A Review of All Available Self-Expanding Transcatheter Valve Clinical Results Ganesh Manoharan Consultant Cardiologist Regional Cardiology Department Royal Victoria Hospital Belfast, UK

Disclosures I am a consultant for: St. Jude Medical Medtronic CardioVascular GDS Inc

Self-Expanding TAVR Systems Clinically approved (European CE Mark) Transfemoral (+Other Access Route) Transapical Emerging Systems Transfemoral

Transfemoral (+Other Access)

Medtronic CoreValve System Trileaflet heart valve Tissue valve sutured to frame Single layer of porcine pericardium

CoreValve ® Full Range of Valve Sizes 26mm Valve 29mm Valve 31mm Valve 20 21 22 23 24 25 26 27 28 29 Annulus Size (mm) AccuTrak® Stability Layer 7mm 15Fr 12Fr 18Fr Over-the-wire 0.035 compatible 18Fr delivery system for all valve/annulus sizes and access routes 20 21 22 23 24 25 26 27 28 29 Annulus Size (mm)

Supra-Annular Valve Design Flexible frame conforms to native annulus shape while maintaining bioprosthesis in a higher position This decoupling of the valve from native annulus shape minimizes the impact of ellipticity at the valve level post deployment1 Data on file at Medtronic

CoreValve® Access Options Direct Aortic Subclavian Transfemoral

Pacemaker Implantation Varies Between Studies Procedural variability, anatomical differences and clinical practice variation impact pacemaker implant rates:9,10 Depth of implant may induce conduction disturbances11 Valvuloplasty balloon size may impact conduction system11 Anatomical and patient-related factors may impact conduction disturbances12 Inter-hospital variability due to physician subjectivity, country-based healthcare norms and reimbursement strategies9 1. Medtronic Data on File. COR 2006-02: 18 Fr Safety& Efficacy Study Re-Analysis, August 14, 2009. 2. Meredith IT. A Snapshot from the Ongoing Australia-New Zealand Medtronic CoreValve® Registry. Transcatheter Cardiovascular Therapeutics 2009, September 21-25, 2009. San Francisco, CA. 3. Avanzas P, Munoz-Garcia AJ, Segura J, et al. Percutaneous implantation of the CoreValve® self-expanding aortic valve prosthesis in patients with severe aortic stenosis: early experience in Spain. Rev Esp Cardiol. 2010;63:141-148. 4. Eltchaninoff. French Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France. 5. Bosmans. Belgian Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France. 6. German Registry data on file. New pacemakers with Corevalve 240/565. 7. Ludman. UK Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France. 8. Petronio. Italian Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France. See Reference slide for sources 1-8 See Reference slide for sources 1-8 See Reference slide for sources 1-8 9. N. Piazza, “AV-Block and Pacemaker Requirements Associated with Medtronic CoreValve TAVI: Incidence, Outcomes and Treatment Strategies”, TCT 2009. 10. Latsios et al. Device Landing Zone” Calcification, Assessed by MSCT, as Predictive Factor for Pacemaker Implantation after TAVI. Catheter Cardiovasc Interv. 2010 [Epub ahead of print]. 11. N. Piazza, “AV-Block and Pacemaker Requirements Associated with Medtronic CoreValve TAVI: Incidence, Outcomes and Treatment Strategies”, TCT 2009. 12. N. Piazza, “Persistent Conduction Abnormalities and Requirments for Pacemaking 6 Months after TAVI”, PCR 2010. 9 9

Medtronic CoreValve® System Subclavian and Direct Aortic Approaches Summary of Clinical Experience UC201104698a_EE1P

Subclavian Access: CoreValve® System Procedure Success Note: Procedure success definition varies among publications 1. Petronio AS. Italian Experience Subclavian vs. Transfemoral. Presented at TCT 2011. 2. Laborde JC. TAVR Access Site Considerations. Presented at TVT 2011. 3. Verkroost MWA. TAVI Using Left Subclavian Route. Presented at TCT 2011. 4. Modine T. TAVI using Axillary/subclavian Access. J Thorac Cardiovasc Surg. 2011; 141(2).

Subclavian Access: CoreValve® System 30D Survival 1. Petronio AS. Italian Experience Subclavian vs. Transfemoral. Presented at TCT 2011. 2. Gilard M. France 2 Registry. Presented at TCT 2011. 3. Blackman D. UK Registry Comparison valve type and access approach. Presented at TCT 2011. 4. Verkroost MWA. TAVI Using Left Subclavian Route. Presented at TCT 2011. 5. Modine T. TAVI using Axillary/subclavian Access. J Thorac Cardiovasc Surg. 2011; 141(2).

Direct Aortic Access: CoreValve® System Dataset A standard dataset was circulated to 19 centres who were believed to have carried out 3 or more cases in their individual centre. A total of 115 cases had been performed in these 19 centres prior to 31/12/11 To date, a completed dataset has been returned from 12 of these centres

Results (N=93) 30 day Mortality In-hospital Stroke 9/93 (9.7%) In-hospital Stroke 3/93 (3.2%) Thoracic Aortic Dissection 0/93 (0%) Life Threatening Bleed (VARC) 4/93 (4.3%) Major Vascular Injury (VARC) Conversion to Full Sternotomy New Permanent Pacemaker 16/93 (17.2%)

CoreValve® US Pivotal Trial Study Design1-3 Extreme Risk Cohort High Risk Cohort CoreValve Observational CoreValve Single Arm SAVR Iliofemoral Access? Up to 100 Randomization 1:1 395a 395 790 487 No Alternative Access Medtronic CoreValve US Pivotal Trial Up to 45 Sites Estimated Enrollment: 1497 Yes Up to 587 aIncludes patients with iliofemoral and alternative access. SAVR=surgical aortic valve replacement. 1. Medtronic CoreValve® U.S. Pivotal Trial. US National Institutes of Health Web site. http://clinicaltrials.gov/ct2/results?term=NCT01240902. Accessed 6/30/11. 2. Medtronic CoreValve® U.S. Pivotal Trial (Extreme Risk Patients). Version 7.0. Mounds View, MN: Medtronic, Inc. Clinical Research; 2011. 3. Medtronic CoreValve® U.S. Pivotal Trial (High Risk Patients). Version 6.0. Mounds View, MN: Medtronic, Inc. Clinical Research; 2011. References: Medtronic CoreValve® U.S. Pivotal Trial. US National Institutes of Health Web site. http://clinicaltrials.gov/ct2/results?term=NCT01240902. Accessed 6/30/11. 2. Medtronic CoreValve® U.S. Pivotal Trial (Extreme Risk Patients). Version 7.0. Mounds View, MN: Medtronic, Inc. Clinical Research; 2011.

Transapical System Approved for Clinical Use in Europe (CE Mark)

Jena Valve Ensures Coronary Flow -low profile Maintains haemodynamics during deployment Feeler guided anatomical positioning Active fixation -Unique Jena Clip Partially retrievable and repositionable

Jena Valve Described as a 2nd generation TAVR device Potential advantages: Feeler guided anatomical positioning Clip fixation on native leaflet Device retrievability CE mark in September 2011

Clinical Research Programme FIH CE Mark Study Post-market Proof of concept Germany (Leipzig) 12 patients enrolled (July 2009 - April 2010) Demonstrate safety and efficacy Germany (7 centres) 73 pts(Nov2010-July2011) FU ongoing Primary endpoint: 30D mortality Evaluation in real world European centres Approx 150 pts

Enrolled N=73 Withdrwan N=6 Procedure Initiated N=67 30 day FU N=66 Withdrawn=1

Symetis Acurate TA System

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Emerging Technologies with Clinical Data

Heart Leaflet Technology

Direct Flow Medical Valve

Medtronic Engager Valve Bovine pericardial valve 3 support arms for fixation at the valve leaflets Nitinol frame for sealing in the LVOT

Sadra-BSC Lotus Valve Locking mechanism Bovine pericardium Nitinol frame Adaptive seal Radial expansion with axial compression

Overview: SJM Portico 23mm Valve St Jude Medical Portico Valve Overview: SJM Portico 23mm Valve General 18F (TF) Nitinol self expanding valve designed to be: Fully re-sheathable* Repositionable* (antegrade and retrograde) at the implant site Retrieveable* Bovine and porcine pericardial valve with Linx™ anti-calcification technology** For annulus range: 19 – 21 mm Cuff tissue and stent geometry designed to minimize PV leak Implanted transfemorally without need for rapid pacing * Until fully deployed ** There is no clinical data currently available that evaluates the long-term impact of anti-calcification tissue treatment in humans.

Access N Procedure success Complication Results Current Status Device Access N Procedure success Complication Results Current Status Heart Leaflet Technology TF 9 N=5 X4 Tamponade Death=3 Devise redesign: animal planned Direct Flow Medical (22F) 31 N=20 X9 not done X2 surgical conversion Death = 2 71% survive at 2 yrs 18F system under evaluation Medtronic Engager TA 10 N=10 X2PPM Mortality=1(at FU) Pivotal study to start Sadra-BSC Lotus (18F) 12 NA Reprise I (S&E) and Reprise II (CE Mark) to start St Jude Portico (18F) None at 30D European CE Mark study started Dec 2011

Conclusions TAVR landscape with self expanding technologies is expanding Standardisation of event reporting (VARC) will allow more transparent comparisons to be made Technological iterations will further enhance the safety and efficacy of this technique Long term durability and outcome awaited