Author + information
- Received February 23, 2009
- Revision received February 11, 2010
- Accepted February 24, 2010
- Published online August 10, 2010.
- Mousumi Moulik, MD*,
- John P. Breinholt, MD†,
- William J. Dreyer, MD‡,
- Debra L. Kearney, MD§,
- Jack F. Price, MD‡,
- Sarah K. Clunie, RN‡,
- Brady S. Moffett, PharmD∥,
- Jeffrey J. Kim, MD‡,
- Joseph W. Rossano, MD‡,
- John Lynn Jefferies, MD, MPH‡,
- Karla R. Bowles, PhD#,
- E. O'Brian Smith, PhD¶,
- Neil E. Bowles, PhD**,
- Susan W. Denfield, MD‡ and
- Jeffrey A. Towbin, MD††,* ()
- ↵*Reprint requests and correspondence:
Dr. Jeffrey A. Towbin, The Heart Institute, Division of Pediatric Cardiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229
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.
This work was supported by fellowship trainee grants from the National Institutes of Health(5T32HL007676, 5T32HL007706) to Dr. Moulik, Pediatric Scientist Development Program Grant from the National Institutes of Child Health and Human Development(K12-HD00850) to Dr. Breinholt, the Abby Glaser Children's Heart Fund(Dr. Towbin) and Children's Cardiomyopathy Foundation(Dr. Towbin). Dr. Moulik is currently supported by a Mentored Clinical Scientist Development Award from the National Institutes of Health(1K08 HL091176). Dr. Bowles is currently employed at Myriad Genetic Laboratories, but the work presented in this paper was performed prior to his employment. Drs. Dreyer, Kearney, Price, Clunie, Moffett, Kim, Rossano, Jefferies, O'Brian Smith, and Denfield have reported that they have no relationships to disclose.
- Received February 23, 2009.
- Revision received February 11, 2010.
- Accepted February 24, 2010.
- American College of Cardiology Foundation