Technology Update and Status of Current Clinical Trials Rhonda Robb

Conflict of Interest Employee of Medtronic, Inc.

Cautionary Statements CoreValve is an Investigational device. Limited by federal (or United States) law to investigational use. Future TAVI systems are not currently available in the USA for clinical trials or for commercialization. Non- USA clinical evaluation for Engager is in progress. Not available for sale. These photographs, statements, and drawings pertain to new technology in clinical research and is not commercially available in the US or any other part of the world. Final design may differ materially from that presented.

Medtronic CoreValve® Available in >50 countries >26,000 patients 23MM & 31MM expand treatable patient population 18-29MM annulus w/18 Fr system for all valve sizes Direct Aortic CE Mark Japan Clinical Trial Start The level of enthusiasm that we are seeing across the world for CoreValve is exceptionally high – the design and self expandable technology are at the heart of what physicians experience in terms of exceptional deliverability, implantability and conformability ~ all of which support the success we are experiencing. Self-expandable platforms are the technology of choice for Transcatheter Aortic Valves. Only self‐expandable platforms can offer controlled deployment, repositionability and recapturability – all of which are critical for optimal implants and clinical outcomes, and highly desirable attributes for experienced implanters. The self expanding frame is designed with in-flow radial force to prevent device migration, conform to the native annulus, which mitigates paravalvular leaks – inherently, the self expanding design also prevents trauma to the valve leaflets. Porcine pericardial tissue and design enables full valve function prior to final release to enable evaluation and adjustment. Supra annular function delivers optimal hemodynamics while intra-annular sealing skirt minimizes paravalvular leaks. CAUTION—Investigational device. Limited by federal (or United States) law to investigational use.

CoreValve® System Clinical Experience Study Study Size 30 - d 6-mo 1 Y 2 Y 3 Y 4 Y 21 Fr EU Safety & Perf Study 52 18 Fr EU Safety & Perf Study 126 Australia-New Zealand Registry 400 REDO Study 18 ADVANCE Study 1000 ACC US Pivotal Trial 1497 Underway Japan Pivotal 50 ADVANCE II 150 SurTAVI >1800 2012 start Belgian Registry 297 UK Registry 460 Italian Registry 772 French Registry 785 Spanish Registry 108 German Registry 588 Medtronic Sponsored ACC 5,093 patients Key Message: The CoreValve® System has significant global experience, and more than 2000 patients have been studied in independent registries. Independent 3,010 patients

CoreValve® US Pivotal Enrollment Complete --------------- Medtronic CoreValve US Pivotal Trial Up to 45 Sites Estimated Enrollment: 1497 Up to 687 790 Extreme Risk Cohort High Risk Cohort Enrollment Complete --------------- Continued Access Available Iliofemoral Access? Randomization 1:1 No Yes Up to 100 487 395a 395 CoreValve Observational CoreValve Single Arm CoreValve SAVR Alternative Access Primary Endpoint: All-cause mortality or major stroke @ 12 months (compare to perf goal) Primary Endpoint: All-cause mortality @ 12 months CAUTION—Investigational device. Limited by federal (or United States) law to investigational use.

CoreValve® US Pivotal Through January, ~10,000 minutes of screening calls 42 heart teams implanting >1,000 patients enrolled in 12 months 40 heart teams contributed to Extreme Risk; 24 enrolled >10 patients National PI’s: J Popma, MD, D Adams, MD Screening Committee: D Adams, J Byrne, J Conte, T Gleason, J Popma, M Reardon, S Yakubov Steering Committee: D Adams, W Anderson, M Buchbinder, J Byrne, B Carabello, J Coselli, M Deeb, J Hermiller, J Popma, M Reardon, P Serruys, S Yakubov CAUTION—Investigational device. Limited by federal (or United States) law to investigational use.

World Class Training and Education Technology All heart teams go through consistent 5 stage training process Dynamic, state-of-the-art simulation systems Case observation & skilled proctor guidance Centralized imaging consultation; dedicated case field support infrastructure Access Critical Skills Curriculum Safe growth, procedural success a top priority

Evaluate Long-term Performance & QOL Evaluate Procedural Best Practices Evaluate Performance in Expanded Patient Populations Strategic Intent: Expansion of TAVI to a broader patient population (intermediate risk) Global trial; including conduct under US IDE Sites with at >30 implants; proven ability to randomize Targeted start early 2012 CoreValve CE Pivotal Trial CoreValve ADVANCE II Registry CoreValve SURTAVI Pivotal Trial CoreValve ANZ Trial CoreValve REDO Study CoreValve ADVANCE Registry CoreValve ADVANCE DA Study CoreValve US Pivotal Trial CoreValve Japan Trial SUrgical Replacement And Transcatheter Aortic Valve Implantation This is an open, prospective, randomized multicenter non-inferiority clinical trial comparing Surgical Aortic Valve Replacement (SAVR) versus Transcatheter Aortic Valve Implantation (TAVI) for patients with (symptomatic) Aortic Stenosis. The purpose of this study is to assess the optimal treatment strategy for patients with symptomatic, severe Aortic valve Stenosis (AS) at intermediate risk by randomizing patients to either Surgical Aortic Valve Replacement (SAVR) or Transcatheter Aortic Valve Implantation (TAVI) with the Medtronic CoreValve System. A total of 1100 patients with symptomatic severe aortic stenosis will be enrolled in the randomized trial (550 TAVI, 550 SAVR). 1000 patients will be included in the registry sub-studies. ≥ 70 years and ≥2 but ≤4 risk factors ≥75 years and ≥1 but≤3 risk factors ≥80 years ≤2 risk factors Primary endpoint: The event free survival of the composite of all cause mortality and major stroke (according to VARC) at a median follow-up duration of 2 years. Secondary endpoints: Composite of all-cause mortality and major stroke at 30 days, 1, 2, 3, 4, and 5 years. All-cause mortality at 30 days, 6 months, 1, 2, 3, 4, and 5 years. Major stroke at 30 days, 6 months, 1, 2, 3, 4 and 5 years. Myocardial infarction according to VARC (Peri-Procedural, and Spontaneous at 30 days, 6 months and 1, 2, 3, 4, and 5 years) Combined Safety Endpoint (at 30 days) (according to VARC) Combined Efficacy Endpoint (at one year) (according to VARC) Device success (according to VARC) Permanent pacemaker implantation or intracardiac defibrillator (ICD) implantation Quality of Life (EQ-5D ) at 1 month, 3 months, 6 months and 1, 2, 3, 4 and 5 years The plan is for this to be an IDE in the US The FDA is requiring participating centers in the US to have at least 30 TAVI implants under their belts We hope to start the Surtavi trial in the US at the start of the calendar year So……..to even be considered for this trial, you will need to have at least 30 implants completed. Of course no promises should be made, but this could really help with our IDE enrollments. Some sites will have one more motivator to enroll patients faster. Engager CE Pivotal Trial CAUTION—Investigational device. Limited by federal (or United States) law to investigational use. 9

Global STS mortality risk ≥4% and ≤10% SURTAVI Heart Team Evaluation including assessment for significant CAD with determination of need for revascularization Meet I/E Criteria and eligible for SAVR and TAVI QoL Questionnaire Chairmen: Prof. P.W. Serruys (Chair), Dr. N. van Mieghem (Deputy Chair) Europe: Prof. S. Windecker, Prof. A.P. Kappetein, Prof. R. Lange, Prof. T. Walther US: David Adams, Jeff Popma, Michael Reardon Randomization with 5 year follow up Neurological Assessments Presence of significant CAD with intended revascularization No intended revascularization TAVI + PCI SAVR + CABG TAVI SAVR Primary Endpoint: All-cause mortality or major stroke @ 24 months CAUTION—Investigational device. Limited by federal (or United States) law to investigational use.

Next Generation TAVI Patient Segments: High and Extreme Risk Intermediate Risk Failed Bioprosthesis Overall Design Goals: Advance Durability Reduce Heart Block < 10% AR/PVL < 1+ Reduce Vascular Complications Improve Ease of Use OD Profile Reduction TECHNOLOGY UNDER DEVELOPMENT 11

Future Self-Expanding Designs EngagerTM CE Pivotal Underway Treated Bovine Pericardium w/Supra Annular Valve Function Self Positioning; Controlled Release w/Accuracy PI’s: J Vanoverschelde MD, PhD  V Falk, MD Started Sept 2011, 11 sites Broad Polyester Skirt to Prevent PVL Transapical or Direct Aortic Delivery CAUTION—Investigational device. Limited by federal (or United States) law to investigational use.

Future Self-Expanding Designs Optimize Profile and Outflow Design Based on Anatomical Data Treated Porcine Pericardium with Supra Annular Valve Function Repositionable for Positioning Accuracy Transfemoral, Subclavian & Direct Aortic Access Routes Profile Reduction Across Platform (true 16Fr OD)

Procedural Solutions Embolic Protection Dedicated Guidewire for increased Safety and Stability Advanced Imaging to Aid Valve Positioning and Sizing Valvuloplasty Balloon to Prepare Landing Zone; Reduce PVL Medtronic is dedicated to improving the clinical outcomes for the entire procedure, not just the valve itself. We are investing in a number of technologies which will improve clinical outcomes and decrease complications all while being easy for the user. Areas of focus and investment include: Embolic Protection to decrease the chance of an embolic event. To reduce the chance for ventricular perforation, a guidewire specifically designed for TAVI. To reduce Vascular complications, along with profile reduction in our delivery systems, we are looking at expandable introducer sheaths and large bore closure systems. And we know imaging plays a critical role in procedure success. We are partnering with the major imaging companies to develop software tailored to our device specifications. Large Bore Closure and Expandable Sheaths to Reduce Vascular Complications 14

Conclusions CoreValve Clinical Program Making Very Strong Progress MDT investing significantly in Innovation CoreValve design provides flexibility for innovation (alternative access, 23 and 31mm) all on a proven platform Self Expanding as Platform of Future to serve unique patient and MD needs Experience based on >26,000 TAVI implants to date and growing