1. Institut de Cardiologie de Montreal
Design and Product Development of the Self-Expanding Transcatheter Valve Technology
Raoul Bonan, MD
Institut de Cardiologie de Montreal

2. Presenter Disclosure Information Raoul Bonan, MD
Scientific Advisory Board and/or Consultant
CoreValve/Medtronic
Clinical Research Agreements
Multiple Medical Device Clinical Investigations
Including CoreValve

3. Clinical Challenges in TAVI
Clinical Need
Design Challenge
Access, even in patients with small or challenging vasculature
Low delivery profile
Alternative—non-femoral—access
Positioning, even in angulated or otherwise challenging anatomies
Step-wise deployment with ability adjust and refine valve position
Conformability to a wide range of patient anatomies—annulus size, shape, calcification
Full range of valve sizes
Conformability at the annulus with circularity at level of valve function
Durability long-term hemodynamic and structural integrity
Optimal tissue selection for strength, pliability and thinness
Frame designed to reduce leaflet stress 1 2 3 4

4. CoreValve® System Components
18Fr AccuTrak® catheter delivery system
Self-expanding Nitinol frame with porcine pericardial valve
Disposable valve loading system

5. CoreValve Evolution: Past to Present
2004
2005
2006
2007
Gen 1
25F
8 mm
Gen 2
21F
7 mm
Gen 3
18F
6 mm
25Fr
21Fr
18Fr

6. Frame Material Selection - Nitinol
Superelasticity
Shape Retention
Proven
Performance
Compact designs and small delivery systems
Self-anchoring without balloon expansion
Controlled retraction for precise delivery and placement
Maintain valve shape
Resistant to corrosion
Low thrombogenicity
Conformable to patient anatomy
Fatigue performance
Nitinol is a equi-atomic nickel-titanium metallic alloy that possesses unique properties:
Superelastic and can be stretched over 10% and still return to its original length; this quality enables:
Compact designs and small delivery systems
Retains shape after thermal or mechanical stress, allowing:
Self-anchoring without balloon expansion
Controlled retraction for precise delivery and placement
Well-established history of biocompatibility for use in implantable medical devices that makes it:
Resistant to corrosion
Possess low thrombogenicity qualities
Comformable and compliant to patient anatomy
Fatigue performance is well understood 6 6

7. Testing to Demonstrate Frame Durability
CT Deformation Data
Combined Loading
FEA
--Focus--
Transverse Strain
Longitudinal Strain
600M Cycle Device
Level Fatigue Test
Linear eT
DeT
DeFL
600M Cycles Device
Radial eL
DeL
Diamond Coupon
(90%, 95%)
600M Cycle Material Test
Frame durability has been demonstrated by utilizing the schema proposed by the ISO 5840 task force.
CT data was used to determine deformations seen in the device. These deformations were used in a finite element model to determine maximum strain levels.
A thorough series of device level testing was conducted in order to demonstrate the durability of the device as well as material characterization testing.

8. Tissue Selection: Porcine Pericardium
Ultimate Tensile Strength Far Exceeds Peak Physiological Stress
Compared side by side, porcine and bovine pericardium are statistically equal in
strength:
Both ultimate tensile strength and suture pull out stress measures are nearly equal.
Both are significantly stronger than peak physiological stresses encountered in vivo.
Sacks MS. Uniaxial mechanical and structural properties of bovine versus porcine pericardial tissue. Medtronic Data on File.
Garcia Paez JM, Carrera A, Herrero EJ, et al.. J Biomater Appl. 2001;16:68-90.
Li, K and Sun, W. Ann Biomed Eng Aug;38(8):

9. Tissue Selection: Porcine Pericardium
Bending Stress More Relevant to Valve Durability
We propose that the more critical factor for long term valve durability in transcatheter valves is cyclic bending stress rather than ultimate tensile strength.
This slide compares bending stresses seen in porcine pericardium and bovine pericardium.
The stresses seen in bovine pericardium are higher than those seen in porcine pericardium.
Medtronic, data on file.

10. Leaflet Geometry Reduces Stress
Areas of high stress can induce collagen degeneration that over time could lead to tearing and valve failure1
Valve designs that reduce leaflet stresses “are likely to have improved performance in long-term applications”2
17 mm tall
14 mm tall
Reducing stress on valve leaflets is critical to valve durability because areas of
high stress can induce collagen degeneration that over time can lead to valve
tearing and failure.
Additionally valve designs that reduce leaflet stresses “are likely to have improved
performance in long-term applications”.
In the case of CoreValve, FEA demonstrates a 12% lower stress rate over shorter, traditional valve designs.
12% Lower Stress In 17 mm Valve
Schoen Frederick. J Cardiac Surg.1987;2:
Sun W., Li K., J Biomech. 2010;43:

11. Wear Testing Demonstrates Excellent Valve Durability
Accelerated wear testing (AWT) was performed on 24 valves (12 of each size) in both circular and elliptical configuration
Minimal macroscopic valve wear evident after 200 million cycles (5 years)1
Bench testing corroborates FEA’s and clinical data on valve durability:
Medtronic performed accelerated bench testing on 24 valves – 12 of each size – in both circular and elliptical deployments.
Valves were cycled for 200 million times, the equivalent of 5 years.
The result was minimal macroscopic wear seen after 200 million cycles.
Data on file at Medtronic

12. CoreValve Tissue Examination After 200M Cycles (5 years)
Histology performed on individual CoreValve leaflet samples after 200 million cycles:
No evidence of internal pericardial leaflet delamination or collagen loss
The laser-cut free margins were fully intact in these sections1
Post accelerated wear testing histopathlogy also showed no evidence of wear:
No evidence of pericardial leaflet delamination or collagen loss.
The laser cut free margins were fully intact.
outflow
inflow
Figure 1. Leaflet as received
Figure 2. Slices submitted for histopathology
Figure 3. The pericardial leaflet section is intact
Data on file at Medtronic

13. PAV Design: Three Levels
Outflow Portion
Low Radial Force
Sits in ascending aorta
Provides PAV alignment
Supra-annular leaflet function
Designed to avoid coronaries
Constrained Portion
(with valve leaflets)
High Hoop Strength
The CoreValve PAV was designed specifically for percutaneous implantation.
Non-cylindrical frame design incorporates three discrete levels into a single construct and exhibits three separate diameters and three completely different degrees of radial and hoop strength.
The inflow portion of the frame exerts higher radial force to ensure secure anchoring in the native aortic annulus.
The compliant nature and constant outward force from the self-expanding frame conforms to the patient annulus while maintaining a sealing surface that minimizes paravalvular leak.
The center portion of the frame is designed to resist size and shape deformation that is seen. The radial force characteristics of the frame act to decouple the valve from distortion in the annular region
The valve leaflets of the bioprosthesis are suprannular. Additionally, the concave design allows for blood flow to the coronary arteries.
The outflow portion exerts only low radial force in order to accommodate the ascending aorta. The primary purpose of the outflow portion is to assure optimal flow-orientation.
High Radial Force
Inflow Portion
(with skirt)
Intra-annular anchoring
Conforms to native annulus
Minimizes paravalvular aortic regurgitation
Photograph provided by Piazza, Serruys, and DeJaegere 13 13

14. Supra-Annular Valve Minimizes Prosthetic Valve Ellipticity
Flexible frame conforms to native annulus shape while maintaining bioprosthesis in a higher position
Decoupling of valve from native annulus minimizes ellipticity at the valve height 1
Frame is designed to maximize valve performance by ensuring that the valve maintains its shape while conforming to patient anatomy.
Data on file at Medtronic

15. CoreValve ® Full Range of Valve Sizes
Outflow: mm
Constrained : mm
Inflow:
26mm Valve
29mm Valve
31mm Valve
Annulus Size (mm)

16. CoreValve Bioprosthesis
Photograph provided by Piazza, Serruys, and DeJaegere
Vertical distance from node to node ~ 4 mm
Skirt height = ~ 12 mm 16 16

17. Valve Visualization Optimal placement of the valve is 6 mm
Between the 1st and 2nd contact point being implanted within the aortic annulus
Note the radiopaque contact points. Counting from the Inflow edge of the frame, each s is 4 mm in vertical distance
The entire skirt portion is 12mm including the scalloped portion
Optimal Implantation Range

18. Self-Expanding Frame Leads to Superior Ease of Use and Potentially Better Outcomes
No rapid pacing required
Physician can take time to deploy properly
Can adjust valve position through the procedure
Can witness valve function before releasing
No trauma to the valve leaflet from a balloon
Ease of use is critical to procedural success
Need to have short term success in order to have long term success
Procedural success in not a small thing. Ease of use is critical.

19. Medtronic CoreValve Revalving System: « a true 18Fr system » for the 3 sizes
Delivery System
Self expanding PAV that is deployed via an 18F delivery system.
PAV is loaded with CLS.
New AccuTrak delivery system. Designed to improve precision of placement.
Compression Loading System
Percutaneous Aortic Valve

20. AccuTrak® Delivery System
AccuTrak® Stability Layer
7mm
15Fr Fr Fr
Over-the-wire compatible
18Fr delivery system for all
valve/annulus sizes and access routes
Annulus Size (mm)

21. AccuTrak® Stability Layer
Inner Shaft
Retractable Shaft
AccuTrak ® Stability Layer

22. CoreValve® Access Options
Direct Aortic
Subclavian
Transfemoral

23. COREVALVE INNOVATION A look at the past 18 months
AccuTrak Stability Layer
Size Expansion
Subclavian and Direct Aortic Indication

24. COREVALVE INNOVATION A look forward to the next 18 months
23 mm Valve
Next generation delivery system
Anti Mineralization Treatment AOA®
Catheter length for alternative access
TAVI specific guidewire
Repositionable

25. Summary
The CoreValve® system was designed as a transcatheter solution with the goals of optimizing device functionality and total device durability
Valve durability has been demonstrated through:
F.E.A. to optimize leaflet stresses and tissue bending
AWT in circular and non-circular conditions
Frame durability has been demonstrated through:
Comprehensive, 3D characterization of in vivo deformations
F.E.A. for combined primary loading modes
Highly-controlled, high cycle material fatigue testing completed
Long-term frame fatigue testing for primary loading modes
18 Fr catheter compatible with multiple access 25 25

26. Slide Title
Level One bullet
Level Two bullet
Level Three bullet

27. CoreValve Bioprosthesis: Two Sizes
“Small”
“Large”
55 mm
53 mm
Height
40 mm
43 mm
Outflow
24 mm
22 mm
Constrained
Purpose:
26 mm
29 mm
Inflow
20 mm to 23 mm
23 mm to 27 mm
Accomodates Annulus of: 27 27

28. Stepwise deployment maintains continuous pressure and obviates the need for rapid pacing
Normal blood pressure before annular contact
Reduced blood pressure only between 1/3 & 2/3 of the deployment
At 2/3 point, BP returns to normal and valve is still repositionable
Sapien or any other Balloon deployable Valve can never do that. Once they start deploying, they have to go all the way, and quickly.

29. 18 French Procedural Progress
Evolution to true percutaneous procedure
Local anesthesia
Beating heart procedure
Oct. 2006
Nov. 2006
18 French Safety & Efficacy Study
General anesthesia
Dec. 2006
Surgical cut-down/repair
Ventricular assistance

30. CoreValve ® Full Range of Valve Sizes
Outflow: mm
Constrained : mm
Inflow:
26mm Valve
29mm Valve
31mm Valve
Annulus Size (mm)