heart-lung transplantation
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HEART-LUNG TRANSPLANTATION. Adult Recipients. 2013. JHLT. 2013 Oct; 32(10): 965-978. Donor, Recipient and Center Characteristics. 2013. JHLT. 2013 Oct; 32(10): 965-978. Adult Heart-Lung Transplants Diagnosis (Transplants: January 1982 – June 2012). 2013. - PowerPoint PPT PresentationTRANSCRIPT
HEART-LUNG TRANSPLANTATION
Adult Recipients
JHLT. 2013 Oct; 32(10): 965-978
2013
Donor, Recipient and Center Characteristics
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsDiagnosis (Transplants: January 1982 – June 2012)
Acquired Heart Disease
5%
Congenital36%
COPD/A1A6%
Cystic Fibrosis14%
Idiopathic Pulmonary Fibrosis4% Idiopathic Pulmonary
Arterial Hypertension27%
Re-Tx2%
Sarcoidosis2%
Other5%
NOTE: “Other” includes cancer, LAM, OB, bronchiectasis
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsDiagnosis (Transplants: January 1982 – June 2012)
Diagnosis N (%)Congenital Heart Disease 1,154 (35.6%)
Idiopathic Pulmonary Arterial Hypertension 890 (27.5%)
Cystic Fibrosis 453 (14.0%)
Acquired Heart Disease 165 (5.1%)
COPD/Emphysema 136 (4.2%)
Idiopathic Pulmonary Fibrosis 119 (3.7%)
Alpha-1 61 (1.9%)
Sarcoidosis 54 (1.7%)
Re-Transplant: Not Obliterative Bronchiolitis 37 (1.1%)
Re-Transplant: Obliterative Bronchiolitis 22 (0.7%)
Bronchiectasis 30 (0.9%)
Obliterative Bronchiolitis (not Re-Transplant) 24 (0.7%)
Other 96 (3.0%)
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsDiagnosis by Era (Transplants: January 1982 – June 2012)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1982-1991 (N=959) 1992-2001 (N=1,453)
2002-6/2012 (N=829)
Other
Sarcoidosis
Re-Tx
Idiopathic Pulmonary Fibrosis
COPD/A1A
Acquired Heart Disease
Cystic Fibrosis
IPAH
Congenital
% o
f Tra
nspl
ants
NOTE: “Other” includes OB (non-Re-Tx) and Bronchiectasis.
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsMajor Indications by Year (%)
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
0102030405060708090
100
Congenital Heart Disease IPAH Cystic FibrosisCOPD/Alpha-1 Retransplant Acquired Heart Disease
Transplant Year
% o
f Tra
nspl
ants
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsMajor Indications By Year (Number)
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
0
20
40
60
80
100
120
140
160
180
Congenital Heart Disease IPAH Cystic Fibrosis
COPD/Alpha-1 Retransplant Acquired Heart Disease
Transplant Year
Num
ber o
f Tra
nspl
ants
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsAge Distribution By Location
(Transplants: January 2000 – June 2012)
Europe North America Other0%
20%
40%
60%
80%
100%
18 - 34 years 35 - 49 years 50 - 59 years 60+ years
% o
f Tra
nspl
ants
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsDiagnosis Distribution By Location(Transplants: January 2000 – June 2012)
Europe North America Other0%
20%
40%
60%
80%
100%
Congenital heart disease IPAH Cystic Fibrosis Acquired heart disease IPF Other
% o
f Tra
nspl
ants
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants Donor Age Distribution By Location
(Transplants: January 2000 – June 2012)
Europe North America Other0%
20%
40%
60%
80%
100%
6-11 12-17 18-34 35-49 50-59 60+
% o
f Don
ors
JHLT. 2013 Oct; 32(10): 965-978
2013
Post-Transplant: Survival and Other Outcomes
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants Kaplan-Meier Survival
(Transplants: January 1982 – June 2011)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240
25
50
75
100
Years
Surv
ival
(%) N = 3,620
Median survival = 3.3 yearsConditional median survival = 10.0 years f
N at risk at 24 years = 17
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants Kaplan-Meier Survival by Era
(Transplants: January 1982 – June 2011)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240
25
50
75
100
1982-1991 (N=1,210)1992-2001 (N=1,598)2002-6/2011 (N=812)
Years
Surv
ival
(%)
1982-1991 vs. 1992-2001: p < 0.00011982-1991 vs. 2002-6/2011: p < 0.00011992-2001 vs. 2002-6/2011: p = 0.0100
Median survival (years): 1982-1991=1.9; 1992-2001=3.6; 2002-6/2011=5.9 Conditional median survival (years): 1982-1991=9.0; 1992-2001=10.0; 2002-6/2011=NA
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsKaplan-Meier Survival By Diagnosis
(Transplants: January 1990 – June 2011)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 190
25
50
75
100Other Congenital (N = 331)
Eisenmenger's Syndrome (N = 630)
IPAH (N = 653)
Years
Surv
ival
(%)
No pair-wise comparisons were significant at p < 0.05
Median survival (years): Congenital=3.3; Eisenmenger's=5.5; IPAH=4.6
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsKaplan-Meier Survival By Diagnosis Conditional on Survival
to 1 Year (Transplants: January 1990 – June 2011)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 190
25
50
75
100Other Congenital (N = 194)
Eisenmenger's Syndrome (N = 420)IPAH (N = 442)
Years
Surv
ival
(%)
No pair-wise comparisons were significant at p < 0.05
Median survival (years): Congenital=13.6; Eisenmenger's=11.1; IPAH=10.1
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsFunctional Status of Surviving Recipients
(Follow-ups: March 2005 – June 2012)
0%
20%
40%
60%
80%
100%
1 Year (N = 172) 2 Years (N = 129)
3 Years (N = 110)
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsEmployment Status of Surviving Recipients
(Follow-ups: April 1994 – June 2012)
0%
20%
40%
60%
80%
100%
1 Year (N = 363) 3 Years (N = 257)
5 Years (N = 228)
Working (FT/PT sta-tus unknown)
Retired
Not Working
Working Part Time
Working Full Time
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsEmployment Status of Surviving Recipients by Era
(Follow-ups: April 1994 – June 2012)
0%
20%
40%
60%
80%
100%
1 year (N = 162)
3 years (N = 109)
5 years (N = 97)
1 year (N = 201)
3 years (N = 148)
5 years (N = 131)
Working (FT/PT sta-tus unknown)
Retired
Not Working
Working Part Time
Working Full Time
4/1994 - 1999 2000 - 6/2012
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsRehospitalization Post-transplant of Surviving Recipients
(Follow-ups: April 1994 – June 2012)
0%
20%
40%
60%
80%
100%
Up to 1 Year (N = 491)
Between 2 and 3 Years (N = 341)
Between 4 and 5 Years (N = 286)
No Hospitalization Hospitalized, Not Rejection/Not InfectionHospitalized, Rejection Only Hospitalized, Infection OnlyHospitalized, Rejection and Infection
JHLT. 2013 Oct; 32(10): 965-978
2013
Induction and Maintenance Immunosuppression
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants Induction Immunosuppression
(Transplants: January 2001 – June 2012)
Any Induction (N=202)
Polyclonal ALG/ATG
(N=68)
OKT3 (N=5) IL-2R Antagonist (N=109)
0
10
20
30
40
50
60
70
% o
f Pat
ient
s
Analysis is limited to patients who were alive at the time of the discharge
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants Induction Immunosuppression
(Transplants: January 2000 – December 2011)
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 20110
20
40
60
80
100
Any Induction Polyclonal ALG/ATG OKT3 IL-2R Antagonist
% o
f Pat
ient
s
Analysis is limited to patients who were alive at the time of the discharge
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants Induction Immunosuppression
(Transplants: January 2000 – December 2011)
2000
2002
2004
2006
2008
2010
2001
2003
2005
2007
2009
2011
2000
2002
2004
2006
2008
2010
2001
2003
2005
2007
2009
2011
0
10
20
30
40
50
60
70
80
90
% o
f Pat
ient
s
Any Induction Polyclonal ALG/ATG
OKT3 IL-2R Antagonist
Analysis is limited to patients who were alive at the time of the discharge
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants Maintenance Immunosuppression at Time of Follow-up
(Follow-ups: January 2001 – June 2012)
Cyclosporine Tacrolimus Sirolimus/Everolimus
MMF/MPA Azathioprine Prednisone0
10
20
30
40
50
60
70
80
90
100
Year 1 (N = 238) Year 5 (N = 146)
% o
f Pat
ient
s
Analysis is limited to patients who were alive at the time of the follow-up
NOTE: Different patients are analyzed in Year 1 and Year 5
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants Maintenance Immunosuppression Drug Combinations at
Time of Follow-up (Follow-ups: January 2001 – June 2012)
0%
20%
40%
60%
80%
100%
Year 1 (N = 238) Year 5 (N = 146)
Other
None
Sirolimus/Everolimus + Calcineurin + Cellcycle
Sirolimus/Everolimus + Calcineurin
Tacrolimus
Tacrolimus + MMF/MPA
Tacrolimus + AZA
Cyclosporine + MMF/MPA
Cyclosporine + AZA
Analysis is limited to patients who were alive at the time of the follow-up
NOTE: Different patients are analyzed in Year 1 and Year 5
JHLT. 2013 Oct; 32(10): 965-978
2013
Post-transplant Morbidities
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsCumulative Morbidity Rates in Survivors within 1 and 5 Years
Post-Transplant (Follow-ups: April 1994 – June 2012)
Outcome Within 1 Year
Total number
with known response
Within 5 Years
Total number
with known response
Hypertension 59.1% (N = 421) 87.8% (N = 148)
Renal Dysfunction 18.2% (N = 466) 45.3% (N = 181)
Abnormal Creatinine ≤ 2.5 mg/dl 11.2% 31.5% Creatinine > 2.5 mg/dl 2.8% 10.5% Chronic Dialysis 4.1% 2.2% Renal Transplant 0.2% 1.1% Hyperlipidemia 26.6% (N = 443) 69.2% (N = 156)
Diabetes 18.8% (N = 469) 27.9% (N = 179)
Coronary Artery Vasculopathy 3.0% (N = 371) 7.6% (N = 92)
Bronchiolitis Obliterans Syndrome 8.6% (N = 441) 28.3% (N = 152)
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsFreedom from Coronary Artery Vasculopathy and
Bronchiolitis Obliterans Syndrome(Follow-ups: April 1994 – June 2012)
0 1 2 3 4 5 6 7 8 9 100
20
40
60
80
100
Freedom from Coronary Artery Vasculopathy Freedom from Bronchiolitis Obliterans Syndrome
Years
% F
ree
from
CA
V an
d B
ronc
hiol
i-tis
Obl
itera
ns S
yndr
ome
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsFreedom from Coronary Artery Vasculopathy
By Diagnosis Type (Follow-ups: April 1994 – June 2012)
0 1 2 3 4 550
60
70
80
90
100
Heart (N=203)Lung (N=60)Heart/Lung (N=99)
Years
% F
ree
from
CA
V
p-value comparing all = 0.7222
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsFreedom from Bronchiolitis Obliterans Syndrome By Diagnosis Type (Follow-ups: April 1994 – June 2012)
0 1 2 3 4 550
60
70
80
90
100Heart (N=236)Lung (N=74)Heart/Lung (N=122)
Years
% F
ree
from
Bro
nchi
oliti
s O
blit-
eran
s Sy
ndro
me
p-value comparing all = 0.9993
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsFreedom from Severe Renal Dysfunction*
(Follow-ups: April 1994 – June 2012)
0 1 2 3 4 5 6 7 8 950
60
70
80
90
100
Years
% F
ree
from
Sev
ere
Ren
al D
ysfu
nctio
n
*Severe renal dysfunction = Creatinine > 2.5 mg/dl (221 μmol/L), dialysis or renal transplant
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsPost Transplant Malignancy (Follow-ups: April 1994 – June 2012)
Cumulative Morbidity Rates in Survivors
Malignancy/Type 1-Year Survivors
5-Year Survivors
10-Year Survivors
No Malignancy 449 (94.5%) 166 (88.8%) 58 (84.1%)
Malignancy (all types combined) 26 (5.5%) 21 (11.2%) 11 (15.9%)
Malignancy Type*
Skin 2 8 9
Lymphoma 18 6 1
Other 4 5 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.
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsFreedom from Malignancy
(Follow-ups: April 1994 – June 2012)
0 1 2 3 4 5 6 7 8 9 1050
60
70
80
90
100
All malignancyLymphomaSkinOther
Years
% F
ree
from
Mal
igna
ncy
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult-Heart Lung TransplantsCause of Death (Deaths: January 1992 – June 2012)
CAUSE OF DEATH 0-30 Days (N = 415)
31 Days - 1 Year (N = 322)
>1 Year - 3 Years (N = 263)
>3 Years - 5 Years (N = 163)
>5 Years (N = 426)
BRONCHIOLITIS 0 13 (4.0%) 64 (24.3%) 36 (22.1%) 92 (21.6%)
ACUTE REJECTION 7 (1.7%) 9 (2.8%) 5 (1.9%) 2 (1.2%) 3 (0.7%)
LYMPHOMA 0 8 (2.5%) 13 (4.9%) 8 (4.9%) 9 (2.1%)
MALIGNANCY, OTHER 1 (0.2%) 7 (2.2%) 12 (4.6%) 5 (3.1%) 27 (6.3%)
CMV 0 2 (0.6%) 1 (0.4%) 1 (0.6%) 1 (0.2%)
INFECTION, NON-CMV 74 (17.8%) 113 (35.1%) 75 (28.5%) 42 (25.8%) 102 (23.9%)
GRAFT FAILURE 112 (27.0%) 68 (21.1%) 36 (13.7%) 29 (17.8%) 59 (13.8%)
CARDIOVASCULAR 32 (7.7%) 14 (4.3%) 19 (7.2%) 16 (9.8%) 37 (8.7%)
TECHNICAL 91 (21.9%) 9 (2.8%) 3 (1.1%) 3 (1.8%) 3 (0.7%)
OTHER 98 (23.6%) 79 (24.5%) 35 (13.3%) 21 (12.9%) 93 (21.8%)
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung TransplantsRelative Incidence of Leading Causes of Death
(Deaths: January 1992 – June 2012)
0-30 Days (N = 415)
31 Days – 1 Year (N = 322)
>1 Year – 3 Years (N = 263)
>3 Years – 5 Years (N = 163)
>5 Years (N = 426)
0
10
20
30
40
50 Bronchiolitis Infection (non-CMV) Graft Failure Cardiovascular
Technical
% o
f Dea
ths
JHLT. 2013 Oct; 32(10): 965-978
2013
Multivariable Analysis
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants (January 1995 – June 2011)Risk Factors For 1 Year Mortality
VARIABLE N Hazard Ratio
P-value 95% Confidence
Interval
Diagnosis: IPAH vs. Other* 446 0.78 0.0171 0.63 - 0.96
Continuous factors (see figures)
Donor age
Transplant center volume (borderline)
N = 1,681* Other = All diagnoses other than IPAH and Congenital
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants (January 1995 – June 2011) Risk Factors For 1 Year Mortality with 95% Confidence Limits
Donor Age
15 20 25 30 35 40 45 500.0
0.5
1.0
1.5
2.0
Donor Age
Haz
ard
Rat
io o
f 1 Y
ear M
orta
lity p = 0.0195
JHLT. 2013 Oct; 32(10): 965-978
2013
Adult Heart-Lung Transplants (January 1995 – June 2011) Risk Factors For 1 Year Mortality with 95% Confidence Limits
Transplant Center Volume
5 10 15 20 25 30 35 40 45 500.0
0.5
1.0
1.5
2.0
Center Volume (cases per year)
Haz
ard
Rat
io o
f 1 Y
ear M
orta
lity p = 0.0519
JHLT. 2013 Oct; 32(10): 965-978
2013