Treatment Of Inflammatory Cardiomyopathy Research Articles

FN14 Signaling Plays a Pathogenic Role in a Mouse Model of Experimental Autoimmune Myocarditis

BackgroundThe pathogenesis of inflammatory cardiomyopathy is affected by the activation of autoimmune-mediated cascades. To study these cascades, we developed an experimental model of troponin I (TnI)-induced autoimmune myocarditis (EAM). One factor playing a pivotal role in the context of autoimmune disorders is the receptor fibroblast growth factor-inducible 14 (FN14). Thus, the impact of FN14 in the development of autoimmune myocarditis was investigated. Methods and ResultsTnI-immunization led to a significantly increased myocardial FN14 mRNA and protein expression in wild-type (wt) mice. To investigate the precise role of FN14 in EAM, FN14 knockout (ko) and wt littermates were immunized with TnI or control buffer. The animals were evaluated for cardiac parameters and indicators of myocardial injury. FN14 deficiency resulted in better cardiac performance, less myocardial inflammation, fibrosis, and cardiac damage. A lower myocardial mRNA expression of inflammatory cytokines and chemokines as well as their receptors could be demonstrated in TnI-immunized FN14ko compared to wt mice also immunized with TnI. Western blot analysis revealed a contribution of nuclear factor kappa-light-chain-enhancer of activated B cells to FN14-induced signaling cascades. ConclusionsIn the pathogenesis of autoimmune myocarditis, the inflammatory response to cardiac injury is attenuated in FN14ko mice. Thus, inhibition of FN14 in patients might represent a novel therapeutic strategy in the treatment of inflammatory cardiomyopathy.

Myocardial Diseases: Current Views on Etiopathogenesis, Diagnostic Modalities, and Therapeutic Options

Myocardial Diseases: Current Views on Etiopathogenesis, Diagnostic Modalities, and Therapeutic Options

Czech Inflammatory Cardiomyopathy Immunosuppression Trial (CZECH-ICIT): Randomized, multicentric study comparing the effect of two regimens of combined immunosuppressive therapy in the treatment of inflammatory cardiomyopathy: The aims and design of the trial

The intent of this article is to inform cardiology community with the aims and design of the open, randomized multicentric study comparing the effect of two regimens of combined immunosuppressive therapy with prednisone and azathioprine in the treatment of patients suffering from inflammatory cardiomyopathy with biopsy proven presence of myocardial inflammation and negative PCR findings for infectious cardiotropic agents. The authors of this study encourage cardiologists to active participation in this research project whose results may significantly contribute to improvement of the therapy of patients with inflammatory cardiomyopathy.

THE ROLE OF PARVOVIRUS B19 IN THE DEVELOPMENT OF INFLAMMATORY CARDIOMYOPATHY

The problem of inflammatory cardiomyopathy is discussed. The etiology, pathogenesis, diagnosis and treatment of inflammatory cardiomyopathy are considered with focus on the role of parvovirus B19.

Mesenchymal Stem Cells and Inflammatory Cardiomyopathy: Cardiac Homing and Beyond

Under conventional heart failure therapy, inflammatory cardiomyopathy usually has a progressive course, merging for alternative interventional strategies. There is accumulating support for the application of cellular transplantation as a strategy to improve myocardial function. Mesenchymal stem cells (MSCs) have the advantage over other stem cells that they possess immunomodulatory features, making them attractive candidates for the treatment of inflammatory cardiomyopathy. Studies in experimental models of inflammatory cardiomyopathy have consistently demonstrated the potential of MSCs to reduce cardiac injury and to improve cardiac function. This paper gives an overview about how inflammation triggers the functionality of MSCs and how it induces cardiac homing. Finally, the potential of intravenous application of MSCs by inflammatory cardiomyopathy is discussed.

Immunosuppressive and Antiviral Treatment of Inflammatory Cardiomyopathy

Inflammatory cardiomyopathy (ICMP) is characterized by myocarditis associated with cardiac dysfunction. Clinical presentation may include acute heart failure and cardiogenic shock, chronic heart failure, ventricular tachyarrhythmias or may mimic an acute coronary syndrome. Inspite of the recent improvements in non-invasive diagnostic techniques, such as cardiac magnetic resonance, the diagnostic gold standard is still the endomyocardial biopsy. In the last years, classical histological Dallas criteria have been significantly improved by the introduction of immunohistochemical and molecular biology techniques. Recent findings using these new diagnostic tests resulted in increased interest in ICMP and a better understanding of its pathophysiology, the recognition in overlap of virus-mediated damage, inflammation, and autoimmune dysregulation. Moreover, there is growing evidence that the treatment of these patients with specific strategies may be effective only if based on their immunological and virological characterization. Several studies suggest that patients with autoimmune ICMP can benefit from immunosuppressive treatment and immunoadsorption, as well as high dose immunoglobulins, showing a significant improvement of left ventricular function and heart failure symptoms. On the other hand, immunosuppressive treatment can be deleterious for ICMP patients with evidence of viral persistence, while antiviral treatments have been proven effective in this subgroup. The present review summarizes the recent advances in the diagnosis and risk stratification of ICMP, and reviews patents and treatment options for these patients.