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

• Published in: Journal of the American College of Cardiology Vol. 56; no. 7; pp. 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: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 10.08.2010; Elsevier; Elsevier Limited
• 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; graft vasculopathy; cardiac transplantation; IVIG; transplant coronary artery disease; virus; CMV; ISHLT; AR; acute rejection; cytomegalovirus; TCAD; EBV; endomyocardial biopsy; International Society of Heart and Lung Transplantation; Epstein-Barr virus; EMB; intravenous immunoglobulin; outcome; PCR; polymerase chain reaction; Human; Heart; Pediatrics; Predictor; Coronary artery; Loss; Cardiovascular disease; Transplantation; Homotransplantation; Coronary heart disease; Infection; Vascular disease; Treatment; Surgery; Viral disease; Risk factor; Graft; Circulatory system; Cardiology; Predictive factor; Child
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2010.02.060

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.