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

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.

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

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

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

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

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

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

Testing Conditions: In Vivo Deformation and Geometry

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

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

Porcine Pericardial Valve Performance Accelerated Wear Testing - Round

Porcine Pericardial Valve Performance Accelerated Wear Testing - Elliptical

Porcine Pericardial Valve Performance Accelerated Wear Testing - Elliptical

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

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

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)

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

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