Human herpesvirus 6-induced inflammatory cardiomyopathy in immunocompetent children

Abstract

Over the last decade, human herpesvirus 6 (HHV-6) has been implicated in the etiology of pediatric myocarditis and subsequent dilated cardiomyopathy (DCM). This review provides an overview of recent literature investigating the pathophysiological relevance of HHV-6 in inflammatory cardiomyopathy. We examined 11 cases of previously published pediatric myocarditis and/or DCM associated with HHV-6 and also our experience of detection of virus particles in vascular endothelium of HHV-6 positive endomyocardial biopsy tissue by electron microscopy. The exact role of the presence of HHV-6 and its load remains controversial as the virus is also found in the heart of healthy controls. Therefore, the question remains open whether and how cardiac HHV-6 may be of pathogenetic importance. Quantitative polymerase chain reaction or mRNA testing allows differentiation between low-level latent virus found in asymptomatic myocardium and active HHV-6 infection. Although only a small number of pediatric cases have been reported in literature, HHV-6 should be considered as a causative agent of inflammatory cardiomyopathy, especially in children under three who might be experiencing a primary infection. Future studies are needed to establish a threshold for determining active infection in biopsy samples and the role of coinfections other cardiotropic viruses.

Keywords: Human herpesvirus 6 cardiomyopathy; myocarditis in children; pediatric-dilated cardiomyopathy.

Figure 1

Possible mechanism of viral myocarditis

Figure 2

Endomyocardial biopsy showing a capillary (C: Capillary lumen; N: Nucleus of endothelial cell) with adjacent myocardium (M). Arrows show herpesvirus particles. Note the myocardial hypoperfusion damage, (×12,000)

Figure 3

Endomyocardial biopsy, higher magnification showing typical human herpesvirus-6A particle (arrow) in an endothelial cell, Bm: Basement membrane, E: Endothelial cells, C: Capillary (×80,000)

Figure 4

PubMed and Ovid Medline review process and outcome summary