2002ISHLT
HEART TRANSPLANTATION
Pediatric Recipients
2002ISHLT
AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS (1982-2001)
0
200
400
600
800
1000
1200
1400
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Recipient Age (Years)
Nu
mb
er o
f T
ran
spla
nts
2002ISHLT
AGE DISTRIBUTION FOR DONORS OF PEDIATRIC HEART RECIPIENTS (1982-2001)
0
200
400
600
800
1000
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18+
Donor Age (Years)
Nu
mb
er o
f T
ran
spla
nts
2002ISHLT
AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS
By Year of Transplant
0
100
200
300
40011-17 Years1-10 Years
<1 Year
Nu
mb
er o
f T
ran
spla
nts
11 942
75109
130
193
254
326365363
385364378
349372
350340
356319
* Numbers may be low due to delayed reporting.
2002ISHLT
NUMBER OF CENTERS REPORTING PEDIATRIC HEART TRANSPLANTS
0
20
40
60
80
100
Transplant Year
Num
ber
of P
edia
tric
Tra
nspl
ant
Cen
ters
* Numbers may be low due to delayed reporting
2002ISHLT
DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: < 1 Year)
0
25
50
75
100
1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
% o
f Cas
es
MyopathyCongenital
20%
1%
75%4%
Myopathy
Congenital
Other
ReTX
2002ISHLT
DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: 1-10 Years)
0
25
50
75
100
1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
% o
f Cas
es
MyopathyCongenital
50% 37%
5% 8%
Myopathy
Congenital
Other
ReTX
2002ISHLT
DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: 11-17 Years)
0
25
50
75
100
1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
% o
f Cas
es
Myopathy Congenital
62%
24%
4% 10%
Myopathy
Congenital
Other
ReTX
2002ISHLT
PEDIATRIC HEART TRANSPLANTATIONActuarial Survival (1982-2001)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Years Post-Transplantation
Su
rviv
al (
%)
<1 Year (N=1,206) 1-10 Years (N=1,862)11-17 Years (N=1,939) Overall (N=5,007)
<1 year vs. 1-10 years: p = 0.0005<1 year vs. 11-17 years: p = 0.001
2002ISHLT
PEDIATRIC HEART TRANSPLANTATIONConditional Actuarial Survival (1982-2001)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Years Post-Transplantation
Su
rviv
al (
%)
<1 Year (N=726) 1-10 Years (N=1,161)11-17 Years (N=1,236) Overall (N=3,123)
Both comparisons with 11-17 years significant at p < 0.0001
2002ISHLT
PEDIATRIC HEART TRANSPLANTATIONConditional Actuarial Survival for Recent Era (1998-2001)
50
60
70
80
90
100
0 1 2 3 4
Years Post-Transplantation
Su
rviv
al (
%)
<1 Year (N=150) 1-10 Years (N=246)11-17 Years (N=217) Overall (N=613)
Comparison of <1 vs. 11-17 years significant at p = 0.01
2002ISHLT
PEDIATRIC HEART TRANSPLANTATION
Actuarial Survival by Era (1982-2001)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10
Years Post-Transplantation
1982-1987 (N=376) 1988-1992 (N=1,501)
1993-1997 (N=1,848) 1998-2001 (N=1,365)
All comparisons with 1998-2001 are significant at p < 0.0001Comparison of 1982-1987 vs. 1988-1992 was significant at p = 0.003Comparison of 1982-1987 vs. 1993-1997 was significant at p < 0.0001
Su
rviv
al (
%)
2002ISHLT
PEDIATRIC HEART TRANSPLANTATION Actuarial Survival by Age Group
For Diagnosis = Cardiomyopathy (1988-2001)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10
Years Post-Transplantation
<1 (N=248)
1-10 (N=940)
11-17 (N=1,212)
Su
rviv
al (
%)
No comparisons were statistically significant.
2002ISHLT
PEDIATRIC HEART TRANSPLANTATION Actuarial Survival By Age Group
For Diagnosis = Congenital Disease (1988-2001)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10
Years Post-Transplantation
<1 (N=898)
1-10 (N=688)
11-17 (N=468)
Comparison of <1 vs. 11-17 was significant at p = 0.01
Su
rviv
al (
%)
2002ISHLT
PEDIATRIC HEART TRANSPLANTS (1996-2001)Risk Factors For 1 Year Mortality
In Descending Order of Magnitude
N=1,554
VARIABLE
Odds Ratio
P-value 95%
Confidence Interval
Diagnosis: Congenital Heart Disease
2.01 <.0001 1.44 -2.80
Ventilator 1.92 0.001 1.30 -2.83
Diagnosis: Other (not Congenital, Cardiomyopathy or Retransplant)
1.92 0.009 1.17 -3.13
VAD 1.85 0.04 1.03 -3.32
Donor COD: Other (not head trauma, CVA, CNS tumor, or anoxia)
1.56 0.04 1.03 -2.38
2002ISHLT
PEDIATRIC HEART TRANSPLANTS (1996-2001) Risk Factors for 1 Year Mortality
Continuous Factors
N=1,554
VARIABLE Odds Ratio p-value Recipient Age – linear 0.007
Recipient Age – quadratic 0.001
0 Years 2.05
3 Years 1.33
6 Years 1.03
9 Years 0.97
12 Years 1.09
15 Years 1.48
2002ISHLT
PEDIATRIC HEART TRANSPLANTS (1996-2001) Factors Not Significant for 1 Year Mortality
•Previous Transplant•Donor history of hypertension•Height (recipient/donor)•Weight (recipient/donor)•Gender (recipient/donor)•Age (donor) •Year of transplant
•In ICU or hospital•Donor clinical infection•ICD•Ischemia time•Center volume•PRA •Total bilirubin
2002ISHLT
PEDIATRIC HEART TRANSPLANTS (April 1994 - December 1996)
Risk Factors For 5 Year MortalityIn Descending Order of Magnitude
N=937
VARIABLE
Odds Ratio
P-value 95%
Confidence Interval
On life support 1.93 <.0001 1.43 -2.60
Year of Transplant: 1994 1.75 0.0006 1.27 -2.41
Diagnosis: Congenital Heart Disease
1.64 0.001 1.21 -2.21
2002ISHLT
PEDIATRIC HEART TRANSPLANTS (April 1994 - December 1996)Risk Factors For 5 Year Mortality
Continuous Factors
N=937
VARIABLE Odds Ratio p-value Recipient BMI – quadratic 0.02
17 1.72
22 1.00
26 1.31
30 3.22
2002ISHLT
PEDIATRIC HEART TRANSPLANTS (April 1994 - December 1996)
Factors Not Significant for 5 Year Mortality
•Donor history of hypertension•Height (recipient/donor)•Weight (donor)•Gender (donor)•Age (donor) •Donor cause of death
•In ICU or hospital•Donor clinical infection•ICD•Ischemia time•Center volume•PRA •Total bilirubin
2002ISHLT
PEDIATRIC HEART TRANSPLANTS (April 1994 - December 1996)
Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year
In Descending Order of Magnitude
N=728
VARIABLE Odds Ratio P-value
95% Confidence
Interval
Previous Transplant 3.39 0.02 1.22 -9.39
Inotropes 3.30 <.0001 2.02 -5.37
Ventilator 0.22 0.007 0.07 -0.66
2002ISHLT
PEDIATRIC HEART RECIPIENTS Functional Status (April 1994-December 2001)
0%
20%
40%
60%
80%
100%
1 Year (N = 1,380) 3 Years (N = 1,142) 5 Years (N = 932)
No Activity Limitations Performs with Some Assistance Requires Total Assistance
2002ISHLT
PEDIATRIC HEART RECIPIENTS Rehospitalization Post-transplant (April 1994 - December 2001)
0%
20%
40%
60%
80%
100%
Up to 1 Year (N = 1,547)
Between 2 and 3 Years (N = 1,219)
Between 4 and 5 Years (N = 983)
No Hospitalization Hospitalized, Not Rejection/Not Infection
Hospitalized, Rejection Hospitalized, Infection Only
Hospitalized, Rejection + Infection
2002ISHLT
0
10
20
30
40
Any Induction (N = 227)
Polyclonal ATG/ALG (N = 160)
OKT3 (N = 45) IL2R-Antagonist (N = 47)
% o
f p
ati
en
ts
PEDIATRIC HEART RECIPIENTS Induction Immunosuppression
For follow-ups between October 1999 and December 2001
2002ISHLT
0
20
40
60
80
100
Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone
% o
f P
ati
en
ts
Year 1 (N = 483)
Year 5 (N = 315)
PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Any Time During Follow-up Period
For follow-ups between October 1999 and December 2001
2002ISHLT
0
20
40
60
80
100
Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone
% o
f P
ati
en
ts
Discharge (N = 429) Year 1 (N = 303)
PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up
For follow-ups between October 1999 and December 2001
2002ISHLT
0
20
40
60
80
100
CalcineurinInhibitor
CellCycle Prednisone CalcineurinInhibitor
CellCycle Prednisone
% o
f P
ati
en
ts
CyA
Tac Tac
CyA
AZAAZA
MMFMMF
PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up
For follow-ups between October 1999 and December 2001
1 Year Follow-up (N=429) 5 Year Follow-up (N = 303)
2002ISHLT
0%
20%
40%
60%
80%
100%
Year 1 (N = 429) Year 5 (N = 303)
% o
f P
atie
nts
None Given
Other
Tacrolimus + MMF
Tacrolimus + AZA
Cyclosporine + MMF
Cyclosporine + AZA
PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up
For follow-ups between October 1999 and December 2001
2002ISHLT
POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Incidence for Survivors (April 1994-December 2001)
Outcome By 1 Year By 5 Years
Hypertension 44.2% (N=1,507) 60.0% (N=365)
Renal Function (N=1,516) (N=389) Normal 94.9% 92.5% Renal Dysfunction 3.2% 5.9% Creatinine>2.5 mg/dl 1.4% 0.8% Chronic Dialysis 0.5% 0.8% Renal Transplant 0.0% 0.0%
Hyperlipidemia
8.6% (N=1,578)
17.1% (N=398) Diabetes 3.2% (N=1,509) 4.9% (N=366)
CAV 2.5% (N=1,363) 11.4% (N=228)
2002ISHLT
Freedom from CAV For Pediatric Heart Recipients (April 1994-December 2000)
50
60
70
80
90
100
0 12 24 36 48 60
Months
% F
ree
from
CA
V
2002ISHLT
Freedom from Renal Dysfunction*For Pediatric Heart Recipients (April 1994-December 2000)
50
60
70
80
90
100
0 12 24 36 48 60
Months
% F
reed
om fr
om R
enal
D
ysfu
nctio
n
* Renal dysfunction = Creatinine > 2.5 mg/dl, dialysis or renal transplant
2002ISHLT
MALIGNANCY POST-HEART TRANSPLANTATION FOR PEDIATRICSCumulative Incidence for Survivors (April 1994-December 2001)
Malignancy/Type 1-Year Survivors 5-Year Survivors
No Malignancy 1,547 (98.2%) 378 (95.2%)
Malignancy (all types combined) 29 (1.8%) 19 (4.8%)
Malignancy Type
Lymph 25 18
Other 3 1
Type Not Reported 1
2002ISHLT
Freedom from MalignancyFor Pediatric Heart Recipients (April 1994-December 2000)
50
60
70
80
90
100
0 12 24 36 48 60
Months
% F
ree
from
Mal
igna
ncy
All malignancy Lymph Skin Other
2002ISHLT
PEDIATRIC HEART TRANSPLANTATIONActuarial Survival Based on Prednisone Use
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Years Post-Transplantation
Su
rviv
al (
%)
Prednisone use at discharge and 1 year (N=921)
No Prednisone at discharge or at 1 year (N=227)
Prednisone at discharge/not at 1 year (N = 148)
p = 0.005
2002ISHLT
PEDIATRIC HEART TRANSPLANTATIONActuarial Survival Based on Rejection within 1st Year
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Years Post-Transplantation
Su
rviv
al (
%)
Free from Rejection during 1st Year (N = 513)Rejection within 1st Year (N = 680)
P = 0.09
2002ISHLT
PEDIATRIC HEART RECIPIENTSRelationship of Prednisone Use and CAD
Transplants: April 1994 – December 1999 Prednisone
Use at Discharge and at 1
Year
Reported CAD between 1st and 2nd years post-
transplant
Reported CAD between 1st and 3rd years post-
transplant
Yes No Yes No
Yes 28
4.8%
558
95.2%
27
7.1%
352
92.9%
No 4
2.8%
138
97.2%
2
2.0%
96
98.0%p = 0.4 p = 0.06
2002ISHLT
PEDIATRIC HEART RECIPIENTSRelationship of Rejection and CAD
Transplants: April 1994 – December 1999 Rejection During 1st
Year
Reported CAD between 1st and 2nd years post-
transplant
Reported CAD between 1st and 3rd years post-
transplant
Yes No Yes No
Yes 19
5.3%
342
94.7%
17
7.1%
222
92.9%
No 6
1.8%
322
98.2%
7
3.2%
212
96.8%p = 0.02 p = 0.09
2002ISHLT
PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 1 and 3 Years
Maintenance Immunosuppression at discharge and 1 year
On immuno:
% HTN reported between 1 and 3
years
Not on immuno:
% HTN reported between 1 and 3
years
P-value
Cyclosporine 20.3% 15.7% 0.6
Tacrolimus 20.5% 19.4% 0.8
Azathioprine 22.3% 15.3% 0.3
Prednisone 29.9% 6.4% <0.0001
2002ISHLT
PEDIATRIC HEART RECIPIENTS Incidence of Hypertension by 3 Years
Maintenance Immunosuppression at discharge and 1 year
On immuno:
% HTN reported by 3 years
Not on immuno:
% HTN reported by 3 years
P-value
Cyclosporine 48.8% 40.6% 0.2
Tacrolimus 44.2% 46.2% 0.8
Azathioprine 51.1% 42.4% 0.1
Prednisone 59.5% 12.1% <0.0001
2002ISHLT
PEDIATRIC HEART RECIPIENTS Growth Following Transplantation: Height
Stratified by Prednisone Use at Discharge and at 1 Year
80
100
120
140
160
180
Listing Immediately Pre-Transplant
1 Year Follow-up 2 Year Follow-up
Time of Measurement
Hei
ght (
cm)
11-17 Years/No Prednisone 11-17 Years/Prednisone
1-5 Years/No Prednisone 1-5 Years/Prednisone
2002ISHLT
PEDIATRIC HEART RECIPIENTS Growth Following Transplantation: Weight
Stratified by Prednisone Use at Discharge and at 1 Year
0
20
40
60
80
Listing Immediately Pre-Transplant
1 Year Follow-up 2 Year Follow-up
Time of Measurement
Wei
ght (
Kg)
11-17 Years/No Prednisone 11-17 Years/Prednisone
1-5 Years/No Prednisone 1-5 Years/Prednisone
2002ISHLT
PEDIATRIC HEART RECIPIENTS: Time of Death (1988-2001)
0%
20%
40%
60%
80%
100%
<1 1-10 11-17Recipient Age (years)
% o
f Dea
ths
0-30 Days 31 Days -1 Year 1 - 3 Years 3 - 5 Years 5+ Years
2002ISHLT
PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (1982-2001)
0%
20%
40%
60%
80%
100%
0-30 Days (N = 398)
31 Days - 1 Year (N = 284)
>1 Year - 3 Years (N = 159)
>3 Years - 5Years (N = 87)
>5 Years (N = 120)
Other
Technical
Graft Failure - Other
Primary Graft Failure
Infection, Non-CMV
Acute Rejection
CMV
Malignancy, Other
Lymphoma
CAV
Timing of Death
Cau
se o
f D
eath
(%
)
2002ISHLT
PEDIATRIC HEART TRANSPLANTS RECIPIENTS: CAUSE OF DEATH BY ERA: Deaths in 0-30 Days
0%
20%
40%
60%
80%
100%
1987-1991 (N = 125)
1992-1996 (N = 151)
1997-2001 (N = 85)
Per
cent
age
of D
eath
s
Other
Technical
Graft Failure - Other
Primary Graft Failure
Infection, Non-CMV
Acute Rejection
CMV
Malignancy, Other
Lymphoma
CAV
2002ISHLT
PEDIATRIC HEART TRANSPLANTS RECIPIENTS: CAUSE OF DEATH BY ERA: Deaths in 31 Days - 1 Year
0%
20%
40%
60%
80%
100%
1987-1991 (N = 81)
1992-1996 (N = 140)
1997-2001 (N = 59)
Per
cent
age
of D
eath
s
Other
Technical
Graft Failure - Other
Primary Graft Failure
Infection, Non-CMV
Acute Rejection
CMV
Malignancy, Other
Lymphoma
CAV
2002ISHLT
PEDIATRIC HEART TRANSPLANTS RECIPIENTS: CAUSE OF DEATH BY ERA: Deaths in >1 Year - 3 Years
0%
20%
40%
60%
80%
100%
1987-1991 (N = 57)
1992-1996 (N = 80)
1997-2001 (N = 21)
Per
cent
age
of D
eath
s
Other
Technical
Graft Failure - Other
Primary Graft Failure
Infection, Non-CMV
Acute Rejection
CMV
Malignancy, Other
Lymphoma
CAV
2002ISHLT
PEDIATRIC HEART TRANSPLANTS RECIPIENTS: CAUSE OF DEATH BY ERA: Deaths in >3 Years - 5 Years
0%
20%
40%
60%
80%
100%
1987-1991 (N = 33)
1992-1996 (N = 48)
1997-2001 (N = 3)
Per
cent
age
of D
eath
s
Other
Technical
Graft Failure - Other
Primary Graft Failure
Infection, Non-CMV
Acute Rejection
CMV
Malignancy, Other
Lymphoma
CAV