Dr. Jan Kovac, MUDr., FACC, FESC Cardiology Division, Glenfield Hospital University of Leicester NHS Trust, Leicester UK

1. Dr. Jan Kovac, MUDr., FACC, FESC Cardiology Division, Glenfield Hospital University of Leicester NHS Trust, Leicester UK The Future of Percutaneous Valve Therapies Presenter Disclosure:None

2. Interventional Cardiology ‘Credo’ “Anything a cardiac surgeon can do, an interventional cardiologist can do as well or better percutaneously” AH Gershlick, 2003

3. Percutaneous Valve Therapies in 2006 1. Percutaneous aortic valve replacement (AS,AI) PVT, Corevalve, Pananigua, 3F, Corazone… 2. Percutaneous therapy of mitral regurgitation leaflet fixation coronary sinus techniques transventricular techniques 3. Pulmonary valve replacement (P.Bohnhoffer)

4. Mechanical Tissue Stentless Homograft Ross The standard for critical AS RX is Surgical AVR

5. Actuarial and "actual" freedom from valve-related morbidity or mortality after AVR and MVR Ikonomidis, J. S. et al.; J Thorac Cardiovasc Surg 2003;126:2022-2031

6. Mortality in Aortic Valve Replacement n = 1.984 %mortality Burr et al.: Annals of Thor Surg, 1995, 60, S264-269

7. Aortic valve replacement Refused for Surgery Euro Heart Survey on Valvular Heart Disease (5001 Patients) 32 % did not undergo surgery ! Iung B. and al, Eur. Heart Journal 2003 : 24, 1231-1243

8. Diseases desperate grown, By desperate appliances are reliev’d, Or not at all” (Hamlet Act IV)

9. Prosthetic Aortic Valve Functions 1. Allow normal LVOT function 2. Restore anulus flexibility 3. Conserve sinus motion and sinus flow dynamics 4. Ensure physiological orientation of trileaflet valve 5. Do better than current valves

10. First Clinical Percutaneous Aortic Valve Alain Cribier - 16/4/02 • Equine pericardial valve • sewn on 23mm BES; • PVT acquired by Edwards • 1/04

11. Percutaneous Aortic Valve Replacement Designs/Trials 1. PVT-Edwards-Cribier 2. COREVALVE 3. Panaguia 4. 3F 5. SORIN 6. CORAZONE 7. SADRA Medical 8. ValveXchange 9. Direct Flow

12. Tricuspid valve, equine pericardium • Stainless steel stent frame • 22mm Numed ballon catheter • Original crimper device • Compatible with 24-Fr sheath

13. Cribier Edwards AV Implant

14. Cribier PVT Trials Inclusion Criteria Patients >70 years of age Aortic valve area < 0.7 cm² Aortic annulus diameter: 19-23 mm Dyspnoea NYHA class IV At extremely high risk for open heart surgery and formally declined by two cardiac surgeons for surgical valve replacement

15. Alan Cribier-Edwards PVT Rouen Experience

16. Alan Cribier-Edwards PVT RECAST Experience

17. CoreValve’s Self-Expanding Prosthesis • HIGHER PART : increases quality of fixation and axes the system • MIDDLE PART : is constrained to avoid coronaries (no rotational positioning) and carries the valve • LOWER PART: High radial force of the frame pushes aside the calcified leaflets and avoids recoil and para-valvular leaks A pericardium porcine tissue valve Fixed to the frame in a surgical manner with PTFE sutures

19. CoreValve StudyResults Phase 1&2: July 2004-Dec 2005 (28 patients) Clinical succes In hospital death Convertion to Surgery Phase 1 Phase 2

20. Phase 2 Clinical Study 7 European Investigative Centers Patient type: High-risk/non-surgical candidates Euroscore higher than 20 Trial initiated: December 2005 Primary endpoints:Acute safety and efficacy Long-term outcomes Leicester 2006

21. 3F Transapical Antegrade Aortic Valve Implant

22. Thin Film Nanotechnology eNitinol MembranePercValve™

23. Aortic Valve Calcification

24. CORAZON percutaneous aortic valve system flexible multilumen central catheter (navigable) soft tip for placement into left ventricle and a balloon for occluding the LV outflow tract below the aortic valve expandable central lumen with temporary aortic valve enabling beating heart aortic valve treatment aortic isolation of treatment area using a compliant bell designed to conform to the shape of aortic valve cusps balanced solution inflow and aspiration

25. CORAZON percutaneous aortic valve system

26. Percutaneous Mitral Valve Therapies

27. Percutaneous Mitral Repair Technologies Percutaneous Transvenous Mitral Reshaping/Annuloplasty through the Coronary Sinus Straightening, Stent based Reshaping/Annuloplasty through the Ventricle Percutaneous/Transatrial edge to edge (E2E or Alfieri) repair Plicating Left Atrial/Ventricular Tissue anchors

28. Percutaneous Mitral E2E Repair

29. EVEREST I Endovascular Valve Edge to edge REpair pair STudy

30. EVEREST I Endovascular Valve Edge to edge REpair pair STudy Freedom from surgery to date 35/47 = 74% •No clip deployed (n=5) for insufficient MR reduction •Operations: 4 repairs, 1 intended replacement after clip deployment (n=7) •Reasons: •1 device malfunction •4 partial detachments •Timing (days): 1, 3, 36, 40, 50, 110, 133 •Surgery: •5 repairs, 2 replacement (1 intended; 1 failed repair) •Concomitant ASD repair (6), MAZE (1), CABG (1) •2 progressive MR

31. EVEREST II Study Design EVEREST II Study Design Prospective, randomized, multicenter study Control: surgical mitral valve repair/ replacement Patients randomized 2:1 37 centers in US and Canada Primary Effectiveness Endpoint Freedom from surgery, death, and moderate to severe (3+) or severe (4+) mitral regurgitation at 12 months. Primary Safety Endpoint Freedom from MAE at one month

32. Placement of a percutaneous stitch inthe free edge(s) of the mitral leaflets, Edwards LilfeSciences Step 1 Step 2 Step 3

33. Mitral Annuloplasty Therapies

34. Viking Edwards PTMA Stent based anchors connected by a tether Anchors at the CS ostium and AIV Time delay contracting tether Cinches the mitral annulus, increases mitral leaflet coaptation

35. CarillonTM, Cardiac Dimensions

36. Viacor • Straightens the coronary sinus • Anteriorly displaces P2 • Begins with a “diagnostic” OTW procedure • Implant placed OTW within a 7 Fr sheath • Implant tethered to a hub in the infraclavicular fossa

37. Quantum Cor RF Tip of probe is smaller to conform to annulus shape 8 electrodes (~1.5x2mm) Delivery of RF energy to electrodes is computer-controlled by maximum temperatures sensed by adjacent thermocouples

38. Combined percutaneous MV Treatment … a bow tie always need a collar

39. Is Percutaneous Mitral Replacement Possible?

40. For Cardiac Surgeons.. "In times of change, the learners inherit the Earth, while thelearned find themselves beautifully equipped to deal with aworld that no longer exists." Eric Hoffer Not quite….for a while

41. UK/ Leicester Perspective • Aortic valve COREVALVE 18 F Trial (2006) • EVEREST III Trial (pending EVEREST II, end 2006) • Compassionate Use ??

42. Very early days 120-130 aortic and mitral implants worldwide Does not stand up to surgical therapy at the moment New skills needed for interventionist-TOE/ICE Old skills refreshed (transseptal, PTMV, CS) Teamwork (blurring boundaries interventionist/ surgeon)

43. Will it ultimately work? S.Oesterle….the Beauty of Stardom No R+D but r+D no Venture Capitalist able to fund >1000 $/patient clinical Trial, quality assurance, manufacturing, regulatory issues, distribution “Make a better mousetrap and world will beat path to your door ” Waldo Emerson

44. I don’t skate where the puck is. I skate, to where the puck is going. Wayne Gretzky NHL All Star 81-99