1. Prospettive nell’utilizzo delle valvole percutanee: oltre la stenosi valvolare aortica degenerativa Luca Testa, MD, PhD Istituto Clinico S. Ambrogio Milano

2. FIRST IN PIG; May 1, 1989 Dr. Henning Rud Andersen PIONEERED Concept

3. First Successful Percutaneous Aortic Valve Replacement Alain Cribier April 16, 2002 Day 8 post-implantation

4. Severe AS should be treated with AVR Ross J, BranwaldE. Aortic Stenosis. Circulation1968; 38(suppl5);61- 7

5. At least 30-40% Of Cardiologists’ AS Patients Go Untreated Severe Symptomatic Aortic Stenosis Percent of Cardiology Patients Treated No AVR AVR

6. Aortic Stenosis: the unmet need and the oppurtunity to make difference with technology US population >65 37M US Census, 2005 Prevalence rate ~4% Cardiovascular Health Study Prevalence ~1.5M Calculation Operable AS (%) 20% L.E.K. Consulting estimate Addressable patients ~300K Annual AVR patients ~60K HRI Calculation ~25% of those who would benefit from AVR actually get it More appropriate application of guidelines could lead to lower excess morbidity/mortality US prevalence of aortic stenosis Sources:C.M. Otto. Valve Disease: Timing of Aortic Valve Surgery. Heart 2000: (84) 211-217 US Census Bureau, Population Estimates Program, July 1 2005 LEK, Project Helium Analysis, November 10, 2005 Health Research International. US Opportunities in Heart Valve Disease Management, July 2005

7. Stainless Steel vs. Nitinol Balloon Expandable vs. Self Expanding Bovine vs. Porcine pericardial tissue

8. ABPS nitinol frame and nitinol membrane leaflet DAT self expanding nitinol stent ATS Enable self expanding nitinol stent (left); Entrata stainless steel balloon expandable stent (right) “Newly” available devices…..

12. Is that all????

13. Surgical Bioprosthetic Cardiac Valves Background Approximately 200,000 surgical aortic valve replacements performed annually in U.S., the majority are bioprostheses. With a life expectancy of 10-20 years, and implantation of bioprosthetic valves in younger patients, it is expected that there will be a significant increase in the number of patients requiring redo surgery for failed bioprostheses.

14. Bioprosthesis Types

15. Way of failure…. Leaflet tissue deterioration: Calcium deposition at sites of greatest leaflet flexion and stress: basal and commissural attachment points Calcium deposition at sites of greatest leaflet flexion and stress: basal and commissural attachment points Leaflet wear and/or tear Leaflet wear and/or tear In situ thrombosis In situ thrombosis Infective endocarditis Infective endocarditis Pannus formation (inflammatory tissue, rich Pannus formation (inflammatory tissue, rich in fibroblasts, at the host–graft interface) in fibroblasts, at the host–graft interface) Paravalvular regurgitation Prosthesis ‐ patient mismatch

17. What have we learned? Regurgitation has a better outcome

18. What have we learned? Large sizes have a better outcome

19. What have we learned? Quality of life is significantly improved

20. What have we learned? Self- Expandable seems to be a better choice

21. What do we fear? High implant, low left coronary ostia, long leaflet with bulky calcified nodules

22. Acute left main occlusion

23. Left Main protection during highest risk Transcatheter Aortic Valve-in-Valve procedure. A proof-of-concept Multicenter Registry. Testa L et al. Eurointervention 2015, in press

24. Is that all????

26. What have we learned? AR vs AS -1 month,23%vs5.9%, OR 4.22 (3.03-8.28), p<0.001 -12 months, 31%vs19%, HR 2.1 (1.5-4.41), p<0.001 AS vs AS + AR - 1 month, 5.9%vs10%, p=0.2 - 12 months, 19%vs17.6%, p=0.1 AR vs AS+AR - 1 month: 23%vs10%, OR 2.2 (1.1-4.8), p=0.05 - 12 months 31%vs 17.6%, HR 1.88 (1.5-3.9), p=0.01 Survival from all cause mortality

27. AR vs AS -1 month,15.3%vs4%, OR 4.01 (2.4-7.66), p<0.001 -12 months, 19.2%vs6%, HR 3.1 (2.09-8.22), p<0.001 AS vs AS + AR - 1 month, 4%vs6.4%, p=0.2 - 12 months, 6%vs10%, p=0.1 AR vs AS+AR - 1 month: 15.3%vs6.4%, p=0.1 - 12 months 19.2%vs10%, p=0.1 Survival from CV mortality What have we learned?

28. What is ahead? The need for long term follow ups (in an octuagenarians population….) The need for long term follow ups (in an octuagenarians population….) The challenge in patients at lower surgical risk The challenge in patients at lower surgical risk The availability of a fully retrievable prosthesis The availability of a fully retrievable prosthesis To minimize the rate of PAVR To minimize the rate of PAVR To minimize the rate of conduction disturbances (cost burden of PM implantation…) To minimize the rate of conduction disturbances (cost burden of PM implantation…) The integration in an evolving scenario with newer prosthesis The integration in an evolving scenario with newer prosthesis

29. Conclusions Patient selection is particularly critical when moving outside the GL/on label indication CT angiography is nowadays gold-standard TAVI is a “team sport”. Hybrid or not the “Lab” must be ready to quickly react to complications

30. Rome, IT Oxford, UK Milan, IT Anzio (RM), IT Thanks for your attention Luca Testa, MD, PhD luctes@gmail.com