HEART TRANSPLANTATION
Pediatric Recipients
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS (Transplants: January 1996 - June 2006)
0
100
200
300
400
500
600
700
800
900
1000
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
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
AGE DISTRIBUTION FOR DONORS OF PEDIATRIC HEART RECIPIENTS
(Transplants: January 1996 - June 2006)
Nu
mb
er o
f T
ran
spla
nts
ISHLT 2007
0
100
200
300
400
500
600
700
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18-25
26-30
31+
Donor Age (Years)
J Heart Lung Transplant 2007;26: 796-807
AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS
By Year of Transplant
0
50
100
150
200
250
300
350
400
45011-17 Years
1-10 Years
<1 Year
Nu
mb
er o
f T
ran
spla
nts
ISHLT 2007
NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of hearts transplanted worldwide has increased and/or decreased in recent years.
J Heart Lung Transplant 2007;26: 796-807
NUMBER OF CENTERS REPORTING PEDIATRIC HEART TRANSPLANTS
0102030405060708090
100110
Nu
mb
er o
f P
edia
tric
Cas
es R
epo
rtin
g
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
AVERAGE CENTER VOLUMEPediatric Heart Transplants: January 1, 1997 - June 30, 2006
121
17
105
16 1490
10
20
30
40
50
60
70
80
90
100
110
120
1-4/yr 5-9/yr 10-19/yr
Average number of heart transplants per year
Nu
mb
er
of
cen
ters
.
1997-2001
2002-6/2006
ISHLT 2007J Heart Lung Transplant 2007;26: 796-807
DISTRIBUTION OF TRANSPLANTS BY CENTER VOLUME
Pediatric Heart Transplants: January 1, 1997 - June 30, 2006
35.328.8 30.629.3 25.9
44.7
0
10
20
30
40
50
1-4 5-9 10-19
Average number of heart transplants per year
% o
f tr
ansp
lan
ts .
1997-2001 2002-6/2006
ISHLT 2007J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART RE-TRANSPLANTSBy Transplant Year
Retransplants: January 1994 – December 2005
0
5
10
15
20
25
30
35
40
Nu
mb
er
of
tran
sp
lan
ts
Year of transplantISHLT 2007J Heart Lung Transplant 2007;26: 796-807
0
20
40
60
80
100
120
<1 month 1-<12 months 12-<36 months 36-<60 months 60+ months Not reported
Nu
mb
er o
f R
e-T
ran
spla
nts
PEDIATRIC HEART RE-TRANSPLANTSBy Intertransplant Interval
Retransplants: January 1994 - June 2005
ISHLT 2007
Time Between Previous and Current Transplant
J Heart Lung Transplant 2007;26: 796-807
50
60
70
80
90
100
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Su
rrviv
al (
%)
<1 month (N=24) 1-<12 months (N=14) 12-<36 months (N=27)
36+ months (N=132) Primary TX (N=4124)
Comparison of survival for re-transplant groups: p < 0.0001
KAPLAN-MEIER SURVIVAL RATES FOR PEDIATRIC HEART RETRANSPLANTS STRATIFIED BY INTER-TRANSPLANT INTERVAL
Retransplants: January 1994 - June 2005
ISHLT 2007
Time (years) since most recent transplant
J Heart Lung Transplant 2007;26: 796-807
50
60
70
80
90
100
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Su
rrviv
al (
%)
<1 Year (N=38) 1-<3 Years (N=27) 3-<5 Years (N=36)
5+ Years (N=96) Primary TX (N=4124)
Comparison of survival for re-transplant groups: p = 0.0436
KAPLAN-MEIER SURVIVAL RATES FOR PEDIATRIC HEART RETRANSPLANTS STRATIFIED BY INTER-TRANSPLANT INTERVAL
Retransplants: January 1994 - June 2005
ISHLT 2007
Time (years) since most recent transplant
J Heart Lung Transplant 2007;26: 796-807
DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: < 1 Year)
02550
75100
Myopathy Congenital
30%
64%
0%
1%
4%
1%
16%
79%
0%
1%
2%
2%
Myopathy
Congenital
CAD
Malignancy
Other
ReTX1988-1995 1/1996-6/2006
% o
f C
ases
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: 1-10 Years)
0
2550
75
100Myopathy Congenital
52%
37%
6%
0%
1%
4%52%
40%
4%
0%
1%
3%Myopathy
Congenital
CAD
Malignancy
Other
ReTX1988-1995 1/1996-6/2006
% o
f C
ases
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: 11-17 Years)
0
2550
75
100Myopathy Congenital
62%
7%
5%
0%
25%
1%66%
2%
3%
0%
27%
2%
Myopathy
Congenital
CAD
Malignancy
Other
ReTX1988-1995 1/1996-6/2006
% o
f C
ases
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival (1/1982-6/2005)
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years
<1 Year (N= 1,682) 1-10 Years (N = 2,432)11-17 Years (N = 2,561) Overall (N= 6,675)
0-<1 vs. 1-10: p = 0.0017; 0-<1 vs. 11-17: p=0.1104; 1-10 vs. 11-17: p=0.0653
Half-life <1: 15.8 Years; 1-10: 14.2 Years; 11-17: 11.4 Years
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONConditional Kaplan-Meier Survival (1/1982-6/2005)
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years
<1 Year (N = 1,148) 1-10 Years (N = 1,845)11-17 Years (N = 1,968) Overall (N = 4,961)
0-<1 vs. 1-10: p = 0.0029; 0-<1 vs. 11-17: p=<.0001;1-10 vs. 11-17: p=<.0001
Half-life: <1: n.c.; 1-10: 17.5 Years; 11-17: 15.2 Years
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONConditional 5-year Kaplan-Meier Survival (1/1982-6/2005)
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years
<1 Year (N = 675) 1-10 Years (N = 1,074)11-17 Years (N = 1,047) Overall (N = 2,796)
0-<1 vs. 1-10: p = <.0001; 0-<1 vs. 11-17: p=<.0001; 1-10 vs. 11-17: p=0.0020
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONConditional Kaplan-Meier Survival for Recent Era
(1/1999-6/2005)
50
60
70
80
90
100
0 1 2 3 4 5 6
Years
<1 Year (N = 418) 1-10 Years (N = 738)11-17 Years (N = 757) Overall (N = 1,913)
0-<1 vs. 1-10: p = 0.8889;0-<1 vs. 11-17: p=0.0063; 1-10 vs. 11-17: p=0.0014
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era (1/1982-6/2005)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years
1982-1989 (N = 860) 1990-1994 (N=1,842)
1995-1999 (N=1,877) 2000-6/2005 (N=2,096)
All p-values significant at p< 0.0001 except comparison of 1995-1999 vs. 2000-6/2005
Half-life 1982-1989: 10.8 years; 1990-1994: 12.0 years; 1995-1999: n.c.; 2000-6/2005: n.c.
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Era (1/1982-6/2005)
Age: < 1 Year
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16Years
1982-1989 (N=167) 1990-1994 (N=562)
1995-1999 (N=480) 2000-6/2005 (N =473)
P-values for era comparisons82-89 vs. 90-94: 0.3879; 82-89 vs. 95-99: <.0001; 82_90 vs. 00-6/05: <.000190-94 vs. 95-99: <.0001; 90-94 vs. 00-6/05: <.0001; 95-99 vs. 00-6/05: 0.7892
Half-life 1982-1989: 10.8 years; 1990-1994: 10.6 years; 1995-1999: n.c. ; 2000-6/2005: n.c.S
urv
ival
(%
)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era (1/1982-6/2005)
Age: 1-10 Years
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Years
1982-1989 (N = 266) 1990-1994 (N=652)
1995-1999 (N=724) 2000-6/2005 (N=790)
P-values for era comparisons82-89 vs. 90-94: 0.0270; 82-89 vs. 95-99: <.0001; 82-89 vs. 00-6/05: <.0001 90-94 vs. 95-99: 0.0021;89-94 vs. 00-6/05: <.0001; 95-99 vs. 00-6/05: 0.2005
Half-life 1982-1989: 10.9; 1990-1994: 12.5; 1995-1999: . ; 2000-6/2005: n.a.
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era (1/1982-6/2005)
Age: 11-17 Years
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Years
1982-1989 (N=427) 1990-1994 (N=628)
1995-1999 (N=673) 2000-6/2005 (N=833)
P-values for era comparisons82-89 vs. 90-94: 0.0465; 82-89 vs. 95-99: 0.0860; 82_90 vs. 88-6/05: <.0001; 90-94 vs. 95-99: 0.6394; 90-94 vs. 00-6/05: 0.0577; 95-99 vs. 00-6/05: 0.2086
Half-life 1982-1989: 9.9; 1990-1994: 11.5; 1995-1999: 10.1; 2000-6/2005: n.a.
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
0%
20%
40%
60%
80%
100%
Europe North America Other
% o
f T
ran
spla
nts
<1 years 1-10 years 11-17 years
PEDIATRIC HEART TRANSPLANTS:AGE DISTRIBUTION BY LOCATION
Transplants between January 2000 and June 2006
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
0%
20%
40%
60%
80%
100%
Europe North America Other
% o
f T
ran
sp
lan
ts
Other
Re-TX/GraftFailure
Malignancy
Coronary ArteryDisease
Congenital
Cardiomyopathy
PEDIATRIC HEART TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION
Transplants between January 2000 and June 2006
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
0%
20%
40%
60%
80%
100%
Europe North America Other
% o
f D
on
ors
<1 1-10 11-17 18-34 35-49 50-64
PEDIATRIC HEART TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION
Transplants between January 2000 and June 2006
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2005)
Risk Factors For 1 Year Mortality
N=3,209
VARIABLE N
Relative Risk
P-value 95% Confidence Interval
Congenital diagnosis, age = 0, on ECMO 51 5.66 <.0001 3.54 -9.06
Congenital diagnosis, age > 0, on ECMO 48 4.30 <.0001 2.58 -7.14
Congenital diagnosis, age > 0, no ECMO 710 2.23 <.0001 1.70 -2.91
Congenital diagnosis, age=0, on PGE 201 2.12 .0003 1.40 -3.20
Retransplant 179 1.91 .0029 1.25 -2.92
Congenital diagnosis, age = 0, no PGE or ECMO 336 1.90 .0004 1.33 -2.70
On ventilator 581 1.45 .0033 1.13 -1.87
Year of Transplant: 1995-96 vs. 1999-2000 547 1.43 .0191 1.06 -1.94
ISHLT 2007
Reference diagnosis = cardiomyopathy
J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2005)
Borderline Significant Risk Factors For 1 Year Mortality
N=3,209
VARIABLE N Relative
Risk P-value
95% Confidence Interval
PRA > 10% 286 1.31 .0744 0.97 -1.77
Hospitalized (including ICU) 2147 1.25 .0781 0.98 -1.60
Female recipient 1401 1.18 .0933 0.97 -1.42
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2005) Risk Factors for 1 Year Mortality
Continuous Factors (see figures) Donor Age
Bilirubin (borderline)
Creatinine
Weight ratio
Pediatric transplant volume
ISHLT 2007
N=3,209
J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2005) Risk Factors for 1 Year Mortality
Donor Age
0
0.5
1
1.5
2
0 10 20 30 40
Donor Age (Years)
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
p = 0.0007
ISHLT 2007 N=3,209J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2005) Risk Factors for 1 Year Mortality
Pre-Transplant Bilirubin
0
0.5
1
1.5
2
0 1 2 3 4 5 6 7 8
Recipient Bilirubin (mg/dl)
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
p = 0.071
ISHLT 2007 N=3,209J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2005) Risk Factors for 1 Year Mortality
Pre-Transplant Creatinine
0
0.5
1
1.5
2
0 0.5 1 1.5 2 2.5
Recipient serum creatinine (mg/dl)
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
p = 0.0002
ISHLT 2007 N=3,209J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2005) Risk Factors for 1 Year Mortality
Weight Ratio
0
0.5
1
1.5
2
2.5
0.5 1 1.5 2 2.5 3
Weight ratio (donor weight/recipient weight)
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
p = 0.018
ISHLT 2007 N=3,209J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2005) Risk Factors for 1 Year Mortality
Center Volume for Pediatric Transplants
0
0.5
1
1.5
2
2.5
0 2 4 6 8 10 12 14 16 18 20
Center Volume (cases per year)
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
p = 0.0055
ISHLT 2007 N=3,209J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2005) Factors Not Significant for 1 Year Mortality
Recipient Factors:IV inotropes, sternotomy, thoracotomy, history of malignancy, height, recent infection, age
Donor Factors:Gender, history of hypertension, height, clinical infection, history of diabetes
Transplant Factors:CMV mismatch, ABO identical/compatible, ischemia time, HLA mismatch
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2005) 1-Year Predicted Survival Model
80%
85%
90%
95%
100%
0 0.2 0.4 0.6 0.8 1
Time (years)
Recipient: 15 y.o., male, wgt = 40kg, on FK506, PRA > 10%, creatinine = 2.0 mg/dl, dx = retransplant w/ 2.5 years between txDonor: 65 kg, female, 35 y.o. Transplant: 3 hrs ischemia time
Recipient: 15 y.o., male, wgt = 40kg, on FK506, PRA < 10%, creatinine = 1.0 mg/dl, Dx = cardiomyopathy, IV inotropesDonor: 50 kg, male, 15 y.o.Transplant : 3 hrs ischemia time
Pre
dic
ted
Su
rviv
al
ISHLT 2007
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001)
Risk Factors For 5 Year Mortality
N=1,896
VARIABLE N Relative
Risk P-
value 95% Confidence
Interval
Congenital diagnosis, age = 0, ECMO 21 3.11 .0020 1.51 -6.39
Congenital diagnosis, age > 0, ECMO 23 2.72 .0127 1.24 -5.96
Congenital diagnosis, age > 0, no ECMO 434 2.30 <.0001 1.66 -3.18
Re-transplant 104 2.17 .0062 1.25 -3.77
Ventilator 311 1.59 .0026 1.18 -2.16
Hospitalized (including ICU) 1224 1.49 .0108 1.10 -2.03
Year of Transplant: 1995-96 vs. 1999-6/2001 547 1.43 .0139 1.08 -1.91
Female recipient 808 1.27 .0489 1.00 -1.62
Female donor 800 1.27 .0494 1.00 -1.60
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001)
Borderline Significant Risk Factors For 5 Year Mortality
VARIABLE N Relative
Risk P-
value 95% Confidence
Interval
Other diagnosis (not congenital, cardiomyopathy or retransplant)
56 1.94 .0594 0.97 -3.88
ISHLT 2007
N=1,896J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001) Risk Factors for 5 Year Mortality
Continuous Factors (see figure)
Recipient age Bilirubin (borderline)
Pediatric transplant volume
ISHLT 2007
N=1,896J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001) Risk Factors for 5 Year Mortality
Recipient Age
0
0.5
1
1.5
2
2.5
0 2 4 6 8 10 12 14 16 18
Recipient Age (Years)
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
p = 0.014
ISHLT 2007
N=1,896J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001) Risk Factors for 5 Year Mortality
Pre-Transplant Bilirubin
0
0.5
1
1.5
2
0 1 2 3 4 5 6 7 8
Recipient Bilirubin (mg/dl)
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
p = 0.057
ISHLT 2007 N=1,896J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001) Risk Factors for 5 Year Mortality
Center Volume for Pediatric Transplants
0
0.5
1
1.5
2
0 2 4 6 8 10 12 14 16 18 20
Center Volume (cases per year)
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
p = 0.043
ISHLT 2007
N=1,896J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001) Factors Not Significant for 5 Year Mortality
Recipient Factors:History of malignancy, PRA, height, weight, creatinine, diabetes, repeat transplant, transfusions
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000) Factors Not Significant for 5 Year Mortality
Donor Factors:Cause of death, history of hypertension, weight, height, age, clinical infection
Transplant Factors:CMV mismatch, ischemia time, HLA mismatch
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001) Conditional 5-Year Predicted Survival Model
50%
60%
70%
80%
90%
100%
0 1 2 3 4 5
Time (years)
Recipient: 4 m.o., cardiomyopathy, creatinine=0.5 mg/dl, wgt = 5 kg, cyclosporine, no rejection within 1st yearDonor: 8 m.o., wgt = 6 kgTransplant: 3 hrs ischemia time, center volume = 16 pediatric txs/year
Recipient: 4 m.o., congenital heart disease, creatinine=1.4 mg/dl, wgt = 5 kg, ECMO, cyclosporine, rejection within 1st yearDonor: 18 m.o., wgt = 14 kgTransplant : 95 minutes ischemia time, center volume = 3 pediatric txs/year
Pre
dic
ted
Su
rviv
al
ISHLT 2007
PEDIATRIC HEART RECIPIENTS Functional Status of Surviving Recipients
(Follow-ups: April 1994 - June 2006)
0%
20%
40%
60%
80%
100%
1 Year (N = 2,070) 5 Year (N = 1,382) 10 Year (N = 7)
No Activity Limitations Performs with Some Assistance Requires Total Assistance
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients
(Follow-ups: April 1994 - June 2006)
0%
20%
40%
60%
80%
100%
1 Year (N = 2,784) 5 Years (N = 1,737) 10 Years (N = 749)
No Hospitalization Hospitalized, Not Rejection/Not Infection
Hospitalized, Rejection Hospitalized, Infection Only
Hospitalized, Rejection + Infection
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
0
10
20
30
40
50
Any Induction (N = 865) Polyclonal ALG/ATG (N= 579)
OKT3 (N = 39) IL2R-antagonist (N =283)
PEDIATRIC HEART RECIPIENTS Induction Immunosuppression
(Transplants: January 2001 - June 2006)
% o
f P
atie
nts
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
0
10
20
30
40
50
60
Any Induction Polyclonal ALG/ATG IL2R-antagonist
% o
f P
ati
en
ts
200120022003200420052006
PEDIATRIC HEART RECIPIENTSInduction Immunosuppression (Transplants: January 2001 - June 2006)
ISHLT 2007
Test of increasing trend over time:Any induction p < 0.0001Polyclonal p < 0.0001IL2 p = 0.0722
J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group
(Transplants: January 2000 – June 2005) Conditional on Survival to 14 Days
50
60
70
80
90
100
0 1 2 3 4
Years
No induction (N =891)
Polyclonal induction (N = 509)
IL2R-antagonist (N =185)
Su
rviv
al (
%)
No comparisons were statistically significant.
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group and Treated for Rejection Between
Transplant Discharge and 1-Year Follow-up (Transplants: January 2000 – June 2004) Conditional on Survival to 1 Year
50
60
70
80
90
100
0 1 2 3 4
Years
No induction/No rejection (N = 287)
Polyclonal induction/No rejection (N = 124)
IL2R-antagonist/No rejection (N = 53)
No induction/Rejection (N = 178)
Polyclonal induction/Rejection (N = 105)
IL2R-antagonist/Rejection (N = 38)
Su
rviv
al (
%)
No pair-wise comparisons of survival by induction were statistically significant within either rejection grouping.
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2005)
Conditional on Survival to 14 DaysAge: < 1 Year
50
60
70
80
90
100
0 1 2 3 4
Years
No induction (N = 185)Polyclonal induction (N = 191)IL2R-antagonist (N = 23)
No comparisons were statistically significant.
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2005)
Conditional on Survival to 14 DaysAge: 1-10 Years
50
60
70
80
90
100
0 1 2 3 4
Years
No induction (N = 358)Polyclonal induction (N = 177)IL2R-antagonist (N = 66)
Su
rviv
al (
%)
ISHLT 2007
No comparisons were statistically significant.
J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2005)
Conditional on Survival to 14 DaysAge: 11-17 Years
50
60
70
80
90
100
0 1 2 3 4
Years
No induction (N = 348)
Polyclonal induction (N = 141)
IL2R-antagonist (N = 96)
No comparisons were statistically significant.
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
0
20
40
60
80
100
Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone
Year 1 (N = 1,471) Year 5 (N = 1,034)
PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up
(Follow-ups: January 2001 - June 2006)
NOTE: Different patients are analyzed in Year 1 and Year 5
% o
f P
atie
nts
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up
for Same Patients at Each Time Point(Follow-ups: January 2001 - June 2006)
% o
f P
atie
nts
ISHLT 2007
0%
20%
40%
60%
80%
100%
Year 1 (N = 311) Year 5 (N = 314)
None
Other
Tacrolimus
Tacrolimus + MMF
Tacrolimus + AZA
Cyclosporine
Cyclosporine + MMF
Cyclosporine + AZA
J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Prednisone Use
Conditional on Survival to 1 Year (Transplants: April 1994 - June 2005)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9
Years
Prednisone use at discharge and 1 year (N = 1,614)
No Prednisone at discharge or at 1 year (N = 297)
Prednisone at discharge/not at 1 year (N = 339)
p = 0.0102
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Prednisone Use for a Recent Era
Conditional on Survival to 1 Year (Transplants: January 1998 – June 2005)
50
60
70
80
90
100
0 1 2 3 4 5 6
Years
Prednisone use at discharge and 1 year (N = 1,282)
No Prednisone at discharge or at 1 year (N = 216)
Prednisone at discharge/not at 1 year (N = 277)
p = 0.1326
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Stratified by Tacrolimus vs. Cyclosporine Use at Discharge
(Transplants: January 1998 - June 2005) Conditional on Survival to 14 Days
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Years
Tacrolimus use at discharge (N = 803)
Cyclosporine use at discharge (N = 1,419)
Su
rviv
al (
%)
ISHLT 2007
p = 0.3486
J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Rejection within 1st Year
(Transplants: April 1994 - June 2004)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Years
Free from Rejection during 1 year (N = 890)Rejection within 1st Year (N =1,089)
p = <.0001
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Rejection within 1st Year
for Recent Transplants
(Transplants: January 2000 – June 2004)
50
60
70
80
90
100
0 1 2 3 4 5 6
Years
Free from Rejection during 1st Year (N = 407)Rejection within 1st Year (N = 478)
p = 0.0034
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Rejection within 1st Year
Stratified by Calcineurin Use at Discharge (Transplants: April 1994 - June 2005)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Years
CyA: Free from Rejection during 1 year (N = 362)
CyA: Rejection within 1st Year (N = 442)
TAC: Free from Rejection during 1 year (N = 203)
TAC: Rejection within 1st Year (N = 232)
Free from Rejection: CyA vs. TAC p = 0.0262Rejection: CyA vs. TAC p = 0.2743 CyA: Rejection vs. no rejection p = 0.0010TAC: Rejection vs. no rejection p = 0.1610
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Rejection within 1st Year
Stratified by Calcineurin Use at Discharge: Age = 0-10 Years (Transplants: April 1994 - June 2005)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Years
CyA: Free from Rejection during 1 year (N = 260)
CyA: Rejection within 1st Year (N = 262)
TAC: Free from Rejection during 1 year (N = 136)
TAC: Rejection within 1st Year (N = 119)
Free from Rejection: CyA vs. TAC p = 0.02230Rejection: CyA vs. TAC p = 06632 CyA: Rejection vs. no rejection p = 0.0003TAC: Rejection vs. no rejection p = 0.2545
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Rejection within 1st Year
Stratified by Calcineurin Use at Discharge: Age = 11-17 Years (Transplants: April 1994 - June 2005)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Years
CyA: Free from Rejection during 1 year (N = 102)
CyA: Rejection within 1st Year (N =180)
TAC: Free from Rejection during 1 year (N = 67)
TAC: Rejection within 1st Year (N = 113)
Free from Rejection: CyA vs. TAC p = 0.6272Rejection: CyA vs. TAC p = 0.3255 CyA: Rejection vs. no rejection p = 0.7865TAC: Rejection vs. no rejection p = 0.5992
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Rejection within 1st Year
for Recent TransplantsStratified by Calcineurin Use at Discharge (Transplants: January 2000 - June 2005)
50
60
70
80
90
100
0 1 2 3 4 5
Years
CyA: Free from Rejection during 1 year (N = 229)
CyA: Rejection within 1st Year (N = 280)
TAC: Free from Rejection during 1 year (N = 163)
TAC: Rejection within 1st Year (N = 159)
Free from Rejection: CyA vs. TAC p = 0.0197Rejection: CyA vs. TAC p = 0.4295 CyA: Rejection vs. no rejection p = 0.0085TAC: Rejection vs. no rejection p = 0.3783
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
0%
20%
40%
60%
80%
100%
Year 1 (N = 1,471) Year 5 (N = 1034)
None
Other
Tacrolimus
Tacrolimus + MMF
Tacrolimus + AZA
Cyclosporine
Cyclosporine + MMF
Cyclosporine + AZA
PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression Drug Combinations at Time of Follow-up
(Follow-ups: January 2001 - June 2006)
NOTE: Different patients are analyzed in Year 1 and Year 5
% o
f P
atie
nts
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEARStratified by Induction (Transplants: January 2000 - June 2005)
0
10
20
30
40
50
60
70
Overall <1 1-10 11-17 F M
No induction Used Induction Used (no OKT3)
Age group Gender
% t
reat
ed f
or
reje
ctio
n w
ith
in 1
yea
r
No within age group or gender comparisons were significant except 1-10 years (p=0.005).
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
NUMBER OF REJECTION EPISODES FOR PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Induction (Transplants: January 2000 - June 2005)
0
0.5
1
1.5
2
2.5
Overall <1 1-10 11-17 F M
No induction Used Induction Used (no OKT3)
No within age group or gender comparisons were significant.
Age group Gender
Ave
rag
e n
um
ber
of
reje
ctio
n e
pis
od
es
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Type of Induction (Transplants: January 2000 - June 2005)
0
10
20
30
40
50
60
70
80
90
Overall <1 1-10 11-17 F M
No induction PolyclonalIL2R-antagonist OKT3
% t
reat
ed f
or
reje
ctio
n w
ith
in 1
yea
r
Overall: No induction vs. OKT3 (p = 0.0032); polyclonal vs. OKT3 (p = 0.024); IL2 vs. OKT3 (p = 0.035). 1-10: No induction vs. polyclonal (p = 0.0047); 11-17: No induction vs. OKT3 (p = 0.0097); polyclonal vs. OKT3 (p = 0.028); IL2R vs. OKT3 (p = 0.013)Female: No induction vs. OKT3 (p = 0.015); polyclonal vs. OKT3 (p = 0.041)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
NUMBER OF REJECTION EPISODES FOR PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Type of Induction (Transplants: January 2000 - June 2005)
0
0.5
1
1.5
2
2.5
Overall <1 1-10 11-17 F M
No induction Polyclonal IL2R-antagonist OKT3
11-17 years: No induction vs. OKT3 (p = 0.04). No other comparisons were significant.
Ave
rag
e n
um
ber
of
reje
ctio
n e
pis
od
es
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Maintenance Immunosuppression and Induction (Transplants: January 2000 - June 2005)
0
10
20
30
40
50
60
70
Overall <1 1-10 11-17
CyA + No induction Used CyA + Induction Used (no OKT3)TAC + No induction Used TAC + Induction Used (no OKT3)
Age group% t
reat
ed f
or
reje
ctio
n w
ith
in 1
yea
r
Overall: CyA + induction vs. TAC + no induction: p = 0.0179<1: CyA + no induction vs. TAC + no induction: p = 0.0471-10 years: CyA + induction vs. TAC + induction: p = 0.017; CyA + induction vs. TAC + no induction: p = 0.0003; CyA + no induction vs. CyA + induction: 0.011.
No other age group differences were significant.
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
NUMBER OF REJECTION EPISODES FOR PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Maintenance Immunosuppression and Induction (Transplants: January 2000 - June 2005)
0
0.5
1
1.5
2
2.5
Overall <1 1-10 11-17
CyA + No induction Used CyA + Induction Used (no OKT3)TAC + No induction Used TAC + Induction Used (no OKT3)
<1 years: CyA + no induction vs. TAC + no induction: p = 0.048.No other age group comparisons were significant.
Age group
Ave
rag
e n
um
ber
of
reje
ctio
n e
pis
od
es
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Maintenance Immunosuppression (Transplants: January 2000 - June 2005)
0
10
20
30
40
50
60
70
Overall <1 1-10 11-17
Cyclosporine + MMF Cyclosporine + AZATacrolimus + MMF Tacrolimus + AZA
% t
reat
ed f
or
reje
ctio
n w
ith
in 1
yea
r
Overall: CyA +MMF vs. TAC + AZA (p = 0.0027); CyA + AZA vs. TAC + AZA (p = 0.013).<1: CyA + MMF vs. TAC + MMF ( p = 0.024); CyA + AZA vs. TAC + MMF (p = 0.021). 1-10: CyA + MMF vs. TAC + AZA (p = 0.0014); TAC + MMF vs. TAC + AZA (p = 0.011); CyA + AZA vs. TAC + AZA (p = 0.016).
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
NUMBER OF REJECTION EPISODES FOR PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR Stratified by Maintenance Immunosuppression (Transplants: January 2000 - June 2005)
0
0.5
1
1.5
2
2.5
Overall <1 1-10 11-17
Cyclosporine + MMF Cyclosporine + AZATacrolimus + MMF Tacrolimus + AZA
Ave
rag
e n
um
ber
of
reje
ctio
n e
pis
od
es
<1 years: CyA + AZA vs. TAC + MMF (p=0.0027); CyA + AZA vs. TAC + AZA (p=0.45). No other age group comparisons were significant.
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEARStratified by Calcineurin Inhibitor Use at Discharge
(Transplants: January 2000 - June 2005)
0
10
20
30
40
50
60
Overall <1 1-10 11-17
Cyclosporine Tacrolimus
Age group
% t
reat
ed f
or
reje
ctio
n w
ith
in 1
yea
r
Overall: CyA vs. TAC (p = 0.0084) 1-10: CyA vs. TAC (p = 0.0079)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
NUMBER OF REJECTION EPISODES FOR PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Calcineurin Inhibitor Use at Discharge (Transplants: January 2000 - June 2005)
0
0.5
1
1.5
2
2.5
Overall <1 1-10 11-17
Cyclosporine Tacrolimus
No comparisons were significant other than <1 years (p = 0.031).
Age group
Ave
rag
e n
um
ber
of
reje
ctio
n e
pis
od
es
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS
Cumulative Prevalence in Survivors within 1 Year Post-Transplant (Follow-ups: April 1994 - June 2006)
Outcome Within 1
Year Total number with known response
Hypertension 46.7% (N = 2,704)
Renal Dysfunction 6.0% (N = 2,710)
Abnormal Creatinine < 2.5 mg/dl 4.0% Creatinine > 2.5 mg/dl 1.2% Chronic Dialysis 0.8% Renal Transplant 0.0%
Hyperlipidemia 11.1% (N = 2,838)
Diabetes 3.5% (N = 2,716)
Coronary Artery Vasculopathy 2.5% (N = 2,495)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 5 Years Post-Transplant
(Follow-ups: April 1994 - June 2006)
Outcome Within 5
Years Total number with known response
Hypertension 63.2% (N = 980)
Renal Dysfunction 9.3% (N = 1,021)
Abnormal Creatinine < 2.5 mg/dl 7.5% Creatinine > 2.5 mg/dl 1.0% Chronic Dialysis 0.6% Renal Transplant 0.2%
Hyperlipidemia 25.6% (N = 1,062)
Diabetes 5.0% (N = 981)
Coronary Artery Vasculopathy 10.9% (N = 724)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 8 Years Post-Transplant
(Follow-ups: April 1994 - June 2006)
Outcome Within 8
Years Total number with known response
Hypertension 67.3% (N = 404)
Renal Dysfunction 10.3% (N = 427) Abnormal Creatinine < 2.5 mg/dl 8.0% Creatinine > 2.5 mg/dl 0.5% Chronic Dialysis 1.4% Renal Transplant 0.5%
Hyperlipidemia 31.4% (N = 446)
Diabetes 5.0% (N = 404)
Coronary Artery Vasculopathy 14.6% (N = 246)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 10 Years Post-Transplant
(Follow-ups: April 1994 - June 2006)
Outcome Within 10
Years Total number with known response
Hypertension 72.3% (N = 177)
Renal Dysfunction 17.4% (N = 190) Abnormal Creatinine < 2.5 mg/dl 13.2% Creatinine > 2.5 mg/dl 1.6% Chronic Dialysis 1.6% Renal Transplant 1.1%
Hyperlipidemia 38.2% (N = 199)
Diabetes 4.5% (N = 179)
Coronary Artery Vasculopathy 16.7% (N = 96)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2006)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Years
% F
reed
om
fro
m C
AV
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2006)
Stratified by Induction
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Years
Induction (N =844)
No Induction (N = 1,343)% F
ree
do
m f
rom
CA
V
p = 0.8381
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2006)
Stratified by Age Group
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Years
<1 Year (N =576)
1-10 Years (N = 826)
11-17 Years (N = 793)
p < 0.0001
% F
ree
do
m f
rom
CA
V
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: January 1999-June 2006)
Stratified by Age Group
50
60
70
80
90
100
0 1 2 3 4 5 6
Years
<1 Year (N = 475)
1-10 Years (N = 727)
11-17 Years (N = 744)
p = <.0001
% F
ree
do
m f
rom
CA
V
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2006)
Stratified by Ischemia Time
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Years
0-<2 hours (N=232)
2-<4 hours (N=1,123)
4+ hours (N=693)
p = 0.0090
% F
ree
do
m f
rom
CA
V
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: January 1999 - June 2006)
Stratified by Ischemia Time for Recent Era
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Years
0-<2 hours (N=149)
2-<4 hours (N=823)
4+ hours (N=501)
p = 0.0081
% F
ree
do
m f
rom
CA
V
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2006)
Stratified by Ischemia Time and Recipient Age
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9
Years
0-<2 hours/0-10 years (N=129)
2+ hours/0-10 years (N=665)
0-<2 hours/11-17 years (N=91)
2+ hours/11-17 years (N=409)
0-10 years: p = 0.0124;11-17 years: p = 0.1837
% F
ree
do
m f
rom
CA
V
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
GRAFT SURVIVAL FOLLOWING REPORT OF CORONARY ARTERY VASCULOPATHY
For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2006)Stratified by Age Group
0
10
20
30
40
50
60
70
80
90
100
0 0.5 1 1.5 2 2.5 3 3.5
Time since Report of CAV (Years)
<1 Year (N = 50)
1-10 Years (N = 94)
11-17 Years (N = 122)
p = 0.0234
Su
rviv
al s
ince
Rep
ort
of
CA
V (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
FREEDOM FROM SEVERE RENAL DYSFUNCTION*For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2006)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9
Years
* Severe renal dysfunction = Creatinine > 2.5 mg/dl (221 μmol/L), dialysis or renal transplant
% F
reed
om
fro
m S
ever
e
Ren
al D
ysfu
nct
ion
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
MALIGNANCY POST-HEART TRANSPLANTATION FOR PEDIATRICSCumulative Prevalence in Survivors (Follow-ups: April 1994 - June 2006)
Malignancy/Type 1-Year Survivors
5-Year Survivors
10-Year Survivors
No Malignancy 2771 (98.1%) 1010 (95%) 186 (93%)
Malignancy (all types combined) 55 (1.9%) 53 (5%) 14 (7%)
Malignancy Type
Lymph 51 48 13
Other 3 6
Skin 1
Type Not Reported 1 1
ISHLT 2007
NOTE: Multiple types may be reported; sum of types may be greater than total number with malignancy.
J Heart Lung Transplant 2007;26: 796-807
FREEDOM FROM MALIGNANCYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2006)
80
85
90
95
100
0 1 2 3 4 5 6 7 8 9 10
Years
All malignancy Lymph Skin Other
% F
reed
om
fro
m M
alig
nan
cy
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 1 and 3 Years
(Transplants: April 1993 - June 2003)
Maintenance Immunosuppression at discharge and 1 year
% HTN reported between 1 and 3 years
P-valueFor Patients
on drugFor Patients not on drug
Azathioprine 21.9 24.2 0.4675
Cyclosporine 20.7 25.0 0.2225
MMF 20.7 22.1 0.6763
Prednisone 29.3 8.0 <.0001
Rapamycin 100.0 21.1 -
Tacrolimus 29.1 19.1 0.0045
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 3 and 8 Years
(Transplants: April 1993 - June 1998)
Maintenance Immunosuppression at discharge and 1 year
% HTN reported between 3 and 8 years
P-valueFor Patients
on drugFor Patients not on drug
Azathioprine 37.0 42.3 0.6119
Cyclosporine 34.7 41.7 0.5062
MMF 38.5 37.4 0.9407
Prednisone 47.8 19.1 0.0002
Rapamycin - 35.8 -
Tacrolimus 38.9 33.1 0.6234
ISHLT 2007
N=204
J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART RECIPIENTSRelationship of Rejection and Coronary Artery Vasculopathy
(Follow-ups: April 1994 – June 2006)
Rejection During 1st Year
Reported CAV between 1st and 3rd years
post-transplant
Reported CAV between 3rd
and 5th years
post-transplant
Yes No All Yes No All
Yes 44
7.7%
529
92.3%
573
100%
23
7.7%
275
92.3%
298
100%
No 18
3.0%
588
97.0%
606
100%
15
4.8%
300
95.2%
315
100%p = 0.0003 p = 0.1293
NOTE: Only those recipients without CAV prior to 3 years were included in the last set of columnsISHLT 2007
J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2006)
CAUSE OF DEATH 0-30 Days (N = 387)
31 Days - 1 Year (N = 332)
>1 Year - 3 Years (N = 249)
>3 Years - 5 Years (N = 169)
>5 Years - 10 Years (N = 237)
>10 Years (N = 103)
CORONARY ARTERY VASCULOPATHY
4 (1.0%) 27 (8.1%) 50 (20.1%) 60 (35.5%) 72 (30.4%) 32 (31.1%)
ACUTE REJECTION 40 (10.3%) 83 (25.0%) 65 (26.1%) 23 (13.6%) 36 (15.2%) 7 (6.8%)
LYMPHOMA 7 (2.1%) 11 (4.4%) 3 (1.8%) 23 (9.7%) 6 (5.8%)
MALIGNANCY, OTHER
4 (1.2%) 2 (0.8%) 1 (0.6%) 3 (1.3%) 7 (6.8%)
CMV 1 (0.3%) 7 (2.1%) 1 (0.4%)
INFECTION, NON-CMV
53 (13.7%) 55 (16.6%) 17 (6.8%) 7 (4.1%) 14 (5.9%) 10 (9.7%)
PRIMARY FAILURE 73 (18.9%) 17 (5.1%) 8 (3.2%) 10 (5.9%) 11 (4.6%) 2 (1.9%)
GRAFT FAILURE 90 (23.3%) 35 (10.5%) 45 (18.1%) 38 (22.5%) 47 (19.8%) 25 (24.3%)
TECHNICAL 21 (5.4%) 2 (0.6%) 2 (0.8%) 1 (0.6%) 2 (0.8%)
OTHER 19 (4.9%) 15 (4.5%) 19 (7.6%) 14 (8.3%) 17 (7.2%) 2 (1.9%)
MULTIPLE ORGAN FAILURE
38 (9.8%) 45 (13.6%) 7 (2.8%) 3 (1.8%) 4 (1.7%) 6 (5.8%)
RENAL FAILURE 1 (0.3%) 5 (1.5%) 1 (0.4%) 1 (1.0%)
PULMONARY 24 (6.2%) 20 (6.0%) 13 (5.2%) 8 (4.7%) 4 (1.7%) 5 (4.9%)
CEREBROVASCULAR 23 (5.9%) 10 (3.0%) 8 (3.2%) 1 (0.6%) 4 (1.7%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807
PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1998 - June 2006)
CAUSE OF DEATH 0-30 Days (N = 164)
31 Days - 1 Year (N = 159)
>1 Year - 3 Years (N = 144)
>3 Years - 5 Years (N = 104)
>5 Years - 10 Years (N = 184)
>10 Years (N = 96)
CAV 1 (0.6%) 11 (6.9%) 25 (17.4%) 36 (34.6%) 56 (30.4%) 30 (31.3%)
ACUTE REJECTION 19 (11.6%) 30 (18.9%) 32 (22.2%) 14 (13.5%) 27 (14.7%) 7 (7.3%)
LYMPHOMA 3 (1.9%) 6 (4.2%) 2 (1.9%) 19 (10.3%) 6 (6.3%)
MALIGNANCY, OTHER
1 (0.6%) 1 (0.7%) 2 (1.1%) 6 (6.3%)
CMV 3 (1.9%) 1 (0.7%)
INFECTION, NON-CMV
24 (14.6%) 22 (13.8%) 8 (5.6%) 2 (1.9%) 12 (6.5%) 8 (8.3%)
PRIMARY FAILURE 30 (18.3%) 5 (3.1%) 4 (2.8%) 3 (2.9%) 5 (2.7%) 2 (2.1%)
GRAFT FAILURE 29 (17.7%) 15 (9.4%) 30 (20.8%) 30 (28.8%) 38 (20.7%) 23 (24.0%)
TECHNICAL 8 (4.9%) . (.%) 2 (1.4%) 2 (1.1%)
OTHER 14 (8.5%) 10 (6.3%) 16 (11.1%) 9 (8.7%) 14 (7.6%) 2 (2.1%)
MULTIPLE ORGAN FAILURE
20 (12.2%) 31 (19.5%) 6 (4.2%) 2 (1.9%) 3 (1.6%) 6 (6.3%)
RENAL FAILURE 5 (3.1%) 1 (0.7%) 1 (1.0%)
PULMONARY 8 (4.9%) 17 (10.7%) 8 (5.6%) 6 (5.8%) 3 (1.6%) 5 (5.2%)
CEREBROVASCULAR 11 (6.7%) 6 (3.8%) 4 (2.8%) 3 (1.6%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 796-807