1. Trans-catheter Aortic Valve Replacement: a UK update. Dr Martyn Thomas Guys and St Thomas’ Hospital

2. So, is there a clinical need for less invasive method of replacing the aortic valve??

3. Severe Symptomatic Aortic Stenosis is a fatal condition. “Surgical intervention should be performed promptly once even… minor symptoms occur” 1 Chart: Ross J Jr, Braunwald E. Aortic stenosis. Circulation 1968;38 (Suppl 1) 1 C.M. Otto. Valve Disease: Timing of Aortic Valve Surgery. Heart 2000 Chart:: Ross J Jr, Braunwald E. Aortic stenosis. Circulation. 1968;38 (Suppl 1):61-7. Valvular Aortic Stenosis in Adults (Average Course)

4. 31.8% did not undergo intervention, most frequently because of comorbidities

5. Treated vs. Untreated

6. Prof. Alain Cribier First Clinical Experiences  First described percutaneous aortic valve interventions in 1985  Proved that a stent could be deployed without removing the diseased native valve  Implanted first percutaneous aortic valve on a patient on April 16, 2002

7. Currently available systems in the UK.  Corevalve: trans-femoral  Registry complete. CE mark. Now in commercial phase.  Edwards Sapien Valve: trans-femoral and transapical.  European Registry complete at the end of Jan. CE mark for both approaches. Now in commercial phase.

8. Diamond cell configuration Nitinol (memory shaped) Multi-level design incorporates three different areas of radial and hoop strength Low radial force area orients the system Constrained area to avoid coronaries and featuring supra-annular valve leaflets High radial force for secure anchoring – no recoil – constant force mitigates leak Radiopaque Self-Expanding Multi-level Support Frame

9. Specifically designed for transcatheter delivery Single layer porcine pericardium Tri-leaflet configuration Tissue valve sutured to frame Standard tissue fixation techniques 200M cycle AWT testing completed Supra-annular valve function Intra-annular implantation and sealing skirt Porcine Pericardial Tissue Valve

10. 18F Delivery Catheter System 12F shaft body 18F distal end Dual speed release handle Over-the-wire 0.035 compatible

11. Generation 1 25F Transcatheter Generation 2 21F Transcatheter Technology Progress & Total Experience Generation 3 18F Percutaneous 14 patients 65 patients* 184 patients** * Including 2 ReDo ** Updated August 30, 2007 Including Expanded Evaluation Registry 2004-2005 2005-2006 Oct 2006

12. CoreValve PAVR ReValving™ System Time Period Implant Phase Device Used Number of Patients July 2004-July 2005 First in Man 25 French 14 August2005-August2006 21F Intl Trial 21 French 65 May 2006-Ongoing 18F Intl Trial 18 French 112 June 2007-Ongoing Expanded Evaluation 18 French 18 French76 Total Worldwide PAVR ReValving™ Patients Treated 267 Updated August 31, 2007

13. Procedural Success161 (92%) ± 77 Minutes Mean Total Procedure Time170 ± 77 Minutes ± Mean ReValving™ Time 11 ± 14 Minutes Discharged with CoreValve 159 (91%) Discharged after surgical conversion 3 (2%) Procedural Results – N=175

14. Access to the aortic valve Edwards SAPIEN ™ THV Transfemoral Approach Transapical Approach

15. Cribier-Edwards ™ and Edwards SAPIEN ™ THV* Aortic Transfemoral/Transapical Trial Implants (21 Dec 07 Update) * The Edwards SAPIEN™ valve incorporates bovine pericardial tissue and TFX™ treatment bovine pericardial tissue and TFX™ treatment 622 Patients 2002-2007 Transfemoral(n=353) AntegradeN=59 RECAST n = 24 iREVIVE n = 22 REVIVE I n = 4 REVIVAL I n = 7 US Compassionate n=2 RetrogradeN=294 REVIVE II n = 101 REVIVAL II n = 55 CANADIAN SPECIAL ACCESS n =90 PARTNER EU n =48 PARTNER IDE PARTNER IDE n ~ 40 Transapical(n=269) TRAVERCE n=145 REVIVAL II n =33 CANADIAN SPECIAL ACCESS n =37 US Compassionate n=2 PARTNER EU n= 52

16. RetroFlex II Offers: Greatly improved native valve crossability Greatly improved native valve crossability Smoother tracking Smoother tracking Improved handle functionality Improved handle functionality Fewer system components Fewer system components RetroFlexRetroFlex II

17. Transfemoral Procedure: Edwards

24. Valve deployment with 3D echo.

25. The UK position  15 centres would like to start a programme.  Active centres, n=6.  Number of cases:  - Corevalve 71  - Edwards 16  Early Mortality approx 7%. 3/87 cath lab deaths, 5/87 in patient deaths (2 non cardiac) and 6/87 deaths at 3/12.  Also pacemaker, surgical conversion, peripheral vascular complications, stroke, pericardial drain.  Complex procedure but considering the patient mix encouraging.

26. Training  Centre selection currently controlled by industry.  Responsible attitude being taken.  MHRA (or whatever they are now called!) happy and do not feel central control is necessary.  Training consists (in general) of theory, simulators, observation and cases performed with proctors.  2008 an interesting, dangerous and challenging year!!

27. UK Funding  Currently undergoing a NICE assessment.  Most centres trying to use a “surgical” tariff.  “Top ups” being locally negotiated with PCTs.  Early “NICE” assessment (like PFO closure) may facilitate the process.

28. Trans-catheter Aortic Valve Replacement: a UK update. Conclusions  2008 will be an exciting but “dangerous” year for trans-catheter heart valve replacement.  Training and case selection is all.  Irresponsible use of the device could set Europe and the UK back for many years.  This exciting development in interventional cardiology could well be the future for tertiary/surgical centre intervention (at least in the medium term!)