HEART-LUNG TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26.

HEART-LUNG TRANSPLANTATION

Overall

ISHLT 2007 J Heart Lung Transplant 2007;26

0

50

100

150

200

250

Nu

mb

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NUMBER OF HEART-LUNG TRANSPLANTS REPORTED BY YEAR

ISHLT 2007NOTE: 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 2007;26

AVERAGE CENTER VOLUMEHeart-Lung Transplants: January 1, 1998 - June 30, 2006

45

33

84

10

5

10

15

20

25

30

35

40

45

1 2 3 4-9 10+

Average number of heart-lung transplants per year

Nu

mb

er

of

cen

ters


DISTRIBUTION OF HEART-LUNG TRANSPLANTS BY CENTER VOLUME

Heart-Lung Transplants: January 1, 1998 - June 30, 2006

0

5

10

15

20

25

30

35

40

1 2 3 4-9 10+

Average number of heart-lung transplants per year

Perc

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eart

-lu

ng

tra

nsp

lan

tss


DISTRIBUTION OF HEART-LUNG TRANSPLANTS BY LUNG CENTER VOLUME

Lung Transplants: January 1, 1998 - June 30, 2006

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

Perc

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-lu

ng

tra

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ts


HEART-LUNG TRANSPLANTATIONKaplan-Meier Survival (Transplants: January 1982 - June 2005)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Years

N=3,184

Half-life = 3.1 yearsConditional Half-life = 8.8 years

Su

rviv

al (

%)

ISHLT 2007

N at risk at 20 years = 7



Adult Recipients


Acquired heart disease

4%Congenital heart disease

35%

COPD/Alpha-16%

CF14%

PPH24%

Re-transplant2%

OTHER12%

IPF3%

DIAGNOSIS IN ADULT HEART-LUNG TRANSPLANTS (January 1982 - June 2006)

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


DIAGNOSIS IN ADULT HEART-LUNG TRANSPLANTS (Transplants: January 1982 - June 2006)

Diagnosis N (%)

Congenital Heart Disease 841 (33.9%)

Primary Pulmonary Hypertension 601 (24.2%)

Cystic Fibrosis 352 (14.2%)

Acquired Heart Disease 110 ( 4.4%)

COPD/Emphysema 92 ( 3.7%)

Idiopathic Pulmonary Fibrosis 71 ( 2.9%)

Alpha-1 53 ( 2.1%)

Re-Transplant: Not Obliterative Bronchiolitis 31 ( 1.2%)

Sarcoidosis 30 ( 1.2%)

Re-Transplant: Obliterative Bronchiolitis 24 ( 1.0%)

Bronchiectasis 18 ( 0.7%)

Obliterative Bronchiolitis (not Re-Transplant)

8 ( 0.3%)

Other 251 (10.1%)


DIAGNOSIS IN ADULT HEART-LUNG TRANSPLANTS BY ERA

0%

20%

40%

60%

80%

100%

1982-1995 1996-1999 2000-2006

% 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 2005

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 2005

Transplant Year

Nu

mb

er o

f T

ran

spla

nts

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


0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Europe North America Other

% o

f T

ran

sp

lan

ts

18 - 34 years 35 - 49 years 50 - 59 years 60+ years

ADULT HEART-LUNG TRANSPLANTS:AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006


0%

20%

40%

60%

80%

100%


% o

f T

ran

spla

nts

-

Acquired heart disease Congenital heart disease Cystic Fibrosis IPF PPH Other

ADULT HEART-LUNG TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2006


0%

20%

40%

60%

80%

100%


% o

f D

onor

s

6-11 12-17 18-34 35-49 50-59 60+

ADULT HEART-LUNG TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION



HEART-LUNG TRANSPLANTATIONKaplan-Meier Survival for Adult Recipients

(Transplants: January 1982 - June 2005)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Years

N=2,571

Half-life = 3.4 YearsConditional Half-life = 9.0 Years

Su

rviv

al (

%)


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

(Transplants: January 1982 - June 2005)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10

Years

1982-1995 (N=1,659)

1996-1999 (N=494)

2000-6/2005 (N=418)

Half-life (Years): 1982-1995 = 3.0; 1996-1999 = 3.4; 2000-6/2005 = 5.2 Conditional Half-life (Years): 1982-1995 = 8.9; 1996-1999 = 9.5; 2000-6/2005 = n/a

Su

rviv

al (

%)

ISHLT 2007

P-value comparing all: 0.0082


ADULT HEART-LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2005)

0

25

50

75

100

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

Su

rviv

al (

%)

Other Congenital (N = 208)Eisenmenger's Syndrome (N = 480)PPH (N=384)

Congenital vs. Eisenmenger's: p = 0.0009Congenital vs. PPH: p = 0.0351Eisenmenger's vs. PPH: p = 0.1370

HALF-LIFE Congenital: 1.5 Years; Eisenmenger's: 5.8 Years; PPH: 3.5 Years


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

(Transplants: January 1990 – June 2005)

0

25

50

75

100

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

Su

rviv

al (

%)

Other Congenital (N = 106)Eisenmenger's Syndrome (N = 320)PPH (N=244)

HALF-LIFE Congenital Years: n.a.;Eisenmenger's: 10.3 Years; PPH: 9.1 Years

Congenital vs. Eisenmenger's: p = 0.6935Congenital vs. PPH: p = 0.4908Eisenmenger's vs. PPH: p = 0.1305


ADULT HEART-LUNG RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: April 1994 – June 2006)

0%

20%

40%

60%

80%

100%

1 Year (N = 258) 3 Years (N = 207) 5 Years (N = 177) 7 Years (N = 145)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


ADULT HEART-LUNG RECIPIENTSEmployment Status of Surviving Recipients

(Follow-ups: April 1994 – June 2006)

0%

20%

40%

60%

80%

100%

1 Year (N = 277) 3 Years (N = 198) 5 Years (N = 187) 7 Years (N = 138)

Working (FT/PTstatus unknown)

Retired

Not Working

Working Part Time

Working Full Time


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

(Follow-ups: April 1994 - June 2006)

0%

20%

40%

60%

80%

100%

Up to 1 Year (N = 332)

Between 2 and 3Years (N = 238)



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 = 94) Polyclonal ALG/ATG (N = 40) OKT3 (N = 5) IL2R-antagonist (N = 51)

% o

f p

ati

en

tsADULT HEART-LUNG RECIPIENTS

Induction ImmunosuppressionFor transplants between January 2001 through June 2006


0

10

20

30

40

50

60

Any Induction Polyclonal ALG/ATG OKT3 IL2R-antagonist

% o

f p

atien

ts

2000 2001 20022003 2004 2005

ADULT HEART-LUNG RECIPIENTSInduction Immunosuppression (Transplants: January 2000 - December 2005)


0

10

20

30

40

50

60

% o

f p

ati

en

ts

ADULT HEART-LUNG RECIPIENTSInduction Immunosuppression (Transplants: January 2000 - December 2005)

ISHLT 2007

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 = 159) Year 5 (N = 98)

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

For follow-ups between January 2001 through June 2006

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


0%

20%

40%

60%

80%

100%

Year 1 (N = 151) Year 5 (N = 103)

% o

f P

atien

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 2006

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 55.6% (N = 329)

Renal Dysfunction 18.3% (N = 327)

Abnormal Creatinine < 2.5 mg/dl 11.0% Creatinine > 2.5 mg/dl 3.1% Chronic Dialysis 4.0% Renal transplant 0.3%

Hyperlipidemia 20.9% (N = 344)

Diabetes 15.4% (N = 331)

Coronary Artery Vasculopathy 2.2% (N = 271)

Bronchiolitis Obliterans 8.4% (N = 308)


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 88.6% (N = 114)

Renal Dysfunction 29.2% (N = 120)

Abnormal Creatinine < 2.5 mg/dl 19.2% Creatinine > 2.5 mg/dl 9.2% Chronic Dialysis 0.8% Renal Transplant 0.0%

Hyperlipidemia 64.5% (N = 121)

Diabetes 20.0% (N = 115)

Coronary Artery Vasculopathy 9.1% (N = 66)

Bronchiolitis Obliterans 27.7% (N = 94)


Freedom from Coronary Artery Vasculopathy

For Adult Heart-Lung Recipients (Follow-ups: April 1994-June 2006)

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 2006)

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

% F

ree f

rom

Bro

nch

ioliti

s O

blite

ran

s


Freedom from Severe Renal Dysfunction*For Adult Heart-Lung Recipients (Follow-ups: April 1994-June 2006)

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

% F

ree fro

m S

evere

Ren

al D

ysfu

nctio

n

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


MALIGNANCY POST-HEART-LUNG TRANSPLANT FOR ADULTSCumulative Prevalence in Survivors (Follow-ups: April 1994-June 2006)

Malignancy/Type 1-Year Survivors

5-Year Survivors

10-Year Survivors

No Malignancy 308 (92.2%) 106 (88.3%) 51 (85%)

Malignancy (all types combined) 26 (7.8%) 14 (11.7%) 9 (15%)

Malignancy Type*

Skin 2 4 9

Lymph 18 6 2

Other 2 2 1

Type Not Reported 4 2 0

ISHLT 2007

* Recipients may have experienced more than one type of malignancy so sum of individual malignancy types may be greater than total number with malignancy.


Freedom from MalignancyFor Adult Heart-Lung Recipients (Follow-ups: April 1994- June 2006)

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 2006)

CAUSE OF DEATH 0-30 Days

(N = 225)

31 Days - 1 Year (N = 145)

>1 Year - 3 Years (N = 124)

>3 Years - 5 Years (N = 70)

>5 Years

(N = 129)

BRONCHIOLITIS 0 4 (2.8%) 34 (27.4%) 28 (40.0%) 31 (24.0%)

ACUTE REJECTION 3 (1.3%) 4 (2.8%) 2 (1.6%) 0 1 (0.8%)

LYMPHOMA 0 5 (3.4%) 9 (7.3%) 3 (4.3%) 1 (0.8%)

MALIGNANCY, OTHER 0 1 (0.7%) 6 (4.8%) 2 (2.9%) 6 (4.7%)

CMV 0 1 (0.7%) 0 1 (1.4%) 0

INFECTION, NON-CMV 40 (17.8%) 58 (40.0%) 34 (27.4%) 7 (10.0%) 22 (17.1%)

GRAFT FAILURE 69 (30.7%) 32 (22.1%) 21 (16.9%) 11 (15.7%) 31 (24.0%)

CARDIOVASCULAR 21 (9.3%) 6 (4.1%) 6 (4.8%) 8 (11.4%) 8 (6.2%)

TECHNICAL 47 (20.9%) 3 (2.1%) 1 (0.8%) 1 (1.4%) 0

OTHER 45 (20.0%) 31 (21.4%) 11 (8.9%) 9 (12.9%) 29 (22.5%)



Pediatric Recipients


AGE DISTRIBUTION OF PEDIATRIC HEART-LUNGRECIPIENTS (Transplants: January 1982 - June 2006)

0

50

100

150

200

250

300

<1 1-5 yrs 6-11 yrs 12-17 yrs

Recipient Age (Years)

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AGE DISTRIBUTION FOR DONORS OF PEDIATRIC HEART-LUNG RECIPIENTS (Transplants: January 1982 - June 2006)

328

88

48 2220

50

100

150

200

250

300

0-11 yrs 12-17 yrs 18-34 35-49 50-59

Donor Age (Years)

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AGE DISTRIBUTION OF PEDIATRIC HEART-LUNG RECIPIENTS

By Year of Transplant

0

5

10

15

20

25

30

35

40

45

11-17 Years1-10 Years

<1 Year

Nu

mb

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f T

ran

spla

nts

ISHLT 2007

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


AGE DISTRIBUTION OF PEDIATRIC HEART-LUNG RECIPIENTS

By Era of Transplant

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1982-1995 1996-6/2006

11-17 Years

1-10 Years

<1 Year

Per

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NUMBER OF CENTERS REPORTING PEDIATRIC HEART-LUNG TRANSPLANTS

ISHLT 2007

NEED TO UPDATE

0

5

10

15

20

25

Transplant Year

# P

edia

tric

Tra

nsp

lan

t C

ente

rs


NUMBER OF CENTERS REPORTING PEDIATRIC HEART-LUNG TRANSPLANTS

Stratified by center volume

0

5

10

15

20

25

Transplant Year

# P

edia

tric

Tra

nsp

lan

t C

ente

rs

1-4/yr 5-9/yr

10-19/yr 20-29/yr


9%

26%21%

16%

1%

3%19%

2%

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

% o

f C

ases

Cystic Fibrosis Congenital PPH

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


0%

20%

40%

60%

80%

100%


% o

f T

ran

sp

lan

ts

0-5 years 6-11 years 12-17 years

PEDIATRIC HEART-LUNG TRANSPLANTS:AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006


0%

20%

40%

60%

80%

100%


% o

f T

ran

sp

lan

ts-

Congenital heart disease Cystic Fibrosis PPH Other

PEDIATRIC HEART-LUNG TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION



0%

20%

40%

60%

80%

100%


% o

f Do

no

rs

0-5 6-11 12-17 18-34 35-49

PEDIATRIC HEART-LUNG TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION



PEDIATRIC HEART-LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2005)

0

25

50

75

100

0 1 2 3 4 5 6 7 8

Years

Su

rviv

al (

%)

Congenital (N = 83)Eisenmenger's Syndrome (N = 45)PPH (N=76)

HALF-LIFE Congenital: 1.8 Years; Eisenmenger's: 2.6 Years; PPH: 3.3 Years

Congenital vs. Eisenmenger's: p= 0.6363Congenital vs. PPH: p = 0.5302Eisenmenger's vs. PPH: p = 0.9015


PEDIATRIC HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival (Transplants: January 1982 - June 2005)

0

25

50

75

100

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

Years

Sur

viva

l (%

)

.

< 1 (N = 13)

1-10 (N = 205)

11-17 (N = 284)

Overall (N = 502)

Half-life <1: 0.2 Years; 1-11: 3.0 Years; 12-17: 3.3 Years

P-values 0-<1 vs. 1-11: p = 0.0003; 0-<1 vs. 12-17: p=0.0002; 1-11 vs. 12-17: p=0.1653


PEDIATRIC HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1982 - June 2005)

0

25

50

75

100

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

1982-1988 (N=109)

1989-1993 (N=176)

1994-1998 (N=127)

1999-6/2005 (N= 88)

Half-life 1982-1988: 1.7; 1989-1993: 3.0; 1994-1998: 3.1; 1999-6/2005: 4.7

P-values 82-88 vs. 89-93: 0.4184; 82-88 vs. 94-98: 0.6217; 82_88 vs. 99-6/2005: 0.0506 89-93 vs. 94-98: 0.7716; 89-93 vs. 99-6/2005: 0.3096; 94-98 vs. 99-6/2005: 0.1706

Su

rviv

al (

%)


PEDIATRIC HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1982 - June 2005)

Conditional on Survival to 1 Year

0

20

40

60

80

100

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

1982-1988 (N=60) 1989-1993 (N=111)

1994-1998 (N=78) 1999-6/2005 (N= 55)

Conditional HALF-LIFE 1982-1988: 8.3; 1989-1993: 7.4; 1994-1998: 6.1; 1999-6/2004:

P-values 82-88 vs. 89-93: 0.5197; 82-88 vs. 94-98: 0.4711; 82_88 vs. 99-6/2005: 0.813489-93 vs. 94-98: 0.9921; 89-93 vs. 99-6/2005: 0.6368; 94-98 vs. 99-6/2005: 0.4671

Su

rviv

al (

%)


PEDIATRIC HEART-LUNG TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2006)

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

31 Days - 1 Year (N= 28 )

>1 Year - 3 Years (N= 26 )

>3 Years - 5 Years (N = 19 )

>5 Years (N = 19)

BRONCHIOLITIS 1 (3.6%) 14 (53.8%) 9 (47.4%) 7 (36.8%)

ACUTE REJECTION 2 (7.1%)

MALIGNANCY, OTHER 1 (5.3%)


GRAFT FAILURE 12 (40.0%) 2 (7.1%) 5 (19.2%) 5 (26.3%) 3 (15.8%)

CARDIOVASCULAR 2 (6.7%) 3 (10.7%) 1 (5.3%) 2 (10.5%)

TECHNICAL 4 (13.3%) 1 (3.6%)


PEDIATRIC HEART-LUNG TRANSPLANT RECIPIENTS: Cause of Death (Deaths: April 1994 - June 2006)

CAUSE OF DEATH 0-30 Days (N = 26)

31 Days - 1 Year (N = 22)

>1 Year - 3 Years (N = 20)

>3 Years - 5 Years (N = 17)

>5 Years

(N = 19)

BRONCHIOLITIS 1 (4.5%) 11 (55.0%) 8 (47.1%) 7 (36.8%)

ACUTE REJECTION 1 (4.5%)

MALIGNANCY, OTHER 1 (5.9%)


GRAFT FAILURE 12 (46.2%) 2 (9.1%) 3 (15.0%) 5 (29.4%) 3 (15.8%)

CARDIOVASCULAR 2 (7.7%) 2 (9.1%) 2 (10.5%)

TECHNICAL 2 (7.7%) 1 (4.5%)


HEART-LUNG TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26.

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Transcript of HEART-LUNG TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26.