1. Technology Update and Status of Current Clinical Trials
Rhonda Robb

2. Conflict of Interest
Employee of Medtronic, Inc.

3. 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.

4. 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.

5. 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 patients have been studied in independent registries.
Independent
3,010 patients

6. 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 12 months (compare to perf goal)
Primary Endpoint: All-cause 12 months
CAUTION—Investigational device. Limited by federal (or United States) law to investigational use.

7. 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.

8. 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

9. 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

10. 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 24 months
CAUTION—Investigational device. Limited by federal (or United States) law to investigational use.

11. 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

12. 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.

13. 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)

14. 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

15. 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