Online Appendix for the following JACC article
TITLE: Viral Endomyocardial Infection Is an Independent Predictor and Potentially
Treatable Risk Factor for Graft Loss and Coronary Vasculopathy in Pediatric Cardiac
Transplant Recipients
AUTHORS: 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, Jeffrey A. Towbin, MD
APPENDIX
Table 1. Schedule for Surveillance Endomyocardial Biopsies After Cardiac
Transplantation
Time From Transplantation
0 - 3 months
3 - 12 months
1 - 5 years
> 5 years
Biopsy Frequency
2 to 4 weekly
3 monthly
6 monthly
annually
Table 2. Classification of TCAD
CTRD class
None
Mild
Moderate
Severe
Coronary Artery Lesion
Normal
< 50% in any branch segment
> 50% in 1 primary vessel or > 50% in branch of 2 vessels
> 50% in 2 primary vessels or> 50% in branches of all 3 systems or
50% left main
Table 3. Causes for Cardiac Allograft Loss in the Study Cohort
Cause of Graft Loss
TCAD
Rejection
MSOF
Sepsis
Arrhythmia
Aplastic Anemia
Malignancy
Pulmonary vein stenosis
PCR Positive Group
(n=11)
5
0
1
1
1
1
1
1
PCR Negative Group
(n=11)
6
1
2
1
1
0
0
0
Table 4. Risk Factors Evaluated for Graft Loss in the Study Cohort
Risk Factors
Recipient
Gender
Ethnicity
Age
Weight
Pretransplant Cardiac Diagnosis
Primary Vs Retransplantation
UNOS Listing Status
Wait Time after listing
Ventilator Dependence
at transplantation
LVAD/ECMO Dependence
at transplantation
Ionotrope Dependence
at transplantation
Hospitalization at transplantation
Pulmonary Systolic Pressure
Pulmonary Capillary Wedge Pressure
CMV sero-status
Histopathologic evidence of
myocarditis in explant heart
Presence of viral genome in
explant heart
Donor
Gender
Ethnicity
Age
Weight
Cold – ischemia time
CMV sero-status
Recipient-Donor Mismatch
Gender Mismatch
Ethnicity Mismatch
CMV Mismatch
(Sero-Negative Recipient
Sero-Positive Donor)
HLA CrossMatch Positive
Post-Transplantation Course
Length of initial hospital stay after tansplantation
Number of early rejection episodes
( 1st 3 months, 1st 6 months, 1st year)
Number of rejection episodes per post-transplantation
year
Initial Immunosuppressive regimen
Final Immunosupressive regimen
Viral Endomyocardial Infection (Positive
Biopsy PCR)
CMV = cytomegalovirus; ECMO = extracorporeal membrane oxygenation; HLA =
human leukocyte antigen; LVAD = left ventricular assist device; PCR = polymerase
chain reaction; UNOS = United Network for Organ Sharing.
Table 5: Risk Factors Predictive of Graft Loss in the Study Cohort on Univariate
and Multivariate Cox Proportional Hazards Regression
Risk factors predictive of Graft Loss on Univariate Analysis
Variable
Hazard
Ratio
7.2
95% CI
P value
Viral endomyocardial
2.79-18.58
< 0.001
infection
Number of Acute Rejection 1.5
1.03-2.21
0.03
episodes in the first year
after transplantation
Number of Acute Rejection 3.5
2.08-6.03
< 0.001
episodes per patient year
after transplantation
Donor age
1.1
1.00-1.15
0.04
Risk factors independently predictive of graft loss on
Multivariate Analysis (Time-dependent Cox regression model
after adjusting for recipient age, recipient weight, recipient
gender , donor age and re-transplantation)
Viral endomyocardial
4.0
1.30-12.40
0.02
infection
Number of Acute Rejection 3.0
1.74-5.27
< 0.001
episodes per patient year
after transplantation