2002 ISHLT J Heart Lung Transplant 2002; 21: 950-970. HEART TRANSPLANTATION Overall

2002ISHLT

J Heart Lung Transplant 2002; 21: 950-970.J Heart Lung Transplant 2002; 21: 950-970.

HEART TRANSPLANTATION

Overall

2002ISHLT


NUMBER OF HEART TRANSPLANTS REPORTED BY YEAR

* Numbers may be low due to delayed reporting.

0

500

1000

1500

2000

2500

3000

3500

4000

45001

98

2

19

83

19

84

19

85

19

86

19

87

19

88

19

89

19

90

19

91

19

92

19

93

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

*

Nu

mb

er o

f T

ran

spla

nts

*

2002ISHLT


HEART TRANSPLANTS: Donor Age by Year of Transplant

0

1500

3000

450019

82

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

Nu

mb

er

of

Tra

ns

pla

nts

0-10 11-17 18-35 36-49 50-59 60+

2002ISHLT


AGE DISTRIBUTIONOF HEART RECIPIENTS (1982-2001)

% o

f T

r%

of

Tra

ns

pla

nts

ns

pla

nts

0

10

20

30

40

50

60

<1 1-5 6-10 11-17 18-34 35-49 50-64 65+

Recipient Age

2002ISHLT


AGE DISTRIBUTION OF HEART TRANSPLANT RECIPIENTS BY ERA

0

10

20

30

40

50

60

<11-

56-

10

11-1

7

18-3

4

35-4

9

50-6

465

+ <11-

56-

10

11-1

7

18-3

4

35-4

9

50-6

465

+

% o

f tr

an

sp

lan

ts

1985-1996 1997-2001

2002ISHLT

J Heart Lung Transplant 2002; 21: 950-970.

HEART TRANSPLANTATION Actuarial Survival (1982-2001)

0

20

40

60

80

100

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

Years Post-Transplantation

Su

rviv

al (

%)

N=60,936

Half-life = 9.3 yearsConditional Half-life = 11.8 years

2002ISHLT


HEART TRANSPLANTATION

Adult Recipients

2002ISHLT


Congenital2%

ReTX2%

Myopathy45%

Misc.2%

Valvular4%

CAD45%

DIAGNOSIS IN ADULT HEART TRANSPLANTS

20

3040

5060

70

1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

% o

f Cas

es

Myopathy CAD

2002ISHLT


ADULT HEART TRANSPLANTATION Actuarial Survival by Era (1982-2001)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8


1982-1987 (N=6,337)

1988-1992 (N=16,596)

1993-1997 (N=18,740)

1998-2001 (N=12,083)

All comparisons significant at p < 0.002

Su

rviv

al (

%)

2002ISHLT


ADULT HEART TRANSPLANTATION Actuarial Survival by Age Group (1982-2001)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8


18-34 (N=5,608) 35-49 (N=15,866)50-64 (N=29,387) 65-69 (N=2,407)70+ (N = 239)

Su

rviv

al (

%)

Survival comparisonsAll pair-wise comparisons are statistically significant at p < 0.05 except:18-34 vs. 35-49 and 65-69 vs. 70+

2002ISHLT


0

20

40

60

80

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

>12-36months

>36-60months

>60 months

Time between previous and current transplant

1 Y

ear

Pat

ien

t S

urv

ival

(%

) 1982-1990

1991-2000

ADULT HEART RE-TRANSPLANTS1-Year Survival

124

170

32

32

29

31

64

95

3588

22 271

2002ISHLT


ADULT HEART TRANSPLANTS (1996-2001) Risk Factors for 1 Year Mortality

In Descending Order of Magnitude

N=13,049

VARIABLE Odds Ratio P-value

95% Confidence

Interval

ECMO 3.00 0.009 1.32 -6.85

Ventilator 2.94 <.0001 2.23 -3.86

Diagnosis: Congenital Heart Disease 2.34 <.0001 1.66 -3.31

IABP 1.53 0.0005 1.21 -1.94

Previous Transplant 1.50 0.01 1.10 -2.06

VAD 1.45 <.0001 1.25 -1.69

2002ISHLT




N=13,049


95% Confidence

Interval Diagnosis: Other than Congenital, Myopathy or Coronary Artery Disease

1.36 0.002 1.12 -1.66

Donor History of Hypertension

1.24 0.01 1.05 -1.47

Male Recipient/Female Donor

1.18 0.005 1.05 -1.33

Diagnosis: Coronary Artery Disease

1.16 0.007 1.04 -1.30

2002ISHLT



Continuous Factors

N=13,049

VARIABLE Odds Ratio p-value Recipient Age – linear < 0.0001

20 years 0.74

35 years 0.85

50 years 0.99

65 years 1.15

Donor Age - linear < 0.0001

20 years 0.84

35 years 1.07

50 years 1.38

65 years 1.77

2002ISHLT



Continuous Factors

N=13,049

VARIABLE Odds Ratio p-value Recipient Height – linear < 0.0001

140 cm 1.66

160 cm 1.23

180 cm 0.91

200 cm 0.67

2002ISHLT



Continuous Factors

N=13,049

VARIABLE Odds Ratio p-value Ischemia Time – linear < 0.0001

Ischemia Time - quadratic 0.009

1 hour 0.69

3 hours 1.04

5 hours 1.45

7 hours 1.90

Center Volume - linear < 0.0001

5 transplants/year 1.21




2002ISHLT



Continuous Factors

N=13,049

VARIABLE Odds Ratio p-value Most Recent PRA – linear < 0.0001

0% 0.96 25% 1.26 50% 1.65 75% 2.16

100% 2.83 Bilirubin (mg/dl) – linear < 0.0001

1 0.97 5 1.11

10 1.31 25 2.14

2002ISHLT


ADULT HEART TRANSPLANTS (1996-2001) Factors Not Significant for 1 Year Mortality

•Year of Transplant•In ICU or hospital prior to transplant•On inotropes for life support•ICD•CMV mismatch•Recipient pregnancy status•Weight (donor or recipient)•Height (donor)•Donor clinical infection•Donor cause of death

2002ISHLT


ADULT HEART TRANSPLANTS (April 1994-December 1996) Risk Factors for 5 Year Mortality


N=9,519


95% Confidence

Interval

Previous Transplant 2.09 <.0001 1.56 -2.79

Donor COD: Other (not head trauma, CVA, CNS tumor, or anoxia)

1.59 <.0001 1.39 -1.80

Ventilator 1.53 0.008 1.12 -2.10

Diagnosis: Coronary Artery Disease 1.23 <.0001 1.12 -1.35

Male Recipient/ Female Donor 1.15 0.01 1.03 -1.29

Implantable Defibrillator 0.70 0.0007 0.56 -0.86

2002ISHLT



Continuous Factors

N=9,519

VARIABLE Odds Ratio p-value Recipient Age – quadratic 0.001

20 years 1.49

35 years 1.11

50 years 1.00

65 years 1.09

Donor Age - linear < 0.0001

20 years 0.82

35 years 1.08

50 years 1.44

65 years 1.90

2002ISHLT



Continuous Factors

N=9,519

VARIABLE Odds Ratio p-value Ischemia Time – linear 0.006

1 hour 0.88

3 hours 1.01

5 hours 1.16

7 hours 1.33

Center Volume - linear 0.0001

Center Volume – quadratic 0.0008





2002ISHLT



Continuous Factors

N=9,519

VARIABLE Odds Ratio p-value Recipient Height – linear < 0.0001

140 cm 1.49

160 cm 1.17

180 cm 0.93

200 cm 0.73

Recipient Bilirubin (mg/dl) - linear 0.02

1 0.98

5 1.09

10 1.26

25 1.91

2002ISHLT


ADULT HEART TRANSPLANTS (April 1994-December 1996) Factors Not Significant for 5 Year Mortality

•Year of Transplant•VAD/ECMO/IABP•In ICU or hospital prior to transplant•On inotropes for life support•CMV mismatch•Recipient pregnancy status•Weight (donor or recipient)•Height (donor)•Donor clinical infection•Donor history of hypertension

2002ISHLT


ADULT HEART TRANSPLANTS (April 1994-December 1996) Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year


N=7,738


95% Confidence

Interval

CAV within 1st Year 1.88 <.0001 1.46 -2.43

Previous Transplant 1.84 0.002 1.26 -2.71

Rejection within 1st Year 1.40 <.0001 1.22 -1.60

Diagnosis: Coronary Artery Disease

1.28 0.0002 1.13 -1.46

Implantable Defibrillator 0.68 0.008 0.52 -0.90

2002ISHLT



Continuous Factors

N=7,738

VARIABLE Odds Ratio p-value Recipient Age – quadratic 0.0002

20 years 1.81

35 years 1.17

50 years 1.00

65 years 1.14

2002ISHLT



Continuous Factors

N=7,738

VARIABLE Odds Ratio p-value Donor Age - linear < 0.0001

Center Volume – linear 0.0001

Interaction of Donor Age (quadratic) and Center Volume (quadratic)

(see graph)

0.03

2002ISHLT


ADULT HEART TRANSPLANTS (April 1994-December 1996) Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year:

Combination of Donor Age and Center Volume

0

0.5

1

1.5

2

20 35 50 65Donor Age

Od

ds

Rat

io f

or

5 Y

ear

Mo

rtal

ity

Center Volume = 5 transplants/yearCenter Volume = 10 transplants/yearCenter Volume = 50 transplants/yearCenter Volume = 100 transplants/year

2002ISHLT


ADULT HEART TRANSPLANTS (April 1994-December 1996) Factors Not Significant for Conditional 5 Year Mortality

•Year of Transplant•Any form of life support•CMV mismatch•Ischemia time•Bilirubin•Donor cause of death

•In ICU or hospital prior to tx •Weight (donor or recipient)•Height (donor or recipient)•Gender (donor or recipient)•Donor clinical infection•Recipient pregnancy status

2002ISHLT


ADULT HEART RECIPIENTS Functional Status (April 1994-December 2001)

0%

20%

40%

60%

80%

100%

1 Year (N=11,908) 3 Years (N=10,446) 5 Years (N=8,873)

No Activity Limitations Performs with Some Assistance Requires Total Assistance

2002ISHLT


ADULT HEART RECIPIENTS Employment Status (U.S. Data: April 1994-December 2001)

0%

20%

40%

60%

80%

100%

1 Year (N=11,126)

3 Years (N=9,606)

5 Years (N=8,083)

Retired

Not Working

Working Part Time

Working Full Time

2002ISHLT


ADULT HEART RECIPIENTSRehospitalization Post-transplant (April 1994 - December 2001)

0%

20%

40%

60%

80%

100%

Up to 1 Year (N=12,889)

Between 2 and 3Years (N=10,993)

Between 4 and 5Years (N=9,336)

No Hospitalization Hospitalized: Not Rejection/Not Infection

Hospitalized: Rejection Only Hospitalized: Infection Only

Hospitalized: Rejection + Infection

2002ISHLT


0

10

20

30

40

50

Any Induction (N = 2,257)

Polyclonal ATG/ALG (N =1,196)

OKT3 (N = 695) IL2-R Antagonist (N =766)

% o

f p

ati

en

tsADULT HEART RECIPIENTS

Induction Immunosuppression For follow-ups between October 1999 and December 2001

2002ISHLT


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

ati

en

ts

Year 1 (N = 4,072)

Year 5 (N = 2,928)

ADULT HEART RECIPIENTS Maintenance Immunosuppression at Any Time During Follow-up Period

For follow-ups between October 1999 and December 2001

2002ISHLT


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

ati

en

ts

Year 1 (N = 3,165) Year 5 (N =2,588)

ADULT HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up


2002ISHLT


0

20

40

60

80

100

CalcineurinInhibitor

CellCycle Prednisone CalcineurinInhibitor

CellCycle Prednisone

% o

f P

ati

en

ts

CyA

TacTac

CyA

AZA

AZA

MMF

MMF



1 Year Follow-up (N = 3,165) 5 Year Follow-up (N = 2,588)

2002ISHLT


0%

20%

40%

60%

80%

100%

Year 1 (N = 3,165) Year 5 (N = 2,588)

% o

f P

ati

en

ts

None Given

Other

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine + MMF

Cyclosporine + AZA



2002ISHLT


POST-HEART TRANSPLANT MORBIDITY FOR ADULTS Cumulative Incidence for Survivors (April 1994-December 2000)

Outcome By 1 Year By 5 Years

Hypertension 72.4% (N=12,496)

95.1% (N=3,465)

Renal Function (N=12,511) (N=3,776)

Normal 74.8% 69.1% Renal Dysfunction 14.9% 17.6% Creatinine>2.5 mg/dl 9.0% 10.4% Chronic Dialysis 1.2% 2.5% Renal Transplant 0.2% 0.4%

Hyperlipidemia

48.7% (N=13,183)

81.3% (N=3,899)

Diabetes 24.1% (N=12,487)

32.0% (N=3,444)

CAV 8.2% (N=11,260) 33.2% (N=2,376)

2002ISHLT


Freedom from CAV and Freedom from Renal Dysfunction*

For Adult Heart Recipients (April 1994-December 2000)

50

60

70

80

90

100

0 12 24 36 48 60 72 84

Months

% F

reed

om fr

om C

AV

or

Free

dom

fr

om R

enal

Dys

func

tion

Freedom from CAV

Freedom from Renal Dysfunction

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

2002ISHLT


MALIGNANCY POST-HEART TRANSPLANTATION FOR ADULTSCumulative Incidence for Survivors (April 1994-December 2001)

Malignancy/Type 1-Year Survivors 5-Year Survivors

No Malignancy 12,671 (96.6%) 3,203 (81.8%)

Malignancy (all types combined) 443 (3.4%) 712 (18.2%)

Malignancy Type

Skin 184 404

Lymph 107 63

Other 103 155

Lymph + Skin 8

Lymph + Other 13

Skin + Other 34

Lymph + Skin + Other 2

Type Not Reported 49 33

2002ISHLT


Freedom from MalignancyFor Adult Heart Recipients (April 1994-December 2000)

50

60

70

80

90

100

0 12 24 36 48 60

Months

% F

ree

fro

m M

alig

nan

cy

All malignancy Lymph Skin Other

2002ISHLT


ADULT HEART TRANSPLANTATION Risk Factors for CAV Within 3 Years (April 1994 - December 1998)

N=6,851

VARIABLE Odds Ratio

P-value

95% Confidence Interval

Male Recipient/

Female Donor 0.76 0.009 0.62 -0.94

Transplant Year: 1997 0.77 0.01 0.63 -0.94

2002ISHLT



Continuous Factors

N=6,851

VARIABLE Odds Ratio p-value Recipient Age – linear 0.03

20 1.27 35 1.13 50 1.01 65 0.90

Donor Age - linear < 0.0001 20 0.74 35 1.12 50 1.71 65 2.59

2002ISHLT



Continuous Factors

N=6,851

VARIABLE Odds Ratio p-value Center Volume – linear < 0.0001

5 Transplants/Year 0.82 10 Transplants/Year 0.84 50 Transplants/Year 1.13

100 Transplants/Year 1.61 Recipient BMI - linear 0.03

15 0.77 20 0.88 25 1.01 30 1.16 35 1.32

2002ISHLT



N=2,546

VARIABLE Odds Ratio

P-value

95% Confidence Interval

Donor history of hypertension

1.71 0.003 1.20 -2.44

Donor cause of death: intracranial hemorrhage or stroke

0.76 0.03 0.58 -0.98

2002ISHLT



Continuous Factors

N=2,546

VARIABLE Odds Ratio p-value Recipient Age – linear 0.002 Recipient Age - quadratic 0.02

20 0.78 35 1.07 50 1.01 65 0.66

Donor Age - linear < 0.0001 20 0.74 35 1.13 50 1.72 65 2.62

2002ISHLT


ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death (1982-2001)

0%

20%

40%

60%

80%

100%

0-30 Days (N = 3,144)

31 Days - 1 Year (N = 2,934)

>1 Year - 3 Years (N = 1,925)

>3 Years - 5 Years (N = 1,363)

>5 Years (N = 2,831)

Per

cen

tag

e o

f d

eath

s

Other

Technical

Graft Failure - Other

Primary Graft Failure

Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

Timing of Death

2002ISHLT


ADULT HEART TRANSPLANTS RECIPIENTS: Cause of Death by Era: Deaths in 0-30 Days

0%

20%

40%

60%

80%

100%

1982-1986 (N = 126)

1987-1991 (N = 966)

1992-1996 (N = 1,377)

1997-2001 (N = 627)

Per

cent

age

of d

eath

s

Other

Technical



Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

Year of Transplant

2002ISHLT


ADULT HEART TRANSPLANTS RECIPIENTS: Cause of Death by Era: Deaths in 31 Days-1 Year

0%

20%

40%

60%

80%

100%

1982-1986 (N = 107)

1987-1991 (N = 1,012)

1992-1996 (N = 1,332)

1997-2001 (N = 483)

Per

cent

age

of d

eath

s

Other

Technical



Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

Year of Transplant

2002ISHLT


ADULT HEART TRANSPLANTS RECIPIENTS: Cause of Death by Era: Deaths in >1 Year - 3 Years

0%

20%

40%

60%

80%

100%

1982-1986 (N = 45)

1987-1991 (N = 713)

1992-1996 (N = 944)

1997-2001 (N = 218)

Per

cent

age

of d

eath

s

Other

Technical

Graft Failure


Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

Year of Transplant

2002ISHLT


ADULT HEART TRANSPLANTS RECIPIENTS: Cause of Death by Era: Deaths in >3 Years - 5 Years

0%

20%

40%

60%

80%

100%

1982-1986 (N = 35)

1987-1991 (N = 657)

1992-1996 (N = 656)

1997-2001 (N = 15)

Pe

rce

nta

ge

of

de

ath

s

Other

Technical



Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

Year of Transplant

2002ISHLT


ADULT HEART TRANSPLANTS RECIPIENTS: Cause of Death by Era: Deaths in >5 Years

0%

20%

40%

60%

80%

100%

1982-1986 (N = 469)

1987-1991 (N = 1,868)

1992-1996 (N = 478)

Pe

rce

nta

ge

of

de

ath

s

Other

Technical



Infection, Non-CMV

Acute Rejection

CMV

Malignancy, Other

Lymphoma

CAV

Year of Transplant

Documents

2002 ISHLT J Heart Lung Transplant 2002; 21: 950-970. HEART TRANSPLANTATION Overall