HEART TRANSPLANTATION

HEART TRANSPLANTATION

Adult Recipients

JHLT. 2013 Oct; 32(10): 951-964

2013

Table of Contents

Donor and recipient characteristics: slides 3-24 Survival slides: slides 25-61 Immunosuppression: slides 62-80 Morbidity: slides 81-106 Multivariable analyses: slides 107-195 2013 focus theme: age: slides 196-237

JHLT. 2013 Oct; 32(10): 951-964

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Diagnosis: slides 4-6 Recipient and donor characteristics: slides 7-24

Donor and Recipient Characteristics:

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Adult Heart TransplantsDiagnosis

Myopathy48%

Congenital2%

ReTX2%

CAD43%

Misc.0%

Valvular4%

1/1982 – 6/2012

Myopathy54%

Congenital3%

ReTX3%

CAD37% Misc.

1%

Valvular3%

1/2006 – 6/2012

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Adult Heart Transplants Diagnosis: Cardiomyopathy vs. CAD by Location

203040506070

Myopathy CAD

% o

f rec

ipie

nts

All Locations

203040506070

Myopathy CAD

% o

f rec

ipie

nts

Europe

203040506070

Myopathy CAD

% o

f rec

ipie

nts

North America

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Adult Heart TransplantsDiagnosis by Location

(Transplants: January 2006 – June 2012)

Myopathy57%

Congenital3%

ReTX1%

CAD34% Misc.

0%Valvular

4%

Europe

Myopathy52%

Congenital3%

ReTX3%

CAD39% Misc.

1%Valvular

2%

North America

Myopathy60%

Congenital2%

ReTX1%

CAD30%

Misc.6%

Valvular2%

Other

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Adult Heart TransplantsDonor and Recipient Characteristics

1992-2000(N = 37,146)

2001-2005(N = 17,183)

2006-6/2012(N = 22,318) p-value

Recipient age (years) 54.0 (28.0 - 65.0) 54.0 (26.0 - 66.0) 54.0 (24.0 - 67.0) <0.0001

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 - 102.0) 77.6 (53.0 - 106.6) 79.4 (53.1 - 110.0) <0.0001

Recipient height (cm) 173.0 (157.0 - 188.0) 174.0 (157.5 - 188.0) 175.0 (157.4 - 188.0) 0.0042

Recipient BMI 22.7 (19.5 - 31.7) 24.2 (19.6 - 33.1) 24.4 (19.6 - 34.3) <0.0001

Donor weight (kg) 75.0 (52.0 - 103.3)1 76.8 (55.0 - 108.8) 79.4 (56.7 - 113.0) <0.0001

Donor height (cm) 175.0 (155.0 - 188.0)1 175.3 (158.0 - 189.0) 175.0 (158.0 - 190.0) <0.0001

Donor BMI 24.2 (18.8 - 32.9)1 24.8 (19.5 - 34.4) 25.5 (19.9 - 36.4) <0.0001

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

1 Based on 4/1994-2000 transplants.

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1992-2000(N = 37,146)

2001-2005(N = 17,183)

2006-6/2012(N = 22,318) p-value

Recipient/donor gender (% male) 80.7%/ 68.4% 77.9%/ 69.1% 75.9%/ 69.2% <0.0001/ 0.1103

Male recipient/ female donor 21.3% 18.5% 16.7% <0.0001

Female recipient/ male donor 9.2% 9.7% 9.9% 0.0055

Recipient/donor diabetes mellitus 13.1%*/ 1.6%1 19.8%/ 2.0% 25.3%/ 3.0% <0.0001/ <0.0001

Recipient prior history of dialysis 3.0%1 4.3% 4.2% <0.0001

Recipient amiodarone use (US only) 21.7%1 29.0% 30.5% <0.0001

Recipient/donor cigarette history -/ 38.0%1 46.6%2/ 29.1% 46.4%/ 18.6% 0.8536/ <0.0001

Recipient/donor hypertension 34.5%1/ 10.8%1 38.1%/ 11.4% 45.3%/ 13.8% <0.0001/ <0.0001

Recipient prior cardiac surgery - 39.1%2 46.4% <0.0001

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

Recipient previous malignancy 3.3%1 4.5% 6.6% <0.0001

Recipient COPD 3.2%1 3.2% 4.3% <0.0001

Ischemic time (hours) 2.9 (1.3 - 4.8) 3.1 (1.5 - 5.0) 3.3 (1.6 - 5.1) <0.0001

Continuous factors are expressed as median (5th-95th percentiles) 1 Based on 4/1994-2000 transplants.2 Based on 7/2004-2005 transplants.

(Cont’d)

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2013


1992-2000(N = 37,146)

2001-2005(N = 17,183)

2006-6/2012(N = 22,318) p-value

Most recent PRA > 10%1

Overall 7.7% 8.9%2 13.8%3 <0.0001

Class I - - 14.4%4 -

Class II - - 9.6%4 -

Creatinine at time of transplant (mg/dL) 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 - 5.5) <0.0001

HLA Mismatches 4.3% 4.4% 3.8%

0-2 40.2% 40.1% 38.4%

0.0003 3-4 55.5% 55.5% 57.8%

5-6 7.7% 8.9% 13.8%


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)

JHLT. 2013 Oct; 32(10): 951-964

2013


1992-2000(N = 37,146)

2001-2005(N = 17,183)

2006-6/2012(N = 22,318) p-value

Diagnosis

Cardiomyopathy 46.2% 48.2% 54.0%

<0.0001

Coronary artery disease 45.8% 42.7% 36.8%

Valvular 3.9% 3.5% 2.8%

Retransplant 1.9% 2.2% 2.5%

Congenital 1.8% 2.7% 2.9%

Other causes 0.4% 0.6% 0.9%

Donor cause of death

Head trauma 45.9% 54.6% 45.8%

<0.0001 Stroke 29.0% 32.9% 24.4%

Other 25.0% 12.5% 29.8%

(Cont’d)

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1992-2000(N = 37,146)

2001-2005(N = 17,183)

2006-6/2012(N = 22,318) p-value

Pre-operative support (multiple items may be reported)

Hospitalized at time of transplant 60.8% 47.9% 44.3% <0.0001

On IV inotropes 55.7%1 47.2% 42.4% <0.0001

LVAD 12.1%2 17.0% 28.5% <0.0001

IABP 6.4% 6.7% 6.1% 0.1650

RVAD - 5.0%3 3.7% 0.0055

Ventilator 3.3% 3.2% 2.7% 0.0092

TAH 0.1%2 0.1% 1.0% <0.0001

ECMO 0.3%4 0.5% 1.1% <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)

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2013

Adult Heart TransplantsRecipient Gender By Location


Europe North America Other0

10

20

30

40

50

60

70

80

90Male Female

% o

f Tra

nspl

ants

N = 6,382

N = 1,989

N = 9,616

N = 3,104

N = 952

N = 275

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Adult Heart TransplantsDonor Gender By Location



10

20

30

40

50

60

70

80Male Female

% o

f Tra

nspl

ants

N = 5,343

N = 2,970

N = 9,137

N = 3,583

N = 910

N = 308

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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 tra

nspl

ants

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

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Adult Heart Transplants % of Patients Bridged with Mechanical Circulatory Support*

(Transplants: January 2000 – December 2011)

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 20110

10

20

30

40

50

Year

% o

f pat

ient

s

* LVAD, RVAD, TAH. ECMO is excluded.

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by Year and Device Type

2005 2006 2007 2008 2009 2010 20110

10

20

30

40

50

TAHLVAD+RVADRVADLVAD

Year

% o

f pat

ient

s


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Adult Heart Transplants Number and % of Combined Organ Transplants Reported

By Year and Type of Transplant

1994 1996 1998 2000 2002 2004 2006 2008 20100

20

40

60

80

100

120

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

Heart-Kidney Heart-LiverHeart-Kidney-Liver Heart-Kidney-PancreasOther Combined Organ Transplants Combined as % of total

Num

ber o

f tra

nspl

ants

% o

f tra

nspl

ants

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2013

Adult Heart TransplantsRecipient BMI Distribution By Location


Europe North America Other0%

20%

40%

60%

80%

100%

<18.5 18.5-<25 25-<30 30-<35 35+

% o

f Tra

nspl

ants

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsRecipient BMI Distribution By Diagnosis


Cardiomyopathy Coronary Artery Disease0%

20%

40%

60%

80%

100%

<18.5 18.5-<25 25-<30 30-<35 35+

% o

f Tra

nspl

ants

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2013

Adult Heart TransplantsRecipient Diabetes Mellitus Distribution By Location



5

10

15

20

25

30

% o

f Tra

nspl

ants

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2013

Adult Heart TransplantsRecipient Diabetes Mellitus Distribution By Diagnosis


Cardiomyopathy Coronary Artery Disease0

5

10

15

20

25

30

35

40

% o

f Tra

nspl

ants

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2013

Adult Heart TransplantsRecipient Cigarette History By Location



10

20

30

40

50

60

% o

f Tra

nspl

ants

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Adult Heart TransplantsRecipient Cigarette and COPD History By Diagnosis


Cardiomyopathy Coronary Artery Disease All Diagnoses0

10

20

30

40

50

60

70

COPD Cigarette history

% o

f Tra

nspl

ants

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Adult Heart Transplants Ischemic time Distribution By Location



20%

40%

60%

80%

100%

< 2 hours 2-<4 hours 4-<6 hours 6+ hours

% o

f Tra

nspl

ants

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2013

Survival Analyses: by era: slides 26-27 and 37-41 by gender: slides 28-31 by diagnosis: slides 32-41 by PVR: slides 42-45 by BMI: slide 46 by comorbidities: slides 47-49 by VAD usage: slides 50-53 by re-transplant: slide 54 by employment status at 1 year post transplant: slide 55 by age: see slides 210-217 in the age theme section by immunosuppression: see slides 66, 72 and 79 in the

immunosuppression section Cause of death: slides 56-61

JHLT. 2013 Oct; 32(10): 951-964

2013

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

1982-1991 (N = 21,342)1992-2001 (N = 38,966)2002-2005 (N = 13,496)2006-6/2011 (N = 18,896)

Years

Surv

ival

(%)

Median survival (years): 1982-1991=8.4; 1992-2001=10.7; 2002-2005=NA; 2006-6/2011=NA

All pair-wise comparisons were significant at p < 0.0001 except 2002-2005 vs. 2006-6/2011 (p = 0.9749)

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Adult Heart TransplantsKaplan-Meier Survival by Era Conditional on Survival to 1

Year (Transplants: January 1982 – June 2011)

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

20

40

60

80

1001982-1991 (N = 15,960)1992-2001 (N = 30,545)2002-2005 (N = 10,845)2006-6/2011 (N = 13,923)

Years

Surv

ival

(%)


All pair-wise comparisons were significant at p < 0.001 except 1992-2001 vs. 2006-6/2011 (p=0.9440) and 2002-2005 vs. 2006-6/2011 (p=0.0569)

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2013

Adult Heart TransplantsKaplan-Meier Survival by Recipient Gender


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

Male (N = 74,179)

Female (N = 18,494)

Years

Surv

ival

(%)

Median survival (years): male = 10.2; female = 11.0

p < 0.0001

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2013

Adult Heart TransplantsKaplan-Meier Survival by Recipient Gender Conditional on

Survival to 1 Year (Transplants: January 1982 – June 2011)

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

Male (N = 56,955)

Female (N = 14,123)

Years

Surv

ival

(%)

Median survival (years): male = 12.9; female = 14.0

p < 0.0001

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2013

Adult Heart TransplantsKaplan-Meier Survival by Donor/Recipient Gender


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

Male/Male (N = 49,836)Male/Female (N = 16,151)Female/Male (N = 7,840)Female/Female (N = 9,247)

Years

Surv

ival

(%)

Median survival: male/male=10.9; male/female=9.5; female/male=11.0; female/female=11.2

All pair-wise comparisons with male/female were significant at p < 0.0001. No other pair-wise comparisons were significant at p < 0.05

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsKaplan-Meier Survival by Donor/Recipient Gender

Conditional on Survival to 1 Year(Transplants: January 1982 – June 2011)

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

Male/Male (N = 39,277)Male/Female (N = 11,886)Female/Male (N = 6,123)Female/Female (N = 7,017)

Years

Surv

ival

(%)

Median survival: male/male=13.2; male/female=12.6; female/male=13.8; female/female=14.3

All pair-wise comparisons were significant at p < 0.05 except male/male vs. female/male and female/male vs. female/female

JHLT. 2013 Oct; 32(10): 951-964

2013

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=42,175) Coronary artery disease (N=38,845)Congenital diagnosis (N=1,853) Retransplant (N=1,895)Valvular (N=3,325)

Years

Surv

ival

(%)

All pair-wise comparisons were significant at p < 0.01 except cardiomyopathy vs. congenital (p=0.9113).

Median survival (years): Cardiomyopathy= 11.6; CAD=9.4; Congenital=14.4; Retransplant=6.3; Valvular=10.9

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2013

Adult Heart TransplantsKaplan-Meier Survival by Diagnosis Conditional on Survival

to 1 Year (Transplants: January 1982 – June 2011)

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=33,030) Coronary artery disease (N=30,120)Congenital diagnosis (N=1,327) Retransplant (N=1,248)Valvular (N=2,430)

Years

Surv

ival

(%)

All pair-wise comparisons were significant at p < 0.0001 except cardiomyopathy vs. valvular (p = 0.9665) and CAD vs. retransplant (p = 0.0659)

Median survival (years): Cardiomyopathy=14.2; CAD=11.9; Congenital=21.2; Retransplant=10.8; Valvular=14.6

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2013

Adult Heart TransplantsKaplan-Meier Survival Within 1 Year by Diagnosis


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

60

70

80

90

100

Cardiomyopathy (N=9,754) Coronary artery disease (N=6,825)

Congenital diagnosis (N=533) Retransplant (N=463)

Valvular (N=540)

Months

Surv

ival

(%)

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

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2013

Adult Heart TransplantsKaplan-Meier Survival by Diagnosis


0 1 2 3 4 5 6 7 850

60

70

80

90

100 Cardiomyopathy (N=14,578) Coronary artery disease (N=10,821)Congenital diagnosis (N=794) Retransplant (N=693)Valvular (N=887)

Years

Surv

ival

(%)

All pair-wise comparisons with cardiomyopathy are significant at p < 0.02. No other pair-wise comparisons were significant at p < 0.05.

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2013

Adult Heart TransplantsKaplan-Meier Survival by Diagnosis Conditional on Survival

to 1 Year (Transplants: January 2003 – June 2011)

0 1 2 3 4 5 6 7 850

60

70

80

90

100

Cardiomyopathy (N=11,168) Coronary artery disease (N=8,319)Congenital diagnosis (N=563) Retransplant (N=506)Valvular (N=626)

Years

Surv

ival

(%)

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

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2013

Adult Heart TransplantsKaplan-Meier Survival by Era (Transplants: January 1982 – June 2011)

Diagnosis: Cardiomyopathy

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

20

40

60

80

100

1982-1991 (N = 9,012)1992-2001 (N = 17,039)2002-2005 (N = 6,370)2006-6/2011 (N = 9,754)

Years

Surv

ival

(%)


All comparisons were significant at p < 0.0001 except 2002-2005 vs. 2006-6/2011 (p=0.9689)

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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

1982-1991 (N = 9,230)1992-2001 (N = 17,271)2002-2005 (N = 5,519)2006-6/2011 (N = 6,825)

Years

Surv

ival

(%)

Median survival (years): 1982-1991=8.0; 1992-2001=9.7; 2002-2005=NA; 2006-6/2011= NA

All comparisons were significant at p < 0.0001 except 2002-2005 vs. 2006-6/2011

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Diagnosis: Congenital

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

20

40

60

80

100

1982-1991 (N = 252)1992-2001 (N = 712)2002-2005 (N = 356)2006-6/2011 (N = 533)

Years

Surv

ival

(%)


No pair-wise comparisons were significant at p < 0.05

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Diagnosis: Retransplant

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

20

40

60

80

100

1982-1991 (N = 400)1992-2001 (N = 730)2002-2005 (N = 302)2006-6/2011 (N = 463)

Years

Surv

ival

(%)


All pair-wise comparisons were significant at p < 0.01 except 2002-2005 vs. 2006-6/2011 (p=0.7527)

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2013


Diagnosis: Valvular

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

20

40

60

80

100

1982-1991 (N = 900)1992-2001 (N = 1,421)2002-2005 (N = 464)

Years

Surv

ival

(%)


No pair-wise comparisons were significant at p < 0.05 except 1982-1991 vs. 1992-2001 (p = 0.0197)

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2013

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 = 8,495) 3-<5 Wood units (N = 2,758)5+ Wood units (N = 889)

Years

Surv

ival

(%)

1-<3 vs. 3-<5: p = 0.0006No other pair-wise comparisons were significant at p < 0.05

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2013

Adult Heart TransplantsKaplan-Meier Survival by Donor/Recipient Weight Ratio

(Transplants: January 2003 – June 2011)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=1,217) 0.8-<0.9 Weight ratio (N=1,695)0.9-<1.1 Weight ratio (N=3,175) 1.1-<1.2 Weight ratio (N=940)1.2+ Weight ratio (N=1,468)

Years

Surv

ival

(%)


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2013


(Transplants: January 2003 – June 2011)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=274) 0.8-<0.9 Weight ratio (N=461)0.9-<1.1 Weight ratio (N=1,030) 1.1-<1.2 Weight ratio (N=370)1.2+ Weight ratio (N=623)

Years

Surv

ival

(%)


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2013


(Transplants: January 2003 – June 2011)For recipients with PVR: 5+ wood units

0 1 2 3 4 5 650

60

70

80

90

100

<0.8 Weight ratio (N=99) 0.8-<0.9 Weight ratio (N=132)0.9-<1.1 Weight ratio (N=301) 1.1-<1.2 Weight ratio (N=121)1.2+ Weight ratio (N=236)

Years

Surv

ival

(%)


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2013

Adult Heart TransplantsKaplan-Meier Survival by BMI Group


0 1 2 3 4 550

60

70

80

90

100

<18.5 (N=422) 18.5-<25 (N=9,955) 25-<30 (N=5,398)

30-<35 (N=2,510) 35+ (N=611)

Years

Surv

ival

(%)

No pair-wise comparisons were significant at p < 0.05 except 18.5<25 vs. 25-<30 (p < 0.0001)

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2013

Adult Heart TransplantsKaplan-Meier Survival by Recipient Diabetes Mellitus


0 1 2 3 4 5 6 7 850

60

70

80

90

100

Diabetes (N=4,155) No diabetes (N=13,537)

Years

Surv

ival

(%)

p < 0.0001

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2013

Adult Heart TransplantsKaplan-Meier Survival by Recipient Cigarette History

(Transplants: July 2004 – June 2011)

0 1 2 3 4 5 6 750

60

70

80

90

100

Cigarette history (N = 6,393) No cigarette history (N = 7,332)

Years

Surv

ival

(%)

p = 0.2024

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2013

Adult Heart TransplantsKaplan-Meier Survival by Recipient COPD History


0 1 2 3 4 5 6 7 850

60

70

80

90

100

COPD (N = 576) No COPD (N = 14,565)

Years

Surv

ival

(%)

p = 0.7302

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2013

Adult Heart TransplantsKaplan-Meier Survival by VAD usage

(Transplants: April 1994 – June 2011)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 1430

40

50

60

70

80

90

100 Pulsatile flow (N=3,738) Continuous flow (N=2,139)

No LVAD / No Inotropes (N=13,352) No LVAD / Inotropes (N=15,365)

Years

Surv

ival

(%)

Pulsatile vs. Continuous: p=0.0127Pulsatile vs. No LVAD/No Inotropes: p = 0.0032No other pair-wise comparisons were significant at p < 0.05

JHLT. 2013 Oct; 32(10): 951-964

2013



0 1 2 3 4 5 6 750

60

70

80

90

100Pulsatile flow (N=2,201) Continuous flow (N=2,114)


Years

Surv

ival

(%)

Pulsatile vs. No LVAD/No Inotropes: p = 0.0077Pulsatile vs. No LVAD/Inotropes: p = 0.0061Continuous vs. No LVAD/Inotropes: p = 0.0229No other pair-wise comparisons were significant at p < 0.05

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsKaplan-Meier Survival by VAD usage Conditional on Survival

to 6 Months (Transplants: January 1999 – June 2011)

0 1 2 3 4 5 6 7 8 9 1050

60

70

80

90

100

Pulsatile flow (N=2,953) Continuous flow (N=1,896)


Years

Surv

ival

(%)

Continuous vs. No LVAD/No Inotropes: p = 0.0297No other pair-wise comparisons were significant at p < 0.05

JHLT. 2013 Oct; 32(10): 951-964

2013



0 1 2 3 4 5 650

60

70

80

90

100 LVAD Pulsatile (N=1,064) LVAD Continuous (N=1,967)LVAD+RVAD Pulsatile (N=408) No LVAD, No Inotropes (N=5,058)No LVAD, Inotropes (N=4,658)

Years

Surv

ival

(%)

All pair-wise comparisons with LVAD+RVAD Pulsatile were significant at p < 0.05 except LVAD Pulsatile vs. LVAD+RVAD PulsatileNo other pair-wise comparisons were significant at p < 0.05.

JHLT. 2013 Oct; 32(10): 951-964

2013

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

1001/1982-12/1992

1/1993-12/2002

1/2003-6/2011

1 Ye

ar P

atie

nt S

urvi

val (

%)

315

205

98

98 85 56

61 89 72 56 400

491

24,6

32

37,4

53

28,0

49

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 1/2003-6/2011: p < 0.0001

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsKaplan-Meier Survival by Employment Status at 1 Year

Conditional on Survival to 1 Year(1 Year Follow-ups: January 2000 – June 2011)

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

20

40

60

80

100

Working (N=4,418) Not Working (N=9,946)

Years

Surv

ival

(%)

p < 0.0001

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsCause of Death (Deaths: January 1994 – June 2012)

CAUSE OF DEATH 0-30 Days (N = 5,297)

31 Days – 1 Year

(N = 4,547)

>1 Year – 3 Years

(N = 3,307)

>3 Years – 5 Years

(N = 2,890)

>5 Years –10 Years

(N = 7,315)

>10 Years – 15 Years (N = 4,774)

>15 Years (N = 3,436)

Cardiac Allograft Vasculopathy 77 (1.5%) 172 (3.8%) 413 (12.5%) 406 (14.0%) 1,020 (13.9%) 675 (14.1%) 299 (12.3%)

Acute Rejection 251 (4.7%) 442 (9.7%) 334 (10.1%) 140 (4.8%) 139 (1.9%) 47 (1.0%) 17 (0.7%)

Lymphoma 3 (0.1%) 56 (1.2%) 78 (2.4%) 98 (3.4%) 275 (3.8%) 149 (3.1%) 69 (2.8%)

Malignancy, Other 4 (0.1%) 111 (2.4%) 408 (12.3%) 563 (19.5%) 1,542 (21.1%) 1,002 (21.0%) 459 (18.8%)

CMV 3 (0.1%) 51 (1.1%) 15 (0.5%) 6 (0.2%) 6 (0.1%) 3 (0.1%) 0

Infection, Non-CMV 690 (13.0%) 1,402 (30.8%) 412 (12.5%) 283 (9.8%) 781 (10.7%) 497 (10.4%) 277 (11.4%)

Graft Failure 2,063 (38.9%) 780 (17.2%) 845 (25.6%) 641 (22.2%) 1,323 (18.1%) 796 (16.7%) 405 (16.6%)

Technical 382 (7.2%) 72 (1.6%) 23 (0.7%) 25 (0.9%) 90 (1.2%) 61 (1.3%) 31 (1.3%)

Other 304 (5.7%) 319 (7.0%) 268 (8.1%) 227 (7.9%) 577 (7.9%) 326 (6.8%) 197 (8.1%)

Multiple Organ Failure 938 (17.7%) 688 (15.1%) 198 (6.0%) 179 (6.2%) 505 (6.9%) 385 (8.1%) 230 (9.4%)

Renal Failure 29 (0.5%) 45 (1.0%) 48 (1.5%) 91 (3.1%) 414 (5.7%) 396 (8.3%) 221 (9.1%)

Pulmonary 160 (3.0%) 176 (3.9%) 134 (4.1%) 130 (4.5%) 313 (4.3%) 195 (4.1%) 108 (4.4%)

Cerebrovascular 393 (7.4%) 233 (5.1%) 131 (4.0%) 101 (3.5%) 330 (4.5%) 242 (5.1%) 123 (5.0%)

Total N of Deaths 5,985 5,147 3,955 3,528 9,025 6,139 3,186

Percentages represent % of deaths in the respective time period. Total number of deaths includes deaths with unknown causes.JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants Cause of Death from Leading Causes by Time since

Transplant and Era (Deaths: January 1994 – June 2012)

0-30 Days (N=2,830)

31 Days - 1 Year

(N=2,327)

>1 Year - 3 Years

(N=1,740)

>3 Years - 5 Years (N=1,490)

>5 Years - 10

Years (N=3,397)

>10 Years

(N=1,142)

0-30 Days (N=2,467)

31 Days - 1 Year

(N=2,220)

>1 Year - 3 Years

(N=1,567)

>3 Years - 5 Years (N=1,400)

>5 Years - 10

Years (N=3,918)

>10 Years

(N=6,068)

0

10

20

30

40

50

60

70

80

90

100

2 515 18 18 20

1 310 10 11 125

11

9 4 2 1

48

11 5 2 1

4117

2419

18 1436

17

2725

19 17

1

1

13

6 8 0

1

23

6 9

1433

128 9 9 12

29

1311

12 11

04 17

25 26 24

03

1220

24 23

CAV Acute Rejection Graft Failure Renal FailureInfection (Non-CMV) Malignancy

% o

f Dea

ths

Deaths 1994 – 2001 Deaths 2002 – 6/2012

Since only leading causes of death are shown, sum of percentages for each time period is less than 100%

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants Relative Incidence of Leading Causes of Death

(Deaths: January 1994 – June 2012)

0-30 Days (N=5,297)

31 Days – 1 Year

(N=4,547)

>1 Year – 3 Years

(N=3,307)


(N=2,890)


(N=7,315)

>10 – 15 Years

(N=4,774)

>15 Years (N=2,436)

0

10

20

30

40

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

% o

f Dea

ths


JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsCumulative 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 RejectionMalignancy (non-Lymph/PTLD) Graft FailureInfection

Years

Inci

denc

e of

Cau

se-S

peci

fic

Dea

ths

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants Relative Incidence of Leading Causes of Death

(Deaths: January 2006 – June 2012)

0-30 Days (N=1,427)

31 Days – 1 Year

(N=1,380)

>1 Year – 3 Years

(N=962)


(N=773)


(N=2,148)

>10 – 15 Years

(N=2,232)

>15 Years (N=1,857)

0

10

20

30

40

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

% o

f Dea

ths


JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants Cumulative Incidence of Leading Causes of Death


0 1 2 3 4 5 6

-2%

0%

2%

4%

6%

8%


Years

Inci

denc

e of

Cau

se-S

peci

fic

Dea

ths

JHLT. 2013 Oct; 32(10): 951-964

2013

Induction: slides 63-66 and 75-76 Maintenance: slides 67-72 and 77-78 Rejection: slides 73-80

Immunosuppression:

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsInduction Immunosuppression


0

10

20

30

40

50

60

% o

f pat

ient

s

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

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsInduction Immunosuppression by Location


Any Induction IL-2R Antagonist Polyclonal ALG/ATG0

10

20

30

40

50

60

Europe North America

% o

f pat

ient

s


JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsInduction Immunosuppression

(Transplants: 2002, 2007 and 1/2012–6/2012)

Any Induction IL-2R Antag-onist

Polyclonal ALG/ATG

OKT3 Alemtuzumab0

10

20

30

40

50

60

2002 2007 1/2012-6/2012

% o

f pat

ient

s


JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsKaplan-Meier Survival by Induction Type

Conditional on Survival to 14 Days(Transplants: January 2001 – June 2011)

0 1 2 3 4 5 6 7 8 950

60

70

80

90

100

No induction (N = 10,021) Polyclonal induction (N = 4,533)IL-2R antagonist (N = 5,041) OKT3 (N = 494)

Years

Surv

ival

(%)

No induction vs. IL-2R: p = 0.0031Polyclonal vs. IL-2R: p = 0.0303No other pair-wise comparisons were significant at p < 0.05

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsMaintenance Immunosuppression at Time of Follow-up

(Follow-ups: January 2008 – June 2012)

Cyclosporine Tacrolimus Sirolimus/ Everolimus

MMF/MPA Azathioprine Prednisone0

20

40

60

80

100

Year 1 (N = 7,804) Year 5 (N = 4,821)

% o

f pat

ient

s

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

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

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants Maintenance Immunosuppression at Time of 1 Year

Follow-up by Year

Cy-closporine

Tacrolimus Sirolimus/ Everolimus


20

40

60

80

100 2000 (N = 1,563) 2005 (N = 2,808) 1/2012-6/2012 (N = 1,477)

% o

f pat

ient

s


NOTE: Different patients are analyzed in each time frame

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants Maintenance Immunosuppression Drug Combinations at

Time of Follow-up (Follow-ups: January 2006 – June 2012)

0%

20%

40%

60%

80%

100%

Year 1 (N = 11,102)

Year 5 (N = 7,264)

None

Other

Sirolimus/Everolimus +calcineurin+cellcycle

Tacrolimus Alone

Cyclosporine Alone

Sirolimus/Everolimus + cellcycle

Sirolimus/Everolimus + calcineurin

Tacrolimus + MMF/MPA

Tacrolimus + AZA

Cyclosporine + MMF/MPA

Cyclosporine + AZA

% o

f Pat

ient

s


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

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants Maintenance Immunosuppression Drug Combinations at

Time of Follow-up (Follow-ups: January 2001 – June 2012) For the Same Patients at Year 1 and 5

0%

20%

40%

60%

80%

100%

Year 1 (N = 8,395)

Year 5 (N = 8,395)

None

Other


Tacrolimus Alone

Cyclosporine Alone




Tacrolimus + AZA


Cyclosporine + AZA

% o

f Pat

ient

s


JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants Maintenance Immunosuppression Drug Combinations at Time

of Follow-up by Location (Follow-ups: January 2006 – June 2012)

0%

20%

40%

60%

80%

100%None

Other


Tacrolimus Alone

Cyclosporine Alone




Tacrolimus + AZA


Cyclosporine + AZA

% o

f Pat

ient

s

Europe EuropeNorth America

North America


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

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsKaplan-Meier Survival by Maintenance Immunosuppression

at 1 year (Transplants: January 2001 – June 2011) Conditional on Survival to 1 Year

0 1 2 3 4 5 6 7 8 950

60

70

80

90

100

Cyclosporine + MMF/MPA (N = 4,428)

Tacrolimus + MMF/MPA (N = 8,646)

Years

Surv

ival

(%)

p = 0.1388

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants % of Recipients Experiencing Treated Rejection Between

Transplant Discharge and 1-Year Follow-Up by Year

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.

2004 2005 2006 2007 2008 2009 20100

10

20

30

40

50

60

% o

f pat

ient

s


JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants % of Recipients Experiencing Any Rejection Between Transplant Discharge and 1-Year Follow-Up by Year

2004 2005 2006 2007 2008 2009 20100

10

20

30

40

50

60

% o

f pat

ient

s


Any rejection = Recipient was reported to (1) have at least one acute rejection episode; or (2) have been hospitalized for rejection.JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants % of Recipients Experiencing Treated Rejection between

Transplant Discharge and 1-Year Follow-Up by Type of Induction(Follow-ups: January 2005 – June 2012)

Overall Female Male0

10

20

30

40

50No induction (N=6,145) Polyclonal (N=2,530)IL-2R antagonist (N=3,563) OKT3 (N=168)

No induction vs. IL-2R (Overall and Male), no induction vs. OKT3 (Overall and Male) and Polyclonal vs. OKT3 (Overall) were significant at p < 0.05. No other pair-wise comparisons were significant at p < 0.05.

% e

xper

ienc

ing

treat

ed re

ject

ion

with

in 1

yea

r

Analysis is limited to patients who were alive at the time of the follow-up 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.JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants % of Recipients Experiencing Any Rejection between Transplant

Discharge and 1-Year Follow-Up by Type of Induction(Follow-ups: January 2005 – June 2012)


10

20

30

40

50No induction (N=6,145) Polyclonal (N=2,530)IL-2R antagonist (N=3,563) OKT3 (N=168)

No induction vs. IL-2R (Overall, Female and Male), no induction vs. OKT3 (Overall) and Polyclonal vs. IL-2R (Overall and Male) were significant at p < 0.05. No other pair-wise comparisons were significant at p < 0.05.

% e

xper

ienc

ing

reje

ctio

n w

ithin

1

year



2013


Transplant Discharge and 1-Year Follow-Up by Maintenance Immunosuppression (Follow-ups: January 2005 – June 2012)


10

20

30

40

50

Cyclosporine + MMF/MPA (N=3,115) Tacrolimus + MMF/MPA (N=7,999)

All pair-wise comparisons between maintenance immunosuppression groups were significant at p < 0.05

% e

xper

ienc

ing

treat

ed re

ject

ion

with

in 1

yea

r



2013


Discharge and 1-Year Follow-Up by Maintenance Immunosuppression (Follow-ups: January 2005 – June 2012)


10

20

30

40

50


All pair-wise comparisons between maintenance immunosuppression groups were significant at p < 0.05

% e

xper

ienc

ing

reje

ctio

n w

ithin

1

year



2013

Adult Heart TransplantsKaplan-Meier Survival by Treatment for Rejection Within 1st

Year (1 Year Follow-ups: January 2005 – June 2011) Conditional on survival to 1 year

0 1 2 3 4 5 650

60

70

80

90

100

No Rejection (N=6,396) Untreated Rejection (N=1,232)

Treated Rejection (N=2,420)

Years

Surv

ival

(%)

All pair-wise comparisons were significant at p < 0.0001 except No rejection vs. Untreated rejection (p = 0.8528)

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.JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Hospitalization for Rejection by Era


0 1 2 3 40

10

20

30

40

50

60

70

80

90

100

4/1994-1999 (N = 4,109) 2000-2004 (N = 3,647)

2005-6/2011 (N = 4,742)

Years

% F

reed

om fr

om h

ospi

taliz

atio

n fo

r re

ject

ion

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

JHLT. 2013 Oct; 32(10): 951-964

2013

Functional status: slide 82 Employment: slides 83-84 Hospitalization: slide 85 CAV: slides 86-93 Renal dysfunction: slides 86-88 and 94-96 Malignancy: slides 97-106

Morbidity:

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFunctional Status of Surviving Recipients by Karnofsky

Score (Follow-ups: January 2006 – June 2012)

0%

20%

40%

60%

80%

100%

1 Year(N = 10,532)

2 Years(N = 8,674)

3 Years(N = 7,521)

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsEmployment Status of Surviving Recipients


0%

20%

40%

60%

80%

100%

1 Year(N = 16,112)

3 Years(N = 14,081)

5 Years(N = 12,447)

Retired

Not Working

Working Part Time

Working Full Time

Working (FT/PT status unknown)

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsEmployment Status of Surviving Recipients

Age at Follow-up: 25-60 Years (Follow-ups: January 2000 – June 2012)

0%

20%

40%

60%

80%

100%

1 Year(N = 9,857)

3 Years(N = 7,717)

5 Years(N = 6,007)

Retired

Not Working

Working Part Time

Working Full Time

Working (FT/PT status unknown)

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsRehospitalization Post-transplant of Surviving Recipients


0%

20%

40%

60%

80%

100%

Up to 1 Year(N = 21,679)

Between 2 and 3 Years (N =

18,377)

Between 4 and 5 Years (N =

16,289)

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

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsCumulative Morbidity Rates in Survivors within 1, 5 and 10

Years Post-Transplant (Follow-ups: January 1995 – June 2012)

Outcome Within 1 Year

Total N with known

response

Within 5 Years

Total N with known

responseWithin

10 YearsTotal N

with known response

Hypertension* 72.3% (N = 26,852) 92.2% (N = 12,534) -

Renal Dysfunction 26.3% (N = 29,301) 52.5% (N = 14,680) 68.4% (N = 4,879)

Abnormal Creatinine ≤ 2.5 mg/dl 18.1% 33.3% 38.3%

Creatinine > 2.5 mg/dl 6.4% 15.1% 20.5%

Chronic Dialysis 1.5% 2.9% 6.0%

Renal Transplant 0.3% 1.2% 3.6%

Hyperlipidemia* 60.0% (N = 28,102) 87.8% (N = 13,876) -

Diabetes* 25.7% (N = 29,289) 38.1% (N = 14,470) -

Cardiac Allograft Vasculopathy 7.8% (N = 26,480) 30.2% (N = 10,651) 50.1% (N = 2,815)

* Data are not available 10 years post transplant

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsCumulative Morbidity Rates in Survivors within 1, 5 and 10

Years Post-Transplant (Follow-ups: January 1995 – June 2002) For the Same Patients


Total N with known

response

Within 5 Years

Total N with known

responseWithin

10 YearsTotal N

with known response

Renal Dysfunction 22.8% (N = 2,233) 49.4% (N = 2,233) 65.9% (N = 2,233)

Abnormal Creatinine ≤ 2.5 mg/dl 16.5% 34.6% 40.3%

Creatinine > 2.5 mg/dl 6.0% 13.0% 17.9%

Chronic Dialysis 0.1% 0.9% 4.3%

Renal Transplant 0.2% 0.9% 3.4%

Cardiac Allograft Vasculopathy 6.8% (N = 2,233) 29.6% (N = 2,233) 49.0% (N = 2,233)

Only patients with known responses reported on every annual follow-up through the 10-year follow-up were included.

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsCumulative Morbidity Rates in Survivors within 1 and 5 Years

Post-Transplant (Follow-ups: January 2001 – June 2007) For the Same Patients


Total N with known

responseWithin 5 Years

Total N with known

response

Hypertension 73.2% (N = 3,439) 88.5% (N = 3,439)

Renal Dysfunction 26.4% (N = 3,439) 50.1% (N = 3,439)

Abnormal Creatinine ≤ 2.5 mg/dl 22.2% 37.7%

Creatinine > 2.5 mg/dl 3.5% 9.5%

Chronic Dialysis 0.5% 1.9%

Renal Transplant 0.3% 1.0%

Hyperlipidemia 72.6% (N = 3,439) 89.5% (N = 3,439)

Diabetes 29.7% (N = 3,439) 40.6% (N = 3,439)

Cardiac Allograft Vasculopathy 5.7% (N = 3,439) 27.0% (N = 3,439)

Only patients with known responses reported on every annual follow-up through the 5-year follow-up were included.

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Cardiac Allograft Vasculopathy by Era


0 1 2 3 4 5 6 7 8 9 100

20

40

60

80

100

Freedom from CAV 4/1994-2002 (N = 12,984)

Years

% F

reed

om fr

om C

AV

p < 0.0001

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Cardiac Allograft Vasculopathy by Ischemia

Time (Transplants: April 1994 – June 2011)

0 1 2 3 4 5 6 7 8 9 10 11 12 130

20

40

60

80

100

<2 hours (N = 3,440)

2-<4 hours (N = 16,896)

4+ hours (N = 4,451)

Years

% F

reed

om fr

om C

AV

p = 0.2240

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Cardiac Allograft Vasculopathy by Gender


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

20

40

60

80

100

Male (N = 20,031)

Female (N = 6,078)

Years

% F

reed

om fr

om C

AV

p < 0.0001

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsSurvival After Report of CAV Within 3 Years of Transplant and

Survival In Patients Without CAV*(Transplants: 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

No CAV (N = 19,138) CAV (N = 4,544)

Time after Report of CAV* (Years)

Surv

ival

(%)

p < 0.0001

* Patient survival for those without CAV within 3 years after transplant was conditioned on survival to median time of CAV development (512 days). Median time to CAV development is based on patients who developed CAV within 3 years of transplant.JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsSurvival After Report of CAV Within 3 Years of Transplant and

Survival In Patients Without CAV* by Era(Transplants: April 1994 – June 2011)

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 = 9,851) CAV 4/1994-2002 (N = 2,437)

No CAV 2003-6/2011 (N = 9,287) CAV 2003-6/2011 (N = 2,107)

Time after Report of CAV* (Years)

Surv

ival

(%)

4/1994-2002: No CAV vs. CAV p < 0.00012003-6/2011: No CAV vs. CAV p < 0.0001No CAV: 4/1994-2002 vs. 2003-6/2011 p = 0.9999CAV: 4/1994-2002 vs. 2003-6/2011 p = 0.0028

* Patient survival for those without CAV within 3 years after transplant was conditioned on survival to median time of CAV development (512 days). Median time to CAV development is based on patients who developed CAV within 3 years of transplant.JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Severe Renal Dysfunction by Era*


0 1 2 3 4 5 6 7 8 9 100

20

40

60

80

100

4/1994-2002 (N = 14,469)2003-6/2011 (N = 14,414)

Years

% F

reed

om fr

om S

ever

e R

enal

Dys

-fu

nctio

n

p < 0.0001

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

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Severe Renal Dysfunction* Stratified by

Ischemia Time (Transplants: April 1994 – June 2011)

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

20

40

60

80

100

<2 hours (N = 3,847)2-<4 hours (N = 18,614)4+ hours (N = 4,881)

Years

% F

reed

om fr

om S

ever

e R

enal

D

ysfu

nctio

n

p = 0.6270


JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsKaplan-Meier Survival by Renal Dysfunction Within 1st Year

Conditional on Survival to 1 Year (1 year 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

No Renal Dysfunction (N=19,564)

Years

Surv

ival

(%)


p < 0.0001

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants Post Transplant Malignancy (Follow-ups: April 1994 – June 2012)

Cumulative Morbidity Rates in Survivors

Malignancy/Type 1-Year Survivors

5-Year Survivors

10-Year Survivors

No Malignancy 30,892 (97.4%) 13,813 (85.9%) 4,073 (72.1%)

Malignancy (all types combined) 827 (2.6%) 2,264 (14.1%) 1,578 (27.9%)

Malignancy Type*

Skin 409 (1.3%) 1,493 (9.3%) 1,119 (19.8%)

Lymphoma 170 (0.5%) 174 (1.1%) 102 (1.8%)

Other 190 (0.6%) 667 (4.1%) 496 (8.8%)

Type Not Reported 58 (0.2%) 46 (0.3%) 18 (0.3%)

* 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.

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Malignancy by Type

(Follow-ups: April 1994 – June 2012)

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

20

40

60

80

100

Any malignancy Lymphoma Skin Other

Years

% F

ree

from

Mal

igna

ncy

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Malignancy by Maintenance

Immunosuppression Combinations at DischargeConditional on Survival to 14 days (Transplants: January 2001 – June 2011)

0 1 2 3 4 5 6 7 8 950

60

70

80

90

100

Tacrolimus+MMF/MPA Cyclosporine+MMF/MPA

Cyclosporine+AZA

Years

% F

ree

from

Mal

igna

ncy

p = 0.0027

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Malignancy by Era


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

60

70

80

90

100

4/1994-2002 2003-6/2011

Years

% F

ree

from

Mal

igna

ncy

p < 0.0001

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Malignancy by Era and Gender


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

60

70

80

90

100

Male 4/1994-2002 Male 2003-6/2011

Female 4/1994-2002 Female 2003-6/2011

Years

% F

ree

from

Mal

igna

ncy

All pair-wise comparisons were significant at p < 0.05 except Female 4/1994-202 vs. Female 2003-06/2011

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Skin Malignancy by Era


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

60

70

80

90

100

4/1994-2002 2003-6/2011

Years

% F

ree

from

Ski

n M

alig

nanc

y

p < 0.0001

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Lymphoma by Era


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

60

70

80

90

100

4/1994-2002 2003-6/2011

Years

% F

ree

from

Lym

phom

a

p < 0.0001

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsFreedom from Other* Malignancy by Era


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

60

70

80

90

100

4/1994-2002 2003-6/2011

Years

% F

ree

from

Oth

er M

alig

nanc

y

p < 0.0001

* Other malignancy includes all types of malignancy except skin and lymphoma

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsSurvival After Report of Malignancy Within 3 Years of

Transplant and Survival In Patients Without Malignancy* (Transplants: 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

No Malignancy (N = 23,584)Malignancy (N = 1,678)

Years

Surv

ival

(%)

p < 0.0001

* Patient survival for those without malignancy within 3 years after transplant was conditioned on survival to median time of malignancy development (545 days). Median time to malignancy development is based on patients who developed malignancy within 3 years of transplant.JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsSurvival After Report of Skin Malignancy or Lymphoma Within 3

Years of Transplant and Survival In Patients Without Malignancy* (Transplants: April 1994 – June 2011)

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

20

40

60

80

100No Malignancy (N = 23,584)Skin Malignancy (N = 838)Lymphoma (N = 678)

Years

Surv

ival

(%)

All pair-wise comparisons were significant at p < 0.0001

* Patient survival for those without malignancy within 3 years after transplant was conditioned on survival to median time of malignancy development (545 days). Median time to malignancy development is based on patients who developed malignancy within 3 years of transplant.JHLT. 2013 Oct; 32(10): 951-964

2013

1 year mortality: slides 108-122 5 year mortality: slides 123-135 5 year mortality conditional on survival to 1 year: slides 136-

145 10 year mortality: slides 146-155 15 year mortality: slides 156-165 20 year mortality: slides 166-170 Developing severe renal dysfunction within 1 year: slides

171-175 Developing severe renal dysfunction within 5 years: slides

176-182 Developing non-skin malignancy within 8 years: slides 183-

189 Developing CAV within 5 years: slides 190-195

Multivariable Analyses:

JHLT. 2013 Oct; 32(10): 951-964

2013

ADULT HEART TRANSPLANTS (2006-6/2011)Risk Factors For 1 Year Mortality

VARIABLE N Hazard Ratio

P-value 95% Confidence Interval

Temporary circulatory support* 163 2.80 <.0001 2.04-3.83

Total artificial heart 98 2.26 0.0004 1.43-3.55

Diagnosis: Congenital vs. cardiomyopathy 266 2.21 <.0001 1.62-3.02

Recipient history of dialysis 274 1.78 <.0001 1.39-2.28Recipient on ventilator at time of transplant 302 1.66 0.0001 1.29-2.15

Chronic pulsatile flow device 952 1.56 <.0001 1.27-1.92

Chronic continuous flow device 1846 1.50 <.0001 1.24-1.81

Previous transplant 311 1.46 0.0125 1.08-1.96

N = 10,473* Temporary circulatory support includes ECMO and temporary pulsatile flow devices.

JHLT. 2013 Oct; 32(10): 951-964

2013

ADULT HEART TRANSPLANTS (2006-6/2011)Risk Factors For 1 Year Mortality (continued)

VARIABLEN Hazard

RatioP-value 95% Confidence

Interval

Male recipient/female donor vs. male recipient/male donor 1569 1.32 0.0009 1.12-1.55

Recipient with infection requiring IV drug therapy within 2 weeks prior to transplant 1063 1.28 0.0043 1.08-1.52

Previous transfusion 2268 1.25 0.0034 1.08-1.45

Not hospitalized just prior to transplant 5742 0.87 0.0372 0.77-0.99

Ventricular remodeling 1835 0.80 0.0107 0.67-0.95

Transplant year: 2006 vs. 2010/2011 1913 1.40 0.0002 1.17-1.68



N = 10,473* Temporary circulatory support includes ECMO and temporary pulsatile flow devices.

JHLT. 2013 Oct; 32(10): 951-964

2013


Continuous Factors (see figures)

Recipient age Ischemia time

Recipient height Recipient pre-transplant bilirubin

BMI ratio Recipient pre-transplant creatinine

Donor age PRA Class II

Transplant center volume Recipient pulmonary artery systolic pressure

JHLT. 2013 Oct; 32(10): 951-964

2013

ADULT HEART TRANSPLANTS (2006-6/2011)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)

Haz

ard

Rat

io o

f 1 Y

ear M

orta

lity p < 0.0001

(N = 10,473)JHLT. 2013 Oct; 32(10): 951-964

2013

20 25 30 35 40 45 50 55 60 650.0

0.5

1.0

1.5

2.0

2.5

1 year mortality (2006-6/2011) 5 year mortality (2002-6/2007)



Haz

ard

Rat

io o

f Mor

talit

y

p-values for recipient age were < 0.001 in all mortality models

ADULT HEART TRANSPLANTSRisk Factors For 1, 5, 10 and 20 Year Mortality

Recipient Age

JHLT. 2013 Oct; 32(10): 951-964

2013


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)

Haz

ard

Rat

io o

f 1 Y

ear M

orta

lity p < 0.0001

(N = 10,473)JHLT. 2013 Oct; 32(10): 951-964

2013

15 20 25 30 35 40 45 50 550.0

0.5

1.0

1.5

2.0

2.5



Donor Age (years)

Haz

ard

Rat

io o

f Mor

talit

y

p-values for donor age were < 0.001 in all mortality models

ADULT HEART TRANSPLANTSRisk Factors For 1, 5, 10 and 20 Year Mortality

Donor Age

JHLT. 2013 Oct; 32(10): 951-964

2013


Recipient Height

150 160 170 180 190 2000.0

0.5

1.0

1.5

2.0

2.5

Recipient Height (cm)

Haz

ard

Rat

io o

f 1 Y

ear M

orta

lity p = 0.0016

(N = 10,473)JHLT. 2013 Oct; 32(10): 951-964

2013


Donor BMI/Recipient BMI ratio

0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.50.0

0.5

1.0

1.5

2.0

Donor BMI/Recipient BMI

Haz

ard

Rat

io o

f 1 Y

ear M

orta

lity p = 0.0029

(N = 10,473)JHLT. 2013 Oct; 32(10): 951-964

2013


Ischemia Time

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)

Haz

ard

Rat

io o

f 1 Y

ear M

orta

lity p < 0.0001

(N = 10,473)JHLT. 2013 Oct; 32(10): 951-964

2013


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)

Haz

ard

Rat

io o

f 1 Y

ear M

orta

lity p = 0.0002

(N = 10,473)JHLT. 2013 Oct; 32(10): 951-964

2013


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

Recipient Bilirubin (mg/dL)

Haz

ard

Rat

io o

f 1 Y

ear M

orta

lity p < 0.0001

(N = 10,473)JHLT. 2013 Oct; 32(10): 951-964

2013


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)

Haz

ard

Rat

io o

f 1 Y

ear M

orta

lity p < 0.0001

(N = 10,473)JHLT. 2013 Oct; 32(10): 951-964

2013


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

Recipient PRA Class II (%)

Haz

ard

Rat

io o

f 1 Y

ear M

orta

lity p = 0.0188

(N = 10,473)JHLT. 2013 Oct; 32(10): 951-964

2013


Pulmonary Artery Systolic Pressure

15 25 35 45 55 65 750.0

0.5

1.0

1.5

2.0

PA Systolic Pressure

Haz

ard

Rat

io o

f 1 Y

ear M

orta

lity p = 0.0001

(N = 10,473)JHLT. 2013 Oct; 32(10): 951-964

2013


VARIABLEN Hazard


Interval

Temporary circulatory support* 160 2.23 <.0001 1.72-2.90Total artificial heart 37 1.77 0.0442 1.01-3.08

Continuous flow device or VAD with type unknown 349 1.71 0.0065 1.16-2.52

Recipient history of dialysis 326 1.70 <.0001 1.43-2.03Diagnosis: Congenital vs. cardiomyopathy 284 1.46 0.0012 1.16-1.83

Recipient on ventilator at time of transplant 301 1.37 0.0034 1.11-1.68

Female recipient with prior pregnancy/ male donor vs. male recipient/male donor 752 1.33 0.0017 1.11-1.58

PRA > 10% 685 1.25 0.003 1.08-1.45

N = 10,332

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

JHLT. 2013 Oct; 32(10): 951-964

2013




Recipient Hep B core (+) 404 1.22 0.0388 1.01-1.47Recipient with infection requiring IV drug therapy within 2 weeks prior to transplant

1117 1.22 0.0018 1.08-1.37

Number of HLA mismatches at A locus (per locus)

0 A MM (N=677) 1 A MM (N=4910)2 A MM (N=4745)

1.18 0.0196 1.03-1.35Donor cause of death: anoxia vs. head trauma 956 1.17 0.0243 1.02-1.33

Recipient history of diabetes 2275 1.15 0.0049 1.04-1.26

Chronic pulsatile flow device 1730 1.15 0.0213 1.02-1.29Diagnosis: coronary artery disease vs. cardiomyopathy 4587 1.12 0.0206 1.02-1.23

Ventricular remodeling 928 0.85 0.0415 0.73-0.99

N = 10,332JHLT. 2013 Oct; 32(10): 951-964

2013




Recipient height Recipient pre-transplant bilirubin

Recipient BMI Recipient pre-transplant creatinine

Donor age Recipient PVR

Donor BMI Recipient diastolic PA pressure

Transplant center volume

JHLT. 2013 Oct; 32(10): 951-964

2013


Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0

2.5


Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p < 0.0001

(N = 10,332)JHLT. 2013 Oct; 32(10): 951-964

2013


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)

Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p < 0.0001

(N = 10,332)JHLT. 2013 Oct; 32(10): 951-964

2013


Recipient Height

150 160 170 180 190 2000.0

0.5

1.0

1.5

2.0

2.5

Recipient Height (cm)

Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p = 0.0022

(N = 10,332)JHLT. 2013 Oct; 32(10): 951-964

2013


Recipient and Donor BMI

20 25 30 350.0

0.5

1.0

1.5

2.0

Recipient BMI Donor BMI

BMI (kg/m2)

Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity

Recipient BMI: p < 0.0001Donor BMI: p = 0.012

(N = 10,332)JHLT. 2013 Oct; 32(10): 951-964

2013


Ischemia Time

60 120 180 240 300 3600.0

0.5

1.0

1.5

2.0

2.5


Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p < 0.0001

(N = 10,332)JHLT. 2013 Oct; 32(10): 951-964

2013


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


Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p = 0.0018

(N = 10,332)JHLT. 2013 Oct; 32(10): 951-964

2013



0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.00.0

0.5

1.0

1.5

2.0


Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p = 0.0029

(N = 10,332)JHLT. 2013 Oct; 32(10): 951-964

2013



0.5 1.0 1.5 2.0 2.50.0

0.5

1.0

1.5

2.0

2.5


Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p < 0.0001

(N = 10,332)JHLT. 2013 Oct; 32(10): 951-964

2013


Pulmonary Vascular Resistance

1 2 3 4 5 6 70.0

0.5

1.0

1.5

2.0

PVR

Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p = 0.0002

(N = 10,332)JHLT. 2013 Oct; 32(10): 951-964

2013


Recipient Pulmonary Artery Diastolic Pressure

5 10 15 20 25 30 35 400.0

0.5

1.0

1.5

2.0

PA Diastolic (mm Hg)

Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p = 0.0112

(N = 10,332)JHLT. 2013 Oct; 32(10): 951-964

2013

ADULT HEART TRANSPLANTS (2002-6/2007)Risk Factors For 5 Year MortalityConditional on Survival to 1 Year



No Cyclo, TAC or Sirolimus at 1 year 136 2.02 <.0001 1.44-2.84

No AZA, MMF/MPA or Sirolimus at 1 year 415 1.75 <.0001 1.47-2.08

Rejection between discharge and 1st year 2153 1.65 <.0001 1.46-1.86

Polyclonal agent and IL-2R antagonist used for induction 113 1.57 0.0207 1.07-2.29

Recipient history of dialysis prior to transplant 220 1.44 0.0168 1.07-1.95

Recipient Hep B core (+) and Hep B surface antigen not positive 317 1.40 0.0115 1.08-1.83

Dialysis prior to discharge 531 1.35 0.006 1.09-1.67

Female recipient with prior pregnancy/ male donor vs. male recipient/male donor 635 1.32 0.03 1.03-1.68

N = 8,873

JHLT. 2013 Oct; 32(10): 951-964

2013


Conditional on Survival to 1 Year (continued)

VARIABLEN Hazard


IntervalDonor cause of death: anoxia vs. head trauma 811 1.26 0.0134 1.05-1.52

Treated for infection prior to discharge 1879 1.24 0.002 1.08-1.42IL-2R antagonist used for induction (no polyclonal agent) 2254 1.19 0.0104 1.04-1.36

Recipient history of diabetes 1930 1.17 0.0268 1.02-1.34

2 mismatches at the A locus 4061 1.16 0.0111 1.03-1.30

Defibrillator prior to transplant 5221 0.89 0.0489 0.78-1.00Ventricular remodeling prior to transplant 799 0.79 0.0467 0.63-1.00

AZA vs. MMF/MPA 442 0.67 0.0174 0.490.93

N = 8,873JHLT. 2013 Oct; 32(10): 951-964

2013

ADULT HEART TRANSPLANTS (2002-6/2007)Risk Factors For 5 Year MortalityConditional on Survival to 1 Year


Recipient age Recipient pre-transplant creatinine

Recipient height Donor/recipient height ratio

Recipient BMI Recipient TPG

Donor age

JHLT. 2013 Oct; 32(10): 951-964

2013


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


Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity

p < 0.0001

(N = 8,873)JHLT. 2013 Oct; 32(10): 951-964

2013


Conditional on Survival to 1 Year Recipient Height

150 160 170 180 1900.0

0.5

1.0

1.5

2.0

Recipient height (cm)

Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p = 0.0134

(N = 8,873)JHLT. 2013 Oct; 32(10): 951-964

2013


Conditional on Survival to 1 Year Recipient BMI

20 25 30 350.0

0.5

1.0

1.5

2.0

Recipient BMI (kg/m2)

Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p = 0.048

(N = 8,873)JHLT. 2013 Oct; 32(10): 951-964

2013


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

Donor Age (years)

Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p = 0.0087

(N = 8,873)JHLT. 2013 Oct; 32(10): 951-964

2013


Conditional on Survival to 1 Year Donor Height/Recipient Height Ratio

0.9 1.0 1.0 1.1 1.10.0

0.5

1.0

1.5

2.0

Donor Height/Recipient Height Ratio

Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity

P = 0.0300

(N = 8,873)JHLT. 2013 Oct; 32(10): 951-964

2013


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


Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity P = 0.0496

(N = 8,873)JHLT. 2013 Oct; 32(10): 951-964

2013


Conditional on Survival to 1 Year Transpulmonary Pressure Gradient

3 6 9 12 150.0

0.5

1.0

1.5

2.0

TPG

Haz

ard

Rat

io o

f 5 Y

ear M

orta

lity p = 0.0025

(N = 8,873)JHLT. 2013 Oct; 32(10): 951-964

2013


VARIABLEN Hazard


Interval

ECMO 32 2.18 0.0003 1.43-3.33

Ventilator at time of transplant 353 1.65 <.0001 1.42-1.91

Recipient on dialysis 259 1.45 <.0001 1.23-1.72

Repeat transplant 283 1.42 <.0001 1.19-1.68

Recipient history of diabetes 2037 1.31 <.0001 1.22-1.41

PRA > 20% 610 1.30 <.0001 1.16-1.46

Female recipient with prior pregnancy 1645 1.29 <.0001 1.18-1.41

Diagnosis: congenital vs. CM 235 1.28 0.0233 1.03-1.58

Transplant year: 1997 vs. 2001/2002 2064 1.20 <.0001 1.09-1.31

N = 11,531JHLT. 2013 Oct; 32(10): 951-964

2013


VARIABLEN Hazard


Interval

Year of transplant: 1998 vs. 2001/2002 2163 1.19 0.0001 1.09-1.30

Prior cerebrovascular event 627 1.17 0.0091 1.04-1.31

Diagnosis: coronary artery disease vs. CM 5699 1.16 <.0001 1.09-1.24



Donor history of hypertension 1314 1.11 0.0189 1.02-1.22

On VAD at time of transplant 1811 1.11 0.0115 1.02-1.20

Not hospitalized at transplant 4666 0.93 0.0269 0.88-0.99

0-4 HLA mismatches (A + B + DR) vs. 5-6 3963 0.87 <.0001 0.82-0.93

N = 11,531JHLT. 2013 Oct; 32(10): 951-964

2013




Recipient weight Recipient pre-transplant bilirubin

Donor age Recipient pre-transplant creatinine


JHLT. 2013 Oct; 32(10): 951-964

2013


Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0

2.5


Haz

ard

Rat

io o

f 10

Year

Mor

talit

y p < 0.0001

(N = 11,531)JHLT. 2013 Oct; 32(10): 951-964

2013


Donor Age

15 20 25 30 35 40 45 50 55 600.0

0.5

1.0

1.5

2.0

Donor Age (years)

Haz

ard

Rat

io o

f 10

Year

Mor

talit

y p < 0.0001

(N = 11,531)JHLT. 2013 Oct; 32(10): 951-964

2013


Recipient Weight

50 60 70 80 90 100 110 120 1300.0

0.5

1.0

1.5

2.0

Recipient Weight (kg)

Haz

ard

Rat

io o

f 10

Year

Mor

talit

y p = 0.0137

(N = 11,531)JHLT. 2013 Oct; 32(10): 951-964

2013


Ischemia Time

60 120 180 240 300 3600.0

0.5

1.0

1.5

2.0


Haz

ard

Rat

io o

f 10

Year

Mor

talit

y p < 0.0001

(N = 11,531)JHLT. 2013 Oct; 32(10): 951-964

2013


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


Haz

ard

Rat

io o

f 10

Year

Mor

talit

y p < 0.0001

(N = 11,531)JHLT. 2013 Oct; 32(10): 951-964

2013



0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.00.0

0.5

1.0

1.5

2.0


Haz

ard

Rat

io o

f 10

Year

Mor

talit

y p = 0.0004

(N = 11,531)JHLT. 2013 Oct; 32(10): 951-964

2013



0.5 1.0 1.5 2.0 2.50.0

0.5

1.0

1.5

2.0

2.5


Haz

ard

Rat

io o

f 10

Year

Mor

talit

y p < 0.0001

(N = 11,531)JHLT. 2013 Oct; 32(10): 951-964

2013


VARIABLEN Hazard


Interval

Retransplant 268 1.67 <.0001 1.44-1.94

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

73 1.66 0.0006 1.25-2.22

On ventilator 338 1.33 <.0001 1.16-1.52

Recipient Hep B Core (+) 265 1.27 0.0024 1.09-1.47

PR A> 20% 534 1.21 0.0006 1.08-1.34


Female recipient/male donor vs. male recipient/male donor 1218 1.16 0.004 1.05-1.28

N = 11,055JHLT. 2013 Oct; 32(10): 951-964

2013


VARIABLEN Hazard


Interval

On VAD at transplant 777 1.16 0.0039 1.05-1.27

Diagnosis: Coronary artery disease vs. cardiomyopathy 5506 1.15 <.0001 1.09-1.22



2 mismatches at DR locus 6774 1.11 <.0001 1.06-1.17


N = 11,055JHLT. 2013 Oct; 32(10): 951-964

2013



Recipient age Transplant center volume

Difference in recipient and donor age Ischemia time

Recipient BMI Recipient pre-transplant creatinine

Donor height

JHLT. 2013 Oct; 32(10): 951-964

2013


Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0


Haz

ard

Rat

io o

f 15

Year

Mor

talit

y p < 0.0001

(N = 11,055)JHLT. 2013 Oct; 32(10): 951-964

2013


Donor Age – Recipient Age

-45 -40 -35 -30 -25 -20 -15 -10 -5 0 50.0

0.5

1.0

1.5

2.0

2.5

Difference in Donor Age and Recipient Age

Haz

ard

Rat

io o

f 15

Year

Mor

talit

y p < 0.0001

(N = 11,055)JHLT. 2013 Oct; 32(10): 951-964

2013


Recipient BMI

18 20 22 24 26 28 30 320.0

0.5

1.0

1.5

2.0


Haz

ard

Rat

io o

f 15

Year

Mor

talit

y p = 0.0002

(N = 11,055)JHLT. 2013 Oct; 32(10): 951-964

2013


Donor Height

150 160 170 180 1900.0

0.5

1.0

1.5

2.0

Donor Height (cm)

Haz

ard

Rat

io o

f 15

Year

Mor

talit

y p = 0.0461

(N = 11,055)JHLT. 2013 Oct; 32(10): 951-964

2013


Ischemia Time

60 120 180 240 300 3600.0

0.5

1.0

1.5

2.0


Haz

ard

Rat

io o

f 15

Year

Mor

talit

y p < 0.0001

(N = 11,055)JHLT. 2013 Oct; 32(10): 951-964

2013


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


Haz

ard

Rat

io o

f 15

Year

Mor

talit

y p = 0.0005

(N = 11,055)JHLT. 2013 Oct; 32(10): 951-964

2013



0.5 1.0 1.5 2.0 2.50.0

0.5

1.0

1.5

2.0


Haz

ard

Rat

io o

f 15

Year

Mor

talit

y p < 0.0001

(N = 11,055)JHLT. 2013 Oct; 32(10): 951-964

2013


VARIABLEN Hazard


Interval

Retransplant 334 2.27 <.0001 2.02-2.56

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

1196 1.22 <.0001 1.13-1.31



Diagnosis: Coronary artery disease vs. cardiomyopathy 8450 1.12 <.0001 1.07-1.16


Female recipient vs. male recipient 3106 0.94 0.0161 0.90-0.99

N = 18,951JHLT. 2013 Oct; 32(10): 951-964

2013



Recipient age Transplant center volume

Donor age

JHLT. 2013 Oct; 32(10): 951-964

2013


Recipient Age

20 25 30 35 40 45 50 55 60 650.0

0.5

1.0

1.5

2.0


Haz

ard

Rat

io o

f 20

Year

Mor

talit

y p < 0.0001

(N = 18,951)JHLT. 2013 Oct; 32(10): 951-964

2013


Donor Age

15 20 25 30 35 40 45 50 550.0

0.5

1.0

1.5

2.0

2.5

Donor Age (years)

Haz

ard

Rat

io o

f 20

Year

Mor

talit

y p < 0.0001

(N = 18,951)JHLT. 2013 Oct; 32(10): 951-964

2013


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


Haz

ard

Rat

io o

f 20

Year

Mor

talit

y p < 0.0001

(N = 18,951)JHLT. 2013 Oct; 32(10): 951-964

2013

ADULT HEART TRANSPLANTS (2006-6/2011)Risk Factors for Developing Severe Renal Dysfunction within 1 Year

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



Dialysis prior to discharge 470 4.56 <.0001 3.60-5.79Female recipient/female donor vs. male recipient/male donor 1126 2.07 <.0001 1.44-2.97

Infection requiring IV antibiotics within 2 weeks prior to transplant 823 1.56 0.0016 1.18-2.06

Rejection prior to discharge 808 1.48 0.0073 1.11-1.98

Cyclosporine vs. Tacrolimus at discharge 2487 1.47 0.0006 1.18-1.84

Post-transplant cardiac re-operation prior to discharge 772 1.47 0.0036 1.13-1.90

Ventilatory support at transplant 564 1.47 0.0262 1.05-2.06

Continuous chronic device 1591 1.44 0.0039 1.12-1.84


Hospitalized (inc. ICU) at transplant 3885 1.25 0.0277 1.02-1.53

Diagnosis: Valvular disease vs. cardiomyopathy 212 0.38 0.0335 0.16-0.93

N = 8,861 *Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis

JHLT. 2013 Oct; 32(10): 951-964

2013




Recipient age Recipient pre-transplant creatinine

Recipient BSA

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

JHLT. 2013 Oct; 32(10): 951-964

2013



Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0


Haz

ard

Rat

io o

f Ren

al D

ysfu

nctio

n w

ithin

1 Y

ear

p = 0.008

(N = 8,861)


JHLT. 2013 Oct; 32(10): 951-964

2013



Recipient BSA

1.5 1.6 1.7 1.8 1.9 2.0 2.1 2.2 2.30.0

0.5

1.0

1.5

2.0

2.5

Recipient BSA (m2)

Haz

ard

Rat

io o

f Ren

al D

ysfu

nctio

n w

ithin

1 Y

ear

p = 0.0103

(N = 8,861)


JHLT. 2013 Oct; 32(10): 951-964

2013




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


Haz

ard

Rat

io o

f Ren

al D

ysfu

nc-

tion

with

in 1

Yea

r

p < 0.0001

(N = 8,861)*Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis

JHLT. 2013 Oct; 32(10): 951-964

2013

ADULT HEART TRANSPLANTS (2002-6/2007)Risk Factors for Developing Severe Renal Dysfunction within 5 Years


VARIABLEN Hazard


Interval

Dialysis prior to discharge 431 2.55 <.0001 2.12-3.06

Multiple induction agents reported vs. none 147 1.78 0.0013 1.25-2.54


Continuous chronic device 251 1.43 0.0263 1.04-1.97

Female recipient 1921 1.39 0.0026 1.12-1.71



JHLT. 2013 Oct; 32(10): 951-964

2013


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

VARIABLEN Hazard


Interval

Pulsatile chronic device 1305 1.36 <.0001 1.17-1.58

Recipient history of diabetes 1803 1.35 <.0001 1.18-1.54

IL-2R antagonist used for induction 2103 1.3 0.0003 1.13-1.49

Cyclosporine vs. Tacrolimus at discharge 3895 1.25 0.0006 1.10-1.42


HLA mismatch (per mismatch) 1.07 0.0345 1.00-1.13


JHLT. 2013 Oct; 32(10): 951-964

2013




Recipient age Recipient pulmonary artery systolic pressure

Recipient weight Recipient pre-transplant creatinine


JHLT. 2013 Oct; 32(10): 951-964

2013



Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0


Haz

ard

Rat

io o

f Ren

al D

ysfu

nctio

n w

ithin

5 Y

ears

p = 0.0077

(N = 8,182)


JHLT. 2013 Oct; 32(10): 951-964

2013



Recipient Weight

50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 1250.0

0.5

1.0

1.5

2.0

Recipient weight (kg)

Haz

ard

Rat

io o

f Ren

al D

ysfu

nctio

n w

ithin

5 Y

ears

p = 0.0061

(N = 8,182)


JHLT. 2013 Oct; 32(10): 951-964

2013




0.5 1.0 1.5 2.0 2.50.0

1.0

2.0

3.0

4.0

5.0


Haz

ard

Rat

io o

f Ren

al D

ysfu

nc-

tion

with

in 5

Yea

rs

p < 0.0001


JHLT. 2013 Oct; 32(10): 951-964

2013



Recipient Pulmonary Artery Systolic Pressure

15 25 35 45 55 65 750.0

0.5

1.0

1.5

2.0

PA Systolic Pressure (mm Hg)

Haz

ard

Rat

io o

f Ren

al D

ysfu

nc-

tion

with

in 5

Yea

rs

p < 0.0001


JHLT. 2013 Oct; 32(10): 951-964

2013

ADULT HEART TRANSPLANTS (2000-6/2004)Risk Factors for Developing Non-Skin Malignancy within 8 Years

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

VARIABLEN Hazard


Interval

Multiple induction agents reported 97 2.38 0.0015 1.40-4.07

Donor history of cancer 84 1.95 0.0242 1.09-3.48

Female recipient/female donor vs. male recipient/male donor 608 1.87 0.0018 1.26-2.78

Pacemaker prior to discharge 178 1.81 0.0074 1.17-2.80



Implantable defibrillator prior to transplant 2178 1.28 0.0194 1.04-1.57

N = 5,179

JHLT. 2013 Oct; 32(10): 951-964

2013




Recipient age Recipient PVR

Ischemia time Recipient PA systolic


JHLT. 2013 Oct; 32(10): 951-964

2013



Recipient Age

20 30 40 50 60 700.0

0.5

1.0

1.5

2.0

2.5

3.0


Haz

ard

Rat

io o

f Non

-Ski

n M

a-lig

nanc

y w

ithin

8 Y

ears

p < 0.0001

(N = 5,179)JHLT. 2013 Oct; 32(10): 951-964

2013



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


Haz

ard

Rat

io o

f Non

-Ski

n M

a-lig

nanc

y w

ithin

8 Y

ears

p = 0.0409

(N = 5,179)JHLT. 2013 Oct; 32(10): 951-964

2013



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


Haz

ard

Rat

io o

f Non

-Ski

n M

a-lig

nanc

y w

ithin

8 Y

ears

p = 0.0007

(N = 5,179)JHLT. 2013 Oct; 32(10): 951-964

2013



Pulmonary Vascular Resistance

0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.50.0

0.5

1.0

1.5

2.0

2.5

3.0

Recipient PVR

Haz

ard

Rat

io o

f Non

-Ski

n M

a-lig

nanc

y w

ithin

8 Y

ears

p = 0.0109

(N = 5,179)JHLT. 2013 Oct; 32(10): 951-964

2013



Pre-Transplant PA Mean Pressure

15 20 25 30 35 40 45 500.0

0.5

1.0

1.5

2.0

Recipient PA Mean (mm Hg)

Haz

ard

Rat

io o

f Non

-Ski

n M

a-lig

nanc

y w

ithin

8 Y

ears

p = 0.036

(N = 5,179)JHLT. 2013 Oct; 32(10): 951-964

2013

ADULT HEART TRANSPLANTS (2002-6/2007)Risk Factors for Developing CAV within 5 YearsConditional on Survival to Transplant Discharge

VARIABLEN Hazard


Interval

OTK3 used for induction 239 1.90 <.0001 1.52-2.39

AZA vs. MMF/MPA at discharge 344 1.36 0.0038 1.11-1.68

Pacemaker prior to discharge 266 1.32 0.0201 1.04-1.67


Cyclosporine vs. Tacrolimus at discharge 3774 1.29 <.0001 1.16-1.42

Donor history of hypertension 877 1.19 0.0129 1.04-1.37

N = 7,778

JHLT. 2013 Oct; 32(10): 951-964

2013


(continued)

VARIABLEN Hazard


Interval

Female recipient/female donor with prior pregnancy vs. male recipient/male donor 581 0.80 0.0204 0.66-0.97


Recipient history of malignancy 354 0.75 0.0227 0.59-0.96

Female recipient without prior pregnancy/ female donor vs. male recipient/male donor 327 0.60 0.0003 0.46-0.79

Diagnosis: Congenital vs. cardiomyopathy 201 0.52 0.0015 0.35-0.78

N = 7,778

JHLT. 2013 Oct; 32(10): 951-964

2013



Recipient BMI Donor age

Donor/recipient BSA ratio

JHLT. 2013 Oct; 32(10): 951-964

2013


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


Haz

ard

Rat

io o

f CA

V w

ithin

5

Year

s

p = 0.0026

(N = 7,778)JHLT. 2013 Oct; 32(10): 951-964

2013


Donor BSA/Recipient BSA

0.8 0.9 1.0 1.1 1.20.0

0.5

1.0

1.5

2.0

Donor/Recipient BSA ratio

Haz

ard

Rat

io o

f CA

V w

ithin

5 Y

ears

p = 0.0108

(N = 7,778)JHLT. 2013 Oct; 32(10): 951-964

2013


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)

Haz

ard

Rat

io o

f CA

V w

ithin

5 Y

ears

p < 0.0001

(N = 7,778)JHLT. 2013 Oct; 32(10): 951-964

2013

2013 Focus Theme: Age Age distribution: slides 197-201 and 208 Recipient characteristics by age: slides 202-207 Age mismatch: slides 208-209 Survival by age: slides 210-217 Age and immunosuppression: slides 218-219 Age and complications: slides 220-229 Age and cause of death: slides 230-237

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsDonor and Recipient Age


18-39 40-59 60-69 70+0%

20%

40%

60%

80%

100%

0-10 11-17 18-39 40-59 60+

Recipient Age

% o

f Tra

nspl

ants

Donor Age:

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsDonor and Recipient Age


0-10 11-17 18-39 40-59 60+0%

20%

40%

60%

80%

100%

18-39 40-59 60-69 70+

Donor Age

% o

f Tra

nspl

ants

Recipient Age:

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsDiagnosis by Age Group


74%

10% 5%

7% 1%2%

18-39 years

55%

2%

2%

37%1%

3%

MyopathyCongenitalReTXCADMisc.Valvular

40-59 years

41%1%

2%

53%1%

3%

60-69 years

37%3%

57%0%

3%

70+ years

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsRecipient Age Distribution by Location



20%

40%

60%

80%

100%

18-39 40-59 60-69 70+

% o

f Rec

ipie

nts

Mean/median recipient age: Europe = 50.2/53.0 North America = 52.2/55.0 Other = 47.2/50.0

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsDonor Age Distribution by Location



20%

40%

60%

80%

100%0-10 11-17 18-39 40-59 60+

% o

f Don

ors

Mean/median donor age: Europe = 40.4/43.0 North America = 31.7/29.0 Other = 31.7/29.0

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsDonor and Recipient Characteristics by Recipient Age Group


18-39(N = 4,053)

40-59(N = 11,632)

60-69(N = 6,287)

70+(N = 346)

p-value

Donor age (years) 30.0 (16.0 - 53.0) 35.0 (17.0 - 56.0) 36.0 (17.0 - 58.0) 36.0 (18.0 - 59.0) <0.0001

Donor and recipient age difference (years) 2.0 (-18.0 - 25.0) -17.0 (-37.0 - 7.0) -28.0 (-47.0 - -5.0) -35.0 (-53.0 - -13.0) <0.0001

Recipient BMI 22.6 (18.2 - 34.3) 24.6 (20.1 - 34.6) 25.0 (20.3 - 33.7) 24.9 (20.1 - 32.0) <0.0001

Donor BMI 24.8 (19.4 - 35.9) 25.7 (20.0 - 36.5) 25.7 (20.1 - 36.6) 26.3 (21.0 - 37.9) <0.0001

Recipient/donor gender (% male) 65.5%/ 67.1% 76.5%/ 69.7% 81.0%/ 69.5% 89.9%/ 68.1% <0.0001/

0.0153Male recipient/ female donor 13.7% 16.4% 18.5% 25.5% <0.0001

Female recipient/ male donor 15.4% 9.7% 7.1% 3.8% <0.0001

Recipient prior cardiac surgery 38.7% 44.6% 52.9% 53.8% <0.0001


JHLT. 2013 Oct; 32(10): 951-964

2013


(Transplants: January 2006 – June 2012)18-39

(N = 4,053)40-59

(N = 11,632)60-69

(N = 6,287)70+

(N = 346)p-

value

Recipient previous malignancy 4.3% 5.3% 9.6% 11.0% <0.0001

Creatinine at time of transplant 1.0 (0.6 - 2.1) 1.2 (0.7 - 2.4) 1.3 (0.8 - 2.3) 1.3 (0.8 - 2.1) <0.0001

Pulmonary vascular resistance (Wood units) 2.0 (0.2 - 5.6) 2.1 (0.3 - 5.4) 2.1 (0.3 - 5.4) 2.1 (0.3 - 5.8) 0.0505

Diagnosis

Cardiomyopathy 74.3% 54.8% 40.5% 36.7% < 0.0001

Coronary artery disease 7.3% 37.4% 53.4% 57.1%

Valvular 1.7% 3.0% 3.3% 2.6%

Retransplant 5.3% 2.0% 1.6% 3.2%

Congenital 9.9% 1.9% 0.5% 0.0%

Other causes 1.4% 0.8% 0.6% 0.3%


(Cont’d)

JHLT. 2013 Oct; 32(10): 951-964

2013



18-39(N = 4,053)

40-59(N = 11,632)

60-69(N = 6,287)

70+(N = 346)

p-value

Pre-operative support (multiple items may be reported) Hospitalized at time of transplant 51.3% 44.2% 41.1% 39.7% <0.0001

On IV inotropes 45.6% 41.6% 42.1% 39.9% 0.0083

LVAD 29.7% 29.6% 26.6% 18.0% <0.0001

IABP 6.5% 6.5% 5.1% 7.5% 0.0214

RVAD 5.7% 4.0% 2.3% 1.3% <0.0001

Ventilator 3.5% 2.7% 2.3% 3.7% 0.0258

TAH 1.1% 1.1% 0.6% 0.0% 0.0140

ECMO 2.1% 1.1% 0.7% 0.0% <0.0001

(Cont’d)

JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsRecipient Age Distribution by Gender


18-39 40-59 60-69 70+0

10

20

30

40

50

60

Male (N = 16,950)

Female (N = 5,368)

Recipient age

% o

f tra

nspl

ants

p < 0.0001

JHLT. 2013 Oct; 32(10): 951-964

2013


by Year, Age Group and Device Type

18-39 40-59 60-69 18-39 40-59 60-690

10

20

30

40

50

TAHLVAD+RVADRVADLVAD

% o

f pat

ient

s

2006 2011


JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart Transplants Number of Combined Organ Transplants Reported

by Year, Age and Type of Transplant

18-39 40-59 60-69 70+ 18-39 40-59 60-69 70+0

20

40

60

80

Heart-Kidney Heart-Liver Heart-Kidney-Liver

Num

ber o

f tra

nspl

ants

2001 2011

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Adult Heart TransplantsDonor and Recipient Age (Transplants: January 2006 – June 2012)

15 20 25 30 35 40 45 50 55 60 65 70 75 800

10

20

30

40

50

60

70

80

Recipient Age

Don

or A

ge

R2 = 0.01, p < 0.0001JHLT. 2013 Oct; 32(10): 951-964

2013

Adult Heart TransplantsDonor and Recipient Age Difference (Transplants: January 2006 – June 2012)

18-39 40-59 60-69 70+0%

20%

40%

60%

80%

100%

<-30 -30 - <-20 -20 - <-10 -10 - <0 0+

Recipient Age

% o

f Tra

nspl

ants

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2013

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

18-39 (N=15,812) 40-59 (N=55,943)

60-69 (N=20,293) 70+ (N=652)

Years

Surv

ival

(%)

Median survival (years): 18-39=12.3; 40-59=10.5; 60-69=9.0; 70+=7.6

All pair-wise comparisons were significant at p < 0.01

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0 1 2 3 4 540

50

60

70

80

90

100

18-39 (N=3,455) 40-59 (N=9,937)

60-69 (N=5,234) 70+ (N=270)

Years

Surv

ival

(%)

No pair-wise comparisons were significant at p < 0.05 except18-39 vs. 60-69: p = 0.019940-59 vs. 60-69: p= 0.0013

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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=6,609) 30-59 (N=65,146)

60-64 (N=14,721) 65-69 (N=5,572)

70-74 (N=608) 75+ (N=44)

Years

Surv

ival

(%)

Median survival (years): 18-29=12.4; 30-59=10.7; 60-64=9.1; 65-69=8.7; 70-74=7.6; 75+=NA

No pair-wise comparisons with 75+ were significant at p < 0.05. All other pair-wise comparisons were significant at p < 0.05 except 60-64 vs. 65-69 and 65-69 vs. 70-74

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Adult Heart TransplantsKaplan-Meier Survival by Donor Age Group


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

20

40

60

80

100

0-10 (N=285) 11-39 (N=56,992)

40-59 (N=26,084) 60+ (N=1,109)

Years

Surv

ival

(%)

Median survival (years): 0-10=11.4; 11-39=11.3; 40-59=9.3; 60+=6.0

All pair-wise comparisons were significant at p < 0.05 except 0-10 vs. 11-39 and 0-10 vs. 40-59

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2013

Adult Heart TransplantsKaplan-Meier Survival by Donor and Recipient Age Difference Recipient Age = 18-39 years (Transplants: January 1982 – June 2011)

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

20

40

60

80

100

-30 - <-20 (N = 535) -20 - <-10 (N = 2,958)

-10 - <0 (N = 4,163) 0+ (N = 6,817)

Years

Surv

ival

(%)

All pair-wise comparisons with 0+ were significant at p < 0.05. No other pair-wise comparisons were significant at p < 0.05.

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

20

40

60

80

100

<-30 (N = 11,937) -30 - <-20 (N = 13,066)-20 - <-10 (N = 11,785) -10 - <0 (N = 9,823)0+ (N= 5,394)

Years

Surv

ival

(%)

All pair-wise comparisons were significant at p < 0.05 except <-30 vs. -30 - <-20 and -10 - <0 vs. 0+

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

20

40

60

80

100

<-30 (N = 9,668) -30 - <-20 (N = 4,201)-20 - <-10 (N = 4,277) -10 - <0 (N = 1,972)0+ (N= 212)

Years

Surv

ival

(%)

All pair-wise comparisons were significant at p < 0.05 except-30 - <-20 vs. -20 - <-10, -20 - <-10 vs. 0+ and -10 - <0 vs. 0+

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Adult Heart TransplantsKaplan-Meier Survival by Donor and Recipient Age Difference

Recipient Age = 70+ years (Transplants: January 1982 – June 2011)

0 1 2 3 4 5 6 7 8 90

20

40

60

80

100

<-30 (N = 400) -30 - <-20 (N = 154)

-20 - <-10 (N = 135)

Years

Surv

ival

(%)

No pair-wise comparisons were significant at p < 0.05 except<-10 vs. -30 - <-20

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Adult Heart TransplantsInduction Immunosuppression by Age Group


Any Induction IL-2R Antagonist Polyclonal OKT3 Alemtuzumab0

10

20

30

40

50

6018-39 (N = 2,572)40-59 (N = 7,472)60-69 (N = 4,390)70+ (N = 301)

% o

f pat

ient

s


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Adult Heart Transplants Maintenance Immunosuppression at Time of 1 Year

Follow-up by Age Group (Follow-ups: January 2006 – June 2012)

Cy-closporine

Tacrolimus Sirolimus/ Everolimus


20

40

60

80

10018-39 (N = 1,882) 40-59 (N = 5,734)60-69 (N = 3,288) 70+ (N = 208)

% o

f pat

ient

s


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2013


Transplant Discharge and 1-Year Follow-Up by Type of Induction(Follow-ups: January 2005 – June 2012)

Overall 18-39 40-59 60-69 70+0

10

20

30

40

50

No induction (N=6,145) Polyclonal (N=2,530) IL-2R antagonist (N=3,563)

No induction vs. IL-2R: Overall – p = 0.004 and 60-69 – p = 0.0157. No other pair-wise comparisons were significant at p < 0.05.

% e

xper

ienc

ing

treat

ed re

ject

ion

with

in 1

yea

r



2013


Discharge and 1-Year Follow-Up by Type of Induction(Follow-ups: January 2005 – June 2012)

Overall 18-39 40-59 60-69 70+0

10

20

30

40

50No induction (N=6,145) Polyclonal (N=2,530) IL-2R antagonist (N=3,563)

No induction vs. IL-2R pair-wise comparisons were significant at p < 0.05 for all groups except 18-39. Polyclonal vs. IL-2R Overall p = 0.0090. No other pair-wise comparisons were significant at p < 0.05.

% e

xper

ienc

ing

reje

ctio

n w

ithin

1

year


Any rejection = Recipient was reported to (1) have at least one acute rejection episode; or (2) have been hospitalized for rejection.

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Transplant Discharge and 1-Year Follow-Up by Maintenance Immunosuppression (Follow-ups: January 2005 – June 2012)

Overall 18-39 40-59 60-69 70+0

10

20

30

40

50


All pair-wise comparisons between maintenance immunosuppression groups were significant at p < 0.05 except for 70+

% e

xper

ienc

ing

treat

ed re

ject

ion

with

in 1

yea

r



2013


Discharge and 1-Year Follow-Up by Maintenance Immunosuppression (Follow-ups: January 2005 – June 2012)

Overall 18-39 40-59 60-69 70+0

10

20

30

40

50 Cyclosporine + MMF/MPA (N=3,115) Tacrolimus + MMF/MPA (N=7,999)

All pair-wise comparisons between maintenance immunosuppression groups were significant at p < 0.05 except 70+

% e

xper

ienc

ing

reje

ctio

n w

ithin

1

year


Any rejection = Recipient was reported to (1) have at least one acute rejection episode; or (2) have been hospitalized for rejection.

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Adult Heart TransplantsFreedom from Cardiac Allograft Vasculopathy by Age Group


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

20

40

60

80

100

18-39 (N = 4,093) 40-59 (N = 14,490)

60-69 (N = 7,170) 70+ (N = 356)

Years

% F

reed

om fr

om C

AV


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Adult Heart TransplantsFreedom From Severe Renal Dysfunction* by Age Group


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

20

40

60

80

100

18-39 (N = 4,492) 40-59 (N = 15,966)

60-69 (N = 8,032) 70+ (N = 393)

Years

% F

reed

om fr

om S

ever

e R

enal

Dys

-fu

nctio

n

All pair-wise comparisons were significant at p < 0.05 except 40-59 vs. 70+ and 60-69 vs. 70+


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2013

Adult Heart TransplantsFreedom from Malignancy by Age Group


0 1 2 3 4 5 6 7 8 9 1020

40

60

80

100

18-39 40-59 60-69 70+

Years

% F

ree

from

Mal

igna

ncy

All pair-wise comparisons were significant at p < 0.0001 except 60-69 vs. 70+ (p=0.9554)

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Adult Heart TransplantsFreedom from Skin Malignancy by Age Group


0 1 2 3 4 5 6 7 8 9 1020

40

60

80

100

18-39 40-59 60-69 70+

Years

% F

ree

from

Ski

n M

alig

nanc

y

All pair-wise comparisons were significant at p < 0.0001 except 60-69 vs. 70+ (p=0.9999)

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Adult Heart TransplantsFreedom from Lymphoma by Age Group


0 1 2 3 4 5 6 7 8 9 1075

80

85

90

95

100

18-39 40-59 60-69 70+

Years

% F

ree

from

Lym

phom

a

No pair-wise comparisons were significant at p < 0.05 except18-39 vs. 60-69: p = 0.018840-49 vs. 60-69: p = 0.0227

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Adult Heart TransplantsFreedom From Non Skin Malignancy by Age Group


0 1 2 3 4 5 6 7 8 9 1050

60

70

80

90

100

18-39 40-59 60-69 70+

Years

% F

ree

from

Non

Ski

n M

alig

nanc

y

All pair-wise comparisons were significant at p < 0.05 except40-49 vs. 70+ and 60-69 vs. 70+

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Adult Heart TransplantsCause of Death for Age = 18-39 (Deaths: January 1994 – June 2012)

CAUSE OF DEATH 0-30 Days (N = 749)

31 Days – 1 Year

(N = 639)

>1 Year – 3 Years (N = 614)

>3 Years – 5 Years (N = 448)

>5 Years –10 Years(N = 867)

>10 Years – 15 Years (N = 555)

>15 Years (N = 372)

Cardiac Allograft Vasculopathy 9 (1.2%) 36 (5.6%) 86 (14.0%) 83 (18.5%) 195 (22.5%) 141 (25.4%) 73 (19.6%)

Acute Rejection 52 (6.9%) 129 (20.2%) 130 (21.2%) 55 (12.3%) 37 (4.3%) 13 (2.3%) 8 (2.2%)

Lymphoma 0 8 (1.3%) 6 (1.0%) 12 (2.7%) 35 (4.0%) 23 (4.1%) 12 (3.2%)

Malignancy, Other 0 9 (1.4%) 8 (1.3%) 18 (4.0%) 65 (7.5%) 53 (9.5%) 42 (11.3%)

CMV 0 7 (1.1%) 1 (0.2%) 1 (0.2%) 0 0 0

Infection, Non-CMV 69 (9.2%) 120 (18.8%) 45 (7.3%) 31 (6.9%) 52 (6.0%) 43 (7.7%) 30 (8.1%)

Graft Failure 302 (40.3%) 153 (23.9%) 199 (32.4%) 163 (36.4%) 271 (31.3%) 151 (27.2%) 95 (25.5%)

Technical 63 (8.4%) 14 (2.2%) 3 (0.5%) 2 (0.4%) 16 (1.8%) 7 (1.3%) 1 (0.3%)

Other 49 (6.5%) 62 (9.7%) 68 (11.1%) 35 (7.8%) 77 (8.9%) 38 (6.8%) 31 (8.3%)


Renal Failure 2 (0.3%) 4 (0.6%) 2 (0.3%) 8 (1.8%) 24 (2.8%) 19 (3.4%) 26 (7.0%)

Pulmonary 26 (3.5%) 18 (2.8%) 24 (3.9%) 10 (2.2%) 21 (2.4%) 10 (1.8%) 12 (3.2%)


Total N of Deaths 849 717 730 560 1,089 698 500


2013



31 Days – 1 Year

(N = 2,458)

>1 Year – 3 Years

(N = 1,816)


(N =1,682)


(N = 4,587)

>10 Years – 15 Years (N = 3,182)

>15 Years (N = 1,700)


Acute Rejection 147 (4.9%) 233 (9.5%) 163 (9.0%) 65 (3.9%) 76 (1.7%) 29 (0.9%) 9 (0.5%)

Lymphoma 2 (0.1%) 32 (1.3%) 47 (2.6%) 56 (3.3%) 176 (3.8%) 108 (3.4%) 50 (2.9%)

Malignancy, Other 4 (0.1%) 59 (2.4%) 224 (12.3%) 331 (19.7%) 998 (21.8%) 689 (21.7%) 346 (20.4%)

CMV 1 (0.0%) 31 (1.3%) 9 (0.5%) 4 (0.2%) 3 (0.1%) 2 (0.1%) 0


Graft Failure 1,160 (38.7%) 412 (16.8%) 492 (27.1%) 357 (21.2%) 794 (17.3%) 524 (16.5%) 255 (15.0%)

Technical 221 (7.4%) 33 (1.3%) 15 (0.8%) 17 (1.0%) 57 (1.2%) 47 (1.5%) 26 (1.5%)

Other 183 (6.1%) 182 (7.4%) 140 (7.7%) 128 (7.6%) 370 (8.1%) 213 (6.7%) 143 (8.4%)


Renal Failure 17 (0.6%) 23 (0.9%) 28 (1.5%) 57 (3.4%) 268 (5.8%) 256 (8.0%) 137 (8.1%)

Pulmonary 83 (2.8%) 83 (3.4%) 56 (3.1%) 81 (4.8%) 194 (4.2%) 135 (4.2%) 80 (4.7%)


Total N of Deaths 3,405 2,785 2,188 2,046 5,647 4,093 2,200


2013



31 Days – 1 Year

(N = 1,385)

>1 Year – 3 Years (N = 838)

>3 Years – 5 Years (N = 734)


(N = 1,803)

>10 Years – 15 Years (N = 1,014)

>15 Years (N = 362)


Acute Rejection 51 (3.4%) 77 (5.6%) 37 (4.4%) 20 (2.7%) 26 (1.4%) 5 (0.5%) 0

Lymphoma 1 (0.1%) 16 (1.2%) 25 (3.0%) 30 (4.1%) 64 (3.5%) 18 (1.8%) 7 (1.9%)

Malignancy, Other 0 41 (3.0%) 170 (20.3%) 205 (27.9%) 463 (25.7%) 254 (25.0%) 71 (19.6%)

CMV 2 (0.1%) 13 (0.9%) 5 (0.6%) 1 (0.1%) 3 (0.2%) 1 (0.1%) 0


Graft Failure 583 (38.8%) 203 (14.7%) 151 (18.0%) 116 (15.8%) 249 (13.8%) 117 (11.5%) 54 (14.9%)

Technical 93 (6.2%) 25 (1.8%) 5 (0.6%) 6 (0.8%) 13 (0.7%) 5 (0.5%) 4 (1.1%)

Other 70 (4.7%) 73 (5.3%) 56 (6.7%) 63 (8.6%) 124 (6.9%) 74 (7.3%) 23 (6.4%)


Renal Failure 10 (0.7%) 16 (1.2%) 18 (2.1%) 26 (3.5%) 115 (6.4%) 116 (11.4%) 58 (16.0%)

Pulmonary 49 (3.3%) 72 (5.2%) 52 (6.2%) 38 (5.2%) 96 (5.3%) 49 (4.8%) 16 (4.4%)


Total N of Deaths 1,672 1,574 993 892 2,217 1,321 484


2013

Adult Heart TransplantsCause of Death for Age = 70+ (Deaths: January 1994 – June 2012)

CAUSE OF DEATH 0-30 Days (N = 52)

31 Days – 1 Year

(N = 65)

>1 Year – 3 Years (N = 39)

>3 Years – 5 Years (N = 26)

>5 Years –10 Years(N = 58)

>10 Years (N = 25)

Cardiac Allograft Vasculopathy 1 (1.9%) 2 (3.1%) 5 (12.8%) 2 (7.7%) 1 (1.7%) 1 (4.0%)

Acute Rejection 1 (1.9%) 3 (4.6%) 4 (10.3%) 0 0 0

Malignancy, non Lymphoma 0 2 (3.1%) 6 (15.4%) 9 (34.6%) 16 (27.6%) 6 (24.0%)

Infection, Non-CMV 9 (17.3%) 22 (33.8%) 7 (17.9%) 4 (15.4%) 5 (8.6%) 2 (8.0%)

Graft Failure 18 (34.6%) 12 (18.5%) 3 (7.7%) 5 (19.2%) 9 (15.5%) 5 (20.0%)

Technical 5 (9.6%) 0 0 0 4 (6.9%) 2 (8.0%)

Other 2 (3.8%) 2 (3.1%) 4 (10.3%) 1 (3.8%) 6 (10.3%) 1 (4.0%)

Multiple Organ Failure 11 (21.2%) 15 (23.1%) 6 (15.4%) 2 (7.7%) 4 (6.9%) 1 (4.0%)

Renal Failure 0 2 (3.1%) 0 0 7 (12.1%) 5 (20.0%)

Pulmonary 2 (3.8%) 3 (4.6%) 2 (5.1%) 1 (3.8%) 2 (3.4%) 1 (4.0%)

Cerebrovascular 3 (5.8%) 2 (3.1%) 2 (5.1%) 2 (7.7%) 4 (6.9%) 1 (4.0%)

Total N of Deaths 59 71 44 30 72 29


2013

Adult Heart TransplantsCumulative Incidence of Leading Causes of Death

Age Group = 18-39 Years (Transplants: January 2005 – June 2011)

0 1 2 3 4 5

-2%

0%

2%

4%

6%

8%


Years

Inci

denc

e of

Cau

se-S

peci

fic

Dea

ths

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2013



0 1 2 3 4 5

-2%

0%

2%

4%

6%

8%


Years

Inci

denc

e of

Cau

se-S

peci

fic

Dea

ths

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2013


Age Group = 70+ Years (Transplants: January 2005 – June 2011)

0 1 2 3 4 5

-2%

0%

2%

4%

6%

8%


Years

Inci

denc

e of

Cau

se-S

peci

fic

Dea

ths

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HEART TRANSPLANTATION

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