J Heart Lung Transplant 2009;28: 989-1049 HEART TRANSPLANTATION Pediatric Recipients ISHLT 2009

J Heart Lung Transplant 2009;28: 989-1049

HEART TRANSPLANTATION

Pediatric Recipients

ISHLT

2009


AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS (Transplants: January 1996 - June 2008)

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

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

2009


AGE DISTRIBUTION FOR DONORS OF PEDIATRIC HEART RECIPIENTS

(Transplants: January 1996 - June 2008)

ISHLT

0

100

200

300

400

500

600

700

800

900

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)

Nu

mb

er

of

Tra

ns

pla

nts

2009


AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS

By Year of Transplant

0

50

100

150

200

250

300

350

400

450

500

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

11-17 Years

1-10 Years

<1 Year

Nu

mb

er

of

Tra

ns

pla

nts

ISHLT

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.

2009


NUMBER OF CENTERS REPORTING PEDIATRIC HEART TRANSPLANTS

0

10

20

30

40

50

60

70

80

90

100

110

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

Nu

mb

er

of

Ce

nte

rs R

ep

ort

ing

ISHLT

2009


NUMBER OF CENTERS REPORTING PEDIATRIC HEART TRANSPLANTS

0

10

20

30

40

50

60

70

80

90

100

110

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

Other

Europe

North America

Nu

mb

er

of

Ce

nte

rs R

ep

ort

ing

ISHLT

2009


AVERAGE CENTER VOLUMEPediatric Heart Transplants: January 1, 1997 - June 30, 2008

120

18

120

18 1490

20

40

60

80

100

120

140

1-4/yr 5-9/yr 10-19/yr

Average number of heart transplants per year

0

5

10

15

20

25

30

35

40

45

50

Number of centers 1997-2000 Number of centers 2001-June 2008

Percentage of transplants 1997-2000 Percentage of transplants 2001-June 2008

Nu

mb

er

of

ce

nte

rs

Pe

rce

nta

ge

of

tra

ns

pla

nts

ISHLT 2009


DISTRIBUTION OF TRANSPLANTS BY CENTER VOLUME

Pediatric Heart Transplants: January 1, 1997 - June 30, 2008

34.429.7 30.628.5 27.6

43.9

0

10

20

30

40

50

1-4 5-9 10-19

Average number of heart transplants per year

1997-2000 2001-June 2008

% o

f tr

an

sp

lan

ts

ISHLT 2009


PEDIATRIC HEART RE-TRANSPLANTSBy Transplant Year

Retransplants: January 1994 – December 2007

0

5

10

15

20

25

30

35

40

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

Nu

mb

er o

f tr

ansp

lan

ts

Year of transplant

ISHLT 2009 Analysis is based on the age at the time of retransplant


0

10

20

30

40

50

<1 month 1-<12 months 12-<36 months 36-<60 months 60+ months Not reported

% o

f R

e-T

ran

spla

nts

Time Between Previous and Current Transplant

PEDIATRIC HEART RE-TRANSPLANTSBy Intertransplant Interval

Retransplants: January 1994 - June 2008



40

50

60

70

80

90

100

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Su

rrv

iva

l (%

)

<1 Year (N=41) 1-<3 Years (N=32) 3-<5 Years (N=45)5+ Years (N=126) Primary TX (N=5,019)

Comparison of survival for re-transplant groups: p = 0.0115

Time (years) since most recent transplant

KAPLAN-MEIER SURVIVAL RATES FOR PEDIATRIC HEART RETRANSPLANTS STRATIFIED BY INTER-TRANSPLANT INTERVAL

Retransplants: January 1994 - June 2007



DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: < 1 Year)

0

25

50

75

100

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

Myopathy Congenital

% o

f C

as

es

31%

63%

5%

1%

1/1996-6/2008

16%

79%4%

1%

Myopathy

Congenital

Other

ReTX

1988-1995

ISHLT

2009


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

2002

2003

2004

2005

2006

2007

2008

Myopathy Congenital

% o

f C

as

es

55%

36%

3%

6%

1/1996-6/2008

52%

40%

4%

4% Myopathy

Congenital

Other

ReTX

1988-1995

ISHLT

2009


DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: 11-17 Years)

0

25

50

75

100

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

Myopathy Congenital

% o

f C

as

es

64%

24%

4%

7%

1/1996-6/2008

66%

26%

5%

3%

Myopathy

Congenital

Other

ReTX

1988-1995

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival (Transplants: 1/1982-6/2007)

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 = 1,976) 1-10 Years (N = 2,788)

11-17 Years (N = 2,869) Overall (N = 7,633)

0-<1 vs. 1-10: p = 0.0007; 0-<1 vs. 11-17: p=0.4922; 1-10 vs. 11-17: p=0.0011.

Half-life <1: 18.4 Years; 1-10: 14.7 Years; 11-17: 11.1 Years

Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONConditional Kaplan-Meier Survival

(Transplants: 1/1982-6/2007)

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 = 1,373) 1-10 Years (N = 2,163)11-17 Years (N =2,289) Overall (N = 5,825)

0-<1 vs. 1-10: p = 0.0044; 0-<1 vs. 11-17: p < 0.0001;1-10 vs. 11-17: p < 0.0001.

Half-life: <1: n.c.; 1-10: 18.5 Years; 11-17: 14.7 Years

Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONConditional Kaplan-Meier Survival for Recent Era

(Transplants: 1/1999-6/2007)

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

<1 Year (N = 606) 1-10 Years (N =1,033)

11-17 Years (N = 1,062) Overall (N = 2,701)

0-<1 vs. 1-10: p = 0.1610;0-<1 vs. 11-17: p = 0.0014; 1-10 vs. 11-17: p < 0.0001

Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era

(Transplants: 1/1982-6/2007)

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=855) 1990-1994 (N=1,861)

1995-1999 (N=1,877) 2000-6/2007 (N=3,040)

All p-values significant at p = 0.01 except comparison of 1995-1999 vs. 2000-6/2007

Half-life 1982-1989: 10.0 years; 1990-1994: 12.4 years; 1995-1999: n.c.; 2000-6/2007: n.c.

Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: 1/1982-6/2007)

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 16

Years

1982-1989 (N=177) 1990-1994 (N=584)

1995-1999 (N=494) 2000-6/2007 (N =721)

P-values for era comparisonsAll p-values significant at p < 0.0001 except comparison of 82-89 vs. 90-94 and 95-99 vs. 00-6/07

Half-life 1982-1989: 12.0 years; 1990-1994: 11.4 years; 1995-1999: n.c. ; 2000-6/2007: n.c.S

urv

iva

l (%

)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: 1/1982-6/2007)

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=657)

1995-1999 (N=720) 2000-6/2007 (N=1,145)

P-values for era comparisonsAll p-values significant at p = 0.01

Half-life 1982-1989: 10.8; 1990-1994: 13.3; 1995-1999: . ; 2000-6/2007: n.a.

Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: 1/1982-6/2007)

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=412) 1990-1994 (N=620)

1995-1999 (N=663) 2000-6/2007 (N=1,174)

P-values for era comparisonsNo p-values significant at p = 0.05 except 82-89 vs. 90-94: p = 0.0250; 82-89 vs. 88-6/07: p < 0.0001;

Half-life 1982-1989: 9.9; 1990-1994: 12.1; 1995-1999: 10.1; 2000-6/2007: n.a.

Su

rviv

al (

%)

ISHLT

2009


0%

20%

40%

60%

80%

100%

Europe North America Other

% o

f T

ran

spla

nts

1-4/year 5-9/year 10-19/year

PEDIATRIC HEART TRANSPLANTS: AVERAGE CENTER VOLUME DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2008

ISHLT

2009


0%

20%

40%

60%

80%

100%


% o

f T

ran

spla

nts

<1 years 1-10 years 11-17 years

PEDIATRIC HEART TRANSPLANTS:AGE DISTRIBUTION BY LOCATION


ISHLT

2009


0%

20%

40%

60%

80%

100%


% o

f T

ran

sp

lan

ts

Other

Re-TX/GraftFailure

Malignancy

Coronary ArteryDisease

Congenital

Cardiomyopathy

PEDIATRIC HEART TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION


ISHLT

2009


0%

20%

40%

60%

80%

100%


% o

f D

on

ors

<1 1-10 11-17 18-34 35-49 50-64

PEDIATRIC HEART TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION


ISHLT

2009


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2007)

Risk Factors For 1 Year Mortality

N=3,756

VARIABLE N Relative

Risk P-value

95% Confidence Interval

Congenital diagnosis, age = 0, on ECMO 74 2.70 0.0003 1.57 -4.63

Congenital diagnosis, age > 0 893 2.17 <0.0001 1.67 -2.83

Retransplant 225 2.09 0.0002 1.42 -3.07

On ventilator 706 1.80 <0.0001 1.45 -2.23

On dialysis 91 1.62 0.021 1.08 -2.43

Year of Transplant: 1995-96 vs. 2001-2002 506 1.55 0.0049 1.14 -2.09

PRA > 10% 344 1.37 0.0228 1.04 -1.79

Infection requiring IV drug therapy (with 2wk/TX) 565 1.29 0.0267 1.03 -1.62

Donor cause of death = anoxia vs. head trauma 863 0.80 0.0468 0.64 -1.00

Not ABO identical 843 0.79 0.0384 0.63 -0.99

Diagnosis other than congenital, no ECMO, age = 0 295 0.46 0.0042 0.27 -0.78

ISHLT

Reference diagnosis = cardiomyopathy2009



Borderline Significant Risk Factors For 1 Year Mortality

N=3,756

VARIABLE N Relative

Risk P-value

95% Confidence

Interval

Donor cause of death = cerebrovascular/ stroke vs head trauma

383 1.29 0.0779 0.97 -1.72

Female recipient 1657 1.19 0.0602 0.99 -1.42

ISHLT

2009


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2007) Risk Factors for 1 Year Mortality

Continuous Factors (see figures)

Recipient age Recipient height

Donor age Donor height

Creatinine Ischemia time (borderline)

Pediatric transplant volume

ISHLT

N=3,756

2009



Recipient Age

0

0.5

1

1.5

2

2.5

3

0 3 6 9 12 15 18


Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.023

ISHLT N=3,756

2009



Donor Age

0

0.5

1

1.5

2

2.5

3

0 5 10 15 20 25 30 35 40

Donor Age (Years)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.015

ISHLT N=3,756

2009



Pre-Transplant Creatinine

0

0.5

1

1.5

2

2.5

3

0 0.5 1 1.5 2 2.5

Recipient serum creatinine (mg/dl)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.023

ISHLT N=3,756

2009



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)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.042

ISHLT N=3,756

2009



Recipient Height

0

0.5

1

1.5

2

2.5

3

3.5

4

55 65 75 85 95 105 115 125 135 145 155 165 175

Height (cm)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.00013

ISHLT N=3,756

2009

NOTE: The impact of height should be considered in the context of age and diagnosis+age.



Donor Height

0

0.5

1

1.5

2

2.5

3

55 65 75 85 95 105 115 125 135 145 155 165 175

Height (cm)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.047

ISHLT N=3,756

2009

NOTE: The impact of height should be considered in the context of age.



Ischemia Time

0

0.5

1

1.5

2

2.5

2 3 4 5 6

Ischemia time (hours)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.080

ISHLT N=3,756

2009


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2007) Factors Not Significant for 1 Year Mortality

Recipient Factors:IV inotropes, sternotomy, history of malignancy, hospitalized, diabetes

Donor Factors:Gender, clinical infection, history of diabetes

Transplant Factors:CMV mismatch, HLA mismatch

ISHLT

2009



Age = <1 YearsRisk Factors For 1 Year Mortality

N=1,014

VARIABLE N

Relative Risk

P-value 95% Confidence Interval

ECMO (diagnosis = congenital) 74 3.31 <0.0001 2.13 -5.15

On dialysis 23 2.24 0.01 1.21 -4.14



On ventilator 343 1.72 0.0011 1.24 -2.38

Donor cause of death = cerebrovascular/stroke vs. head trauma

54 1.71 0.0399 1.03 -2.86

Infection requiring IV drug therapy (with 2wk/TX) 260 1.40 0.0377 1.02 -1.93

Donor clinical infection 163 0.63 0.0378 0.41 -0.97

Diagnosis = cardiomyopathy 285 0.53 0.0109 0.33 -0.86

ISHLT

Reference diagnosis = congenital without PGE or ECMO2009



Age = <1 YearsBorderline Significant Risk Factors For 1 Year Mortality

N=1,014

VARIABLE N Relative

Risk P-value

95% Confidence

Interval

Ventricular assist device (excluding patients on ECMO)

23 2.23 0.0858 0.89 -5.55

PRA > 10% 76 1.62 0.0738 0.95 -2.76

ISHLT

2009



Age = <1 Years Risk Factors for 1 Year Mortality


Creatinine Recipient height


ISHLT

N=1,014

2009


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2007) Risk Factors for 1 Year Mortality in Age = <1 Years


0

0.5

1

1.5

2

2.5

0 0.2 0.4 0.6 0.8 1


Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.019

ISHLT N=1,014

2009




0

0.5

1

1.5

2

0 2 4 6 8 10 12 14 16 18 20


Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0097

ISHLT N=1,014

2009



Recipient Height

0

0.5

1

1.5

2

2.5

3

45 50 55 60 65 70 75

Height (cm)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.019

ISHLT N=1,014

2009



Age = 1-10 YearsRisk Factors For 1 Year Mortality

N=1,412

VARIABLE N Relative

Risk P-value


Diagnosis = congenital 546 2.13 <0.0001 1.51 -3.01

Diagnosis = retransplant 101 2.02 0.0334 1.06 -3.86

Transfusions prior to transplant 349 1.65 0.0057 1.16 -2.36


Donor cause of death = anoxia vs. head trauma 318 0.61 0.0213 0.41 -0.93

ISHLT




Age = 1-10 YearsBorderline Significant Risk Factors For 1 Year Mortality

N=1,412

VARIABLE N Relative

Risk P-value



ISHLT

2009



Age = 1-10 Years Risk Factors for 1 Year Mortality


Creatinine Donor height

BSA ratio Bilirubin (borderline)

ISHLT

N=1,412

2009


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2007) Risk Factors for 1 Year Mortality in Age = 1-10 Years


0

0.5

1

1.5

2

2.5

0 0.2 0.4 0.6 0.8 1 1.2


Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.032

ISHLT N=1,412

2009



BSA Ratio

0

0.5

1

1.5

2

2.5

3

0.8 1 1.2 1.4 1.6 1.8

Donor BSA/Recipient BSA

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0014

ISHLT N=1,412

2009



Donor Height

0

0.5

1

1.5

2

70 80 90 100 110 120 130 140 150 160

Height (cm)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001

ISHLT N=1,412

2009



Recipient Bilirubin

0

0.5

1

1.5

2

0 0.5 1 1.5 2 2.5 3 3.5

Bilirubin (mg/dL)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.076

ISHLT N=1,412

2009



Age = 11-17 YearsRisk Factors For 1 Year Mortality

N=1,330

VARIABLE N Relative

Risk P-value

95% Confidence

Interval


Diagnosis = congenital 347 2.32 <0.0001 1.61 -3.35

ECMO 45 2.28 0.0159 1.17 -4.45

On ventilator 123 2.04 0.0051 1.24 -3.37

ISHLT




Age = 11-17 YearsBorderline Significant Risk Factors For 1 Year Mortality

N=1,330

VARIABLE N Relative

Risk P-value

95% Confidence

Interval

On dialysis 42 1.83 0.0884 0.91 -3.66

PRA > 10% 115 1.50 0.0932 0.93 -2.42

HLA mismatches at DR locus (per increasing mismatch, compared to 0 mismatches)

0 MM: N = 45 1 MM: N = 530 2 MM: N = 755

0.76 0.0542 0.57 -1.01

Transplant Year: 2003-04 vs. 2001-02 239 0.59 0.0822 0.33 -1.07

ISHLT

2009



Age = 11-17 Years Risk Factors for 1 Year Mortality


Donor Age

ISHLT

N=1,330

2009



Donor Age

0

0.5

1

1.5

2

2.5

10 15 20 25 30 35 40

Donor age (years)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.011

ISHLT N=1,330

2009




N=2,364

VARIABLE N Relative

Risk P-value


Congenital diagnosis, age = 0, on ECMO 36 2.12 0.0072 1.23 -3.67

Retransplant, age > 0 131 1.86 0.0002 1.34 -2.59

On dialysis 49 1.59 0.0337 1.04 -2.43

PRA > 10% 240 1.45 0.0019 1.15 -1.83

Congenital diagnosis, age > 0 586 1.38 0.0039 1.11 -1.71

On ventilator 445 1.30 0.0169 1.05 -1.61


Diagnosis other than congenital, no ECMO, age = 0 185 0.53 0.005 0.34 -0.83

ISHLT





N=2,364

VARIABLE N Relative

Risk P-value

95% Confidence

Interval

Cerebrovascular event prior to transplant 67 1.44 0.0698 0.97 -2.14


ISHLT

2009




Recipient age Recipient height (borderline)

Donor age Bilirubin (borderline)


ISHLT

N=2,364

2009



Recipient Age

0

0.5

1

1.5

2

2.5

3

0 3 6 9 12 15 18


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001

ISHLT N=2,364

2009



Donor Age

0

0.5

1

1.5

2

2.5

3

0 5 10 15 20 25 30 35 40

Donor Age (Years)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.023

ISHLT N=2,364

2009



Pre-Transplant Bilirubin

0

0.5

1

1.5

2

2.5

3

0 0.5 1 1.5 2 2.5 3 3.5

Recipient bilirubin (mg/dl)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.085

ISHLT N=2,364

2009




0

0.5

1

1.5

2

2.5

0 2 4 6 8 10 12 14 16 18 20


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.0078

ISHLT N=2,364

2009



Recipient Height

0

0.5

1

1.5

2

2.5

3

55 65 75 85 95 105 115 125 135 145 155 165 175

Height (cm)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.054

ISHLT N=2,364

2009

NOTE: The impact of height should be considered in the context of age and diagnosis+age.




N=915

VARIABLE N Relative

Risk P-

value 95% Confidence

Interval

Diagnosis = congenital 447 2.24 0.0001 1.49 -3.37

On ventilator 144 1.78 0.0068 1.17 -2.71

Female donor 394 1.54 0.009 1.11 -2.14

Transplant year: 1997-98 vs 1995-96 409 0.71 0.0449 0.50 -0.99

ISHLT

Reference diagnosis = cardiomyopathy

2009




N=915

VARIABLE N Relative

Risk P-value 95% Confidence

Interval


Age = 0 years* 289 0.61 0.0794 0.35 -1.06

* Effect should be considered in the context of continuous recipient age and height (see subsequent slides)

ISHLT


2009




Creatinine (borderline) Recipient age

Pediatric transplant volume (borderline)

Recipient weight

ISHLT

N=9152009



Recipient Age

0

0.5

1

1.5

2

2.5

3

3.5

0 2 4 6 8 10 12 14 16 18

Age (Years)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p = 0.011

ISHLT

N=6972009



Recipient Weight

0

0.5

1

1.5

2

2.5

3

3.5

4

0 10 20 30 40 50 60 70 80

Recipient weight (kg)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p < 0.0001

ISHLT N=915

2009




0

0.5

1

1.5

2

0 2 4 6 8 10 12 14 16 18 20


Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p = 0.071

ISHLT

N=9152009




0

0.5

1

1.5

2

2.5

0 0.5 1 1.5 2

Creatinine (mg/dl)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p = 0.085

ISHLT

N=9152009


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000) Factors Not Significant for 10 Year Mortality

Recipient Factors:PRA, diabetes, repeat transplant, transfusions, hospitalized, gender, PGE, VAD, bilirubin

Donor Factors:Cause of death, weight, height, age, clinical infection

Transplant Factors:Ischemia time, HLA mismatch, CMV mismatch

ISHLT

2009



Risk Factors for the Development of CAV within 5 Years

N=1,391

VARIABLE N Relative

Risk P-

value 95% Confidence

Interval


Number of mismatches at the A locus 0 A MM (N=72) 1 A MM (N=572) 2 A MM (N=747)

1.32 0.0422 1.01 -1.72

ISHLT


2009



Borderline Significant Risk Factors for the Development of CAV within 5 Years

N=1,391

VARIABLE N Relative

Risk P-value 95% Confidence

Interval

Induction with IL2R-antagonist 91 1.69 0.0582 0.98 -2.91

Diagnosis = congenital 580 1.37 0.0855 0.96 -1.95

Female donor 561 0.74 0.0649 0.53 -1.02

On ventilator 234 0.60 0.0531 0.36 -1.01

Neither AZA or MMF for discharge maintenance immunosuppression

188 0.55 0.0535 0.30 -1.01

ISHLT


2009


PEDIATRIC HEART TRANSPLANTS (7/1996-6/2003) Risk Factors for the Development of CAV within 5 Years


Donor age Bilirubin

Total transplant volume

ISHLT

N=1,3912009



Donor Age

0

1

2

3

4

5

0 5 10 15 20 25 30 35 40

Donor Age (Years)

Re

lati

ve

Ris

k o

f C

AV

wit

hin

5 Y

ea

rs

p < 0.0001

ISHLT

N=6972009



Center Volume of All Age Transplants

0

0.5

1

1.5

2

0 5 10 15 20 25 30 35 40


Re

lati

ve

Ris

k o

f C

AV

wit

hin

5 Y

ea

rs

p = 0.018

ISHLT

N=1,3912009



Pre-Transplant Bilirubin

0

0.5

1

1.5

2

2.5

0 0.5 1 1.5 2

Bilirubin (mg/dl)

Re

lati

ve

Ris

k o

f C

AV

wit

hin

5 Y

ea

rs

p = 0.034

ISHLT

N=1,3912009


PEDIATRIC HEART RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: April 1994 - June 2008)

0%

20%

40%

60%

80%

100%

1 Year (N = 2,146) 5 Year (N = 1,418) 10 Year (N = 557)

No Activity Limitations Performs with Some Assistance Requires Total Assistance

ISHLT

2009



(Follow-ups: April 1994 - June 2008)For the Same Patients

0%

20%

40%

60%

80%

100%

1 Year (N = 758) 3 Year (N = 758) 5 Year (N = 758)


ISHLT

2009



(Follow-ups: April 1994 - June 2008)Age: <1 Year

0%

20%

40%

60%

80%

100%



ISHLT

2009



(Follow-ups: April 1994 - June 2008)Age: 1-10 Years

0%

20%

40%

60%

80%

100%



ISHLT

2009



(Follow-ups: April 1994 - June 2008)Age: 11-17 Years

0%

20%

40%

60%

80%

100%



ISHLT

2009


PEDIATRIC HEART RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients

(Follow-ups: April 1994 - June 2008)

0%

20%

40%

60%

80%

100%

1 Year (N = 3,431) 5 Years (N =2,143) 10 Years (N = 944)

No Hospitalization Hospitalized, Not Rejection/Not Infection

Hospitalized, Rejection Hospitalized, Infection Only

Hospitalized, Rejection + Infection

ISHLT

2009


0

10

20

30

40

50

Any Induction (N =1,237)

Polyclonal ALG/ATG (N = 818)

OKT3 (N = 48) IL2R-antagonist (N =407)

PEDIATRIC HEART RECIPIENTS Induction Immunosuppression

(Transplants: January 2001 - June 2008)

% o

f P

atie

nts

ISHLT

Analysis is limited to patients who were alive at the time of the follow-up2009


0

10

20

30

40

50

60

70

Any Induction Polyclonal ALG/ATG IL2R-antagonist

% o

f P

ati

en

ts

20012002200320042005200620072008

PEDIATRIC HEART RECIPIENTSInduction Immunosuppression (Transplants: January 2001 - June 2008)

ISHLT

Test of increasing trend over time:Any induction p < 0.0001Polyclonal p < 0.0001IL2 p < 0.0001Analysis is limited to patients who were alive at the time of the follow-up

2009


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group

(Transplants: January 2000 – June 2007) Conditional on Survival to 14 Days

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

No induction (N = 1,150)

Polyclonal induction (N = 763)

IL2R-antagonist (N = 313)

No comparisons were statistically significant.

Su

rviv

al

(%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group and Treated Rejection Between

Transplant Discharge and 1-Year Follow-up (1-Year Follow-ups: July 2004 - June 2007)

Conditional on Survival to 1 Year

50

60

70

80

90

100

0 1 2 3

Years

No induction/No rejection (N = 242)

Polyclonal induction/No rejection (N = 183)

IL2R-antagonist/No rejection (N = 66)

No induction/Treated Rejection (N = 86)

Polyclonal induction/Treated Rejection (N = 77)

IL2R-antagonist/Treated Rejection (N = 38)

Su

rviv

al (

%)

No pair-wise comparisons of survival by induction were statistically significant within either rejection grouping

ISHLT

Treated rejection = Recipient was reported to (1) have at least one acute rejection episode that was treated with an anti-rejection agent; or (2) have been hospitalized for rejection.

No rejection = Recipient had (i) no acute rejection episodes and (ii) was reported either as not hospitalized for rejection or did not receive anti-rejection agents.

2009


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2007)

Conditional on Survival to 14 DaysAge: < 1 Year

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

No induction (N = 237)Polyclonal induction (N = 271)IL2R-antagonist (N = 41)


Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2007)

Conditional on Survival to 14 DaysAge: 1-10 Years

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

No induction (N = 465)Polyclonal induction (N = 260)IL2R-antagonist (N = 122)


Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2007)

Conditional on Survival to 14 DaysAge: 11-17 Years

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

No induction (N = 448)

Polyclonal induction (N = 232)

IL2R-antagonist (N = 150)


Su

rviv

al (

%)

ISHLT

2009


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

Year 1 (N = 1,946) Year 5 (N = 1,293)

PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

(Follow-ups: January 2001 - June 2008)

NOTE: Different patients are analyzed in Year 1 and Year 5

% o

f P

atie

nts

ISHLT



PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

for Same Patients at Each Time Point(Follow-ups: January 2001 - June 2008)

% o

f P

atie

nts

ISHLT

0%

20%

40%

60%

80%

100%

Year 1 (N = 631) Year 5 (N = 631)

None

Other

Tacrolimus

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine

Cyclosporine + MMF

Cyclosporine + AZA


0%

20%

40%

60%

80%

100%

Year 1 (N = 1,946) Year 5 (N = 1,293)

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 2008)

NOTE: Different patients are analyzed in Year 1 and Year 5

% o

f P

atie

nts

ISHLT

Analysis is limited to patients who were alive at the time of the follow-up

2009J Heart Lung Transplant 2009;28: 989-1049


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Prednisone Use

Conditional on Survival to 1 Year (Transplants: April 1994 - June 2007)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years

Prednisone use at discharge and 1 year (N = 1,970)

No Prednisone at discharge or at 1 year (N = 435)

Prednisone at discharge/not at 1 year (N = 388)

p < 0.0001

Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Prednisone Use for a Recent Era

Conditional on Survival to 1 Year (Transplants: January 1998 – June 2007)

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 = 1,506)

No Prednisone at discharge or at 1 year (N = 315)

Prednisone at discharge/not at 1 year (N = 304)

p = 0.0289

Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Stratified by Tacrolimus vs. Cyclosporine Use at Discharge

(Transplants: January 1998 - June 2007) Conditional on Survival to 14 Days

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Years

Tacrolimus use at discharge (N = 1,218)

Cyclosporine use at discharge (N = 1,428)

p = 0.0454

Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Stratified by Tacrolimus vs. Cyclosporine Use

Conditional on Survival to 1 Year (Transplants: January 1998 - June 2007)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Years

Cyclosporine use at discharge and 1 year (N = 845)

Tacrolimus use at discharge and 1 year (N = 891)

Cyclosporine use at discharge/Tacrolimus at 1 year (N = 109)

Tacrolimus use at discharge/Cyclosporine at 1 year (N = 20)

p = 0.0015

Su

rviv

al (

%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Treated Rejection within 1st Year

Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2007)

50

60

70

80

90

100

0 1 2 3

Years

Free from Rejection during 1 year (N = 347)Treated Rejection within 1st Year (N = 190)

p = 0.2875

Su

rviv

al (

%)

ISHLT



2009



Stratified by Calcineurin Use at Discharge Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2007)

50

60

70

80

90

100

0 1 2 3

Years

CyA: Free from Rejection during 1 year (N = 103)

CyA: Treated Rejection within 1st Year (N = 73)

TAC: Free from Rejection during 1 year (N = 218)

TAC: Treated Rejection within 1st Year (N = 95)

Free from Rejection: CyA vs. TAC p = 0.1253Treated Rejection: CyA vs. TAC p = 0..4397 CyA: Rejection vs. no rejection p = 0.3024TAC: Rejection vs. no rejection p = 0.4076

Su

rviv

al (

%)

ISHLT



2009



Stratified by Calcineurin Use at Discharge: Age = 0-10 Years Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2007)

50

60

70

80

90

100

0 1 2 3

Years

CyA: Free from Rejection during 1 year (N = 72)

CyA: Treated Rejection within 1st Year (N = 53)

TAC: Free from Rejection during 1 year (N = 131)


Free from Rejection: CyA vs. TAC p = 0.5082Rejection: CyA vs. TAC p = 0.8950 CyA: Rejection vs. no rejection p = 0.5133TAC: Rejection vs. no rejection p = 0.5413

Su

rviv

al (

%)

ISHLT



2009



Stratified by Calcineurin Use at Discharge: Age = 11-17 Years Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2007)

50

60

70

80

90

100

0 1 2 3

Years

CyA: Free from Rejection during 1st Year (N = 31)

CyA: Treated Rejection within 1st Year (N =20)

TAC: Free from Rejection during 1st Year (N = 87)


Free from Rejection: CyA vs. TAC p = 0.0746Rejection: CyA vs. TAC p = 0.3449 CyA: Rejection vs. no rejection p = 0.2482TAC: Rejection vs. no rejection p = 0.5380

Su

rviv

al (

%)

ISHLT



2009


PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS EXPERIENCING ACUTE REJECTION BETWEEN TRANSPLANT

DISCHARGE AND 1-YEAR FOLLOW-UP Stratified by Induction (Follow-ups: July 2004 - June 2008)

0

10

20

30

40

50

60

70No induction Used, Treatment No induction Used, No Treatment

Induction Used (no OKT3), Treatment Induction Used (no OKT3), No Treatment

% e

xper

ien

cin

g a

cute

rej

ecti

on

wit

hin

1 y

ear

Overall: p = 0.042

ISHLT

Overall < 1 1-10 10-17 Female Male




2009


PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS EXPERIENCING ACUTE REJECTION BETWEEN TRANSPLANT DISCHARGE

AND 1-YEAR FOLLOW-UP Stratified by Type of Induction (Follow-ups: July 2004 - June 2008)

0

10

20

30

40

50

60

70 No induction, Treatment No induction, No TreatmentPolyclonal, Treatment Polyclonal, No TreatmentIL2R-antagonist, Treatment IL2R-antagonist, No Treatment

% e

xper

ien

cin

g a

cute

rej

ecti

on

wit

hin

1 y

ear

Overall: No induct vs. IL2R (p=0.024); 11-17: No induction vs. IL2R (p=0.021)

ISHLT

Overall < 1 1-10 10-17 Female Male




2009



AND 1-YEAR FOLLOW-UP Stratified by Maintenance Immunosuppression and Induction (Follow-ups: July 2004 - June 2008)

0

10

20

30

40

50

60

70CyA + No induction, Treatment CyA + No induction, No TreatmentCyA + Induction (no OKT3), Treatment CyA + Induction (no OKT3), No TreatmentTAC + No induction, Treatment TAC + No induction, No TreatmentTAC + Induction (no OKT3), Treatment TAC + Induction (no OKT3), No Treatment

% e

xper

ien

cin

g a

cute

rej

ecti

on

wit

hin

1 y

ear

Overall: all comparisons were statistically significant at 0.05 except CyA + no induction vs. CyA + induction and TAC + no induction vs. TAC + induction<1 year: CyA + no induction vs. TAC + no induction ( p=0.016); 1-10 years: all comparisons were statistically significant at 0.05 except CyA + no induction vs. CyA + induction and TAC + no induction vs. TAC + induction

11-17 years: CyA + no induction vs. TAC + no induction (p = 0.004); CyA + induction vs. TAC + no induction (p < 0.001); CyA + induction vs. TAC + induction ( p =0.001)

ISHLT

Overall < 1 1-10 10-17




2009


PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS EXPERIENCING ACUTE REJECTION BETWEEN TRANSPLANT

DISCHARGE AND 1-YEAR FOLLOW-UP Stratified by Maintenance Immunosuppression (Follow-ups: July 2004 - June 2008)

0

10

20

30

40

50

60

70

Cyclosporine + MMF, Treatment Cyclosporine + MMF, No TreatmentCyclosporine + AZA, Treatment Cyclosporine + AZA, No TreatmentTacrolimus + MMF, Treatment Tacrolimus + MMF, No TreatmentTacrolimus + AZA, Treatment Tacrolimus + AZA, No Treatment

% e

xper

ien

cin

g a

cute

rej

ecti

on

wit

hin

1 y

ear

Overall: all comparisons were statistically significant at 0.05 except CyA +MMF vs. CyA +AZA and TAC + MMF vs. TAC + AZA. <1: CyA + MMF vs. TAC + MMF (p =0.017).1-10: CyA + MMF vs. TAC + MMF (p = 0.001); CyA + AZA vs. TAC + MMF (p=0.004).11-17: CyA + MMF vs. TAC + MMF (p =0.001); CyA + MMF vs. TAC + AZA (p=0.033).

ISHLT

Overall < 1 1-10 10-17




2009



AND 1-YEAR FOLLOW-UP Stratified by Calcineurin Inhibitor Use at Discharge

(Follow-ups: July 2004 - June 2008)

0

10

20

30

40

50

60Cyclosporine, Treatment Cyclosporine, No TreatmentTacrolimus, Treatment Tacrolimus, No Treatment

% e

xper

ien

cin

g a

cute

rej

ect

ion

wit

hin

1 y

ear

Overall: CyA vs. TAC (p < 0.0001)<1: CyA vs. TAC (p=0.031) 1-10: CyA vs. TAC (p < 0.0001)11-17: CyA vs. TAC (p < 0.0001)

ISHLT

Overall < 1 1-10 10-17



No rejection = Recipient had (i) no acute rejection episodes and (ii) was reported either as not hospitalized for rejection or did not receive anti-rejection agents.2009


FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years

% F

ree

do

m f

rom

CA

V

ISHLT

2009


FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008)

Stratified by Induction

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Years

Induction (N = 1,267)

No Induction (N = 1,769)

p = 0.4696

% F

ree

do

m f

rom

CA

V

ISHLT

2009


FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: 1999 - June 2008)

Stratified by Tacrolimus vs. Cyclosporine Use Conditional on Survival to 1 Year

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years





p = 0.2242

% F

ree

do

m f

rom

CA

V

ISHLT

2009


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008)

Stratified by Age Group

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Years

<1 Year (N = 801)

1-10 Years (N = 1,134)

11-17 Years (N = 1,113)

p < 0.0001

% F

ree

do

m f

rom

CA

V

ISHLT

2009


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: January 1999-June 2008)

Stratified by Age Group

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years

<1 Year (N = 553)

1-10 Years (N = 833)

11-17 Years (N = 833)

p < 0.0001

% F

ree

do

m f

rom

CA

V

ISHLT 2009



Stratified by Ischemia Time

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Years

0-<2 hours (N=321)

2-<4 hours (N=1,559)

4+ hours (N=969)

p = 0.0090

% F

ree

do

m f

rom

CA

V

ISHLT

2009


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: January 1999 - June 2008)

Stratified by Ischemia Time for Recent Era

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

0-<2 hours (N=208)

2-<4 hours (N=1,125)

4+ hours (N=708)

p = 0.0144

% F

ree

do

m f

rom

CA

V

ISHLT

2009



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=182)

2+ hours/0-10 years (N=1,625)

0-<2 hours/11-17 years (N=139)

2+ hours/11-17 years (N=903)

0-10 years: p = 0.0051;11-17 years: p = 0.2992

% F

ree

do

m f

rom

CA

V

ISHLT

2009


GRAFT SURVIVAL FOLLOWING REPORT OF CORONARY ARTERY VASCULOPATHY

For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008)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 4

Time since Report of CAV (Years)

<1 Year (N = 80)

1-10 Years (N = 135)

11-17 Years (N = 176)

p = 0.8363

Su

rviv

al s

ince

Rep

ort

of

CA

V (

%)

ISHLT

2009


FREEDOM FROM SEVERE RENAL DYSFUNCTION*For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years

% F

ree

do

m f

rom

Se

ve

re

Re

na

l Dy

sfu

nc

tio

n

* Severe renal dysfunction = Creatinine > 2.5 mg/dl (221 μmol/L), dialysis or renal transplant

ISHLT

2009


FREEDOM FROM SEVERE RENAL DYSFUNCTION*For Pediatric Heart Recipients (Follow-ups: 1999 - June 2008)


50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years





p = 0.1663

% F

ree

do

m f

rom

Se

ve

re

Re

na

l Dy

sfu

nc

tio

n

* Severe renal dysfunction = Creatinine > 2.5 mg/dl (221 μmol/L), dialysis or renal transplant

ISHLT

2009


MALIGNANCY POST-HEART TRANSPLANTATION FOR PEDIATRICSCumulative Prevalence in Survivors (Follow-ups: April 1994 - June 2008)

Malignancy/Type 1-Year Survivors

5-Year Survivors

10-Year Survivors

No Malignancy 3,361 (98.1%) 1,343 (95.2%) 332 (92.2%)

Malignancy (all types combined) 64 (1.9%) 68 (4.8%) 28 (7.8%)

Malignancy Type

Lymph 59 64 26

Other 4 5 2

Skin 1

Type Not Reported 1

ISHLT

NOTE: Multiple types may be reported; sum of types may be greater than total number with malignancy.

2009


FREEDOM FROM MALIGNANCYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008)

80

85

90

95

100

0 1 2 3 4 5 6 7 8 9 10

Years

All malignancy Lymph Skin Other% F

ree

do

m f

rom

Ma

lign

an

cy

ISHLT

2009


FREEDOM FROM MALIGNANCYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008)


80

85

90

95

100

0 1 2 3 4 5 6 7 8 9

Years





p = 0.0042

% F

ree

do

m f

rom

Ma

lig

na

nc

y

ISHLT

2009


FREEDOM FROM LYMPHOMAFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008)


80

85

90

95

100

0 1 2 3 4 5 6 7 8 9 10

Years

Induction No Induction

p = 0.9366

% F

ree

do

m f

rom

Ly

mp

ho

ma

ISHLT

2009


PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 1 and 3 Years

(Transplants: April 1993 - June 2005)

Maintenance Immunosuppression at discharge and 1 year

% HTN reported between 1 and 3 years

P-valueFor Patients

on drugFor Patients not on drug

Azathioprine 22.0 26.0 0.1643

Cyclosporine 21.4 26.2 0.1083

MMF 23.4 22.7 0.8049

Prednisone 29.6 10.7 <.0001

Rapamycin 37.5 22.5 -

Tacrolimus 28.8 20.3 0.0039

ISHLT

2009


PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 3 and 8 Years

(Transplants: April 1993 - June 2000)

Maintenance Immunosuppression at discharge and 1 year

% HTN reported between 3 and 8 years

P-valueFor Patients

on drugFor Patients not on drug

Azathioprine 37.5 48.9 0.1623

Cyclosporine 36.5 43.8 0.4302

MMF 41.4 37.6 0.6949

Prednisone 47.1 20.2 <.0001

Rapamycin . 37.6 -

Tacrolimus 42.3 34.8 0.4484

ISHLT

2009


FREEDOM FROM CMVFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008)


40

50

60

70

80

90

100

0 1 2 3 4Years

Induction (N = 299) No Induction (N = 420)

p = 0.3026

% F

ree

do

m f

rom

CM

V

ISHLT

2009



Stratified by Induction and Donor CMV Status

30

40

50

60

70

80

90

100

0 1 2 3 4Years

Induction/CMV(-) Donor (N = 134)

No Induction/CMV(-) Donor (N = 192)

Induction/CMV(+) Donor (N = 160)

No Induction/CMV(+) Donor (N = 219)

p < 0.0001

% F

ree

do

m f

rom

CM

V

ISHLT

2009 Analysis is limited to patients who were CMV negative at transplant.



Stratified by Donor CMV Status/ Recipient CMV status Induction

0

20

40

60

80

100

0 1 2 3Years

D(-)/R(-) (N=134) D(-)/R(+) (N=65)

D(+)/R(-) (N=160) D(+)/R(+) (N=98)

p < 0.0001

% F

ree

do

m f

rom

CM

V

ISHLT

2009



Stratified by Donor CMV Status/ Recipient CMV statusNo Induction

0

20

40

60

80

100

0 1 2 3 4Years

D(-)/R(-) (N=192) D(-)/R(+) (N=128)

D(+)/R(-) (N=219) D(+)/R(+) (N=121)

p < 0.0001

% F

ree

do

m f

rom

CM

V

ISHLT

2009


PEDIATRIC HEART RECIPIENTSRelationship of Rejection and Coronary Artery Vasculopathy

(Follow-ups: July 2004 – June 2008)

Rejection During 1st

Year

Reported CAV between 1st and 3rd years

post-transplant

Yes No All

Yes 5

5.9%

80

94.1%

85

100%

No 6

4.1%

142

95.9%

148

100%p = 0.5265

ISHLT

2009


PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2008)

CAUSE OF DEATH 0-30 Days (N = 461)

31 Days - 1 Year (N =

421)

>1 Year - 3 Years (N = 307)

>3 Years - 5 Years (N = 226)

>5 Years - 10 Years (N = 350)

>10 Years (N = 172)

CORONARY ARTERY VASCULOPATHY

5 (1.1%) 30 (7.1%) 62 (20.2%) 69 (30.5%) 98 (28.0%) 49 (28.5%)

ACUTE REJECTION 44 (9.5%) 100 (23.8%) 71 (23.1%) 31 (13.7%) 45 (12.9%) 10 (5.8%)

LYMPHOMA 10 (2.4%) 12 (3.9%) 6 (2.7%) 33 (9.4%) 11 (6.4%)

MALIGNANCY, OTHER 4 (1.0%) 2 (0.7%) 1 (0.4%) 5 (1.4%) 11 (6.4%)

CMV 1 (0.2%) 11 (2.6%) 1 (0.3%)

INFECTION, NON-CMV 54 (11.7%) 65 (15.4%) 20 (6.5%) 8 (3.5%) 17 (4.9%) 13 (7.6%)

PRIMARY FAILURE 102 (22.1%) 23 (5.5%) 10 (3.3%) 15 (6.6%) 18 (5.1%) 5 (2.9%)

GRAFT FAILURE 97 (21.0%) 45 (10.7%) 62 (20.2%) 53 (23.5%) 74 (21.1%) 44 (25.6%)

TECHNICAL 27 (5.9%) 3 (0.7%) 2 (0.7%) 2 (0.9%) 4 (1.1%) 1 (0.6%)

OTHER 25 (5.4%) 26 (6.2%) 29 (9.4%) 24 (10.6%) 30 (8.6%) 10 (5.8%)

MULTIPLE ORGAN FAILURE

46 (10.0%) 54 (12.8%) 11 (3.6%) 6 (2.7%) 10 (2.9%) 8 (4.7%)

RENAL FAILURE 1 (0.2%) 4 (1.0%) 1 (0.3%) 1 (0.4%) 1 (0.3%) 3 (1.7%)

PULMONARY 29 (6.3%) 30 (7.1%) 15 (4.9%) 8 (3.5%) 8 (2.3%) 5 (2.9%)

CEREBROVASCULAR 30 (6.5%) 16 (3.8%) 9 (2.9%) 2 (0.9%) 7 (2.0%) 2 (1.2%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1998 - June 2008)

CAUSE OF DEATH 0-30 Days (N = 213)

31 Days - 1 Year (N = 241)

>1 Year - 3 Years (N = 192)

>3 Years - 5 Years (N = 153)

>5 Years - 10 Years (N = 286)

>10 Years (N =165)

CAV 2 (0.9%) 14 (5.8%) 33 (17.2%) 43 (28.1%) 77 (26.9%) 47 (28.5%)

ACUTE REJECTION 22 (10.3%) 45 (18.7%) 36 (18.8%) 23 (15.0%) 36 (12.6%) 10 (6.1%)

LYMPHOMA 6 (2.5%) 7 (3.6%) 4 (2.6%) 28 (9.8%) 11 (6.7%)

MALIGNANCY, OTHER

1 (0.4%) 1 (0.5%) 4 (1.4%) 10 (6.1%)

CMV 7 (2.9%) 1 (0.5%)

INFECTION, NON-CMV

26 (12.2%) 31 (12.9%) 11 (5.7%) 3 (2.0%) 13 (4.5%) 11 (6.7%)

PRIMARY FAILURE 44 (20.7%) 9 (3.7%) 4 (2.1%) 6 (3.9%) 10 (3.5%) 5 (3.0%)

GRAFT FAILURE 31 (14.6%) 25 (10.4%) 48 (25.0%) 44 (28.8%) 66 (23.1%) 42 (25.5%)

TECHNICAL 14 (6.6%) 2 (1.0%) 4 (1.4%) 1 (0.6%)

OTHER 19 (8.9%) 20 (8.3%) 24 (12.5%) 17 (11.1%) 26 (9.1%) 10 (6.1%)

MULTIPLE ORGAN FAILURE

27 (12.7%) 40 (16.6%) 10 (5.2%) 5 (3.3%) 8 (2.8%) 8 (4.8%)

RENAL FAILURE 4 (1.7%) 1 (0.5%) 1 (0.7%) 1 (0.3%) 3 (1.8%)

PULMONARY 11 (5.2%) 27 (11.2%) 10 (5.2%) 6 (3.9%) 7 (2.4%) 5 (3.0%)

CEREBROVASCULAR 17 (8.0%) 12 (5.0%) 4 (2.1%) 1 (0.7%) 6 (2.1%) 2 (1.2%)

ISHLT

2009


PEDIATRIC HEART TRANSPLANT RECIPIENTS: Relative Incidence of Leading Causes of Death

(Deaths: January 1998 - June 2008)

0

10

20

30

40

0-30 Days (N= 213)

31 Days – 1Year (N =

241)

>1 Year – 3Years (N =

192)

>3 Years – 5Years (N =

153)

>5 Years – 10Years (N =

286 )

>10 Years (N= 165)

CAV Acute Rejection Infection (non-CMV)

Primary Failure Graft Failure

Pe

rce

nta

ge

of

De

ath

s

ISHLT

2009

Documents

J Heart Lung Transplant 2009;28: 989-1049 HEART TRANSPLANTATION Pediatric Recipients ISHLT 2009