Portico™ Transcatheter Aortic Valve Replacement Program CRT 2013 Hasan Jilaihawi, M.D. Raj R. Makkar, M.D. Cedars-Sinai Heart Institute Los Angeles, CA

Hasan Jilaihawi, MD, MRCP Consulting: Edwards Lifesciences, LLC, St. Jude Medical, Inc., Venus Medtech Off-Label: Discussion pertaining to transcatheter valve therapies

Portico Design Features Stent retainer tabs Leaflet commissure attachments Bovine pericardial leaflets Porcine pericardial skirt Inflow cut-outs Rounded inflow edges Outflow view

Portico Valve Design Features Both leaflets and cuff are treated with LinxTM AC treatment* Same anticalcification technology used on Epic and Trifecta surgical valves Nonflared annulus section of the stent Portico 23 mm Valve *There is no clinical data currently available that evaluates the long-term impact of anticalcification tissue treatment in humans.

Annulus sizes treated (mm) SJM Portico TAVI Valve size (mm) Annulus sizes treated (mm) Aortic diameter Height 23 19 – 21 41 50 25 21 – 23 43 52 Valve sizes 27 & 29 mm are in development and will be added to the IDE H2 2013

SJM Portico Design – Comparison Sapien / Sapien XT CoreValve Portico Technology Balloon expandable Self-expanding Placement Intra-annular Supra-annular Stent Stainless steel/ CoCr Nitinol Stent geometry Scaffold Diamond cell High density Low density Valve sizes 20 / 23 / 26 / 29 23 / 26 / 29 / 31 23 / 25 / 27 / 29 Leaflet tissue type Bovine Porcine Transfemoral delivery system 18 /19 / 22 / 24 Fr 18 Fr Transapical delivery system 26 Fr Requires sheath N/A 24 Fr (Sheathless)

SJM Portico Design – Comparison Stent retainers (2) High profile (3) Low profile Cell Density- aortic 9X2 15X4 stent integrated cell/tissue Commissures Waist V e r t i c a l T p d Vertical versus taper may facilitate annular sealing to minimize PV leak Cell Density- annulus 9X2 15X5 Medtronic CoreValve SJM Portico

Stent Design: Large Cell Geometry Large stent cells in the aortic section of the stent, allows access to coronary ostia post-implant Aortic Section Annulus Section Manoharan, G., St. Jude Medical Portico™ Transcatheter Aortic Valve Clinical Experience, EuroPCR, 05/17/2012.

Stent Design: Large Cell Geometry Large stent cells within annulus section of the stent Less metal Minimizes risk of stent strut resting against a calcific nodule More tissue Allows for tissue to conform around calcific nodules Calcific nodules

Calcific Nodule Simulation Three randomly placed nodules simulate calcification within the native aortic annulus Large cell geometry allows cuff tissue to conform around calcific nodules Calcific Nodules Potential area for PV Leak jet Speakers Notes: * This is bench testing data where three randomly placed nodules simulate calcification within the native aortic annulus. * The large cell design in the annulus section of the Portico stent allows the cuff tissue to conform around calcific nodules, minimizing the risk of PV leak. Note: Irregular “D” shape of stent Calcific Nodules Portico CoreValve

Portico: Intra-annular Placement Conformable stent frame adapts to anatomical variations and annulus calcification Leaflet geometry designed to optimally function in both round and ellipse configurations Leaflets function at partial deployment allowing for a gradual, controlled deployment while avoiding hemodynamic instability MDCT 3-dimensional reconstruction of Portico valve Speakes Notes; Portico’s conformable stent frame adapts to anatomical variations The leaflet geometry is designed to function in both round and ellipse configurations The leaflets function at partial deployment allowing for gradual, controlled deployment wile avoiding hemodynamic instability Stent eccentricity at (C) inflow level, (D) valvular level and (E) outflow level Willson A, et al. Transcatheter aortic valve replacement with the St Jude Medical Portico. J. Am Coll Cardiol. 2012;60(7):581-586

Portico™ Transcatheter Aortic Valve Portico is designed for leaflet coaptation in round and elliptical annulus configurations In-vitro testing over the valve’s use range, and in various annulus configurations to assess durability and hydrodynamic performance Circular Configuration Elliptical Configuration The Portico system is not available for sale. 

Resheathing and Repositioning Feature The unique valve and delivery system design of Portico allows the ability to fully resheath* the valve: Reposition proximally or distally*, in situ Retrieve* the valve, if necessary Resheathability is designed to enable optimized valve positioning during implantation *Until fully deployed Speaker’s notes: It is not just the valve, or the delivery system design that allows for Portico’s resheathing feature. Design elements of both the valve and delivery system provide the ability for the valve to be completely resheathed within the delivery catheter. Manoharan, G., St. Jude Medical Portico™ Transcatheter Aortic Valve Clinical Experience, EuroPCR, 05/17/2012.

Portico Valve Loading System Loading Tools include: Loading tube Loading funnel Loading base Base insert Leaflet tester Preparation and valve loading performed at room temperature Portico TF Loading Tools

Portico Transfemoral Delivery System Compatible with 18 F introducer sheath Designed for flexibility and trackability Leaflet functionality after partial deployment, allowing controlled deployment to assess: Valve placement Repositioning* Retrieval* of valve, if necessary Fully Sheathed Partially Unsheathed Functioning leaflets during deployment Majority Unsheathed *Until fully deployed

Portico Transfemoral Delivery System Distal End Protective Sheath Retainer Receptacle Radiopaque Tip Protective Sheath Marker Inner Shaft Inner Shaft Marker Band

Portico Transfemoral Delivery System Control Handle Features Deployment / Resheath Wheel — deploy clockwise 80% Release Lever Sliding Mechanism Buttons — used during valve loading Lumen Flush Port Sheath Flush Port Locking Buttons Resheath — counterclockwise

Baseline Characteristics Belfast FIH Canadian FIH n 10 11 Age, yrs 85.8±2.7 82.9±5.7 Female 100% NYHA class III (pre-TAVI) 7 8 STS score (mortality) 6.5±2.4 7.8±3.2 Logistic Euroscore 18.9±9.6 NA Aortic valve area (cm2) 0.7±0.2 0.62±0.15 Mean gradient (mmHg) 40.7±12.6 46.2±17.5 Left ventricular ejection fraction 64.4±6.8 57.3±13.8

Procedural Information Belfast FIH Canadian FIH n 10 11 Anaesthesia All under local anaesthesia All under general anaesthesia Procedure Time (mins) 54 ± 10.4 NA Multiple valves in same patient 1 Valve resheathing 2 4 Depth of implant below NCC 5.65±1.15 6.4±1.0 New Left bundle branch block New Permanent pacemaker

Clinical Safety Results Belfast FIH Canadian FIH n 10 11 5* 30D 1 yr Death Major stroke New Pacemaker Implantation Myocardial Infarction Left Bundle Branch Block 3 Aortic regurgitation over mild Minor vascular complication 1 * Total patients who have thus far met the 1 year follow up timeline “Transcatheter Aortic Valve Replacement with the St. Jude Medical Portico Valve” Willson, et al, JACC Vol. 60, No. 7, 2012, August 14, 2012:581–6

Echo Data: Mean and Peak Gradients Belfast FIH Canada FIH N=5 N=6 N=11 Changes observed from baseline to 30 days were sustained at the 12 mo follow-up

Aortic Regurgitation Belfast FIH Baseline 3 month 6 month 12 month Canada FIH n=11 n=11 n=6 n=5

Portico Transapical Delivery System 24 F outer diameter Does not require an external sheath for apical access Use of an external sheath results in a larger apex puncture site Portico Transapical Delivery System Single operator deployment / resheath wheel Protective sheath covers the valve Atraumatic, radiopaque tip

Portico Transapical Delivery System Annulus-first deployment Majority of stent can be unsheathed allowing leaflet functionality, to assess: Valve placement Repositioning Retrieval of valve, if necessary Functioning leaflets during deployment Fully Sheathed Partially Unsheathed Majority Unsheathed Transapical Portico over .035” wire Portico transapical delivery system not commercially available.

Portico TA First-in-Human Case, November 15, 2012. Drs Portico TA First-in-Human Case, November 15, 2012 Drs. Cheung and Webb, St Paul’s Hospital, Vancouver 73 yo Asian female 37 KG, 154 cm (82 lbs, 5’1”) Severe Aortic Stenosis, Preserved LV Function Prior CABG, patent grafts Moderate MR Failed TF, Sapien XT Unable to pass valve through 14F eSheath Vascular injury Esophageal Injury Recovered, considered for Transapical TAVR

Portico TA First-in-Human Case, November 15, 2012. Drs Portico TA First-in-Human Case, November 15, 2012 Drs. Cheung and Webb, St Paul’s Hospital, Vancouver

Portico Transapical FIH Extubated early post operatively Discharged POD 4 Pre-Discharge TTE Trace PVL Mean Gradient 10 mmHg Doing well 3 weeks later

Proposed Trial Design Multi-Cohort Study High Risk Extreme Risk Valve-in-Valve Registry Access (≥ 7-8 mm femoral access) Assess A-TAVR* TF Access ( ≥7-8 mm femoral access) Yes No Yes No 1:1 Randomization Non-inferiority TF A-TAVR* TF Portico 6 mm to < 7-8 mm applicable to femoral access TA Portico TA A-TAVR* 1:1 Randomization Non-inferiority Yes No 1:1 Randomization Non-inferiority Portico TF Registry Portico TA Registry TF Portico TF A-TAVR* *A-TAVR: Approved TAVR valve 28 CONFIDENTIAL

Portico Program Status 23mm TF: CE Mark approved 23mm TA: FIH series completed 25mm TF: Enrollment in EU clinical trial underway 27/29mm: EU clinical trial enrollment 1H 2014 US IDE: Submitted Q4 2012 US clinical trial to commence in 2H 2013

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