Direct Flow Medical Experience with a Conformable, Repositionable, Retrievable, Percutaneous Aortic Valve Reginald Low MD University of California,Davis

Disclosure Direct Flow Medical - Consultant

MEDTRONIC (CoreValve) EDWARDS (Sapien) MEDTRONIC (CoreValve) DIRECT FLOW MEDICAL

Desireable Features - Percutaneous Aortic Valve Function Large Effective Orifice Area (EOA) Durable - >10 years Excellent Securement Good apposition (No paravalvular leak) No coronary obstruction Multiple sizes Deliverability Low profile - 18 French or smaller Flexible and trackable Precise positioning Repositionable Retriveable Direct Flow Medical Percutaneous Aortic Valve

Direct Flow Medical - PAV Design Features Leaflets - Bovine Pericardium (anti-calcification therapy) Surgical Valve Design - Stentless Balloon supported Polyester Fabric Cuff Initial deployment with saline/contrast inflation When final position and function is confirmed, saline/contrast replaced with water soluble polymer media under constant pressure in-situ First generation - 22 French Present generation - 18 French Sizes 23mm, 25mm, 27mm 3 one way check valves 3 positioning-fill lumen Immediately functional when unsheathed and distal ring is inflated Check Valves Position Fill Lumens

Direct Flow Medical - PAV Design Features Delivery System Polymer nylon sleeve Multilumen catheter 3 position and fill lumen 1 guide wire lumen Flexible nose cone Non-metallic delivery system and valve Flexible and trackable Precise positioning Retrievable with deflation and withdrawl into retrieval basket Position & Fill Lumens Aortic Ring Ventricular Ring Guidewire Lumen

Direct Flow Medical - PAV Valve loaded in Delivery System Valve Unsheathed Valve Inflated & Steering System Valve in Retrieval Basket

Direct Flow Medical - PAV Positioning, Securement, Sealing

Direct Flow Animation 8

Direct Flow Retrieval

European Safety & Feasibility Study 22F System University Medical Center, Hamburg-Eppendorf (n=25) Helios Heart Center - Siegburg (n=6) High risk patients for cardiac surgery Patients Enrollment Number 31 / 22 Implants / 2 Surgical Conversions Age 82 ± 4 years Female/Male 16/15 NYHA III – IV 71% Logistic EuroSCORE 29 ± 7% Mean transvalvular gradient 49 ± 14 mmHg Aortic valve area 0.54 ± 0.13 cm2 LVEF 53 ± 15 Investigational device not for sale in or outside the United States

Difficult Peripheral & Aortic Anatomy 87 year old male Euroscore = 36.2 Moderately Calcified Native Annulus Extensive Calcification Marked Tortuosity 6 Month CT Pt # 03-01-021 HF Current Status: 20 Months Post-Procedure Final Position Investigational device not for sale in or outside the United States 11

Deliverability Flexibility, Trackability, Profile Pt # 03-01-17 UN 22F Direct Flow Medical 1

Difficult Valve Anatomy Final Position 79 year old female Euroscore = 20.3 6 Month CT Pt # 03-01-016 MN Extensive Calcification 15 Month CT Current Status: 23 Months Post-Procedure Investigational device not for sale in or outside the United States 1

Sealing Minimizes Paravalvular Insufficiency Pt # 03-01-17 UN Conformable cuff design – improves sealing 1

1 Year Data (22 French)

1 Year Data (22 French) As measured by TTE Investigational device not for sale in or outside the United States

First Patient Treated MPG = 10 mmHg EOA = 1.98 cm² NYHA Class I 81 year old male EuroSCORE = 25.8 Current Status: 2 Year Visit Complete MPG = 10 mmHg EOA = 1.98 cm² NYHA Class I Screening rs Final Positioning Post Op CT Investigational device not for sale in or outside the United States 1

Extended Follow Up Follow-up 12 to 24 Months In all patients, no significant changes : Mean/peak gradients Effective orifice area Aortic regurgitation, paravalvular leaks LVEF NYHA functional class Investigational device not for sale in or outside the United States

Latest Generation 18 French Profile Reduction 22 F 18 F Increased Radial Force Improved Positioning Simplified Valve Retrieval Improved Valve Loading Atraumatic Tip Investigational device not for sale in or outside the United States 1

Summary Direct Flow Medical PAV Non-metallic fabric covered balloon supported bovine pericardial valve Repositionable and retrievable Mechanical securement with conformability and sealing Formed in-situ with exchange polymer media Design permits functional and hemodynamic assessment before final deployment Next generation 18 French improves profile, positioning, valve loading into delivery sheath, radial force Feasibility, safety and efficacy demonstrated with 22 F system European study with longest implant of 2.4 years Final design validation and testing for next generation 18 French in progress before European Trial in Q4 2010