1. CRT 2010
Washington DC, January 21, 2010
The durability of Transcatheter Valves should be the same as Surgically Implanted Valves?
Eberhard Grube, MD, FACC, FSCAI
St.Elisabeth Hospital, Essen, Germany
Heart Center Rhein-Ruhr
Instituto Cardiologico Dante Pazzanese, São Paulo, Brazil

2. Eberhard Grube, MD DISCLOSURES Consulting Fees Honoraria
Abbott Vascular, Boston Scientific Corporation, Cordis, a Johnson & Johnson Company, Medtronic CardioVascular, Inc.
Honoraria
Biosensors International , Boston Scientific Corporation, Medtronic CardioVascular, Inc
Ownership Interest (Stocks, Stock Options or Other Ownership Interest)
Biosensors International , Medtronic CardioVascular, Inc.
I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation.
I intend to reference off-label use of stents and valve prosthesis.

3. Surgical Replacement is the Gold Standard today
But the “Gold Standard’ has seen evolution over the years:
First Mechanical Valves
Then Biological Tissue Valves
And in the Future, Transcatheter Valves?
We need to leverage learning from these last two waves of evolution in order to not repeat the mistakes of the past 1 2 3

4. Surgical Replacement Durability in Context
Valves released with equivalent of 5 years on accelerated wear tester (200M cycles)
Current valves on the market are 3rd, 4th, or 5th generation from the various manufacturers
Pericardial tissue valves have 20 years of patient experience

5. Considerations for TAVI Durability
Nitinol (Nickel Titanium) Frame
Tissue Leaflet Construction
Tissue Leaflet Anti-Calcification Treatment
Testing Conditions
Understanding the dynamic nature of the interaction between the frame and the anatomy

6. Frame Design Diamond cell configuration
Nitinol: memory shaped/no recoil
Material used in medical devices for years with low fracture incidence
Pre-clinical testing equivalent of 15 year (600M cycles) with clinical equivalent loads, stress, and compression

7. Leaflet Design
Valve height and construction designed to reduce leaflet stresses and accommodate non-circular LVOT and annulus

8. Anti-Calcification Treatment
Various anti-calcification treatment, proven on surgical valves, will also be used.
Blood Cells
Calcium
Tissue Matrix
Glutaraldehyde
Alpha Oleic Acid
Alpha Oleic Acid, covalently (chemically) bonded to the aldehyde groups extending from the glutaraldehyde-preserved tissue, mitigates leaflet calcification

9. Testing Conditions: In Vivo Deformation and Geometry

10. Testing Conditions: Implanted Environment
Elliptical LVOT
Bounding of perimeter
Non-contractile tissue
Muscle
Modified from Wilcox, Cook, and Anderson, Surgical Anatomy of the Heart, 2005. LA
LA/LV
Understanding the dynamic nature of the interaction between the frame and the anatomy
Muscle RV
Muscle RV
10mm below aortic annulus
Aortic annulus

11. Porcine Pericardial Valve Performance
Accelerated Wear Testing (200 millions cycles: 5years)

12. Porcine Pericardial Valve Performance
Accelerated Wear Testing - Round

13. Porcine Pericardial Valve Performance
Accelerated Wear Testing - Elliptical

14. Porcine Pericardial Valve Performance
Accelerated Wear Testing - Elliptical

15. Durability is a relative concept
Life Expectancy with Therapy (will the device outlive the patient in any case?)
Has to be taken into account with the following considerations:
Patient’s co-morbidities
Procedure invasiveness
Post-operative Length of Stay
Safety
Efficacy
Quality of Life
Cost Effectiveness
Valve in Valve concept opens new opportunity to:
Extend durability without risk and invasiveness of open surgery
Bank on future innovations and iterations

16. As TAVI experience grows the landscape will shift over the years
TAVI PROGRESSION IN PATIENTS GROUPS
HIGH RISK / INOP
No good surgical option
Short life expectancy
MEDIUM/LOWER RISK
Current surgical candidates
>20 year data on patient outcomes

17. Evidence, Product Iterations and New Technologies will occur in parallel
TAVI PROGRESSION IN PATIENTS GROUPS
HIGH RISK / INOP
No good surgical option
Short life expectancy
MEDIUM/LOWER RISK
Current surgical candidates
>20 year data on patient outcomes
Accumulation of Evidence
Product Iterations / Course Correction
New Technologies and Options (e.g. Valve in Valve)

18. So what do we know about Durability of TAVI today?
Bench testing can provide key insight into the durability of the design
Equivalency with surgical valves established through accelerated wear testing, an FDA requirement
Frame accelerated wear testing completed up to 15 years
With over 7,500 patients implanted to date,
No reports of premature ageing of the leaflets
No frame fracture of the nitinol frame
Survival experience continues to accumulate, with the longest surviving patient being implanted in 2004

19. So in brief:
YES, TAVI should strive to match Surgical on Durability, especially if we want it to displace Surgical from the Medium/Lower risk patient group
NO, it doesn’t need to happen all at once, it will happen over time, through evidence gathering, product iterations and new technologies