Viral Endomyocardial Infection Is an Independent Predictor and Potentially Treatable Risk Factor for Graft Loss and Coronary Vasculopathy in Pediatric Cardiac Transplant Recipients

Objectives This study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation. Background Viral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2010-08, Vol.56 (7), p.582-592
Main Authors: Moulik, Mousumi, MD, Breinholt, John P., MD, Dreyer, William J., MD, Kearney, Debra L., MD, Price, Jack F., MD, Clunie, Sarah K., RN, Moffett, Brady S., PharmD, Kim, Jeffrey J., MD, Rossano, Joseph W., MD, Jefferies, John Lynn, MD, MPH, Bowles, Karla R., PhD, O'Brian Smith, E., PhD, Bowles, Neil E., PhD, Denfield, Susan W., MD, Towbin, Jeffrey A., MD
Format: Article
Language:English
Subjects:
Adenovirus
Adolescent
Biological and medical sciences
Biopsy
cardiac transplantation
Cardiology
Cardiology. Vascular system
Cardiovascular
Cardiovascular disease
Child
Child, Preschool
Coronary Disease - virology
Coronary heart disease
Cytomegalovirus
Female
Genome, Viral
Graft Rejection - virology
Graft Survival
graft vasculopathy
Heart
Heart Transplantation
Humans
Infant
Infant, Newborn
Infections
Infectious diseases
Internal Medicine
Male
Medical sciences
Myocarditis - epidemiology
Myocarditis - virology
outcome
Polymerase Chain Reaction
Prevalence
Risk Factors
TCAD
Transplants & implants
Viral diseases
Viral infections
virus
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Summary:Objectives This study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation. Background Viral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac allograft reduces graft survival. Methods Between June 1999 and November 2004, 94 pediatric cardiac transplant patients were screened for the presence of viral genome in serial endomyocardial biopsies (EMBs) using polymerase chain reaction (PCR) assays. Graft loss, advanced transplant coronary artery disease (TCAD), and acute rejection (AR) were compared in the PCR-positive (n = 37) and PCR-negative (n = 57) groups, using time-dependent Kaplan-Meier and Cox regression analyses. From November 2002 to November 2004, intravenous immunoglobulin therapy (IVIG) was administered to patients with PCR-positive EMBs. The outcomes of the IVIG-treated, PCR-positive patients (n = 20) were compared with IVIG-untreated, PCR-positive patients (n = 17). Results Viral genomes were detected in EMBs from 37 (39%) patients; parvovirus B19, adenovirus, and Epstein-Barr virus (EBV) were the most common. The PCR-positive group (n = 37, 25% graft loss at 2.4 years) had decreased graft survival (p < 0.001) compared with the PCR-negative group (n = 57, 25% graft loss at 8.7 years) and developed advanced TCAD prematurely (p = 0.001). The number of AR episodes was similar in both groups. On multivariate analysis, presence of viral genome was an independent risk factor for graft loss (relative risk: 4.2, p = 0.015). The time to advanced TCAD after becoming PCR-positive was longer in the IVIG-treated patients (p = 0.03) with a trend toward improved graft survival (p = 0.06). Conclusions Viral endomyocardial infection is an independent predictor of graft loss in pediatric cardiac transplant recipients. This effect appears to be mediated through premature development of advanced TCAD. IVIG therapy in this subgroup may improve survival and merits further investigation.
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2010.02.060