Twelve Months and Beyond: Long-Term Results of the Direct Flow Medical Repositionable and Retrievable Pericardial Valve for Percutaneous Aortic Valve Replacement Joachim Schofer Medical Care Center Prof. Mathey, Prof. Schofer Hamburg University Cardiovascular Center Hamburg, Germany

Disclosure Statement of Financial Interest I, Joachim Schofer, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

Percutaneous Aortic Valve Replacement To date, clinical studies of percutaneous treatment of severe aortic valve stenosis in patients at high surgical risk have utilized metallic aortic valve prostheses of the balloon- expandable (SAPIEN™) or self-expanding type (CoreValve ® ). Once deployed, neither type of valve prosthesis can be repositioned or retrieved. Emergent cardiac surgery may be necessary in cases of improper deployment. The Direct Flow Medical (DFM) nonmetallic aortic valve prosthesis for transfemoral placement can be retrieved, repositioned or exchanged prior to permanent implantation.

The DFM Aortic Valve Prosthesis Tri-leaflet valve constructed of bovine pericardium 3 position/fill lumens (PFLs) To position/reposition valve Complete inflation media exchange Aortic and ventricular rings Inflate independently so that device can be repositioned May be completely deflated so that device can be fully retrieved Multilumen

The DFM AV Prosthesis European Clinical Trial Objective To assess the feasibility and safety of percutaneous implantation of the DFM 22-F aortic valve prosthesis in high-surgical risk patients with severe aortic valve stenosis Patients enrolled in Hamburg N =25; 82 ± 4 years; 10 men (40%) NYHA IIn=8 (32%) NYHA IIIn=17 (68%) Logistic EuroSCORE29 ± 7% Mean transvalvular pressure gradient52 ± 12 mmHg Aortic valve area0.53 ± 0.14 cm 2

The DFM AV Prosthesis European Clinical Trial Pre-interventional Diagnostics Transthoracic echocardiography Aortic valve dimensions Severity of aortic stenosis/regurgitation Coronary angiography Exclude clinically relevant coronary stenoses Multi-slice computed tomography Cross-sectional diameters of entire aortic valve apparatus, from 15 mm below to 30 mm above annulus in 5-mm increments Distance of coronary ostia from annulus Valvular calcification Access route for a 22-F system from iliofemoral vasculature to aortic root

ITT population n = 25 Device implanted n = 18 (72%) Discharged with permanent implant n = 15 (60%) Surgical 7 days (n=2) No iliac access (n=2) Site: Hamburg, Germany Functionally bicuspid native valve (n=2) Excessive valvular calcification (n=3) (  Intraprocedural death [n=2]) In-hospital death (n=1) The DFM AV Prosthesis European Clinical Trial

Post-discharge major adverse events out to 1 year Deathn=2  142d: unknown cause  193d: respiratory failure Stroken=1  1d AV block  PMn=3  1 after surgical conversion Mortality 1-year all-cause mortalityn=5/25 (20%) Procedure-relatedn=3/25 (12%)

The DFM AV Prosthesis European Clinical Trial Mean/peak transvalvular pressure gradients † † % C.I. † P=0.196 vs. 30d † P= Hamburg pts discharged with permanent implant

The DFM AV Prosthesis European Clinical Trial Effective aortic orifice area * cm *P=0.015 vs. 30d 95% C.I. 15 Hamburg pts discharged with permanent implant

The DFM AV Prosthesis European Clinical Trial Aortic regurgitation in patients discharged with a permanent implant Baseline (n=15) Post (n=15) 30d (n=13) 365d (n=12) 11 9 ParavalvularParavalvular + CentralCentral 15 Hamburg pts discharged with permanent implant

NYHA I NYHA IINYHA III The DFM AV Prosthesis European Clinical Trial NYHA functional class (Surviving Hamburg pts) Baseline30d90d180d365d n=10 n=3n=5 n=8n=12n=10n=8 n=3n=5n=1

The DFM AV Prosthesis European Clinical Trial Follow-up beyond 12 months 24-month F/U1 patient 18-Month F/U5 patients In all 6 patients, no significant changes were seen in  Mean/peak gradients  Effective orifice area  Aortic regurgitation, paravalvular leaks  LVEF  NYHA functional class

The DFM AV Prosthesis European Trial – Conclusions (1) This single-center first-in-man experience attests to the 1-year safety and efficacy of transfemoral implantation of the DFM 22-F nonmetallic aortic valve prosthesis. In patients discharged with a permanent implant, effective orifice area decreased gradually, from 30 days to 1 year, by 20%. However, mean and peak transvalvular pressure gradients remained essentially stable over that period. Clinically, all surviving patients but 1 had improved by at least 1 NYHA functional class at 1 year. Follow-up beyond 12 months in 6 patients revealed stable clinical and echocardiographic parameters.

The DFM AV Prosthesis European Trial – Conclusions (2) Our implantation success rate of 72% points to the importance of pre-interventional assessment of calcification quantity and pattern – both in the peripheral vasculature and within the native valve apparatus.