HEART-LUNG TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26

NUMBER OF HEART-LUNG TRANSPLANTS REPORTED BY YEAR This figure includes only the heart-lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not necessarily be construed as evidence that the number of heart-lung transplants performed worldwide has declined. ISHLT NOTE: This figure includes only the heart-lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of heart-lung transplants worldwide has declined in recent years. 2007 J Heart Lung Transplant 2007;26

AVERAGE CENTER VOLUME Heart-Lung Transplants: January 1, 1998 - June 30, 2006 ISHLT 2007 J Heart Lung Transplant 2007;26

DISTRIBUTION OF HEART-LUNG TRANSPLANTS BY CENTER VOLUME Heart-Lung Transplants: January 1, 1998 - June 30, 2006 ISHLT 2007 J Heart Lung Transplant 2007;26

DISTRIBUTION OF HEART-LUNG TRANSPLANTS BY LUNG CENTER VOLUME Lung Transplants: January 1, 1998 - June 30, 2006 ISHLT 2007 J Heart Lung Transplant 2007;26

HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival (Transplants: January 1982 - June 2005) Half-life = 3.1 years Conditional Half-life = 8.8 years N=3,184 Survival (%) N at risk at 20 years = 7 Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. Therefore, 95% confidence limits are provided about the survival rate estimate; the survival rate shown is the best estimate but the true rate will most likely fall within these limits. The half-life is the estimated time point at which 50% of all of the recipients have died. The conditional half-life is the estimated time point at which 50% of the recipients who survive to at least 1 year have died. Because the decline in survival is greatest during the first year following transplantation, the conditional survival provides a more realistic expectation of survival time for recipients who survive the early post-transplant period. ISHLT 2007 J Heart Lung Transplant 2007;26

HEART-LUNG TRANSPLANTATION Adult Recipients ISHLT 2007 J Heart Lung Transplant 2007;26

DIAGNOSIS IN ADULT HEART-LUNG TRANSPLANTS (January 1982 - June 2006) “Other” includes cancer, LAM, OB, sarcoidosis, bronchiectasis ISHLT 2007 J Heart Lung Transplant 2007;26

DIAGNOSIS IN ADULT HEART-LUNG TRANSPLANTS (Transplants: January 1982 - June 2006) Congenital Heart Disease 841 (33.9%) Primary Pulmonary Hypertension 601 (24.2%) Cystic Fibrosis 352 (14.2%) Acquired Heart Disease 110 ( 4.4%) COPD/Emphysema 92 ( 3.7%) Idiopathic Pulmonary Fibrosis 71 ( 2.9%) Alpha-1 53 ( 2.1%) Re-Transplant: Not Obliterative Bronchiolitis 31 ( 1.2%) Sarcoidosis 30 ( 1.2%) Re-Transplant: Obliterative Bronchiolitis 24 ( 1.0%) Bronchiectasis 18 ( 0.7%) Obliterative Bronchiolitis (not Re-Transplant) 8 ( 0.3%) Other 251 (10.1%) ISHLT 2007 J Heart Lung Transplant 2007;26

DIAGNOSIS IN ADULT HEART-LUNG TRANSPLANTS BY ERA “Other” includes OB (non-ReTX), Bronchiectasis, Sarcoidosis ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG TRANSPLANTATION Indications By Year (%) ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG TRANSPLANTATION Indications By Year (Number) ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG TRANSPLANTS: AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006 ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG TRANSPLANTS: DIAGNOSIS DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006 NOTE: Transplants with unknown diagnoses are excluded from this tabulation. ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG TRANSPLANTS: DONOR AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006 NOTE: Transplants with unknown diagnoses are excluded from this tabulation. ISHLT 2007 J Heart Lung Transplant 2007;26

HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival for Adult Recipients (Transplants: January 1982 - June 2005) Half-life = 3.4 Years Conditional Half-life = 9.0 Years Survival (%) N=2,571 Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. Therefore, 95% confidence limits are provided about the survival rate estimate; the survival rate shown is the best estimate but the true rate will most likely fall within these limits. The half-life is the estimated time point at which 50% of all of the recipients have died. The conditional half-life is the estimated time point at which 50% of the recipients who survive to at least 1 year have died. Because the decline in survival is greatest during the first year following transplantation, the conditional survival provides a more realistic expectation of survival time for recipients who survive the early post-transplant period. ISHLT 2007 J Heart Lung Transplant 2007;26

HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival for Adult Recipients by Era (Transplants: January 1982 - June 2005) Half-life (Years): 1982-1995 = 3.0; 1996-1999 = 3.4; 2000-6/2005 = 5.2 Conditional Half-life (Years): 1982-1995 = 8.9; 1996-1999 = 9.5; 2000-6/2005 = n/a Survival (%) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. Survival rates were compared using the log-rank test statistic. The half-life is the estimated time point at which 50% of all of the recipients have died. The conditional half-life is the estimated time point at which 50% of the recipients who survive to at least 1 year have died. Because the decline in survival is greatest during the first year following transplantation, the conditional survival provides a more realistic expectation of survival time for recipients who survive the early post-transplant period. P-value comparing all: 0.0082 ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2005) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. Survival rates were compared using the log-rank test statistic. The half-life is the estimated time point at which 50% of all of the recipients have died. ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival By Diagnosis Conditional on Survival to 1 Year (Transplants: January 1990 – June 2005) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. Survival rates were compared using the log-rank test statistic. The half-life is the estimated time point at which 50% of all of the recipients have died. ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG RECIPIENTS Functional Status of Surviving Recipients (Follow-ups: April 1994 – June 2006) This figure shows the functional status reported on the 1-year, 3-year, 5-year and 7-year annual follow-ups. Because all follow-ups between April 1994 and June 2006 were included, the bars do not include the same patients. ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG RECIPIENTS Employment Status of Surviving Recipients (Follow-ups: April 1994 – June 2006) This figure shows the employment status reported on the 1-year, 3-year, 5-year and 7-year annual follow-ups. Because all follow-ups between April 1994 and June 2006 were included, the bars do not include the same patients. ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG RECIPIENTS: Rehospitalization Post-transplant of Surviving Recipients (Follow-ups: April 1994 - June 2006) This figure shows the hospitalizations reported on the 1-year, 3-year, 5-year and 7-year annual follow-ups, representing the hospitalizations between discharge and 1 year, between the 2-year and 3-year follow-up, between the 4-year and 5-year follow-up and between the 6-year and 7-year follow-up, respectively. Because all follow-ups between April 1994 and June 2006 were included, the bars do not include the same patients. ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG RECIPIENTS Induction Immunosuppression For transplants between January 2001 through June 2006 ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG RECIPIENTS Induction Immunosuppression (Transplants: January 2000 - December 2005) ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG RECIPIENTS Induction Immunosuppression (Transplants: January 2000 - December 2005) Any Induction Polyclonal ALG/ATG OKT3 IL2R-antagonist ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up For follow-ups between January 2001 through June 2006 This figure shows the maintenance immunosuppression reported as being provided at the time of the 1-year and 5-year annual follow-up forms. To provide a snapshot of current practice, only follow-ups occurring between January 2001 and June 2006 were included. Therefore, this figure does not represent changes in practice between the 1-year follow-up and 5-year follow-up on a cohort of patients. The patients in the 1-year tabulation are not the same patients as in the 5-year tabulation. NOTE: Different patients are analyzed in Year 1 and Year 5 ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG RECIPIENTS Maintenance Immunosuppression Drug Combinations at Time of Follow-up For follow-ups between January 2001 through June 2006 This figure shows the maintenance immunosuppression reported as being provided at the time of the 1-year and 5-year annual follow-up forms. To provide a snapshot of current practice, only follow-ups occurring between January 2001 and June 2006 were included. Therefore, this figure does not represent changes in practice between the 1-year follow-up and 5-year follow-up on a cohort of patients. The patients in the 1-year tabulation are not the same patients as in the 5-year tabulation. NOTE: Different patients are analyzed in Year 1 and Year 5 ISHLT 2007 J Heart Lung Transplant 2007;26

POST-HEART-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 Year Post-Transplant (Follow-ups: April 1994 - June 2006) This table shows the percentage of patients experiencing various morbidities as reported on the 1-year annual follow-up form. The percentages are based on patients with known responses. Because the outcomes are reported to be unknown at different rates the number with known responses for each outcome are also provided. ISHLT 2007 J Heart Lung Transplant 2007;26

POST-HEART-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 5 Years Post-Transplant (Follow-ups: April 1994 - June 2006) This table shows the percentage of patients experiencing various morbidities as reported within 5 years following transplantation. The percentages are based on patients with known responses. To reduce bias, only patients with responses reported on every follow-up through the 5-year annual follow-up were included. Because the outcomes are reported to be unknown at different rates the number with known responses for each outcome are also provided. ISHLT 2007 J Heart Lung Transplant 2007;26

Freedom from Coronary Artery Vasculopathy For Adult Heart-Lung Recipients (Follow-ups: April 1994-June 2006) Freedom from CAV rates were computed using the Kaplan-Meier method. The development of CAV is reported on annual follow-ups; a date of diagnosis is not provided. For this figure the date of follow-up was used as the date of occurrence. Patients were included in the analysis until an unknown response for CAV was reported. Therefore, the rates seen here may differ from those reported in the cumulative prevalence slide which is based on only those patients with known responses for CAV at all follow-up time points. ISHLT 2007 J Heart Lung Transplant 2007;26

Freedom from Bronchiolitis Obliterans For Adult Heart-Lung Recipients (Follow-ups: April 1994-June 2006) Freedom from bronchiolitis obliterans rates were computed using the Kaplan-Meier method. The development of bronchiolitis obliterans is reported on annual follow-ups; a date of diagnosis is not provided. For this figure the date of follow-up was used as the date of occurrence. Patients were included in the analysis until an unknown response for bronchiolitis obliterans was reported. Therefore, the rates seen here may differ from those reported in the cumulative prevalence slide which is based on only those patients with known responses for bronchiolitis obliterans at all follow-up time points. ISHLT 2007 J Heart Lung Transplant 2007;26

Freedom from Severe Renal Dysfunction Freedom from Severe Renal Dysfunction* For Adult Heart-Lung Recipients (Follow-ups: April 1994-June 2006) *Severe renal dysfunction = Creatinine > 2.5 mg/dl (221 μmol/L), dialysis or renal transplant Freedom from severe renal dysfunction rates were computed using the Kaplan-Meier method. The development of severe renal dysfunction is reported on annual follow-ups; a date of diagnosis is not provided. For this figure the date of follow-up was used as the date of occurrence. Patients were included in the analysis until an unknown response for severe renal dysfunction was reported. Therefore, the rates seen here may differ from those reported in the cumulative prevalence slide which is based on only those patients with known responses for severe renal dysfunction at all follow-up time points. ISHLT 2007 J Heart Lung Transplant 2007;26

MALIGNANCY POST-HEART-LUNG TRANSPLANT FOR ADULTS Cumulative Prevalence in Survivors (Follow-ups: April 1994-June 2006) Malignancy/Type 1-Year Survivors 5-Year Survivors 10-Year Survivors No Malignancy 308 (92.2%) 106 (88.3%) 51 (85%) Malignancy (all types combined) 26 (7.8%) 14 (11.7%) 9 (15%) Malignancy Type* Skin 2 4 9 Lymph 18 6 Other 1 Type Not Reported This table shows the percentage of patients with malignancies reported within 1 year, within 5 years and within 10 years following transplantation. The percentages are based on patients with known responses. To reduce bias, only patients with responses reported on every follow-up through the 5-year (or 10-year) annual follow-up were included in the “5-Year Survivors” (or “10-Year Survivors”) column. * Recipients may have experienced more than one type of malignancy so sum of individual malignancy types may be greater than total number with malignancy. ISHLT 2007 J Heart Lung Transplant 2007;26

Freedom from Malignancy For Adult Heart-Lung Recipients (Follow-ups: April 1994- June 2006) Freedom from malignancy rates were computed using the Kaplan-Meier method. The development of malignancy is reported on annual follow-ups; a date of diagnosis is not provided. For this figure the date of follow-up was used as the date of occurrence. Patients were included in the analysis until an unknown response for malignancy was reported. Therefore, the rates seen here may differ from those reported in the cumulative prevalence slide which is based on only those patients with known responses for malignancy at all follow-up time points. ISHLT 2007 J Heart Lung Transplant 2007;26

ADULT HEART-LUNG TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2006) 0-30 Days (N = 225) 31 Days - 1 Year (N = 145) >1 Year - 3 Years (N = 124) >3 Years - 5 Years (N = 70) >5 Years (N = 129) BRONCHIOLITIS 4 (2.8%) 34 (27.4%) 28 (40.0%) 31 (24.0%) ACUTE REJECTION 3 (1.3%) 2 (1.6%) 1 (0.8%) LYMPHOMA 5 (3.4%) 9 (7.3%) 3 (4.3%) MALIGNANCY, OTHER 1 (0.7%) 6 (4.8%) 2 (2.9%) 6 (4.7%) CMV 1 (1.4%) INFECTION, NON-CMV 40 (17.8%) 58 (40.0%) 7 (10.0%) 22 (17.1%) GRAFT FAILURE 69 (30.7%) 32 (22.1%) 21 (16.9%) 11 (15.7%) CARDIOVASCULAR 21 (9.3%) 6 (4.1%) 8 (11.4%) 8 (6.2%) TECHNICAL 47 (20.9%) 3 (2.1%) OTHER 45 (20.0%) 31 (21.4%) 11 (8.9%) 9 (12.9%) 29 (22.5%) Percentages are based on only known causes of death. ISHLT 2007 J Heart Lung Transplant 2007;26

HEART-LUNG TRANSPLANTATION Pediatric Recipients ISHLT 2007 J Heart Lung Transplant 2007;26

AGE DISTRIBUTION OF PEDIATRIC HEART-LUNG RECIPIENTS (Transplants: January 1982 - June 2006) ISHLT 2007 J Heart Lung Transplant 2007;26

AGE DISTRIBUTION FOR DONORS OF PEDIATRIC HEART-LUNG RECIPIENTS (Transplants: January 1982 - June 2006) NOTE: Transplants where donor age is unknown are excluded from this tabulation. ISHLT 2007 J Heart Lung Transplant 2007;26

AGE DISTRIBUTION OF PEDIATRIC HEART-LUNG RECIPIENTS By Year of Transplant Number of Transplants This figure includes only the pediatric heart-lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not necessarily be construed as evidence that the number of pediatric heart-lung transplants performed worldwide has declined. 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 pediatric heart-lung transplants worldwide has declined in recent years. ISHLT 2007 J Heart Lung Transplant 2007;26

AGE DISTRIBUTION OF PEDIATRIC HEART-LUNG RECIPIENTS By Era of Transplant Percentage of Transplants This figure includes only the pediatric heart-lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not necessarily be construed as evidence that the number of pediatric heart-lung transplants performed worldwide has declined. ISHLT 2007 J Heart Lung Transplant 2007;26

NUMBER OF CENTERS REPORTING PEDIATRIC HEART-LUNG TRANSPLANTS NEED TO UPDATE ISHLT 2007 J Heart Lung Transplant 2007;26

NUMBER OF CENTERS REPORTING PEDIATRIC HEART-LUNG TRANSPLANTS Stratified by center volume ISHLT 2007 J Heart Lung Transplant 2007;26

DIAGNOSIS IN PEDIATRIC HEART –LUNG TRANSPLANT RECIPIENTS (Age: 11-17 Years) “Other” includes Bronchiectasis, Alpha-1, and OB (non-ReTX) ISHLT 2007 J Heart Lung Transplant 2007;26

PEDIATRIC HEART-LUNG TRANSPLANTS: AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006 ISHLT 2007 J Heart Lung Transplant 2007;26

PEDIATRIC HEART-LUNG TRANSPLANTS: DIAGNOSIS DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006 ISHLT 2007 J Heart Lung Transplant 2007;26

PEDIATRIC HEART-LUNG TRANSPLANTS: DONOR AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006 ISHLT 2007 J Heart Lung Transplant 2007;26

PEDIATRIC HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2005) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. Survival rates were compared using the log-rank test statistic. ISHLT 2007 J Heart Lung Transplant 2007;26

PEDIATRIC HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival (Transplants: January 1982 - June 2005) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not know for all patients. The half-life is the estimated time point at which 50% of all of the recipients have died. Survival rates were compared using the log-rank test statistic. ISHLT 2007 J Heart Lung Transplant 2007;26

PEDIATRIC HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1982 - June 2005) Survival (%) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not know for all patients. The half-life is the estimated time point at which 50% of all of the recipients have died. The conditional half-life is the estimated time point at which 50% of the recipients who survive to at least 1 year have died. Because the decline in survival is greatest during the first year following transplantation, the conditional survival provides a more realistic expectation of survival time for recipients who survive the early post-transplant period. Survival rates were compared using the log-rank test statistic. ISHLT 2007 J Heart Lung Transplant 2007;26

PEDIATRIC HEART-LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1982 - June 2005) Conditional on Survival to 1 Year Survival (%) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not know for all patients. The half-life is the estimated time point at which 50% of all of the recipients have died. The conditional half-life is the estimated time point at which 50% of the recipients who survive to at least 1 year have died. Because the decline in survival is greatest during the first year following transplantation, the conditional survival provides a more realistic expectation of survival time for recipients who survive the early post-transplant period. Survival rates were compared using the log-rank test statistic. ISHLT 2007 J Heart Lung Transplant 2007;26

PEDIATRIC HEART-LUNG TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2006) 0-30 Days (N = 30) 31 Days - 1 Year (N= 28 ) >1 Year - 3 Years (N= 26 ) >3 Years - 5 Years (N = 19 ) >5 Years (N = 19) BRONCHIOLITIS 1 (3.6%) 14 (53.8%) 9 (47.4%) 7 (36.8%) ACUTE REJECTION 2 (7.1%) MALIGNANCY, OTHER 1 (5.3%) INFECTION, NON-CMV 6 (20.0%) 9 (32.1%) 5 (19.2%) 5 (26.3%) GRAFT FAILURE 12 (40.0%) 3 (15.8%) CARDIOVASCULAR 2 (6.7%) 3 (10.7%) 2 (10.5%) TECHNICAL 4 (13.3%) Percentages are based on only known causes of death. ISHLT 2007 J Heart Lung Transplant 2007;26

PEDIATRIC HEART-LUNG TRANSPLANT RECIPIENTS: Cause of Death (Deaths: April 1994 - June 2006) 0-30 Days (N = 26) 31 Days - 1 Year (N = 22) >1 Year - 3 Years (N = 20) >3 Years - 5 Years (N = 17) >5 Years (N = 19) BRONCHIOLITIS 1 (4.5%) 11 (55.0%) 8 (47.1%) 7 (36.8%) ACUTE REJECTION MALIGNANCY, OTHER 1 (5.9%) INFECTION, NON-CMV 4 (15.4%) 7 (31.8%) 4 (20.0%) 5 (26.3%) GRAFT FAILURE 12 (46.2%) 2 (9.1%) 3 (15.0%) 5 (29.4%) 3 (15.8%) CARDIOVASCULAR 2 (7.7%) 2 (10.5%) TECHNICAL Percentages are based on only known causes of death. ISHLT 2007 J Heart Lung Transplant 2007;26