Differences in Virus Prevalence and Load in the Hearts of Patients with Idiopathic Dilated Cardiomyopathy with and without Immune-Mediated Inflammatory Diseases

Abstract

dInfections with cardiotrophic viruses and immune-mediated responses against the heart have been suggested to play a dominant role in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). Furthermore, immune-mediated inflammatory diseases (IMIDs) may result in DCM. It has not previously been assessed whether DCM patients with and without an IMID have different prevalences and quantities of cardiotrophic viruses in the heart. Therefore, we compared the profiles of cardiotrophic viruses in heart tissue of DCM patients with and without an IMID. Serum and myocardial tissue samples were obtained from 159 consecutive patients with DCM and 20 controls. Patients were subdivided into three groups, the first two based on the presence (n ‫؍‬ 34) or absence (n ‫؍‬ 125) of an IMID and the third being a control group. The parvovirus B19 virus genome was detected in equal quantities in the non-IMID DCM patients (100/125) and the control group (15/20) but in lower quantities in the IMID patients (21/34, P ‫؍‬ 0.02). Both the non-IMID and IMID DCM patients demonstrated increased myocardial inflammation compared to controls: 12.5 ؎ 1.8 and 14.0 ؎ 3.2 CD45-positive inflammatory cells, respectively, versus 5.1 ؎ 0.7 for the controls (P < 0.05 for both). Importantly, significantly higher parvovirus B19 copy numbers could be amplified in non-IMID than in IMID patients (561 ؎ 97 versus 191 ؎ 92 copies/g DNA, P < 0.001) and control subjects (103 ؎ 47 copies/g DNA, P < 0.001). The present study shows decreased parvovirus B19 prevalence and copy numbers in hearts of DCM patients with an IMID compared to those without an IMID. These findings may suggest that DCM patients with an IMID have a different pathophysiologic mechanism from that which is present in the virus-induced form of DCM.

Prevalence and prognostic relevance of cardiac involvement in ANCA-associated vasculitis: Eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis

“…Interestingly, EMBs revealed increased myocardial inflammation in the majority of AAV patients of whom all were in remission. Considering the almost total absence of significant myocardial viral loads, this may suggest that the ongoing inflammation is predominantly immune-mediated instead of reactive, as suggested in previous literature [53]. Of note, although this is currently the largest AAV-population undergoing EMB, it represents only 14% of this total study population.…”

Parvovirus B19 Achievements and Challenges

“…In particular, the definition of a possible role of B19V in the development of chronic cardiomyopathies and cardiac dysfunction is a matter of ongoing debate. Correlation between B19V and cardiomyopathies, in particular dilated cardiomyopathy and ventricular dysfunction, has been proposed by several studies comparing selected groups of patients versus controls [197][198][199][200][201][202][203][204][205], but on the opposite, a lack of significant clinical association has been supported by other groups [206][207][208][209][210][211][212].…”

Telbivudine in chronic lymphocytic myocarditis and human parvovirus B19 transcriptional activity

“…Recent findings further indicate that a subgroup of myocarditis patients characterized by transcriptionally active cardiotropic B19V have an altered cardiac gene expression compared with control patients and myocarditis patients with latent B19V, suggesting that probably active replicating B19V with detectable viral RNA is related to myocarditis. 16 Besides the extent of the viral load 17,18 and the replicative status/transcriptional activity of B19V, 16 other studies further suggest that the relevance of B19V in myocarditis and DCM depends on the presence of other cardiotropic viruses. 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.…”