2002 ishlt j heart lung transplant 2002; 21: 827-840. heart transplantation pediatric recipients

2002ISHLT

J Heart Lung Transplant 2002; 21: 827-840.

HEART TRANSPLANTATION

Pediatric Recipients

2002ISHLT


AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS (1982-2001)

0

200

400

600

800

1000

1200

1400

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Recipient Age (Years)

Nu

mb

er o

f T

ran

spla

nts

2002ISHLT


AGE DISTRIBUTION FOR DONORS OF PEDIATRIC HEART RECIPIENTS (1982-2001)

0

200

400

600

800

1000

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18+

Donor Age (Years)

Nu

mb

er o

f T

ran

spla

nts

2002ISHLT


AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS

By Year of Transplant

0

100

200

300

40011-17 Years1-10 Years

<1 Year

Nu

mb

er o

f T

ran

spla

nts

11 942

75109

130

193

254

326365363

385364378

349372

350340

356319

* Numbers may be low due to delayed reporting.

2002ISHLT


NUMBER OF CENTERS REPORTING PEDIATRIC HEART TRANSPLANTS

0

20

40

60

80

100

Transplant Year

Num

ber

of P

edia

tric

Tra

nspl

ant

Cen

ters

* Numbers may be low due to delayed reporting

2002ISHLT


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

0

25

50

75

100

1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

% o

f Cas

es

MyopathyCongenital

20%

1%

75%4%

Myopathy

Congenital

Other

ReTX

2002ISHLT


DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: 1-10 Years)

0

25

50

75

100

1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

% o

f Cas

es

MyopathyCongenital

50% 37%

5% 8%

Myopathy

Congenital

Other

ReTX

2002ISHLT


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

0

25

50

75

100

1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

% o

f Cas

es

Myopathy Congenital

62%

24%

4% 10%

Myopathy

Congenital

Other

ReTX

2002ISHLT


PEDIATRIC HEART TRANSPLANTATIONActuarial Survival (1982-2001)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years Post-Transplantation

Su

rviv

al (

%)

<1 Year (N=1,206) 1-10 Years (N=1,862)11-17 Years (N=1,939) Overall (N=5,007)

<1 year vs. 1-10 years: p = 0.0005<1 year vs. 11-17 years: p = 0.001

2002ISHLT


PEDIATRIC HEART TRANSPLANTATIONConditional Actuarial Survival (1982-2001)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10


Su

rviv

al (

%)

<1 Year (N=726) 1-10 Years (N=1,161)11-17 Years (N=1,236) Overall (N=3,123)

Both comparisons with 11-17 years significant at p < 0.0001

2002ISHLT


PEDIATRIC HEART TRANSPLANTATIONConditional Actuarial Survival for Recent Era (1998-2001)

50

60

70

80

90

100

0 1 2 3 4


Su

rviv

al (

%)

<1 Year (N=150) 1-10 Years (N=246)11-17 Years (N=217) Overall (N=613)

Comparison of <1 vs. 11-17 years significant at p = 0.01

2002ISHLT


PEDIATRIC HEART TRANSPLANTATION

Actuarial Survival by Era (1982-2001)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10


1982-1987 (N=376) 1988-1992 (N=1,501)

1993-1997 (N=1,848) 1998-2001 (N=1,365)

All comparisons with 1998-2001 are significant at p < 0.0001Comparison of 1982-1987 vs. 1988-1992 was significant at p = 0.003Comparison of 1982-1987 vs. 1993-1997 was significant at p < 0.0001

Su

rviv

al (

%)

2002ISHLT


PEDIATRIC HEART TRANSPLANTATION Actuarial Survival by Age Group

For Diagnosis = Cardiomyopathy (1988-2001)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10


<1 (N=248)

1-10 (N=940)

11-17 (N=1,212)

Su

rviv

al (

%)

No comparisons were statistically significant.

2002ISHLT


PEDIATRIC HEART TRANSPLANTATION Actuarial Survival By Age Group

For Diagnosis = Congenital Disease (1988-2001)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10


<1 (N=898)

1-10 (N=688)

11-17 (N=468)

Comparison of <1 vs. 11-17 was significant at p = 0.01

Su

rviv

al (

%)

2002ISHLT


PEDIATRIC HEART TRANSPLANTS (1996-2001)Risk Factors For 1 Year Mortality

In Descending Order of Magnitude

N=1,554

VARIABLE

Odds Ratio

P-value 95%

Confidence Interval

Diagnosis: Congenital Heart Disease

2.01 <.0001 1.44 -2.80

Ventilator 1.92 0.001 1.30 -2.83

Diagnosis: Other (not Congenital, Cardiomyopathy or Retransplant)

1.92 0.009 1.17 -3.13

VAD 1.85 0.04 1.03 -3.32

Donor COD: Other (not head trauma, CVA, CNS tumor, or anoxia)

1.56 0.04 1.03 -2.38

2002ISHLT


PEDIATRIC HEART TRANSPLANTS (1996-2001) Risk Factors for 1 Year Mortality

Continuous Factors

N=1,554

VARIABLE Odds Ratio p-value Recipient Age – linear 0.007

Recipient Age – quadratic 0.001

0 Years 2.05

3 Years 1.33

6 Years 1.03

9 Years 0.97

12 Years 1.09

15 Years 1.48

2002ISHLT


PEDIATRIC HEART TRANSPLANTS (1996-2001) Factors Not Significant for 1 Year Mortality

•Previous Transplant•Donor history of hypertension•Height (recipient/donor)•Weight (recipient/donor)•Gender (recipient/donor)•Age (donor) •Year of transplant

•In ICU or hospital•Donor clinical infection•ICD•Ischemia time•Center volume•PRA •Total bilirubin

2002ISHLT


PEDIATRIC HEART TRANSPLANTS (April 1994 - December 1996)

Risk Factors For 5 Year MortalityIn Descending Order of Magnitude

N=937

VARIABLE

Odds Ratio

P-value 95%

Confidence Interval

On life support 1.93 <.0001 1.43 -2.60

Year of Transplant: 1994 1.75 0.0006 1.27 -2.41

Diagnosis: Congenital Heart Disease

1.64 0.001 1.21 -2.21

2002ISHLT


PEDIATRIC HEART TRANSPLANTS (April 1994 - December 1996)Risk Factors For 5 Year Mortality

Continuous Factors

N=937

VARIABLE Odds Ratio p-value Recipient BMI – quadratic 0.02

17 1.72

22 1.00

26 1.31

30 3.22

2002ISHLT



Factors Not Significant for 5 Year Mortality

•Donor history of hypertension•Height (recipient/donor)•Weight (donor)•Gender (donor)•Age (donor) •Donor cause of death

•In ICU or hospital•Donor clinical infection•ICD•Ischemia time•Center volume•PRA •Total bilirubin

2002ISHLT



Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year

In Descending Order of Magnitude

N=728

VARIABLE Odds Ratio P-value

95% Confidence

Interval

Previous Transplant 3.39 0.02 1.22 -9.39

Inotropes 3.30 <.0001 2.02 -5.37

Ventilator 0.22 0.007 0.07 -0.66

2002ISHLT


PEDIATRIC HEART RECIPIENTS Functional Status (April 1994-December 2001)

0%

20%

40%

60%

80%

100%

1 Year (N = 1,380) 3 Years (N = 1,142) 5 Years (N = 932)

No Activity Limitations Performs with Some Assistance Requires Total Assistance

2002ISHLT


PEDIATRIC HEART RECIPIENTS Rehospitalization Post-transplant (April 1994 - December 2001)

0%

20%

40%

60%

80%

100%

Up to 1 Year (N = 1,547)

Between 2 and 3 Years (N = 1,219)

Between 4 and 5 Years (N = 983)

No Hospitalization Hospitalized, Not Rejection/Not Infection

Hospitalized, Rejection Hospitalized, Infection Only

Hospitalized, Rejection + Infection

2002ISHLT


0

10

20

30

40

Any Induction (N = 227)

Polyclonal ATG/ALG (N = 160)

OKT3 (N = 45) IL2R-Antagonist (N = 47)

% o

f p

ati

en

ts

PEDIATRIC HEART RECIPIENTS Induction Immunosuppression

For follow-ups between October 1999 and December 2001

2002ISHLT


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

ati

en

ts

Year 1 (N = 483)

Year 5 (N = 315)

PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Any Time During Follow-up Period


2002ISHLT


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

ati

en

ts

Discharge (N = 429) Year 1 (N = 303)

PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up


2002ISHLT


0

20

40

60

80

100

CalcineurinInhibitor

CellCycle Prednisone CalcineurinInhibitor

CellCycle Prednisone

% o

f P

ati

en

ts

CyA

Tac Tac

CyA

AZAAZA

MMFMMF



1 Year Follow-up (N=429) 5 Year Follow-up (N = 303)

2002ISHLT


0%

20%

40%

60%

80%

100%

Year 1 (N = 429) Year 5 (N = 303)

% o

f P

atie

nts

None Given

Other

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine + MMF

Cyclosporine + AZA



2002ISHLT


POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Incidence for Survivors (April 1994-December 2001)

Outcome By 1 Year By 5 Years

Hypertension 44.2% (N=1,507) 60.0% (N=365)

Renal Function (N=1,516) (N=389) Normal 94.9% 92.5% Renal Dysfunction 3.2% 5.9% Creatinine>2.5 mg/dl 1.4% 0.8% Chronic Dialysis 0.5% 0.8% Renal Transplant 0.0% 0.0%

Hyperlipidemia

8.6% (N=1,578)

17.1% (N=398) Diabetes 3.2% (N=1,509) 4.9% (N=366)

CAV 2.5% (N=1,363) 11.4% (N=228)

2002ISHLT


Freedom from CAV For Pediatric Heart Recipients (April 1994-December 2000)

50

60

70

80

90

100

0 12 24 36 48 60

Months

% F

ree

from

CA

V

2002ISHLT


Freedom from Renal Dysfunction*For Pediatric Heart Recipients (April 1994-December 2000)

50

60

70

80

90

100

0 12 24 36 48 60

Months

% F

reed

om fr

om R

enal

D

ysfu

nctio

n

* Renal dysfunction = Creatinine > 2.5 mg/dl, dialysis or renal transplant

2002ISHLT


MALIGNANCY POST-HEART TRANSPLANTATION FOR PEDIATRICSCumulative Incidence for Survivors (April 1994-December 2001)

Malignancy/Type 1-Year Survivors 5-Year Survivors

No Malignancy 1,547 (98.2%) 378 (95.2%)

Malignancy (all types combined) 29 (1.8%) 19 (4.8%)

Malignancy Type

Lymph 25 18

Other 3 1

Type Not Reported 1

2002ISHLT


Freedom from MalignancyFor Pediatric Heart Recipients (April 1994-December 2000)

50

60

70

80

90

100

0 12 24 36 48 60

Months

% F

ree

from

Mal

igna

ncy

All malignancy Lymph Skin Other

2002ISHLT


PEDIATRIC HEART TRANSPLANTATIONActuarial Survival Based on Prednisone Use

50

60

70

80

90

100

0 1 2 3 4 5 6 7


Su

rviv

al (

%)

Prednisone use at discharge and 1 year (N=921)

No Prednisone at discharge or at 1 year (N=227)

Prednisone at discharge/not at 1 year (N = 148)

p = 0.005

2002ISHLT


PEDIATRIC HEART TRANSPLANTATIONActuarial Survival Based on Rejection within 1st Year

50

60

70

80

90

100

0 1 2 3 4 5 6 7


Su

rviv

al (

%)

Free from Rejection during 1st Year (N = 513)Rejection within 1st Year (N = 680)

P = 0.09

2002ISHLT


PEDIATRIC HEART RECIPIENTSRelationship of Prednisone Use and CAD

Transplants: April 1994 – December 1999 Prednisone

Use at Discharge and at 1

Year

Reported CAD between 1st and 2nd years post-

transplant

Reported CAD between 1st and 3rd years post-

transplant

Yes No Yes No

Yes 28

4.8%

558

95.2%

27

7.1%

352

92.9%

No 4

2.8%

138

97.2%

2

2.0%

96

98.0%p = 0.4 p = 0.06

2002ISHLT


PEDIATRIC HEART RECIPIENTSRelationship of Rejection and CAD

Transplants: April 1994 – December 1999 Rejection During 1st

Year

Reported CAD between 1st and 2nd years post-

transplant

Reported CAD between 1st and 3rd years post-

transplant

Yes No Yes No

Yes 19

5.3%

342

94.7%

17

7.1%

222

92.9%

No 6

1.8%

322

98.2%

7

3.2%

212

96.8%p = 0.02 p = 0.09

2002ISHLT


PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 1 and 3 Years

Maintenance Immunosuppression at discharge and 1 year

On immuno:

% HTN reported between 1 and 3

years

Not on immuno:

% HTN reported between 1 and 3

years

P-value

Cyclosporine 20.3% 15.7% 0.6

Tacrolimus 20.5% 19.4% 0.8

Azathioprine 22.3% 15.3% 0.3

Prednisone 29.9% 6.4% <0.0001

2002ISHLT


PEDIATRIC HEART RECIPIENTS Incidence of Hypertension by 3 Years

Maintenance Immunosuppression at discharge and 1 year

On immuno:

% HTN reported by 3 years

Not on immuno:

% HTN reported by 3 years

P-value

Cyclosporine 48.8% 40.6% 0.2

Tacrolimus 44.2% 46.2% 0.8

Azathioprine 51.1% 42.4% 0.1

Prednisone 59.5% 12.1% <0.0001

2002ISHLT


PEDIATRIC HEART RECIPIENTS Growth Following Transplantation: Height

Stratified by Prednisone Use at Discharge and at 1 Year

80

100

120

140

160

180

Listing Immediately Pre-Transplant

1 Year Follow-up 2 Year Follow-up

Time of Measurement

Hei

ght (

cm)

11-17 Years/No Prednisone 11-17 Years/Prednisone


2002ISHLT


PEDIATRIC HEART RECIPIENTS Growth Following Transplantation: Weight

Stratified by Prednisone Use at Discharge and at 1 Year

0

20

40

60

80

Listing Immediately Pre-Transplant

1 Year Follow-up 2 Year Follow-up

Time of Measurement

Wei

ght (

Kg)



2002ISHLT


PEDIATRIC HEART RECIPIENTS: Time of Death (1988-2001)

0%

20%

40%

60%

80%

100%

<1 1-10 11-17Recipient Age (years)

% o

f Dea

ths

0-30 Days 31 Days -1 Year 1 - 3 Years 3 - 5 Years 5+ Years

2002ISHLT


PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (1982-2001)

0%

20%

40%

60%

80%

100%

0-30 Days (N = 398)

31 Days - 1 Year (N = 284)

>1 Year - 3 Years (N = 159)

>3 Years - 5Years (N = 87)

>5 Years (N = 120)

Other

Technical

Graft Failure - Other

Primary Graft Failure

Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

Timing of Death

Cau

se o

f D

eath

(%

)

2002ISHLT


PEDIATRIC HEART TRANSPLANTS RECIPIENTS: CAUSE OF DEATH BY ERA: Deaths in 0-30 Days

0%

20%

40%

60%

80%

100%

1987-1991 (N = 125)

1992-1996 (N = 151)

1997-2001 (N = 85)

Per

cent

age

of D

eath

s

Other

Technical



Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

2002ISHLT


PEDIATRIC HEART TRANSPLANTS RECIPIENTS: CAUSE OF DEATH BY ERA: Deaths in 31 Days - 1 Year

0%

20%

40%

60%

80%

100%

1987-1991 (N = 81)

1992-1996 (N = 140)

1997-2001 (N = 59)

Per

cent

age

of D

eath

s

Other

Technical



Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

2002ISHLT


PEDIATRIC HEART TRANSPLANTS RECIPIENTS: CAUSE OF DEATH BY ERA: Deaths in >1 Year - 3 Years

0%

20%

40%

60%

80%

100%

1987-1991 (N = 57)

1992-1996 (N = 80)

1997-2001 (N = 21)

Per

cent

age

of D

eath

s

Other

Technical



Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

2002ISHLT


PEDIATRIC HEART TRANSPLANTS RECIPIENTS: CAUSE OF DEATH BY ERA: Deaths in >3 Years - 5 Years

0%

20%

40%

60%

80%

100%

1987-1991 (N = 33)

1992-1996 (N = 48)

1997-2001 (N = 3)

Per

cent

age

of D

eath

s

Other

Technical



Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

2002 ishlt j heart lung transplant 2002; 21: 827-840. heart transplantation pediatric recipients

Documents

ishlt j heart lung transplant

year slide

delayed reporting slide

cause of death

number of centers