HEART-LUNG TRANSPLANTATION

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