1. Improved Technology: Evaluating Device Modifications
Rhonda Robb
Medtronic

2. Conflict of Interest
Employee of Medtronic, Inc.

3. Cautionary Statement
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 are not commercially available in the US or any other part of the world. Final design may differ materially from that presented.

4. CoreValve Experience Innovation & Evidence Fuel Growth New Markets
Serving Patients in Over 60 Countries US
Japan
Canada
Chile
Ukrane
S. Korea
Mexico
India
Taiwan
2007
2008
2009
2010
2011
2012
Improved Delivery
AccuTrak
Expanded Populations
Valve-in-Valve and TA
New Access Options
DA and Subclavian
Expanded Treatment Range
31mm and Evolut 23mm

5. Valid Scientific Evidence
Changfu Wu, PhD
FDA at DMD 2012

6. Computational Modeling
Valve durability:
F.E.A. to optimize leaflet stresses and tissue bending
AWT in circular and non-circular conditions
Frame durability:
Comprehensive, 3D characterization of in-vivo deformations
F.E.A. for combined primary loading modes
Highly-controlled, high cycle material fatigue testing
Long-term frame fatigue testing for primary loading modes

7. Bench Testing Delivery System Testing: Valve Testing:
Hydrodynamic testing
Valve durability testing to 200M cycles
Frame structural integrity testing to 600M cycles (15 year in vivo equivalent)
Loading simulations
Delivery System Testing:
Dimensional/Physical attribute testing
Tensile strength to verify catheter integrity
Catheter track testing through tortuous anatomies
Simulated use testing with physicians
Full system biocompatibility

8. Animal Study Acute and chronic animal studies No aortic stenosis model
Deliverability – acute
Implant performance; 30, 90, 180 d
No aortic stenosis model
Additional tools to augment
Visible Heart Lab for in vivo simulation
Perfused Cadaver
Animal models can often be used to bolster bench testing to show additional safety signals.
We use them in two ways:
First to understand acute performance of delivery and deployment
Secondly to look at chronic effects/performance of the implant at multiple timepoints. We then harvest and perform histopathology
Unfortunately there is not an animal model that provides aortic stenosis, so efficacy is not able to be determined.
We are also able to look at a number of other simulated animal/cadaver models to look at acute performance as well

9. Clinical Trial: CoreValve® US Pivotal
Medtronic CoreValve US Pivotal Trial
Up to 45 Sites
Estimated Enrollment: 1497
Up to 687
790
Extreme Risk Cohort
High Risk Cohort
Iliofemoral Access?
Randomization 1:1 No
Yes
Up to 200
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

10. Clinical Data Confirm Efficacy and Optimize Practice
Expand Access to New Populations and Markets
Augmenting with all of our international clinical data
Demonstrate Safety and Efficacy 10

11. CoreValve Study Timeline
First Implants
Dec 2010
Commercial Release
Continued Access
ER Enrollment
Complete
Jan 2012
ER FU Complete
Feb 2013
SURTAVI US Start
Continued Access
HR Enrollment
Complete
Aug 2012
HR FU Complete
Sep 2013
Expanded Use: Low output/low gradient, severe MR/TR, ESRD
ViV
DA & SC Access
CoreValve
31 mm
CoreValve Evolut 23mm
AOA Anti-Calcification
AccuTrak
Delivery System
EnVeo Delivery System

12. Medtronic TAVI Future Developments
Today
CoreValve Evolut R
EnVeo R w/InLine Sheath
23/26/29/31
EnVeo™
Delivery System
Engager™
TAVI System
Next
Future TAVI Platform
Future Mitral
Advanced Tissue
&
Self Expanding
Frame Constructs
Procedural Solutions
Compatible with CoreValve Evolut & CoreValve Legacy
26/29/31 mm
Transapical and Direct Aortic TAVI system
Adaptive Sheath, Guidewire

13. Evaluating Device Modifications
RCT to SOC
High
Single - Arm
OPC
TVT
Degree of Change
Medium
Speed of Innovation,
Market Forces, Ability to Execute
Bench
Low
Low
Medium
High
Degree of Risk

14. Challenges/Opportunities for Novel Devices
Guidance documents and precedents
Development of increasingly relevant pre-clinical testing
Risk Analysis to define/analyze potential adverse events
Suitability of animal models
Innovation moving faster than our ability to study
Economics of current clinical path
Risk analysis – if it’s a truly novel device, than not all risks will be identified until clinical – may cause redesign of product which has happened with most TAVI designs to date. Clinically relevant testing models difficult to develop and validate e.g. determining appropriate device loading modes without clinical data. How do we prove that strains are clinically relevant in the absence of clinical data for novel products?
Animal models are not suitable for TAVI designs. Alternative option of modifying device to allow evaluation in animals.
Long term nature of clinical evaluation means that we are coming to mkt in US with Gen 1 when Gen 2 or 3 is available in EU. Need mechanism to bridge to new iterations to accelerate innovation.

15. Thank You