heart transplantation overall ishlt 2006 j heart lung transplant 2006;25:869-79
TRANSCRIPT
HEART TRANSPLANTATION
Overall
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
NUMBER OF HEART TRANSPLANTS REPORTED BY YEAR
189 316661
1179
2145
2701
31143330
3980 4148 4187 4346 4428 4409 4242 41443820
3536 3396 3345 3283 31872954
0
500
1000
1500
2000
2500
3000
3500
4000
4500
Nu
mb
er
of
Tra
ns
pla
nts
ISHLT 2006
NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of hearts transplanted worldwide has declined in recent years.
J Heart Lung Transplant 2006;25:869-79
AVERAGE CENTER VOLUMEHeart Transplants: January 1, 1991 - June 30, 1995
and January 1, 2001 – June 30, 2005
61 55
81
44
15
47 51
74
2914 3 6 2455
0
10
20
30
40
50
60
70
80
90
1-4 5-9 10-19 20-29 30-39 40-49 50-74 75+
Average number of heart transplants per year
Nu
mb
er
of
cen
ters
.
1991-6/1995
2001-6/2005
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
DISTRIBUTION OF TRANSPLANTS BY CENTER VOLUMEHeart Transplants: January 1, 1991 - June 30, 1995
and January 1, 2001 – June 30, 2005
28
25 23
128 9
13
310
30
21
15
4
116
0
5
10
15
20
25
30
35
1-4 5-9 10-19 20-29 30-39 40-49 50-74 75+
Average number of heart transplants per year
Per
cen
tag
e o
f tr
ansp
lan
ts
1991-6/1995
2001-6/2005
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
% o
f T
ran
sp
lan
ts
0-10 11-17 18-34 35-49 50-59 60+
0
5
10
15
20
25
30
35
Me
an
do
no
r a
ge
(y
ea
rs)
Mean Age
HEART TRANSPLANTS: Donor Age by Year of Transplant
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
AGE DISTRIBUTIONOF HEART RECIPIENTS (1/1982-6/2005)
% o
f T
r%
of
Tra
ns
pla
nts
ns
pla
nts
0
5
10
15
20
25
30
35
40
0-9 10-19 20-29 30-39 40-49 50-59 60+
Recipient Age
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
AGE DISTRIBUTION OF HEART TRANSPLANT RECIPIENTS BY ERA
0
5
10
15
20
25
30
35
40
0-9 10-19 20-29 30-39 40-49 50-59 60+
Recipient Age
% o
f tr
an
sp
lan
ts
1982-1988 (N = 9,672)1989-1993 (N = 19,386)1994-1998 (N = 20,624)1999-2004 (N = 19,679)
P < 0.0001
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2004)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Years
Su
rviv
al (%
) .
Half-life = 9.9 yearsConditional Half-life = 13 years
N=69,536
ISHLT 2006
N followed at longest time point: 28,463
J Heart Lung Transplant 2006;25:869-79
HEART TRANSPLANTATION
Adult Recipients
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
Congenital2%
ReTX2%
Myopathy45%
Misc.1%
Valvular4%
CAD46%
1982-1999
DIAGNOSIS IN ADULT HEART TRANSPLANTS
203040506070
% o
f Cas
es
Myopathy CAD
CAD42%
Valvular3%
Misc.5%
Myopathy46%
ReTX2%
Congenital2%
1/2001-6/2005
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: 1/1982 – 6/2004)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Years
1982-1988 (N=9,071)
1989-1993 (N=17,685)
1994-1998 (N=18,758)
1999-6/2004 (N=16,227)
All comparisons significant at p < 0.0001
HALF-LIFE 1982-1988: 8.2 years; 1989-1993: 9.7 years; 1994-1998: 10.2 years
Su
rviv
al (
%)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: 1/1982-6/2004)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years
Su
rviv
al (%
) .
18-34 (N= 6,485) 35-49 (N=17,962)50-59 (N=24,430) 60-64 (N=9,263)65-69 (N= 3,036) 70+ (N= 318)
HALF-LIFE 18-34: 12.0 years; 35-49: 10.7 years; 50-59: 9.6 years; 60-64: 8.7 years; 65-69: 8.0 years; 70+: 7.0 years
All pair-wise comparisons are statistically significant at p < 0.005 except 65-69 vs. 70+
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: 1/1998-6/2004)
0
20
40
60
80
100
0 1 2 3 4 5 6 7
Years
Su
rviv
al (%
) .
18-34 (N= 1,911) 35-49 (N= 4,956)50-59 (N=7,370) 60-64 (N=3,545)65-69 (N= 1,598) 70+ (N= 205)
All pair-wise comparisons are statistically significant at p < 0.05 except 18-34 vs. 50-64, 18-34 vs. 60-64 and 65-69 vs. 70+
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis (Transplants: 1/1982-6/2004)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years
Su
rviv
al (
%)
Cardiomyopathy (N = 25,637) Coronary artery disease (N = 25,952)Congenital diagnosis (N = 955) Retransplant (1,181)Valvular (N= 1,931) Other (N= 788)
HALF-LIFE Cardiomyopathy: 10.7 years; CAD: 9.0 years; Congenital: 11.7 years; Retransplant: 4.6 years; Valvular: 10.2 years; Other: 11.3 years
All pair-wise comparisons with Cardiomyopathy are significant at p < 0.05 except for Congenital; Coronary Artery Disease vs. ReTx: p < 0.0001; Coronary Artery Disease vs. Valvular: p = 0.01; Valvular vs. ReTx: p < 0.0001; Congenital vs. ReTx: p < 0.0001; ReTx vs. Other: p < 0.0001
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis
Conditional on Survival to 1 Year (Transplants: 1/1982-6/2004)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years
Su
rviv
al (
%)
Cardiomyopathy (N = 19,654)Coronary artery disease (N = 19,611)Congenital diagnosis (N = 658)Retransplant (703)Valvular (N= 1,353)Other (N= 449)
All pair-wise comparisons are significant except Cardiomyopathy vs. valvular, valvular vs. other, and congenital vs. other
HALF-LIFE Cardiomyopathy: 12.9 years; CAD: 11.1 years; Congenital: 11.5 years; Retransplant: 9.0 years; Valvular: 13.2 years; Other: 14.2 years
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis (Transplants: 1/1998-6/2004)
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Years
Su
rviv
al (
%)
Cardiomyopathy (N=8,399) Coronary artery disease (N=8,197)
Congenital Diagnosis (N=383) Retransplant (N=407)
Valvular (N=501) Other (N=410)
All pair-wise comparisons with Cardiomyopathy are significant at p < 0.05; Coronary Artery Disease vs. ReTX: p < 0.0001
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis Conditional on Survival to 1 Year (Transplants: 1/1998-6/2004)
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Years
Su
rviv
al (
%)
Cardiomyopathy (N=6,559) Coronary artery disease (N=6,264)
Congenital Diagnosis (N=252) Retransplant (N=273)
Valvular (N=354) Other (N=210)
Cardiomyopathy vs. CAD: p = 0.009; Cardiomyopathy vs. ReTx: p = 0.0005; CAD vs. Congenital: p = 0.07; CAD vs. Valvular: p = 0.16; Valvular vs. ReTx: p = 0.005; Congenital vs. ReTx: p = 0.003
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by PVR (Transplants: 1/2002-6/2004)
50
60
70
80
90
100
0 1 2 3
Years
Su
rviv
al (
%)
1-<3 Wood units (N= 2,421) 3-<5 Wood units (N= 719)
5+ Wood units (N= 266)
1-<3 vs. 3-<5: p = 0.0002
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by VAD usage (Transplants: 1/1999-6/2004)
50
60
70
80
90
100
0 1 2 3 4 5
Years
Su
rviv
al (
%)
Pulsatile flow (N=1,813) No LVAD (N=14,154)
p < 0.0001
ISHLT 2006
Note: Only 42 transplants involving continuous flow devices; too few to analyze.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by VAD usage and Era (Transplants: 1/1999-6/2004)
50
60
70
80
90
100
0 1 2 3 4 5
Years
Su
rviv
al (
%)
Pulsatile, 1999-2001 (N = 825) No LVAD, 1999-2001 (N=8,130)
Pulsatile, 2002-6/2004 (N=859) No LVAD, 2002-6/2004 (N=6,024)
p < 0.0001
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS5-Year Predicted Survival Model (Transplants: 1/1997-6/2000)
Impact of Pre-Transplant VAD
ISHLT 2006
50%
60%
70%
80%
90%
100%
0 1 2 3 4 5
Time (years)
Pre
dic
ted
Su
rviv
al No Pre-op VAD
Pre-op pulsatile VAD
Recipient: 54 y.o. male, Dx=CAD, PRA < 10%, weight=75 kg, height=69 in, PVR=2, volume=25/year, year of tx=99/00, bilirubin=0.9, PA diastolic=23, creatinine=1.2 mg/dl, ischemia=180 min;
Donor: 32 y.o. male, COD = MVA, weight = 72 kg, height = 70 in.
J Heart Lung Transplant 2006;25:869-79
0
20
40
60
80
100
0-2 months >2-6 months >6-12months
>12-36months
>36-60months
>60 months
Time between previous and current transplant
1 Y
ear
Pat
ien
t S
urv
ival
(%
) 1/1982-12/19901/1991-12/19991/2000-6/2004
Comparison of survival for interval < 12 months vs. > 12 months: p < 0.0001Comparison of survival for interval < 12 months vs. > 12 months for 1/00-6/2004: p < 0.0001
124
143
32 19 2731 66 863722 25 231
50 2 2 81 21 19015
ADULT HEART RE-TRANSPLANTS1-Year Survival
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART RECIPIENTS Functional Status of Surviving Recipients
(Follow-ups: 1995 - June 2005)
0%
20%
40%
60%
80%
100%
1 Year (N = 15,406) 3 Years (N = 13,612) 5 Years (N = 11,872) 7 Years (N = 9,313)
No Activity Limitations Performs with Some Assistance Requires Total Assistance
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART RECIPIENTSEmployment Status of Surviving Recipients
(Follow-ups: 1995 - June 2005)
0%
20%
40%
60%
80%
100%
1 Year (N = 15,030) 3 Year (N = 13,133) 5 Year (N = 11,279) 7 Year (N = 9,077)
Retired
Not Working
Working Part Time
Working Full Time
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART RECIPIENTSRehospitalization Post-transplant of Surviving Recipients
(Follow-ups: 1995 - June 2005)
0%
20%
40%
60%
80%
100%
Up to 1 Year (N = 17,817)
Between 2 and 3 Years (N = 15,349)
Between 4 and 5 Years (N = 13,224)
Between 6 and 7 Years (N = 10,618)
No Hospitalization Hospitalized: Not Rejection/Not InfectionHospitalized: Rejection Only Hospitalized: Infection OnlyHospitalized: Rejection + Infection
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
0
10
20
30
40
50
Polyclonal ALG/ATG (N = 2,242) OKT3 (N = 510) IL2R-antagonist (N = 2,253)
% o
f p
ati
en
tsADULT HEART RECIPIENTS
Induction Immunosuppression (Transplants: January 2001 – June 2005)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
0
10
20
30
40
50
60
Any Induction PolyclonalALG/ATG
OKT3 IL2R-antagonist
% o
f p
atien
ts
1996 2000 2004
ADULT HEART RECIPIENTSInduction Immunosuppression (Transplants: 1996, 2000 and 2004)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival Stratified by Use of Any Induction
(Transplants: 1/2000-6/2004, conditional on survival to 14 days)
50
60
70
80
90
100
0 1 2 3 4
Years
Su
rviv
al (
%)
No induction (N= 4,573) Any induction (N= 4,473)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Type
(Transplants: 1/2000-6/2004, conditional on survival to 14 days)
50
60
70
80
90
100
0 1 2 3 4
Years
Su
rviv
al (
%)
No induction (N= 4,573) Polyclonal induction (N= 2,055)
IL2-R antagonist (N= 1,876) OKT3 (N= 542)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
0
20
40
60
80
100
Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone
% o
f P
ati
en
ts .
Year 1 (N = 5,558) Year 5 (N = 4,577)
ADULT HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up
(Follow-ups: January 2002 - June 2005)
NOTE: Different patients are analyzed in Year 1 and Year 5
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
0
20
40
60
80
100
Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone
% o
f P
atie
nts
.
1999 (N=685) 2003 (N = 2,949) Jan 2005 - Jun 2005 (N = 1,411)
ADULT HEART RECIPIENTS Maintenance Immunosuppression at Time of 1 Year Follow-up
NOTE: Different patients are analyzed in each time frame.
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
0%
20%
40%
60%
80%
100%
Year 1 (N = 5,558) Year 5 (N = 4,577)
% o
f P
atie
nts
.
Other
Tacrolimus
Cyclosporine
Rapa + cellcycle
Rapa + calcineurin
Tacrolimus + MMF
Tacrolimus + AZA
Cyclosporine + MMF
Cyclosporine + AZA
ADULT HEART RECIPIENTS Maintenance Immunosuppression Drug Combinations at Time of Follow-up
(Follow-ups: January 2003 - June 2005)
NOTES: Different patients are analyzed in Year 1 and Year 5. In the Year 1 cohort 76.5% of patients were on prednisone; in the Year 5 cohort 61% of patients were on prednisone.
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
PERCENTAGE OF ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Type of Induction (Transplants: January 1, 2000 - June 30, 2004)
0
10
20
30
40
50
60
70
Overall 18-44 45-62 63+ F M% t
rea
ted
fo
r re
jec
tio
n w
ith
in 1
ye
ar
.
No induction (N = 4,455) Polyclonal (N = 2,045)IL2R-antagonist (N = 1,872) OKT3 (N = 540)
For females: no induction vs. OKT3 (p = 0.0003); polyclonal vs. OKT3 (p = 0.0011); IL2R vs. OKT3 (p = 0.0048)For males: no induction vs. OKT3 (p = 0.0015); polyclonal vs. OKT3 (p = 0.0007); IL2R vs. OKT3 (p = 0.0365)
Overall: no induction vs. OKT3 (p < 0.0001); polyclonal vs. OKT3 (p < 0.0001); IL2R vs. OKT3 (p = 0.0017).45-62: All comparisons with OKT3 were significant at p < 0.0001. No other comparisons within age groups were statistically significant.
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
NUMBER OF REJECTION EPISODES FOR ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Type of Induction (Transplants: January 1, 2000 - June 30, 2004)
0
0.5
1
1.5
2
2.5
3
Overall 18-44 45-62 63+ F M
Ave
rag
e n
um
ber
of
reje
ctio
n e
pis
od
es
No induction (N = 4,455) Polyclonal (N = 2,045)IL2R-antagonist (N = 1,872) OKT3 (N = 540)
Overall: no induction vs. OKT3 (p = 0.0021); polyclonal vs. OKT3 (p=0.0077); IL2 vs. OKT3 (p=0.0003). 18-44: no induction vs. IL2 (p = 0.033).45-62: no induction vs. OKT3 (p = 0.0031); IL2 vs. OKT3 (p = 0.0034).63+: polyclonal vs. OKT3 (p = 0.0228).For females: no induction vs. OKT3 (p = 0.0082); IL2 vs. OKT3 (p = 0.0493). For males: no induction vs. OKT3 (p =0.046); IL2 vs. OKT3 (p = 0.0021).
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
PERCENTAGE OF ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Maintenance Immunosuppression (Transplants: January 1, 2000 - June 30, 2004)
0
10
20
30
40
50
60
70
Overall 18-44 45-62 63+ F M
% t
reat
ed f
or
reje
ctio
n w
ith
in 1
yea
r
Cyclosporine + MMF (N = 2,906) Cyclosporine + AZA (N = 587)Tacrolimus + MMF (N = 973) Tacrolimus + AZA (N = 78)
Overall: CyA + MMF vs. TAC + MMF (p<0.0001); CyA + MMF vs. TAC + AZA (p=0.0102); CyA + AZA vs. TAC + MMF (p<0.0001); CyA + AZA vs. TAC + AZA (p=0.0054).
18-44: CyA + MMF vs. TAC + MMF (p=0.0085); CyA + MMF vs. TAC + AZA (p=0.0119); CyA + AZA vs. TAC + MMF (p=0.031); CyA + AZA vs. TAC + AZA (p=0.0108).
45-62: CyA + MMF vs. TAC + MMF (p<0.0001); CyA + AZA vs. TAC + MMF (p<0.0001). 63+: CyA + MMF vs. TAC + MMF (p=0.0395); CyA + AZA vs. TAC + MMF (p=0.0027). For females all comparisons are significant except TAC + MMF vs. TAC + AZA. For males: CyA + MMF vs. TAC + MMF (p<0.0001); CyA + AZA vs. TAC + MMF (p<0.0001)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
NUMBER OF REJECTION EPISODES FOR ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR Stratified by Maintenance Immunosuppression (Transplants: January 1, 2000 - June 30, 2004)
0
0.5
1
1.5
2
2.5
Overall 18-44 45-62 63+ F M
Ave
rag
e n
um
ber
of
reje
ctio
n e
pis
od
es
Cyclosporine + MMF (N = 2,906) Cyclosporine + AZA (N = 587)Tacrolimus + MMF (N = 973) Tacrolimus + AZA (N = 78)
Overall: CyA + MMF vs. TAC + MMF (p = 0.0391); CyA + AZA vs. TAC + MMF (p = 0.0067)18-44: CyA + MMF vs. TAC + MMF (p = 0.0474); CyA + TAC + MMF (p = 0.0434)Male: CyA + MMF vs. CyA + AZA (p = 0.0493); CyA + AZA vs. TAC + MMF (p = 0.0033)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival Stratified by Rejection Within 1st Year
Conditional on survival to 1 year for transplants: 1/1995-6/2003
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Years
Su
rviv
al (
%)
No rejection (N=7,032) Rejection (N=6,336)
p < 0.0001
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival Stratified by Rejection between Transplant
Discharge and 1 YearConditional on survival to 1 year for transplants: 1/1995-6/2003
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Years
Su
rviv
al (
%)
No rejection (N=4,697) Rejection (N=4,613)
p < 0.0001
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
POST-HEART TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors at 1 Year Post-Transplant
(Follow-ups: April 1994 – December 1997 and January 2001 - June 2005)
Follow-ups: April 1994-
December 1997 Follow-ups: January 2001 –
June 2005
Outcome Within 1
Years Total N with
known response Within 1
Year Total N with
known response
Hypertension 68.9% (N = 6,428) 75.9% (N = 7,174)
Renal Dysfunction 20.4% (N = 6,381) 31.7% (N = 7,267)
Abnormal Creatinine < 2.5 mg/dl 11.3% 22.4% Creatinine > 2.5 mg/dl 8.1% 7.3% Chronic Dialysis 1.0% 1.5% Renal Transplant 0.1% 0.4%
Hyperlipidemia 33.3% (N = 6,816) 68.6% (N = 7,689)
Diabetes 20.9% (N = 6,436) 30.8% (N = 7,208)
Cardiac Allograft Vasculopathy 7.9% (N = 5,950) 7.9% (N = 6,515)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
POST-HEART TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors at 5 and 8 Years Post-Transplant
(Follow-ups: April 1994 - June 2005)
Outcome Within 5
Years Total N with
known response Within 8
Years Total N with
known response
Hypertension 94.1% (N = 7,298) 97.4% (N = 3,232)
Renal Dysfunction 33.2% (N = 7,785) 35.9% (N = 3,114)
Abnormal Creatinine < 2.5 mg/dl 21.4% 20.6% Creatinine > 2.5 mg/dl 8.7% 10.0% Chronic Dialysis 2.6% 4.3% Renal Transplant 0.5% 0.9%
Hyperlipidemia 86.3% (N = 8,123) 91.4% (N = 3,232)
Diabetes 34.3% (N = 7,244) 37.2% (N = 2,798)
Cardiac Allograft Vasculopathy 32.1% (N = 5,207) 44.3% (N = 1,723)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
FREEDOM FROM CARDIAC ALLOGRAFT VASCULOPATHY AND FREEDOM FROM SEVERE RENAL DYSFUNCTION* For Adult Heart Recipients (Follow-ups: April 1994-June 2005)
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Years
% F
ree
fro
m C
AV
or
Fre
ed
om
fro
m
Se
ve
re R
en
al
Dy
sfu
nc
tio
n
Freedom from CAV
Freedom from Severe Renal Dysfunction
* Severe renal dysfunction = Creatinine > 2.5 mg/dl, dialysis or renal transplant
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
FREEDOM FROM CARDIAC ALLOGRAFT VASCULOPATHY Stratified by Rejection Within 1st Year
For Adult Heart Recipients (Transplants: April 1994-June 2003) Conditional on Survival to 1 Year
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Years
% F
ree
fro
m C
AV
No rejection (N = 5,250) Rejection (N = 4,456)
p = 0.0001
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
PATIENT SURVIVAL AFTER REPORT OF CAV AND PATIENT SURVIVAL IN PATIENTS WITHOUT CAV*
(Transplants: April 1994-June 2003)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Time after Report of CAV (Years)
Su
rviv
al
(%)
CAV (N = 3,349)
No CAV (N = 9,946)
p < 0.0001
ISHLT 2006
* Patients without CAV conditioned on survival to median time of CAV development (562 days)
J Heart Lung Transplant 2006;25:869-79
MALIGNANCY POST-HEART TRANSPLANTATION FOR ADULTSCumulative Prevalence in Survivors (Follow-ups: April 1994 - June 2005)
Malignancy/Type 1-Year Survivors
5-Year Survivors
8-Year Survivors
No Malignancy 18851 (97.1%) 6802 (84.4%) 2360 (74.0%)
Malignancy (all types combined) 572 (2.9%) 1257 (15.6%) 830 (26.0%)
Malignancy Type
Skin 262 843 552
Lymph 136 121 55
Other 123 321 165
Type Not Reported 51 38 115
”Other” includes: prostate (11, 33, 23), adenocarcinoma (7, 3, 2), lung (5, 3, 1), bladder (4, 5, 4), sarcoma (3, 2, 1), breast (2, 7, 4), cervical (2, 4, 1), colon (2, 3, 3), and renal (2, 5, 2). Numbers in parentheses are those reported within 1 year, 5 years and 8 years, respectively.
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
FREEDOM FROM MALIGNANCYFor Adult Heart Recipients (Follow-ups: April 1994 - June 2005)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Years
% F
ree
fro
m M
ali
gn
an
cy
All malignancy Lymph Skin Other
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2005)
CAUSE OF DEATH 0-30 Days
(N = 3,198)31 Days - 1 Year
(N = 2,635)>1 Year - 3 Years
(N = 1,985)>3 Years - 5 Years
(N = 1,724)>5 Years
(N = 5,364)
CARDIAC ALLOGRAFT VASCULOPATHY
54 (1.7%) 116 (4.4%) 272 (13.7%) 279 (16.2%) 767 (14.3%)
ACUTE REJECTION 208 (6.5%) 316 (12.0%) 195 (9.8%) 72 (4.2%) 76 (1.4%)
LYMPHOMA 2 (0.1%) 48 (1.8%) 81 (4.1%) 89 (5.2%) 236 (4.4%)
MALIGNANCY, OTHER 2 (0.1%) 55 (2.1%) 206 (10.4%) 312 (18.1%) 994 (18.5%)
CMV 4 (0.1%) 32 (1.2%) 16 (0.8%) 3 (0.2%) 5 (0.1%)
INFECTION, NON-CMV 414 (12.9%) 866 (32.9%) 260 (13.1%) 164 (9.5%) 554 (10.3%)
PRIMARY FAILURE 831 (26.0%) 194 (7.4%) 132 (6.6%) 73 (4.2%) 217 (4.0%)
GRAFT FAILURE 445 (13.9%) 287 (10.9%) 337 (17.0%) 272 (15.8%) 790 (14.7%)
TECHNICAL 237 (7.4%) 27 (1.0%) 16 (0.8%) 17 (1.0%) 49 (0.9%)
OTHER 213 (6.7%) 185 (7.0%) 175 (8.8%) 146 (8.5%) 447 (8.3%)
MULTIPLE ORGAN FAILURE
431 (13.5%) 276 (10.5%) 104 (5.2%) 101 (5.9%) 447 (8.3%)
RENAL FAILURE 18 (0.6%) 12 (0.9%) 35 (1.8%) 63 (3.7%) 341 (6.4%)
PULMONARY 134 (4.2%) 97 (3.4%) 89 (4.5%) 76 (4.4%) 223 (4.2%)
CEREBROVASCULAR 205 (6.4%) 113 (4.3%) 67 (3.4%) 57 (3.3%) 218 (4.1%)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death from Leading Causes by Era
(Deaths: January 1992 - June 2005)
CAUSE OF DEATH
DATE OF DEATH
0-30 Days
(N = 3,198)31 Days - 1 Year
(N = 2,635)>1 Year - 3 Years
(N = 1,985)>3 Years - 5 Years
(N = 1,724)>5 Years
(N = 5,364)
ACUTE REJECTION
1992-1997 117 (6.7%) 217 (13.8%) 106 (8.9%) 36 (4.0%) 18 (1.2%)
1998-6/2005 91 (6.2%) 99 (9.4%) 89 (11.1%) 36 (4.4%) 58 (1.5%)
CARDIAC ALLOGRAFT VASCULOPATHY
1992-1997 33 (1.9%) 78 (4.9%) 175 (14.8%) 179 (19.8%) 281 (18.1%)
1998-6/2005 21 (1.4%) 38 (3.6%) 97 (12.1%) 100 (12.2%) 486 (12.8%)
GRAFT FAILURE1992-1997
261 (15.0%)
177 (11.2%) 194 (16.4%) 119 (13.1%) 192 (12.3%)
1998-6/2005184
(12.6%)110 (10.4%) 143 (17.9%) 153 (18.7%) 598 (15.7%)
MALIGNANCY, OTHER
1992-1997 2 (0.1%) 39 (2.5%) 115 (9.7%) 168 (18.5%) 267 (17.2%)
1998-6/2005 16 (1.5%) 91 (11.4%) 144 (17.6%) 727 (19.1%)
PRIMARY FAILURE
1992-1997 500
(28.8%)169 (10.7%) 105 (8.9%) 48 (5.3%) 108 (6.6%)
1998-6/2005 331
(22.7%)25 (2.4%) 27 (3.4%) 25 (3.1%) 109 (2.9%)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANT RECIPIENTS: Cumulative Incidence of Leading Causes of Death
(Transplants: January 1992 - June 2004)
0.0%
1.0%
2.0%
3.0%
4.0%
5.0%
6.0%
0 1 2 3 4 5 6 7 8 9 10
Time (years)
% c
au
se
-sp
ec
ific
de
ath
s
CAV Acute Rejection
Malignancy (non-Lymph/PTLD) Primary Failure
Graft Failure CMV
Infection (non-CMV)
ISHLT 2006 J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year Mortality
4/1994-1998 (N=16,838)
2001-6/2004 (N=9,511)
Risk Factor N Relative
Risk p-value N
Relative Risk
p-value
Temporary circulatory support* 35 2.22 .0034 110 2.76 <.0001
Diagnosis: Congenital heart disease 257 1.77 <.0001 220 2.32 <.0001
Dialysis 161 1.87 <.0001 209 1.71 .0001
Female recipient 3353 1.18 .0394 2229 1.40 .0015
Diagnosis: Valvular heart disease 499 1.17 .1316 247 1.40 .0352
Donor cause of death: cerebrovascular/stroke
4037 1.09 .0077 2300 1.36 <.0001
Recipient cerebrovascular event prior to transplant
449 0.90 .4053 421 1.31 .0278
Hospitalized at transplant (including ICU) 12352 1.01 .8082 5845 1.31 .0003
2006ISHLTNote: All factors were significant at p < 0.05 in at least one of the eras.
* Temporary circulatory support includes ECMO and Abiomed.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year Mortality
4/1994-1998 (N=16,838)
2001-6/2004 (N=9,511)
Risk Factor N Relative Risk
p-value
N Relative Risk
p-value
Ventilator 272 1.81 <.0001 235 1.29 .0953
Repeat transplant 378 2.33 <.0001 230 1.29 .1598
Pulsatile chronic device** 197 1.41 .0415 1237 1.28 .0166
Not ABO identical vs. ABO identical 2719 1.01 .8473 1221 1.27 .0018
Diagnosis: Coronary artery disease 7311 1.24 <.0001 3883 1.26 .0009
Infection requiring IV drug therapy within 2 weeks prior to transplant
778 1.22 .0305 808 1.18 .093
PRA > 10% 765 1.39 .0001 517 1.13 .3058
HLA DR mismatches (per mismatch) 1 DR MM –
5041 2 DR MM –
11089 1.09 .0136
1 DR MM – 2870
2 DR MM – 6219
1.12 .0342
2006ISHLTNote: All factors were significant at p < 0.05 in at least one of the eras.
**VAD type collected for only part of era. Only those with known type were included in this group.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year Mortality
4/1994-1998 (N=16,838)
2001-6/2004 (N=9,511)
Risk Factor N Relative Risk
p-value
N Relative Risk
p-value
Female donor 5446 1.19 .0006 3057 1.11 .1590
Intra-aortic balloon pump 594 1.23 .03 433 0.98 .8757
HLA B mismatches (per mismatch) 1 B MM – 3340 2 B MM – 13197 1.15 .0021 1 B MM 1825
2 B MM – 7522 0.98 .7216
Diagnosis: Other 1770 0.77 .0004 1039 0.97 .8186
Recipient previous transfusions 1466 1.19 .0134 1412 0.96 .6687
Donor history of hypertension 1030 1.2 0.0239 701 0.87 0.2125
Recipient IV inotropes 5941 1.14 .0256 3303 0.85 .0359
Donor CMV +/Recipient CMV - 2966 1.00 .9468 1754 0.85 .0302
2006ISHLTNote: All factors were significant at p < 0.05 in at least one of the eras.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTSBorderline Significant Risk Factors for 1 Year Mortality
4/1994-1998 (N=16,838)
2001-6/2004 (N=9,511)
Risk Factor N Relative
Risk p-value N
Relative Risk
p-value
Female donor, female recipient 1790 0.87 .1579 1239 0.77 .0587
2006ISHLTNote: All factors were significant at 0.5 < p < 0.1 in at least one of the eras.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTSRisk Factors for 1 Year Mortality
Continuous Factors (see figures)
Recipient age
Recipient weight
Donor age
Donor weight (borderline)
Transplant center volume
PA diastolic pressure
Ischemia time
Bilirubin
Serum creatinine
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year Mortality
Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
Re
lati
ve
Ris
k o
f 1
Ye
ar
Mo
rta
lity
4/1994-1998
2001-6/2004
p = 0.0001p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year Mortality
Donor Age
0
0.5
1
1.5
2
15 25 35 45 55
Donor Age
Re
lati
ve
Ris
k o
f 1
Ye
ar
Mo
rta
lity
4/1994-1998
2001-6/2004
p < 0.0001p = 0.0011
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year MortalityPre-Transplant Recipient Weight
0
0.5
1
1.5
2
50 60 70 80 90 100 110
Recipient Weight (kg)
Re
lati
ve
Ris
k o
f 1
Ye
ar
Mo
rta
lity
4/1994-1998
2001-6/2004
p = 0.0022p = 0.125
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year Mortality
Donor Weight
0
0.5
1
1.5
2
50 60 70 80 90 100 110
Donor Weight (kg)
Re
lati
ve
Ris
k o
f 1
Ye
ar
Mo
rta
lity
4/1994-1998
2001-6/2004
p = 0.12p = 0.06
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year Mortality
Center Volume
0
0.5
1
1.5
2
0 10 20 30 40 50 60 70
Center Volume (cases per year)
Re
lati
ve
Ris
k o
f 1
Ye
ar
Mo
rta
lity 4/1994-1998
2001-6/2004
p < 0.0001p = 0.0006
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year Mortality
Ischemia Time
0
0.5
1
1.5
2
1 2 3 4 5
Ischemia time (hours)
Re
lati
ve
Ris
k o
f 1
Ye
ar
Mo
rta
lity 4/1994-1998
2001-6/2004
p < 0.0001p = 0.0004
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year Mortality
Pre-Transplant Bilirubin
0
0.5
1
1.5
2
0.5 1.5 2.5 3.5 4.5
Recipient bilirubin (mg/dl)
Re
lati
ve
Ris
k o
f 1
Ye
ar
Mo
rta
lity
4/1994-1998
2001-6/2004
p = 0.024p = 0.0067
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year Mortality
Pre-Transplant Creatinine
0
0.5
1
1.5
2
2.5
0.6 1.1 1.6 2.1 2.6
Recipient creatinine (mg/dl)
Re
lati
ve
Ris
k o
f 1
Ye
ar
Mo
rta
lity
4/1994-1998
2001-6/2004
p < 0.0001p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 1 Year MortalityRecipient PA Diastolic Pressure
0
0.5
1
1.5
2
5 10 15 20 25 30 35 40
PA Diastolic Pressure (mm Hg)
Re
lati
ve
Ris
k o
f 1
Ye
ar
Mo
rta
lity 4/1994-1998
2001-6/2004
p = 0.16p = 0.006
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Factors Not Significant for 1 Year Mortality
Recipient Factors: Pneumothorax, sternotomy, thoracotomy, ventricular remodeling, pulmonary embolism, prior malignancy, pulmonary vascular resistance, PCW
Donor Factors: Clinical infection, history of diabetes, height
Transplant Factors: Year of transplant
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality
4/1994-1996 (N=10,048)
1997-6/2000 (N=11,363)
Risk Factor N Relative Risk
p-value
N Relative Risk
p-value
Repeat transplant 225 2.05 .0000 262 1.94 .0000
Ventilator 176 1.39 .0112 239 1.65 .0000
Diagnosis: congenital disease 150 1.24 .1470 168 1.55 .0019
Recipient dialysis 86 2.37 .0000 154 1.31 .0397
Recipient history of diabetes 733 1.03 .6435 1297 1.26 .0000
Intra-aortic balloon pump 352 1.04 .6975 443 1.25 .0116
Prior transfusion 764 1.08 .3080 1284 1.20 .0032
Hospitalized (including ICU) 7344 0.94 .3058 8044 1.20 .0003
Previous pregnancy 777 0.91 .3242 1064 1.20 .0226
Donor history of diabetes 81 0.58 .0299 132 1.18 .2843
HLA DR mismatches (per mismatch) 1 DR MM – 5659 2 DR MM – 3983 1.02 .5721
1 DR MM 2289 2 DR MM –
8893 1.14 .0001
2006ISHLTNote: All factors were significant at p < 0.05 in at least one of the eras.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality
4/1994-1996 (N=10,048)
1997-6/2000 (N=11,363)
Risk Factor N Relative Risk
p-value
N Relative Risk
p-value
Donor history of hypertension 564 1.14 .0985 811 1.14 .0488
Infection requiring IV drug therapy within 2 weeks prior to transplant
455 1.23 .0210 628 1.14 .0838
PRA > 10% 436 1.25 .0097 545 1.14 .1123
Prior sternotomy 2124 0.98 .6850 2855 1.12 .0288
Female recipient 1917 1.15 .0358 2494 1.11 .1070
Diagnosis: coronary artery disease 4324 1.21 .0000 4969 1.09 .0572
HLA B mismatches (per mismatch) 1 B MM – 1972 2 B MM – 7884 1.10 .0199 1 B MM – 2289
2 B MM – 8893 1.08 .0584
Female donor 3223 1.16 .0016 3808 0.99 .7753
Defibrillator 549 0.82 .0296 1483 0.95 .3834
Recipient prior malignancy 149 1.37 .0247 264 0.91 .4707
Diagnosis: Other 1077 0.77 .0006 1148 0.87 .0658
2006ISHLTNote: All factors were significant at p < 0.05 in at least one of the eras.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTSBorderline Significant Risk Factors for 5 Year Mortality
4/1994-1996 (N=10,048)
1997-6/2000 (N=11,363)
Risk Factor N Relative
Risk p-value N
Relative Risk
p-value
Recipient on IV inotropes 3385 1.12 .0772 4074 0.94 .2558
Not ABO identical vs. ABO identical 1775 0.98 .7268 1537 0.90 .0689
2006ISHLTNote: All factors were significant at 0.5 < p < 0.1 in at least one of the eras.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTSRisk Factors for 5 Year Mortality
Continuous Factors (see figures)
Recipient age
Recipient BMI
Donor age
Donor weight
Transplant center volume
PA diastolic pressure (borderline)
Ischemia time
Bilirubin
Serum creatinine
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality
Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity
4/1994-1996
1997-6/2000
p = 0.0022p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality
Donor Age
0
0.5
1
1.5
2
15 25 35 45 55
Donor Age
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity
4/1994-1996
1997-6/2000
p < 0.0001p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality
Pre-Transplant Recipient BMI
0
0.5
1
1.5
2
17 23 29 35
Recipient BMI (kg/m2)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity
4/1994-1996
1997-6/2000
p < 0.0001p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality
Donor Weight
0
0.5
1
1.5
2
50 60 70 80 90 100 110
Donor Weight (kg)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity
4/1994-1996
1997-6/2000
p = 0.68p = 0.008
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality
Center Volume
0
0.5
1
1.5
2
0 10 20 30 40 50 60 70
Center Volume (cases per year)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity 4/1994-1996
1997-6/2000
p = 0.0001p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality
Ischemia Time
0
0.5
1
1.5
2
1 2 3 4 5
Ischemia time (hours)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity 4/1994-1996
1997-6/2000
p = 0.0028p = 0.0014
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality
Pre-Transplant Bilirubin
0
0.5
1
1.5
2
0.5 1.5 2.5 3.5 4.5
Recipient bilirubin (mg/dl)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity
4/1994-1996
1997-6/2000
p = 0.078p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality
Pre-Transplant Creatinine
0
0.5
1
1.5
2
0.6 1.1 1.6 2.1 2.6
Recipient creatinine (mg/dl)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity 4/1994-1996
1997-6/2000
p < 0.0001p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year MortalityRecipient PA Diastolic Pressure
0
0.5
1
1.5
2
5 10 15 20 25 30 35 40
PA Diastolic Pressure (mm Hg)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity 4/1994-1996
1997-6/2000
p = 0.089p = 0.36
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Factors Not Significant for 5 Year Mortality
Recipient Factors: VAD, gender, pulmonary vascular resistance, thoracotomy, pneumothorax, pulmonary embolism
Donor Factors:History of cancer, clinical infection, cause of death
Transplant Factors: Year of transplant, CMV mismatch
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS 5-Year Predicted Survival Model
Impact of Donor Characteristics (I)
50%
60%
70%
80%
90%
100%
0 1 2 3 4 5
Time (years)
Pre
dic
ted
Su
rviv
all
Cohort average
Donor: 50 y.o. female, COD = CVA, weight = 70 kg, height = 65 in.
Donor: 30 y.o. male, COD = MVA, weight = 80 kg, height = 70 in.
ISHLT 2006
Recipient: 30 y.o. female, PRA < 10%, weight=75 kg, height=65 in, center volume=25/year, year of tx=99/00, bilirubin=0.9, PA diastolic=23, creatinine=1.2 mg/dl, ischemia=180 min, PVR=2
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS5-Year Predicted Survival Model
Impact of Donor Characteristics (II)
50%
60%
70%
80%
90%
100%
0 1 2 3 4 5
Time (years)
Pre
dic
ted
Su
rviv
all Cohort average
Donor: 30 y.o. male, COD = MVA, weight = 80 kg, height = 70 in.
Donor: 50 y.o. female, COD = CVA, weight = 70 kg, height = 65 in.
ISHLT 2006
Recipient: 63 y.o. male, Dx=CAD, puls. LVAD, PRA < 10%, weight=85 kg, height=70 in, PVR=2, volume=25/year, year of tx=99/00, bilirubin=0.9, PA diastolic=23, creatinine=1.3 mg/dl, ischemia=180 min
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year
4/1994-1996 (N=5736)
1997-6/2000 (N=8799) Risk Factors
N Relative Risk
p-value
N Relative Risk
p-value
Stroke prior to discharge 61 1.37 .2542 96 1.81 .0040
Repeat transplant 108 1.42 .1204 173 1.53 .0254
CAV within 1st year 219 1.85 <.0001 423 1.45 .0011
Drug-treated infection prior to discharge 614 1.12 .3032 1222 1.45 <.0001
Recipient cerebrovascular event prior to transplant
162 1.26 .1904 335 1.33 .0241
Recipient history of diabetes 486 1.07 .5945 1008 1.33 .0007
2006ISHLTNote: All factors were significant at p < 0.05 in at least one of the eras.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year
Risk Factor 4/1994-1996 (N=5736)
1997-6/2000 (N=8799)
N Relative Risk
p-value
N Relative Risk
p-value
Treated for rejection during 1st year 1486 1.19 .0232 2705 1.32 <.0001
Recipient female 1109 1.20 .1030 1928 1.21 .0243
Diagnosis: coronary artery disease vs. cardiomyopathy
2455 1.28 .0034 3831 1.02 .7787
Infection requiring IV drug therapy within 2 weeks prior to transplant
243 1.34 .0437 470 0.95 .6960
3 or 4 total HLA mismatches vs. 5 or 6 1684 1.13 .0963 2606 0.82 .0030
2006ISHLTNote: All factors were significant at p < 0.05 in at least one of the eras.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Borderline Significant Risk Factors for 5 Year Mortality
Conditional on Survival to 1 Year
4/1994-1996 (N=5736)
1997-6/2000 (N=8799) Post-Transplant Risk Factor
N Relative Risk
p-value
N Relative Risk
p-value
Additional surgery required prior to discharge
220 1.34 .0574 534 1.12 .3193
0, 1 or 2 total HLA mismatches vs. 5 or 6 mismatches
177 0.62 .0648 277 0.93 .6519
Diagnosis = valvular heart disease vs. cardiomyopathy
160 0.60 .0883 197 0.65 .0635
2006ISHLTNote: All factors were significant at p < 0.05 in at least one of the eras.
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTSRisk Factors for 5 Year Mortality Conditional on Survival to 1 Year
Continuous Factors (see figures)
Recipient age
Recipient weight
Donor age
Donor BMI
Bilirubin
Serum creatinine
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year MortalityConditional on Survival to 1 Year
Recipient Age
0
0.5
1
1.5
2
2.5
20 25 30 35 40 45 50 55 60 65
Recipient Age
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity
4/1994-1996
1997-6/2000
p < 0.0001p = 0.0036
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year MortalityConditional on Survival to 1 Year
Donor Age
0
0.5
1
1.5
2
15 25 35 45 55
Donor Age
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity
4/1994-1996
1997-6/2000
p < 0.0001p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year MortalityConditional on Survival to 1 Year
Donor BMI
0
0.5
1
1.5
2
17 23 29 35
Donor BMI (kg/m2)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity
4/1994-1996
1997-6/2000
p = 0.035p = 0.5
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year MortalityConditional on Survival to 1 YearPre-transplant Recipient Weight
0
0.5
1
1.5
2
50 60 70 80 90 100 110
Recipient Weight (kg)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity
4/1994-1996
1997-6/2000
p = 0.9p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year MortalityConditional on Survival to 1 Year
Pre-Transplant Bilirubin
0
0.5
1
1.5
2
0.5 1.5 2.5 3.5 4.5
Recipient bilirubin (mg/dl)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity
4/1994-1996
1997-6/2000
p = 0.2p = 0.008
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 5 Year MortalityConditional on Survival to 1 Year
Pre-Transplant Creatinine
0
0.5
1
1.5
2
0.6 1.1 1.6 2.1 2.6
Recipient creatinine (mg/dl)
Re
lati
ve
Ris
k o
f 5
Ye
ar
Mo
rta
lity 4/1994-1996
1997-6/2000
p = 0.010p = 0.26
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 10 Year Mortality (Transplants: 1990-6/1994)
Risk Factor N p-value Relative
Risk
Repeat transplant 382 <.0001 2.45
Recipient on VAD 29 0.0003 2.31
Recipient on ventilator 251 <.0001 1.55
Recipient on IV inotropes 2073 0.0016 1.12
Number of HLA DR mismatches (RR per mismatch) 690 0 DR MM
9331 1 DR MM 6181 2 DR MM
<.0001 1.12
Diagnosis: coronary artery disease vs. cardiomyopathy
6824 0.0002 1.11
Number of HLA B mismatches (RR per mismatch 301 0 B MM: 3274 1 B MM
12627 2 B MM 0.0422 1.05
ABO identical 12811 0.0018 0.91
Diagnosis: other vs. cardiomyopathy 1850 0.0223 0.90
Female donor/female recipient 1336 0.0064 0.86
2006ISHLT
(N=16,202)
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTSBorderline Significant Risk Factors for 10 Year Mortality
(Transplants: 1990-6/1994)
Risk Factor N Relative
Risk p-value
Female donor 4539 1.06 .0582
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTSRisk Factors for 10 Year Mortality
Continuous Factors (see figures)
Recipient age
Recipient height
Donor age
Transplant center volume
Ischemia time
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 10 Year Mortality
Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
Re
lati
ve
Ris
k o
f 1
0 Y
ea
r M
ort
alit
y
p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 10 Year Mortality
Donor Age
0
0.5
1
1.5
15 25 35 45 55
Donor Age
Re
lati
ve
Ris
k o
f 1
0 Y
ea
r M
ort
alit
y
p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 10 Year MortalityPre-Transplant Recipient Height
0
0.5
1
1.5
2
150 160 170 180 190
Recipient height (cm)
Re
lati
ve
Ris
k o
f 1
0 Y
ea
r M
ort
alit
y
p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 10 Year Mortality
Center Volume
0
0.5
1
1.5
2
0 10 20 30 40 50 60 70
Center Volume (cases per year)
Re
lati
ve
Ris
k o
f 1
0 Y
ea
r M
ort
alit
y
p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 10 Year Mortality
Ischemia Time
0
0.5
1
1.5
2
1 2 3 4 5
Ischemia time (hours)
Re
lati
ve
Ris
k o
f 1
0 Y
ea
r M
ort
alit
y
p = 0.0005
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS10-Year Predicted Survival Model
Impact of Donor Characteristics (I)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1 2 3 4 5 6 7 8 9 10
Time (years)
Pre
dic
ted
Su
rviv
all
Donor: 50 y.o. female, COD = CVA, weight = 70 kg, height = 65 in.
Cohort average
Donor: 30 y.o. male, COD = MVA, weight = 80 kg, height =70 in.
ISHLT 2006
Recipient: 30 y.o. female, PRA < 10%, weight=75 kg, height=65 in, center volume=25/year, year of tx=1993/94, bilirubin=0.9, PA diastolic=23, creatinine=1.2 mg/dl, ischemia=180 min, PVR=2
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS10-Year Predicted Survival Model
Impact of Donor Characteristics (II)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1 2 3 4 5 6 7 8 9 10
Time (years)
Pre
dic
ted
Su
rviv
all
Cohort average
Donor: 50 y.o. female, COD = CVA, weight = 75 kg, height = 65 in.
Donor: 30 y.o. male, COD = MVA, weight = 80 kg, height = 70 in.
ISHLT 2006
Recipient: 63 y.o. male, Dx=CAD, puls. LVAD, PRA < 10%, weight=85 kg, height=70 in, PVR=2, volume=25/year, year of tx=93/94, bilirubin =0.9, PA diastolic=23, creatinine=1.3 mg/dl, ischemia=180 min
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 10 Year Mortality
Conditional on Survival to 3 Years (Transplants: 1990-6/1994)
Risk Factor N p-value Relative
Risk
Repeat transplant 165 .0005 1.61
Diagnosis: coronary artery disease vs. cardiomyopathy
4738 <.0001 1.18
2006ISHLT
(N=11,113)
J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 10 Year Mortality Conditional on 3 Year Survival
Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
Re
lati
ve
Ris
k o
f 1
0 Y
ea
r M
ort
ali
ty
p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 10 Year Mortality Conditional on 3 Year Survival
Donor Age
0
0.5
1
1.5
2
15 25 35 45 55
Donor Age
Re
lati
ve
Ris
k o
f 1
0 Y
ea
r M
ort
alit
y
p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS Risk Factors for 10 Year Mortality Conditional on 3 Year Survival
BMI Ratio
0
0.5
1
1.5
2
0.5 0.6 0.7 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5
Donor BMI/Recipient BMI
Re
lati
ve
Ris
k o
f 1
0 Y
ea
r M
ort
alit
y
p < 0.0001
2006ISHLT J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS (1997-6/2002) Risk Factors for Developing Cardiac Allograft Vasculopathy
within 3 Years
VARIABLE Relative
RIsk P-value
95% Confidence
Interval
Transplant year = 1997 vs. 2001/2002 1.31 .0012 1.11 -1.55
Transplant year = 1998 vs. 2001/2002 1.25 .0083 1.06 -1.47
Donor history of hypertension 1.23 .0099 1.05 -1.45
Infection requiring IV drug therapy within 2 weeks of transplant
1.22 .0324 1.02 -1.46
(N=7,072)
ISHLT
Note: Donor gender was not significant as an independent risk factor but was significant as an interaction with donor age.
2006J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS (1997-6/2002) Risk Factors for Developing Cardiac Allograft Vasculopathy
within 3 Years
Continuous Factors (see figures)
Donor age
Donor age*donor gender interaction
Recipient BMI
Transplant center volume
ISHLT 2006J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS (1997-6/2002)Risk Factors for Developing Cardiac Allograft Vasculopathy
within 3 YearsDonor Age and Donor Gender
0
0.5
1
1.5
2
2.5
3
15 20 25 30 35 40 45 50 55
Donor Age
Ris
k o
f C
AV
wit
hin
3 Y
ears
.
Male DonorFemale Donor
p < 0.0001
ISHLT 2006J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS (1997-6/2002) Risk Factors for Developing Cardiac Allograft Vasculopathy
within 3 Years Pre-Transplant Recipient BMI
0
0.5
1
1.5
2
18 20 22 24 26 28 30 32 34 36
Recipient BMI
Ris
k o
f C
AV
wit
hin
3 Y
ears
.
p = 0.0005
ISHLT 2006J Heart Lung Transplant 2006;25:869-79
ADULT HEART TRANSPLANTS (1997-6/2002)Risk Factors for Developing Cardiac Allograft Vasculopathy
within 3 YearsCenter Volume
0
0.5
1
1.5
2
0 10 20 30 40 50 60 70
Center Volume (cases per year)
Ris
k o
f C
AV
wit
hin
3 Y
ears
.
p < 0.0001
ISHLT 2006J Heart Lung Transplant 2006;25:869-79