Transcript HEART-LUNG TRANSPLANTATION Adult Recipients JHLT. 2014 Oct; 33(10): 1009-1024 Table of Contents  Donor and recipient characteristics: slides 3-14  Post transplant survival and other outcomes:

HEART-LUNG TRANSPLANTATION
Adult Recipients
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Table of Contents

Donor and recipient characteristics: slides 3-14

Post transplant survival and other outcomes: slides 1524

Induction and maintenance immunosuppression: slides
25-30

Post transplant morbidities: slides 31-41

Multivariable analyses: slides 42-44
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Donor and Recipient Characteristics
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Number of Transplants Reported by Year
Number of Transplants
300
250
200
150
100
50
0
2014
JHLT. 2014 Oct; 33(10): 1009-1024
NOTE: This figure includes only the heart-lung
transplants that are reported to the ISHLT Transplant
Registry. As such, this should not be construed as
evidence that the number of heart-lung transplants
worldwide has declined in recent years.
Adult Heart-Lung Retransplants
by Year of Retransplant
9
9
N
%
7
7
6
5
5
4
3
3
2
% of retransplants
Number of retransplants
8
1
1
0
-1
Year of retransplant
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Only patients who were less than 18 years
old at the time of retransplant are included.
Adult Heart-Lung Retransplants
by Inter-Transplant Interval
(Retransplants: January 1982 – June 2013)
60
% of retransplants
50
40
30
20
10
0
<1 month
1 month<1 year
1-<3 years 3-<5 years 5-<10 years 10+ years
Time Between Previous and Current Transplant
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Not
reported
Adult Heart-Lung Transplants
Diagnosis (Transplants: January 1982 – June 2013)
Cystic Fibrosis
14%
Idiopathic
Pulmonary
Fibrosis
4%
COPD/A1A
6%
Idiopathic
Pulmonary
Arterial
Hypertension
27%
Retx
2%
Sarcoidosis
2%
Other
5%
Acquired Heart
Disease
5%
Congenital
36%
2014
JHLT. 2014 Oct; 33(10): 1009-1024
NOTE: “Other” includes cancer, LAM, OB, bronchiectasis
For some retransplants diagnosis other than
retransplant is reported, so the total percentage of
retransplants may be greater.
Adult Heart-Lung Transplants
Diagnosis (Transplants: January 1982 – June 2013)
Diagnosis
N (%)
Congenital Heart Disease
1178 (35.5%)
Idiopathic Pulmonary Arterial Hypertension
907 (27.4%)
Cystic Fibrosis
459 (13.9%)
Acquired Heart Disease
180 ( 5.4%)
COPD/Emphysema
141 ( 4.3%)
Idiopathic Pulmonary Fibrosis
121 ( 3.7%)
Alpha-1
62 ( 1.9%)
Sarcoidosis
54 ( 1.6%)
Retransplant: Not Obliterative Bronchiolitis
32 ( 1.0%)
Retransplant: Obliterative Bronchiolitis
24 ( 0.7%)
Bronchiectasis
30 ( 0.9%)
Obliterative Bronchiolitis (not Retransplant)
25 ( 0.8%)
Other
101 ( 3.0%)
2014
JHLT. 2014 Oct; 33(10): 1009-1024
For some retransplants diagnosis other than
retransplant is reported, so the total number and
percentage of retransplants may be greater.
Adult Heart-Lung Transplants
Diagnosis by Era (Transplants: January 1982 – June 2013)
% of Transplants
100%
90%
Other
80%
Sarcoidosis
70%
Retx
Idiopathic Pulmonary Fibrosis
60%
COPD/A1A
50%
Acquired Heart Disease
40%
Cystic Fibrosis
30%
IPAH
20%
Congenital
10%
0%
1982-1991
(N=967)
1992-2001
(N=1,457)
2014
JHLT. 2014 Oct; 33(10): 1009-1024
2002-6/2013
(N=890)
NOTE: “Other” includes OB (non-Re-Tx) and
Bronchiectasis.
Adult Heart-Lung Transplants
Major Indications by Year (%)
100
Congenital Heart Disease
Cystic Fibrosis
Retransplant
IPAH
COPD/Alpha-1
Acquired Heart Disease
% of Transplants
90
80
70
60
50
40
30
20
10
0
Transplant Year
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Major Indications by Year (Number)
Number of Transplants
180
Congenital Heart Disease
Cystic Fibrosis
Retransplant
160
140
120
100
80
60
40
20
0
Transplant Year
2014
JHLT. 2014 Oct; 33(10): 1009-1024
IPAH
COPD/Alpha-1
Acquired Heart Disease
Adult Heart-Lung Transplants
Age Distribution by Location
(Transplants: January 2000 – June 2013)
18 - 34 years
35 - 49 years
50 - 59 years
60+ years
100%
% of Transplants
80%
60%
40%
20%
0%
Europe
North America
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Other
Adult Heart-Lung Transplants
Diagnosis Distribution by Location
(Transplants: January 2000 – June 2013)
Congenital heart disease
IPAH
Cystic Fibrosis
Acquired heart disease
100%
% of Transplants
80%
60%
40%
20%
0%
Europe
North America
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Other
IPF
Other
Adult Heart-Lung Transplants
Donor Age Distribution by Location
(Transplants: January 2000 – June 2013)
6-11
12-17
18-34
35-49
50-59
60+
100%
% of Donors
80%
60%
40%
20%
0%
Europe
North America
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Other
Post Transplant Survival and Other
Outcomes
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Kaplan-Meier Survival
(Transplants: January 1982 – June 2012)
100
Median survival = 3.3 years
Conditional median survival = 10.0 years
Survival (%)
75
N = 3,698
50
N at risk at 25 years = 12
25
0
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
Years
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Kaplan-Meier Survival by Transplant Type
(Transplants: January 1982 – June 2012)
100
p < 0.0001
Primary (N=3,605)
First Retransplant (N=90)
Survival (%)
80
60
Median survival (years):
Primary: 3.5; Conditional=10.3
Retransplant: 0.3; Conditional=7.9
40
20
0
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
Years
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Kaplan-Meier Survival by Era
(Transplants: January 1982 – June 2012)
100
Median survival (years): 1982-1991=1.9; 1992-2001=3.6; 2002-6/2012=5.6
Conditional median survival (years): 1982-1991=9.0; 1992-2001=10.0; 2002-6/2012=NA
Survival (%)
75
1982-1991 (N=1,216)
1992-2001 (N=1,599)
2002-6/2012 (N=883)
50
25
All pair-wise comparisons were significant at p < 0.01
0
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
Years
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Kaplan-Meier Survival by Diagnosis
(Transplants: January 1990 – June 2012)
100
Other Congenital (N = 343)
Eisenmenger's Syndrome (N = 648)
Survival (%)
75
IPAH (N = 662)
Median survival (years): Congenital=3.3;
Eisenmenger's=5.5; IPAH=4.5
50
25
No pair-wise comparisons were significant at p < 0.05
0
0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18 19
Years
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Kaplan-Meier Survival by Diagnosis Conditional on Survival
to 1 Year (Transplants: January 1990 – June 2012)
100
Other Congenital (N = 200)
Eisenmenger's Syndrome (N = 432)
IPAH (N = 447)
Survival (%)
75
50
Median survival (years): Congenital=13.6;
Eisenmenger's=11.1; IPAH=10.1
25
No pair-wise comparisons were significant at p < 0.05
0
0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18 19
Years
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Functional Status of Surviving Recipients
(Follow-ups: March 2005 – June 2013)
100%
10%
20%
80%
30%
40%
60%
50%
60%
40%
70%
80%
90%
20%
100%
0%
1 Year (N = 197)
2 Years (N = 149)
2014
JHLT. 2014 Oct; 33(10): 1009-1024
3 Years (N = 130)
Adult Heart-Lung Transplants
Employment Status of Surviving Recipients
(Follow-ups: April 1994 – June 2013)
100%
80%
Working (FT/PT
status unknown)
Retired
60%
Not Working
Working Part Time
40%
Working Full Time
20%
0%
1 Year (N = 376)
3 Years (N = 269)
2014
JHLT. 2014 Oct; 33(10): 1009-1024
5 Years (N = 230)
Adult Heart-Lung Transplants
Employment Status of Surviving Recipients by Era
(Follow-ups: April 1994 – June 2013)
100%
Working (FT/PT
status unknown)
80%
Retired
60%
Not Working
40%
Working Part Time
Working Full Time
20%
0%
1 Year
3 Years
(N = 162) (N = 110)
5 Years
(N = 96)
4/1994 - 1999
1 Year
(N = 214)
3 Years
5 Years
(N = 159) (N = 134)
2000 - 6/2013
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Rehospitalization Post-transplant of Surviving Recipients
(Follow-ups: April 1994 – June 2013)
100%
80%
60%
40%
20%
No Hospitalization
Hospitalized, Rejection Only
Hospitalized, Rejection and Infection
Hospitalized, Not Rejection/Not Infection
Hospitalized, Infection Only
0%
Up to 1 Year
(N =523)
Between 2 and 3
Years (N = 362)
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Between 4 and 5
Years (N = 300)
Induction and Maintenance
Immunosuppression
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Induction Immunosuppression
(Transplants: January 2001 – June 2013)
70
% of Patients
60
50
40
30
20
10
0
Any Induction
(N=213)
Polyclonal ALG/ATG
(N=73)
2014
JHLT. 2014 Oct; 33(10): 1009-1024
OKT3 (N=5)
IL-2R Antagonist
(N=117)
Analysis is limited to patients who were
alive at the time of the discharge
Adult Heart-Lung Transplants
Induction Immunosuppression by Year
(Transplants: January 2000 – December 2012)
100
Any Induction
Polyclonal ALG/ATG
OKT3
IL-2R Antagonist
% of Patients
80
60
40
20
0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Analysis is limited to patients who were
alive at the time of the discharge
Adult Heart-Lung Transplants
Induction Immunosuppression
(Transplants: January 2000 – December 2012)
90
80
% of Patients
70
60
50
40
30
20
10
0
Any Induction
Polyclonal ALG/ATG
2014
JHLT. 2014 Oct; 33(10): 1009-1024
OKT3
IL-2R Antagonist
Analysis is limited to patients who were
alive at the time of the discharge
Adult Heart-Lung Transplants
Maintenance Immunosuppression at Time of Follow-up
(Follow-ups: January 2001 – June 2013)
100
90
Year 1 (N = 259)
Year 5 (N = 154)
% of Patients
80
70
60
50
40
30
20
10
0
Cyclosporine
Tacrolimus
Sirolimus/
MMF/MPA Azathioprine
Everolimus
NOTE: Different patients are analyzed in Year 1 and Year 5
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Prednisone
Analysis is limited to patients who were
alive at the time of the follow-up
Adult Heart-Lung Transplants
Maintenance Immunosuppression Drug Combinations at
Time of Follow-up (Follow-ups: January 2001 – June 2013)
100%
Other
None
80%
Sirolimus/Everolimus + Calcineurin +
Cellcycle
Sirolimus/Everolimus + Calcineurin
60%
Tacrolimus
40%
Tacrolimus + MMF/MPA
Tacrolimus + AZA
20%
Cyclosporine + MMF/MPA
0%
Cyclosporine + AZA
Year 5 (N = 154)
Year 1 (N = 259)
NOTE: Different patients are analyzed in Year 1 and Year 5
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Analysis is limited to patients who were
alive at the time of the follow-up
Post Transplant Morbidities
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Cumulative Post Transplant Morbidity Rates in Survivors
within 1 and 5 Years (Follow-ups: April 1994 – June 2013)
Within
1 Year
Total
number
with known
response
Within
5 Years
Total
number
with known
response
Hypertension
59.6%
(N = 433)
88.1%
(N = 151)
Renal Dysfunction
18.8%
(N = 489)
45.5%
(N = 189)
Outcome
Abnormal Creatinine ≤ 2.5 mg/dl
11.7%
31.7%
Creatinine > 2.5 mg/dl
3.1%
10.6%
Chronic Dialysis
3.9%
2.1%
Renal Transplant
0.2%
1.1%
Hyperlipidemia
26.7%
(N = 453)
70.0%
(N = 160)
Diabetes
18.5%
(N = 496)
28.5%
(N = 186)
Coronary Artery Vasculopathy
2.8%
(N = 394)
8.2%
(N = 97)
Bronchiolitis Obliterans Syndrome
8.1%
(N = 458)
28.7%
(N = 157)
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Freedom from Coronary Artery Vasculopathy and
Bronchiolitis Obliterans Syndrome
(Follow-ups: April 1994 – June 2013)
% Free from CAV and Bronchiolitis
Obliterans Syndrome
100
80
60
40
Freedom from Coronary Artery Vasculopathy
20
Freedom from Bronchiolitis Obliterans Syndrome
0
0
1
2
3
4
5
6
Years
2014
JHLT. 2014 Oct; 33(10): 1009-1024
7
8
9
10
11
Adult Heart-Lung Transplants
Freedom from Coronary Artery Vasculopathy
by Diagnosis Type (Follow-ups: April 1994 – June 2013)
100
% Free from CAV
80
60
40
Heart (N=210)
Lung (N=68)
20
p-value comparing all = 0.5325
Heart/Lung (N=106)
0
0
1
2
3
Years
2014
JHLT. 2014 Oct; 33(10): 1009-1024
4
5
Adult Heart-Lung Transplants
Freedom from Bronchiolitis Obliterans Syndrome
by Diagnosis Type (Follow-ups: April 1994 – June 2013)
100
% Free from Bronchiolitis
Obliterans Syndrome
Heart (N=242)
Lung (N=80)
80
Heart/Lung (N=128)
60
40
20
p-value comparing all = 0.8307
0
0
1
2
3
Years
2014
JHLT. 2014 Oct; 33(10): 1009-1024
4
5
Adult Heart-Lung Transplants
Freedom from Severe Renal Dysfunction*
% Free from Severe Renal Dysfunction
(Follow-ups: April 1994 – June 2013)
100
90
80
70
*Severe renal dysfunction = Creatinine > 2.5 mg/dl
(221 μmol/L), dialysis or renal transplant
60
50
0
1
2
3
4
5
6
Years
2014
JHLT. 2014 Oct; 33(10): 1009-1024
7
8
9
10
11
Adult Heart-Lung Transplants
Cumulative Post Transplant Malignancy Rates in Survivors
(Follow-ups: April 1994 – June 2013)
1-Year
Survivors
Malignancy/Type
No Malignancy
Malignancy (all types combined)
Malignancy
Type*
5-Year
Survivors
10-Year
Survivors
477 (94.5%) 173 (88.7%)
63 (84.0%)
28 (5.5%)
22 (11.3%)
12 (16.0%)
Skin
2
8
10
Lymphoma
20
6
1
Other
4
6
2
Type Not Reported
2
2
0
* Recipients may have experienced more than one type of malignancy so sum of
individual malignancy types may be greater than total number with malignancy.
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Freedom from Malignancy
(Follow-ups: April 1994 – June 2013)
% Free from Malignancy
100
90
80
70
All malignancy
Lymphoma
60
Skin
Other
50
0
1
2
3
4
5
Years
2014
JHLT. 2014 Oct; 33(10): 1009-1024
6
7
8
9
10
Adult-Heart Lung Transplants
Cause of Death (Deaths: January 1992 – June 2013)
0-30 Days
(N = 425)
31 Days - 1 Year
(N = 337)
>1 Year - 3 Years
(N = 268)
>3 Years - 5
Years (N = 167)
>5 Years
(N = 441)
0
13 (3.9%)
65 (24.3%)
38 (22.8%)
97 (22.0%)
7 (1.6%)
9 (2.7%)
5 (1.9%)
2 (1.2%)
3 (0.7%)
0
8 (2.4%)
13 (4.9%)
8 (4.8%)
9 (2.0%)
1 (0.2%)
7 (2.1%)
12 (4.5%)
6 (3.6%)
29 (6.6%)
0
2 (0.6%)
1 (0.4%)
1 (0.6%)
1 (0.2%)
INFECTION, NON-CMV
75 (17.6%)
115 (34.1%)
76 (28.4%)
42 (25.1%)
103 (23.4%)
GRAFT FAILURE
112 (26.4%)
70 (20.8%)
36 (13.4%)
29 (17.4%)
61 (13.8%)
CARDIOVASCULAR
32 (7.5%)
15 (4.5%)
20 (7.5%)
18 (10.8%)
41 (9.3%)
TECHNICAL
93 (21.9%)
10 (3.0%)
3 (1.1%)
3 (1.8%)
4 (0.9%)
OTHER
105 (24.7%)
88 (26.1%)
37 (13.8%)
20 (12.0%)
93 (21.1%)
CAUSE OF DEATH
BRONCHIOLITIS
ACUTE REJECTION
LYMPHOMA
MALIGNANCY, OTHER
CMV
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants
Cause of Death Stratified by Transplant Type
(Deaths: January 1992 – June 2013)
Transplant
Type
Cause of Death
0-30 Days
31 Days - 1
Year
>1 Year - 3
Years
>3 Years - 5
Years
>5 Years
0
13 (4.0%)
65 (24.6%)
38 (23.6%)
95 (21.8%)
1 (0.2%)
14 (4.3%)
24 (9.1%)
14 (8.7%)
38 (8.7%)
Infection
73 (17.8%)
112 (34.5%)
76 (28.8%)
41 (25.5%)
103 (23.7%)
Graft Failure
107 (26.0%)
69 (21.2%)
36 (13.6%)
28 (17.4%)
61 (14.0%)
Cardiovascular
30 (7.3%)
13 (4.0%)
19 (7.2%)
17 (10.6%)
38 (8.7%)
Technical
92 (22.4%)
10 (3.1%)
3 (1.1%)
3 (1.9%)
4 (0.9%)
411
325
264
161
435
Bronchiolitis
0
0
0
0
2 (33.3%)
Malignancy
0
1 (8.3%)
1 (25.0%)
0
0
2 (14.3%)
5 (41.7%)
1 (25.0%)
2 (33.3%)
1 (16.7%)
5 (35.7%)
1 (8.3%)
0
1 (16.7%)
0
Cardiovascular
2 (14.3%)
2 (16.7%)
1 (25.0%)
1 (16.7%)
3 (50.0%)
Technical
1 (7.1%)
0
0
0
0
14
12
4
6
6
Bronchiolitis
Malignancy
Primary
All known causes
Infection
Retransplant Graft Failure
All known causes
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Acute rejection and other causes of death
are not shown on the slide
Adult Heart-Lung Transplants
Relative Incidence of Leading Causes of Death
(Deaths: January 1992 – June 2013)
50
Bronchiolitis
Infection (non-CMV)
Cardiovascular
Technical
Graft Failure
% of Deaths
40
30
20
10
0
0-30 Days
(N = 425)
31 Days – 1
>1 Year – 3
>3 Years – 5
Year (N = 337) Years (N = 268) Years (N = 167)
2014
JHLT. 2014 Oct; 33(10): 1009-1024
>5 Years
(N = 441)
Multivariable Analysis
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Adult Heart-Lung Transplants (January 1995 – June 2011)
Risk Factors For 1 Year Mortality
VARIABLE
Diagnosis: IPAH vs. Other*
N
Hazard
Ratio
P-value
446
0.78
0.0171
95%
Confidence
Interval
0.63 - 0.96
Continuous factors (see figures)
Donor age
N = 1,681
2014
JHLT. 2014 Oct; 33(10): 1009-1024
* Other = All diagnoses other than
IPAH and Congenital
Adult Heart-Lung Transplants (January 1995 – June 2011)
Risk Factors For 1 Year Mortality with 95% Confidence Limits
Donor Age
Hazard Ratio of 1 Year Mortality
2.0
p = 0.0195
1.5
1.0
0.5
0.0
15
20
25
30
35
Donor Age
2014
JHLT. 2014 Oct; 33(10): 1009-1024
40
45
50