abstract:
Persistence of cardiotropic viruses (enterovirus, adenovirus) and anticardiac autoimmunity constitute the predominant etiopathogenic pathways of dilated cardiomyopathy (DCM). The diagnosis of inflammatory cardiomyopathy (InfCM) imposes sensitivity and specificity requirements, which are not fulfilled by the histological Dallas Criteria. The immunohistological quantification and characterization of immunocompetent infiltrates and cell adhesion molecule (CAM) expression has endorsed a new entity of secondary cardiomyopathies acknowledged by the World Health Organization (WHO), InfCM, in approximately 50% of DCM patients. In the absence of viral persistence, InfCM patients benefit from immunosuppressive treatment. Enteroviral and adenoviral genomes have been detected in a significant proportion of DCM patients. Enteroviral persistence is associated with an adverse prognosis. The induction of the coxsackie-adenovirus receptor (CAR) exclusively in 63% of DCM patients, but not in other cardiomyopathies, might constitute a key molecular determinant for cardiotropic viral infections in DCM. In InfCM patients with enterovirus or adenoviral persistence, interferon-beta administration leads to viral elimination and cessation of the intramyocardial inflammation, paralleled by a significant improvement of left ventricular systolic function and heart failure symptoms. The biopsy-guided etiopathogenic differentiation of DCM has endorsed specific treatment strategies: immunosuppressive regimens are favorable in autoimmune InfCM, whereas patients with viral persistence benefit from antiviral immunomodulation.