Viral endomyocardial infection is an independent predictor and potentially treatable risk factor for graft loss and coronary vasculopathy in pediatric cardiac transplant recipients

Mousumi Moulik, John P. Breinholt, William J. Dreyer, Debra L. Kearney, Jack F. Price, Sarah K. Clunie, Brady S. Moffett, Jeffrey J. Kim, Joseph W. Rossano, John Jefferies, Karla R. Bowles, E. O'Brian Smith, Neil E. Bowles, Susan W. Denfield, Jeffrey Towbin

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)582-592
Number of pages11
JournalJournal of the American College of Cardiology
Volume56
Issue number7
DOIs
StatePublished - Aug 10 2010
Externally publishedYes

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Virus Diseases
Pediatrics
Transplants
Passive Immunization
Polymerase Chain Reaction
Intravenous Immunoglobulins
Coronary Artery Disease
Viral Genome
Graft Survival
Heart Transplantation
Biopsy
Transplant Recipients
Parvovirus
Human Herpesvirus 4
Adenoviridae
Allografts
Multivariate Analysis
Heart Failure
Regression Analysis
Survival

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Viral endomyocardial infection is an independent predictor and potentially treatable risk factor for graft loss and coronary vasculopathy in pediatric cardiac transplant recipients. / Moulik, Mousumi; Breinholt, John P.; Dreyer, William J.; Kearney, Debra L.; Price, Jack F.; Clunie, Sarah K.; Moffett, Brady S.; Kim, Jeffrey J.; Rossano, Joseph W.; Jefferies, John; Bowles, Karla R.; O'Brian Smith, E.; Bowles, Neil E.; Denfield, Susan W.; Towbin, Jeffrey.

In: Journal of the American College of Cardiology, Vol. 56, No. 7, 10.08.2010, p. 582-592.

Research output: Contribution to journalArticle

Moulik, M, Breinholt, JP, Dreyer, WJ, Kearney, DL, Price, JF, Clunie, SK, Moffett, BS, Kim, JJ, Rossano, JW, Jefferies, J, Bowles, KR, O'Brian Smith, E, Bowles, NE, Denfield, SW & Towbin, J 2010, 'Viral endomyocardial infection is an independent predictor and potentially treatable risk factor for graft loss and coronary vasculopathy in pediatric cardiac transplant recipients', Journal of the American College of Cardiology, vol. 56, no. 7, pp. 582-592. https://doi.org/10.1016/j.jacc.2010.02.060
Moulik, Mousumi ; Breinholt, John P. ; Dreyer, William J. ; Kearney, Debra L. ; Price, Jack F. ; Clunie, Sarah K. ; Moffett, Brady S. ; Kim, Jeffrey J. ; Rossano, Joseph W. ; Jefferies, John ; Bowles, Karla R. ; O'Brian Smith, E. ; Bowles, Neil E. ; Denfield, Susan W. ; Towbin, Jeffrey. / Viral endomyocardial infection is an independent predictor and potentially treatable risk factor for graft loss and coronary vasculopathy in pediatric cardiac transplant recipients. In: Journal of the American College of Cardiology. 2010 ; Vol. 56, No. 7. pp. 582-592.
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abstract = "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.",
author = "Mousumi Moulik and Breinholt, {John P.} and Dreyer, {William J.} and Kearney, {Debra L.} and Price, {Jack F.} and Clunie, {Sarah K.} and Moffett, {Brady S.} and Kim, {Jeffrey J.} and Rossano, {Joseph W.} and John Jefferies and Bowles, {Karla R.} and {O'Brian Smith}, E. and Bowles, {Neil E.} and Denfield, {Susan W.} and Jeffrey Towbin",
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T1 - Viral endomyocardial infection is an independent predictor and potentially treatable risk factor for graft loss and coronary vasculopathy in pediatric cardiac transplant recipients

AU - Moulik, Mousumi

AU - Breinholt, John P.

AU - Dreyer, William J.

AU - Kearney, Debra L.

AU - Price, Jack F.

AU - Clunie, Sarah K.

AU - Moffett, Brady S.

AU - Kim, Jeffrey J.

AU - Rossano, Joseph W.

AU - Jefferies, John

AU - Bowles, Karla R.

AU - O'Brian Smith, E.

AU - Bowles, Neil E.

AU - Denfield, Susan W.

AU - Towbin, Jeffrey

PY - 2010/8/10

Y1 - 2010/8/10

N2 - 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.

AB - 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.

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