1. Advances in Heart Transplantation and Mechanical Circulatory Support
Jeffrey Alexis, MD
University of Rochester Medical Center

2. 1st Heart Transplant
Dr. Christiaan Barnard
South Africa, December
Donor was a 25 year old woman who died following an auto accident
Recipient was a 55 year old man, lived 18 days, died from pneumonia

5. Subsequent Rush to do Heart Transplants
1st transplant in US: December 6, 1967
Dr. Adrian Kantrowitz- Maimonides Medical Center in Brooklyn NY
18 day old male received a transplant from 2 day old male, died 6 hours later- acidosis

6. 3rd Heart Transplant: Dr
3rd Heart Transplant: Dr. Christiaan Barnard January 2, 1968, 58 yr old man received a heart from a 24 year old man
1st Adult US Transplant: January 6, 1968, Dr. Norman Shumway, Stanford University, 54 year old man received a heart from a 43 year old man, recipient died 15 days later of multiple systemic complications

7. 100 heart transplants done in 1968
Poor outcomes, 80% of patients died within 1 year
Immunosuppression was the major problem
18 transplants done in 1970

9. Immunosuppressive Drugs in Organ Transplantation
Year
Therapy
1959
Total Body irradiation
6-Mercaptopurine and azathioprine
Steroids used systemically
1978
Cyclosporine
1989
Tacrolimus
1997
Mycophenolate mofetil
1998
Sirolimus

10. Immunosuppressive Drugs

11. Azathioprine Derived from 6-mercaptopurine
Inhibits cell cycle; impairs DNA synthesis
Developed by Gertrude Elion and George Hitchings who won a share of the 1988 Nobel Prize

12. Immunosuppressive Drugs

13. Azathioprine Myelosuppression Leukopenia (White blood cell count)
--Side Effects
Myelosuppression
Leukopenia (White blood cell count)
Thrombocytopenia (Platelet count)
Anemia (Red blood cell count)
Malignancies (cutaneous)

14. Corticosteroids
Anti-inflammatory- inhibit leukotrienes and prostaglandins
Immunosuppressive- Impair rate of transcription of genes that encode regulatory cytokines.

15. Corticosteroids
Inhibit white blood cell transmigration through blood vessels
Reduce adhesion molecule expression

16. Corticosteroids Side Effects Diabetes Obesity Cushingoid Features
Wound Healing
Bone Disorders
Colonic perforation
Hypertension

17. Cyclosporine
Inhibits Calcineurin pathway- forms complex with cellular protein called immunophilin (Cyclophilin). Inhibits production of IL-2 and other cytokines.
Revolutionized solid organ transplantation

18. Immunosuppressive Drugs

19. Cyclosporine Side effects Kidney Disease High blood pressure
Elevated lipids

20. Tacrolimus
First isolated in 1984 from bacteria Streptomyces tsukubaensis
First used as replacement therapy for cyclosporine in liver transplant patients with intractable rejection
Inhibits Calcineurin.

21. Immunosuppressive Drugs

22. Tacrolimus Side Effects Kidney Disease Neurologic- tremor, headache
Glucose intolerance
Elevated Potassium

23. Cellcept- blocks the pathway proliferation of T and B cells
Mycophenolate
Cellcept- blocks the pathway proliferation of T and B cells
Compared with Azathioprine, reduced mortality at 1 yr (6.2% vs. 11.4%; p=0.031), reduction in requirement of treatment for rejection (65.7% vs. 73.7%; p=0.031)
Kobashigawa J et al. Transplantation 1998;
Compared with Azathioprine at 3 yrs, risk of death or repeat transplant reduced (11.8% vs. 18.3%; p<0.01)
Eisen HJ et al. J Heart Lung Transplant 2005;24:

24. Mycophenolate
Side Effects:
GI—Nausea, diarrhea
Leukopenia

25. Sirolimus
Inhibitor of TOR (Target of Rapamycin), a cytoplasmic enzyme that is critical in connecting signals from T-cell surface to cell nucleus for stimulation of growth and proliferation of lymphocytes
Side Effects:
Hyperlipidemia
Thrombocytopenia (low platelets)

26. Current State of Heart Transplants
1 year survival 85-90%
Median survival 11 years
Patients have lived 30 years post transplant
4000 done world wide each year
2000 done in the US each year
Long waiting times

27. Long Waiting Times
Number of donors is flat
Decreased deaths from motor vehicle accidents and homicides
No living related donors

28. Awaiting Transplant- UNOS Status
Status 1A
Status 1B
Status 2

31. UNOS Region 9
Long Waiting Times
Most transplants are Status 1A
Even as Status 1A, wait can be 1 year!
Many patients wait for transplant in the hospital

32. Long Waiting Times, limited number of organs, has led to increase of Mechanical Circulatory Support:
Ventricular assist devices (VAD)
Total Artificial Heart (TAH)
Extracorporeal Membrane Oxygenation (ECMO)

34. Dr. Cooley used Dr. Debakey’s device without authorization- 40 yr feud
History of MCS
1966/67-First Ventricular Assist Device placed by Dr. Michael Debakey- Methodist Hospital in Houston
1969- First TAH placed by Dr. Denton Cooley, at the Texas Heart Institute - device lasted 64 hours
Dr. Cooley used Dr. Debakey’s device without authorization- 40 yr feud
1988

35. History of MCS
1982- First totally implanted artificial heart for permanent use, was implanted- Jarvik 7 to patient Barney Clark who survived 112 days
1988

36. 1988- First continuous flow pump- Hemopump
History of MCS
1986 First pneumatic pulsatile LVAD – Dr. Bud Frazier- Heartmate IP
1988- First continuous flow pump- Hemopump
1988

37. HeartMate II LVAD

38. Heartware LVAD

39. HeartMate3 LVAD

40. Ventricular Assist Devices
No wait time for implant
Can be placed as bridge to transplant or as destination therapy
Median survival 4 years
Heartware device can be used to support the left heart and the right heart

41. Ventricular Assist Devices
While not common, heart function can sometimes improve while a patient is supported with a VAD
The VAD can sometimes be removed (this is not common)

42. ECHO

46. ECHO

47. Syncardia TAH

48. Syncardia TAH

49. Total Artificial Heart
Beneficial when patient has left and right heart disease
Beneficial when patient has dangerous arrhythmias- especially ventricular tachycardia

50. Extracorporeal Membrane Oxygenation

51. ECMO
Can stabilize patients until stable for longer term therapy or heart function recovers

52. Patient Management
Assess Severity of Illness
Assess if Sick Enough for Advanced Heart Failure Therapy
Assess Candidacy of Advanced HF Therapy
Recommend Treatment