Lack in Treatment Options for Virus-Induced Inflammatory Cardiomyopathy

Abstract

Downloaded from Van Linthout et al iPSCs and Virus-Induced Inflammatory Cardiomyopathy 541of human iPS-CM and CVB3 copy number in endomyocardial biopsies of corresponding patients are desired. As such, iPS-CM might have a prognostic value, only in relation to endomyocardial biopsies, the diagnostic gold standard. 24 It should also be recognized that via using iPS-CM as antiviral drug platform, only 1 aspect of the viral pathogenesis, that is, the direct cytotoxic effect of CVB3 in cardiomyocytes, is taken into account and not the systemic immune effects, 9 which are triggered by the virus. In addition, it should be addressed that concentrations of antiviral drugs tested on iPS-CM combining efficacy with absence of toxicity cannot necessarily be extrapolated to the human in vivo condition. Last, but most importantly, the prevalence of enteroviral-positive patients is relatively low today. Predominantly, patients with inflammatory cardiomyopathy have Parvovirus B19-positive endomyocardial biopsies.25 In contrast to enteroviruses for which immunomodulation with interferon might be a therapeutic option, there are no specific antiviral strategies for Parvovirus B19 identified so far. Hereby, it is important to take into account that Parvovirus B19 leads, in contrast to enteroviruses, to a predominant endothelial infection. 26,27 Therefore, it will be a further challenge and need to set up iPS-derived endothelial cells and to screen for anti-Parvovirus B19 pharmaca in the near future, too. AcknowledgmentsThis study is supported by the German Center for Cardiovascular Research (DZHK) to S. Van Linthout and C. Tschöpe. DisclosuresNone. Nature. 2011;471:225-229. 22 References

Clinical impact of the presence of macrophages in endomyocardial biopsies of patients with dilated cardiomyopathy

“…The disease progression of dilated cardiomyopathy (DCM) is highly diverse because of its aetiological and pathophysiological heterogeneity . Recent clinical and experimental evidence has suggested that immune activation and the consequential inflammatory response in the myocardium may be involved in the process of deteriorating cardiac function, providing a rationale for immunosuppressive therapy in patients with virus‐negative inflammatory cardiomyopathy . Some of the clinical investigations showed a favourable outcome resulting from immunosuppression, in particular for patients selected on the basis of their immunohistochemical histology .…”

Immunomodulation by adoptive regulatory T‐cell transfer improves Coxsackievirus B3‐induced myocarditis

“…Global immunosuppressive interventions with corticosteroids or calcineurin-inhibitors applied during viral persistence phases failed because of an exacerbation of the virus and have been shown to be limited in efficacy during the later phase of the disease as early damages were not reversible. Similarly, interventions with immunoglobulin were ineffective, and antiviral approaches with IFN are still a matter of debate (8,9). Myocarditis remains a major challenge in modern cardiology and underscores the need to explore innovative therapeutic options and specific immunomodulatory interventions that allow a sufficient antiviral defense with a balanced cytokine response that prevents hyperactive inflammatory toxicity.…”

Telbivudine in chronic lymphocytic myocarditis and human parvovirus B19 transcriptional activity

“…Parvovirus B19 is implicated as a pathogen in the majority of chronic myocarditis cases . However, direct evidence showing a direct causal relationship between B19V cardiac presence and myocarditis is still missing, as well as therapies for B19V‐associated inflammatory cardiomyopathy …”

“…3 However, direct evidence showing a direct causal relationship between B19V cardiac presence and myocarditis is still missing, as well as therapies for B19V-associated inflammatory cardiomyopathy. 19 The strongest risk factor for impaired outcome in chronic myocarditis and inflammatory cardiomyopathy is the Figure 5 In situ tissue typing of endomyocardial biopsies in parvovirus B19-positive myocarditis patients before (mRNA+) and after telbivudine treatment (mRNAÀ) via imaging mass spectrometry. (A) Probabilistic latent semantic analysis could distinguish the protein signatures of the B19V mRNA+ (red) and B19V mRNAÀ (blue) patients (Patients 3 and 4 of Table 1).…”

“…17 The unclarity about the pathogenic role of B19V in myocarditis and DCM, partly due to the absence of experimental in vivo models, has hampered the search for potential B19V-targeted therapies. 19 Nevertheless, there is evidence from cell culture experiments showing that B19V modulates inflammatory signalling and apoptosis in endothelial cells 20 and that its capsid protein VP1 damages circulating angiogenic cells, 21 resulting in dysfunctional endogenous vascular repair. 21 The same authors further demonstrated that B19V infection has a direct VP2-mediated negative impact on trafficking of circulating angiogenic cells in the presence of impaired cardiac regeneration.…”