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

2. Cardiomyopathy Restrictive cardiomyopathy Hypertrophic cardiomyopathy Dilated cardiomyopathy*

4. Frank Starling Curve

5. Causes of DCM in Children Genetic Infectious Metabolic Arrhythmias

6. Causes of DCM in Children Inflammatory Nutritional Structural heart disease Chemotherapy

7. CHF symptoms in Adults

8. 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

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

10. ECMO

12. Long – term devices specific for children

13. 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

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

15. 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

16. 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

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

18. 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

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

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

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

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

23. PEDIATRIC HEART RECIPIENTS Functional Status of Surviving Recipients (Follow-ups: April 1994 - June 2008) ISHLT 2009

24. PEDIATRIC HEART RECIPIENTS Functional Status of Surviving Recipients (Follow-ups: April 1994 - June 2008) For the Same Patients ISHLT 2009

25. PEDIATRIC HEART RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients (Follow-ups: April 1994 - June 2008) ISHLT 2009

26. PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up for Same Patients at Each Time Point (Follow-ups: January 2001 - June 2008) % of Patients ISHLT Analysis is limited to patients who were alive at the time of the follow-up 2009

27. FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008) ISHLT 2009

28. GRAFT SURVIVAL FOLLOWING REPORT OF CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008) Stratified by Age Group ISHLT 2009

29. FREEDOM FROM SEVERE RENAL DYSFUNCTION* For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008) ISHLT 2009

30. MALIGNANCY POST-HEART TRANSPLANTATION FOR PEDIATRICS Cumulative Prevalence in Survivors (Follow-ups: April 1994 - 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 596426 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

31. FREEDOM FROM MALIGNANCY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2008) ISHLT 2009

32. PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 1 and 3 Years (Transplants: April 1993 - 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 Azathioprine22.026.00.1643 Cyclosporine21.426.20.1083 MMF23.422.70.8049 Prednisone29.610.7<.0001 Rapamycin37.522.5- Tacrolimus28.820.30.0039 ISHLT 2009

33. PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 3 and 8 Years (Transplants: April 1993 - 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 Azathioprine37.548.90.1623 Cyclosporine36.543.80.4302 MMF41.437.60.6949 Prednisone47.120.2<.0001 Rapamycin.37.6- Tacrolimus42.334.80.4484 ISHLT 2009

34. PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - 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

35. PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1998 - 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

36. PEDIATRIC HEART TRANSPLANT RECIPIENTS: Relative Incidence of Leading Causes of Death (Deaths: January 1998 - June 2008) ISHLT 2009