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

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.

Risk factors and mode of death in isolated hypertrophic cardiomyopathy in children.

OBJECTIVES: This study was designed to review outcomes of pediatric isolated hypertrophic cardiomyopathy (HCM) managed uniformly at a single institution and assess whether reported adult risk factors for sudden death are predictive in pediatric HCM. BACKGROUND: Cardiac death in HCM occurs suddenly (SCD) or may be nonsudden (non-SCD). Little data exists on non-SCD in children. Risk factors for SCD in adult HCM are characterized and consensus management strategies detailed. Their application to children is uncertain and treatment strategies vary. METHODS: A retrospective cohort study of children with HCM was performed. Primary end points were cardiac death and transplantation. Frequency and outcomes of known adult risk factors were assessed. Outcomes analysis was performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: Ninety-six patients were included. The average age at diagnosis was 10.6 +/- 5.4 years, and mean follow-up was 6.4 +/- 5.2 years. Primary end points occurred in 11 patients over the 20-year follow-up (11%), 4 underwent cardiac transplant and 7 died (3 suddenly). Extreme left ventricular hypertrophy (z-score: >6) and an abnormal blood pressure response to exercise were predictive of non-SCD (p < 0.02 and p < 0.03, respectively). Kaplan-Meier survival analysis predicts an 82% survival over a 20-year period. CONCLUSIONS: In children with isolated HCM managed primarily with exercise restriction and medication, cardiac death occurred infrequently. Non-SCD or transplant was at least as common as SCD. Extreme left ventricular hypertrophy and blunted blood pressure response to exercise were associated with an increased risk of non-SCD.

Myocardial pro-inflammatory cytokine expression and cellular rejection in pediatric heart transplant recipients.

BACKGROUND: Accumulating evidence suggests that immune-mediated injury is important in the development of rejection after heart transplantation. We hypothesized that pro-inflammatory cytokine expression would increase in biopsy samples that manifest cellular rejection and that this would correlate with the development and progression of transplant cellular rejection. METHODS: Children with heart transplants were prospectively enrolled from July 2004 to November 2005. Right ventricular endomyocardial biopsies were obtained during routine catheterization for rejection surveillance. Cellular rejection was graded using criteria established by the International Society for Heart and Lung Transplantation. RNA was extracted from biopsy samples and reverse transcription was used for complementary DNA synthesis. The cDNA product was evaluated by quantitative real-time polymerase chain reaction (PCR) to measure the following cytokines: interleukin (IL)-1beta, IL-6 and IL-18; tumor necrosis factor-alpha (TNF-alpha); and interferon-gamma (IFN-gamma). Normalized cytokine mRNA transcripts were correlated with cellular rejection scores and the presence of viral genome. RESULTS: Seventy-four children (mean age 9.6 +/- 5.5 years, range 0.2 to 20.5 years) were enrolled and 95 biopsies were obtained. None of the cytokines demonstrated a correlation with the cellular rejection score, even within individual patients for whom multiple, serial biopsy samples were studied. Eighteen biopsy samples were found to have parvovirus B19 genome present, but there was no correlation between cytokine levels and the presence of parvovirus. CONCLUSIONS: Cytokine transcripts in heart transplants do not correlate with cellular rejection. In addition, there is no correlation between cytokine transcripts and the presence of viral genome.