SSA Hearing on Compassionate Allowances Janet N Scheel MD November 9,2010

Cardiomyopathy Restrictive cardiomyopathy Hypertrophic cardiomyopathy Dilated cardiomyopathy*

Frank Starling Curve

Causes of DCM in Children Genetic Infectious Metabolic Arrhythmias

Causes of DCM in Children Inflammatory Nutritional Structural heart disease Chemotherapy

CHF symptoms in Adults

CHF Symptoms in Children Ross Classification Class I- no symptoms Class II-Mild tachypnea or diaphoresis with feedings/exertion. No growth failure Class III-Marked tachypnea or diaphoresis with feedings/exertion;prolonged feeding time;growth failure Class IV-Symptomatic at rest

Treatment options Oral medical therapy IV inotropes Pacing ECMO/VAD Transplant

ECMO

Long – term devices specific for children

Selection for Pediatric Heart Transplant End stage congenital heart disease not amenable to surgical or medical therapy –Ross Classification III-IV –Failure to thrive –Protein losing enteropathy –Intractable arrhythmias –Plastic bronchitis

Selection for Pediatric Heart Transplant Dilated Cardiomyopathy –symptomatic on maximal medical therapy Restrictive Cardiomyopathy

Exclusion Criteria Genetic syndrome with poor long term prognosis Neurologic abnormalities with poor long term prognosis Irreversible end-organ damage Socio-economic factors leading to poor long term compliance

Exclusion Criteria Genetic syndrome with poor long term prognosis Neurologic abnormalities with poor long term prognosis Irreversible end-organ damage Socio-economic factors leading to poor long term compliance

Exclusion Criteria Pulmonary Hypertension (>5-6 woods units) –Unresponsive to oxygen or pulmonary vasodilators –Transpulmonary gradient > 15mmHg Pulmonary vein stenosis Active infection Active malignancy

AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS By Year of Transplant ISHLT 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. 2009

PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival (Transplants: 1/1982-6/2007) ISHLT 2009

PEDIATRIC HEART TRANSPLANTATION Conditional Kaplan-Meier Survival (Transplants: 1/1982-6/2007) ISHLT 2009

PEDIATRIC HEART TRANSPLANTATION Conditional Kaplan-Meier Survival for Recent Era (Transplants: 1/1999-6/2007) ISHLT 2009

PEDIATRIC HEART TRANSPLANTS (1/1995-6/2007) Risk Factors For 1 Year Mortality N=3,756 ISHLT Reference diagnosis = cardiomyopathy 2009

PEDIATRIC HEART RECIPIENTS Functional Status of Surviving Recipients (Follow-ups: April June 2008) ISHLT 2009

PEDIATRIC HEART RECIPIENTS Functional Status of Surviving Recipients (Follow-ups: April June 2008) For the Same Patients ISHLT 2009

PEDIATRIC HEART RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients (Follow-ups: April June 2008) ISHLT 2009

PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up for Same Patients at Each Time Point (Follow-ups: January June 2008) % of Patients ISHLT Analysis is limited to patients who were alive at the time of the follow-up 2009

FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April June 2008) ISHLT 2009

GRAFT SURVIVAL FOLLOWING REPORT OF CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April June 2008) Stratified by Age Group ISHLT 2009

FREEDOM FROM SEVERE RENAL DYSFUNCTION* For Pediatric Heart Recipients (Follow-ups: April June 2008) ISHLT 2009

MALIGNANCY POST-HEART TRANSPLANTATION FOR PEDIATRICS Cumulative Prevalence in Survivors (Follow-ups: April June 2008) Malignancy/Type1-Year Survivors 5-Year Survivors 10-Year Survivors No Malignancy 3,361 (98.1%)1,343 (95.2%)332 (92.2%) Malignancy (all types combined) 64 (1.9%)68 (4.8%)28 (7.8%) Malignancy Type Lymph Other 452 Skin 1 Type Not Reported 1 ISHLT NOTE: Multiple types may be reported; sum of types may be greater than total number with malignancy. 2009

FREEDOM FROM MALIGNANCY For Pediatric Heart Recipients (Follow-ups: April June 2008) ISHLT 2009

PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 1 and 3 Years (Transplants: April June 2005) Maintenance Immunosuppression at discharge and 1 year % HTN reported between 1 and 3 years P-value For Patients on drug For Patients not on drug Azathioprine Cyclosporine MMF Prednisone <.0001 Rapamycin Tacrolimus ISHLT 2009

PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 3 and 8 Years (Transplants: April June 2000) Maintenance Immunosuppression at discharge and 1 year % HTN reported between 3 and 8 years P-value For Patients on drug For Patients not on drug Azathioprine Cyclosporine MMF Prednisone <.0001 Rapamycin Tacrolimus ISHLT 2009

PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January June 2008) CAUSE OF DEATH 0-30 Days (N = 461) 31 Days - 1 Year (N = 421) >1 Year - 3 Years (N = 307) >3 Years - 5 Years (N = 226) >5 Years - 10 Years (N = 350) >10 Years (N = 172) CORONARY ARTERY VASCULOPATHY 5 (1.1%)30 (7.1%)62 (20.2%)69 (30.5%)98 (28.0%)49 (28.5%) ACUTE REJECTION 44 (9.5%)100 (23.8%)71 (23.1%)31 (13.7%)45 (12.9%)10 (5.8%) LYMPHOMA 10 (2.4%)12 (3.9%)6 (2.7%)33 (9.4%)11 (6.4%) MALIGNANCY, OTHER 4 (1.0%)2 (0.7%)1 (0.4%)5 (1.4%)11 (6.4%) CMV 1 (0.2%)11 (2.6%)1 (0.3%) INFECTION, NON-CMV 54 (11.7%)65 (15.4%)20 (6.5%)8 (3.5%)17 (4.9%)13 (7.6%) PRIMARY FAILURE 102 (22.1%)23 (5.5%)10 (3.3%)15 (6.6%)18 (5.1%)5 (2.9%) GRAFT FAILURE 97 (21.0%)45 (10.7%)62 (20.2%)53 (23.5%)74 (21.1%)44 (25.6%) TECHNICAL 27 (5.9%)3 (0.7%)2 (0.7%)2 (0.9%)4 (1.1%)1 (0.6%) OTHER 25 (5.4%)26 (6.2%)29 (9.4%)24 (10.6%)30 (8.6%)10 (5.8%) MULTIPLE ORGAN FAILURE 46 (10.0%)54 (12.8%)11 (3.6%)6 (2.7%)10 (2.9%)8 (4.7%) RENAL FAILURE 1 (0.2%)4 (1.0%)1 (0.3%)1 (0.4%)1 (0.3%)3 (1.7%) PULMONARY 29 (6.3%)30 (7.1%)15 (4.9%)8 (3.5%)8 (2.3%)5 (2.9%) CEREBROVASCULAR 30 (6.5%)16 (3.8%)9 (2.9%)2 (0.9%)7 (2.0%)2 (1.2%) ISHLT 2009

PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January June 2008) CAUSE OF DEATH 0-30 Days (N = 213) 31 Days - 1 Year (N = 241) >1 Year - 3 Years (N = 192) >3 Years - 5 Years (N = 153) >5 Years - 10 Years (N = 286) >10 Years (N =165) CAV 2 (0.9%)14 (5.8%)33 (17.2%)43 (28.1%)77 (26.9%)47 (28.5%) ACUTE REJECTION 22 (10.3%)45 (18.7%)36 (18.8%)23 (15.0%)36 (12.6%)10 (6.1%) LYMPHOMA 6 (2.5%)7 (3.6%)4 (2.6%)28 (9.8%)11 (6.7%) MALIGNANCY, OTHER 1 (0.4%)1 (0.5%)4 (1.4%)10 (6.1%) CMV 7 (2.9%)1 (0.5%) INFECTION, NON- CMV 26 (12.2%)31 (12.9%)11 (5.7%)3 (2.0%)13 (4.5%)11 (6.7%) PRIMARY FAILURE 44 (20.7%)9 (3.7%)4 (2.1%)6 (3.9%)10 (3.5%)5 (3.0%) GRAFT FAILURE 31 (14.6%)25 (10.4%)48 (25.0%)44 (28.8%)66 (23.1%)42 (25.5%) TECHNICAL 14 (6.6%)2 (1.0%)4 (1.4%)1 (0.6%) OTHER 19 (8.9%)20 (8.3%)24 (12.5%)17 (11.1%)26 (9.1%)10 (6.1%) MULTIPLE ORGAN FAILURE 27 (12.7%)40 (16.6%)10 (5.2%)5 (3.3%)8 (2.8%)8 (4.8%) RENAL FAILURE 4 (1.7%)1 (0.5%)1 (0.7%)1 (0.3%)3 (1.8%) PULMONARY 11 (5.2%)27 (11.2%)10 (5.2%)6 (3.9%)7 (2.4%)5 (3.0%) CEREBROVASCULAR 17 (8.0%)12 (5.0%)4 (2.1%)1 (0.7%)6 (2.1%)2 (1.2%) ISHLT 2009

PEDIATRIC HEART TRANSPLANT RECIPIENTS: Relative Incidence of Leading Causes of Death (Deaths: January June 2008) ISHLT 2009