HEART TRANSPLANTATION by 6S8whiQ

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									HEART TRANSPLANTATION

                      Pediatric Recipients




    ISHLT                                2010
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
AGE DISTRIBUTION OF PEDIATRIC HEART
  RECIPIENTS (Transplants: January 1996 - June 2009)
                        1400
                        1300
                        1200
                        1100
Number of Transplants




                        1000
                         900
                         800
                         700
                         600
                         500
                         400
                         300
                         200
                         100
                           0
                               0    1     2    3    4    5    6    7    8    9   10 11   12   13 14   15   16   17
                                                             Recipient Age (Years)
                               ISHLT                              2010
                         J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                           AGE DISTRIBUTION FOR DONORS OF
                             PEDIATRIC HEART RECIPIENTS
                                           (Transplants: January 1996 - June 2009)
                        1000
                        900
                        800
Number of Transplants




                        700
                        600
                        500
                        400
                        300
                        200
                        100
                          0
                               0       2        4         6        8       10      12   14   16   18-   31+
                                                                                                  25
                                                                Donor Age (Years)

                               ISHLT                                2010
                           J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                                      AGE DISTRIBUTION OF
                                   PEDIATRIC HEART RECIPIENTS
                                                             By Year of Transplant
                        500
                        450                  11-17 Years
Number of Transplants




                        400                  1-10 Years

                        350                  <1 Year

                        300
                        250
                        200
                        150
                        100
                        50
                         0
                          82
                               83
                                    84
                                         85
                                              86
                                                   87
                                                        88
                                                             89
                                                                  90
                                                                       91
                                                                            92
                                                                                 93
                                                                                      94
                                                                                           95
                                                                                                96
                                                                                                     97
                                                                                                          98
                                                                                                                99
                                                                                                                     00
                                                                                                                          01
                                                                                                                               02
                                                                                                                                    03
                                                                                                                                         04
                                                                                                                                              05
                                                                                                                                                   06
                                                                                                                                                         07
                                                                                                                                                              08
                         19
                              19
                                   19
                                        19
                                             19
                                                  19
                                                       19
                                                            19
                                                                 19
                                                                      19
                                                                           19
                                                                                19
                                                                                     19
                                                                                          19
                                                                                               19
                                                                                                    19
                                                                                                         19
                                                                                                              19
                                                                                                                   20
                                                                                                                        20
                                                                                                                             20
                                                                                                                                  20
                                                                                                                                       20
                                                                                                                                            20
                                                                                                                                                 20
                                                                                                                                                      20
                                                                                                                                                           20
                                                                                                     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 increased and/or decreased in recent years.
                               ISHLT                                                 2010
                         J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                                                                           Number of Centers Reporting




                                                                           10
                                                                                20
                                                                                     30
                                                                                          40
                                                                                               50
                                                                                                    60
                                                                                                         70
                                                                                                              80
                                                                                                                   90
                                                                                                                        100
                                                                                                                              110




                                                                       0
                                                                19
                                                                  8
                                                                19 2
                                                                  8
                                                                19 3
                                                                  8
                                                                19 4
                                                                  8
                                                                19 5
                                                                  8




                                                        ISHLT
                                                                19 6
                                                                  8
                                                                19 7
                                                                  8
                                                                19 8
                                                                  8
                                                                19 9
                                                                  9
                                                                19 0
                                                                  9
                                                                19 1
                                                                  9
                                                                19 2
                                                                  9
                                                                19 3
                                                                  9
                                                                19 4




                                                        2010
                                                                  9
                                                                19 5
                                                                  9




J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                                                                19 6
                                                                  9
                                                                19 7
                                                                  9
                                                                19 8
                                                                  9
                                                                20 9
                                                                  0
                                                                20 0
                                                                  0
                                                                20 1
                                                                  0
                                                                20 2
                                                                  0
                                                                20 3
                                                                  0
                                                                20 4
                                                                  0
                                                                20 5
                                                                                                                                    PEDIATRIC HEART TRANSPLANTS




                                                                  0
                                                                                                                                    NUMBER OF CENTERS REPORTING




                                                                20 6
                                                                  0
                                                                20 7
                                                                  08
                                    NUMBER OF CENTERS REPORTING
                                    PEDIATRIC HEART TRANSPLANTS
                              110
Number of Centers Reporting




                              100       Other
                              90        North America

                              80        Europe

                              70
                              60
                              50
                              40
                              30
                              20
                              10
                               0
                              19 2
                              19 3
                              19 4
                              19 5
                              19 6
                              19 7
                              19 8
                              19 9
                              19 0
                              19 1
                              19 2
                              19 3
                              19 4
                              19 5
                              19 6
                              19 7
                              19 8
                              20 9
                              20 0
                              20 1
                              20 2
                              20 3
                              20 4
                              20 5
                              20 6
                              20 7
                                08
                                8
                                8
                                8
                                8
                                8
                                8
                                8
                                8
                                9
                                9
                                9
                                9
                                9
                                9
                                9
                                9
                                9
                                9
                                0
                                0
                                0
                                0
                                0
                                0
                                0
                                0
                              19




                                     ISHLT                               2010
                                J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                    AVERAGE CENTER VOLUME AND PERCENTAGE
                       OF TRANSPLANTS BY CENTER VOLUME
      Pediatric Heart Transplants: January 1, 1997 - June 30, 2009
                    140                                                                                              49




                                                                                                                          Percentage of transplants
                    120                                                                                              42
Number of centers




                    100                                                                                              35

                     80                                                                                              28

                     60           123      126                                                                       21

                     40                                                                                              14

                     20                                                                                              7
                                                               18            16                         16
                     0                                                                          9                    0
                                      1-4/yr                        5-9/yr                       10-19/yr
                                        Average number of heart transplants per year
                      Number of centers 1997-2000                                 Number of centers 2001-June 2009
                      Percentage of transplants 1997-2000                         Percentage of transplants 2001-June 2009


                              ISHLT                                 2010
                          J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                            DISTRIBUTION OF TRANSPLANTS
                                 BY CENTER VOLUME
Pediatric Heart Transplants: January 1, 1997 - June 30, 2009
                   50
                                                      1997-2000          2001-June 2009

                   40
% of transplants




                   30

                                                                                                         46.3
                   20
                             34.8
                                           29.3             29.5                          30.4
                                                                         24.4
                   10


                   0
                                    1-4                            5-9                           10-19
                                          Average number of heart transplants per year
                        ISHLT                                2010
                    J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                             PEDIATRIC HEART RE-TRANSPLANTS
                                                       By Transplant Year
                                       Re-transplants: January 1994 – December 2008
                        40

                        35
Number of transplants




                        30

                        25

                        20

                        15

                        10

                         5

                         0
                           94

                                  95

                                         96

                                                97

                                                       98

                                                              99

                                                                     00

                                                                            01

                                                                                   02


                                                                                          03

                                                                                                 04

                                                                                                        05

                                                                                                                06

                                                                                                                        07

                                                                                                                                 08
                         19

                                19

                                       19

                                              19

                                                     19

                                                            19

                                                                   20

                                                                          20

                                                                                 20


                                                                                        20

                                                                                               20

                                                                                                      20

                                                                                                              20

                                                                                                                      20

                                                                                                                               20
                                                                    Year of re-transplant
                                 ISHLT                                    2010                 Only patients who were less than 18 years
                                                                                               old at the time of re-transplant are included.
                             J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                       PEDIATRIC HEART RE-TRANSPLANTS
                                                  By Inter-transplant Interval
                                          Re-transplants: January 1994 - June 2009
                      50

                                     0-10 Years         11-17 Years
% of Re-Transplants




                      40


                      30


                      20


                      10


                       0
                              <1 month           1-<12           12-<36           36-<60         60+ months Not reported
                                                months           months           months
                                          Time Between Previous and Current Transplant

                                ISHLT                                   2010     Only patients who were less than 18 years old at
                                                                                 the time of re-transplant are included. Analysis is
                           J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141 based on the age at the time of re-transplant
      KAPLAN-MEIER SURVIVAL RATES FOR PEDIATRIC HEART
   RETRANSPLANTS STRATIFIED BY INTER-TRANSPLANT INTERVAL
             Re-transplants: January 1994 - June 2008
                                     <1 Year (N=48)            1-<3 Years (N=34)             3-<5 Years (N=48)
                                     5+ Years (N=145)          Primary TX (N=5,417)
                100
                                                                                  Comparison of survival for
                                                                                  re-transplant groups: p = 0.0019
                90
Surrvival (%)




                80

                70

                60

                50

                40
                       0       0.5        1       1.5      2        2.5       3          3.5          4         4.5          5

                                         Time (years) since most recent transplant

                           ISHLT                               2010
                                                                                      Only patients who were less than 18 years
                                                                                      old at the time of re-transplant are included.
                      J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
           DIAGNOSIS IN PEDIATRIC HEART
        TRANSPLANT RECIPIENTS (Age: < 1 Year)
                                                                                33%
                                                            Myopathy
             17%

                                                            Congenital
      1%                                                                   0%
                                                            Other          3%
       2%                                   80%
                                                            ReTX                                 63%

                         1988-1995                                               1/1996-6/2009
             100
% of Cases




             75
             50                      Myopathy            Congenital

             25
              0
               86
               87
               88
               89
               90
               91
               92
               93
               94
               95
               96
               97
               98
               99
               00
               01
               02
               03
               04
               05
               06
               07
               08
               09
             19
             19
             19
             19
             19
             19
             19
             19
             19
             19
             19
             19
             19
             19
             20
             20
             20
             20
             20
             20
             20
             20
             20
             20
                       ISHLT                                2010
                   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
    DIAGNOSIS IN PEDIATRIC HEART
TRANSPLANT RECIPIENTS (Age: 1-10 Years)
              4%                                                            5%
                                          53%             Myopathy
             2%                                                                                   55%
                                                                           3%
                                                          Congenital

                                                          Other


              41%                                         ReTX              37%

                        1988-1995                                                 1/1996-6/2009
             100
% of Cases




                                     Myopathy            Congenital
             75
             50
             25
              0
               86
               87
               88
               89
               90
               91
               92
               93
               94
               95
               96
               97
               98
               99
               00
               01
               02
               03
               04
               05
               06
               07
               08
               09
             19
             19
             19
             19
             19
             19
             19
             19
             19
             19
             19
             19
             19
             19
             20
             20
             20
             20
             20
             20
             20
             20
             20
             20
                       ISHLT                                2010
                   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
    DIAGNOSIS IN PEDIATRIC HEART
TRANSPLANT RECIPIENTS (Age: 11-17 Years)
                                                          Myopathy
                                                                                                        25%
                                           27%
                                                          Congenital

             68%                                          Other                 65%                      3%
                                           3%
                                                                                                        8%
                                          2%              ReTX
                         1988-1995                                                      1/1996-6/2009
             100
% of Cases




                                                     Myopathy              Congenital
              75
              50
              25
               0
                86
                87
                88
                89
                90
                91
                92
                93
                94
                95
                96
                97
                98
                99
                00
                01
                02
                03
                04
                05
                06
                07
                08
                09
              19
              19
              19
              19
              19
              19
              19
              19
              19
              19
              19
              19
              19
              19
              20
              20
              20
              20
              20
              20
              20
              20
              20
              20
                       ISHLT                                2010
                   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
               PEDIATRIC HEART TRANSPLANTATION
               Kaplan-Meier Survival (Transplants: 1/1982-6/2008)
               100
                                                      <1 Year (N = 2,049)                1-10 Years (N = 2,929)
                90                                    11-17 Years (N = 3,027)            Overall (N = 8,005)
                80

                70
Survival (%)




                60
                         0-<1 vs. 1-10: p < 0.0001;
                50       0-<1 vs. 11-17: p=0.3284;
                         1-10 vs. 11-17: p=0.0003.
                40

                30

                20

                10       Half-life <1: 18.3 Years; 1-10: 15.5 Years; 11-17: 11.3 Years

                 0
                     0     1    2    3     4    5      6    7    8    9     10 11 12 13 14 15 16 17 18 19 20
                                                                          Years
                         ISHLT                                       2010
                J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                PEDIATRIC HEART TRANSPLANTATION
                                 Conditional Kaplan-Meier Survival
                                                  (Transplants: 1/1982-6/2008)
               100
                                                           Half-life: <1: 21.4; 1-10: 19.3 Years; 11-17: 15.2 Years
               90

               80
Survival (%)




               70

                         0-<1 vs. 1-10: p = 0.0138;
               60        0-<1 vs. 11-17: p < 0.0001;
                         1-10 vs. 11-17: p < 0.0001.
               50

               40                  <1 Year      (N = 1,422)          1-10 Years (N = 2,272)
                                   11-17 Years (N =2,399)            Overall     (N = 6,093)
               30
                     0      1    2     3    4    5     6   7     8    9    10 11 12 13 14 15 16 17 18 19 20
                                                                          Years
                            ISHLT                                    2010
                     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
               PEDIATRIC HEART TRANSPLANTATION
                      Conditional Kaplan-Meier Survival for Recent Era
                                              (Transplants: 1/1999-6/2008)
               100


               90
Survival (%)




               80           0-<1 vs. 1-10: p = 0.0251
                            0-<1 vs. 11-17: p = 0.0010;
                            1-10 vs. 11-17: p < 0.0001

               70


               60
                              <1 Year      (N = 683)           1-10 Years (N =1,184)
                              11-17 Years (N = 1,201)          Overall       (N = 3,068)
               50
                     0             1              2           3               4            5   6   7
                                                                  Years
                         ISHLT                                2010
                     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
               PEDIATRIC HEART TRANSPLANTATION
                    Kaplan-Meier Survival by Era
                                          (Transplants: 1/1982-6/2008)

               100
                                                       1982-1989 (N=846)                      1990-1994 (N=1,803)
                                                       1995-1999 (N=1,846)                    2000-6/2008 (N=3,510)
                80                                      Half-life 1982-1989: 9.5 years; 1990-1994: 11.7 years; 1995-
                                                        1999: 14.3; 2000-6/2008: n.c.
Survival (%)




                60


                40


                20
                                                       All p-values 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
                                                                 Years

                         ISHLT                              2010
                J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
  PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival by Era (Transplants: 1/1982-6/2008)
                                                           Age: < 1 Year
                100
                                                              1982-1989 (N=176)                    1990-1994 (N=571)
                                                              1995-1999 (N=479)                    2000-6/2008 (N =823)
                80
 Survival (%)




                60


                          Half-life 1982-1989: 10.8 years; 1990-1994: 9.7 years; 1995-
                40
                          1999: n.c. ; 2000-6/2008: n.c.

                          P-values for era comparisons
                20        All p-values significant at p < 0.0001 except comparison of 82-89 vs. 90-94 and
                          95-99 vs. 00-6/08

                 0
                      0      1     2      3     4      5     6      7     8      9       10   11   12    13    14      15   16
                                                                        Years

                           ISHLT                                    2010
                      J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
  PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival by Era (Transplants: 1/1982-6/2008)
                                                         Age: 1-10 Years
          100
                                                          1982-1989 (N = 263)                 1990-1994 (N=633)
                                                          1995-1999 (N=708)                   2000-6/2008 (N=1,325)
                80
 Survival (%)




                60


                40
                         P-values for era comparisons
                         All p-values significant at p = 0.01 except
                         for 82-89 vs. 90-94
                20
                         Half-life 1982-1989: 9.1; 1990-1994: 12.4; 1995-1999: 13.6 ; 2000-6/2008: n.a.
                0
                     0      1     2     3     4      5     6     7       8     9   10    11     12    13   14     15   16
                                                                       Years
                           ISHLT                                  2010
                     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
  PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival by Era (Transplants: 1/1982-6/2008)
                                                       Age: 11-17 Years
                100
                                                              1982-1989 (N=407)                  1990-1994 (N=599)
                                                              1995-1999 (N=659)                  2000-6/2008 (N=1,362)
                80
 Survival (%)




                60


                40
                          Half-life 1982-1989: 9.3; 1990-1994: 11.8; 1995-1999: 10.3;
                          2000-6/2008: n.a.
                20
                           P-values for era comparisons
                           No p-values significant at p = 0.05 except 82-89 vs. 90-94: p = 0.0341; 82-
                           89 vs. 00-6/08: p < 0.0001;
                 0
                      0      1    2     3    4     5    6     7    8     9    10 11 12 13 14 15 16 17 18 19
                                                                        Years

                          ISHLT                                     2010
                  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                          PEDIATRIC HEART TRANSPLANTS:
AVERAGE CENTER VOLUME DISTRIBUTION BY LOCATION
                              Transplants between January 2000 and June 2009

                                      1-4/year              5-9/year        10-19/year
                   100%
% of Transplants




                   80%


                   60%


                   40%


                   20%


                    0%
                                    Europe                  North America            Other



                       ISHLT                                2010
                   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
               PEDIATRIC HEART TRANSPLANTATION
                Kaplan-Meier Patient vs. Graft Survival
                                              (Transplants: 1/1999-6/2008)
                     Average Center Volume: 1-4 Transplants per Year
               100


               80
Survival (%)




               60


               40
                           p = 0.2878

               20
                                    Patient (N=1,172)                Graft (N=1,172)

                0
                     0          1         2             3      4           5           6   7   8   9
                                                                   Years

                         ISHLT                                2010
                     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
               PEDIATRIC HEART TRANSPLANTATION
                Kaplan-Meier Patient vs. Graft Survival
                                                 (Transplants: 1/1999-6/2008)
                     Average Center Volume: 5-9 Transplants per Year
               100


               80
Survival (%)




               60


               40
                           p = 0.1670

               20
                                        Patient (N=900)               Graft (N=900)

                0
                     0          1            2            3    4           5          6   7   8   9
                                                                   Years

                         ISHLT                                2010
                     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
               PEDIATRIC HEART TRANSPLANTATION
                Kaplan-Meier Patient vs. Graft Survival
                                              (Transplants: 1/1999-6/2008)
                 Average Center Volume: 10-19 Transplants per Year
               100


               80
Survival (%)




               60


               40
                           p = 0.0201

               20
                                    Patient (N=1,801)                Graft (N=1,801)

                0
                     0          1         2             3      4           5           6   7   8   9
                                                                   Years

                         ISHLT                                2010
                     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                          PEDIATRIC HEART TRANSPLANTS:
                                AGE DISTRIBUTION BY LOCATION
                              Transplants between January 2000 and June 2009

                                    <1 years            1-10 years         11-17 years
                   100%
% of Transplants




                   80%


                   60%


                   40%


                   20%


                    0%
                                   Europe                 North America            Other



                       ISHLT                                2010
                   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                            PEDIATRIC HEART TRANSPLANTS:
                            DIAGNOSIS DISTRIBUTION BY LOCATION
                                Transplants between January 2000 and June 2009
                   100%

                                                                                     Other
                   80%
% of Transplants




                                                                                     Re-TX/Graft
                                                                                     Failure
                   60%                                                               Malignancy

                                                                                     Coronary Artery
                   40%                                                               Disease
                                                                                     Congenital

                   20%                                                               Cardiomyopathy



                    0%
                                Europe            North America              Other



                          ISHLT                               2010
                     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                      PEDIATRIC HEART TRANSPLANTS:
                   DONOR AGE DISTRIBUTION BY LOCATION
                         Transplants between January 2000 and June 2009

                               <1        1-10        11-17            18-34   35-49           50-64
               100%


                80%
% of Donors




                60%


                40%


                20%


                 0%
                                Europe                 North America                  Other



                  ISHLT                                2010
              J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
    PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
                       Risk Factors For 1 Year Mortality
                                                                Relative             95% Confidence
VARIABLE                                                  N                P-value
                                                                 Risk                   Interval
Congenital diagnosis, age = 0, on ECMO                    81     2.86      <0.0001     1.99 -4.09

Congenital diagnosis, age > 0                            921     2.02      <0.0001     1.60 -2.56

Retransplant                                             230     1.96      0.0007      1.33 -2.89

Year of Transplant: 1996-1997 vs. 2002-2003              523     1.68      0.0013      1.22 -2.32

On dialysis                                               83     1.66      0.0217      1.08 -2.55

On ventilator                                            717     1.54      0.0002      1.23 -1.94

Year of Transplant: 1998-1999 vs. 2002-2003              509     1.49      0.0166      1.08 -2.07

PRA > 10%                                                349     1.36      0.0263      1.04 -1.79
Donor cause of death = cerebrovascular/stroke vs.
                                                         387     1.35      0.0401      1.01 -1.81
head trauma
Male donor/female recip vs. male donor/male recip        971     1.24      0.0404      1.01 -1.51

Diagnosis other than congenital, no ECMO, age = 0        290     0.47      0.0005      0.31 -0.72

                                              N=3,838
               ISHLT                             2010                Reference diagnosis = cardiomyopathy
        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
  PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
 Borderline Significant Risk Factors For 1 Year Mortality


                                                                                     95%
                                                             Relative
VARIABLE                                           N                    P-value   Confidence
                                                              Risk
                                                                                   Interval
Infection requiring IV drug therapy (with
                                                  584         1.24      0.0735    0.98 -1.56
2wk/TX)

Transfusions prior to transplant                 1159         1.23      0.0525    1.00 -1.52

Donor cause of death = anoxia vs head
                                                  898         0.81       0.065    0.65 -1.01
trauma




                                          N=3,838
         ISHLT                                2010
     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS                                        (1/1996-6/2008)
                  Risk Factors for 1 Year Mortality



                     Continuous Factors (see figures)
  Recipient age                                 Recipient height

  Donor age                                     Ischemia time

  Creatinine




                                       N=3,838
      ISHLT                                2010
  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
                                                    Risk Factors for 1 Year Mortality
                                                             Recipient Age
                                           4
      Relative Risk of 1 Year Mortality


                                                    p = 0.0024
                                          3.5
                                           3
                                          2.5
                                           2
                                          1.5
                                           1
                                          0.5
                                           0
                                                0        3         6          9   12          15            18
                                                                                         NOTE: The impact of age
                                                                 Recipient Age (Years)   should be considered in the
                                                                                         context of height and
                             ISHLT                                     2010              diagnosis+age.

   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                         N=3,838
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
                                                     Risk Factors for 1 Year Mortality
                                                            Recipient Height
                                           4
      Relative Risk of 1 Year Mortality


                                                                            p < 0.0001
                                          3.5

                                           3

                                          2.5

                                           2

                                          1.5

                                           1

                                          0.5

                                           0
                                                55   65   75   85   95    105   115   125   135    145    155     165    175

                                                                     Height (cm)            NOTE: The impact of height should
                                                                                            be considered in the context of age
                                                                                            and diagnosis+age.
                             ISHLT                                       2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                                    N=3,838
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
                                                    Risk Factors for 1 Year Mortality
                                                              Donor Age
                                           3
      Relative Risk of 1 Year Mortality


                                                      p = 0.027
                                          2.5
                                           2
                                          1.5
                                           1
                                          0.5
                                           0
                                                0       5     10      15    20    25    30   35
                                                                  Donor Age (Years)
                             ISHLT                                  2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                N=3,838
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
                                                    Risk Factors for 1 Year Mortality
                                                       Pre-Transplant Creatinine
                                           3
      Relative Risk of 1 Year Mortality



                                          2.5
                                           2
                                          1.5
                                           1
                                          0.5
                                                                                  p = 0.004
                                           0
                                                0           0.5          1         1.5          2
                                                      Recipient serum creatinine (mg/dl)
                             ISHLT                                2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                   N=3,838
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
                                                    Risk Factors for 1 Year Mortality
                                                            Ischemia Time
                                          2.5
      Relative Risk of 1 Year Mortality




                                           2

                                          1.5

                                           1

                                          0.5
                                                     p = 0.0075
                                           0
                                                2            3           4           5         6

                                                             Ischemia time (hours)

                             ISHLT                                2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                 N=3,838
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
           Factors Not Significant for 1 Year Mortality
Recipient Factors:
IV inotropes, sternotomy, history of malignancy,
hospitalized, diabetes

Donor Factors:
Gender, clinical infection, history of diabetes

Transplant Factors:
CMV mismatch, HLA mismatch, center volume




        ISHLT                                2010
    J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
  PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
               Age = <1 Years
                     Risk Factors For 1 Year Mortality
                                                               Relative
VARIABLE                                                                P-value 95% Confidence
                                                       N        Risk               Interval
ECMO (diagnosis = congenital)                          81       3.25    <0.0001       2.14 -4.95

ECMO, diagnosis other than congenital                  42       2.59     0.0147       1.21 -5.57

Year of Transplant: 1996-1997 vs. 2002-2003           162       2.33     0.0029       1.34 -4.07

On dialysis                                            21       2.22     0.0173       1.15 -4.29

Year of Transplant: 2006-2008 vs. 2002-2003           231        1.8     0.0266       1.07 -3.03
Donor cause of death = cerebrovascular/stroke
                                                       48       1.79     0.0359       1.04 -3.10
vs. head trauma
On ventilator                                         354       1.72     0.001        1.24 -2.37
Infection requiring IV drug therapy (within 2
                                                      259       1.52     0.0099       1.11 -2.08
weeks prior to transplant)
Diagnosis = cardiomyopathy                            296       0.48     0.004        0.29 -0.79

                                            N=1,009
              ISHLT                             2010              Reference diagnosis = congenital
                                                                  without PGE or ECMO
       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
             Age = <1 Years
Borderline Significant Risk Factors For 1 Year Mortality

                                                                             95%
                                                     Relative
VARIABLE                                      N                 P-value   Confidence
                                                      Risk
                                                                           Interval

Transplant Year: 1998-1999 vs. 2002-
                                             134       1.72     0.0691    0.96 -3.10
2003

PRA > 10%                                     76       1.60     0.0849    0.94 -2.73

Donor clinical infection                     182       0.71      0.081    0.48 -1.04




                                        N=1,009
        ISHLT                               2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS                                     (1/1996-6/2008)
                               Age = <1 Years
                  Risk Factors for 1 Year Mortality


                     Continuous Factors (see figures)
  Ischemia time                          Recipient height (borderline)
                                         Pediatric transplant volume
  Creatinine (borderline)
                                         (borderline)




                                       N=1,009
      ISHLT                                2010
  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
   Risk Factors for 1 Year Mortality in Age = <1 Years
                     Ischemia Time
                                          2.5
      Relative Risk of 1 Year Mortality




                                           2

                                          1.5

                                           1

                                          0.5
                                                    p = 0.038
                                           0
                                                2           3           4           5         6

                                                            Ischemia time (hours)

                             ISHLT                               2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                N=1,009
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
   Risk Factors for 1 Year Mortality in Age = <1 Years
               Pre-Transplant Creatinine
                                          2.5
      Relative Risk of 1 Year Mortality




                                           2

                                          1.5

                                           1

                                          0.5
                                                                                 p = 0.051
                                           0
                                                0      0.2      0.4       0.6      0.8        1
                                                    Recipient serum creatinine (mg/dl)
                             ISHLT                              2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                 N=1,009
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
   Risk Factors for 1 Year Mortality in Age = <1 Years
        Center Volume for Pediatric Transplants
                                           2
      Relative Risk of 1 Year Mortality




                                          1.5

                                           1

                                          0.5
                                                    p = 0.062
                                           0
                                                0    2     4    6    8     10   12   14   16    18   20
                                                         Center Volume (cases per year)

                             ISHLT                                  2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                       N=1,009
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
   Risk Factors for 1 Year Mortality in Age = <1 Years
                    Recipient Height
                                           3
      Relative Risk of 1 Year Mortality


                                                          p = 0.089
                                          2.5

                                           2

                                          1.5

                                           1

                                          0.5

                                           0
                                                45   50    55          60   65   70    75

                                                            Height (cm)

                             ISHLT                              2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                         N=1,009
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
            Age = 1-10 Years
                   Risk Factors For 1 Year Mortality

                                                             Relative               95% Confidence
VARIABLE                                             N                    P-value
                                                              Risk                     Interval

Diagnosis = congenital                              563       2.30        <0.0001       1.62 -3.25

Transfusions prior to transplant                    349       1.82         0.0009       1.28 -2.59

Female recipient                                    713       1.48         0.0144       1.08 -2.04

Donor cause of death = anoxia vs. head trauma       337       0.59         0.0131       0.39 -0.90




                                          N=1,448
          ISHLT                               2010                      Reference diagnosis = cardiomyopathy
     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
            Age = 1-10 Years
Borderline Significant Risk Factors For 1 Year Mortality

                                                   Relative             95% Confidence
VARIABLE                                    N                 P-value
                                                    Risk                   Interval

Diagnosis = re-transplant                   99       1.86     0.0639      0.96 -3.60

Not ABO identical                          288       0.68     0.0768      0.44 -1.04




                                       N=1,448
       ISHLT                               2010
  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS                                  (1/1996-6/2008)
                             Age = 1-10 Years
                  Risk Factors for 1 Year Mortality


                     Continuous Factors (see figures)
   Creatinine                                    Bilirubin

   Recipient height




                                       N=1,448
      ISHLT                                2010
  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
  Risk Factors for 1 Year Mortality in Age = 1-10 Years
               Pre-Transplant Creatinine
                                          3.5
      Relative Risk of 1 Year Mortality



                                           3
                                          2.5
                                           2
                                          1.5
                                           1
                                          0.5
                                                                                    p = 0.0002
                                           0
                                                0.2    0.4     0.6       0.8    1          1.2   1.4
                                                      Recipient serum creatinine (mg/dl)

                             ISHLT                                2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                    N=1,448
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
  Risk Factors for 1 Year Mortality in Age = 1-10 Years
                    Recipient Height
                                           2
      Relative Risk of 1 Year Mortality


                                                               p = 0.0045

                                          1.5


                                           1


                                          0.5


                                           0
                                                70   80   90      100    110   120   130   140   150

                                                                 Height (cm)

                             ISHLT                                2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                   N=1,448
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
  Risk Factors for 1 Year Mortality in Age = 1-10 Years
                   Recipient Bilirubin
                                          2.5
      Relative Risk of 1 Year Mortality


                                                    p = 0.022
                                           2

                                          1.5

                                           1

                                          0.5

                                           0
                                                0    0.5    1    1.5   2    2.5     3   3.5     4   4.5

                                                                Bilirubin (mg/dL)

                             ISHLT                                 2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                      N=1,448
PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
            Age = 11-17 Years
                   Risk Factors For 1 Year Mortality

                                                                                           95%
                                                                Relative      P-
VARIABLE                                            N                                   Confidence
                                                                 Risk        value
                                                                                         Interval
ECMO                                               48            3.03       0.0015       1.53 -6.01

Diagnosis = retransplant                          125             2.4       0.0008       1.44 -4.01

Diagnosis = congenital                            358            1.86       0.0024       1.25 -2.79

                                             0 DR MM: N = 48
HLA mismatches at DR locus (per increasing
mismatch, compared to 0 mismatches)
                                             1 DR MM: N = 552    0.72        0.03        0.54 -0.97
                                             2 DR MM: N = 781




                                             N=1,381
          ISHLT                                2010                     Reference diagnosis = cardiomyopathy
     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
 PEDIATRIC HEART TRANSPLANTS (1/1996-6/2008)
             Age = 11-17 Years
Borderline Significant Risk Factors For 1 Year Mortality
                                                                                  95%
                                                            Relative
VARIABLE                                              N              P-value   Confidence
                                                             Risk
                                                                                Interval

On dialysis                                           39     1.88    0.0961    0.89 -3.95

PRA > 10%                                            118     1.59    0.0614    0.98 -2.58

Donor cause of death = anoxia vs. head
                                                     175     0.57    0.0944    0.30 -1.10
trauma




                                         N=1,381
        ISHLT                                2010
    J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS                               (1/1996-6/2008)
                            Age = 11-17 Years
                  Risk Factors for 1 Year Mortality


                     Continuous Factors (see figures)
   Ischemia time (borderline)




                                       N=1,381
      ISHLT                                2010
  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS                                                             (1/1996-6/2008)
  Risk Factors for 1 Year Mortality in Age = 11-17 Years
                      Ischemia Time
                                          2.5
      Relative Risk of 1 Year Mortality




                                           2

                                          1.5

                                           1

                                          0.5
                                                    p = 0.094
                                           0
                                                2           3           4           5             6

                                                            Ischemia time (hours)

                             ISHLT                               2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                 N=1,381
     PEDIATRIC HEART TRANSPLANTS (1/1995-6/2003)
                       Risk Factors For 5 Year Mortality
                                                                  Relative         95% Confidence
VARIABLE                                                    N              P-value
                                                                   Risk               Interval
Congenital diagnosis, age = 0, on ECMO                      43     1.71     0.025       1.07 -2.74

On dialysis                                                 49     1.69    0.0174       1.10 -2.62

Retransplant                                               140     1.48    0.0166       1.07 -2.04

PRA > 10%                                                  259     1.48    0.0009       1.17 -1.86

On ventilator                                              459     1.29    0.0177       1.05 -1.59

Prior sternotomy                                           885     1.24    0.0346       1.02 -1.52

Female recipient                                           1041    1.22    0.0143       1.04 -1.44

Diagnosis other than congenital, no ECMO, age = 0          183     0.47    0.0006       0.31 -0.72



                                             N=2,420
              ISHLT                              2010                Reference diagnosis = cardiomyopathy
        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
 PEDIATRIC HEART TRANSPLANTS (1/1995-6/2003)
Borderline Significant Risk Factors For 5 Year Mortality


                                                                                    95%
                                                            Relative
VARIABLE                                          N                    P-value   Confidence
                                                             Risk
                                                                                  Interval
Infection requiring IV drug therapy (within
                                                 348         1.20      0.0957    0.97 -1.50
2 weeks prior to transplant)
Donor cause of death = anoxia vs. head
                                                 515         0.82      0.0587    0.67 -1.01
trauma




                                         N=2,420
         ISHLT                               2010
    J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS                                         (1/1995-6/2003)
                  Risk Factors for 5 Year Mortality



                     Continuous Factors (see figures)
  Recipient age                                  Recipient height

  Donor age                                      Ischemia time (borderline)
  Pediatric transplant volume
                                                 BSA ratio (borderline)
  (borderline)




                                       N=2,420
      ISHLT                                2010
  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2003)
                                                 Risk Factors for 5 Year Mortality
                                                          Recipient Age
                                       3.5
   Relative Risk of 5 Year Mortality




                                                                 p < 0.0001
                                        3
                                       2.5
                                        2
                                       1.5
                                        1
                                       0.5
                                        0
                                             0      3       6          9      12       15                 18
                                                                                   NOTE: The impact of age should be
                                                           Recipient Age (Years)   considered in the context of height
                                                                                   and diagnosis+age.

                                        ISHLT                   2010
                     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                 N=2,420
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2003)
                                                     Risk Factors for 5 Year Mortality
                                                            Recipient Height
                                           3
      Relative Risk of 5 Year Mortality


                                                                            p = 0.013
                                          2.5

                                           2

                                          1.5

                                           1

                                          0.5

                                           0
                                                55   65   75   85   95    105   115   125   135    145    155     165    175

                                                                     Height (cm)            NOTE: The impact of height should
                                                                                            be considered in the context of age
                                                                                            and diagnosis+age.
                             ISHLT                                       2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                                    N=2,420
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2003)
                                                    Risk Factors for 5 Year Mortality
                                                              Donor Age
                                           3
      Relative Risk of 5 Year Mortality


                                                      p = 0.026
                                          2.5
                                           2
                                          1.5
                                           1
                                          0.5
                                           0
                                                0      5    10     15      20   25    30   35   40
                                                                  Donor Age (Years)
                             ISHLT                                  2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                   N=2,420
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2003)
                                              Risk Factors for 5 Year Mortality
                                           Center Volume for Pediatric Transplants
                                          2.5
      Relative Risk of 5 Year Mortality




                                           2

                                          1.5

                                           1

                                          0.5
                                                    p = 0.064
                                           0
                                                0    2     4    6    8     10   12   14   16    18   20
                                                         Center Volume (cases per year)

                             ISHLT                                  2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                       N=2,420
PEDIATRIC HEART TRANSPLANTS                                                             (1/1995-6/2003)
                                                   Risk Factors for 5 Year Mortality
                                                           Ischemia Time
                                         2.5
     Relative Risk of 5 Year Mortality




                                          2

                                         1.5

                                          1

                                         0.5
                                                    p = 0.063
                                          0
                                               2            3           4           5             6

                                                            Ischemia time (hours)

                            ISHLT                                2010
  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                  N=2,420
PEDIATRIC HEART TRANSPLANTS                                                              (1/1995-6/2003)
                                                     Risk Factors for 5 Year Mortality
                                                               BSA Ratio
                                         2.5
     Relative Risk of 5 Year Mortality




                                          2

                                         1.5

                                          1

                                         0.5
                                                      p = 0.063
                                          0
                                               0.8        1        1.2      1.4   1.6    1.8      2

                                                              Donor BSA/Recipient BSA

                            ISHLT                                    2010
  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                   N=2,420
PEDIATRIC HEART TRANSPLANTS (1/1995-6/1998)
                     Risk Factors For 10 Year Mortality
                                                                             Relative        P-        95% Confidence
VARIABLE                                                         N
                                                                              Risk          value         Interval
Female recipient/male donor vs. male
recipient/male donor
                                                                372             1.41       0.0239           1.05 -1.90

Female donor/male recipient vs. male
recipient/male donor
                                                                386             1.40       0.0201           1.05 -1.86

HLA mismatches at A locus (per increasing                 0 DR MM: N = 57

mismatch compared to 0 mismatches
                                                          1 DR MM: N = 306      1.25       0.0198           1.04 -1.51
                                                          2 DR MM: N = 547


Female recipient/female donor vs. male
recipient/male donor
                                                                154             0.62       0.0378           0.40 -0.97


Diagnosis = cardiomyopathy, age = 0 years*                       58             0.44       0.0141           0.23 -0.85


     * Impact should be considered in context of donor age and recipient BSA shown in subsequent figures.



                                                                                       Reference diagnosis = cardiomyopathy

           ISHLT                                          2010                                     N=910
     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1995-6/1998)
Borderline Significant Risk Factors For 10 Year Mortality


                                                       Relative                95% Confidence
  VARIABLE                                     N                   P-value
                                                        Risk                      Interval

  Infection requiring IV drug therapy
                                              103           1.33     0.087          0.96 -1.83
  (within 2 weeks prior to transplant)




                                                                   Reference diagnosis = cardiomyopathy

        ISHLT                                2010                            N=910
    J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS                                         (1/1995-6/1998)
                 Risk Factors for 10 Year Mortality



                      Continuous Factors (see figures)
  Creatinine                                        Donor age
  Pediatric transplant volume                       Recipient BSA
  (borderline)




      ISHLT                                2010                 N=910
  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1995-6/1997)
                                                    Risk Factors for 10 Year Mortality
                                                               Donor Age
                                          3.5
     Relative Risk of 10 Year Mortality



                                           3
                                          2.5
                                           2
                                          1.5
                                           1
                                                                                  p < 0.0001
                                          0.5
                                           0
                                                0       5     10    15    20      25     30    35
                                                              Donor Age (Years)

                                          ISHLT                   2010                 N=910
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1995-6/1997)
                                                   Risk Factors for 10 Year Mortality
                                                            Recipient BSA
                                            2
      Relative Risk of 10 Year Mortality


                                                                                         p = 0.0045

                                           1.5

                                            1

                                           0.5

                                            0
                                                 0.2   0.4   0.6   0.8   1   1.2   1.4    1.6   1.8   2
                                                                   Recipient BSA (m2)
                              ISHLT                                  2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                                        N=910
PEDIATRIC HEART TRANSPLANTS (1/1995-6/1997)
                                                   Risk Factors for 10 Year Mortality
                                                       Pre-Transplant Creatinine
                                           2.5
      Relative Risk of 10 Year Mortality



                                                                                   p = 0.011
                                            2

                                           1.5

                                            1

                                           0.5

                                            0
                                                 0.2   0.4   0.6   0.8   1   1.2    1.4   1.6   1.8   2
                                                                   Creatinine (mg/dl)
                              ISHLT                                  2010                 N=910
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1995-6/1997)
                                              Risk Factors for 10 Year Mortality
                                           Center Volume for Pediatric Transplants
                                           2
     Relative Risk of 10 Year Mortality




                                          1.5

                                           1

                                          0.5
                                                    p = 0.084
                                           0
                                                0    2     4    6    8     10   12   14   16   18   20
                                                         Center Volume (cases per year)

                                          ISHLT                     2010                  N=910
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000)
          Factors Not Significant for 10 Year Mortality

Recipient Factors:
PRA, diabetes, repeat transplant, transfusions,
hospitalized, PGE, VAD, bilirubin

Donor Factors:
Cause of death, weight, height, age, clinical infection

Transplant Factors:
Ischemia time, CMV mismatch



        ISHLT                                2010
    J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (7/1997-6/2004)
Risk Factors for the Development of CAV within 5 Years


                                                             Relative  P-       95% Confidence
VARIABLE                                         N
                                                              Risk    value        Interval
Diagnosis = retransplant                         96           2.13     0.0033       1.29 -3.53




                                                                     Reference diagnosis = cardiomyopathy

          ISHLT                               2010                              N=1,470
     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
  PEDIATRIC HEART TRANSPLANTS (7/1997-6/2004)
Borderline Significant Risk Factors for the Development of
                    CAV within 5 Years

                                                      Relative               95% Confidence
  VARIABLE                                    N                  P-value
                                                       Risk                     Interval
  Diagnosis = other                          24         2.03      0.0999          0.87 -4.72

  PRA > 10%                                 171         1.45      0.0807          0.96 -2.21

  Diagnosis = congenital                    595         1.36      0.0797          0.96 -1.91
  No steroids reported for discharge
                                            233         0.61      0.0716          0.35 -1.04
  maintenance immunosuppression




                                                                 Reference diagnosis = cardiomyopathy

         ISHLT                                2010                         N=1,470
     J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS                                  (7/1997-6/2004)
 Risk Factors for the Development of CAV within 5 Years



                       Continuous Factors (see figures)
   Donor height

   Total transplant volume




       ISHLT                                2010           N=1,470
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (7/1997-6/2004)
 Risk Factors for the Development of CAV within 5 Years
                       Donor Height
                                          2
   Relative Risk of CAV within 5 Years




                                         1.5


                                          1


                                         0.5
                                                                                    p < 0.0001
                                          0
                                               50   60   70   80   90 100 110 120 130 140 150 160 170 180

                                                                   Donor Height (cm)
                                         ISHLT                        2010                 N=1,470
                        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC HEART TRANSPLANTS (7/1997-6/2004)
 Risk Factors for the Development of CAV within 5 Years
          Center Volume of All Age Transplants
   Relative Risk of CAV within 5 Years


                                          2

                                         1.5

                                          1

                                         0.5
                                                   p = 0.0026
                                          0
                                               0     5    10    15     20   25   30    35    40
                                                      Center Volume (cases per year)

                                         ISHLT                  2010               N=1,470
    J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
            PEDIATRIC HEART RECIPIENTS
                 Cross-Sectional Analysis
          Functional Status of Surviving Recipients
                        (Follow-ups: April 1994 - June 2009)
100%



80%


60%



40%


20%

                No Activity Limitations   Performs with Some Assistance   Requires Total Assistance

 0%
               1 Year (N = 2,171)              5 Year (N = 1,428)             10 Year (N = 561)


           ISHLT                                2010
       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
       PEDIATRIC HEART RECIPIENTS
                Longitudinal Analysis
       Functional Status of Surviving Recipients
                   (Follow-ups: April 1994 - June 2009)
                          For the Same Patients
100%


80%


60%


40%


20%

           No Activity Limitations   Performs with Some Assistance   Requires Total Assistance

 0%
            1 Year (N = 792)               3 Year (N = 792)              5 Year (N = 792)

       ISHLT                               2010
  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
            PEDIATRIC HEART RECIPIENTS
       Functional Status of Surviving Recipients
                        (Follow-ups: April 1994 - June 2009)
                                   Age: <1 Year
100%


80%


60%


40%


20%

            No Activity Limitations     Performs with Some Assistance   Requires Total Assistance

 0%
              1 Year (N = 547)                 3 Year (N = 477)             5 Year (N = 215)


           ISHLT                                2010
       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
            PEDIATRIC HEART RECIPIENTS
       Functional Status of Surviving Recipients
                         (Follow-ups: April 1994 - June 2009)
                                   Age: 1-10 Years
100%


80%


60%


40%


20%

               No Activity Limitations   Performs with Some Assistance   Requires Total Assistance

 0%
              1 Year (N = 831)                 3 Year (N = 522)              5 Year (N = 179)


           ISHLT                                2010
       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
            PEDIATRIC HEART RECIPIENTS
       Functional Status of Surviving Recipients
                        (Follow-ups: April 1994 - June 2009)
                                 Age: 11-17 Years
100%


80%


60%


40%


20%

               No Activity Limitations   Performs with Some Assistance   Requires Total Assistance

 0%
              1 Year (N = 793)                 3 Year (N = 429)              5 Year (N = 167)


           ISHLT                                2010
       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
         PEDIATRIC HEART RECIPIENTS
       Functional Status of Surviving Recipients
                   (Follow-ups: March 2005 - June 2009)
                           US Recipients Only
100%
                                                                          Not Applicable (patient <
                                                                          1 year old)
                                                                          10%

80%                                                                       20%

                                                                          30%

60%                                                                       40%

                                                                          50%

                                                                          60%
40%
                                                                          70%

                                                                          80%
20%
                                                                          90%

                                                                          100%

 0%
        1 Year (N = 1,103)    2 Years (N = 972)       3 Years (N = 897)

        ISHLT                               2010
   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
            PEDIATRIC HEART RECIPIENTS
Rehospitalization Post-transplant of Surviving Recipients
                        (Follow-ups: April 1994 - June 2009)
100%


80%


60%



40%

               No Hospitalization                           Hospitalized, Not Rejection/Not Infection
20%            Hospitalized, Rejection                      Hospitalized, Infection Only
               Hospitalized, Rejection + Infection


 0%
            1 Year (N = 3,783)                  5 Years (N =2,366)              10 Years (N = 958)



           ISHLT                                     2010
       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                           PEDIATRIC HEART RECIPIENTS
                                     Induction Immunosuppression
                                  (Transplants: January 2001 - June 2009)
                60

                50


                40
% of Patients




                30

                20

                10

                 0
                     Any Induction (N = Polyclonal ALG/ATG              OKT3 (N = 48)      IL2R-antagonist (N
                           1,489)            (N = 997)                                           = 485)



                     ISHLT                               2010                     Analysis is limited to patients who
                                                                                  were alive at the time of the follow-up
                J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                         PEDIATRIC HEART RECIPIENTS
Induction Immunosuppression (Transplants: January 2001 - June 2009)
                   70
                                                                                             2001
                                                                                             2002
                   60                                                                        2003
                                                                                             2004
                                                                                             2005
                   50                                                                        2006
   % of Patients




                                                                                             2007
                                                                                             2008
                   40                                                                        2009

                   30

                   20

                   10

                    0
                              Any Induction            Polyclonal ALG/ATG         IL2R-antagonist
                                                                            Test of increasing trend over time:
                                                                            Any induction p < 0.0001
                                                                            Polyclonal p < 0.0001
                        ISHLT                               2010            IL2 p < 0.0001
                                                                            Analysis is limited to patients who
                   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141    were alive at the time of the follow-up
                     PEDIATRIC HEART TRANSPLANTATION
                           Kaplan-Meier Survival by Induction Group
          (Transplants: January 2000 – June 2008) Conditional on Survival to 14 Days
               100
                                                  No comparisons were statistically significant.

               90
Survival (%)




               80



               70
                                    No induction (N = 1,261)
                                    Polyclonal induction (N = 888)
               60
                                    IL2R-antagonist (N = 378)

               50
                     0          1            2             3             4          5              6   7

                                                               Years
                         ISHLT                            2010
                 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                     PEDIATRIC HEART TRANSPLANTATION
               Kaplan-Meier Survival by Induction Group and Treated Rejection Between
                             Transplant Discharge and 1-Year Follow-up
                             (1-Year Follow-ups: July 2004 - June 2008)
                                  Conditional on Survival to 1 Year
               100



                90
Survival (%)




                80
                         No pair-wise comparisons of survival by induction were statistically
                         significant within either rejection grouping

                70               No induction/No rejection (N = 303)
                                 Polyclonal induction/No rejection (N = 266)
                                 IL2R-antagonist/No rejection (N = 114)
                60               No induction/Treated Rejection (N = 108)
                                 Polyclonal induction/Treated Rejection (N = 116)
                                 IL2R-antagonist/Treated Rejection (N = 53)
                50
                     0                          1                           2                               3                                    4
                                                                       Years        Treated rejection = Recipient was reported to (1) have at least
                                                                                    one acute rejection episode that was treated with an anti-
                         ISHLT                                   2010
                                                                                    rejection agent; or (2) have been hospitalized for rejection.
                                                                                    No rejection = Recipient had (i) no acute rejection episodes
                                                                                    and (ii) was reported either as not hospitalized for rejection or
                 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141              did not receive anti-rejection agents.
                     PEDIATRIC HEART TRANSPLANTATION
 Kaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2008)
                                           Conditional on Survival to 14 Days
                                                       Age: < 1 Year
               100



               90
Survival (%)




               80

                         No comparisons were statistically significant.
               70


                                         No induction (N = 267)
               60                        Polyclonal induction (N = 300)
                                         IL2R-antagonist (N = 52)

               50
                     0               1                2              3    4     5   6
                                                                  Years
                         ISHLT                              2010
                J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                           PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2008)
                                       Conditional on Survival to 14 Days
                                                Age: 1-10 Years
               100



               90
Survival (%)




               80

                          No comparisons were statistically significant.
               70



               60             No induction (N = 506)
                              Polyclonal induction (N = 309)
                              IL2R-antagonist (N = 148)
               50
                     0             1              2              3         4   5   6
                                                               Years

                         ISHLT                           2010
                J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                          PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2008)
                                       Conditional on Survival to 14 Days
                                               Age: 11-17 Years
               100



               90
Survival (%)




               80

                          No comparisons were statistically significant.
               70


                              No induction (N = 488)
               60
                              Polyclonal induction (N = 279)
                              IL2R-antagonist (N = 178)
               50
                     0             1              2               3        4   5   6
                                                               Years

                         ISHLT                            2010
                 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                        PEDIATRIC HEART RECIPIENTS
                      Maintenance Immunosuppression at Time of Follow-up
                             (Follow-ups: January 2001 - June 2009)
                100
                                  Year 1 (N = 2,235)                  Year 5 (N = 1,441)
                 80
% of Patients




                 60


                 40


                 20


                  0
                      Cyclosporine    Tacrolimus      Rapamycin           MMF     Azathioprine        Prednisone
                                      NOTE: Different patients are analyzed in Year 1 and Year 5

                      ISHLT                                2010                     Analysis is limited to patients who
                                                                                    were alive at the time of the follow-up
                  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                            PEDIATRIC HEART RECIPIENTS
                        Maintenance Immunosuppression at Time of Follow-up
                                for Same Patients at Each Time Point
                               (Follow-ups: January 2001 - June 2009)
                100%

                                                             None
                80%
                                                             Other
% of Patients




                                                             Tacrolimus
                60%
                                                             Tacrolimus + MMF

                                                             Tacrolimus + AZA
                40%
                                                             Cyclosporine

                                                             Cyclosporine + MMF
                20%
                                                             Cyclosporine + AZA


                 0%
                                     Year 1 (N = 789)                             Year 5 (N = 789)


                       ISHLT                              2010                     Analysis is limited to patients who
                                                                                   were alive at the time of the follow-up
                 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                            PEDIATRIC HEART RECIPIENTS
  Maintenance Immunosuppression Drug Combinations at Time of Follow-up
                 (Follow-ups: January 2001 - June 2009)
                100%

                                                                                     None
                80%
                                                                                     Other

                                                                                     Tacrolimus
% of Patients




                60%
                                                                                     Tacrolimus + MMF

                                                                                     Tacrolimus + AZA
                40%
                                                                                     Cyclosporine

                                                                                     Cyclosporine + MMF
                20%
                                                                                     Cyclosporine + AZA

                 0%
                           Year 1 (N = 2,235)             Year 5 (N = 1,441)
                                 NOTE: Different patients are analyzed in Year 1 and Year 5
                       ISHLT                              2010                    Analysis is limited to patients who
                                                                                  were alive at the time of the follow-up
                 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
               PEDIATRIC HEART TRANSPLANTATION
                     Kaplan-Meier Survival Based on Prednisone Use
               Conditional on Survival to 1 Year (Transplants: 1998 - June 2008)
               100


                90
Survival (%)




                80
                          p = 0.0147

                70
                            Prednisone use at discharge and 1 year (N = 1,644)

                60          No Prednisone at discharge or at 1 year (N = 384)
                            Prednisone at discharge/not at 1 year (N = 371)
                50
                     0       1         2      3        4          5     6   7    8   9   10

                                                             Years
                         ISHLT                             2010
                J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
               PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival Based on Prednisone Use for a Recent Era
          Conditional on Survival to 1 Year (Transplants: January 1998 – June 2008)

               100


                90
Survival (%)




                80


                70
                            Prednisone use at discharge and 1 year (N = 1,644)       p = 0.0147

                60          No Prednisone at discharge or at 1 year (N = 384)

                            Prednisone at discharge/not at 1 year (N = 371)
                50
                     0       1         2         3         4            5        6   7       8    9

                                                               Years
                         ISHLT                           2010
                J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                       PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival Stratified by Tacrolimus vs. Cyclosporine Use at Discharge
                    (Transplants: January 1998 - June 2008)
                       Conditional on Survival to 14 Days
                 100
                                                                                  p = 0.2594
                  90
  Survival (%)




                  80


                  70
                             Tacrolimus use at discharge (N = 1,423)
                  60
                             Cyclosporine use at discharge (N = 1,482)

                  50
                       0       1         2         3         4            5   6   7       8    9

                                                                 Years
                           ISHLT                           2010
                  J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                     PEDIATRIC HEART TRANSPLANTATION
                 Kaplan-Meier Survival Stratified by Tacrolimus vs. Cyclosporine Use
               Conditional on Survival to 1 Year (Transplants: January 1998 - June 2008)

               100
                                                                                          p = 0.0333
                90
Survival (%)




                80


                70
                           Cyclosporine use at discharge and 1 year (N = 902)

                60         Tacrolimus use at discharge and 1 year (N = 1,070)
                           Cyclosporine use at discharge/Tacrolimus at 1 year (N = 267)
                           Tacrolimus use at discharge/Cyclosporine at 1 year (N = 30)
                50
                     0        1          2         3          4           5         6      7           8   9

                                                                  Years
                         ISHLT                              2010
                 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
            PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival Based on Treated Rejection within 1st Year
Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2008)
                100


                 90
 Survival (%)




                 80
                          p = 0.1693

                 70


                 60
                                 Free from Rejection during 1 year (N = 526)
                                 Treated Rejection within 1st Year (N = 283)
                 50
                      0                    1                     2                           3                              4
                                                                         Treated rejection = Recipient was reported to (1) have at
                                                              Years      least one acute rejection episode that was treated with an
                                                                         anti-rejection agent; or (2) have been hospitalized for
                                                                         rejection.
                          ISHLT                           2010           No rejection = Recipient had (i) no acute rejection
                                                                         episodes and (ii) was reported either as not hospitalized
                 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141   for rejection or did not receive anti-rejection agents.
            PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival Based on Treated Rejection within 1st Year
                                 Stratified by Calcineurin Use at Discharge
Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2008)
                100


                 90
 Survival (%)




                      Free from Rejection: CyA vs. TAC p = 0.2682
                 80
                      Treated Rejection: CyA vs. TAC p = 0.1586
                      CyA: Rejection vs. no rejection p = 0.6131
                      TAC: Rejection vs. no rejection p = 0.1430
                 70
                                       CyA: Free from Rejection during 1 year (N = 144)
                                       CyA: Treated Rejection within 1st Year (N = 101)
                 60
                                       TAC: Free from Rejection during 1 year (N = 347)
                                       TAC: Treated Rejection within 1st Year (N = 150)
                 50
                      0                        1                           2                       3                               4
                                                                               Treated rejection = Recipient was reported to (1) have at
                                                                      Years    least one acute rejection episode that was treated with an
                                                                               anti-rejection agent; or (2) have been hospitalized for
                                                                               rejection.
                          ISHLT                                     2010       No rejection = Recipient had (i) no acute rejection
                                                                               episodes and (ii) was reported either as not hospitalized
                 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141         for rejection or did not receive anti-rejection agents.
            PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival Based on Treated Rejection within 1st Year
                  Stratified by Calcineurin Use at Discharge: Age = 0-10 Years
Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2008)
                100


                 90
 Survival (%)




                 80       Free from Rejection: CyA vs. TAC p = 0.8741
                          Rejection: CyA vs. TAC p = 0.7176
                          CyA: Rejection vs. no rejection p = 0.8305
                          TAC: Rejection vs. no rejection p = 0.3347
                 70
                                         CyA: Free from Rejection during 1 year (N = 103)
                                         CyA: Treated Rejection within 1st Year (N = 69)
                 60
                                         TAC: Free from Rejection during 1 year (N = 221)
                                         TAC: Treated Rejection within 1st Year (N = 83)
                 50
                      0                          1                         2                            3                                   4

                                                                        Years    Treated rejection = Recipient was reported to (1) have at least
                                                                                 one acute rejection episode that was treated with an anti-
                                                                                 rejection agent; or (2) have been hospitalized for rejection.

                          ISHLT                                     2010         No rejection = Recipient had (i) no acute rejection episodes
                                                                                 and (ii) was reported either as not hospitalized for rejection or
                                                                                 did not receive anti-rejection agents.
                 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
            PEDIATRIC HEART TRANSPLANTATION
Kaplan-Meier Survival Based on Treated Rejection within 1st Year
                 Stratified by Calcineurin Use at Discharge: Age = 11-17 Years
Conditional on survival to 1 year (1-Year Follow-ups: July 2004 - June 2008)
                100


                 90
 Survival (%)




                          Free from Rejection: CyA vs. TAC p = 0.0338
                 80
                          Rejection: CyA vs. TAC p = 0.1014
                          CyA: Rejection vs. no rejection p = 0.1693
                          TAC: Rejection vs. no rejection p = 0.3492
                 70
                                        CyA: Free from Rejection during 1st Year (N = 41)
                                        CyA: Treated Rejection within 1st Year (N =32)
                 60
                                        TAC: Free from Rejection during 1st Year (N = 126)
                                        TAC: Treated Rejection within 1st Year (N = 67)
                 50
                      0                          1                        2                          3                               4
                                                                                 Treated rejection = Recipient was reported to (1) have at
                                                                        Years    least one acute rejection episode that was treated with an
                                                                                 anti-rejection agent; or (2) have been hospitalized for
                                                                                 rejection.
                          ISHLT                                    2010          No rejection = Recipient had (i) no acute rejection
                                                                                 episodes and (ii) was reported either as not hospitalized
                 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141           for rejection or did not receive anti-rejection agents.
                                       PERCENTAGE OF PEDIATRIC HEART TRANSPLANT
RECIPIENTS EXPERIENCING ACUTE REJECTION BETWEEN TRANSPLANT
                 DISCHARGE AND 1-YEAR FOLLOW-UP
       Stratified by Induction (Follow-ups: July 2004 - June 2009)
 % experiencing acute rejection within 1 year




                                                   70            No induction Used, Treatment                No induction Used, No Treatment

                                                   60            Induction Used (no OKT3), Treatment         Induction Used (no OKT3), No Treatment


                                                   50
                                                   40
                                                   30
                                                   20
                                                   10
                                                     0
                                                             Overall                <1          1-10       10-17                  Female             Male
                                                                                                       Treated rejection = Recipient was reported to (1) have at least
                                                Overall: p = 0.6601                                    one acute rejection episode that was treated with an anti-
                                                                                                       rejection agent; or (2) have been hospitalized for rejection.
                                                                                                       No rejection = Recipient had (i) no acute rejection episodes and
                                                                                                       (ii) was reported either as not hospitalized for rejection or did not
                                                         ISHLT                                  2010   receive anti-rejection agents.

                                                                                                                               Analysis is limited to patients who
                                                   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                       were alive at the time of the follow-up
 PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS
EXPERIENCING ACUTE REJECTION BETWEEN TRANSPLANT DISCHARGE
                        AND 1-YEAR FOLLOW-UP
   Stratified by Type of Induction (Follow-ups: July 2004 - June 2009)
                                                  70             No induction, Treatment                   No induction, No Treatment
 % experiencing acute rejection within 1 year




                                                                 Polyclonal, Treatment                     Polyclonal, No Treatment
                                                                 IL2R-antagonist, Treatment                IL2R-antagonist, No Treatment
                                                  60
                                                  50
                                                  40
                                                  30
                                                  20
                                                  10
                                                    0        Overall                <1           1-10    10-17                  Female              Male

                                                                                                         Treated rejection = Recipient was reported to (1) have at least
                                                No comparisons were statistically significant at 0.05.   one acute rejection episode that was treated with an anti-
                                                                                                         rejection agent; or (2) have been hospitalized for rejection.
                                                                                                         No rejection = Recipient had (i) no acute rejection episodes
                                                                                                         and (ii) was reported either as not hospitalized for rejection or

                                                        ISHLT                                     2010
                                                                                                         did not receive anti-rejection agents.

                                                                                                                               Analysis is limited to patients who
                                                   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141                       were alive at the time of the follow-up
                            PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS
                EXPERIENCING ACUTE REJECTION BETWEEN TRANSPLANT DISCHARGE
                                   AND 1-YEAR FOLLOW-UP
                 Stratified by Maintenance Immunosuppression and Induction (Follow-ups: July 2004 - June 2009)
                                                 CyA + No induction, Treatment                  CyA + No induction, No Treatment
% experiencing acute rejection within




                                        70       CyA + Induction (no OKT3), Treatment           CyA + Induction (no OKT3), No Treatment
                                                 TAC + No induction, Treatment                  TAC + No induction, No Treatment
                                                 TAC + Induction (no OKT3), Treatment           TAC + Induction (no OKT3), No Treatment
                                        60
                                        50
               1 year




                                        40
                                        30
                                        20
                                        10
                                         0
                                                    Overall                      <1                     1-10                        10-17
        Overall: all comparisons were statistically significant at 0.05 except CyA + no induction vs. CyA + induction and TAC + no
        induction vs. TAC + induction
        <1 year: CyA + no induction vs. TAC + no induction ( p=0.0268);
        1-10 years: all comparisons were statistically significant at 0.05 except CyA + no induction vs. CyA + induction and TAC + no
        induction vs. TAC + induction
        11-17 years: CyA + no induction vs. TAC + no induction (p = 0.0005); CyA + induction vs. TAC + no induction (p < 0.0001); CyA
        + induction vs. TAC + induction ( p =0.0025)                              Treated rejection = Recipient was reported to (1) have at least one acute
                                                                                           rejection episode that was treated with an anti-rejection agent; or (2)
                                                                                           have been hospitalized for rejection.
                                                                                           No rejection = Recipient had (i) no acute rejection episodes and (ii) was

                                             ISHLT                               2010
                                                                                           reported either as not hospitalized for rejection or did not receive anti-
                                                                                           rejection agents.

                                                                                                      Analysis is limited to patients who were alive at the time
                                        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141         of the follow-up
                  PERCENTAGE OF PEDIATRIC HEART TRANSPLANT
  RECIPIENTS EXPERIENCING ACUTE REJECTION BETWEEN TRANSPLANT
                DISCHARGE AND 1-YEAR FOLLOW-UP
                     Stratified by Maintenance Immunosuppression (Follow-ups: July 2004 - June 2009)
                                                 Cyclosporine + MMF, Treatment               Cyclosporine + MMF, No Treatment
    % experiencing acute rejection within



                                                 Cyclosporine + AZA, Treatment               Cyclosporine + AZA, No Treatment
                                            70   Tacrolimus + MMF, Treatment                 Tacrolimus + MMF, No Treatment
                                                 Tacrolimus + AZA, Treatment                 Tacrolimus + AZA, No Treatment
                                            60
                                            50
                   1 year




                                            40
                                            30
                                            20
                                            10
                                             0
                                                   Overall                     <1                         1-10                        10-17
Overall: all comparisons were statistically significant at 0.05 except CyA +MMF vs. CyA +AZA and TAC + MMF vs. TAC + AZA.
<1: CyA + MMF vs. TAC + MMF (p =0.0076).
1-10: CyA + MMF vs. TAC + MMF (p = 0.0008); CyA + AZA vs. TAC + MMF (p=0.0007).
11-17: all comparisons were statistically significant at 0.05 except CyA +MMF vs. CyA +AZA TAC + MMF vs. TAC + AZA.
                                                                                      Treated rejection = Recipient was reported to (1) have at least one acute
                                                                                      rejection episode that was treated with an anti-rejection agent; or (2)
                                                                                      have been hospitalized for rejection.
                                                                                      No rejection = Recipient had (i) no acute rejection episodes and (ii) was

                                            ISHLT                            2010
                                                                                      reported either as not hospitalized for rejection or did not receive anti-
                                                                                      rejection agents.

                                                                                                Analysis is limited to patients who were alive at the time
                                    J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141       of the follow-up
PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS
EXPERIENCING ACUTE REJECTION BETWEEN TRANSPLANT DISCHARGE
                   AND 1-YEAR FOLLOW-UP
                                                               Stratified by Calcineurin Inhibitor Use at Discharge
                                                                         (Follow-ups: July 2004 - June 2009)
% experiencing acute rejection within 1 year




                                                               Cyclosporine, Treatment             Cyclosporine, No Treatment
                                               60              Tacrolimus, Treatment               Tacrolimus, No Treatment

                                               50

                                               40

                                               30

                                               20

                                               10

                                                0
                                                              Overall                    <1                    1-10                  10-17
                                                    Overall: CyA vs. TAC (p < 0.0001)                  Treated rejection = Recipient was reported to (1) have at least
                                                    <1: CyA vs. TAC (p=0.0356)                         one acute rejection episode that was treated with an anti-
                                                    1-10: CyA vs. TAC (p < 0.0001)                     rejection agent; or (2) have been hospitalized for rejection.
                                                    11-17: CyA vs. TAC (p < 0.0001)                    No rejection = Recipient had (i) no acute rejection episodes

                                                     ISHLT                               2010
                                                                                                       and (ii) was reported either as not hospitalized for rejection or
                                                                                                       did not receive anti-rejection agents.

                                                                                                                Analysis is limited to patients who were alive at the
                                               J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141            time of the follow-up
                     FREEDOM FROM CORONARY ARTERY VASCULOPATHY
                     For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

                     100



                     90
% Freedom from CAV




                     80



                     70



                     60



                     50
                           0     1        2        3        4        5         6   7   8   9   10
                                                                  Years
                               ISHLT                            2010
                       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
 FREEDOM FROM CORONARY ARTERY VASCULOPATHY
For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)
                                                       Stratified by Induction
                      100



                      90
 % Freedom from CAV




                      80
                                p = 0.5133

                      70


                      60                 Induction (N = 1,455)

                                         No Induction (N = 1,880)

                      50
                            0        1           2         3         4           5   6   7   8   9
                                                                         Years
                                ISHLT                               2010
                        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
        FREEDOM FROM CORONARY ARTERY VASCULOPATHY
        For Pediatric Heart Recipients (Follow-ups: 1999 - June 2009)
                                       Stratified by Tacrolimus vs. Cyclosporine Use
                                               Conditional on Survival to 1 Year
                     100
% Freedom from CAV




                     90


                     80
                                p = 0.6217

                     70
                                          Cyclosporine use at discharge and 1 year (N = 850)
                                          Tacrolimus use at discharge and 1 year (N = 960)
                     60
                                          Cyclosporine use at discharge/Tacrolimus at 1 year (N = 252)
                                          Tacrolimus use at discharge/Cyclosporine at 1 year (N = 29)
                     50
                           0          1             2            3           4            5              6   7   8
                                                                       Years

                               ISHLT                                 2010
                       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
 FREEDOM FROM CORONARY ARTERY VASCULOPATHY
For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)
                                                     Stratified by Age Group
                      100
 % Freedom from CAV




                       90



                       80
                                        p < 0.0001

                       70

                                        <1 Year (N = 869)

                       60               1-10 Years (N = 1,251)

                                        11-17 Years (N = 1,230)


                       50
                            0     1        2          3          4          5   6   7   8   9   10
                                                                       Years
                                ISHLT                                2010
                       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
 FREEDOM FROM CORONARY ARTERY VASCULOPATHY
For Pediatric Heart Recipients (Follow-ups: January 1999-June 2009)
                                                      Stratified by Age Group
                      100



                      90
 % Freedom from CAV




                      80
                                         p < 0.0001

                      70

                                           <1 Year (N = 623)
                                           1-10 Years (N = 950)
                      60
                                           11-17 Years (N = 948)


                      50
                            0        1            2         3             4    5   6   7   8
                                                                     Years
                                ISHLT                              2010
                       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
 FREEDOM FROM CORONARY ARTERY VASCULOPATHY
For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)
                                                   Stratified by Ischemia Time
                      100


                      90
 % Freedom from CAV




                      80
                                         p = 0.0080

                      70


                                        0-<2 hours (N=349)
                      60
                                        2-<4 hours (N=1,705)

                                        4+ hours (N=1,067)
                      50
                            0       1          2             3     4            5   6   7   8   9
                                                                       Years

                                ISHLT                            2010
                        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
  FREEDOM FROM CORONARY ARTERY VASCULOPATHY
                 For Pediatric Heart Recipients (Follow-ups: January 1999 - June 2009)
                             Stratified by Ischemia Time for Recent Era
                     100


                     90
% Freedom from CAV




                     80
                                         p = 0.0105

                     70

                                    0-<2 hours (N=234)
                     60
                                    2-<4 hours (N=1,271)

                                    4+ hours     (N=808)
                     50
                           0         1                2        3              4   5   6   7
                                                                   Years

                               ISHLT                           2010
                      J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
 FREEDOM FROM CORONARY ARTERY VASCULOPATHY
For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)
                                     Stratified by Ischemia Time and Recipient Age
                      100



                      90
 % Freedom from CAV




                      80
                                0-10 years: p = 0.0049;
                                11-17 years: p = 0.3641

                      70
                                            0-<2 hours/0-10 years (N=197)

                                            2+ hours/0-10 years    (N=1,776)
                      60
                                            0-<2 hours/11-17 years (N=152)

                                            2+ hours/11-17 years   (N=996)
                      50
                            0         1          2         3          4           5   6   7   8   9
                                                                          Years
                                ISHLT                                2010
                        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
  GRAFT SURVIVAL FOLLOWING REPORT OF CORONARY
              ARTERY VASCULOPATHY
                         For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)
                          100
                                               Stratified by Age Group
Survival since Report of CAV (%)




                                                                                             <1 Year       (N = 86)
                                   90
                                                                                             1-10 Years (N = 150)
                                   80
                                                                                             11-17 Years (N = 198)
                                   70

                                   60

                                   50

                                   40

                                   30

                                   20
                                                  p = 0.6115
                                   10

                                   0
                                        0      0.5         1         1.5         2         2.5         3              3.5   4
                                                               Time since Report of CAV (Years)
                                            ISHLT                           2010
                                   J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
FREEDOM FROM SEVERE RENAL DYSFUNCTION*
                 For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

                    100
% Freedom from Severe




                        90
   Renal Dysfunction




                        80
                                 * Severe renal dysfunction = Creatinine > 2.5 mg/dl
                                 (221 μmol/L), dialysis or renal transplant
                        70



                        60



                        50
                             0         1          2         3         4         5      6   7   8   9   10
                                                                             Years
                                 ISHLT                                 2010
                        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
FREEDOM FROM SEVERE RENAL DYSFUNCTION*
                         For Pediatric Heart Recipients (Follow-ups: 1999 - June 2009)
                                          Stratified by Tacrolimus vs. Cyclosporine Use
                                                  Conditional on Survival to 1 Year
                        100
% Freedom from Severe




                         90
   Renal Dysfunction




                                  p = 0.1311

                         80
                                  * Severe renal dysfunction = Creatinine > 2.5 mg/dl (221 μmol/L), dialysis
                                  or renal transplant
                         70
                                               Cyclosporine use at discharge and 1 year (N = 887)
                                               Tacrolimus use at discharge and 1 year (N = 1,054)
                         60
                                               Cyclosporine use at discharge/Tacrolimus at 1 year (N = 258)
                                               Tacrolimus use at discharge/Cyclosporine at 1 year (N = 30)

                         50
                              0            1            2           3            4            5            6   7   8
                                                                              Years
                              ISHLT                                     2010
                        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
  FREEDOM FROM RENAL REPLACEMENT THERAPY*
                  For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

                   100
% Freedom from Renal




                       90
Replacemetn Therapy




                       80
                                * Renal replacement therapy = dialysis or renal
                                transplant

                       70



                       60



                       50
                            0         1          2         3         4            5   6   7   8   9   10
                                                                            Years
                                ISHLT                                 2010
                       J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
MALIGNANCY POST-HEART TRANSPLANTATION FOR PEDIATRICS
Cumulative Prevalence in Survivors (Follow-ups: April 1994 - June 2009)

 Malignancy/Type                                 1-Year             5-Year            10-Year
                                                Survivors          Survivors         Survivors
 No Malignancy                                3,684 (98.2%)       1,521 (94.9%)      411 (92.6%)

 Malignancy (all types combined)                 69 (1.8%)          82 (5.1%)         33 (7.4%)

 Malignancy                       Lymph                      64                 77           31
       Type                                                   4                  6                3
                                    Other
                                     Skin                                        1                1

                  Type Not Reported                           1



                    NOTE: Multiple types may be reported; sum of types
                    may be greater than total number with malignancy.

        ISHLT                                2010
    J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                                      FREEDOM FROM MALIGNANCY
                            For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)

                            100
% Freedom from Malignancy




                            95




                            90



                            85

                                           All malignancy            Lymph                Skin           Other


                            80
                                  0    1       2        3     4       5        6      7          8   9      10   11   12
                                                                             Years

                                      ISHLT                            2010
                              J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                                     FREEDOM FROM MALIGNANCY
                            For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)
                                            Stratified by Tacrolimus vs. Cyclosporine Use
                                                    Conditional on Survival to 1 Year
                        100
% Freedom from Malignancy




                                                                                                        p = 0.0214

                            95



                            90


                                          Cyclosporine use at discharge and 1 year (N = 900)
                            85            Tacrolimus use at discharge and 1 year (N = 997)
                                          Cyclosporine use at discharge/Tacrolimus at 1 year (N = 257)
                                          Tacrolimus use at discharge/Cyclosporine at 1 year (N = 31)
                            80
                                 0      1          2         3          4            5    6        7            8    9
                                                                            Years
                                     ISHLT                            2010
                             J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                                     FREEDOM FROM LYMPHOMA
                          For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2009)
                                               Stratified by Induction
                          100
% Freedom from Lymphoma




                          95

                                           p = 0.7922


                          90



                          85

                                             Induction                No Induction

                          80
                                0      1        2        3        4         5        6   7   8   9   10
                                                                      Years

                                    ISHLT                             2010
                            J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
      PEDIATRIC HEART RECIPIENTS
Incidence of Hypertension between 1 and 3 Years
                 (Transplants: April 1993 - June 2006)

     Maintenance                   % HTN reported between 1 and
Immunosuppression at                         3 years
 discharge and 1 year                                                  P-value
                                    For Patients        For Patients
                                      on drug           not on drug
Azathioprine                              20.1             25.1        0.0639
Cyclosporine                              21.3             22.6        0.6409
MMF                                       24.0             22.3        0.5552
Prednisone                                28.9              11.9       <.0001
Rapamycin                                 36.4             22.0           -
Tacrolimus                                26.0             20.4        0.0408



    ISHLT                                2010
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
      PEDIATRIC HEART RECIPIENTS
Incidence of Hypertension between 3 and 8 Years
                 (Transplants: April 1993 - June 2001)

     Maintenance                   % HTN reported between 3 and
Immunosuppression at                         8 years
 discharge and 1 year                                                  P-value
                                    For Patients        For Patients
                                      on drug           not on drug
Azathioprine                              35.1             54.3        0.0339
Cyclosporine                              36.0             46.7        0.2637
MMF                                       41.4             37.8        0.7112
Prednisone                                47.1             20.2        <.0001
Rapamycin                                   -              37.5          -
Tacrolimus                                40.7             34.8         0.541



    ISHLT                                2010
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
           PEDIATRIC HEART RECIPIENTS
Relationship of Rejection and Coronary Artery Vasculopathy
            (Follow-ups: July 2004 – June 2009)


        Rejection            Reported CAV between 1st and 3rd years
        During 1st                      post-transplant
          Year
                                   Yes                   No     All
            Yes                     9                    168     177
                                  5.1%                  94.9%   100%
             No                     9                    255     264
                                  3.4%                  96.6%   100%



                                        p = 0.3834

    ISHLT                                2010
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
          PEDIATRIC HEART TRANSPLANT RECIPIENTS:
                  Cause of Death (Deaths: January 1992 - June 2009)
 CAUSE OF DEATH        0-30 Days    31 Days - 1     >1 Year - 3       >3 Years - 5     >5 Years - 10    >10 Years
                       (N = 475)    Year (N =     Years (N = 318)   Years (N = 246)   Years (N = 371)   (N = 197)
                                       443)
CORONARY ARTERY
                       5 (1.1%)      30 (6.8%)      62 (19.5%)        72 (29.3%)       105 (28.3%)      54 (27.4%)
VASCULOPATHY
ACUTE REJECTION        45 (9.5%)    108 (24.4%)     75 (23.6%)        35 (14.2%)        46 (12.4%)      12 (6.1%)
LYMPHOMA               1 (0.2%)      9 (2.0%)        12 (3.8%)         8 (3.3%)          35 (9.4%)      15 (7.6%)
MALIGNANCY, OTHER                    4 (0.9%)        2 (0.6%)          2 (0.8%)          5 (1.3%)       10 (5.1%)

CMV                    1 (0.2%)      12 (2.7%)       1 (0.3%)

INFECTION, NON-CMV    55 (11.6%)    68 (15.3%)       21 (6.6%)         8 (3.3%)          18 (4.9%)      18 (9.1%)

PRIMARY FAILURE       108 (22.7%)    24 (5.4%)       10 (3.1%)         16 (6.5%)         21 (5.7%)       7 (3.6%)
GRAFT FAILURE         101 (21.3%)   51 (11.5%)      64 (20.1%)        60 (24.4%)        76 (20.5%)      49 (24.9%)

TECHNICAL              27 (5.7%)     3 (0.7%)        2 (0.6%)          3 (1.2%)          4 (1.1%)        2 (1.0%)

OTHER                  23 (4.8%)     26 (5.9%)      32 (10.1%)         24 (9.8%)         34 (9.2%)      10 (5.1%)

MULTIPLE ORGAN
                      48 (10.1%)    56 (12.6%)       10 (3.1%)         7 (2.8%)          10 (2.7%)      10 (5.1%)
FAILURE
RENAL FAILURE          1 (0.2%)      5 (1.1%)        1 (0.3%)          1 (0.4%)          1 (0.3%)        3 (1.5%)
PULMONARY              29 (6.1%)     31 (7.0%)       16 (5.0%)         8 (3.3%)          9 (2.4%)        5 (2.5%)

CEREBROVASCULAR        31 (6.5%)     16 (3.6%)       10 (3.1%)         2 (0.8%)          7 (1.9%)        2 (1.0%)



            ISHLT                                 2010
        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
          PEDIATRIC HEART TRANSPLANT RECIPIENTS:
                      Cause of Death (Deaths: January 1998 - June 2009)
 CAUSE OF DEATH       0-30 Days      31 Days - 1      >1 Year - 3       >3 Years - 5     >5 Years - 10    >10 Years
                      (N = 226)    Year (N = 266)   Years (N = 202)   Years (N = 173)   Years (N = 306)   (N =190)
CAV                    2 (0.9%)      14 (5.3%)        33 (16.3%)        46 (26.6%)        84 (27.5%)      52 (27.4%)

ACUTE REJECTION       23 (10.2%)     53 (19.9%)       40 (19.8%)        27 (15.6%)        37 (12.1%)      12 (6.3%)
LYMPHOMA                              6 (2.3%)         7 (3.5%)          6 (3.5%)          29 (9.5%)      15 (7.9%)
MALIGNANCY,
                                      1 (0.4%)         1 (0.5%)          1 (0.6%)          4 (1.3%)        9 (4.7%)
OTHER
CMV                                   8 (3.0%)         1 (0.5%)

INFECTION, NON-
                      27 (11.9%)     34 (12.8%)        12 (5.9%)         3 (1.7%)          14 (4.6%)      16 (8.4%)
CMV
PRIMARY FAILURE       50 (22.1%)     10 (3.8%)         4 (2.0%)          7 (4.0%)          13 (4.2%)       7 (3.7%)
GRAFT FAILURE         35 (15.5%)     31 (11.7%)       50 (24.8%)        51 (29.5%)        68 (22.2%)      47 (24.7%)

TECHNICAL             14 (6.2%)                        2 (1.0%)          1 (0.6%)          4 (1.3%)        2 (1.1%)

OTHER                 17 (7.5%)      21 (7.9%)        27 (13.4%)         17 (9.8%)         30 (9.8%)      10 (5.3%)

MULTIPLE ORGAN
                      29 (12.8%)     43 (16.2%)        9 (4.5%)          6 (3.5%)          8 (2.6%)       10 (5.3%)
FAILURE
RENAL FAILURE                         5 (1.9%)         1 (0.5%)          1 (0.6%)          1 (0.3%)        3 (1.6%)
PULMONARY             11 (4.9%)      28 (10.5%)        11 (5.4%)         6 (3.5%)          8 (2.6%)        5 (2.6%)

CEREBROVASCULAR       18 (8.0%)      12 (4.5%)         4 (2.0%)          1 (0.6%)          6 (2.0%)        2 (1.1%)



            ISHLT                                   2010
        J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
                              PEDIATRIC HEART TRANSPLANT RECIPIENTS:
                            Relative Incidence of Leading Causes of Death
                                                 (Deaths: January 1998 - June 2009)
                       40                              CAV                     Acute Rejection    Infection (non-CMV)

                                                       Primary Failure         Graft Failure
Percentage of Deaths




                       30



                       20



                       10



                       0
                              0-30 Days (N 31 Days – 1         >1 Year – 3     >3 Years – 5 >5 Years – 10 >10 Years (N
                                 = 226)     Year (N =          Years (N =       Years (N =   Years (N =      = 190)
                                               266)               173)             173)         306 )



                                ISHLT                                2010
                            J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

								
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