Enterovirus RNA Replication in Cases of Dilated Cardiomyopathy: Light Microscopic In Situ Hybridization and Virological Analyses of Myocardial Specimens Obtained at Partial Left Ventriculectomy

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Abstract
Recently, attention has been focused on enteroviral infection of the heart in the genesis of dilated cardiomyopathy (DCM). To determine the location of enteroviral RNA in the myocardium, we performed light microscopic in situ hybridization (ISH) and virological analyses of myocardial specimens obtained at partial left ventriculectomy (PLV). Posterolateral walls of the left ventricle from 26 DCM patients were examined. Myocardial specimens were tested for the presence of enteroviral genomes by polymerase chain reaction (PCR). We selected two age-matched groups (10 patients each) in which enteroviruses were either present (EV-plus group) or not (EV-minus group). For both groups, we examined in situ localization of enteroviral RNA in the myocardium by ISH. In PCR studies, both sense and antisense enteroviral RNA were detected in the myocardium of seven patients in the EV-plus group. The presence of this RNA indicates active viral replication in the myocardium. Five of seven patients who exhibited both sense and antisense enteroviral RNA died early after surgery. On ISH, three patients had evidence of active replication of enteroviral genomes. Viral genomes were present in myocardial lesions, especially in endocardial sites. Viral signals were found in degenerating myocardial cells, interstitial inflammatory cells, and endothelial cells of small vessels. These positive signals were not detected in the myocardium of the EV-negative group. We detected both sense and antisense enteroviral RNA in various myocardial lesions. This suggests that active enteroviral replication plays a role in the development of myocardial lesions in DCM patients. Active viral replication appears to be a prognostic factor for DCM after PLV. Further study of active viral replication in myocardial lesions will provide information useful for evaluating different therapeutic strategies for DCM.

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