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. 2020 Oct-Dec;13(4):301-308.
doi: 10.4103/apc.APC_124_19. Epub 2020 Sep 1.

Detection of parvovirus B19 and human herpesvirus 6 in pediatric dilated cardiomyopathy: Impact after heart transplantation

Bibhuti B Das  1 , Bhupesh K Prusty  2 , Jianli Niu  3 , Meei-Li Huang  4 , Haiying Zhu  4 , Eva Eliassen  5 , Jane M Kuypers  4 , Keith R Jerome  4
Affiliations

Detection of parvovirus B19 and human herpesvirus 6 in pediatric dilated cardiomyopathy: Impact after heart transplantation

Bibhuti B Das et al. Ann Pediatr Cardiol. 2020 Oct-Dec.

Abstract

Objectives: The aim of this study is to evaluate HHV-6 and PVB19 infection using polymerase chain reaction (PCR) and immunofluorescent assay (IFA) in the myocardium of pediatric patients with dilated cardiomyopathy (DCM) and the impact of viral persistence in the cardiac allograft after heart transplantation (HT).

Methods: Multiplex droplet digital PCR was used to analyze the prevalence of viral sequences in myocardial samples from 48 pediatric DCM patients and 10 control subjects. Of the 48 DCM patients, 44 underwent HT. After HT, consecutive endomyocardial biopsy (EMB) samples were analyzed for the presence of PVB19 and HHV-6 antigens using IFA and the patients were evaluated for rejections, coronary vasculopathy, and graft loss.

Results: Of the 48 DCM patients, 14 had positive viral PCR results in explanted/autopsy hearts. Among them, PVB19 was found in 8/48, HHV6 in 4/48, both PVB19 and HHV6 in 1/48, and enterovirus in one, but no adenovirus was found. The EMB samples obtained after HT were positive for PVB19 and HHV-6 in 7/44 and 3/44 cases, respectively. Viral presence in both the explanted heart and the cardiac allograft was demonstrated in 4 patients, 3 of whom were positive for PVB19, and one of whom was positive for HHV-6 pretransplant. Coronary vasculopathy and graft loss were more common in patients with PVB19-positive myocardial tissues versus those who were PVB19-negative.

Conclusions: There is an association between PVB19 and HHV-6 infection and DCM in children. The study suggests the persistence of PVB19 and HHV-6 in the host can lead to subsequent viral reactivation in the transplanted heart, even in those recipients who do not have active myocarditis. PVB19 in the cardiac allograft tended toward higher adverse post-HT events.

Keywords: Cardiotropic viruses; coronary vasculopathy; dilated cardiomyopathy; immunofluorescent assay; pediatric heart transplantation; polymerase chain reaction.

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Conflict of interest statement

There are no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meir survival after heart transplantation in pediatric dilated cardiomyopathy cohort
Figure 2
Figure 2
Representative images showing immunofluorescence analysis of PVB19 in PVB19 negative (control group), and positive PVB19 in cardiac tissue from dilated cardiomyopathy patient and myocardial biopsy samples from cardiac allograft after heart transplantation in the same patient. Troponin (green) staining was used as a control for cardiac tissue-specific staining. PVB19 positive areas (red) are indicated with white arrowhead. Expanded images of PVB19 positive staining are shown within white boxes wherever necessary. The scale bar represents 10 μm
Figure 3
Figure 3
Representative images showing Immunofluorescence analysis of HHV-6B specific staining in cardiac allograft tissues using HHV-6B OHV-3 antibody. Troponin (red) staining was used as a control for cardiac tissue specific staining. HHV-6B positive areas (green) are indicated with white arrowhead. Expanded image of HHV-6B positive staining is shown within a white box. The scale bar represents 10 μm
Figure 4
Figure 4
Kaplan–Meier analysis of overall graft survival rates after heart transplantation in pediatric dilated cardiomyopathy patients with virus-positive compared to virus-negative in the explanted heart
Figure 5
Figure 5
Kaplan–Meier analysis of overall graft survival rates after heart transplant in pediatric dilated cardiomyopathy patients with PVB19-positive compared to HHV-6-positive in explanted heart
See this image and copyright information in PMC

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