heart transplantation overall ishlt 2012 j heart lung transplant. 2012 oct; 31(10): 1045-1095

HEART TRANSPLANTATION

Overall

ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095

NUMBER OF HEART TRANSPLANTSBY YEAR

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

2010

0

500

1000

1500

2000

2500

3000

3500

4000

4500

50001

87

32

2 67

0 1,2

55 2

,35

2

2,9

91

3,5

08

3,8

01

4,4

64

4,6

79

4,6

46

4,8

51

4,7

61

4,7

55

4,6

30

4,5

38

4,2

81

3,9

95

3,8

58

3,8

36

3,7

26

3,6

50

3,6

10

3,7

09

3,7

72

3,7

77

3,7

45

3,7

74

3,8

92

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, the presented data may not mirror the changes in the number of heart transplants performed worldwide .ISHLT 2012

J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095

NUMBER OF HEART TRANSPLANTSBY YEAR AND LOCATION

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

2010

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000Other

Europe

North America

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, the presented data may not mirror the changes in the number of heart transplants performed worldwide .ISHLT 2012


AVERAGE CENTER VOLUMEHeart Transplants: January 2006 – June 2011

1-4 5-9 10-19 20-29 30-39 40-49 50-74 75+0

10

20

30

40

50

60

70

80

90

100

110

0

5

10

15

20

25

30

35

40

45

50

55

4358

104

37

10 4 8 2

Number of centers Percentage of transplants

Average number of heart transplants per year

Nu

mb

er

of

ce

nte

rs

% o

f tr

an

sp

lan

ts


HEART TRANSPLANTSDonor Age by Year of Transplant

19821984

19861988

19901992

19941996

19982000

20022004

20062008

20100%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0

5

10

15

20

25

30

35

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

% o

f tr

an

sp

lan

ts

Me

dia

n d

on

or

ag

e (

ye

ars

)


HEART TRANSPLANTSMedian Donor Age by Location

ISHLT 2012

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

0

5

10

15

20

25

30

35

40

45

Europe North America Other

Me

dia

n d

on

or

ag

e (

ye

ars

)


AGE DISTRIBUTION OF HEART TRANSPLANTRECIPIENTS BY ERA

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70+0

5

10

15

20

25

30

35

40

1982-1995 (N = 42,890)

1996-2005 (N = 39,797)

2006-6/2011 (N = 20,645)

Recipient age

% o

f tr

an

sp

lan

ts

p < 0.0001


HEART TRANSPLANTSKaplan-Meier Survival

(Transplants: January 1982 - June 2010)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 250

25

50

75

100

Years

Su

rviv

al (

%)

Half-life = 10 yearsConditional half-life = 13 years

ISHLT 2012 Survival is based on adult and pediatric transplant recipients

N = 96,273

N at risk at 25 years = 112


HEART TRANSPLANTATION

Adult Recipients


DIAGNOSIS IN ADULT HEART TRANSPLANTS

Myopathy48%

Congenital2%

ReTX2%

CAD44%

Misc.0%

Valvular4%

1/1982 – 6/2011

ISHLT 2012

Myopathy54%

Congenital3%

ReTX3%

CAD37% Misc.

1%

Valvular3%

1/2006 – 6/2011


ADULT HEART TRANSPLANTS Diagnosis: Cardiomyopathy vs. CAD by Location

ISHLT 2012

20

30

40

50

60

70Myopathy CAD

% o

f cases All Locations

20

30

40

50

60

70Myopathy CAD

% o

f cases Europe

20

30

40

50

60

70

Myopathy CAD

% o

f cases North America


ADULT HEART TRANSPLANTSDiagnosis by Location

(Transplants: January 2006 – June 2011)

Myopathy58%

Congenital4%

ReTX1%

CAD33% Misc.

0%

Valvular3%

Europe

ISHLT 2012

Myopathy51%

Congenital3%

ReTX3%

CAD40% Misc.

1%Valvular

2%

North America

Myopathy57%

Congenital2%

ReTX1%

CAD32%

Misc.6%

Valvular2%

Other


ADULT HEART TRANSPLANTSDonor and Recipient Characteristics

ISHLT 2012

1992-2000(N = 36,507)

2001-2005(N = 16,352)

2006-6/2011(N = 17,868) p-value

Recipient age (years) 54.0 (28.0-65.0) 54.0 (26.0-66.0) 54.0 (24.0-67.0) 0.0064

Donor age (years) 31.0 (15.0-54.0) 33.0 (16.0-55.0) 34.0 (17.0-56.0) <0.0001

Donor and Recipient Age Difference (years) -19.0 (-44.0-7.0) -17.0 (-43.0-10.0) -16.0 (-43.0-12.0) <0.0001

Recipient weight (kg) 75.0 (51.0-101.6) 77.6 (53.0-106.6) 79.4 (53.1-110.2) <0.0001

Recipient height (cm) 173.0 (157.0-188.0) 174.0 (157.5-188.0) 175.0 (157.5-188.0) <0.0001

Recipient BMI 25.0 (18.9-32.7) 25.6 (19.2-33.8) 26.0 (19.2-34.9) <0.0001

Donor weight (kg) 74.8 (52.0-103.0)1 76.7 (55.0-108.6) 79.4 (56.7-113.0) <0.0001

Donor height (cm) 175.0 (155.0-188.0)1 175.0 (157.0-189.0) 175.0 (158.0-190.0) <0.0001

Donor BMI 24.2 (18.8-32.9)1 24.8 (19.5-34.3) 25.5 (19.9-36.2) <0.0001

Continuous factors are expressed as median (5th-95th percentiles)

1 Based on 4/1994-2000 transplants.



ISHLT 2012

1992-2000(N = 36,507)

2001-2005(N = 16,352)

2006-6/2011(N = 17,868) p-value

Recipient/donor gender (% male) 80.7%/ 68.4% 77.7%/ 69.0% 76.3%/ 69.4% <0.0001/ 0.0545

Male recipient/ female donor 21.2% 18.4% 16.6% <0.0001

Female recipient/ male donor 9.1% 9.7% 9.7% 0.0327

Recipient/donor diabetes mellitus 17.8%1/ 1.6%1 20.2%/ 2.0% 25.4%/ 2.8% <0.0001/ <0.0001

Recipient amiodarone use (US only) 21.7%1 29.0% 30.2% <0.0001

Recipient/donor cigarette history -/ 38.0%1 46.6%2/ 29.1% 46.5%/ 19.2% 0.9848/ <0.0001

Recipient/donor hypertension 34.2%1/ 10.8%1 38.1%/ 11.4% 44.1%/ 13.4% <0.0001/ <0.0001

Recipient prior cardiac surgery - 38.9%2 45.4% <0.0001

Recipient Peripheral Vascular Disease 3.8%1 3.2% 2.9% 0.0002

Recipient previous malignancy 3.2%1 4.5% 6.4% <0.0001

Recipient COPD 3.2%1 3.2% 4.2% 0.0001

Ischemic time (hours) 2.6 (0.0-4.5) 2.9 (0.0-4.9) 3.1 (0.0-5.0) <0.0001


1 Based on 4/1994-2000 transplants.2 Based on 7/2004-2005 transplants.

(Cont’d)



ISHLT 2012

1992-2000(N = 36,507)

2001-2005(N = 16,352)

2006-6/2011(N = 17,868) p-value

Most recent PRA > 10%1

Overall 7.7% 8.8%2 12.7%3 <0.0001

Class I - - 14.2%4 -

Class II - - 9.1%4 -

Creatinine at time of transplant 1.2 (0.7-2.5) 1.2 (0.7-2.4) 1.2 (0.7-2.3) <0.0001

Pulmonary vascular resistance (Wood units) 2.2 (0.4-6.1)5 2.0 (0.3-5.6) 2.1 (0.3-5.4) <0.0001

HLA Mismatches

0-2 4.3% 4.4% 3.8%

0.0051 3-4 40.2% 40.0% 38.9%

5-6 55.5% 55.5% 57.4%


2 Based on US 2001-6/2004 transplants and non US 2001 - 2005 transplants.3 Based on non US transplants.4 Based on US transplants.5 Based on 4/1994-2000 transplants.

1 PRA was collected as a single percentage outside of US. Until mid-2004 PRA was collected in US as a single percentage. After this date, PRA was collected separately for Class I and Class II.

(Cont’d)



ISHLT 2012

1992-2000(N = 36,507)

2001-2005(N = 16,352)

2006-6/2011(N = 17,868) p-value

Diagnosis

Cardiomyopathy 46.4% 48.5% 53.8%

<0.0001

Coronary artery disease 45.8% 42.6% 37.1%

Valvular 3.8% 3.3% 2.6%

Retransplant 1.9% 2.2% 2.6%

Congenital 1.8% 2.7% 3.0%

Other causes 0.4% 0.6% 0.9%

Donor cause of death

Head trauma 44.6% 54.5% 46.6%

<0.0001 Stroke 28.2% 33.0% 24.8%

Other 27.2% 12.5% 28.6%

(Cont’d)



ISHLT 2012

1992-2000(N = 36,507)

2001-2005(N = 16,352)

2006-6/2011(N = 17,868) p-value

Pre-operative support (multiple items may be reported)

Hospitalized at time of transplant 60.2% 47.8% 44.6% <0.0001

On IV inotropes 55.8%1 47.3% 42.6% <0.0001

LVAD 12.12 17.0% 27.3% <0.0001

IABP 6.8% 6.9% 6.2% 0.0731

RVAD - 5.0%3 3.8% 0.0125

Ventilator 3.5% 3.3% 2.9% 0.0141

TAH 0.1%2 0.1% 0.9% <0.0001

ECMO 0.3%4 0.5% 1.0% <0.0001

1 Based on 4/1994-2000 transplants.2 Based on 11/1999-2000 transplants.3 Based on 2005 transplants.4 Based on 5/1995-2000 transplants.

(Cont’d)


ADULT HEART TRANSPLANTSDonor and Recipient Age


18-19 20-29 30-39 40-49 50-59 60-69 70+0%

20%

40%

60%

80%

100%

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

Recipient Age

% o

f T

ran

sp

lan

ts

Donor Age:


ADULT HEART TRANSPLANTSDonor and Recipient Age


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

20%

40%

60%

80%

100%

18-19 20-29 30-39 40-49 50-59 60-69 70+

Donor Age

% o

f T

ran

sp

lan

ts

Recipient Age:


ADULT HEART TRANSPLANTS PRA Distribution


0 1-9 10-39 40-79 80+0

10

20

30

40

50

60

70

80

PRA

% o

f tr

an

sp

lan

ts

ISHLT 2012If Class I and Class II values were reported separately, the higher of the two values was used.


ADULT HEART TRANSPLANTS % of Patients Bridged with Mechanical Circulatory Support*

(Transplants: January 2000 – December 2010)

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 20100

10

20

30

40

50

Year

% o

f p

ati

en

ts

ISHLT 2012* LVAD, RVAD, TAH


ADULT HEART TRANSPLANTS % of Patients Bridged with Mechanical Circulatory Support*

by Year and Device Type

2005 2006 2007 2008 2009 20100

10

20

30

40

50

TAH

LVAD+RVAD

RVAD

LVAD

Year

% o

f p

ati

en

ts

ISHLT 2012* LVAD, RVAD, TAH


ADULT HEART TRANSPLANTS Number of Combined Organ Transplants Reported

By Year and Type of Transplant

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 20100

10

20

30

40

50

60

70

80

90Other Combined Organ TransplantsHeart-Kidney-PancreasHeart-Kidney-LiverHeart-LiverHeart-Kidney

Nu

mb

er

of

tra

ns

pla

nts


ADULT HEART TRANSPLANTS % of Combined Organ Transplants Reported By Year

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 20100

1

2

3

4

% o

f tr

an

sp

lan

ts


ADULT HEART TRANSPLANTSDonor Age Distribution By Location


Europe North America Other0%

20%

40%

60%

80%

100%

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

% o

f D

on

ors

ISHLT 2012

Mean/median donor age: Europe = 40.2/42.0 North America = 31.6/29.0 Other = 32.2/30.0J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095

ADULT HEART TRANSPLANTSRecipient Age Distribution By Location



20%

40%

60%

80%

100%

18-19 years 20-29 years 30-39 years 40-49 years 50-59 years60-69 years 70+ years

% o

f D

on

ors

ISHLT 2012

Mean/median recipient age: Europe = 49.6/52.0 North America = 52.0/55.0 Other = 48.5/51.0J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095

ADULT HEART TRANSPLANTSRecipient BMI Distribution By Location



20%

40%

60%

80%

100%

<18.5 18.5-<25 25-<30 30-<40 40+

% o

f T

ran

sp

lan

ts


ADULT HEART TRANSPLANTSRecipient BMI Distribution By Diagnosis


Cardiomyopathy Coronary Artery Disease0%

20%

40%

60%

80%

100%

<18.5 18.5-<25 25-<30 30-<40 40+

% o

f T

ran

sp

lan

ts


ADULT HEART TRANSPLANTSRecipient Diabetes Mellitus Distribution By Location



20%

40%

60%

80%

100%

Diabetes No diabetes

% o

f T

ran

sp

lan

ts


ADULT HEART TRANSPLANTSRecipient Diabetes Mellitus Distribution By Diagnosis



20%

40%

60%

80%

100%

Diabetes No diabetes

% o

f T

ran

sp

lan

ts


ADULT HEART TRANSPLANTSRecipient Cigarette History By Location



20%

40%

60%

80%

100%

Cigarette history No cigarette history

% o

f T

ran

sp

lan

ts


ADULT HEART TRANSPLANTSRecipient Cigarette History By Diagnosis



20%

40%

60%

80%

100%

Cigarette history No cigarette history

% o

f T

ran

sp

lan

ts


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Era


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 150

20

40

60

80

100

1982-1992 (N = 25,138)1993-2002 (N = 37,193)2003-6/2010 (N = 24,021)

Years

Su

rviv

al (

%)

HALF-LIFE 1982-1992: 8.5 years; 1993-2002: 10.9 years; 2003-6/2010: NA

1982-1992 vs. 1993-2002: p < 0.00011982-1992 vs. 2003-6/2010: p <0.0001 1993-2002 vs. 2003-6/2010: p <0.0001


ADULT HEART TRANSPLANTSConditional Kaplan-Meier Survival by Era


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 150

20

40

60

80

100

1982-1992 (N = 18,877)1993-2002 (N = 29,293)2003-6/2010 (N = 18,021)

Years

Su

rviv

al (

%)


1982-1992 vs. 1993-2002: p < 0.00011982-1992 vs. 2003-6/2010: p <0.0001 1993-2002 vs. 2003-6/2010: p = 0.3073


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Age Group


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 200

20

40

60

80

100

18-29 (N=6,134) 30-39 (N=8,623)

40-49 (N=19,179) 50-59 (N=33,178)

60-69 (N=18,655) 70+ (N=573)

Years

Su

rviv

al (

%)

HALF-LIFE 18-29: 12.2 years; 30-39: 12.0 years; 40-49: 11.1 years; 50-59: 10.0 years; 60-69: 8.9 years; 70+: 7.4 years

All pair-wise comparisons are statistically significant at p < 0.01 except 18-29 vs. 30-39 (p=0.8452)


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Age Group


0 1 2 3 4 5 6 70

20

40

60

80

100

18-29 (N=2,068) 30-39 (N=2,413)

40-49 (N=4,602) 50-59 (N=8,283)

60-69 (N=6,362) 70+ (N=293)

Years

Su

rviv

al (

%)

All pair-wise comparisons are statistically significant at p < 0.05 except 18-29 vs. 60-69; 18-29 vs. 70+, 30-39 vs. 40-49 and 60-69 vs. 70+


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Diagnosis


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 200

20

40

60

80

100 Cardiomyopathy (N=39,096) Coronary artery disease (N=36,430)

Congenital diagnosis (N=1,690) Retransplant (N=1,740)

Valvular (N=3,010)

Years

Su

rviv

al (

%)

All pair-wise comparisons are statistically significant at < 0.001 except cardiomyopathy vs. congenital (p=0.6340).

ISHLT 2012

HALF-LIFE Cardiomyopathy: 11.4 years; CAD: 9.4 years; Congenital: 13.7 years; Retransplant: 6.0 years; Valvular: 10.9 years


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Diagnosis Conditional on Survival

to 1 Year (Transplants: January 1982 - June 2010)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 200

20

40

60

80

100

Cardiomyopathy (N=30,529) Coronary artery disease (N=28,163)

Congenital diagnosis (N=1,195) Retransplant (N=1,153)

Valvular (N=2,206)

Years

Su

rviv

al (

%)

All pair-wise comparisons are significant at p < 0.05 except cardiomyopathy vs. valvular

ISHLT 2012

HALF-LIFE Cardiomyopathy: 14.0 years; CAD: 11.7 years; Congenital: 20.4 years; Retransplant: 10.7 years; Valvular: 14.3 years


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Era (Transplants: January 1982 - June 2010)

Diagnosis: Cardiomyopathy

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 150

20

40

60

80

100

1982-1992 (N = 10,582)1993-2002 (N = 16,370)2003-6/2010 (N = 12,144)

Years

Su

rviv

al (

%)


All comparisons are significant at p < 0.0001



Diagnosis: Coronary Artery Disease

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 150

20

40

60

80

100

1982-1992 (N = 10,820)

1993-2002 (N = 16,572)

2003-6/2010 (N = 9,038)

Years

Su

rviv

al (

%)





Diagnosis: Congenital

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 150

20

40

60

80

100

1982-1992 (N = 320)

1993-2002 (N = 710)

2003-6/2010 (N = 660)

Years

Su

rviv

al (

%)


No comparisons are significant at < 0.05 except 1993-2002 vs. 2003-6/2010: p = 0.0489



Diagnosis: Retransplant

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 150

20

40

60

80

1001982-1992 (N = 470)

1993-2002 (N = 697)

2003-6/2010 (N = 573)

Years

Su

rviv

al (

%)





Diagnosis: Valvular

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 150

20

40

60

80

100

1982-1992 (N = 1,038)

1993-2002 (N = 1,298)

2003-6/2010 (N = 674)

Years

Su

rviv

al (

%)


All comparisons are significant at < 0.05 except 1993-2002 vs. 2003-6/2010


ADULT HEART TRANSPLANTSKaplan-Meier 1 Year Survival by Diagnosis


0 1 2 3 4 5 6 7 8 9 10 11 1250

60

70

80

90

100


Congenital diagnosis (N=660) Retransplant (N=573)

Valvular (N=674)

Months

Su

rviv

al (

%)

All pair-wise comparisons are significant at p < 0.05 except CAD vs. retransplant, valvular vs. congenital, valvular vs. retransplant and congenital vs. retransplant


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Diagnosis


0 1 2 3 4 5 6 750

60

70

80

90

100Cardiomyopathy (N=12,144) Coronary artery disease (N=9,038)


Valvular (N=674)

Years

Su

rviv

al (

%)

All pair-wise comparisons are significant at p < 0.05 except CAD vs. congenital, valvular vs. congenital, valvular vs. retransplant and congenital vs. retransplant


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Diagnosis Conditional on Survival

to 1 Year (Transplants: January 2003 – June 2010)

0 1 2 3 4 5 6 750

60

70

80

90

100



Valvular (N=481)

Years

Su

rviv

al (

%)

No pair-wise comparisons are significant at < 0.05 except cardiomyopathy vs. CAD, cardiomyopathy vs. retransplant, CAD vs. congenital and congenital vs. retransplant


ADULT HEART TRANSPLANTSKaplan-Meier Survival by PVR


0 1 2 3 4 5 6 750

60

70

80

90

100

1-<3 Wood units (N = 7,270) 3-<5 Wood units (N = 2,350)

5+ Wood units (N = 768)

Years

Su

rviv

al (

%)

1-<3 vs. 3-<5: p < 0.00011-<3 vs. 5+: p = 0.34833-<5 vs. 5+: p = 0.1762


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Donor/Recipient Weight Ratio


For recipients with PVR: 1–<3 wood units

0 1 2 3 4 5 6 750

60

70

80

90

100

<0.8 Weight ratio (N=1,039) 0.8-<0.9 Weight ratio (N= 1,430)0.9-<1.1 Weight ratio (N=2,735) 1.1-<1.2 Weight ratio (N=798)1.2+ Weight ratio (N=1,268)

Years

Su

rviv

al (

%)

No pair-wise comparisons are statistically significant at p < 0.05




For recipients with PVR: 3–<5 wood units

0 1 2 3 4 5 6 750

60

70

80

90

100

<0.8 Weight ratio (N=220) 0.8-<0.9 Weight ratio (N=390)

0.9-<1.1 Weight ratio (N=886) 1.1-<1.2 Weight ratio (N=312)

1.2+ Weight ratio (N=542)

Years

Su

rviv

al (

%)





For recipients with PVR: 5+ wood units

0 1 2 3 4 550

60

70

80

90

100

<0.8 Weight ratio (N=84) 0.8-<0.9 Weight ratio (N=113)0.9-<1.1 Weight ratio (N=258) 1.1-<1.2 Weight ratio (N=107)1.2+ Weight ratio (N=206)

Years

Su

rviv

al (

%)



ADULT HEART TRANSPLANTSKaplan-Meier Survival by BMI Group


0 1 2 3 4 5 650

60

70

80

90

100

<18.5 (N=581) 18.5-<25 (N=12,217) 25-<30 (N=7,388) 30-<40 (N=3,761)

40+ (N=74)

Years

Su

rviv

al (

%)

p = 0.0007


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Recipient Diabetes Mellitus


0 1 2 3 4 5 6 750

60

70

80

90

100

Diabetes (N=3,599) No diabetes (N=11,945)

Years

Su

rviv

al (

%)

p = 0.0007


ADULT HEART TRANSPLANTSKaplan-Meier Survival by Recipient Cigarette History

(Transplants: July 2004 – June 2010)

0 1 2 3 4 5 650

60

70

80

90

100

Cigarette history (N = 5,431) No cigarette history (N = 6,169)

Years

Su

rviv

al (

%)

p = 0.1663


ADULT HEART TRANSPLANTSKaplan-Meier Survival by VAD usage

(Transplants: April 1994 – June 2010)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 140

10

20

30

40

50

60

70

80

90

100

Pulsatile flow (N=3,681) Continuous flow (N=1,434)

No LVAD / No Inotropes (N=13,053) No LVAD / Inotropes (N=14,829)

Years

Su

rviv

al (

%)

Pulsatile vs. Continuous: p=0.0207Pulsatile vs. No LVAD/No Inotropes: p = 0.0005Pulsatile vs. No LVAD/Inotropes: p = 0.0187No other pair-wise comparisons are statistically significant at p < 0.05




0 1 2 3 4 5 6 750

60

70

80

90

100Pulsatile flow (N=2,142) Continuous flow (N=1,408)


Years

Su

rviv

al (

%)

Pulsatile vs. No LVAD/No Inotropes: p = 0.0012Pulsatile vs. No LVAD/Inotropes: p = 0.0008Continuous vs. No LVAD/No Inotropes: p = 0.0027Continuous vs. No LVAD/Inotropes: p = 0.0006No other pair-wise comparisons are statistically significant at p < 0.05


ADULT HEART TRANSPLANTSKaplan-Meier Survival by VAD usage Conditional on Survival to 6 Months


0 1 2 3 4 5 6 7 8 9 1050

60

70

80

90

100

Pulsatile flow (N=2,903) Continuous flow (N=1,270)


Years

Su

rviv

al (

%)

Continuous vs. No LVAD/No Inotropes: p = 0.0038No other pair-wise comparisons are statistically significant at p < 0.05




0 1 2 3 4 550

60

70

80

90

100 LVAD Pulsatile (N=1,045) LVAD Continuous (N=1,291)LVAD+RVAD Pulsatile (N=367) No LVAD, No Inotropes (N=4,428)No LVAD, Inotropes (N=3,959)

Years

Su

rviv

al (

%)

All pair-wise comparisons with LVAD+RVAD Pulsatile are statistically significant at p < 0.001.LVAD Continuous vs. No LVAD/ Inotropes: p= 0.0239No other pair-wise comparisons are statistically significant at p < 0.05.


ADULT HEART RE-TRANSPLANTS 1 Year Survival

0-12 months >12-36 months >36-60 months >60 months Primary transplant

0

10

20

30

40

50

60

70

80

90

100

1/1982-12/1992

1/1993-12/2002

1/2003-6/2010

1 Y

ea

r P

ati

en

t S

urv

iva

l (%

)

305

188

76

95 80 46

61 86 57 55 389

408

24,4

01

36,3

32

23,3

15

ISHLT 2012

Time between previous and current transplant

Comparison of survival for interval ≤ 12 months vs. > 12 months: p < 0.0001Comparison of survival for interval ≤ 12 months vs. > 12 months for 1/2003-6/2010: p < 0.0001


ADULT HEART RECIPIENTS Cross-Sectional Analysis

Functional Status of Surviving Recipients (Follow-ups: January 2000 – June 2011)

1 Year (N = 8,060) 3 Years (N = 7,324) 5 Years (N = 6,534)0%

20%

40%

60%

80%

100%

No Activity Limitations Performs with Assistance Total Assistance


ADULT HEART RECIPIENTSFunctional Status of Surviving Recipients

US Recipients Only(Follow-ups: January 2006 – June 2011)

0%

20%

40%

60%

80%

100%

1 Year (N = 8,740)

2 Years (N = 7,848)

3 Years (N = 7,265)

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%


ADULT HEART RECIPIENTSEmployment Status of Surviving Recipients

(Follow-ups: January 2000 – June 2011)

0%

20%

40%

60%

80%

100%

1 Year(N = 14,729)

3 Years(N = 12,973)

5 Years(N = 11,413)

Retired

Not Working

Working Part Time

Working Full Time

Working (FT/PT status unknown)


ADULT HEART RECIPIENTSEmployment Status of Surviving Recipients

Age at Follow-up: 25-55 Years (Follow-ups: January 2000 – June 2011)

0%

20%

40%

60%

80%

100%

1 Year(N = 6,213)

3 Years(N = 4,740)

5 Years(N = 3,563)

Retired

Not Working

Working Part Time

Working Full Time

Working (FT/PT status unknown)


ADULT HEART RECIPIENTSRehospitalization Post-transplant of Surviving Recipients


0%

20%

40%

60%

80%

100%

Up to 1 Year(N = 19,800)

Between 2 and 3 Years (N =

16,940)

Between 4 and 5 Years (N =

14,930)

No Hospitalization Hospitalized, Not Rejection/Not Infection

Hospitalized, Rejection Hospitalized, Infection Only

Hospitalized, Rejection + Infection


ADULT HEART RECIPIENTSInduction Immunosuppression


0

10

20

30

40

50

60

% o

f p

ati

en

ts

Analysis is limited to patients who were alive at the time of the dischargeISHLT 2012


ADULT HEART RECIPIENTSInduction Immunosuppression by Location


Any Induction IL-2R Antagonist Polyclonal ALG/ATG0

10

20

30

40

50

60

70

Europe North America

% o

f p

ati

en

ts

Analysis is limited to patients who were alive at the time of the dischargeISHLT 2012


ADULT HEART RECIPIENTSInduction Immunosuppression

(Transplants: 2002, 2007 and 1/2011–6/2011)

Any Induction IL-2R Antag-onist

Polyclonal ALG/ATG

OKT3 Alemtuzumab0

10

20

30

40

50

60

2002 2007 1/2011-6/2011

% o

f p

ati

en

ts

Analysis is limited to patients who were alive at the time of the follow-upISHLT 2012


ADULT HEART RECIPIENTSKaplan-Meier Survival by Induction Type

Conditional on Survival to 14 Days(Transplants: January 2001 – June 2010)

0 1 2 3 4 5 6 7 8 950

60

70

80

90

100

No induction (N = 8,556) Polyclonal induction (N = 3,989)

IL-2R antagonist (N = 4,582) OKT3 (N = 509)

Years

Su

rviv

al (

%)

No induction vs. IL-2R: p = 0.0002Polyclonal vs. IL-2R: p = 0.0131IL-2R vs. OKT3: p = 0.0368


ADULT HEART RECIPIENTSMaintenance Immunosuppression at Time of Follow-up


Cyclosporine Tacrolimus Sirolimus/ Everolimus

MMF/MPA Azathioprine Prednisone0

20

40

60

80

100

Year 1 (N = 5,840) Year 5 (N = 3,559)

% o

f p

ati

en

ts

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



ADULT HEART RECIPIENTS Maintenance Immunosuppression at Time of 1 Year

Follow-up

Cy-closporine

Tacrolimus Sirolimus/ Everolimus

MMF/MPA Azathioprine Prednisone0

20

40

60

80

1002000 (N = 1,538) 2005 (N = 2,768) 1/2011-6/2011 (N = 1,459)

% 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 each time frame


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

For the Same Patients(Follow-ups: January 2001 – June 2011)

0%

20%

40%

60%

80%

100%

Year 1 (N = 7,060)

Year 5 (N = 7,060)

None

Other

Sirolimus/Everolimus +calcineurin+cellcycle

Tacrolimus

Cyclosporine

Sirolimus/Everolimus + cellcycle

Sirolimus/Everolimus + calcineurin

Tacrolimus + MMF/MPA

Tacrolimus + AZA

Cyclosporine + MMF/MPA

Cyclosporine + AZA

% o

f P

ati

en

ts





0%

20%

40%

60%

80%

100%

Year 1 (N = 9,120)

Year 5 (N = 5,975)

None

Other


Tacrolimus

Cyclosporine




Tacrolimus + AZA


Cyclosporine + AZA

% o

f P

ati

en

ts


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



by Location(Follow-ups: January 2006 – June 2011)

0%

20%

40%

60%

80%

100%None

Other


Tacrolimus

Cyclosporine




Tacrolimus + AZA


Cyclosporine + AZA

% o

f P

ati

en

ts

Europe EuropeNorth America

North America


NOTE: Different patients are analyzed in Year 1 and Year 5ISHLT 2012

Year 1 Year 5


PERCENTAGE OF ADULT HEART RECIPIENTS Rejection between Transplant Discharge and 1-Year Follow-Up by Year

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

ISHLT 2012

Transplant Year

Rejection, Treated Rejection, Untreated

No Rejection Total

N % N % N % N %

2004 399 25.5 106 6.8 1,058 67.7 1,563 100.0

2005 386 23.1 96 5.7 1,192 71.2 1,674 100.0

2006 375 21.6 157 9.1 1,202 69.3 1,734 100.0

2007 311 17.9 199 11.4 1,230 70.7 1,740 100.0

2008 258 15.6 196 11.8 1,202 72.6 1,656 100.0

2009 276 16.0 242 14.0 1,208 70.0 1,726 100.0


PERCENTAGE OF ADULT HEART RECIPIENTS Experiencing Rejection between Transplant Discharge and 1-Year Follow-Up

Stratified by Type of Induction (Follow-ups: January 2005 – June 30, 2011)

0

10

20

30

40

50

60 No induction, Treatment No induction, No TreatmentPolyclonal, Treatment Polyclonal, No TreatmentIL-2R antagonist, Treatment IL-2R antagonist, No Treatment OKT3, Treatment OKT3, No Treatment

% e

xp

eri

en

cin

g r

eje

cti

on

wit

hin

1 y

ea

r

Overall 18-44 45-62 63+ FemaleAll groups: all no induct vs. poly and no induct vs. IL-2R comparisons are significant at p < 0.05 except 45-62: no induct vs. poly and M: no induct vs. polyOverall: no induct vs. OKT3 (p=0.0130); poly vs. IL-2R (p=0.0005)45-62: poly vs. IL-2R (p=0.0030)63+: no induct vs. OKT3 (p=0.0440)F: no induct vs. OKT3 (p=0.0338)M: poly vs. IL-2R (p=0.0004)

Male


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.

ISHLT 2012

No induction: N=5,192Polyclonal: N=2,161IL-2R antagonist: N=3,094OKT3: N=168J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095

PERCENTAGE OF ADULT HEART RECIPIENTS Experiencing Rejection between Transplant Discharge and 1-Year Follow-Up Stratified by Maintenance Immunosuppression (Follow-ups: 2005 – June 30, 2011)

0

10

20

30

40

50

60 Cyclosporine + MMF/MPA, Treatment Cyclosporine + MMF/MPA, No Treatment

Tacrolimus + MMF/MPA, Treatment Tacrolimus + MMF/MPA, No Treatment

% e

xp

eri

en

cin

g r

eje

cti

on

wit

hin

1 y

ea

r

Overall 18-44 45-62 63+ Female

Overall: p < 0.000118-44: p < 0.000145-62: p < 0.000163+: p = 0.0026Female: p < 0.0001Male: p < 0.0001

Male



ISHLT 2012

Cyclosporine + MMF/MPA: N = 2,966Tacrolimus + MMF/MPA: N = 6,493

NOTE: There were 138 patients with cyclosporine + AZA and 62 with tacrolimus+AZA. These groups were excluded due to small numbers.


ADULT HEART TRANSPLANTSKaplan-Meier Survival Stratified by Treatment for Rejection Within 1st Year

Conditional on survival to 1 year (1 Year follow-ups: 2005 – 6/2010)

0 1 2 3 4 5 650

60

70

80

90

100

No Rejection (N=6,401) Treated Rejection (N=5,455)

Years

Su

rviv

al (

%)

ISHLT 2012

p < 0.0001



FREEDOM FROM HOSPITALIZATION FOR REJECTION BY ERA

For Adult Heart Recipients (Transplants: April 1994 – June 2010)

0 1 2 3 40

10

20

30

40

50

60

70

80

90

100

4/1994-1999 (N = 4,107) 2000-2004 (N = 3,660) 2005-6/2010 (N = 4,089)

Years

% F

reed

om f

rom

hos

pit

aliz

atio

n f

or r

ejec

tion

ISHLT 2012

All pair-wise comparisons are statistically significant at p < 0.0001


POST-HEART TRANSPLANT MORBIDITY FOR ADULTSCumulative Morbidity Rates in Survivors within 1, 5 and 10 Years Post-

Transplant (Follow-ups: January 1995 – June 2011)

Outcome Within 1 Year

Total N with known

response

Within 5 Years

Total N with known

response

Within 10 Years

Total N with known response

Hypertension* 72.8% (N = 25,542) 92.6% (N = 11,853) –

Renal Dysfunction 26.7% (N = 27,478) 53.0% (N = 13,481) 68.2% (N = 4,339)

Abnormal Creatinine < 2.5 mg/dl 18.3% 33.2% 37.5%

Creatinine > 2.5 mg/dl 6.6% 15.8% 21.1%

Chronic Dialysis 1.5% 2.9% 6.1%

Renal Transplant 0.3% 1.2% 3.6%

Hyperlipidemia* 60.2% (N = 26,810) 88.0% (N = 13,191) –

Diabetes* 26.5% (N = 27,474) 38.0% (N = 13,306) –

Cardiac Allograft Vasculopathy 7.9% (N = 24,790) 30.4% (N = 9,819) 49.7% (N = 2,482)

ISHLT 2012* Data are not available 10 years post transplant


POST-HEART TRANSPLANT MORBIDITY FOR ADULTSCumulative Morbidity Rates in Survivors within 1, 5 and 10 Years Post-

Transplant (Follow-ups: January 1995 – June 2001) For the Same Patients


Total N with known

response

Within 5 Years

Total N with known

response

Within 10 Years

Total N with known response

Renal Dysfunction 21.3% (N = 1,902) 48.6% (N = 1,902) 65.4% (N = 1,902)

Abnormal Creatinine < 2.5 mg/dl 14.7% 33.1% 39.2%

Creatinine > 2.5 mg/dl 6.3% 13.7% 18.7%

Chronic Dialysis 0.1% 0.9% 4.0%

Renal Transplant 0.3% 0.9% 3.5%

Cardiac Allograft Vasculopathy 6.8% (N = 1,902) 29.6% (N = 1,902) 48.9% (N = 1,902)


POST-HEART TRANSPLANT MORBIDITY FOR ADULTSCumulative Morbidity Rates in Survivors within 1 and 5 Years

Post-Transplant (Follow-ups: January 2001 - June 2006) For the Same Patients


Total N with known

response

Within 5 Years

Total N with known

response

Hypertension 73.0% (N = 3,000) 88.3% (N = 3,000)

Renal Dysfunction 26.4% (N = 3,000) 50.6% (N = 3,000)

Abnormal Creatinine < 2.5 mg/dl 22.2% 38.1%

Creatinine > 2.5 mg/dl 3.5% 9.7%

Chronic Dialysis 0.5% 1.8%

Renal Transplant 0.2% 0.9%

Hyperlipidemia 72.4% (N = 3,000) 89.9% (N = 3,000)

Diabetes 29.3% (N = 3,000) 40.6% (N = 3,000)

Cardiac Allograft Vasculopathy 5.4% (N = 3,000) 26.7% (N = 3,000)


ADULT HEART TRANSPLANTSKaplan-Meier Survival Stratified by Renal Dysfunction Within 1st Year

Conditional on survival to 1 year (1 Year follow-ups: April 1994-June 2010)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 140

20

40

60

80

100

No Renal Dysfunction (N=18,277)

Years

Su

rviv

al (

%)

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

ISHLT 2012

p < 0.0001


FREEDOM FROM CARDIAC ALLOGRAFT VASCULOPATHY For Adult Heart Recipients (Transplants: April 1994 – June 2010)

0 1 2 3 4 5 6 7 8 9 100

20

40

60

80

100

Freedom from CAV 4/1994-2002 (N = 12,981)

Years

% F

ree

do

m f

rom

CA

V

ISHLT 2012

p < 0.0001


FREEDOM FROM CARDIAC ALLOGRAFT VASCULOPATHYStratified by Ischemia Time


0 1 2 3 4 5 6 7 8 9 10 11 120

20

40

60

80

100

<2 hours (N = 3,244)

2-<4 hours (N = 15,789)

4+ hours (N = 4,125)

Years

% F

ree

do

m f

rom

CA

V

ISHLT 2012

p = 0.5705


FREEDOM FROM CARDIAC ALLOGRAFT VASCULOPATHYStratified by Recipient Age Group


0 1 2 3 4 5 6 7 8 9 10 110

20

40

60

80

100

18-29 (N = 1,710) 30-39 (N = 2,117)

40-49 (N = 4,563) 50-59 (N = 9,101)

60-69 (N = 6,637) 70+ (N = 309)

Years

% F

ree

do

m f

rom

CA

V

ISHLT 2012

p = 0.5938


FREEDOM FROM SEVERE RENAL DYSFUNCTION BY ERA* For Adult Heart Recipients (Transplants: April 1994 – June 2010)

0 1 2 3 4 5 6 7 8 9 100

20

40

60

80

100

Freedom from Severe Renal Dysfunction 4/1994-2002 (N = 14,469)

Years

% F

ree

do

m f

rom

Se

ve

re R

en

al D

ys

-fu

nc

tio

n

ISHLT 2012

p < 0.0001



FREEDOM FROM SEVERE RENAL DYSFUNCTION*Stratified by Ischemia Time


0 1 2 3 4 5 6 7 8 9 10 11 120

20

40

60

80

100

<2 hours (N = 3,638)

2-<4 hours (N = 17,436)

4+ hours (N = 4,514)

Years

% F

ree

do

m f

rom

Se

ve

re R

en

al D

ys

-fu

nc

tio

n

ISHLT 2012

p = 0.5729



FREEDOM FROM SEVERE RENAL DYSFUNCTION*Stratified by Age Group


0 1 2 3 4 5 6 7 8 9 10 110

20

40

60

80

100

18-29 (N = 1,884) 30-39 (N = 2,322)

40-49 (N = 5,031) 50-59 (N = 10,040)

60-69 (N = 7,460) 70+ (N = 344)

Years

% F

ree

do

m f

rom

Se

ve

re R

en

al D

ys

-fu

nc

tio

n

ISHLT 2012

p < 0.0001


Patient Survival After Report of CAV Within 3 Years of Transplant and Patient Survival In Patients Without CAV*


0 1 2 3 4 5 6 7 8 9 10 11 12 13 140

20

40

60

80

100

No CAV (N = 17,865)CAV (N = 4,235)

Time after Report of CAV* (Years)

Su

rviv

al (

%)

ISHLT 2012

p < 0.0001

* Survival for patients without CAV within 3 years after transplant was conditioned on survival to median time of CAV development (501 days). Median time to CAV development is based on patients who developed CAV within 3 years of transplant.


Patient Survival After Report of CAV Within 3 Years of Transplant and Patient Survival In Patients Without CAV* by Era


0 1 2 3 4 5 6 7 8 9 10 11 12 13 140

20

40

60

80

100

No CAV 4/1994-2002 (N = 9,862) CAV 4/1994-2002 (N = 2,434)

No CAV 2003-6/2010 (N = 8,003) CAV 2003-6/2010 (N = 1,801)

Time after Report of CAV* (Years)

Su

rviv

al (

%)

ISHLT 2012

4/1994-2002: No CAV vs. CAV p < 0.00012003-6/2010: No CAV vs. CAV p < 0.0001No CAV: 4/1994-2002 vs. 2003-6/2010 p = 0.5210CAV: 4/1994-2002 vs. 2003-6/2010 p = 0.0154

* Survival for patients without CAV within 3 years after transplant was conditioned on survival to median time of CAV development (501 days). Median time to CAV development is based on patients who developed CAV within 3 years of transplant.


MALIGNANCY POST-HEART TRANSPLANT FOR ADULTSCumulative Morbidity Rates in Survivors

(Follow-ups: April 1994 – June 2011)

Malignancy/Type 1-Year Survivors

5-Year Survivors

10-Year Survivors

No Malignancy 29,101 (97.3%) 12,750 (85.8%) 3,565 (71.2%)

Malignancy (all types combined) 795 (2.7%) 2,102 (14.2%) 1,439 (28.8%)

Malignancy Type*

Skin390 1,402 1,020

Lymphoma165 162 97

Other185 608 455

Type Not Reported55 42 16

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

“Other” includes: prostate (11, 35, 21), adenocarcinoma (7, 7, 4), lung (6, 4, 1), bladder (4, 5, 4), Kaposi's sarcoma (0, 3, 1), breast (2, 7, 2), cervical (2, 5, 2), colon (2, 4, 2), 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 2011)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 150

20

40

60

80

100

All malignancy Lymphoma Skin Other

Years

% F

ree

fro

m M

alig

na

nc

y


FREEDOM FROM MALIGNANCYby Maintenance Immunosuppression Combinations at Discharge

For Adult Heart Recipients (Transplants: January 2001 - June 2010) Conditional on Survival to 14 days

0 1 2 3 4 5 6 7 850

60

70

80

90

100

TAC+MMF/MPA CyA+MMF/MPA CyA+AZA

Years

% F

ree

fro

m M

alig

na

nc

y

ISHLT 2012

p = 0.0015


FREEDOM FROM MALIGNANCYFor Adult Heart Recipients (Transplants: April 1994 – June 2010)

0 1 2 3 4 5 6 7 8 9 10 11 1250

60

70

80

90

100

Freedom from malignancy 4/1994-2002

Freedom from malignancy 2003-6/2010

Years

% F

ree

fro

m M

alig

na

nc

y

ISHLT 2012

p < 0.0001


FREEDOM FROM SKIN MALIGNANCYFor Adult Heart Recipients (Transplants: April 1994 – June 2010)

0 1 2 3 4 5 6 7 8 9 10 11 1250

60

70

80

90

100

Freedom from skin malignancy 4/1994-2002

Freedom from skin malignancy 2003-6/2010

Years

% F

ree

fro

m S

kin

Ma

lign

an

cy

ISHLT 2012

p < 0.0001


FREEDOM FROM LYMPHOMA For Adult Heart Recipients (Transplants: April 1994 – June 2010)

0 1 2 3 4 5 6 7 8 9 10 11 1250

60

70

80

90

100

Freedom from lymphoma 4/1994-2002

Freedom from lymphoma 2003-6/2010

Years

% F

ree

fro

m L

ym

ph

om

a

ISHLT 2012

p < 0.0001


FREEDOM FROM LYMPHOMA By Recipient Age Group

For Adult Heart Recipients (Follow-ups: April 1994 – June 2011)

0 1 2 3 4 5 6 7 8 9 1075

80

85

90

95

100

18-29 30-39 40-49

50-59 60-69 70+

Years

% F

ree

fro

m L

ym

ph

om

a

ISHLT 2012

p = 0.0074


FREEDOM OTHER MALIGNANCYFor Adult Heart Recipients (Transplants: April 1994 – June 2010)

0 1 2 3 4 5 6 7 8 9 10 11 1250

60

70

80

90

100

Freedom from other malignancy 4/1994-2002

Years

% F

ree

fro

m O

the

r M

alig

na

nc

y

ISHLT 2012

p < 0.0001


FREEDOM FROM NON SKIN MALIGNANCYBy Recipient Age Group

For Adult Heart Recipients (Follow-ups: April 1994 – June 2011)

0 1 2 3 4 5 6 7 8 9 1050

60

70

80

90

100

18-29 30-39 40-49

50-59 60-69 70+

Years

% F

ree

fro

m N

on

Sk

in M

alig

na

nc

y

ISHLT 2012

p < 0.0001


ADULT HEART TRANSPLANT RECIPIENTS:Cause of Death (Deaths: January 1994 – June 2011)

CAUSE OF DEATH 0-30 Days (N = 4,092)

31 Days – 1 Year

(N = 3,801)

>1 Year – 3 Years

(N = 2,846)

>3 Years – 5 Years

(N = 2,547)

>5 Years –10 Years

(N = 6,617)

>10 Years – 15 Years (N =4,221)

>15 Years (N =1,937)

Cardiac Allograft Vasculopathy 71 (1.7%) 161 (4.2%) 373 (13.1%) 369 (14.5%) 951 (14.4%) 619 (14.7%) 248 (12.8%)

Acute Rejection 222 (5.4%) 394 (10.4%) 296 (10.4%) 127 (5.0%) 127 (1.9%) 42 (1.0%) 13 (0.7%)

Lymphoma 3 (0.1%) 59 (1.6%) 81 (2.8%) 105 (4.1%) 283 (4.3%) 163 (3.9%) 66 (3.4%)

Malignancy, Other 1 (0.0%) 91 (2.4%) 326 (11.5%) 472 (18.5%) 1,344 (20.3%) 847 (20.1%) 345 (17.8%)

CMV 3 (0.1%) 42 (1.1%) 14 (0.5%) 6 (0.2%) 6 (0.1%) 2 (0.0%) 0

Infection, Non-CMV 548 (13.4%) 1,155 (30.4%) 354 (12.4%) 241 (9.5%) 703 (10.6%) 432 (10.2%) 226 (11.7%)

Graft Failure 1,522 (37.2%) 631 (16.6%) 688 (24.2%) 543 (21.3%) 1,150 (17.4%) 670 (15.9%) 305 (15.7%)

Technical 307 (7.5%) 53 (1.4%) 21 (0.7%) 24 (0.9%) 78 (1.2%) 59 (1.4%) 27 (1.4%)

Other 199 (4.9%) 305 (8.0%) 253 (8.9%) 201 (7.9%) 547 (8.3%) 311 (7.4%) 167 (8.6%)

Multiple Organ Failure 716 (17.5%) 533 (14.0%) 164 (5.8%) 155 (6.1%) 455 (6.9%) 345 (8.2%) 175 (9.0%)

Renal Failure 31 (0.8%) 39 (1.0%) 45 (1.6%) 85 (3.3%) 392 (5.9%) 359 (8.5%) 175 (9.0%)

Pulmonary 142 (3.5%) 158 (4.2%) 123 (4.3%) 126 (4.9%) 282 (4.3%) 173 (4.1%) 88 (4.5%)

Cerebrovascular 327 (8.0%) 180 (4.7%) 108 (3.8%) 93 (3.7%) 299 (4.5%) 199 (4.7%) 102 (5.3%)

ISHLT 2012 Percentages represent % of deaths in the respective time period


ADULT HEART RECIPIENTS Cause of Death from Leading Causes by Time since

Transplant and Era (Deaths: January 1994 - June 2011)

0-30 Days (N=2,275)

31 Days - 1 Year

(N=2,051)

>1 Year - 3 Years

(N=1,601)

>3 Years - 5 Years (N=1,435)

>5 Years - 10

Years (N=3,296)

>10 Years

(N=1,123)

0-30 Days (N=1,817)

31 Days - 1 Year

(N=1,750)

>1 Year - 3 Years

(N=1,245)

>3 Years - 5 Years (N=1,112)

>5 Years - 10

Years (N=3,321)

>10 Years

(N=5,035)

0

10

20

30

40

50

60

70

80

90

100

612 9 5 1 1 4 9 12

5 2 1

2

516

1818 21

13

10

1011 13

4017

2219

17 1434

17

27

2518 16

1

1

23

6 8 0

1

2

4

6 9

1432

118 9 9 13

29

14

1112 11

04 17

25 26 24

0

3

1120

23 23

Acute Rejection CAV Graft Failure Renal Failure

Infection (Non-CMV) Malignancy

% o

f D

ea

ths

ISHLT 2012

Deaths 1994 – 2001 Deaths 2002 – 6/2011


ADULT HEART TRANSPLANT RECIPIENTS Relative Incidence of Leading Causes of Death

(Deaths: January 1994 - June 2011)

0-30 Days (N=4,092)

31 Days – 1 Year

(N=3,801)

>1 Year – 3 Years

(N=2,846)


(N=2,547)


(N=6,617)

>10 – 15 Years

(N=4,221)

>15 Years (N=1,937)

0

10

20

30

40

50CAV Acute RejectionMalignancy (non-Lymph/PTLD) Infection (non-CMV)Graft Failure Multiple Organ FailureRenal Failure

% o

f D

ea

ths


ADULT HEART TRANSPLANT RECIPIENTS Cumulative Incidence of Leading Causes of Death


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

0%

2%

4%

6%

8%

10%

12%

14%CAV Acute Rejection

Malignancy (non-Lymph/PTLD) Graft Failure

Infection

Years

Inc

ide

nc

e o

f C

au

se

-Sp

ec

ific

D

ea

ths


ADULT HEART TRANSPLANT RECIPIENTS Relative Incidence of Leading Causes of Death

(Deaths: January 2004 - June 2011)

0-30 Days (N=1,444)

31 Days – 1 Year

(N=1,410)

>1 Year – 3 Years

(N=999)


(N=857)


(N=2,494)

>10 – 15 Years

(N=2,510)

>15 Years (N=1,707)

0

10

20

30

40

50CAV Acute RejectionMalignancy (non-Lymph/PTLD) Infection (non-CMV)Graft Failure Multiple Organ FailureRenal Failure

% o

f D

ea

ths


ADULT HEART TRANSPLANT RECIPIENTS Cumulative Incidence of Leading Causes of Death


0 1 2 3 4 5

-2%

0%

2%

4%

6%

8%

10%CAV Acute Rejection

Malignancy (non-Lymph/PTLD) Graft Failure

Infection

Years

Inc

ide

nc

e o

f C

au

se

-Sp

ec

ific

D

ea

ths


ADULT HEART TRANSPLANTS (2005-6/2010)

Risk Factors For 1 Year Mortality

VARIABLEN Relative

RiskP-value 95% Confidence

Interval

Temporary circulatory support* 175 3.05 <.0001 2.26-4.10

Diagnosis: Congenital vs. cardiomyopathy 274 2.11 <.0001 1.56-2.86

Total artificial heart 77 1.90 0.0137 1.14-3.16

Temporary continuous flow device 49 1.84 0.0261 1.08-3.15

Recipient history of dialysis 231 1.72 <.0001 1.33-2.23

Recipient on ventilator at time of transplant 300 1.63 0.0002 1.26-2.09

Chronic continuous flow device 1241 1.53 <.0001 1.25-1.88

Previous transplant 297 1.53 0.004 1.14-2.04

Chronic pulsatile flow device 1237 1.38 0.0012 1.14-1.68

N = 10,288

ISHLT 2012* Temporary circulatory support includes ECMO and temporary pulsatile flow devices.



Risk Factors For 1 Year Mortality (continued)

VARIABLEN Relative


Interval

Prior transfusion 2202 1.35 <.0001 1.17-1.57

Recipient with infection requiring IV drug therapy within 2 weeks prior to transplant 1044 1.25 0.0093 1.06-1.49

Ventricular remodeling 1556 0.76 0.0033 0.64-0.91

Transplant year: 2006 vs. 2009/2010 1927 1.36 0.0007 1.14-1.63



N = 10,288



Borderline Significant Risk Factors For 1 Year Mortality

VARIABLEN Relative


Interval


Diagnosis: coronary artery disease vs. cardiomyopathy 4196 1.14 0.0561 1.00-1.30

Not hospitalized just prior to transplant 5593 0.89 0.0717 0.78-1.01

N = 10,288Reference group = Cardiomyopathy, year=2009/2010




Continuous Factors (see figures)

Recipient age Ischemia time

Recipient height Recipient pre-transplant bilirubin

Recipient weight Recipient pre-transplant creatinine

Donor age PRA Class II

Donor BMI Recipient mean pulmonary artery pressure

Transplant center volume



Risk Factors For 1 Year Mortality with 95% Confidence Limits Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0

2.5

Recipient Age (years)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001

ISHLT 2012 (N = 10,288)J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095


Risk Factors For 1 Year Mortality with 95% Confidence Limits Donor Age

15 20 25 30 35 40 45 50 55 600.0

0.5

1.0

1.5

2.0

2.5

Donor Age (years)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001



Risk Factors For 1 Year Mortality with 95% Confidence Limits Recipient Height

155 160 165 170 175 180 185 1900.0

0.5

1.0

1.5

2.0

2.5

Recipient Height (cm)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001

ISHLT 2012(N = 10,288)

* The risk associated with recipient height should be considered in conjunction with the risk associated with recipient weight and donor BMI.



Risk Factors For 1 Year Mortality with 95% Confidence Limits Recipient Weight

50 60 70 80 90 100 110 120 1300.0

0.5

1.0

1.5

2.0

2.5

Recipient Weight (kg)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0051

ISHLT 2012(N = 10,288)

* The risk associated with recipient weight should be considered in conjunction with the risk associated with recipient height and donor BMI.



Risk Factors For 1 Year Mortality with 95% Confidence Limits Donor BMI

20 25 30 35 400.0

0.5

1.0

1.5

2.0

Donor BMI (kg/m2)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0182

ISHLT 2012(N = 10,288)

* The risk associated with donor BMI should be considered in conjunction with the risk associated with recipient weight and recipient height.



Risk Factors For 1 Year Mortality with 95% Confidence Limits Ischemia Time

30 60 90 120 150 180 210 240 270 300 330 3600.0

0.5

1.0

1.5

2.0

2.5

Ischemia time (minutes)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001



Risk Factors For 1 Year Mortality with 95% Confidence Limits Center Volume

5 10 15 20 25 30 35 40 45 50 55 60 65 700.0

0.5

1.0

1.5

2.0

Center Volume (cases per year)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0256



Risk Factors For 1 Year Mortality with 95% Confidence Limits Recipient Pre-Transplant Bilirubin

0.5 1.0 1.5 2.0 2.5 3.0 3.50.0

0.5

1.0

1.5

2.0

2.5

Recipient Bilirubin (mg/dL)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0026



Risk Factors For 1 Year Mortality with 95% Confidence Limits Recipient Pre-Transplant Creatinine

0.5 1.0 1.5 2.0 2.50.0

0.5

1.0

1.5

2.0

2.5

Recipient Creatinine (mg/dL)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001



Risk Factors For 1 Year Mortality with 95% Confidence Limits PRA Class II (%)

0 10 20 30 40 50 60 70 80 90 1000.0

0.5

1.0

1.5

2.0

2.5

3.0

Recipient PRA Class II (%)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0028



Risk Factors For 1 Year Mortality with 95% Confidence Limits Mean Pulmonary Artery Pressure

10 15 20 25 30 35 40 45 50 550.0

0.5

1.0

1.5

2.0

Mean PA Pressure

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0073




VARIABLEN Relative


Interval

Temporary circulatory support* 175 2.49 <.0001 1.96-3.16

Total artificial heart 45 1.70 0.0420 1.02-2.82

Recipient history of dialysis 328 1.67 <.0001 1.40-2.00

Diagnosis: Congenital vs. cardiomyopathy 292 1.47 0.0008 1.17-1.84

Recipient on ventilator at time of transplant 314 1.41 0.0008 1.15-1.72

Number of HLA mismatches at A locus (per locus)

0 A MM (N=665) 1 A MM (N=5089)2 A MM (N=4753)

1.29 0.0003 1.13-1.49

N = 10,507ISHLT 2012

* Temporary circulatory support includes ECMO and temporary pulsatile flow devices.




VARIABLEN Relative


Interval

Female recipient with prior pregnancy/ male donor vs. male recipient/male donor 780 1.22 0.0286 1.02-1.45

PRA > 10% 766 1.21 0.0066 1.06-1.40


Recipient history of diabetes 2177 1.14 0.0062 1.04-1.26

Diagnosis: coronary artery disease vs. cardiomyopathy 4792 1.14 0.0063 1.04-1.25

Not hospitalized just prior to transplant 5516 0.92 0.0475 0.84-1.00

N = 10,507ISHLT 2012




VARIABLEN Relative


Interval

Recipient Hep B core (+) 397 1.20 0.06 0.99-1.44

Male recipient/female donor vs. male recipient/male donor 1763 1.11 0.0762 0.99-1.24

Not ABO identical 1487 1.10 0.0968 0.98-1.22

N = 10,507





Recipient age Transplant center volume

Recipient height Ischemia time

Recipient BMI Recipient pre-transplant bilirubin

Donor age Recipient pre-transplant creatinine

Donor weight Recipient PVR




20 30 40 50 60 700.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001




15 20 25 30 35 40 45 50 55 600.0

0.5

1.0

1.5

2.0

2.5

Donor Age (years)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001




155 160 165 170 175 180 185 1900.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.0018

ISHLT 2012(N = 10,507)

* The risk associated with recipient height should be considered in conjunction with the risk associated with recipient BMI and donor weight.



Risk Factors For 5 Year Mortality with 95% Confidence Limits Recipient BMI

20 25 30 350.0

0.5

1.0

1.5

2.0

Recipient BMI (kg/m2)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001

ISHLT 2012(N = 10,507)

* The risk associated with recipient BMI should be considered in conjunction with the risk associated with recipient height and donor weight.



Risk Factors For 5 Year Mortality with 95% Confidence Limits Donor Weight

50 60 70 80 90 100 110 120 1300.0

0.5

1.0

1.5

2.0

Donor Weight (kg)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.0083

ISHLT 2012(N = 10,507)

* The risk associated with donor weight should be considered in conjunction with the risk associated with recipient weight and recipient BMI.




30 60 90 120 150 180 210 240 270 300 330 3600.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001




5 10 15 20 25 30 35 40 45 50 55 60 65 700.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001




0.5 1.0 1.5 2.0 2.5 3.0 3.50.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001




0.5 1.0 1.5 2.0 2.50.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001



Risk Factors For 5 Year Mortality with 95% Confidence Limits Pulmonary Vascular Resistance

0 2 4 6 8 100.0

0.5

1.0

1.5

2.0

2.5

3.0

PVR

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.0003



Risk Factors For 5 Year MortalityConditional on Survival to 1 Year

VARIABLEN Relative


Interval

Rejection between discharge and 1st year 2427 1.63 <.0001 1.45-1.83

No AZA, MMF/MPA or Sirolimus at 1 year 726 1.59 <.0001 1.31-1.95

No Cyclo, TAC or Sirolimus at 1 year 316 1.48 0.0052 1.13-1.96

Dialysis prior to discharge 531 1.43 0.0011 1.15-1.76

Recipient history of dialysis prior to transplant 216 1.39 0.0334 1.03-1.87

Female recipient with prior pregnancy/ male donor vs. male recipient/male donor 657 1.31 0.0117 1.06-1.61

Number of HLA mismatches at A locus (per mismatch)

0 A MM: N = 5851 A MM: N = 44442 A MM: N = 3953

1.28 0.0097 1.06-1.55

N = 8,982ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095


Risk Factors For 5 Year MortalityConditional on Survival to 1 Year (continued)

VARIABLEN Relative


Interval

Treated for infection prior to discharge 1879 1.23 0.003 1.07-1.40


Diagnosis: Coronary artery disease vs. cardiomyopathy 4068 1.17 0.0187 1.03-1.34

IL-2R antagonist used for induction 2334 1.15 0.0272 1.02-1.30

Not hospitalized at transplant 4807 0.88 0.0259 0.78-0.98


N = 8,982



Borderline Significant Risk Factors For 5 Year MortalityConditional on Survival to 1 Year

VARIABLEN Relative


Interval


Recipient history of malignancy 404 1.25 0.0741 0.98-1.60



Diagnosis: Congenital vs. cardiomyopathy 223 0.72 0.0976 0.50 -1.06

N = 8,982



Risk Factors For 5 Year MortalityConditional on Survival to 1 Year


Recipient age Recipient pre-transplant creatinine

Recipient BMI Recipient TPG

Donor age


ADULT HEART TRANSPLANTS (2001-6/2006)Risk Factors For 5 Year Mortality with 95% Confidence Limits

Conditional on Survival to 1 Year Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0

2.5

3.0


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001



Conditional on Survival to 1 Year Donor Age

15 20 25 30 35 40 45 50 55 600.0

0.5

1.0

1.5

2.0

2.5

Donor Age (years)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.0005



Conditional on Survival to 1 Year Recipient BMI

20 25 30 350.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.0026

ISHLT 2012(N = 8,982)J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095


Conditional on Survival to 1 Year Recipient Pre-Transplant Creatinine

0.5 1.0 1.5 2.0 2.50.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

P = 0.0187



Conditional on Survival to 1 Year Transpulmonary Pressure Gradient

3 6 9 12 150.0

0.5

1.0

1.5

2.0

TPG

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.0033




VARIABLEN Relative


Interval

ECMO 29 1.82 0.0107 1.15-2.87

Ventilator at time of transplant 346 1.65 <.0001 1.43-1.92

Recipient on dialysis 233 1.50 <.0001 1.26-1.78

Repeat transplant 283 1.43 <.0001 1.21-1.70

Recipient history of diabetes 1967 1.28 <.0001 1.19-1.37

PRA > 20% 599 1.27 <.0001 1.13-1.43

Transplant year: 1996 vs. 2000/2001 2054 1.23 <.0001 1.12-1.34

Diagnosis: coronary artery disease vs. cardiomyopathy 5762 1.18 <.0001 1.11-1.26

N = 11,531ISHLT 2012




VARIABLE N Relative Risk

P-value 95% Confidence Interval


Prior cerebrovascular event 603 1.15 0.0225 1.02-1.29

On VAD at time of transplant 1605 1.13 0.006 1.03-1.23

Year of transplant: 1997 vs. 2000/2001 2084 1.11 0.016 1.02-1.21

Donor history of hypertension 1293 1.11 0.0251 1.01-1.21

Year of transplant: 1998 vs. 2000/2001 2162 1.10 0.0263 1.01-1.20

Total HLA mismatches (per mismatch)

0/1 MM (N=67)2 MM (N=304)3 MM (N=1102)4 MM (N=2520)5 MM (N=5600)6 MM (N=1938)

1.04 0.0048 1.01-1.07

Not hospitalized at transplant 4337 0.93 0.0321 0.88-0.99

N = 11,531ISHLT 2012




VARIABLE

N Relative Risk



Recipient prior pregnancy 1617 1.09 0.0654 0.99-1.20

N = 11,531







Recipient weight Recipient pre-transplant bilirubin

Donor age Recipient pre-transplant creatinine

Donor weight




20 30 40 50 60 700.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

alit

y

p < 0.0001




15 20 25 30 35 40 45 50 55 600.0

0.5

1.0

1.5

2.0

2.5

Donor Age (years)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

alit

y

p < 0.0001




155 160 165 170 175 180 185 1900.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

alit

y

p < 0.0001

ISHLT 2012(N = 11,531)

* The risk associated with recipient height should be considered in conjunction with the risk associated with recipient weight and donor weight.




50 60 70 80 90 100 110 120 1300.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

alit

y

p = 0.0023

ISHLT 2012(N = 11,531)

* The risk associated with recipient BMI should be considered in conjunction with the risk associated with recipient height and donor weight.



Risk Factors For 10 Year Mortality with 95% Confidence Limits Donor Weight

50 60 70 80 90 100 110 120 1300.0

0.5

1.0

1.5

2.0

Donor Weight (kg)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

alit

y

p = 0.0299

ISHLT 2012(N = 11,531)

* The risk associated with donor weight should be considered in conjunction with the risk associated with recipient weight and recipient height.




30 60 90 120 150 180 210 240 270 300 330 3600.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

alit

y

p < 0.0001




5 10 15 20 25 30 35 40 45 50 55 60 65 700.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

alit

y

p < 0.0001




0.5 1.0 1.5 2.0 2.5 3.0 3.50.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

alit

y

p = 0.0006




0.5 1.0 1.5 2.0 2.50.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

alit

y

p < 0.0001




VARIABLEN Relative


Interval

Retransplant 273 1.82 <.0001 1.56-2.11

Diagnosis: not cardiomyopathy, coronary artery disease, congenital heart disease, valvular heart disease or retransplant vs. cardiomopathy

113 1.35 0.0191 1.05-1.74

On ventilator 338 1.34 0.0002 1.15-1.56

Recipient Hep B Core (+) 244 1.33 0.0004 1.14-1.56

PR A> 20% 487 1.19 0.0021 1.07-1.33

Male recipient/female donor vs. male recipient/male donor 2253 1.19 <.0001 1.09-1.30

N = 10,888ISHLT 2012




VARIABLEN Relative


Interval

On VAD at transplant 578 1.15 0.0124 1.03-1.29

Diagnosis: Coronary artery disease vs. cardiomyopathy 5295 1.14 <.0001 1.08-1.20




0-3 vs. 4-6 total HLA mismatches 1497 0.91 0.0103 0.85-0.98

N = 10,888ISHLT 2012






Female recipient/female donor vs. male recipient/male donor 1006 1.13 0.0758 0.99-1.29

Hospitalized (inc. ICU) at transplant 6431 1.05 0.0899 0.99-1.10

N = 10,888







Recipient weight Recipient pre-transplant creatinine

Donor age




20 30 40 50 60 700.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 1

5 Y

ea

r M

ort

alit

y

p < 0.0001




15 20 25 30 35 40 45 50 55 600.0

0.5

1.0

1.5

2.0

2.5

Donor Age (years)

Re

lati

ve

Ris

k o

f 1

5 Y

ea

r M

ort

alit

y

p < 0.0001




155 160 165 170 175 180 185 1900.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 1

5 Y

ea

r M

ort

alit

y

p = 0.0003

ISHLT 2012(N = 11,531)

* The risk associated with recipient height should be considered in conjunction with the risk associated with recipient weight.




50 60 70 80 90 100 110 120 1300.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 1

5 Y

ea

r M

ort

alit

y

p = 0.0009

ISHLT 2012(N = 11,531)

* The risk associated with recipient BMI should be considered in conjunction with the risk associated with recipient height.




30 60 90 120 150 180 210 240 270 300 330 3600.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 1

5 Y

ea

r M

ort

alit

y

p < 0.0001




5 10 15 20 25 30 35 40 45 50 55 60 65 700.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 1

5 Y

ea

r M

ort

alit

y

p = 0.0015




0.5 1.0 1.5 2.0 2.50.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 1

5 Y

ea

r M

ort

alit

y

p < 0.0001




VARIABLEN Relative


Interval

Retransplant 294 2.19 <.0001 1.92-2.49

Diagnosis: not cardiomyopathy, coronary artery disease, congenital heart disease, valvular heart disease or retransplant vs. cardiomopathy

1170 1.39 <.0001 1.29-1.50



Diagnosis: Coronary artery disease vs. cardiomyopathy

7444 1.11 <.0001 1.06-1.16



Female recipient vs. male recipient 2687 0.94 0.0225 0.89-0.99

Diagnosis: congenital vs. cardiomyopathy 194 0.78 0.0159 0.64-0.96

N = 10,888ISHLT 2012






Donor age Ischemia time




20 30 40 50 60 700.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f 2

0 Y

ea

r M

ort

alit

y

p < 0.0001




15 20 25 30 35 40 45 50 55 600.0

0.5

1.0

1.5

2.0

2.5

Donor Age (years)

Re

lati

ve

Ris

k o

f 2

0 Y

ea

r M

ort

alit

y

p < 0.0001




30 60 90 120 150 180 210 240 270 300 330 3600.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 2

0 Y

ea

r M

ort

alit

y

p = 0.0068




5 10 15 20 25 30 35 40 45 50 55 60 65 700.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f 2

0 Y

ea

r M

ort

alit

y

p < 0.0001


ADULT HEART TRANSPLANTS (2005-6/2010)Risk Factors for Developing Severe Renal Dysfunction within 1 Year

Limited to Recipients without Severe Renal Dysfunction* Pre-TransplantConditional on Survival to Transplant Discharge

VARIABLEN Relative


Interval

Dialysis prior to discharge 480 3.80 <.0001 2.99-4.82

Continuous chronic device 1090 1.61 0.0004 1.24-2.08

Infection requiring IV antibiotics within 2 weeks prior to transplant

834 1.60 0.0005 1.23-2.08

Rejection prior to discharge 824 1.59 0.0013 1.20-2.12


Female donor 2352 1.43 0.0016 1.14-1.78

Cyclosporine vs. Tacrolimus at discharge 2487 1.31 0.0115 1.06-1.61

Total number of HLA mismatches (per mismatch)

1.10 0.0421 1.00-1.21

Diagnosis: Coronary artery disease vs. cardiomyopathy

3574 0.81 0.0486 0.66-1.00

N = 8,794ISHLT 2012

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


ADULT HEART TRANSPLANTS (2005-6/2010)Borderline Significant Risk Factors for Developing Severe Renal Dysfunction within 1 Year


VARIABLE

N Relative Risk


AZA vs. MMF/MPA at discharge 135 1.72 0.0798 0.94-3.15

Stroke prior to discharge 135 1.62 0.0833 0.94-2.79


N = 8,794

ISHLT 2012*Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis






Recipient weight Recipient systolicpulmonary artery pressure (borderline)





Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f R

en

al D

ys

fun

cti

on

w

ith

in 1

Ye

ar

p = 0.0013

ISHLT 2012(N = 8,794)





Recipient Weight

50 60 70 80 90 100 110 120 1300.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5


Re

lati

ve

Ris

k o

f R

en

al D

ys

fun

cti

on

w

ith

in 1

Ye

ar

p = 0.0043

ISHLT 2012(N = 8,794)





Recipient Pre-Transplant Creatinine

0.5 1.0 1.5 2.0 2.50.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0


Re

lati

ve

Ris

k o

f R

en

al D

ys

fun

c-

tio

n w

ith

in 1

Ye

ar

p < 0.0001

ISHLT 2012 (N = 8,794)




Risk Factors for Developing Severe Renal Dysfunction within 1 YearLimited to Recipients without Severe Renal Dysfunction* Pre-Transplant

Conditional on Survival to Transplant Discharge Systolic Pulmonary Artery Pressure

5 10 15 20 25 30 35 400.0

0.5

1.0

1.5

2.0

Systolic PA Pressure

Re

lati

ve

Ris

k o

f R

en

al D

ys

fun

cti

on

w

ith

in 1

Ye

ar

p = 0.0952

ISHLT 2012 (N = 8,794)



ADULT HEART TRANSPLANTS (2001-6/2006)Risk Factors for Developing Severe Renal Dysfunction within 5 Years


VARIABLEN Relative


Interval

Dialysis prior to discharge 407 3.17 <.0001 2.49-4.03

Donor cause of death: CNS tumor vs. head trauma 97 2.13 0.0046 1.26-3.59




Pacemaker prior to discharge 278 1.52 0.0266 1.05-2.21

No AZA, MMF/MPA or Sirolimus at discharge 392 1.50 0.029 1.04-2.16

N = 8,168ISHLT 2012




Limited to Recipients without Severe Renal Dysfunction* Pre-TransplantConditional on Survival to Transplant Discharge (continued)

VARIABLEN Relative


Interval

Cyclosporine vs. Tacrolimus at discharge 4385 1.41 0.0004 1.17-1.71

Pulsatile chronic device 1384 1.32 0.0113 1.06-1.63


Diagnosis: Coronary artery disease vs. cardiomyopathy 3752 0.81 0.0213 0.67-0.97

Polyclonal agent used for induction 1570 0.79 0.0486 0.62-1.00


N = 8,168ISHLT 2012



ADULT HEART TRANSPLANTS (2001-6/2006)Borderline Significant Risk Factors for Developing Severe Renal Dysfunction within 5 Years


VARIABLEN Relative


Interval

Hospitalized (inc. ICU) at transplant 3792 1.16 0.0931 0.98-1.37

N = 8,168







Donor/recipient height ratio Transplant center volume (borderline)





Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f R

en

al D

ys

fun

cti

on

w

ith

in 5

Ye

ars

p = 0.0017

ISHLT 2012(N = 8,168)





Donor Height/Recipient Height Ratio

0.85 0.95 1.05 1.150.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Donor height/recipient height

Re

lati

ve

Ris

k o

f R

en

al D

ys

fun

cti

on

w

ith

in 5

Ye

ars

p = 0.0313

ISHLT 2012(N = 8,168)





Recipient Pre-Transplant Creatinine

0.5 1.0 1.5 2.0 2.50.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0


Re

lati

ve

Ris

k o

f R

en

al D

ys

fun

c-

tio

n w

ith

in 5

Ye

ars

p < 0.0001

ISHLT 2012 (N = 8,168)





Center Volume

5 10 15 20 25 30 35 40 45 50 55 60 65 700.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f R

en

al D

ys

fun

c-

tio

n w

ith

in 5

Ye

ars

p = 0.0985

ISHLT 2012 (N = 8,168)



ADULT HEART TRANSPLANTS (1999-6/2003)Risk Factors for Developing Non-Skin Malignancy within 8 Years

Limited to Recipients without Malignancy Pre-TransplantConditional on Survival to Transplant Discharge

VARIABLEN Relative


Interval


Retransplant 82 2.97 0.0006 1.60-5.52

Donor history of cancer 89 2.83 <.0001 1.72-4.65

Female recipient/female donor vs. male recipient/male donor 585 1.71 0.009 1.14-2.56



Implantable defibrillator prior to transplant 1761 1.28 0.0145 1.05-1.56

N = 4,846ISHLT 2012


ADULT HEART TRANSPLANTS (1999-6/2003)Borderline Significant Risk Factors for

Developing Non-Skin Malignancy within 8 YearsLimited to Recipients without Malignancy Pre-Transplant

Conditional on Survival to Transplant Discharge

VARIABLEN Relative


Interval




Prior sternotomy 2232 0.83 0.0865 0.67-1.03

N = 4,846






Ischemia time (borderline)




Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0

2.5

3.0


Re

lati

ve

Ris

k o

f N

on

-Sk

in M

a-

lign

an

cy

wit

hin

8 Y

ea

rs

p < 0.0001




Center Volume

5 10 15 20 25 30 35 40 45 50 55 60 65 700.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f N

on

-Sk

in M

a-

lign

an

cy

wit

hin

8 Y

ea

rs p = 0.0006




Ischemia Time

30 60 90 120 150 180 210 240 270 300 330 3600.0

0.5

1.0

1.5

2.0

2.5


Re

lati

ve

Ris

k o

f N

on

-Sk

in M

a-

lign

an

cy

wit

hin

8 Y

ea

rs

p = 0.052


ADULT HEART TRANSPLANTS (2001-6/2006)Risk Factors for Developing CAV within 5 YearsConditional on Survival to Transplant Discharge

VARIABLEN Relative


Interval

OTK3 used for induction 333 1.74 <.0001 1.43-2.11

AZA vs. MMF/MPA at discharge 497 1.56 <.0001 1.31-1.85

Pulmonary embolism prior to transplant 121 1.43 0.0362 1.02-1.99


Rejection prior to discharge 1094 1.30 <.0001 1.14-1.49

Cyclosporine vs. Tacrolimus at discharge 4256 1.30 <.0001 1.17-1.45

Donor history of hypertension 869 1.16 0.0381 1.01-1.33

Recipient CMV(-)/Donor CMV(+) 1485 1.14 0.0238 1.02-1.28

N = 7,788ISHLT 2012



(continued)






Female recipient with prior pregnancy/female donor vs. male recipient/male donor 591 0.78 0.0099 0.65-0.94



Female recipient without prior pregnancy/ female donor vs. male recipient/male donor 325 0.54 <.0001 0.40-0.73

N = 7,788ISHLT 2012


ADULT HEART TRANSPLANTS (2001-6/2006)Borderline Significant Risk Factors for Developing CAV within 5 Years

Conditional on Survival to Transplant Discharge

VARIABLEN Relative


Interval

No Cyclosporine, Tacrolimus or Sirolimus at discharge 195 1.35 0.0816 0.96-1.90

Donor history of cancer 136 1.33 0.054 1.00-1.78

N = 7,788




Recipient BMI Donor age

Donor/recipient height difference Ischemia time (borderline)



Recipient BMI

20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 350.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f C

AV

wit

hin

5

Ye

ars

p = 0.0103



Difference Between Donor Height and Recipient Height

-30 -20 -10 0 10 20 300.0

0.5

1.0

1.5

2.0

Donor Height – Recipient Height (cm)

Re

lati

ve

Ris

k o

f C

AV

wit

hin

5 Y

ea

rs

p = 0.0293



Donor Age

15 20 25 30 35 40 45 50 55 600.0

0.5

1.0

1.5

2.0

2.5

3.0

Donor Age (years)

Re

lati

ve

Ris

k o

f C

AV

wit

hin

5 Y

ea

rs

p < 0.0001


ADULT HEART TRANSPLANTS (2001-6/2006)Risk Factors for Developing CAV within 5 Years

Conditional on Survival to Transplant Discharge Ischemia Time

30 60 90 120 150 180 210 240 270 300 330 3600.0

0.5

1.0

1.5

2.0


Re

lati

ve

Ris

k o

f C

AV

wit

hin

5

Ye

ars

p = 0.0552


heart transplantation overall ishlt 2012 j heart lung transplant. 2012 oct; 31(10): 1045-1095

Documents

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heart transplantsdonor

ishlt transplant registry

early posttransplant

conditional survival

survival rates

estimated time point

time of death