HEART TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781.

HEART TRANSPLANTATION

Overall

ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781

NUMBER OF HEART TRANSPLANTS REPORTED BY YEAR

189 317665

1182

2158

2710

31373362

4001 4171 4197 4365 4439 4399 4263 41673833

3563 3410 3367 3269 3180 3026 3095

0

500

1000

1500

2000

2500

3000

3500

4000

4500

Nu

mb

er

of

Tra

nsp

lan

ts

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 hearts transplanted worldwide has declined in recent years.

J Heart Lung Transplant 2007;26: 769-781

AVERAGE CENTER VOLUMEHeart Transplants: January 1, 1992 - June 30, 1996

and January 1, 2002 – June 30, 2006

58 59

81

49

15

4055

80

2515 3 4 3455

0

10

20

30

40

50

60

70

80

90

1-4 5-9 10-19 20-29 30-39 40-49 50-74 75+

Average number of heart transplants per year

Nu

mb

er

of

cen

ters

.

1992-6/1996

2002-6/2006


DISTRIBUTION OF TRANSPLANTS BY CENTER VOLUMEHeart Transplants: January 1, 1992 - June 30, 1996

and January 1, 2002 – June 30, 2006

28

24 26

129

6

14

2

11

33

18 16

47 9

0

5

10

15

20

25

30

35

1-4 5-9 10-19 20-29 30-39 40-49 50-74 75+

Average number of heart transplants per year

Per

cen

tag

e o

f tr

ansp

lan

ts

1992-6/1996

2002-6/2006


0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

% o

f T

ran

sp

lan

ts

0-10 11-17 18-34 35-49 50-59 60+

0

5

10

15

20

25

30

35

Me

an

do

no

r a

ge

(y

ea

rs)

Mean Age

HEART TRANSPLANTS: Donor Age by Year of Transplant


AGE DISTRIBUTIONOF HEART RECIPIENTS (1/1982-6/2006)

% o

f T

r%

of

Tra

ns

pla

nts

ns

pla

nts

0

5

10

15

20

25

30

35

40

0-9 10-19 20-29 30-39 40-49 50-59 60+

Recipient Age


AGE DISTRIBUTION OF HEART TRANSPLANT RECIPIENTS BY ERA

0

5

10

15

20

25

30

35

40

0-9 10-19 20-29 30-39 40-49 50-59 60+

Recipient Age

% o

f tr

an

sp

lan

ts

1982-1991 (N = 20,991)

1992-2001 (N = 39,801)

2002 - 6/2006 (N = 14,041)

P < 0.0001


HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2005)

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 21 22

Years

Su

rviv

al (%

)

Half-life = 10.0 yearsConditional Half-life = 13.0 years

N=70,702

ISHLT 2007

N at risk at 22 years: 33

HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2005)


HEART TRANSPLANTATION

Adult Recipients


Congenital2%

ReTX2%

Myopathy45%

Misc.3%

Valvular3%

CAD45%

1/1982-6/2006

DIAGNOSIS IN ADULT HEART TRANSPLANTS

203040506070

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

% o

f Cas

es

Myopathy CAD

CAD38%

Valvular2%

Misc.10%

Myopathy45%

ReTX2%

Congenital3%

1/2003-6/2006


0%

20%

40%

60%

80%

100%

Europe North America Other

10-19 years 20-29 years 30-39 years 40-49 years50-59 years 60+ years

% o

f T

ran

sp

lan

tsADULT HEART TRANSPLANTS:

RECIPIENT AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006


0%

20%

40%

60%

80%

100%

Europe North America Other

% o

f Do

nors

0-10 years 11-17 years 18-34 years35-49 years 50-59 years 60+ years

ADULT HEART TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2006


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: 1/1982 – 6/2005)

0

20

40

60

80

100

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

Years

1982-1991 (N=18,844)

1992-2001 (N=34,987)

2002-6/2005 (N=9,459)

All comparisons significant at p < 0.0001

HALF-LIFE 1982-1991: 8.9 years; 1992-2001: 10.3 years; 2002-6/2005: NA

Su

rviv

al (

%)


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: 1/1982-6/2005)

0

20

40

60

80

100

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

Years

Su

rviv

al

(%)

18-34 (N= 6,688) 35-49 (N=17,969)50-59 (N=25,166) 60-64 (N=9,648)65-69 (N= 3,241) 70+ (N= 346)

HALF-LIFE 18-34: 11.9 years; 35-49: 10.8 years; 50-59: 9.7 years; 60-64: 8.8 years; 65-69: 8.1 years; 70+: 6.9 years

All pair-wise comparisons are statistically significant at p < 0.01


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: 1/1998-6/2005)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

Years

Su

rviv

al

(%)

18-34 (N= 2,248) 35-49 (N= 5,244)50-59 (N=8,292) 60-64 (N=4,001)65-69 (N= 1,814) 70+ (N= 235)

All pair-wise comparisons are statistically significant at p < 0.05

except 18-34 vs. 50-64; 18-34 vs. 60-64; and 65-69 vs. 70+

ISHLT 2007

HALF-LIFE 18-34: NA; 35-49: NA; 50-59: NA;

60-64: 8.3 years; 65-69: 8.1 years; 70+: 7.3 years


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis (Transplants: 1/1982-6/2005)

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

Su

rviv

al (

%)

Cardiomyopathy (N = 27,393) Coronary artery disease (N = 27,846)Congenital diagnosis (N = 1,081) Retransplant (1,255)Valvular (N= 2,027) Other (N= 1,578)

HALF-LIFE Cardiomyopathy: 11.0 years; CAD: 9.1 years; Congenital: 13.4 years; Retransplant: 4.6 years; Valvular: 10.6 years; Other: 11.8 years

All pair-wise comparisons with Cardiomyopathy are significant at p < 0.005 except for Congenital; CAD vs. ReTx: p < 0.0001; CAD vs. Valvular: p = 0.005; Valvular vs. ReTx: p < 0.0001; Congenital vs. ReTx: p < 0.0001; ReTx vs. Other: p < 0.0001


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis

Conditional on Survival to 1 Year (Transplants: 1/1982-6/2005)

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

Su

rviv

al (

%)

Cardiomyopathy (N = 21,707)Coronary artery disease (N = 21,661)Congenital diagnosis (N = 773)Retransplant (766)Valvular (N= 1,506)Other (N= 929)

All pair-wise comparisons are significant at p <.05 except Cardiomyopathy vs. valvular (p = 34), valvular vs. other (p= .14), andCongenital vs. other (p = .12).

HALF-LIFE Cardiomyopathy: 13.3 years; CAD: 11.3 years; Congenital: 17.1 years; Retransplant: 9.3 years; Valvular: 13.4 years; Other: 14.4 years


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis (Transplants: 1/2000-6/2005)

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

Su

rviv

al (

%)

Cardiomyopathy (N=6,722) Coronary artery disease (N=6,520)

Congenital Diagnosis (N=358) Retransplant (N=318)

Valvular (N=405) Other (N=903)

All pair-wise comparisons with Cardiomyopathy are significant at p < 0.001; All pair-wise comparisons with CAD are significant at p < 0.5 except CAD vs. valvular. All other pair-wise comparisons were not statistically significant.


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis Conditional on Survival to 1 Year

(Transplants: 1/2000-6/2005)

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

Su

rviv

al (%

)

Cardiomyopathy (N=5,344) Coronary artery disease (N=5.096)

Congenital Diagnosis (N=251) Retransplant (N=230)

Valvular (N=305) Other (N=449)

ISHLT 2007

Cardiomyopathy vs. Re-TX: p = .006; Cardiomyopathy vs. Other: p = .02; CAD vs. Re-TX: p = .03; Congenital vs. Re-TX: p = .01; Valvular vs. Other: = .01; Re-TX vs. Other: p = .0003


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by PVR (Transplants: 1/2002-6/2005)

50

60

70

80

90

100

0 1 2 3 4

Years

Su

rviv

al (

%)

1-<3 Wood units (N= 3,352) 3-<5 Wood units (N= 1,019)

5+ Wood units (N= 365)

1-<3 vs. 3-<5: p < .0001; 1-<3 vs. 5+: p = .04; 3-<5 vs. 5+: p = .55


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by VAD usage (Transplants: 1/1999-6/2005)

50

60

70

80

90

100

0 1 2 3 4 5

Years

Su

rviv

al (

%)

Pulsatile flow (N=2,043) No LVAD / No Inotropes (N=10,710)

No LVAD / Inotropes (N = 5,521)

Pulsatile vs. No LVAD/Inotropes: p = .002;Pulsatile vs. No LVAD/No inotropes: p = 0.0007; No LVAD/No inotropes vs. No LVAD/Inotropes: p = .95

NOTE: There were 96 transplants with continuous flow VADs


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by VAD usage and Era (Transplants: 1/1999-6/2005)

50

60

70

80

90

100

0 1 2 3 4 5

Years

Su

rviv

al (

%)

Pulsatile, 1999-2002 (N = 1,187) No LVAD/Inotrope, 1999-2002 (N=3,699)

Pulsatile, 2003-6/2005 (N=856) No LVAD/Inotrope, 2003-6/2005 (N=1,822)

Pulsatile vs. no LVAD/Inotropes (1999-2002): p = 0.07Pulsatile vs. no LVAD/Inotropes (2003-6/2005): p = .001


ADULT HEART TRANSPLANTS1-Year Predicted Survival Model (Transplants: 1/2002-6/2005)

Impact of Pre-Transplant VAD

ISHLT 2007

75%

80%

85%

90%

95%

100%

0 30 60 90 120 150 180 210 240 270 300 330 360

Time (days)

Pre

dic

ted

Su

rviv

al

No Pre-op VAD

Pre-op pulsatile VAD

Recipient: 54 y.o., Dx=cardiomyopathy, weight=78 kg, PVR=2.2, volume=22/year, bilirubin=0.8, PA systolic=40, creatinine=1.3 mg/dl, ischemia=180 min

Donor: 30 y.o., weight = 77 kg


0

20

40

60

80

100

0-2 months >2-6 months >6-12months

>12-36months

>36-60months

>60 months

Time between previous and current transplant

1 Y

ear

Pat

ien

t S

urv

ival

(%

) 1/1982-12/19911/1992-12/20011/2002-6/2005

Comparison of survival for interval < 12 months vs. > 12 months: p < 0.0001Comparison of survival for interval < 12 months vs. > 12 months for 1/00-6/2004: p = 0.0006

150

148

38 2139 77 8351 35 287

28 2 76 133

N=13 N=4 N=5 N=15 N=14

ADULT HEART RE-TRANSPLANTS1-Year Survival


ADULT HEART RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: 1995 - June 2006)

0%

20%

40%

60%

80%

100%

1 Year (N = 15,388) 3 Years (N = 13,600) 5 Years (N = 11,698) 7 Years (N = 9,306)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


ADULT HEART RECIPIENTSEmployment Status of Surviving Recipients


0%

20%

40%

60%

80%

100%

1 Year (N = 16,161) 3 Year (N = 14,165) 5 Year (N = 12,175) 7 Year (N = 9,910)

Retired

Not Working

Working Part Time

Working Full Time

Working (FT/PTstatus unknown)


ADULT HEART RECIPIENTSRehospitalization Post-transplant of Surviving Recipients


0%

20%

40%

60%

80%

100%

Up to 1 Year (N = 19,425)

Between 2 and 3 Years (N = 16,781)



No Hospitalization Hospitalized: Not Rejection/Not InfectionHospitalized: Rejection Only Hospitalized: Infection OnlyHospitalized: Rejection + Infection


0

10

20

30

40

50

60

Any Induction (N = 5,850) Polyclonal ALG/ATG (N =2,595)

OKT3 (N = 557) IL2R-antagonist (N =2,917)

% o

f p

ati

en

tsADULT HEART RECIPIENTS

Induction Immunosuppression (Transplants: January 2001 – June 2006)


0

10

20

30

40

50

60

Any Induction PolyclonalALG/ATG

OKT3 IL2R-antagonist

% o

f p

ati

en

ts

1995 2000 2005

ADULT HEART RECIPIENTSInduction Immunosuppression (Transplants: 1995, 2000 and 2005)


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Type

(Transplants: 1/2000-6/2005, conditional on survival to 14 days)

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

Su

rviv

al (

%)

No induction (N= 5,389) Polyclonal induction (N= 2,339)

IL2-R antagonist (N= 2,361) OKT3 (N= 586)


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

ati

en

ts

Year 1 (N = 6,313) Year 5 (N = 5,418)

ADULT HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

(Follow-ups: January 2003 - June 2006)

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


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

atie

nts

2000 (N=3,486) 2003 (N = 3,630) Jan. 2006 - Jun 2006 (N = 1,508)

ADULT HEART RECIPIENTS Maintenance Immunosuppression at Time of 1 Year Follow-up

NOTE: Different patients are analyzed in each time frame.


0%

20%

40%

60%

80%

100%

Year 1 (N = 4,369) Year 5 (N = 3,732)

None

Other

Tacrolimus

Cyclosporine

Rapa + cellcycle

Rapa + calcineurin

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine + MMF

Cyclosporine + AZA

% o

f P

ati

en

tsADULT HEART RECIPIENTS

Maintenance Immunosuppression Drug Combinations at Time of Follow-up(Follow-ups: January 2004 - June 2006)

NOTES: Different patients are analyzed in Year 1 and Year 5. In the Year 1 cohort 73.9% of patients were on prednisone; in the Year 5 cohort 56.8% of patients were on prednisone.


0%

20%

40%

60%

80%

100%

Europe: Year1 (N = 552)

NorthAmerica: Year1 (N = 3,772)

Other: Year 1(N = 45)

Europe: Year5 (N = 639)

NorthAmerica: Year5 (N = 3,064)

Other: Year 5(N = 29)

Cyclosporine + AZA Cyclosporine + MMF Tacrolimus + AZA Tacrolimus + MMF

Rapa + calcineurin Rapa + cellcycle Other None

% o

f P

ati

en

ts

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

(Follow-ups: January 2004 - June 2006)

NOTES: Different patients are analyzed in Year 1 and Year 5. ISHLT 2007


0%

20%

40%

60%

80%

100%

Year 1 (N = 4,447) Year 5 (N = 4,447)

% o

f P

atie

nts

None

Other

Tacrolimus

Cyclosporine

Rapa + cellcycle

Rapa + calcineurin

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine + MMF

Cyclosporine + AZA

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

For the Same Patients(Follow-ups: January 1999 - June 2006)


PERCENTAGE OF ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR

Stratified by Type of Induction (Transplants: January 1, 2000 - June 30, 2005)

0

10

20

30

40

50

60

70

Overall 18-44 45-62 63+ F M

% t

reate

d f

or

reje

cti

on

wit

hin

1 y

ear

.

No induction (N = 5,327) Polyclonal (N = 2,461) IL2R-antagonist (N = 2,353) OKT3 (N = 583)

For females: no induction vs. OKT3 (p = 0.0006); polyclonal vs. OKT3 (p = 0.004); IL2R vs. OKT3 (p = 0.0157)For males: no induction vs. OKT3 (p = 0.0038); polyclonal vs. OKT3 (p = 0.0386); IL2R vs. OKT3 (p = 0.002)

Overall: no induct vs. OKT3 (p<0.0001); poly vs. OKT3 (p<0.0001); poly vs. IL2 (p=0.026); IL2 vs. OKT3 (p=0.013)45-62: All comparisons with OKT3 (p=0.0005 or less). No other comparisons within age groups were statistically significant at 0.05.


NUMBER OF REJECTION EPISODES FOR ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR

Stratified by Type of Induction (Transplants: January 1, 2000 - June 30, 2005)

0

0.5

1

1.5

2

2.5

3

Overall 18-44 45-62 63+ F M

Ave

rag

e n

um

ber

of

reje

ctio

n e

pis

od

es

No induction Polyclonal IL2R-antagonist OKT3

Overall: no induction vs. OKT3 (p = 0.0017); polyclonal vs. OKT3 (p=0.0065); IL2 vs. OKT3 (p=0.0003). 18-44: no induction vs. IL2 (p = 0.037).45-62: no induction vs. OKT3 (p = 0.0025); IL2 vs. OKT3 (p = 0.0034).63+: polyclonal vs. OKT3 (p = 0.0228).For females: no induction vs. OKT3 (p = 0.0078); IL2 vs. OKT3 (p = 0.0466). For males: no induction vs. OKT3 (p =0.040); polyclonal vs. OKT3 (p=0.045); IL2 vs. OKT3 (p = 0.0022).


PERCENTAGE OF ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR

Stratified by Maintenance Immunosuppression (Transplants: January 1, 2000 - June 30, 2005)

0

10

20

30

40

50

60

Overall 18-44 45-62 63+ F M

Cyclosporine + MMF (N = 4,973) Tacrolimus + MMF (N = 2,527)

% tre

ate

d fo

r re

jectio

n w

ith

in 1

year

Overall: p<0.000118-44: p<0.0001Male: p<0.0001

ISHLT 2007

NOTE: There were 1,119 patients with cyclosporine+AZA and 138 with tacrolimus+AZA. These groups were excluded due to small numbers.


NUMBER OF REJECTION EPISODES FOR ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR Stratified by Maintenance Immunosuppression (Transplants: January 1, 2000 - June 30, 2005)

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

Overall 18-44 45-62 63+ F M

Cyclosporine + MMF Tacrolimus + MMF

Overall: p=0.037818-44: p=0.049

Avera

ge n

um

ber

of re

jectio

n e

pis

do

es

ISHLT 2007

NOTE: Cyclosporine+AZA and tacrolimus+AZA were excluded due to small numbers.


ADULT HEART TRANSPLANTATION Kaplan-Meier Survival Stratified by Rejection Within 1st Year

Conditional on survival to 1 year for transplants: 1/1999-6/2004

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

Su

rviv

al (

%)

No rejection (N=4,832) Rejection (N=3,694)

p < 0.0001


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

(Follow-ups: April 1994 – December 1997 and January 2002 - June 2006)

Follow-ups: April 1994-

December 1997 Follow-ups: January 2002 –

June 2006

Outcome Within 1

Year Total N with

known response Within 1

Year Total N with

known response

Hypertension 68.9% (N = 6,425) 74.4% (N = 7,099)

Renal Dysfunction 20.4% (N = 6,378) 30.4% (N = 7.247)

Abnormal Creatinine < 2.5 mg/dl 11.3% 22.4% Creatinine > 2.5 mg/dl 8.1% 5.9% Chronic Dialysis 1.0% 1.6% Renal Transplant 0.1% 0.4%

Hyperlipidemia 33.3% (N = 6,816) 67.8% (N = 7,640)

Diabetes 20.9% (N = 6,433) 31.5% (N = 7,199)

Cardiac Allograft Vasculopathy 7.9% (N = 5,847) 7.1% (N = 6,556)


POST-HEART TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors at 5 and 10 Years Post-Transplant

(Follow-ups: April 1994 - June 2006)

Outcome Within 5

Years Total N with

known response Within 10

Years Total N with

known response

Hypertension 93.8% (N = 8,266) 98.5% (N = 1,586)

Renal Dysfunction 32.6% (N = 8,859) 38.7% (N = 1,829)

Abnormal Creatinine < 2.5 mg/dl 21.2% 24.4% Creatinine > 2.5 mg/dl 8.4% 8.2% Chronic Dialysis 2.5% 4.9% Renal Transplant 0.5% 1.2%

Hyperlipidemia 87.1% (N = 9,237) 93.3% (N = 1,890)

Diabetes 34.8% (N = 8,219) 36.7% (N = 1,601)

Cardiac Allograft Vasculopathy 31.5% (N = 5,944) 52.7% (N = 896)


FREEDOM FROM CARDIAC ALLOGRAFT VASCULOPATHY AND FREEDOM FROM SEVERE RENAL DYSFUNCTION* For Adult Heart Recipients (Follow-ups: April 1994-June 2006)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years

Freedom from CAV (N= 18,278)

Freedom from Severe Renal Dysfunction (N= 20,115)

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

% F

reed

om

fro

m C

AV

or

Fre

ed

om

fro

m S

evere

Ren

al D

ysfu

cn

tio

n


PATIENT SURVIVAL AFTER REPORT OF CAV AND PATIENT SURVIVAL IN PATIENTS WITHOUT CAV*

(Transplants: April 1994-June 2004)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Time after Report of CAV* (Years)

Su

rviv

al (%

)

No CAV (N = 10,330)

CAV (N = 2,597)

p < 0.0001

ISHLT 2007

* Patients without CAV conditioned on survival to median time of CAV development (514 days)


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

Malignancy/Type 1-Year Survivors

5-Year Survivors

10-Year Survivors

No Malignancy 20441 (97.1%) 7780 (84.9%) 1264 (68.1%)

Malignancy (all types combined) 612 (2.9%) 1389 (15.1%) 592 (31.9%)

Malignancy Type

Skin 282 937 360

Lymph 142 127 38

Other 132 359 108

Type Not Reported 56 39 126

”Other” includes: prostate (11, 34, 17), adenocarcinoma (7, 4, 2), lung (5, 4, 1), bladder (4, 5, 4), sarcoma (3, 3, 1), breast (2, 8, 3), cervical (2, 4, 0), colon (2, 3, 1), and renal (2, 7, 2). Numbers in parentheses are those reported within 1 year, 5 years and 10 years, respectively.


FREEDOM FROM MALIGNANCYFor Adult Heart Recipients (Follow-ups: April 1994 - June 2006)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years

All malignancy Lymph Skin Other

% F

ree f

rom

Malig

nan

cy


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

CAUSE OF DEATH 0-30 Days

(N = 3,006)

31 Days –

1 Year

(N = 2,722)

>1 Year –

3 Years

(N = 2,135)

>3 Years –

5 Years

(N = 1,857)

>5 Years –

10 Years

(N = 4,054)

>10 Years

(N = 2,107)

CARDIAC ALLOGRAFT VASCULOPATHY

52 (1.7%) 127 (4.7%) 298 (14.0%) 299 (16.1%) 581 (14.3%) 309 (14.7%)

ACUTE REJECTION 193 (6.4%) 338 (12.4%) 220 (10.3%) 82 (4.4%) 69 (1.7%) 26 (1.2%)

LYMPHOMA 2 (0.1%) 54 (2.0%) 85 (4.0%) 96 (5.2%) 195 (4.8%) 73 (3.5%)

MALIGNANCY, OTHER 1 (0.0%) 57 (2.1%) 218 (10.2%) 340 (18.3%) 749 (18.5%) 392 (18.6%)

CMV 4 (0.1%) 34 (1.2%) 16 (0.7%) 3 (0.2%) 5 (0.1%) 1 (0.0%)

INFECTION, NON-CMV 393 (13.1%) 896 (32.9%) 276 (12.9%) 180 (9.7%) 442 (10.9%) 213 (10.1%)

PRIMARY FAILURE 804 (26.7%) 196 (7.2%) 134 (6.3%) 81 (4.4%) 186 (4.6%) 43 (2.0%)

GRAFT FAILURE 453 (15.1%) 304 (11.2%) 365 (17.1%) 298 (16.0%) 579 (14.3%) 310 (14.7%)

TECHNICAL 233 (7.8%) 28 (1.0%) 17 (0.8%) 17 (0.9%) 36 (0.9%) 20 (0.9%)

OTHER 162 (5.4%) 175 (6.4%) 187 (8.8%) 147 (7.9%) 339 (8.4%) 175 (8.3%)

MULTIPLE ORGAN FAILURE

356 (11.8%) 268 (9.8%) 117 (5.5%) 102 (5.5%) 309 (7.6%) 190 (9.0%)

RENAL FAILURE 20 (0.7%) 25 (0.9%) 36 (1.7%) 65 (3.5%) 225 (5.6%) 173 (8.2%)

PULMONARY 133 (4.4%) 108 (4.0%) 96 (4.5%) 85 (4.6%) 172 (4.2%) 99 (4.7%)

CEREBROVASCULAR 200 (6.7%) 112 (4.1%) 70 (3.3%) 62 (3.3%) 167 (4.1%) 83 (3.9%)


ISHLT

ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death from Leading Causes by Era

(Deaths: January 1992 - June 2006)

CAUSE OF DEATH

DATE OF DEATH

0-30 Days

(N = 3,005)

31 Days –

1 Year

(N = 2,722)

>1 Year –

3 Years

(N = 2,135)

>3 Years –

5 Years

(N = 1,857)

>5 Years – 10 Years

(N = 4,054)>10 Years

(N = 2,107)

ACUTE REJECTION

1992-1997 122 (7.1%) 231 (14.3%) 113 (9.3%) 41 (4.4%) 16 (1.1%) 16 (1.1%)

1998-6/2006 71 (5.5%) 107 (9.7%) 107 (11.7%) 41 (4.4%) 53 (2.0%) 53 (2.0%)

CARDIAC ALLOGRAFT VASCULOPATHY

1992-1997 32 (1.9%) 83 (5.1%) 184 (15.1%) 189 (20.1%) 262 (18.3%) 262 (18.3%)

1998-6/2006 20 (1.6%) 44 (4.0%) 114 (12.4%) 110 (12.0%) 319 (12.2%) 319 (12.2%)

GRAFT FAILURE1992-1997 258 (15.0%) 179 (11.0%) 200 (16.4%) 119 (12.7%) 174 (12.1%) 174 (12.1%)

1998-6/2006 195 (15.2%) 125 (11.4%) 165 (18.0%) 179 (18.8%) 405 (15.5%) 405 (15.5%)

MALIGNANCY, OTHER

1992-1997 1 (0.1%) 40 (2.5%) 118 (9.7%) 177 (18.8%) 257 (17.9%) 257 (17.9%)

1998-6/2006 0 (0.0%) 17 (1.5%) 100 (10.9%) 163 (17.8%) 492 (18.8%) 492 (18.8%)

PRIMARY FAILURE

1992-1997 508 (29.5%) 168 (10.4%) 105 (8.6%) 49 (5.2%) 99 (6.9%) 99 (6.9%)

1998-6/2006 296 (23.1%) 28 (2.5%) 29 (3.2%) 32 (3.5%) 87 (3.3%) 87 (3.3%)


ADULT HEART TRANSPLANT RECIPIENTS: Cumulative Incidence of Leading Causes of Death

(Transplants: January 1992 - June 2005)

0%

1%

2%

3%

4%

5%

6%

0 1 2 3 4 5 6 7 8 9 10

Time (years)

CAV Acute Rejection

Malignancy (non-Lymph/PTLD) Primary Failure

Graft Failure CMV

Infection (non-CMV)

Incid

en

ce o

f C

au

se-S

pecif

ic D

eath

s


ADULT HEART TRANSPLANTS (1/2002-6/2005) Risk Factors for 1 Year Mortality

2007ISHLT (N=7,024)

VARIABLE N

Relative Risk

P-value 95% Confidence

Interval

Temporary circulatory support* 52 3.38 <0.0001 2.11 -5.42

Diagnosis: Congenital vs. cardiomyopathy

170 2.13 0.0001 1.47 -3.10

VAD (unknown type) 57 1.99 0.0203 1.11 -3.55

Recipient history of insulin-dependent diabetes

62 1.87 0.0424 1.02 -3.41

Recipient on ventilator at time of transplant

203 1.83 0.0001 1.36 -2.46

Recipient history of dialysis 217 1.56 0.0019 1.18 -2.07

Recipient cerebrovascular event prior to transplant

390 1.29 0.049 1.00 -1.67

* Temporary circulatory support includes ECMO and Abiomed.



2007ISHLT (N=7,024)

VARIABLE N

Relative Risk

P-value 95% Confidence Interval

Recipient previous pregnancy 962 1.28 0.0162 1.05 -1.57

Recipient with infection requiring IV drug therapy within 2 weeks prior to transplant

779 1.27 0.0168 1.04 -1.55

Chronic pulsatile device 1157 1.27 0.0153 1.05 -1.55

Recipient prior sternotomy 2376 1.22 0.0114 1.05 -1.42

Donor CMV +/Recipient CMV - 1229 0.81 0.0342 0.67 -0.98



Continuous Factors (see figures)

Recipient age

Recipient weight

Donor age

Ischemia time

Transplant center volume

PA systolic pressure

PVR

Bilirubin

Serum creatinine

2007ISHLT J Heart Lung Transplant 2007;26: 769-781

ADULT HEART TRANSPLANTS (1/2002-6/2005) Relative Risk of 1 Year Mortality with 95% Confidence Limits

Recipient Age

0

0.5

1

1.5

2

20 25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

2007ISHLT (N=7,024)J Heart Lung Transplant 2007;26: 769-781


Donor Age

0

0.5

1

1.5

2

2.5

15 20 25 30 35 40 45 50 55 60

Donor Age

p < 0.0001

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Recipient Weight

0

0.5

1

1.5

2

50 60 70 80 90 100

Recipient Weight (kg)

p = 0.012

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Ischemia Time

0

0.5

1

1.5

2

2.5

3

30 60 90 120 150 180 210 240 270 300 330 360

Ischemia Time (minutes)

p = 0.020Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50 55 60 65 70

Center Volume (cases per year)

p < 0.0001Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Pre-Transplant Bilirubin

0

0.5

1

1.5

2

0.2 1.2 2.2 3.2

Bilirubin (mg/dl)

p = 0.0008Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Pre-Transplant Creatinine

0

0.5

1

1.5

2

2.5

3

0.5 1 1.5 2 2.5 3

Recipient Creatinine (mg/dl)

p < 0.0001

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Recipient PA Systolic Pressure

0

0.5

1

1.5

2

20 25 30 35 40 45 50 55 60 65 70

PA Systolic (mm Hg)

p = 0.041

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Recipient PVR

0

0.5

1

1.5

2

0 1 2 3 4

PVR (Wood units)

p = 0.001

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality


ADULT HEART TRANSPLANTS (1/2002-6/2005)

Factors Not Significant for 1 Year Mortality

Recipient Factors: Prior malignancy, PCW, gender, hospitalized, prior transfusions

Donor Factors: Clinical infection, history of diabetes, height, weight, gender, history of hypertension, cause of death, history of malignancy


ADULT HEART TRANSPLANTS (1/2002-6/2005) 1-Year Predicted Survival Model

75%

80%

85%

90%

95%

100%

0 30 60 90 120 150 180 210 240 270 300 330 360

Time (days)

Cohort average

Recipient: Creatinine=1.7 mg/dl; inotropes; balloon pump; bilirubin=1.1 mg/dl. Donor: 60 y.o.

Recipient: Creatinine=1.3 mg/dl; pulsatile chronic VAD; bilirubin=0.8 mg/d. Donor: 30 y.o. P

red

icte

d S

urv

ival

ISHLT 2007

Recipient: 55 y.o., Dx=CAD, weight=78 kg, PVR=2.2, volume=22/year, PA systolic=40, ischemia=180 min

Donor: Weight = 77 kg



2007ISHLT (N=5,147)

VARIABLE N

Relative Risk


Interval

Ventilator 201 2.16 <.00001 1.74 -2.67

Recipient on dialysis 129 1.79 <.00001 1.37 -2.33

Diagnosis: Congenital vs. cardiomyopathy 91 1.65 .0107 1.12 -2.41

Diagnosis: Other* vs cardiomyopathy 165 1.49 .0049 1.13 -1.96

Recipient history of diabetes 939 1.27 .0004 1.11 -1.45

Male recipient/female donor 999 1.20 .0093 1.05 -1.37

Hospitalized (including ICU) 2803 1.16 .0155 1.03 -1.30

Diagnosis: Coronary artery disease vs. cardiomyopathy

2491 1.15 .0226 1.02 -1.31

Total number of HLA mismatches

1 MM (n=14) 2 MM (N=144) 3 MM (N= 491) 4 MM (N=1102) 5 MM (N=2599) 6 MM (N = 797)

1.09 .0023 1.03 -1.16

* Other = not cardiomyopathy, coronary artery disease, valvular

heart disease, or congenital heart disease




Recipient age

Donor age

Donor/recipient BMI ratio


Ischemia time

Bilirubin

Serum creatinine


ADULT HEART TRANSPLANTS (1/1999-6/2001)

Relative Risk of 5 Year Mortality with 95% Confidence Limits

Recipient Age

0

0.5

1

1.5

2

20 25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rela

tive R

isk o

f 5 Y

ear

Mo

rtality



Donor Age

0

0.5

1

1.5

2

15 20 25 30 35 40 45 50 55 60

Donor Age

p < 0.0001Rela

tive R

isk o

f 5 Y

ear

Mo

rtality



Ischemia Time

0

0.5

1

1.5

2

2.5

30 60 90 120 150 180 210 240 270 300 330 360

Ischemia time (minutes)

p < 0.0001

Rela

tive R

isk o

f 5 Y

ear

Mo

rtality



Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50 55 60 65 70

Center volume (cases per year)

p < 0.0001

Rela

tive R

isk o

f 5 Y

ear

Mo

rtality


ADULT HEART TRANSPLANTS (1/1999-6/2001) Relative Risk of 5 Year Mortality with 95% Confidence

LimitsBMI Ratio

0

0.5

1

1.5

2

0.5 0.7 0.9 1.1 1.3 1.5

Donor BMI/Recipient BMI

p = 0.0002

Rela

tive R

isk o

f 5 Y

ear

Mo

rtality


ADULT HEART TRANSPLANTS (1/1999-6/2001)Relative Risk of 5 Year Mortality with 95% Confidence Limits

Pre-Transplant Bilirubin

0

0.5

1

1.5

2

0.2 1.2 2.2 3.2

Bilirubin (mg/dl)

p = 0.0002Rela

tive R

isk o

f 5 Y

ear

Mo

rtality



Pre-Transplant Creatinine

0

0.5

1

1.5

2

0.5 1 1.5 2 2.5 3

Creatinine (mg/dl)

p = 0.0011

Rela

tive R

isk o

f 5 Y

ear

Mo

rtality


ADULT HEART TRANSPLANTS (1/1999-6/2001) Factors Not Significant for 5 Year Mortality

Recipient Factors: VAD, thoracotomy, sternotomy, pulmonary embolism, IV inotropes, prior malignancy, PRA

Donor Factors: History of cancer, clinical infection, cause of death, history of hypertension

Transplant Factors: CMV mismatch, ABO match


ADULT HEART TRANSPLANTS (1/1999-6/2001) 5-Year Predicted Survival Model

50%

60%

70%

80%

90%

100%

0 1 2 3 4 5

Time (years)

Cohort average

Recipient: Creatinine = 1.7 mg/dl; bilirubin = 1.1 mg/dl; inotropes; in hospitalDonor: 60 y.o.

Recipient: Creatinine = 1.3 mg/dl; bilirubin = 0.8 mg/dl; pulsatile chronic VAD; no inotropes; not hospitalizedDonor: 30 y.o.

Pre

dic

ted

Su

rviv

al

ISHLT 2007

Recipient: 55 y.o., Dx=CAD, weight=78 kg, PVR=2.2, volume=24/year, PA systolic=42, ischemia=180 min; BMI ratio = 1; HLA mismatch = 5

Donor: Weight = 75 kg


ADULT HEART TRANSPLANTS (1/1999-6/2001) Risk Factors for 5 Year MortalityConditional on Survival to 1 Year

2007ISHLT (N=4,079)

VARIABLE N

Relative Risk


Interval

Repeat transplant 91 3.86 .0036 1.55 -9.57

CAV within 1st year 237 2.06 <.0001 1.57 -2.70

Ventilator at time of transplant 114 1.61 .0180 1.09 -2.39

Recipient history of diabetes 742 1.52 <.0001 1.25 -1.86

Drug-treated rejection prior to discharge 757 1.48 .0001 1.21 -1.80

Drug-treated infection prior to discharge 825 1.37 .0018 1.12 -1.66

Rejection between discharge and 1st year 1556 1.26 .0103 1.06 -1.50

0-4 total HLA mismatches 2017 0.78 .0034 0.66 -0.92

PRA > 10% 273 0.61 .0125 0.41 -0.90


ADULT HEART TRANSPLANTS (1/1999-6/2001) Borderline Significant Risk Factors for 5 Year Mortality

Conditional on Survival to 1 Year

2007ISHLT (N=4,079)

VARIABLE N

Relative Risk


Interval

Other surgical procedures (excl. cardiac re-operation) prior to discharge

428 1.27 .0598 0.99 -1.63

Diagnosis: coronary artery disease vs. cardiomyopathy

1987 1.20 .0570 0.99 -1.45


ADULT HEART TRANSPLANTS (1/1999-6/2001) Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year


Recipient age

Donor age

Donor/recipient BMI ratio



Conditional on Survival to 1 Year Recipient Age

0

0.5

1

1.5

2

2.5

3

3.5

20 25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rela

tive R

isk o

f 5 Y

ear

Mo

rtality



Conditional on Survival to 1 Year Donor Age

0

0.5

1

1.5

2

15 20 25 30 35 40 45 50 55 60

Donor Age

p = 0.0002

Rela

tive R

isk o

f 5 Y

ear

Mo

rtality



Conditional on Survival to 1 Year BMI Ratio

0

0.5

1

1.5

2

0.5 0.7 0.9 1.1 1.3 1.5

Donor BMI/Recipient BMI

p = 0.012

Rela

tive R

isk o

f 5 Y

ear

Mo

rtality


ADULT HEART TRANSPLANTS (1991-6/1995) Risk Factors for 10 Year Mortality

2007ISHLT

(N=11,870)

VARIABLE N

Relative Risk


Repeat transplant 272 1.84 <.0001 1.47 -2.32

Ventilator at time of transplant 261 1.56 <.0001 1.33 -1.84


5729 1.13 <.0001 1.07 -1.20

Number of HLA mismatches at the DR locus 0 DR MM (N=575)

1 DR MM (N=7036) 2 DR MM (N=4315)

1.09 .0003 1.04 -1.14

Male recipient/ female donor 2549 1.08 .0309 1.01 -1.17

Number of HLA mismatches at the B locus 0 B MM (N=254)

1 B MM (N=2719) 2 B MM (N=8953)

1.06 .0424 1.00 -1.12

Diagnosis: Other* vs. cardiomyopathy 441 121 .0561 0.99 -1.48

* Other = not cardiomyopathy, coronary artery disease, valvular heart disease, or congenital heart disease




Recipient age

Recipient height

Donor age

PRA


Ischemia time

2007ISHLT

(N=11,870)


ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits

Recipient Age

0

0.5

1

1.5

2

20 25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rela

tive R

isk o

f 10 Y

ear

Mo

rtality

2007ISHLT

(N=11,870)



Donor Age

0

0.5

1

1.5

2

15 25 35 45 55

Donor Age

p < 0.0001Rela

tive R

isk o

f 10 Y

ear

Mo

rtality

2007ISHLT

(N=11,870)



Pre-Transplant Recipient Height

0

0.5

1

1.5

2

150 160 170 180 190

Recipient height (cm)

p < 0.0001

Rela

tive R

isk o

f 10 Y

ear

Mo

rtality

2007ISHLT

(N=11,870)



Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50 55 60 65 70


p = 0.0008

Rela

tive R

isk o

f 10 Y

ear

Mo

rtality

2007ISHLT

(N=11,870)



Ischemia Time

0

0.5

1

1.5

2

30 60 90 120 150 180 210 240 270 300 330 360

Ischemia time (minutes)

p = 0.0057

Rela

tive R

isk o

f 10 Y

ear

Mo

rtality

2007ISHLT

(N=11,870)



Pre-transplant PRA

0

0.5

1

1.5

2

0 20 40 60 80 100

Most recent PRA prior to transplant (%)

p = 0.011

Rela

tive R

isk o

f 10 Y

ear

Mo

rtality

2007ISHLT

(N=11,870)J Heart Lung Transplant 2007;26: 769-781

ADULT HEART TRANSPLANTS (1991-6/1995) Risk Factors for 10 Year Mortality Conditional on Survival to 3 Years

2007ISHLT

(N=8,426)

VARIABLE N

Relative Risk

P-value 95%

Confidence Interval

Prior pregnancy before transplant 916 1.26 .0006 1.11 -1.44


4076 1.18 .0003 1.08 -1.29

Number of HLA mismatches at the DR locus

0 DR MM (N=459) 1 DR MM (N=4960) 2 DR MM (N=3039)

1.08 .0226 1.01 -1.16

Diagnosis: valvular heart disease vs. cardiomyopathy

279 0.79 .0739 0.60 -1.02


ADULT HEART TRANSPLANTSRisk Factors for 10 Year MortalityConditional on Survival to 3 Years


Recipient age

Recipient weight

Donor age

Donor weight (borderline)

2007ISHLT

(N=8,426)



Conditional on Survival to 3 YearsRecipient Age

0

0.5

1

1.5

2

20 25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rela

tive R

isk o

f 10 Y

ear

Mo

rtality

2007ISHLT

(N=8,426)



Conditional on Survival to 3 YearsDonor Age

0

0.5

1

1.5

2

15 25 35 45 55

Donor Age

p < 0.0001

Rela

tive R

isk o

f 10 Y

ear

Mo

rtality

2007ISHLT

(N=8,426)



Conditional on Survival to 3 YearsPre-Transplant Recipient Weight

0

0.5

1

1.5

2

50 55 60 65 70 75 80 85 90 95 100 105

Recipient weight (kg)

p = 0.0002

Rela

tive R

isk o

f 10 Y

ear

Mo

rtality

2007ISHLT

(N=8,426)



Conditional on Survival to 3 YearsDonor Weight

0

0.5

1

1.5

2

50 55 60 65 70 75 80 85 90 95 100 105

Donor weight (kg)

p = 0.057

Rela

tive R

isk o

f 10 Y

ear

Mo

rtality

2007ISHLT

(N=8,426)



2007ISHLT

(N=3,500)

VARIABLE N

Relative Risk


Repeat transplant 77 1.59 .0463 1.01 -2.51

Ventilator at time of transplant 110 1.35 .0136 1.06 -1.71


1862 1.25 <.0001 1.13 -1.37

Balloon pump at time of transplant 304 1.20 .0199 1.03 -1.41

Male recipient/female donor 610 1.13 .0334 1.01 -1.25

Number of HLA mismatches at the A locus 0 A MM (N=285)

1 A MM (N=1636) 2 A MM (N=1579)

1.10 .0058 1.03 -1.17

Hospitalized at transplant (incl. ICU) 1889 0.90 .0273 0.83 -0.99

Number of HLA mismatches at the DR locus

0 DR MM (N=234) 1 DR MM (N=1843) 2 DR MM (N=1423)

1.06 .0870 0.99 -1.14


160 0.81 .0711 0.64 -1.02


ADULT HEART TRANSPLANTSRisk Factors for 15 Year Mortality


Recipient age

Donor age

2007ISHLT

(N=3,500)



Recipient Age

0

0.5

1

1.5

2

20 25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rela

tive R

isk o

f 15 Y

ear

Mo

rtality

2007ISHLT

(N=3,500)



Donor Age

0

0.5

1

1.5

2

15 25 35 45 55

Donor Age

p < 0.0001

Rela

tive R

isk o

f 15 Y

ear

Mo

rtality

2007ISHLT

(N=3,500)


ADULT HEART TRANSPLANTS (1988-6/1991) Risk Factors for 15 Year MortalityConditional on Survival to 5 Years

2007ISHLT

(N=2,322)

VARIABLE N

Relative Risk


Diagnosis: other* vs. cardiomyopathy 53 1.58 .0149 1.09 -2.29


1211 1.27 .0006 1.11 -1.45

Number of HLA mismatches at the A locus 0 A MM (N=189)

1 A MM (N=1109) 2 A MM (N=1024)

1.12 .0164 1.02 -1.22


114 0.73 .0581 0.53 -1.01

* Other = not cardiomyopathy, coronary artery disease, valvular heart disease, or congenital heart disease


ADULT HEART TRANSPLANTSRisk Factors for 15 Year Mortality Conditional on Survival to 5 Years


Recipient age

Donor age

2007ISHLT

(N=2,322)



Conditional on Survival to 5 Years Recipient Age

0

0.5

1

1.5

2

20 25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rela

tive R

isk o

f 15 Y

ear

Mo

rtality

2007ISHLT

(N=2,322)



Conditional on Survival to 5 Years Donor Age

0

0.5

1

1.5

2

15 25 35 45 55

Donor Age

p = 0.027Rela

tive R

isk o

f 15 Y

ear

Mo

rtality

2007ISHLT

(N=2,322)


ADULT HEART TRANSPLANTS (1995-6/2001) Risk Factors for Developing Cardiac Allograft Vasculopathy

within 5 Years

VARIABLE Relative

RIsk P-value

95% Confidence

Interval

Female donor * .0043 -

Donor history of hypertension 1.33 <.0001 1.17 -1.51

Diagnosis: Coronary artery disease (vs. cardiomyopathy)

1.20 .0004 1.08 -1.32

Transplant year = 1996 vs. 2000/2001 1.15 .0411 1.01 -1.31

Number of HLA mismatches at DR locus 1.13 .0021 1.04 -1.21

Number of HLA mismatches at B locus 0.91 .0425 0.84 -1.00

Donor cause of death: Anoxia 0.81 .0342 0.67 -.098

(N=7,711)ISHLT

* Due to the statistically significant interaction of donor gender and donor age, the relative risk for donor gender must be considered in the context of donor age rather than independently.

2007 J Heart Lung Transplant 2007;26: 769-781

ADULT HEART TRANSPLANTS (1995-6/2001) Risk Factors for Developing Cardiac Allograft Vasculopathy

within 5 Years


Recipient age

Donor age

Donor age*donor gender interaction


ISHLT 2007


ADULT HEART TRANSPLANTS (1995-6/2001)Relative Risk of Developing Cardiac Allograft Vasculopathy within 5 Years

with 95% Confidence LimitsDonor Age, Donor Gender and Recipient Gender

0

0.5

1

1.5

2

2.5

3

3.5

15 20 25 30 35 40 45 50 55

Donor Age

Male Recip/Male Donor Male Recip/Female Donor

Female Recip/Male Donor Female Recip/Female Donor

p < 0.0001

Rela

tive R

isk o

f C

AV

wit

hin

5 Y

ears

ISHLT 2007

(N=7,711)

Relative risk includes impact of donor gender, recipient gender and donor age.


ADULT HEART TRANSPLANTS (1995-6/2001) Relative Risk of Developing Cardiac Allograft Vasculopathy within 5 Years

with 95% Confidence Limits Recipient Age

0

0.5

1

1.5

2

20 25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rela

tive R

isk o

f C

AV

wit

hin

5 Y

ears

ISHLT 2007


ADULT HEART TRANSPLANTS (1995-6/2001) Relative Risk of Developing Cardiac Allograft Vasculopathy within 5 Years

with 95% Confidence Limits Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50 55 60 65 70


p < 0.0001

Rela

tive R

isk o

f C

AV

wit

hin

5 Y

ears

ISHLT 2007


ADULT HEART TRANSPLANTS (4/1994-6/2001) Risk Factors for Developing Renal Dysfunction within 5 Years

Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant

VARIABLE Relative

RIsk P-value

95% Confidence

Interval

Recipient diabetes 1.47 <.0001 1.33 -1.62

Year of transplant: 1994/1995 1.24 0.0008 1.09 -1.40


Recipient with infection requiring IV drug therapy within 2 weeks prior to transplant

1.22 0.0047 1.06 -1.40

IV Inotropes at transplant 1.19 <.0001 1.10 -1.29


Recipient treated for hypertension pre-transplant

1.15 0.0011 1.06 -1.25

(N=11,145)ISHLT 2007

*Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis



Limited to Recipients without Severe Renal Dysfunction Pre-Transplant


Recipient age

Recipient creatinine

Recipient weight

Recipient PRA

Donor weight

ISHLT 2007

(N=11,145)




Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant Recipient Pre-Transplant Creatinine

0

0.5

1

1.5

2

2.5

3

0.5 1 1.5 2 2.5

Creatinine (mg/dl)

p < 0.0001

Rela

tive R

isk o

f R

en

al

Dysfu

ncti

on

wit

hin

5 Y

ears

ISHLT 2007

(N=11,145)




Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant Recipient Age

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rela

tive R

isk o

f R

en

al

Dysfu

ncti

on

wit

hin

5 Y

ears

ISHLT 2007

(N=11,145)




Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant Recipient Weight

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

50 60 70 80 90 100 110

Recipient Weight (kg)

p < 0.0001

Rela

tive R

isk o

f R

en

al

Dysfu

ncti

on

wit

hin

5 Y

ears

ISHLT 2007

(N=11,145)




Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant Donor Weight

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

50 60 70 80 90 100 110

Donor Weight (kg)

p = 0.049

Rela

tive R

isk o

f R

en

al

Dysfu

ncti

on

wit

hin

5 Y

ears

ISHLT 2007

(N=11,145)




Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant Recipient PRA

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

0 5 10 15 20 25 30 35 40

Recipient PRA (%)

p = 0.0047

Rela

tive R

isk o

f R

en

al

Dysfu

ncti

on

wit

hin

5 Y

ears

ISHLT 2007

(N=11,145)



HEART TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781.

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Transcript of HEART TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781.