heart-lung transplantation overall ishlt 2006 j heart lung transplant 2006;25: 880-892

HEART-LUNG TRANSPLANTATION

Overall

ISHLT 2006 J Heart Lung Transplant 2006;25: 880-892

0

50

100

150

200

250

Num

ber

of T

rans

plan

ts

NUMBER OF HEART-LUNG

TRANSPLANTS REPORTED BY YEAR

ISHLT 2006

NOTE: This figure includes only the heart-lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of heart-lung transplants worldwide has declined in recent years.

J Heart Lung Transplant 2006;25: 880-892

AVERAGE CENTER VOLUMEHeart-Lung Transplants: January 1, 1998 - June 30, 2005

40

32

12

3 20

5

10

15

20

25

30

35

40

1 2 3 4-9 10+

Average number of heart-lung transplants per year

Nu

mb

er

of

ce

nte

rs


DISTRIBUTION OF HEART-LUNG TRANSPLANTS BY CENTER VOLUME

Heart-Lung Transplants: January 1, 1998 - June 30, 2005

0

5

10

15

20

25

30

35

1 2 3 4-9 10+

Average number of heart-lung transplants per year

Pe

rce

nta

ge

of

he

art

-lu

ng

tra

ns

pla

nts

s


DISTRIBUTION OF HEART-LUNG TRANSPLANTS BY LUNG CENTER VOLUME

Lung Transplants: January 1, 1998 - June 30, 2005

0

10

20

30

40

1-4 5-9 10-19 20-29 30-39 40-49 50+

Average number of lung transplants per year

Pe

rce

nta

ge

of

he

art

-lu

ng

tra

ns

pla

nts


HEART-LUNG TRANSPLANTATIONKaplan-Meier Survival (Transplants: January 1982 - June 2004)

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

Years

N=3,086

Half-life = 3.1 yearsConditional Half-life = 8.7 years

Su

rviv

al (

%)

ISHLT 2006

N alive at 18 years = 18



Adult Recipients


Acquired heart disease

4%Congenital heart disease

33%

COPD/Alpha-16%

CF16%

IPF3%

PPH24%

Re-transplant2%

Other 12%

DIAGNOSIS IN ADULT HEART-LUNG TRANSPLANTS (1/1982-6/2005)

“Other” includes cancer, LAM, OB, sarcoidosis, bronchiectasis


DIAGNOSIS IN ADULT HEART-LUNG TRANSPLANTS (Transplants: January 1982 - June 2005)

Diagnosis N (%)

Congenital Heart Disease 702 (32.2%)

Primary Pulmonary Hypertension 531 (24.4%)

Cystic Fibrosis 342 (15.7%)

Acquired Heart Disease 97 ( 4.5%)

COPD/Emphysema 83 ( 3.8%)

Idiopathic Pulmonary Fibrosis 62 ( 2.8%)

Alpha-1 38 ( 1.7%)

Re-Transplant: Not Obliterative Bronchiolitis 29 ( 1.3%)

Sarcoidosis 28 ( 1.3%)

Re-Transplant: Obliterative Bronchiolitis 23 ( 1.1%)

Bronchiectasis 14 ( 0.6%)

Obliterative Bronchiolitis

(not Re-Transplant)

9 ( 0.4%)

Other 221 (10.1%)


DIAGNOSIS IN ADULT HEART-LUNG TRANSPLANTS BY ERA

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1982-1995 1996-1999 2000-2005

% o

f T

ran

sp

lan

ts

Other

Re-TX

PPH

IPF

CF

Acquired Heart Disease

Congenital Heart Disease

COPD/Alpha-1

“Other” includes OB (non-ReTX), Bronchiectasis, Sarcoidosis


ADULT HEART-LUNG TRANSPLANTATIONIndications By Year (%)

0

20

40

60

80

100

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

Transplant Year

% o

f T

ran

spla

nts

Congenital Heart Disease Primary Pulmonary HypertensionCystic Fibrosis COPD/Alpha-1Acquired Heart Disease


ADULT HEART-LUNG TRANSPLANTATIONIndications By Year (Number)

0

50

100

150

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

Transplant Year

Nu

mb

er o

f T

ran

spla

nts

Congenital Heart Disease Primary Pulmonary HypertensionCystic Fibrosis COPD/Alpha-1Acquired Heart Disease


HEART-LUNG TRANSPLANTATIONKaplan-Meier Survival for Adult Recipients

(Transplants: January 1982 - June 2004)

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

Years

N=2,496

Half-life = 3.5 yearsConditional Half-life = 9.0 years

Su

rviv

al (

%)


HEART-LUNG TRANSPLANTATIONKaplan-Meier Survival for Adult Recipients by Era

(Transplants: January 1982 - June 2004)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10

Years

1982-1995 (N=1,633)

1996-1999 (N=491)

2000-6/2004 (N=372)

Half-life: 1982-1995 = 3.1 years; 1996-1999 = 3.6 years; 2000-6/2005 = 5 yearsConditional Half-life: 1982-1995 = 8.9 years

Su

rviv

al (

%)


ADULT HEART-LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2004)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10Years

Su

rviv

al (

%)

Other Congenital (N = 179)Eisenmenger's Syndrome (N = 377)PPH (N=322)

Congenital vs. Eisenmenger's: p = 0.0035Congenital vs. PPH: p = 0.049Eisenmenger's vs. PPH: p = 0.25

HALF-LIFE Congenital: 1.5 Years; Eisenmenger's: 5.4 Years; PPH: 3.4 Years


ADULT HEART-LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on Survival to 1 Year

(Transplants: January 1990 – June 2004)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10Years

Su

rviv

al (

%)

Other Congenital (N = 90)Eisenmenger's Syndrome (N = 240)PPH (N=197)

No comparisons were statistically different.

HALF-LIFE Congenital: 8.4 Years; Eisenmenger's: 10.0 Years; PPH: 9.1 Years


ADULT HEART-LUNG RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: April 1994 – June 2005)

0%

20%

40%

60%

80%

100%

1 Year (N = 258) 3 Years (N = 207) 5 Years (N = 177) 7 Years (N = 148)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


ADULT HEART-LUNG RECIPIENTSEmployment Status of Surviving Recipients

(Follow-ups: April 1994 – June 2005)

0%

20%

40%

60%

80%

100%

1 Year (N = 254) 3 Years (N = 191) 5 Years (N = 174) 7 Years (N = 134)

Working Full Time Working Part Time Not Working Retired


ADULT HEART-LUNG RECIPIENTS: Rehospitalization Post-transplant of Surviving Recipients

(Follow-ups: April 1994 - June 2005)

0%

20%

40%

60%

80%

100%

Up to 1 Year (N = 302)

Between 2 and 3Years (N = 228)



No Hospitalization Hospitalized, Not Rejection/Not Infection

Hospitalized, Rejection Only Hospitalized, Infection Only

Hospitalized, Rejection and Infection


0

5

10

15

20

25

30

35

40

45

50

55

Any Induction (N = 88) Polyclonal ALG/ATG (N= 42)

OKT3 (N = 5) IL2R-antagonist (N =43)

% o

f p

ati

en

tsADULT HEART-LUNG RECIPIENTS

Induction ImmunosuppressionFor transplants between January 2001 through June 2005


0

10

20

30

40

50

60

Any Induction Polyclonal ALG/ATG OKT3 IL2R-antagonist

% o

f p

ati

en

ts

2000 2001 20022003 2004

ADULT HEART-LUNG RECIPIENTSInduction Immunosuppression (Transplants: January 2000 - December 2004)


0

10

20

30

40

50

60

20002001

20022003

20042000

20012002

20032004

20002001

20022003

20042000

20012002

20032004

% o

f p

atie

nts

ADULT HEART-LUNG RECIPIENTS

Induction Immunosuppression (Transplants: January 2000 - December 2004)

ISHLT 2006

Any Induction Polyclonal ALG/ATG OKT3 IL2R-antagonist


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

atie

nts

Year 1 (N = 80) Year 5 (N = 58)

ADULT HEART-LUNG RECIPIENTSMaintenance Immunosuppression at Time of Follow-up

For follow-ups between January 2001 through June 2005

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


0%

20%

40%

60%

80%

100%

Year 1 (N = 75) Year 5 (N = 63)

% o

f P

ati

en

ts

Other

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine + MMF

Cyclosporine + AZA

ADULT HEART-LUNG RECIPIENTSMaintenance Immunosuppression Drug Combinations at Time of Follow-up

For follow-ups between January 2001 through June 2005

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


POST-HEART-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 Year Post-Transplant


Outcome Within 1

Year Total number with known response

Hypertension 55.3% (N = 300)

Renal Dysfunction 17.9% (N = 296)

Abnormal Creatinine < 2.5 mg/dl 10.5% Creatinine > 2.5 mg/dl 3.4% Chronic Dialysis 3.7% Renal transplant 0.3%

Hyperlipidemia 19.5% (N = 313)

Diabetes 14.0% (N = 300)

Coronary Artery Vasculopathy 2.4% (N = 250)

Bronchiolitis Obliterans 9.4% (N = 278)


POST-HEART-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 5 Years Post-Transplant


Outcome Within 5 Years

Total number with known response

Hypertension 87.5% (N = 96)

Renal Dysfunction 27.7% (N = 101)

Abnormal Creatinine < 2.5 mg/dl 18.8% Creatinine > 2.5 mg/dl 7.0% Chronic Dialysis 1.0% Renal Transplant 0.0%

Hyperlipidemia 64.7% (N = 102)

Diabetes 21.6% (N = 97)

Coronary Artery Vasculopathy 8.9% (N = 56)

Bronchiolitis Obliterans 28.2% (N = 78)


Freedom from Coronary Artery Vasculopathy

For Adult Heart-Lung Recipients (Follow-ups: April 1994-June 2005)

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

% F

ree

fro

m C

AV


Freedom from Bronchiolitis Obliterans For Adult Heart-Lung Recipients (Follow-ups: April 1994-June 2005)

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

% F

ree

fro

m B

ron

ch

ioli

tis

Ob

lite

ran

s


Freedom from Severe Renal Dysfunction*For Adult Heart-Lung Recipients (Follow-ups: April 1994-June 2005)

50

60

70

80

90

100

0 1 2 3 4 5

Years

% F

ree

fro

m S

ev

ere

Re

na

l D

ys

fun

cti

on

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


MALIGNANCY POST-HEART-LUNG TRANSPLANT FOR ADULTSCumulative Prevalence in Survivors (Follow-ups: April 1994-June 2005)

Malignancy/Type 1-Year Survivors

5-Year Survivors

10-Year Survivors

No Malignancy 278 (91.7%) 90 (89.1%) 47 (83.9%)

Malignancy (all types combined) 25 (8.3%) 11 (10.9%) 9 (16.1%)

Malignancy Type

Skin 2 3 5

Lymph 18 5 2

Other 1 1 1

Type Not Reported 4 2 1


Freedom from MalignancyFor Adult Heart-Lung Recipients (Follow-ups: April 1994- June 2005)

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

% F

ree

from

Mal

igna

ncy

All malignancy

Lymph

Skin

Other


ADULT HEART-LUNG TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2005)

CAUSE OF DEATH 0-30 Days

(N = 205)

31 Days - 1 Year (N = 127)

>1 Year - 3 Years (N = 100)

>3 Years - 5 Years (N = 59)

>5 Years

(N = 106)

BRONCHIOLITIS 0 5 (3.9%) 26 (26.0%) 23 (39.0%) 21 (19.8%)

ACUTE REJECTION 2 (1.0%) 3 (2.4%) 1 (1.0%) 0 1 (0.9%)

LYMPHOMA 0 4 (3.1%) 4 (4.0%) 3 (5.1%) 1 (0.9%)

MALIGNANCY, OTHER 0 1 (0.8%) 6 (6.0%) 2 (3.4%) 5 (4.7%)

CMV 0 1 (0.8%) 0 1 (1.7%) 0

INFECTION, NON-CMV 39 (19.0%) 52 (40.9%) 31 (31.0%) 3 (5.1%) 16 (15.1%)

GRAFT FAILURE 64 (31.2%) 26 (20.5%) 17 (17.0%) 10 (16.9%) 27 (25.5%)

CARDIOVASCULAR 19 (9.3%) 7 (5.5%) 5 (5.0%) 7 (11.9%) 8 (7.5%)

TECHNICAL 39 (19.0%) 2 (1.6%) 1 (1.0%) 1 (1.7%) 0

OTHER 42 (20.5%) 26 (20.5%) 9 (9.0%) 9 (15.3%) 27 (25.5%)



Pediatric Recipients

ISHLT 2006 J Heart Lung Transplant 2006;25:904-911

AGE DISTRIBUTION OF PEDIATRIC HEART-LUNGRECIPIENTS (Transplants: January 1982 - June 2005)

0

10

20

30

40

50

60

70

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-LUNG RECIPIENTS (Transplants: January 1982 - June 2005)

0

5

10

15

20

25

30

35

40

45

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 o

f T

ran

spla

nts


AGE DISTRIBUTION OF PEDIATRIC HEART-LUNG RECIPIENTS

By Year of Transplant

0

5

10

15

20

25

30

35

40

45

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

11-17 Years1-10 Years

<1 Year

Nu

mb

er o

f T

ran

spla

nts

ISHLT 2006

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 pediatric heart-lung transplants worldwide has declined in recent years.

J Heart Lung Transplant 2006;25:904-911

AGE DISTRIBUTION OF PEDIATRIC HEART-LUNG RECIPIENTS

By Era of Transplant

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1982-1995 1996-6/2005

11-17 Years

1-10 Years

<1 Year

Per

cen

tag

e o

f T

ran

spla

nts


NUMBER OF CENTERS REPORTING PEDIATRIC HEART-LUNG TRANSPLANTS

0

5

10

15

20

25

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

Transplant Year

Nu

mb

er o

f P

edia

tric

Tra

nsp

lan

t C

ente

rs


9%

25%21%

16%

1%

2% 20%

3%

3%

Acquired Heart Disease

CF

Congenital (other)Eisenmenger's Syndrome

IPF

Other

PPHRetx: Non-OB

Retx: OB

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

0

25

50

75

100

1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

% o

f C

ases

Cystic Fibrosis Congenital PPH

“Other” includes Bronchiectasis, Alpha-1, and OB (non-ReTX)


PEDIATRIC HEART-LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2004)

0

25

50

75

100

0 1 2 3 4 5 6 7Years

Su

rviv

al

(%)

Congenital (N = 74)Eisenmenger's Syndrome (N = 37)PPH (N=68)

Congenital vs. Eisenmenger's: p= 0.4Congenital vs. PPH: p = 0.4Eisenmenger's vs. PPH: p = 0.9


PEDIATRIC HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival (Transplants: January 1982 - June 2004)

0

20

40

60

80

100

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

Years

Sur

viva

l (%

)

.

< 1 (N = 12)

1-10 (N = 164)

11-17 (N = 267)

Overall (N = 443)

HALF-LIFE 1-10: 2.0 Years; 11-17: 3.3 Years


PEDIATRIC HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1982 - June 2004)

0

20

40

60

80

100

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

1982-1988 (N=99)) 1989-1993 (N=158)

1994-1998 (N=116) 1999-6/2004 (N=68)

HALF-LIFE Unconditional 1982-1988: 1.7 Years; 1989-1993: 2.9 Years; 1994-1998: 3.2 Years; 1999-6/2004: 3.0 YearsConditional 1982-1988: 8.0 Years; 1989-1993: 7.2 Years; 1994-1998: 6.1 Years; 1999-6/2004: .

No comparisons are statistically significant

Su

rviv

al (

%)


PEDIATRIC HEART-LUNG TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2005)

CAUSE OF DEATH 0-30 Days (N = 27)

31 Days - 1 Year (N = 28)

>1 Year - 3 Years (N = 25)

>3 Years - 5 Years (N = 17)

>5 Years

(N = 18)

BRONCHIOLITIS 1 (3.6%) 14 (53.8%) 8 (47.1%) 7 (35.0%)

ACUTE REJECTION 2 (7.1%)

INFECTION, NON-CMV 5 (19.2%) 9 (32.1%) 5 (19.2%) 1 (5.9%) 5 (25.0%)

GRAFT FAILURE 13 (50.0%) 2 (7.1%) 5 (19.2%) 5 (29.4%) 3 (15.0%)

CARDIOVASCULAR 2 (7.7%) 3 (10.7%) 1 (5.9%) 2 (10.0%)

TECHNICAL 3 (11.5%) 1 (3.6%)

OTHER 3 (11.5%) 10 (35.7%) 2 (7.7%) 2 (11.8%) 3 (15.0%)


heart-lung transplantation overall ishlt 2006 j heart lung transplant 2006;25: 880-892

Documents

number of heart

distribution of heart

heart disease97

ishlt transplant registry

congenital heart disease702

year ishlt

adult recipients transplants

year transplants