1. QUEST FOR ULTIMATE CURE “MODEL T” to “DREAM THERAPY” Where is the MIRACLE BULLET? Chittoor B. Sai Sudhakar, MD, FRCS

2. The Holy Grail !!!!!!!!

3. Treatment of Symptomatic CHF 5 classes of drug ACE inhibitors Beta blockers Aldosterone antagonist Nitrates and Hydralazine Angiogenesis II receptor blockers

5. First Device as BTT Designed by Dr. Domingo Liotta, 1969 This heart was the first to be implanted in a human being as a bridge to transplant by Dr. Denton A. Cooley. The patient survived for almost three days with the artificial heart and 36 hours more with a transplanted heart.

6. Jarvik-7 Drs. Willem Kolff, Donald Olsen, and Robert Jarvik First human implant 1982 –Destination Therapy 200 patients bridged (Jarvik-7/Symbion)

7. Heartmate XV & XVE Has been the workhorse for a long time Does not need anti-coagulation Bulky Lasts for a 12-24 months Our record is 32 months and going

8. REMATCH Trial ( R andomized E valuation of M echanical A ssistance for the T reatment of C ongestive H eart failure) Inclusion criteria resembled those for Heart TX Class IV CHF LVEF <25% Peak oxygen consumption <12-14ml/kg/min Inotrope dependent

9. Stevenson, L. W. et al. Circulation 2003;108:3059-3063 Profiles of HF in different trials REMATCH patients were much sicker Group intermediate in severity between Status I & II heart transplant candidates

10. REMATCH Survival LVAD60%49%28% OMM39%24%11% 6 mth 1 year 2year Inotrope dependent at randomization – 91pts Not on inotrope at randomization – 38pts LVAD61%57% OMM67%40%

13. Heartmate II

14. VentrAssist 298 gms, 6 cms, size of a hockey puck Single moving part – hemodynamically suspended impeller Electromagnetic field rotates the impeller

15. HeartWare Miniaturized centrifugal pump Totally Intrapericardial Single moving part and no mechanical bearings

16. Long Term Support

17. The difficult part is the selection

18. Patient Profile/ Status: INTERMACS Levels 1. Critical cardiogenic shock 2. Progressive decline 3. Stable but inotrope dependent 4. Recurrent advanced HF 5. Exertion intolerant 6. Exertion limited 7. Advanced NYHA III INTERMACS: Patient Selection

19. PROFILE-LEVEL # Pts Yr 1 Official Shorthand General time frame for support INTERMACS LEVEL 1 82 “Crash and burn” Hours INTERMACS LEVEL 2 81 “Sliding fast” Days to week INTERMACS LEVEL 3 18 Stable but Dependent Weeks INTERMACS LEVEL 4 9 “Frequent flyer” Weeks to few months, if baseline restored INTERMACS LEVEL 5 4“Housebound” Weeks to months INTERMACS LEVEL 6 3 “Walking wounded” Months, if nutrition and activity maintained INTERMACS LEVEL 7 4 Advanced Class III

20. Stevenson, L. W. et al. Circulation 2003;108:3059-3063 Definition of heart failure populations with decreasing estimated mortality

21. Seattle Heart Failure Model

22. Right Heart Failure predictor Elevated CVP is the single most important factor Other factors: PA pressures RVSW RVSWI Degree of RV dysfunction Tricuspid Annular Excursion

23. Even more difficult : post- op management

24. INTERMACS Kirklin JK, et al. J Heart Lung Transplant ; 2008:1065-1072

25. 50 YO M ICM Heartmate XVE placed 4/13/06 –Complicated by persistent Enterococcus bacteremia Replaced with Heartmate XVE 11/2/06 –Infection cleared, was doing well Admitted 3 months later because high power utilization and batteries burning out Case Report M. Firstenberg

26. LVAD Thrombosis M. Firstenberg

27. LVAD Thrombosis M. Firstenberg

28. VAD endocarditis M. Firstenberg

29. VAD Thrombosis

30. LOH 4 months Post-op Migration

31. GF 10days post-op Migration

32. Lead Fractures : Multi-Institutional Experience OSU, St. Vincent’s (Indiana), U of Minnesota

33. HIGH TECH PROBLEM!!!!! Lead fracture in Ventrassist

34. LOW TECH SOLUTION

35. Other therapies – Immune Adsorption Several antibodies against the cardiac proteins IA removes these antibodies

36. 9 patients in each arm High anti beta-1 adrenoceptor auto antibodies IA for five courses followed by IgG substitution Improvement in functional class at 3 months Immune Adsorption

37. In our lab at OSU Ovine model of heart failure Embolization technique Beads Aggregated platelets LAD ligation

38. Picture 1. Fluoroscopy picture of left circumflex artery cannulated with 6F catheter and injected with 90um polyester micro beads

39. Cytokines Thrombus embolized Bead embolized LAD ligated GFR alpha-3 532247641609 MIG509225051739 IL-1 alpha 498344872815 TGF-beta 1 468125801282 IL-15466136732536 IFN-gamma408723021348 IL-3408715721961 IL-133857541622 GRO341622621914 MCP-1298822751821 IFN-alpha / beta R2 28782226666 MCP-226891342 Fas / TNFRSF6 241223881344 ICAM-121091671 Epiregulin21031826483 Cytokine Expression Chandrakala

40. Our ongoing Investigation Autoantibodies to CEC & ERP Inhibit the homing mechanisms of BM derived EPC Inhibition of Angiogenesis, Neovascularization and Repair

41. Are there any magic bullets for cure out there?

42. If there is one then we can sing praises: Shot through the heart, you give VAD a bad name

43. Thank you