heart transplantation pediatric recipients 2010 ishlt j heart lung transplant. 2010 oct; 29 (10):...

HEART TRANSPLANTATION

Pediatric Recipients

2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS (Transplants: January 1996 - June 2009)

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

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


AGE DISTRIBUTION FOR DONORS OF PEDIATRIC HEART RECIPIENTS

(Transplants: January 1996 - June 2009)

0

100

200

300

400

500

600

700

800

900

1000

0 2 4 6 8 10 12 14 16 18-25

31+

Donor Age (Years)

Nu

mb

er

of

Tra

ns

pla

nts


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

2008

11-17 Years

1-10 Years

<1 Year

Nu

mb

er

of

Tra

ns

pla

nts

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.


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

2008

Nu

mb

er

of

Ce

nte

rs R

ep

ort

ing


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

2008

Other

North America

Europe

Nu

mb

er

of

Ce

nte

rs R

ep

ort

ing


AVERAGE CENTER VOLUME AND PERCENTAGE OF TRANSPLANTS BY CENTER VOLUME

Pediatric Heart Transplants: January 1, 1997 - June 30, 2009

123

18

126

16 1690

20

40

60

80

100

120

140

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

Average number of heart transplants per year

0

7

14

21

28

35

42

49

Number of centers 1997-2000 Number of centers 2001-June 2009

Percentage of transplants 1997-2000 Percentage of transplants 2001-June 2009

Nu

mb

er

of

ce

nte

rs

Pe

rce

nta

ge

of

tra

ns

pla

nts


DISTRIBUTION OF TRANSPLANTS BY CENTER VOLUME

Pediatric Heart Transplants: January 1, 1997 - June 30, 2009

34.829.5 30.429.3

24.4

46.3

0

10

20

30

40

50

1-4 5-9 10-19

Average number of heart transplants per year

1997-2000 2001-June 2009

% o

f tr

an

sp

lan

ts


PEDIATRIC HEART RE-TRANSPLANTSBy Transplant Year

Re-transplants: January 1994 – December 2008

0

5

10

15

20

25

30

35

40

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

Nu

mb

er o

f tr

ansp

lan

ts

Year of re-transplant

Only patients who were less than 18 years old at the time of re-transplant are included.


0

10

20

30

40

50

<1 month 1-<12months

12-<36months

36-<60months

60+ months Not reported

% o

f R

e-T

ran

spla

nts

0-10 Years 11-17 Years

Time Between Previous and Current Transplant

PEDIATRIC HEART RE-TRANSPLANTSBy Inter-transplant Interval

Re-transplants: January 1994 - June 2009

Only patients who were less than 18 years old at the time of re-transplant are included. Analysis is based on the age at the time of re-transplant


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=48) 1-<3 Years (N=34) 3-<5 Years (N=48)5+ Years (N=145) Primary TX (N=5,417)

Comparison of survival for re-transplant groups: p = 0.0019

Time (years) since most recent transplant

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

Re-transplants: January 1994 - June 2008

Only patients who were less than 18 years old at the time of re-transplant are included.


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

2009

Myopathy Congenital

% o

f C

as

es

33%

63%

3%

0%

1/1996-6/2009

17%

80%2%

1%

Myopathy

Congenital

Other

ReTX

1988-1995


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

2009

Myopathy Congenital

% o

f C

as

es

55%

37%

3%

5%

1/1996-6/2009

53%

41%

2%

4%Myopathy

Congenital

Other

ReTX

1988-1995


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

2009

Myopathy Congenital

% o

f C

as

es

65%

25%

3%

8%

1/1996-6/2009

68%

27%

3%

2%

Myopathy

Congenital

Other

ReTX

1988-1995


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival (Transplants: 1/1982-6/2008)

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 = 2,049) 1-10 Years (N = 2,929)

11-17 Years (N = 3,027) Overall (N = 8,005)

0-<1 vs. 1-10: p < 0.0001; 0-<1 vs. 11-17: p=0.3284; 1-10 vs. 11-17: p=0.0003.

Half-life <1: 18.3 Years; 1-10: 15.5 Years; 11-17: 11.3 Years

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONConditional Kaplan-Meier Survival

(Transplants: 1/1982-6/2008)

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 = 1,422) 1-10 Years (N = 2,272)11-17 Years (N =2,399) Overall (N = 6,093)

0-<1 vs. 1-10: p = 0.0138; 0-<1 vs. 11-17: p < 0.0001;1-10 vs. 11-17: p < 0.0001.

Half-life: <1: 21.4; 1-10: 19.3 Years; 11-17: 15.2 Years

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONConditional Kaplan-Meier Survival for Recent Era

(Transplants: 1/1999-6/2008)

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

<1 Year (N = 683) 1-10 Years (N =1,184)

11-17 Years (N = 1,201) Overall (N = 3,068)

0-<1 vs. 1-10: p = 0.02510-<1 vs. 11-17: p = 0.0010; 1-10 vs. 11-17: p < 0.0001

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era

(Transplants: 1/1982-6/2008)

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=846) 1990-1994 (N=1,803)

1995-1999 (N=1,846) 2000-6/2008 (N=3,510)

All p-values significant at p = 0.01

Half-life 1982-1989: 9.5 years; 1990-1994: 11.7 years; 1995-1999: 14.3; 2000-6/2008: n.c.

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: 1/1982-6/2008)

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=176) 1990-1994 (N=571)

1995-1999 (N=479) 2000-6/2008 (N =823)

P-values for era comparisonsAll p-values significant at p < 0.0001 except comparison of 82-89 vs. 90-94 and 95-99 vs. 00-6/08

Half-life 1982-1989: 10.8 years; 1990-1994: 9.7 years; 1995-1999: n.c. ; 2000-6/2008: n.c.S

urv

iva

l (%

)


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: 1/1982-6/2008)

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 = 263) 1990-1994 (N=633)

1995-1999 (N=708) 2000-6/2008 (N=1,325)

P-values for era comparisonsAll p-values significant at p = 0.01 except for 82-89 vs. 90-94

Half-life 1982-1989: 9.1; 1990-1994: 12.4; 1995-1999: 13.6 ; 2000-6/2008: n.a.

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: 1/1982-6/2008)

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=407) 1990-1994 (N=599)

1995-1999 (N=659) 2000-6/2008 (N=1,362)

P-values for era comparisonsNo p-values significant at p = 0.05 except 82-89 vs. 90-94: p = 0.0341; 82-89 vs. 00-6/08: p < 0.0001;

Half-life 1982-1989: 9.3; 1990-1994: 11.8; 1995-1999: 10.3; 2000-6/2008: n.a.

Su

rviv

al (

%)


0%

20%

40%

60%

80%

100%

Europe North America Other

% o

f T

ran

sp

lan

ts

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

PEDIATRIC HEART TRANSPLANTS: AVERAGE CENTER VOLUME DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2009


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Patient vs. Graft Survival

(Transplants: 1/1999-6/2008)

Average Center Volume: 1-4 Transplants per Year

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9

Years

Patient (N=1,172) Graft (N=1,172)

p = 0.2878Su

rviv

al (

%)



(Transplants: 1/1999-6/2008)


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9

Years

Patient (N=900) Graft (N=900)

p = 0.1670Su

rviv

al (

%)



(Transplants: 1/1999-6/2008)


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9

Years

Patient (N=1,801) Graft (N=1,801)

p = 0.0201Su

rviv

al (

%)


0%

20%

40%

60%

80%

100%


% o

f T

ran

sp

lan

ts

<1 years 1-10 years 11-17 years

PEDIATRIC HEART TRANSPLANTS:AGE DISTRIBUTION BY LOCATION



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



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



PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)

Risk Factors For 1 Year Mortality

N=3,838

VARIABLE N Relative

Risk P-value

95% Confidence Interval

Congenital diagnosis, age = 0, on ECMO 81 2.86 <0.0001 1.99 -4.09

Congenital diagnosis, age > 0 921 2.02 <0.0001 1.60 -2.56

Retransplant 230 1.96 0.0007 1.33 -2.89

Year of Transplant: 1996-1997 vs. 2002-2003 523 1.68 0.0013 1.22 -2.32

On dialysis 83 1.66 0.0217 1.08 -2.55

On ventilator 717 1.54 0.0002 1.23 -1.94


PRA > 10% 349 1.36 0.0263 1.04 -1.79

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

387 1.35 0.0401 1.01 -1.81

Male donor/female recip vs. male donor/male recip 971 1.24 0.0404 1.01 -1.51

Diagnosis other than congenital, no ECMO, age = 0 290 0.47 0.0005 0.31 -0.72

Reference diagnosis = cardiomyopathy



Borderline Significant Risk Factors For 1 Year Mortality

N=3,838

VARIABLE N Relative

Risk P-value

95% Confidence

Interval

Infection requiring IV drug therapy (with 2wk/TX)

584 1.24 0.0735 0.98 -1.56

Transfusions prior to transplant 1159 1.23 0.0525 1.00 -1.52

Donor cause of death = anoxia vs head trauma

898 0.81 0.065 0.65 -1.01


PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008) Risk Factors for 1 Year Mortality

Continuous Factors (see figures)

Recipient age Recipient height

Donor age Ischemia time

Creatinine

N=3,838



Recipient Age

0

0.5

1

1.5

2

2.5

3

3.5

4

0 3 6 9 12 15 18


Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0024

N=3,838

NOTE: The impact of age should be considered in the context of height and diagnosis+age.2010ISHLT

J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141


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 < 0.0001

N=3,838

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



Donor Age

0

0.5

1

1.5

2

2.5

3

0 5 10 15 20 25 30 35

Donor Age (Years)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.027

N=3,8382010ISHLT



Pre-Transplant Creatinine

0

0.5

1

1.5

2

2.5

3

0 0.5 1 1.5 2

Recipient serum creatinine (mg/dl)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.004

N=3,8382010ISHLT



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 = 0.0075

N=3,8382010ISHLT


PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008) 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, center volume



Age = <1 YearsRisk Factors For 1 Year Mortality

N=1,009

VARIABLE N

Relative Risk

P-value 95% Confidence Interval

ECMO (diagnosis = congenital) 81 3.25 <0.0001 2.14 -4.95

ECMO, diagnosis other than congenital 42 2.59 0.0147 1.21 -5.57


On dialysis 21 2.22 0.0173 1.15 -4.29


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

48 1.79 0.0359 1.04 -3.10

On ventilator 354 1.72 0.001 1.24 -2.37

Infection requiring IV drug therapy (within 2 weeks prior to transplant)

259 1.52 0.0099 1.11 -2.08

Diagnosis = cardiomyopathy 296 0.48 0.004 0.29 -0.79

Reference diagnosis = congenital without PGE or ECMO2010ISHLT



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

N=1,009

VARIABLE N Relative

Risk P-value

95% Confidence

Interval

Transplant Year: 1998-1999 vs. 2002-2003

134 1.72 0.0691 0.96 -3.10

PRA > 10% 76 1.60 0.0849 0.94 -2.73

Donor clinical infection 182 0.71 0.081 0.48 -1.04



Age = <1 Years Risk Factors for 1 Year Mortality


Ischemia time Recipient height (borderline)

Creatinine (borderline) Pediatric transplant volume (borderline)

N=1,009


PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008) Risk Factors for 1 Year Mortality in Age = <1 Years

Ischemia Time

0

0.5

1

1.5

2

2.5

2 3 4 5 6


Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.038

N=1,0092010ISHLT




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 = 0.051

N=1,0092010ISHLT



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)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.062

N=1,0092010ISHLT



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 = 0.089

N=1,0092010ISHLT



Age = 1-10 YearsRisk Factors For 1 Year Mortality

N=1,448

VARIABLE N Relative

Risk P-value


Diagnosis = congenital 563 2.30 <0.0001 1.62 -3.25

Transfusions prior to transplant 349 1.82 0.0009 1.28 -2.59

Female recipient 713 1.48 0.0144 1.08 -2.04

Donor cause of death = anoxia vs. head trauma 337 0.59 0.0131 0.39 -0.90




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

N=1,448

VARIABLE N Relative

Risk P-value


Diagnosis = re-transplant 99 1.86 0.0639 0.96 -3.60

Not ABO identical 288 0.68 0.0768 0.44 -1.04



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


Creatinine Bilirubin

Recipient height

N=1,448


PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008) Risk Factors for 1 Year Mortality in Age = 1-10 Years


0

0.5

1

1.5

2

2.5

3

3.5

0.2 0.4 0.6 0.8 1 1.2 1.4


Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0002

N=1,4482010ISHLT



Recipient Height

0

0.5

1

1.5

2

70 80 90 100 110 120 130 140 150

Height (cm)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0045

N=1,4482010ISHLT



Recipient Bilirubin

0

0.5

1

1.5

2

2.5

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5

Bilirubin (mg/dL)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.022

N=1,4482010ISHLT



Age = 11-17 YearsRisk Factors For 1 Year Mortality

N=1,381

VARIABLE N Relative

Risk P-

value

95% Confidence

Interval

ECMO 48 3.03 0.0015 1.53 -6.01

Diagnosis = retransplant 125 2.4 0.0008 1.44 -4.01

Diagnosis = congenital 358 1.86 0.0024 1.25 -2.79

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

0 DR MM: N = 48 1 DR MM: N = 552 2 DR MM: N = 781

0.72 0.03 0.54 -0.97




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

N=1,381

VARIABLE N Relative

Risk P-value

95% Confidence

Interval

On dialysis 39 1.88 0.0961 0.89 -3.95

PRA > 10% 118 1.59 0.0614 0.98 -2.58

Donor cause of death = anoxia vs. head trauma

175 0.57 0.0944 0.30 -1.10



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


Ischemia time (borderline)

N=1,381



Risk Factors for 1 Year Mortality in Age = 11-17 YearsIschemia Time

0

0.5

1

1.5

2

2.5

2 3 4 5 6


Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.094

N=1,3812010ISHLT




N=2,420

VARIABLE N Relative

Risk P-value


Congenital diagnosis, age = 0, on ECMO 43 1.71 0.025 1.07 -2.74

On dialysis 49 1.69 0.0174 1.10 -2.62

Retransplant 140 1.48 0.0166 1.07 -2.04

PRA > 10% 259 1.48 0.0009 1.17 -1.86

On ventilator 459 1.29 0.0177 1.05 -1.59

Prior sternotomy 885 1.24 0.0346 1.02 -1.52

Female recipient 1041 1.22 0.0143 1.04 -1.44

Diagnosis other than congenital, no ECMO, age = 0 183 0.47 0.0006 0.31 -0.72





N=2,420

VARIABLE N Relative

Risk P-value

95% Confidence

Interval


348 1.20 0.0957 0.97 -1.50

Donor cause of death = anoxia vs. head trauma

515 0.82 0.0587 0.67 -1.01




Recipient age Recipient height

Donor age Ischemia time (borderline)

Pediatric transplant volume (borderline)

BSA ratio (borderline)

N=2,420



Recipient Age

0

0.5

1

1.5

2

2.5

3

3.5

0 3 6 9 12 15 18


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001

N=2,420

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



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 = 0.013

N=2,420

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



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 = 0.026

N=2,4202010ISHLT




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 = 0.064

N=2,4202010ISHLT



Risk Factors for 5 Year MortalityIschemia Time

0

0.5

1

1.5

2

2.5

2 3 4 5 6


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.063

N=2,4202010ISHLT



Risk Factors for 5 Year MortalityBSA Ratio

0

0.5

1

1.5

2

2.5

0.8 1 1.2 1.4 1.6 1.8 2

Donor BSA/Recipient BSA

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.063

N=2,4202010ISHLT




N=910

VARIABLE N Relative

Risk P-

value 95% Confidence

Interval

Female recipient/male donor vs. male recipient/male donor 372 1.41 0.0239 1.05 -1.90

Female donor/male recipient vs. male recipient/male donor 386 1.40 0.0201 1.05 -1.86

HLA mismatches at A locus (per increasing mismatch compared to 0 mismatches

0 DR MM: N = 57 1 DR MM: N = 306 2 DR MM: N = 547

1.25 0.0198 1.04 -1.51

Female recipient/female donor vs. male recipient/male donor 154 0.62 0.0378 0.40 -0.97

Diagnosis = cardiomyopathy, age = 0 years* 58 0.44 0.0141 0.23 -0.85


* Impact should be considered in context of donor age and recipient BSA shown in subsequent figures.




N=910

VARIABLE N Relative

Risk P-value 95% Confidence

Interval


103 1.33 0.087 0.96 -1.83





Creatinine Donor age

Pediatric transplant volume (borderline)

Recipient BSA

N=9102010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141


Donor Age

0

0.5

1

1.5

2

2.5

3

3.5

0 5 10 15 20 25 30 35

Donor Age (Years)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p < 0.0001



Recipient BSA

0

0.5

1

1.5

2

0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2

Recipient BSA (m2)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p = 0.0045

N=9102010ISHLT




0

0.5

1

1.5

2

2.5

0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2

Creatinine (mg/dl)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p = 0.011




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 = 0.084


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

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

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

Transplant Factors:Ischemia time, CMV mismatch



Risk Factors for the Development of CAV within 5 Years

N=1,470

VARIABLE N Relative

Risk P-

value 95% Confidence

Interval

Diagnosis = retransplant 96 2.13 0.0033 1.29 -3.53




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

N=1,470

VARIABLE N Relative

Risk P-value 95% Confidence

Interval

Diagnosis = other 24 2.03 0.0999 0.87 -4.72

PRA > 10% 171 1.45 0.0807 0.96 -2.21

Diagnosis = congenital 595 1.36 0.0797 0.96 -1.91

No steroids reported for discharge maintenance immunosuppression

233 0.61 0.0716 0.35 -1.04



PEDIATRIC HEART TRANSPLANTS (7/1997-6/2004) Risk Factors for the Development of CAV within 5 Years


Donor height

Total transplant volume

N=1,4702010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141


Donor Height

0

0.5

1

1.5

2

50 60 70 80 90 100 110 120 130 140 150 160 170 180

Donor Height (cm)

Re

lati

ve

Ris

k o

f C

AV

wit

hin

5 Y

ea

rs

p < 0.0001



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 = 0.0026


PEDIATRIC HEART RECIPIENTS Cross-Sectional Analysis

Functional Status of Surviving Recipients(Follow-ups: April 1994 - June 2009)

0%

20%

40%

60%

80%

100%

1 Year (N = 2,171) 5 Year (N = 1,428) 10 Year (N = 561)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


PEDIATRIC HEART RECIPIENTS Longitudinal Analysis

Functional Status of Surviving Recipients(Follow-ups: April 1994 - June 2009)

For the Same Patients

0%

20%

40%

60%

80%

100%

1 Year (N = 792) 3 Year (N = 792) 5 Year (N = 792)



PEDIATRIC HEART RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: April 1994 - June 2009)Age: <1 Year

0%

20%

40%

60%

80%

100%





(Follow-ups: April 1994 - June 2009)Age: 1-10 Years

0%

20%

40%

60%

80%

100%





(Follow-ups: April 1994 - June 2009)Age: 11-17 Years

0%

20%

40%

60%

80%

100%





(Follow-ups: March 2005 - June 2009)US Recipients Only

0%

20%

40%

60%

80%

100%

1 Year (N = 1,103) 2 Years (N = 972) 3 Years (N = 897)

Not Applicable (patient <1 year old)10%

20%

30%

40%

50%

60%

70%

80%

90%

100%


PEDIATRIC HEART RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients

(Follow-ups: April 1994 - June 2009)

0%

20%

40%

60%

80%

100%

1 Year (N = 3,783) 5 Years (N =2,366) 10 Years (N = 958)

No Hospitalization Hospitalized, Not Rejection/Not InfectionHospitalized, Rejection Hospitalized, Infection OnlyHospitalized, Rejection + Infection


0

10

20

30

40

50

60

Any Induction (N =1,489)

Polyclonal ALG/ATG(N = 997)

OKT3 (N = 48) IL2R-antagonist (N= 485)

% o

f P

ati

en

tsPEDIATRIC HEART RECIPIENTS

Induction Immunosuppression(Transplants: January 2001 - June 2009)

Analysis is limited to patients who were alive at the time of the follow-up2010ISHLT


0

10

20

30

40

50

60

70

Any Induction Polyclonal ALG/ATG IL2R-antagonist

% o

f P

ati

en

ts

200120022003200420052006200720082009

PEDIATRIC HEART RECIPIENTSInduction Immunosuppression (Transplants: January 2001 - June 2009)

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


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group

(Transplants: January 2000 – June 2008) Conditional on Survival to 14 Days

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

No induction (N = 1,261)

Polyclonal induction (N = 888)

IL2R-antagonist (N = 378)

No comparisons were statistically significant.

Su

rviv

al

(%)


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 2008)

Conditional on Survival to 1 Year

50

60

70

80

90

100

0 1 2 3 4

Years

No induction/No rejection (N = 303)

Polyclonal induction/No rejection (N = 266)

IL2R-antagonist/No rejection (N = 114)

No induction/Treated Rejection (N = 108)

Polyclonal induction/Treated Rejection (N = 116)

IL2R-antagonist/Treated Rejection (N = 53)

Su

rviv

al (

%)

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

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.


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2008)

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 = 267)Polyclonal induction (N = 300)IL2R-antagonist (N = 52)


Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2008)

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 = 506)Polyclonal induction (N = 309)IL2R-antagonist (N = 148)


Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2008)

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 = 488)

Polyclonal induction (N = 279)

IL2R-antagonist (N = 178)


Su

rviv

al (

%)


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

Year 1 (N = 2,235) Year 5 (N = 1,441)

PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

(Follow-ups: January 2001 - June 2009)

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

% o

f P

atie

nts



PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

for Same Patients at Each Time Point(Follow-ups: January 2001 - June 2009)

0%

20%

40%

60%

80%

100%

Year 1 (N = 789) Year 5 (N = 789)

None

Other

Tacrolimus

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine

Cyclosporine + MMF

Cyclosporine + AZA

% o

f P

ati

en

ts



PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression Drug Combinations at Time of Follow-up

(Follow-ups: January 2001 - June 2009)

0%

20%

40%

60%

80%

100%

Year 1 (N = 2,235) Year 5 (N = 1,441)

None

Other

Tacrolimus

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine

Cyclosporine + MMF

Cyclosporine + AZA

% o

f P

ati

en

ts

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

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


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Prednisone Use

Conditional on Survival to 1 Year (Transplants: 1998 - June 2008)

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 = 1,644)

No Prednisone at discharge or at 1 year (N = 384)

Prednisone at discharge/not at 1 year (N = 371)

p = 0.0147

Su

rviv

al (

%)


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

Conditional on Survival to 1 Year (Transplants: January 1998 – June 2008)

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 = 1,644)

No Prednisone at discharge or at 1 year (N = 384)

Prednisone at discharge/not at 1 year (N = 371)

p = 0.0147

Su

rviv

al (

%)


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

(Transplants: January 1998 - June 2008) 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 = 1,423)

Cyclosporine use at discharge (N = 1,482)

p = 0.2594

Su

rviv

al (

%)


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

Conditional on Survival to 1 Year (Transplants: January 1998 - June 2008)

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 = 902)

Tacrolimus use at discharge and 1 year (N = 1,070)

Cyclosporine use at discharge/Tacrolimus at 1 year (N = 267)

Tacrolimus use at discharge/Cyclosporine at 1 year (N = 30)

p = 0.0333

Su

rviv

al (

%)


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 2008)

50

60

70

80

90

100

0 1 2 3 4

Years

Free from Rejection during 1 year (N = 526)Treated Rejection within 1st Year (N = 283)

p = 0.1693

Su

rviv

al (

%)




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

Stratified by Calcineurin Use at Discharge Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2008)

50

60

70

80

90

100

0 1 2 3 4

Years

CyA: Free from Rejection during 1 year (N = 144)

CyA: Treated Rejection within 1st Year (N = 101)

TAC: Free from Rejection during 1 year (N = 347)

TAC: Treated Rejection within 1st Year (N = 150)

Free from Rejection: CyA vs. TAC p = 0.2682Treated Rejection: CyA vs. TAC p = 0.1586 CyA: Rejection vs. no rejection p = 0.6131TAC: Rejection vs. no rejection p = 0.1430

Su

rviv

al (

%)





Stratified by Calcineurin Use at Discharge: Age = 0-10 Years Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2008)

50

60

70

80

90

100

0 1 2 3 4

Years

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

CyA: Treated Rejection within 1st Year (N = 69)

TAC: Free from Rejection during 1 year (N = 221)


Free from Rejection: CyA vs. TAC p = 0.8741Rejection: CyA vs. TAC p = 0.7176 CyA: Rejection vs. no rejection p = 0.8305TAC: Rejection vs. no rejection p = 0.3347

Su

rviv

al (

%)





Stratified by Calcineurin Use at Discharge: Age = 11-17 Years Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2008)

50

60

70

80

90

100

0 1 2 3 4

Years

CyA: Free from Rejection during 1st Year (N = 41)

CyA: Treated Rejection within 1st Year (N =32)

TAC: Free from Rejection during 1st Year (N = 126)


Free from Rejection: CyA vs. TAC p = 0.0338Rejection: CyA vs. TAC p = 0.1014 CyA: Rejection vs. no rejection p = 0.1693TAC: Rejection vs. no rejection p = 0.3492

Su

rviv

al (

%)




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 2009)

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 = 0.6601

Overall < 1 1-10 10-17 Female Male



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.2010ISHLT


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 2009)

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

No comparisons were statistically significant at 0.05.

Overall < 1 1-10 10-17 Female Male






AND 1-YEAR FOLLOW-UP Stratified by Maintenance Immunosuppression and Induction (Follow-ups: July 2004 - June 2009)

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

year

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=0.0268); 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 = 0.0005); CyA + induction vs. TAC + no induction (p < 0.0001); CyA + induction vs. TAC + induction ( p =0.0025)

Overall < 1 1-10 10-17





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 2009)

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

year

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 =0.0076).1-10: CyA + MMF vs. TAC + MMF (p = 0.0008); CyA + AZA vs. TAC + MMF (p=0.0007).

11-17: all comparisons were statistically significant at 0.05 except CyA +MMF vs. CyA +AZA TAC + MMF vs. TAC + AZA.

Overall < 1 1-10 10-17






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

(Follow-ups: July 2004 - June 2009)

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=0.0356) 1-10: CyA vs. TAC (p < 0.0001)11-17: CyA vs. TAC (p < 0.0001)

Overall < 1 1-10 10-17





FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

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


FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

Stratified by Induction

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Years

Induction (N = 1,455)

No Induction (N = 1,880)

p = 0.5133

% F

ree

do

m f

rom

CA

V


FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: 1999 - June 2009)

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


Tacrolimus use at discharge and 1 year (N = 960)



p = 0.6217

% F

ree

do

m f

rom

CA

V


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

Stratified by Age Group

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years

<1 Year (N = 869)

1-10 Years (N = 1,251)

11-17 Years (N = 1,230)

p < 0.0001

% F

ree

do

m f

rom

CA

V


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: January 1999-June 2009)

Stratified by Age Group

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years

<1 Year (N = 623)

1-10 Years (N = 950)

11-17 Years (N = 948)

p < 0.0001

% F

ree

do

m f

rom

CA

V



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=349)

2-<4 hours (N=1,705)

4+ hours (N=1,067)

p = 0.0080

% F

ree

do

m f

rom

CA

V


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: January 1999 - June 2009)

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=234)

2-<4 hours (N=1,271)

4+ hours (N=808)

p = 0.0105

% F

ree

do

m f

rom

CA

V



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=197)

2+ hours/0-10 years (N=1,776)

0-<2 hours/11-17 years (N=152)

2+ hours/11-17 years (N=996)

0-10 years: p = 0.0049;11-17 years: p = 0.3641

% F

ree

do

m f

rom

CA

V


GRAFT SURVIVAL FOLLOWING REPORT OF CORONARY ARTERY VASCULOPATHY

For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)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 = 86)

1-10 Years (N = 150)

11-17 Years (N = 198)

p = 0.6115

Su

rviv

al s

ince

Rep

ort

of

CA

V (

%)


FREEDOM FROM SEVERE RENAL DYSFUNCTION*For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

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


FREEDOM FROM SEVERE RENAL DYSFUNCTION*For Pediatric Heart Recipients (Follow-ups: 1999 - June 2009)


50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years


Tacrolimus use at discharge and 1 year (N = 1,054)



p = 0.1311

% 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


FREEDOM FROM RENAL REPLACEMENT THERAPY*For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years

% F

ree

do

m f

rom

R

en

al

Re

pla

ce

me

tn T

he

rap

y

* Renal replacement therapy = dialysis or renal transplant


MALIGNANCY POST-HEART TRANSPLANTATION FOR PEDIATRICSCumulative Prevalence in Survivors (Follow-ups: April 1994 - June 2009)

Malignancy/Type 1-Year Survivors

5-Year Survivors

10-Year Survivors

No Malignancy 3,684 (98.2%) 1,521 (94.9%) 411 (92.6%)

Malignancy (all types combined) 69 (1.8%) 82 (5.1%) 33 (7.4%)

Malignancy Type

Lymph 64 77 31

Other 4 6 3

Skin 1 1

Type Not Reported 1

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


FREEDOM FROM MALIGNANCYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

80

85

90

95

100

0 1 2 3 4 5 6 7 8 9 10 11 12

Years

All malignancy Lymph Skin Other% F

ree

do

m f

rom

Ma

lign

an

cy


FREEDOM FROM MALIGNANCYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)


80

85

90

95

100

0 1 2 3 4 5 6 7 8 9

Years


Tacrolimus use at discharge and 1 year (N = 997)



p = 0.0214

% F

ree

do

m f

rom

Ma

lig

na

nc

y


FREEDOM FROM LYMPHOMAFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

Stratified by Induction

80

85

90

95

100

0 1 2 3 4 5 6 7 8 9 10

Years

Induction No Induction

p = 0.7922

% F

ree

do

m f

rom

Ly

mp

ho

ma


PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 1 and 3 Years

(Transplants: April 1993 - June 2006)

Maintenance Immunosuppression at discharge and 1 year

% HTN reported between 1 and 3 years

P-valueFor Patients

on drugFor Patients not on drug

Azathioprine 20.1 25.1 0.0639

Cyclosporine 21.3 22.6 0.6409

MMF 24.0 22.3 0.5552

Prednisone 28.9 11.9 <.0001

Rapamycin 36.4 22.0 -

Tacrolimus 26.0 20.4 0.0408


PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 3 and 8 Years

(Transplants: April 1993 - June 2001)

Maintenance Immunosuppression at discharge and 1 year

% HTN reported between 3 and 8 years

P-valueFor Patients

on drugFor Patients not on drug

Azathioprine 35.1 54.3 0.0339

Cyclosporine 36.0 46.7 0.2637

MMF 41.4 37.8 0.7112

Prednisone 47.1 20.2 <.0001

Rapamycin - 37.5 -

Tacrolimus 40.7 34.8 0.541


PEDIATRIC HEART RECIPIENTSRelationship of Rejection and Coronary Artery Vasculopathy

(Follow-ups: July 2004 – June 2009)

Rejection During 1st

Year

Reported CAV between 1st and 3rd years

post-transplant

Yes No All

Yes 9

5.1%

168

94.9%

177

100%

No 9

3.4%

255

96.6%

264

100%

p = 0.3834


PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2009)

CAUSE OF DEATH 0-30 Days (N = 475)

31 Days - 1 Year (N =

443)

>1 Year - 3 Years (N = 318)

>3 Years - 5 Years (N = 246)

>5 Years - 10 Years (N = 371)

>10 Years (N = 197)

CORONARY ARTERY VASCULOPATHY

5 (1.1%) 30 (6.8%) 62 (19.5%) 72 (29.3%) 105 (28.3%) 54 (27.4%)

ACUTE REJECTION 45 (9.5%) 108 (24.4%) 75 (23.6%) 35 (14.2%) 46 (12.4%) 12 (6.1%)

LYMPHOMA 1 (0.2%) 9 (2.0%) 12 (3.8%) 8 (3.3%) 35 (9.4%) 15 (7.6%)

MALIGNANCY, OTHER 4 (0.9%) 2 (0.6%) 2 (0.8%) 5 (1.3%) 10 (5.1%)

CMV 1 (0.2%) 12 (2.7%) 1 (0.3%)

INFECTION, NON-CMV 55 (11.6%) 68 (15.3%) 21 (6.6%) 8 (3.3%) 18 (4.9%) 18 (9.1%)

PRIMARY FAILURE 108 (22.7%) 24 (5.4%) 10 (3.1%) 16 (6.5%) 21 (5.7%) 7 (3.6%)

GRAFT FAILURE 101 (21.3%) 51 (11.5%) 64 (20.1%) 60 (24.4%) 76 (20.5%) 49 (24.9%)

TECHNICAL 27 (5.7%) 3 (0.7%) 2 (0.6%) 3 (1.2%) 4 (1.1%) 2 (1.0%)

OTHER 23 (4.8%) 26 (5.9%) 32 (10.1%) 24 (9.8%) 34 (9.2%) 10 (5.1%)

MULTIPLE ORGAN FAILURE

48 (10.1%) 56 (12.6%) 10 (3.1%) 7 (2.8%) 10 (2.7%) 10 (5.1%)

RENAL FAILURE 1 (0.2%) 5 (1.1%) 1 (0.3%) 1 (0.4%) 1 (0.3%) 3 (1.5%)

PULMONARY 29 (6.1%) 31 (7.0%) 16 (5.0%) 8 (3.3%) 9 (2.4%) 5 (2.5%)

CEREBROVASCULAR 31 (6.5%) 16 (3.6%) 10 (3.1%) 2 (0.8%) 7 (1.9%) 2 (1.0%)


PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1998 - June 2009)

CAUSE OF DEATH 0-30 Days (N = 226)

31 Days - 1 Year (N = 266)

>1 Year - 3 Years (N = 202)

>3 Years - 5 Years (N = 173)

>5 Years - 10 Years (N = 306)

>10 Years (N =190)

CAV 2 (0.9%) 14 (5.3%) 33 (16.3%) 46 (26.6%) 84 (27.5%) 52 (27.4%)

ACUTE REJECTION 23 (10.2%) 53 (19.9%) 40 (19.8%) 27 (15.6%) 37 (12.1%) 12 (6.3%)

LYMPHOMA 6 (2.3%) 7 (3.5%) 6 (3.5%) 29 (9.5%) 15 (7.9%)

MALIGNANCY, OTHER

1 (0.4%) 1 (0.5%) 1 (0.6%) 4 (1.3%) 9 (4.7%)

CMV 8 (3.0%) 1 (0.5%)

INFECTION, NON-CMV

27 (11.9%) 34 (12.8%) 12 (5.9%) 3 (1.7%) 14 (4.6%) 16 (8.4%)

PRIMARY FAILURE 50 (22.1%) 10 (3.8%) 4 (2.0%) 7 (4.0%) 13 (4.2%) 7 (3.7%)

GRAFT FAILURE 35 (15.5%) 31 (11.7%) 50 (24.8%) 51 (29.5%) 68 (22.2%) 47 (24.7%)

TECHNICAL 14 (6.2%) 2 (1.0%) 1 (0.6%) 4 (1.3%) 2 (1.1%)

OTHER 17 (7.5%) 21 (7.9%) 27 (13.4%) 17 (9.8%) 30 (9.8%) 10 (5.3%)

MULTIPLE ORGAN FAILURE

29 (12.8%) 43 (16.2%) 9 (4.5%) 6 (3.5%) 8 (2.6%) 10 (5.3%)

RENAL FAILURE 5 (1.9%) 1 (0.5%) 1 (0.6%) 1 (0.3%) 3 (1.6%)

PULMONARY 11 (4.9%) 28 (10.5%) 11 (5.4%) 6 (3.5%) 8 (2.6%) 5 (2.6%)

CEREBROVASCULAR 18 (8.0%) 12 (4.5%) 4 (2.0%) 1 (0.6%) 6 (2.0%) 2 (1.1%)


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

(Deaths: January 1998 - June 2009)

0

10

20

30

40

0-30 Days (N= 226)

31 Days – 1Year (N =

266)

>1 Year – 3Years (N =

173)

>3 Years – 5Years (N =

173)

>5 Years – 10Years (N =

306 )

>10 Years (N= 190)

CAV Acute Rejection Infection (non-CMV)

Primary Failure Graft Failure

Pe

rce

nta

ge

of

De

ath

s


heart transplantation pediatric recipients 2010 ishlt j heart lung transplant. 2010 oct; 29 (10):...

Documents

ishlt j heart lung transplant

transplant year

ishlt transplant registry

transplant interval

distribution of transplants

location transplants

percentage of transplants

time of retransplant