Viral epidemiologic shift in inflammatory heart disease: the increasing involvement of parvovirus B19 in the myocardium of pediatric cardiac transplant patients

Abstract

Background: Detection of viral genome in rejecting cardiac transplant patients has been reported, with coxsackievirus and adenovirus causing premature graft failure. Recently, parvovirus B19 (PVB19) genome in myocardial samples has been increasingly reported, but its role in cardiac pathology and effect on transplant graft survival are unknown. The objectives of this study were to determine if changes in the viruses identified in the myocardium represent an epidemiologic shift in viral myocardial disease and whether PVB19 adversely affects transplant graft survival.

Methods: From September 2002 to December 2005, nested polymerase chain reaction was used to evaluate endomyocardial biopsy specimens for 99 children (aged 3 weeks-18 years) with heart transplants for the presence of viral genome. Cellular rejection was assessed by histology of specimens. Transplant coronary artery disease (TCAD) was diagnosed by coronary angiography or histopathology.

Results: Specimens from 700 biopsies were evaluated from 99 patients; 121 specimens had viral genome, with 100 (82.6%) positive for PVB19, 24 for Epstein-Barr virus (EBV; 7 positive for PVB19 and EBV), 3 for CMV, and 1 for adenovirus. Presence of PVB19 genome did not correlate with rejection score, nor did a higher viral copy number. Early development of advanced TCAD (p < 0.001) occurred in 20 children with persistent PVB19 infection (> 6 months).

Conclusions: PVB19 is currently the predominant virus detected in heart transplant surveillance biopsy specimens, possibly representing an epidemiologic shift. Cellular rejection does not correlate with the presence or quantity of PVB19 genome in the myocardium, but children with chronic PVB19 infection have increased risk for earlier TCAD, supporting the hypothesis that PVB19 negatively affects graft survival.

Figure 1. Distribution of viral genomes

1a. Distribution of virus types in 700 biopsies from 99 patients. 1b. Frequency of virus types in 121 virus-positive biopsies from 45 patients. Total frequency of parvovirus B19 was 83%; total frequency of EBV was 20%

Figure 1. Distribution of viral genomes

1a. Distribution of virus types in 700 biopsies from 99 patients. 1b. Frequency of virus types in 121 virus-positive biopsies from 45 patients. Total frequency of parvovirus B19 was 83%; total frequency of EBV was 20%

Figure 2

Kaplan-Meier analysis of graft survival in pediatric cardiac transplant patients with parvovirus B19 amplified from biopsy samples (PVB19 +) compared to patients with no history of parvovirus B19 genome in biopsy samples (PVB19 −)

Figure 3

Figure 3a. Kaplan-Meier analysis of freedom from the development of advanced transplant coronary artery disease in pediatric cardiac transplant patients with PVB19-positive versus PVB19-negative EMBs. (p=0.01) Figure 3b. Kaplan-Meier analysis of freedom from advanced transplant coronary artery disease in pediatric cardiac transplant patients with chronic parvovirus B19 (CPV) versus no history of parvovirus B19 (PV −) (p < 0.001) and acute parvovirus B19 (APV) versus PV − (p = 0.27)

Figure 3

Figure 3a. Kaplan-Meier analysis of freedom from the development of advanced transplant coronary artery disease in pediatric cardiac transplant patients with PVB19-positive versus PVB19-negative EMBs. (p=0.01) Figure 3b. Kaplan-Meier analysis of freedom from advanced transplant coronary artery disease in pediatric cardiac transplant patients with chronic parvovirus B19 (CPV) versus no history of parvovirus B19 (PV −) (p < 0.001) and acute parvovirus B19 (APV) versus PV − (p = 0.27)

Figure 4. Epidemiology of Virus Types Identified in Endomyocardial Biopsy Samples

Data from our institution published by Shirali et al.(16) (1993–1998 (Transplant)) and Bowles et al.(12) (1988–1999 (Myocarditis)) compared to the current era (2002–2005 (Transplant))