J Heart Lung Transplant 2009;28: 989-1049 HEART TRANSPLANTATION Pediatric Recipients ISHLT 2009.
HEART TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781.
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Transcript of HEART TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781.
HEART TRANSPLANTATION
Overall
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
NUMBER OF HEART TRANSPLANTS REPORTED BY YEAR
189 317665
1182
2158
2710
31373362
4001 4171 4197 4365 4439 4399 4263 41673833
3563 3410 3367 3269 3180 3026 3095
0
500
1000
1500
2000
2500
3000
3500
4000
4500
Nu
mb
er
of
Tra
nsp
lan
ts
ISHLT 2007
NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of hearts transplanted worldwide has declined in recent years.
J Heart Lung Transplant 2007;26: 769-781
AVERAGE CENTER VOLUMEHeart Transplants: January 1, 1992 - June 30, 1996
and January 1, 2002 – June 30, 2006
58 59
81
49
15
4055
80
2515 3 4 3455
0
10
20
30
40
50
60
70
80
90
1-4 5-9 10-19 20-29 30-39 40-49 50-74 75+
Average number of heart transplants per year
Nu
mb
er
of
cen
ters
.
1992-6/1996
2002-6/2006
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
DISTRIBUTION OF TRANSPLANTS BY CENTER VOLUMEHeart Transplants: January 1, 1992 - June 30, 1996
and January 1, 2002 – June 30, 2006
28
24 26
129
6
14
2
11
33
18 16
47 9
0
5
10
15
20
25
30
35
1-4 5-9 10-19 20-29 30-39 40-49 50-74 75+
Average number of heart transplants per year
Per
cen
tag
e o
f tr
ansp
lan
ts
1992-6/1996
2002-6/2006
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
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 2007 J Heart Lung Transplant 2007;26: 769-781
AGE DISTRIBUTIONOF HEART RECIPIENTS (1/1982-6/2006)
% o
f T
r%
of
Tra
ns
pla
nts
ns
pla
nts
0
5
10
15
20
25
30
35
40
0-9 10-19 20-29 30-39 40-49 50-59 60+
Recipient Age
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
AGE DISTRIBUTION OF HEART TRANSPLANT RECIPIENTS BY ERA
0
5
10
15
20
25
30
35
40
0-9 10-19 20-29 30-39 40-49 50-59 60+
Recipient Age
% o
f tr
an
sp
lan
ts
1982-1991 (N = 20,991)
1992-2001 (N = 39,801)
2002 - 6/2006 (N = 14,041)
P < 0.0001
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2005)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Years
Su
rviv
al (%
)
Half-life = 10.0 yearsConditional Half-life = 13.0 years
N=70,702
ISHLT 2007
N at risk at 22 years: 33
HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2005)
J Heart Lung Transplant 2007;26: 769-781
HEART TRANSPLANTATION
Adult Recipients
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
Congenital2%
ReTX2%
Myopathy45%
Misc.3%
Valvular3%
CAD45%
1/1982-6/2006
DIAGNOSIS IN ADULT HEART TRANSPLANTS
203040506070
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
% o
f Cas
es
Myopathy CAD
CAD38%
Valvular2%
Misc.10%
Myopathy45%
ReTX2%
Congenital3%
1/2003-6/2006
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
0%
20%
40%
60%
80%
100%
Europe North America Other
10-19 years 20-29 years 30-39 years 40-49 years50-59 years 60+ years
% o
f T
ran
sp
lan
tsADULT HEART TRANSPLANTS:
RECIPIENT AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
0%
20%
40%
60%
80%
100%
Europe North America Other
% o
f Do
nors
0-10 years 11-17 years 18-34 years35-49 years 50-59 years 60+ years
ADULT HEART TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION
Transplants between January 2000 and June 2006
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: 1/1982 – 6/2005)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years
1982-1991 (N=18,844)
1992-2001 (N=34,987)
2002-6/2005 (N=9,459)
All comparisons significant at p < 0.0001
HALF-LIFE 1982-1991: 8.9 years; 1992-2001: 10.3 years; 2002-6/2005: NA
Su
rviv
al (
%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: 1/1982-6/2005)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years
Su
rviv
al
(%)
18-34 (N= 6,688) 35-49 (N=17,969)50-59 (N=25,166) 60-64 (N=9,648)65-69 (N= 3,241) 70+ (N= 346)
HALF-LIFE 18-34: 11.9 years; 35-49: 10.8 years; 50-59: 9.7 years; 60-64: 8.8 years; 65-69: 8.1 years; 70+: 6.9 years
All pair-wise comparisons are statistically significant at p < 0.01
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: 1/1998-6/2005)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8
Years
Su
rviv
al
(%)
18-34 (N= 2,248) 35-49 (N= 5,244)50-59 (N=8,292) 60-64 (N=4,001)65-69 (N= 1,814) 70+ (N= 235)
All pair-wise comparisons are statistically significant at p < 0.05
except 18-34 vs. 50-64; 18-34 vs. 60-64; and 65-69 vs. 70+
ISHLT 2007
HALF-LIFE 18-34: NA; 35-49: NA; 50-59: NA;
60-64: 8.3 years; 65-69: 8.1 years; 70+: 7.3 years
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis (Transplants: 1/1982-6/2005)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years
Su
rviv
al (
%)
Cardiomyopathy (N = 27,393) Coronary artery disease (N = 27,846)Congenital diagnosis (N = 1,081) Retransplant (1,255)Valvular (N= 2,027) Other (N= 1,578)
HALF-LIFE Cardiomyopathy: 11.0 years; CAD: 9.1 years; Congenital: 13.4 years; Retransplant: 4.6 years; Valvular: 10.6 years; Other: 11.8 years
All pair-wise comparisons with Cardiomyopathy are significant at p < 0.005 except for Congenital; CAD vs. ReTx: p < 0.0001; CAD vs. Valvular: p = 0.005; Valvular vs. ReTx: p < 0.0001; Congenital vs. ReTx: p < 0.0001; ReTx vs. Other: p < 0.0001
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis
Conditional on Survival to 1 Year (Transplants: 1/1982-6/2005)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years
Su
rviv
al (
%)
Cardiomyopathy (N = 21,707)Coronary artery disease (N = 21,661)Congenital diagnosis (N = 773)Retransplant (766)Valvular (N= 1,506)Other (N= 929)
All pair-wise comparisons are significant at p <.05 except Cardiomyopathy vs. valvular (p = 34), valvular vs. other (p= .14), andCongenital vs. other (p = .12).
HALF-LIFE Cardiomyopathy: 13.3 years; CAD: 11.3 years; Congenital: 17.1 years; Retransplant: 9.3 years; Valvular: 13.4 years; Other: 14.4 years
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis (Transplants: 1/2000-6/2005)
50
60
70
80
90
100
0 1 2 3 4 5 6
Years
Su
rviv
al (
%)
Cardiomyopathy (N=6,722) Coronary artery disease (N=6,520)
Congenital Diagnosis (N=358) Retransplant (N=318)
Valvular (N=405) Other (N=903)
All pair-wise comparisons with Cardiomyopathy are significant at p < 0.001; All pair-wise comparisons with CAD are significant at p < 0.5 except CAD vs. valvular. All other pair-wise comparisons were not statistically significant.
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Diagnosis Conditional on Survival to 1 Year
(Transplants: 1/2000-6/2005)
50
60
70
80
90
100
0 1 2 3 4 5 6
Years
Su
rviv
al (%
)
Cardiomyopathy (N=5,344) Coronary artery disease (N=5.096)
Congenital Diagnosis (N=251) Retransplant (N=230)
Valvular (N=305) Other (N=449)
ISHLT 2007
Cardiomyopathy vs. Re-TX: p = .006; Cardiomyopathy vs. Other: p = .02; CAD vs. Re-TX: p = .03; Congenital vs. Re-TX: p = .01; Valvular vs. Other: = .01; Re-TX vs. Other: p = .0003
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by PVR (Transplants: 1/2002-6/2005)
50
60
70
80
90
100
0 1 2 3 4
Years
Su
rviv
al (
%)
1-<3 Wood units (N= 3,352) 3-<5 Wood units (N= 1,019)
5+ Wood units (N= 365)
1-<3 vs. 3-<5: p < .0001; 1-<3 vs. 5+: p = .04; 3-<5 vs. 5+: p = .55
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by VAD usage (Transplants: 1/1999-6/2005)
50
60
70
80
90
100
0 1 2 3 4 5
Years
Su
rviv
al (
%)
Pulsatile flow (N=2,043) No LVAD / No Inotropes (N=10,710)
No LVAD / Inotropes (N = 5,521)
Pulsatile vs. No LVAD/Inotropes: p = .002;Pulsatile vs. No LVAD/No inotropes: p = 0.0007; No LVAD/No inotropes vs. No LVAD/Inotropes: p = .95
NOTE: There were 96 transplants with continuous flow VADs
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by VAD usage and Era (Transplants: 1/1999-6/2005)
50
60
70
80
90
100
0 1 2 3 4 5
Years
Su
rviv
al (
%)
Pulsatile, 1999-2002 (N = 1,187) No LVAD/Inotrope, 1999-2002 (N=3,699)
Pulsatile, 2003-6/2005 (N=856) No LVAD/Inotrope, 2003-6/2005 (N=1,822)
Pulsatile vs. no LVAD/Inotropes (1999-2002): p = 0.07Pulsatile vs. no LVAD/Inotropes (2003-6/2005): p = .001
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS1-Year Predicted Survival Model (Transplants: 1/2002-6/2005)
Impact of Pre-Transplant VAD
ISHLT 2007
75%
80%
85%
90%
95%
100%
0 30 60 90 120 150 180 210 240 270 300 330 360
Time (days)
Pre
dic
ted
Su
rviv
al
No Pre-op VAD
Pre-op pulsatile VAD
Recipient: 54 y.o., Dx=cardiomyopathy, weight=78 kg, PVR=2.2, volume=22/year, bilirubin=0.8, PA systolic=40, creatinine=1.3 mg/dl, ischemia=180 min
Donor: 30 y.o., weight = 77 kg
J Heart Lung Transplant 2007;26: 769-781
0
20
40
60
80
100
0-2 months >2-6 months >6-12months
>12-36months
>36-60months
>60 months
Time between previous and current transplant
1 Y
ear
Pat
ien
t S
urv
ival
(%
) 1/1982-12/19911/1992-12/20011/2002-6/2005
Comparison of survival for interval < 12 months vs. > 12 months: p < 0.0001Comparison of survival for interval < 12 months vs. > 12 months for 1/00-6/2004: p = 0.0006
150
148
38 2139 77 8351 35 287
28 2 76 133
N=13 N=4 N=5 N=15 N=14
ADULT HEART RE-TRANSPLANTS1-Year Survival
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART RECIPIENTS Functional Status of Surviving Recipients
(Follow-ups: 1995 - June 2006)
0%
20%
40%
60%
80%
100%
1 Year (N = 15,388) 3 Years (N = 13,600) 5 Years (N = 11,698) 7 Years (N = 9,306)
No Activity Limitations Performs with Some Assistance Requires Total Assistance
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART RECIPIENTSEmployment Status of Surviving Recipients
(Follow-ups: 1995 - June 2006)
0%
20%
40%
60%
80%
100%
1 Year (N = 16,161) 3 Year (N = 14,165) 5 Year (N = 12,175) 7 Year (N = 9,910)
Retired
Not Working
Working Part Time
Working Full Time
Working (FT/PTstatus unknown)
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART RECIPIENTSRehospitalization Post-transplant of Surviving Recipients
(Follow-ups: 1995 - June 2006)
0%
20%
40%
60%
80%
100%
Up to 1 Year (N = 19,425)
Between 2 and 3 Years (N = 16,781)
Between 4 and 5 Years (N = 14,451)
Between 6 and 7 Years (N = 11,746)
No Hospitalization Hospitalized: Not Rejection/Not InfectionHospitalized: Rejection Only Hospitalized: Infection OnlyHospitalized: Rejection + Infection
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
0
10
20
30
40
50
60
Any Induction (N = 5,850) Polyclonal ALG/ATG (N =2,595)
OKT3 (N = 557) IL2R-antagonist (N =2,917)
% o
f p
ati
en
tsADULT HEART RECIPIENTS
Induction Immunosuppression (Transplants: January 2001 – June 2006)
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
0
10
20
30
40
50
60
Any Induction PolyclonalALG/ATG
OKT3 IL2R-antagonist
% o
f p
ati
en
ts
1995 2000 2005
ADULT HEART RECIPIENTSInduction Immunosuppression (Transplants: 1995, 2000 and 2005)
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Type
(Transplants: 1/2000-6/2005, conditional on survival to 14 days)
50
60
70
80
90
100
0 1 2 3 4 5 6
Years
Su
rviv
al (
%)
No induction (N= 5,389) Polyclonal induction (N= 2,339)
IL2-R antagonist (N= 2,361) OKT3 (N= 586)
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
0
20
40
60
80
100
Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone
% o
f P
ati
en
ts
Year 1 (N = 6,313) Year 5 (N = 5,418)
ADULT HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up
(Follow-ups: January 2003 - June 2006)
NOTE: Different patients are analyzed in Year 1 and Year 5
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
0
20
40
60
80
100
Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone
% o
f P
atie
nts
2000 (N=3,486) 2003 (N = 3,630) Jan. 2006 - Jun 2006 (N = 1,508)
ADULT HEART RECIPIENTS Maintenance Immunosuppression at Time of 1 Year Follow-up
NOTE: Different patients are analyzed in each time frame.
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
0%
20%
40%
60%
80%
100%
Year 1 (N = 4,369) Year 5 (N = 3,732)
None
Other
Tacrolimus
Cyclosporine
Rapa + cellcycle
Rapa + calcineurin
Tacrolimus + MMF
Tacrolimus + AZA
Cyclosporine + MMF
Cyclosporine + AZA
% o
f P
ati
en
tsADULT HEART RECIPIENTS
Maintenance Immunosuppression Drug Combinations at Time of Follow-up(Follow-ups: January 2004 - June 2006)
NOTES: Different patients are analyzed in Year 1 and Year 5. In the Year 1 cohort 73.9% of patients were on prednisone; in the Year 5 cohort 56.8% of patients were on prednisone.
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
0%
20%
40%
60%
80%
100%
Europe: Year1 (N = 552)
NorthAmerica: Year1 (N = 3,772)
Other: Year 1(N = 45)
Europe: Year5 (N = 639)
NorthAmerica: Year5 (N = 3,064)
Other: Year 5(N = 29)
Cyclosporine + AZA Cyclosporine + MMF Tacrolimus + AZA Tacrolimus + MMF
Rapa + calcineurin Rapa + cellcycle Other None
% o
f P
ati
en
ts
ADULT HEART RECIPIENTS Maintenance Immunosuppression Drug Combinations at Time of Follow-up
(Follow-ups: January 2004 - June 2006)
NOTES: Different patients are analyzed in Year 1 and Year 5. ISHLT 2007
J Heart Lung Transplant 2007;26: 769-781
0%
20%
40%
60%
80%
100%
Year 1 (N = 4,447) Year 5 (N = 4,447)
% o
f P
atie
nts
None
Other
Tacrolimus
Cyclosporine
Rapa + cellcycle
Rapa + calcineurin
Tacrolimus + MMF
Tacrolimus + AZA
Cyclosporine + MMF
Cyclosporine + AZA
ADULT HEART RECIPIENTS Maintenance Immunosuppression Drug Combinations at Time of Follow-up
For the Same Patients(Follow-ups: January 1999 - June 2006)
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
PERCENTAGE OF ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Type of Induction (Transplants: January 1, 2000 - June 30, 2005)
0
10
20
30
40
50
60
70
Overall 18-44 45-62 63+ F M
% t
reate
d f
or
reje
cti
on
wit
hin
1 y
ear
.
No induction (N = 5,327) Polyclonal (N = 2,461) IL2R-antagonist (N = 2,353) OKT3 (N = 583)
For females: no induction vs. OKT3 (p = 0.0006); polyclonal vs. OKT3 (p = 0.004); IL2R vs. OKT3 (p = 0.0157)For males: no induction vs. OKT3 (p = 0.0038); polyclonal vs. OKT3 (p = 0.0386); IL2R vs. OKT3 (p = 0.002)
Overall: no induct vs. OKT3 (p<0.0001); poly vs. OKT3 (p<0.0001); poly vs. IL2 (p=0.026); IL2 vs. OKT3 (p=0.013)45-62: All comparisons with OKT3 (p=0.0005 or less). No other comparisons within age groups were statistically significant at 0.05.
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
NUMBER OF REJECTION EPISODES FOR ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Type of Induction (Transplants: January 1, 2000 - June 30, 2005)
0
0.5
1
1.5
2
2.5
3
Overall 18-44 45-62 63+ F M
Ave
rag
e n
um
ber
of
reje
ctio
n e
pis
od
es
No induction Polyclonal IL2R-antagonist OKT3
Overall: no induction vs. OKT3 (p = 0.0017); polyclonal vs. OKT3 (p=0.0065); IL2 vs. OKT3 (p=0.0003). 18-44: no induction vs. IL2 (p = 0.037).45-62: no induction vs. OKT3 (p = 0.0025); IL2 vs. OKT3 (p = 0.0034).63+: polyclonal vs. OKT3 (p = 0.0228).For females: no induction vs. OKT3 (p = 0.0078); IL2 vs. OKT3 (p = 0.0466). For males: no induction vs. OKT3 (p =0.040); polyclonal vs. OKT3 (p=0.045); IL2 vs. OKT3 (p = 0.0022).
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
PERCENTAGE OF ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR
Stratified by Maintenance Immunosuppression (Transplants: January 1, 2000 - June 30, 2005)
0
10
20
30
40
50
60
Overall 18-44 45-62 63+ F M
Cyclosporine + MMF (N = 4,973) Tacrolimus + MMF (N = 2,527)
% tre
ate
d fo
r re
jectio
n w
ith
in 1
year
Overall: p<0.000118-44: p<0.0001Male: p<0.0001
ISHLT 2007
NOTE: There were 1,119 patients with cyclosporine+AZA and 138 with tacrolimus+AZA. These groups were excluded due to small numbers.
J Heart Lung Transplant 2007;26: 769-781
NUMBER OF REJECTION EPISODES FOR ADULT HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR Stratified by Maintenance Immunosuppression (Transplants: January 1, 2000 - June 30, 2005)
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
Overall 18-44 45-62 63+ F M
Cyclosporine + MMF Tacrolimus + MMF
Overall: p=0.037818-44: p=0.049
Avera
ge n
um
ber
of re
jectio
n e
pis
do
es
ISHLT 2007
NOTE: Cyclosporine+AZA and tacrolimus+AZA were excluded due to small numbers.
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTATION Kaplan-Meier Survival Stratified by Rejection Within 1st Year
Conditional on survival to 1 year for transplants: 1/1999-6/2004
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Years
Su
rviv
al (
%)
No rejection (N=4,832) Rejection (N=3,694)
p < 0.0001
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
POST-HEART TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors at 1 Year Post-Transplant
(Follow-ups: April 1994 – December 1997 and January 2002 - June 2006)
Follow-ups: April 1994-
December 1997 Follow-ups: January 2002 –
June 2006
Outcome Within 1
Year Total N with
known response Within 1
Year Total N with
known response
Hypertension 68.9% (N = 6,425) 74.4% (N = 7,099)
Renal Dysfunction 20.4% (N = 6,378) 30.4% (N = 7.247)
Abnormal Creatinine < 2.5 mg/dl 11.3% 22.4% Creatinine > 2.5 mg/dl 8.1% 5.9% Chronic Dialysis 1.0% 1.6% Renal Transplant 0.1% 0.4%
Hyperlipidemia 33.3% (N = 6,816) 67.8% (N = 7,640)
Diabetes 20.9% (N = 6,433) 31.5% (N = 7,199)
Cardiac Allograft Vasculopathy 7.9% (N = 5,847) 7.1% (N = 6,556)
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
POST-HEART TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors at 5 and 10 Years Post-Transplant
(Follow-ups: April 1994 - June 2006)
Outcome Within 5
Years Total N with
known response Within 10
Years Total N with
known response
Hypertension 93.8% (N = 8,266) 98.5% (N = 1,586)
Renal Dysfunction 32.6% (N = 8,859) 38.7% (N = 1,829)
Abnormal Creatinine < 2.5 mg/dl 21.2% 24.4% Creatinine > 2.5 mg/dl 8.4% 8.2% Chronic Dialysis 2.5% 4.9% Renal Transplant 0.5% 1.2%
Hyperlipidemia 87.1% (N = 9,237) 93.3% (N = 1,890)
Diabetes 34.8% (N = 8,219) 36.7% (N = 1,601)
Cardiac Allograft Vasculopathy 31.5% (N = 5,944) 52.7% (N = 896)
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
FREEDOM FROM CARDIAC ALLOGRAFT VASCULOPATHY AND FREEDOM FROM SEVERE RENAL DYSFUNCTION* For Adult Heart Recipients (Follow-ups: April 1994-June 2006)
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Years
Freedom from CAV (N= 18,278)
Freedom from Severe Renal Dysfunction (N= 20,115)
* Severe renal dysfunction = Creatinine > 2.5 mg/dl, dialysis or renal transplant
% F
reed
om
fro
m C
AV
or
Fre
ed
om
fro
m S
evere
Ren
al D
ysfu
cn
tio
n
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
PATIENT SURVIVAL AFTER REPORT OF CAV AND PATIENT SURVIVAL IN PATIENTS WITHOUT CAV*
(Transplants: April 1994-June 2004)
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Time after Report of CAV* (Years)
Su
rviv
al (%
)
No CAV (N = 10,330)
CAV (N = 2,597)
p < 0.0001
ISHLT 2007
* Patients without CAV conditioned on survival to median time of CAV development (514 days)
J Heart Lung Transplant 2007;26: 769-781
MALIGNANCY POST-HEART TRANSPLANTATION FOR ADULTSCumulative Prevalence in Survivors (Follow-ups: April 1994 - June 2006)
Malignancy/Type 1-Year Survivors
5-Year Survivors
10-Year Survivors
No Malignancy 20441 (97.1%) 7780 (84.9%) 1264 (68.1%)
Malignancy (all types combined) 612 (2.9%) 1389 (15.1%) 592 (31.9%)
Malignancy Type
Skin 282 937 360
Lymph 142 127 38
Other 132 359 108
Type Not Reported 56 39 126
”Other” includes: prostate (11, 34, 17), adenocarcinoma (7, 4, 2), lung (5, 4, 1), bladder (4, 5, 4), sarcoma (3, 3, 1), breast (2, 8, 3), cervical (2, 4, 0), colon (2, 3, 1), and renal (2, 7, 2). Numbers in parentheses are those reported within 1 year, 5 years and 10 years, respectively.
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
FREEDOM FROM MALIGNANCYFor Adult Heart Recipients (Follow-ups: April 1994 - June 2006)
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Years
All malignancy Lymph Skin Other
% F
ree f
rom
Malig
nan
cy
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2006)
CAUSE OF DEATH 0-30 Days
(N = 3,006)
31 Days –
1 Year
(N = 2,722)
>1 Year –
3 Years
(N = 2,135)
>3 Years –
5 Years
(N = 1,857)
>5 Years –
10 Years
(N = 4,054)
>10 Years
(N = 2,107)
CARDIAC ALLOGRAFT VASCULOPATHY
52 (1.7%) 127 (4.7%) 298 (14.0%) 299 (16.1%) 581 (14.3%) 309 (14.7%)
ACUTE REJECTION 193 (6.4%) 338 (12.4%) 220 (10.3%) 82 (4.4%) 69 (1.7%) 26 (1.2%)
LYMPHOMA 2 (0.1%) 54 (2.0%) 85 (4.0%) 96 (5.2%) 195 (4.8%) 73 (3.5%)
MALIGNANCY, OTHER 1 (0.0%) 57 (2.1%) 218 (10.2%) 340 (18.3%) 749 (18.5%) 392 (18.6%)
CMV 4 (0.1%) 34 (1.2%) 16 (0.7%) 3 (0.2%) 5 (0.1%) 1 (0.0%)
INFECTION, NON-CMV 393 (13.1%) 896 (32.9%) 276 (12.9%) 180 (9.7%) 442 (10.9%) 213 (10.1%)
PRIMARY FAILURE 804 (26.7%) 196 (7.2%) 134 (6.3%) 81 (4.4%) 186 (4.6%) 43 (2.0%)
GRAFT FAILURE 453 (15.1%) 304 (11.2%) 365 (17.1%) 298 (16.0%) 579 (14.3%) 310 (14.7%)
TECHNICAL 233 (7.8%) 28 (1.0%) 17 (0.8%) 17 (0.9%) 36 (0.9%) 20 (0.9%)
OTHER 162 (5.4%) 175 (6.4%) 187 (8.8%) 147 (7.9%) 339 (8.4%) 175 (8.3%)
MULTIPLE ORGAN FAILURE
356 (11.8%) 268 (9.8%) 117 (5.5%) 102 (5.5%) 309 (7.6%) 190 (9.0%)
RENAL FAILURE 20 (0.7%) 25 (0.9%) 36 (1.7%) 65 (3.5%) 225 (5.6%) 173 (8.2%)
PULMONARY 133 (4.4%) 108 (4.0%) 96 (4.5%) 85 (4.6%) 172 (4.2%) 99 (4.7%)
CEREBROVASCULAR 200 (6.7%) 112 (4.1%) 70 (3.3%) 62 (3.3%) 167 (4.1%) 83 (3.9%)
J Heart Lung Transplant 2007;26: 769-781
ISHLT
ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death from Leading Causes by Era
(Deaths: January 1992 - June 2006)
CAUSE OF DEATH
DATE OF DEATH
0-30 Days
(N = 3,005)
31 Days –
1 Year
(N = 2,722)
>1 Year –
3 Years
(N = 2,135)
>3 Years –
5 Years
(N = 1,857)
>5 Years – 10 Years
(N = 4,054)>10 Years
(N = 2,107)
ACUTE REJECTION
1992-1997 122 (7.1%) 231 (14.3%) 113 (9.3%) 41 (4.4%) 16 (1.1%) 16 (1.1%)
1998-6/2006 71 (5.5%) 107 (9.7%) 107 (11.7%) 41 (4.4%) 53 (2.0%) 53 (2.0%)
CARDIAC ALLOGRAFT VASCULOPATHY
1992-1997 32 (1.9%) 83 (5.1%) 184 (15.1%) 189 (20.1%) 262 (18.3%) 262 (18.3%)
1998-6/2006 20 (1.6%) 44 (4.0%) 114 (12.4%) 110 (12.0%) 319 (12.2%) 319 (12.2%)
GRAFT FAILURE1992-1997 258 (15.0%) 179 (11.0%) 200 (16.4%) 119 (12.7%) 174 (12.1%) 174 (12.1%)
1998-6/2006 195 (15.2%) 125 (11.4%) 165 (18.0%) 179 (18.8%) 405 (15.5%) 405 (15.5%)
MALIGNANCY, OTHER
1992-1997 1 (0.1%) 40 (2.5%) 118 (9.7%) 177 (18.8%) 257 (17.9%) 257 (17.9%)
1998-6/2006 0 (0.0%) 17 (1.5%) 100 (10.9%) 163 (17.8%) 492 (18.8%) 492 (18.8%)
PRIMARY FAILURE
1992-1997 508 (29.5%) 168 (10.4%) 105 (8.6%) 49 (5.2%) 99 (6.9%) 99 (6.9%)
1998-6/2006 296 (23.1%) 28 (2.5%) 29 (3.2%) 32 (3.5%) 87 (3.3%) 87 (3.3%)
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANT RECIPIENTS: Cumulative Incidence of Leading Causes of Death
(Transplants: January 1992 - June 2005)
0%
1%
2%
3%
4%
5%
6%
0 1 2 3 4 5 6 7 8 9 10
Time (years)
CAV Acute Rejection
Malignancy (non-Lymph/PTLD) Primary Failure
Graft Failure CMV
Infection (non-CMV)
Incid
en
ce o
f C
au
se-S
pecif
ic D
eath
s
ISHLT 2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Risk Factors for 1 Year Mortality
2007ISHLT (N=7,024)
VARIABLE N
Relative Risk
P-value 95% Confidence
Interval
Temporary circulatory support* 52 3.38 <0.0001 2.11 -5.42
Diagnosis: Congenital vs. cardiomyopathy
170 2.13 0.0001 1.47 -3.10
VAD (unknown type) 57 1.99 0.0203 1.11 -3.55
Recipient history of insulin-dependent diabetes
62 1.87 0.0424 1.02 -3.41
Recipient on ventilator at time of transplant
203 1.83 0.0001 1.36 -2.46
Recipient history of dialysis 217 1.56 0.0019 1.18 -2.07
Recipient cerebrovascular event prior to transplant
390 1.29 0.049 1.00 -1.67
* Temporary circulatory support includes ECMO and Abiomed.
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Risk Factors for 1 Year Mortality
2007ISHLT (N=7,024)
VARIABLE N
Relative Risk
P-value 95% Confidence Interval
Recipient previous pregnancy 962 1.28 0.0162 1.05 -1.57
Recipient with infection requiring IV drug therapy within 2 weeks prior to transplant
779 1.27 0.0168 1.04 -1.55
Chronic pulsatile device 1157 1.27 0.0153 1.05 -1.55
Recipient prior sternotomy 2376 1.22 0.0114 1.05 -1.42
Donor CMV +/Recipient CMV - 1229 0.81 0.0342 0.67 -0.98
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Risk Factors for 1 Year Mortality
Continuous Factors (see figures)
Recipient age
Recipient weight
Donor age
Ischemia time
Transplant center volume
PA systolic pressure
PVR
Bilirubin
Serum creatinine
2007ISHLT J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Relative Risk of 1 Year Mortality with 95% Confidence Limits
Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
p < 0.0001
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
2007ISHLT (N=7,024)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Relative Risk of 1 Year Mortality with 95% Confidence Limits
Donor Age
0
0.5
1
1.5
2
2.5
15 20 25 30 35 40 45 50 55 60
Donor Age
p < 0.0001
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
2007ISHLT (N=7,024)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Relative Risk of 1 Year Mortality with 95% Confidence Limits
Recipient Weight
0
0.5
1
1.5
2
50 60 70 80 90 100
Recipient Weight (kg)
p = 0.012
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
2007ISHLT (N=7,024)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Relative Risk of 1 Year Mortality with 95% Confidence Limits
Ischemia Time
0
0.5
1
1.5
2
2.5
3
30 60 90 120 150 180 210 240 270 300 330 360
Ischemia Time (minutes)
p = 0.020Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
2007ISHLT (N=7,024)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Relative Risk of 1 Year Mortality with 95% Confidence Limits
Center Volume
0
0.5
1
1.5
2
5 10 15 20 25 30 35 40 45 50 55 60 65 70
Center Volume (cases per year)
p < 0.0001Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
2007ISHLT (N=7,024)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Relative Risk of 1 Year Mortality with 95% Confidence Limits
Pre-Transplant Bilirubin
0
0.5
1
1.5
2
0.2 1.2 2.2 3.2
Bilirubin (mg/dl)
p = 0.0008Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
2007ISHLT (N=7,024)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Relative Risk of 1 Year Mortality with 95% Confidence Limits
Pre-Transplant Creatinine
0
0.5
1
1.5
2
2.5
3
0.5 1 1.5 2 2.5 3
Recipient Creatinine (mg/dl)
p < 0.0001
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
2007ISHLT (N=7,024)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Relative Risk of 1 Year Mortality with 95% Confidence Limits
Recipient PA Systolic Pressure
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65 70
PA Systolic (mm Hg)
p = 0.041
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
2007ISHLT (N=7,024)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) Relative Risk of 1 Year Mortality with 95% Confidence Limits
Recipient PVR
0
0.5
1
1.5
2
0 1 2 3 4
PVR (Wood units)
p = 0.001
Rela
tive R
isk o
f 1 Y
ear
Mo
rtality
2007ISHLT (N=7,024)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005)
Factors Not Significant for 1 Year Mortality
Recipient Factors: Prior malignancy, PCW, gender, hospitalized, prior transfusions
Donor Factors: Clinical infection, history of diabetes, height, weight, gender, history of hypertension, cause of death, history of malignancy
2007ISHLT J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/2002-6/2005) 1-Year Predicted Survival Model
75%
80%
85%
90%
95%
100%
0 30 60 90 120 150 180 210 240 270 300 330 360
Time (days)
Cohort average
Recipient: Creatinine=1.7 mg/dl; inotropes; balloon pump; bilirubin=1.1 mg/dl. Donor: 60 y.o.
Recipient: Creatinine=1.3 mg/dl; pulsatile chronic VAD; bilirubin=0.8 mg/d. Donor: 30 y.o. P
red
icte
d S
urv
ival
ISHLT 2007
Recipient: 55 y.o., Dx=CAD, weight=78 kg, PVR=2.2, volume=22/year, PA systolic=40, ischemia=180 min
Donor: Weight = 77 kg
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Risk Factors for 5 Year Mortality
2007ISHLT (N=5,147)
VARIABLE N
Relative Risk
P-value 95% Confidence
Interval
Ventilator 201 2.16 <.00001 1.74 -2.67
Recipient on dialysis 129 1.79 <.00001 1.37 -2.33
Diagnosis: Congenital vs. cardiomyopathy 91 1.65 .0107 1.12 -2.41
Diagnosis: Other* vs cardiomyopathy 165 1.49 .0049 1.13 -1.96
Recipient history of diabetes 939 1.27 .0004 1.11 -1.45
Male recipient/female donor 999 1.20 .0093 1.05 -1.37
Hospitalized (including ICU) 2803 1.16 .0155 1.03 -1.30
Diagnosis: Coronary artery disease vs. cardiomyopathy
2491 1.15 .0226 1.02 -1.31
Total number of HLA mismatches
1 MM (n=14) 2 MM (N=144) 3 MM (N= 491) 4 MM (N=1102) 5 MM (N=2599) 6 MM (N = 797)
1.09 .0023 1.03 -1.16
* Other = not cardiomyopathy, coronary artery disease, valvular
heart disease, or congenital heart disease
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Risk Factors for 5 Year Mortality
Continuous Factors (see figures)
Recipient age
Donor age
Donor/recipient BMI ratio
Transplant center volume
Ischemia time
Bilirubin
Serum creatinine
2007ISHLT (N=5,147)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001)
Relative Risk of 5 Year Mortality with 95% Confidence Limits
Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
p < 0.0001
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
2007ISHLT (N=5,147)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Relative Risk of 5 Year Mortality with 95% Confidence Limits
Donor Age
0
0.5
1
1.5
2
15 20 25 30 35 40 45 50 55 60
Donor Age
p < 0.0001Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
2007ISHLT (N=5,147)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Relative Risk of 5 Year Mortality with 95% Confidence Limits
Ischemia Time
0
0.5
1
1.5
2
2.5
30 60 90 120 150 180 210 240 270 300 330 360
Ischemia time (minutes)
p < 0.0001
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
2007ISHLT (N=5,147)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Relative Risk of 5 Year Mortality with 95% Confidence Limits
Center Volume
0
0.5
1
1.5
2
5 10 15 20 25 30 35 40 45 50 55 60 65 70
Center volume (cases per year)
p < 0.0001
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
2007ISHLT (N=5,147)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Relative Risk of 5 Year Mortality with 95% Confidence
LimitsBMI Ratio
0
0.5
1
1.5
2
0.5 0.7 0.9 1.1 1.3 1.5
Donor BMI/Recipient BMI
p = 0.0002
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
2007ISHLT (N=5,147)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001)Relative Risk of 5 Year Mortality with 95% Confidence Limits
Pre-Transplant Bilirubin
0
0.5
1
1.5
2
0.2 1.2 2.2 3.2
Bilirubin (mg/dl)
p = 0.0002Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
2007ISHLT (N=5,147)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Relative Risk of 5 Year Mortality with 95% Confidence Limits
Pre-Transplant Creatinine
0
0.5
1
1.5
2
0.5 1 1.5 2 2.5 3
Creatinine (mg/dl)
p = 0.0011
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
2007ISHLT (N=5,147)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Factors Not Significant for 5 Year Mortality
Recipient Factors: VAD, thoracotomy, sternotomy, pulmonary embolism, IV inotropes, prior malignancy, PRA
Donor Factors: History of cancer, clinical infection, cause of death, history of hypertension
Transplant Factors: CMV mismatch, ABO match
2007ISHLT J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) 5-Year Predicted Survival Model
50%
60%
70%
80%
90%
100%
0 1 2 3 4 5
Time (years)
Cohort average
Recipient: Creatinine = 1.7 mg/dl; bilirubin = 1.1 mg/dl; inotropes; in hospitalDonor: 60 y.o.
Recipient: Creatinine = 1.3 mg/dl; bilirubin = 0.8 mg/dl; pulsatile chronic VAD; no inotropes; not hospitalizedDonor: 30 y.o.
Pre
dic
ted
Su
rviv
al
ISHLT 2007
Recipient: 55 y.o., Dx=CAD, weight=78 kg, PVR=2.2, volume=24/year, PA systolic=42, ischemia=180 min; BMI ratio = 1; HLA mismatch = 5
Donor: Weight = 75 kg
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Risk Factors for 5 Year MortalityConditional on Survival to 1 Year
2007ISHLT (N=4,079)
VARIABLE N
Relative Risk
P-value 95% Confidence
Interval
Repeat transplant 91 3.86 .0036 1.55 -9.57
CAV within 1st year 237 2.06 <.0001 1.57 -2.70
Ventilator at time of transplant 114 1.61 .0180 1.09 -2.39
Recipient history of diabetes 742 1.52 <.0001 1.25 -1.86
Drug-treated rejection prior to discharge 757 1.48 .0001 1.21 -1.80
Drug-treated infection prior to discharge 825 1.37 .0018 1.12 -1.66
Rejection between discharge and 1st year 1556 1.26 .0103 1.06 -1.50
0-4 total HLA mismatches 2017 0.78 .0034 0.66 -0.92
PRA > 10% 273 0.61 .0125 0.41 -0.90
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Borderline Significant Risk Factors for 5 Year Mortality
Conditional on Survival to 1 Year
2007ISHLT (N=4,079)
VARIABLE N
Relative Risk
P-value 95% Confidence
Interval
Other surgical procedures (excl. cardiac re-operation) prior to discharge
428 1.27 .0598 0.99 -1.63
Diagnosis: coronary artery disease vs. cardiomyopathy
1987 1.20 .0570 0.99 -1.45
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year
Continuous Factors (see figures)
Recipient age
Donor age
Donor/recipient BMI ratio
2007ISHLT (N=4,079)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Relative Risk of 5 Year Mortality with 95% Confidence Limits
Conditional on Survival to 1 Year Recipient Age
0
0.5
1
1.5
2
2.5
3
3.5
20 25 30 35 40 45 50 55 60 65
Recipient Age
p < 0.0001
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
2007ISHLT (N=4,079)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Relative Risk of 5 Year Mortality with 95% Confidence Limits
Conditional on Survival to 1 Year Donor Age
0
0.5
1
1.5
2
15 20 25 30 35 40 45 50 55 60
Donor Age
p = 0.0002
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
2007ISHLT (N=4,079)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1/1999-6/2001) Relative Risk of 5 Year Mortality with 95% Confidence Limits
Conditional on Survival to 1 Year BMI Ratio
0
0.5
1
1.5
2
0.5 0.7 0.9 1.1 1.3 1.5
Donor BMI/Recipient BMI
p = 0.012
Rela
tive R
isk o
f 5 Y
ear
Mo
rtality
2007ISHLT (N=4,079)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Risk Factors for 10 Year Mortality
2007ISHLT
(N=11,870)
VARIABLE N
Relative Risk
P-value 95% Confidence Interval
Repeat transplant 272 1.84 <.0001 1.47 -2.32
Ventilator at time of transplant 261 1.56 <.0001 1.33 -1.84
Diagnosis: coronary artery disease vs. cardiomyopathy
5729 1.13 <.0001 1.07 -1.20
Number of HLA mismatches at the DR locus 0 DR MM (N=575)
1 DR MM (N=7036) 2 DR MM (N=4315)
1.09 .0003 1.04 -1.14
Male recipient/ female donor 2549 1.08 .0309 1.01 -1.17
Number of HLA mismatches at the B locus 0 B MM (N=254)
1 B MM (N=2719) 2 B MM (N=8953)
1.06 .0424 1.00 -1.12
Diagnosis: Other* vs. cardiomyopathy 441 121 .0561 0.99 -1.48
* Other = not cardiomyopathy, coronary artery disease, valvular heart disease, or congenital heart disease
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Risk Factors for 10 Year Mortality
Continuous Factors (see figures)
Recipient age
Recipient height
Donor age
PRA
Transplant center volume
Ischemia time
2007ISHLT
(N=11,870)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits
Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
p < 0.0001
Rela
tive R
isk o
f 10 Y
ear
Mo
rtality
2007ISHLT
(N=11,870)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits
Donor Age
0
0.5
1
1.5
2
15 25 35 45 55
Donor Age
p < 0.0001Rela
tive R
isk o
f 10 Y
ear
Mo
rtality
2007ISHLT
(N=11,870)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits
Pre-Transplant Recipient Height
0
0.5
1
1.5
2
150 160 170 180 190
Recipient height (cm)
p < 0.0001
Rela
tive R
isk o
f 10 Y
ear
Mo
rtality
2007ISHLT
(N=11,870)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits
Center Volume
0
0.5
1
1.5
2
5 10 15 20 25 30 35 40 45 50 55 60 65 70
Center Volume (cases per year)
p = 0.0008
Rela
tive R
isk o
f 10 Y
ear
Mo
rtality
2007ISHLT
(N=11,870)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits
Ischemia Time
0
0.5
1
1.5
2
30 60 90 120 150 180 210 240 270 300 330 360
Ischemia time (minutes)
p = 0.0057
Rela
tive R
isk o
f 10 Y
ear
Mo
rtality
2007ISHLT
(N=11,870)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits
Pre-transplant PRA
0
0.5
1
1.5
2
0 20 40 60 80 100
Most recent PRA prior to transplant (%)
p = 0.011
Rela
tive R
isk o
f 10 Y
ear
Mo
rtality
2007ISHLT
(N=11,870)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Risk Factors for 10 Year Mortality Conditional on Survival to 3 Years
2007ISHLT
(N=8,426)
VARIABLE N
Relative Risk
P-value 95%
Confidence Interval
Prior pregnancy before transplant 916 1.26 .0006 1.11 -1.44
Diagnosis: coronary artery disease vs. cardiomyopathy
4076 1.18 .0003 1.08 -1.29
Number of HLA mismatches at the DR locus
0 DR MM (N=459) 1 DR MM (N=4960) 2 DR MM (N=3039)
1.08 .0226 1.01 -1.16
Diagnosis: valvular heart disease vs. cardiomyopathy
279 0.79 .0739 0.60 -1.02
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTSRisk Factors for 10 Year MortalityConditional on Survival to 3 Years
Continuous Factors (see figures)
Recipient age
Recipient weight
Donor age
Donor weight (borderline)
2007ISHLT
(N=8,426)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits
Conditional on Survival to 3 YearsRecipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
p < 0.0001
Rela
tive R
isk o
f 10 Y
ear
Mo
rtality
2007ISHLT
(N=8,426)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits
Conditional on Survival to 3 YearsDonor Age
0
0.5
1
1.5
2
15 25 35 45 55
Donor Age
p < 0.0001
Rela
tive R
isk o
f 10 Y
ear
Mo
rtality
2007ISHLT
(N=8,426)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits
Conditional on Survival to 3 YearsPre-Transplant Recipient Weight
0
0.5
1
1.5
2
50 55 60 65 70 75 80 85 90 95 100 105
Recipient weight (kg)
p = 0.0002
Rela
tive R
isk o
f 10 Y
ear
Mo
rtality
2007ISHLT
(N=8,426)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1991-6/1995) Relative Risk of 10 Year Mortality with 95% Confidence Limits
Conditional on Survival to 3 YearsDonor Weight
0
0.5
1
1.5
2
50 55 60 65 70 75 80 85 90 95 100 105
Donor weight (kg)
p = 0.057
Rela
tive R
isk o
f 10 Y
ear
Mo
rtality
2007ISHLT
(N=8,426)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1988-6/1991) Risk Factors for 15 Year Mortality
2007ISHLT
(N=3,500)
VARIABLE N
Relative Risk
P-value 95% Confidence Interval
Repeat transplant 77 1.59 .0463 1.01 -2.51
Ventilator at time of transplant 110 1.35 .0136 1.06 -1.71
Diagnosis: coronary artery disease vs. cardiomyopathy
1862 1.25 <.0001 1.13 -1.37
Balloon pump at time of transplant 304 1.20 .0199 1.03 -1.41
Male recipient/female donor 610 1.13 .0334 1.01 -1.25
Number of HLA mismatches at the A locus 0 A MM (N=285)
1 A MM (N=1636) 2 A MM (N=1579)
1.10 .0058 1.03 -1.17
Hospitalized at transplant (incl. ICU) 1889 0.90 .0273 0.83 -0.99
Number of HLA mismatches at the DR locus
0 DR MM (N=234) 1 DR MM (N=1843) 2 DR MM (N=1423)
1.06 .0870 0.99 -1.14
Diagnosis: valvular heart disease vs. cardiomyopathy
160 0.81 .0711 0.64 -1.02
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTSRisk Factors for 15 Year Mortality
Continuous Factors (see figures)
Recipient age
Donor age
2007ISHLT
(N=3,500)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1988-6/1991) Relative Risk of 15 Year Mortality with 95% Confidence Limits
Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
p < 0.0001
Rela
tive R
isk o
f 15 Y
ear
Mo
rtality
2007ISHLT
(N=3,500)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1988-6/1991) Relative Risk of 15 Year Mortality with 95% Confidence Limits
Donor Age
0
0.5
1
1.5
2
15 25 35 45 55
Donor Age
p < 0.0001
Rela
tive R
isk o
f 15 Y
ear
Mo
rtality
2007ISHLT
(N=3,500)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1988-6/1991) Risk Factors for 15 Year MortalityConditional on Survival to 5 Years
2007ISHLT
(N=2,322)
VARIABLE N
Relative Risk
P-value 95% Confidence Interval
Diagnosis: other* vs. cardiomyopathy 53 1.58 .0149 1.09 -2.29
Diagnosis: coronary artery disease vs. cardiomyopathy
1211 1.27 .0006 1.11 -1.45
Number of HLA mismatches at the A locus 0 A MM (N=189)
1 A MM (N=1109) 2 A MM (N=1024)
1.12 .0164 1.02 -1.22
Diagnosis: valvular heart disease vs. cardiomyopathy
114 0.73 .0581 0.53 -1.01
* Other = not cardiomyopathy, coronary artery disease, valvular heart disease, or congenital heart disease
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTSRisk Factors for 15 Year Mortality Conditional on Survival to 5 Years
Continuous Factors (see figures)
Recipient age
Donor age
2007ISHLT
(N=2,322)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1988-6/1991) Relative Risk of 15 Year Mortality with 95% Confidence Limits
Conditional on Survival to 5 Years Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
p < 0.0001
Rela
tive R
isk o
f 15 Y
ear
Mo
rtality
2007ISHLT
(N=2,322)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1988-6/1991) Relative Risk of 15 Year Mortality with 95% Confidence Limits
Conditional on Survival to 5 Years Donor Age
0
0.5
1
1.5
2
15 25 35 45 55
Donor Age
p = 0.027Rela
tive R
isk o
f 15 Y
ear
Mo
rtality
2007ISHLT
(N=2,322)
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1995-6/2001) Risk Factors for Developing Cardiac Allograft Vasculopathy
within 5 Years
VARIABLE Relative
RIsk P-value
95% Confidence
Interval
Female donor * .0043 -
Donor history of hypertension 1.33 <.0001 1.17 -1.51
Diagnosis: Coronary artery disease (vs. cardiomyopathy)
1.20 .0004 1.08 -1.32
Transplant year = 1996 vs. 2000/2001 1.15 .0411 1.01 -1.31
Number of HLA mismatches at DR locus 1.13 .0021 1.04 -1.21
Number of HLA mismatches at B locus 0.91 .0425 0.84 -1.00
Donor cause of death: Anoxia 0.81 .0342 0.67 -.098
(N=7,711)ISHLT
* Due to the statistically significant interaction of donor gender and donor age, the relative risk for donor gender must be considered in the context of donor age rather than independently.
2007 J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1995-6/2001) Risk Factors for Developing Cardiac Allograft Vasculopathy
within 5 Years
Continuous Factors (see figures)
Recipient age
Donor age
Donor age*donor gender interaction
Transplant center volume
ISHLT 2007
(N=7,711)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1995-6/2001)Relative Risk of Developing Cardiac Allograft Vasculopathy within 5 Years
with 95% Confidence LimitsDonor Age, Donor Gender and Recipient Gender
0
0.5
1
1.5
2
2.5
3
3.5
15 20 25 30 35 40 45 50 55
Donor Age
Male Recip/Male Donor Male Recip/Female Donor
Female Recip/Male Donor Female Recip/Female Donor
p < 0.0001
Rela
tive R
isk o
f C
AV
wit
hin
5 Y
ears
ISHLT 2007
(N=7,711)
Relative risk includes impact of donor gender, recipient gender and donor age.
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1995-6/2001) Relative Risk of Developing Cardiac Allograft Vasculopathy within 5 Years
with 95% Confidence Limits Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
p < 0.0001
Rela
tive R
isk o
f C
AV
wit
hin
5 Y
ears
ISHLT 2007
(N=7,711)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (1995-6/2001) Relative Risk of Developing Cardiac Allograft Vasculopathy within 5 Years
with 95% Confidence Limits Center Volume
0
0.5
1
1.5
2
5 10 15 20 25 30 35 40 45 50 55 60 65 70
Center Volume (cases per year)
p < 0.0001
Rela
tive R
isk o
f C
AV
wit
hin
5 Y
ears
ISHLT 2007
(N=7,711)J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (4/1994-6/2001) Risk Factors for Developing Renal Dysfunction within 5 Years
Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant
VARIABLE Relative
RIsk P-value
95% Confidence
Interval
Recipient diabetes 1.47 <.0001 1.33 -1.62
Year of transplant: 1994/1995 1.24 0.0008 1.09 -1.40
Year of transplant: 1996/1997 1.22 0.001 1.09 -1.38
Recipient with infection requiring IV drug therapy within 2 weeks prior to transplant
1.22 0.0047 1.06 -1.40
IV Inotropes at transplant 1.19 <.0001 1.10 -1.29
Year of transplant: 1998/1999 1.17 0.0084 1.04 -1.32
Recipient treated for hypertension pre-transplant
1.15 0.0011 1.06 -1.25
(N=11,145)ISHLT 2007
*Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (4/1994-6/2001) Risk Factors for Developing Renal Dysfunction within 5 Years
Limited to Recipients without Severe Renal Dysfunction Pre-Transplant
Continuous Factors (see figures)
Recipient age
Recipient creatinine
Recipient weight
Recipient PRA
Donor weight
ISHLT 2007
(N=11,145)
*Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (4/1994-6/2001) Risk Factors for Developing Renal Dysfunction within 5 Years
Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant Recipient Pre-Transplant Creatinine
0
0.5
1
1.5
2
2.5
3
0.5 1 1.5 2 2.5
Creatinine (mg/dl)
p < 0.0001
Rela
tive R
isk o
f R
en
al
Dysfu
ncti
on
wit
hin
5 Y
ears
ISHLT 2007
(N=11,145)
*Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (4/1994-6/2001) Risk Factors for Developing Renal Dysfunction within 5 Years
Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant Recipient Age
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
25 30 35 40 45 50 55 60 65
Recipient Age
p < 0.0001
Rela
tive R
isk o
f R
en
al
Dysfu
ncti
on
wit
hin
5 Y
ears
ISHLT 2007
(N=11,145)
*Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (4/1994-6/2001) Risk Factors for Developing Renal Dysfunction within 5 Years
Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant Recipient Weight
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
50 60 70 80 90 100 110
Recipient Weight (kg)
p < 0.0001
Rela
tive R
isk o
f R
en
al
Dysfu
ncti
on
wit
hin
5 Y
ears
ISHLT 2007
(N=11,145)
*Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (4/1994-6/2001) Risk Factors for Developing Renal Dysfunction within 5 Years
Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant Donor Weight
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
50 60 70 80 90 100 110
Donor Weight (kg)
p = 0.049
Rela
tive R
isk o
f R
en
al
Dysfu
ncti
on
wit
hin
5 Y
ears
ISHLT 2007
(N=11,145)
*Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis
J Heart Lung Transplant 2007;26: 769-781
ADULT HEART TRANSPLANTS (4/1994-6/2001) Risk Factors for Developing Renal Dysfunction within 5 Years
Limited to Recipients without Severe Renal Dysfunction* Pre-Transplant Recipient PRA
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
0 5 10 15 20 25 30 35 40
Recipient PRA (%)
p = 0.0047
Rela
tive R
isk o
f R
en
al
Dysfu
ncti
on
wit
hin
5 Y
ears
ISHLT 2007
(N=11,145)
*Severe renal dysfunction = creatinine > 2.5 mg/dl or dialysis
J Heart Lung Transplant 2007;26: 769-781