PD Dr. med. U Schäfer Abteilung für Allgemeine und Interventionelle Kardiologie

1. Embolic protection during transcatheter aortic valve implantation with the Claret MontageTM Filtration System U. Schäfer, T. Thielsen, D. Schewel, J. Schewel, T. Spangenberg, K.-H. Kuck, C. Frerker AK St. Georg, Hamburg PD Dr. med. U Schäfer Abteilung für Allgemeine und Interventionelle Kardiologie Universitäres Herzzentrum UKE, Hamburg

2. Disclosure Statement of Financial Interest I, Ulrich Schäfer MD, 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.

3. Paravalvular Regurgitation Cerebrovascular Accident Vascular Complications Kodali. NEJM 2012;366:1686 Stortecky. EuroIntervention 2012;8:623 Challenges with Current TAVI Devices Significant Predictors of Mortality Lange. Eur J Cardio-Thoracic Surg 2011;40:1105 PD Dr. U. Schäfer

4. Cerebrovascular Accident DW-MR Signature of Silent lesions after TAVI Ghanem et al, JACC 2010;55:1427-32, Khalert et al, Circulation 2010;121:870-8, Rodes-Cabau et al, JACC 2011;57:18-28. PD Dr. U. Schäfer

5. Cerebrovascular Accident Stroke Related Mortality After TAVI TAVR Embolic Debris: Release Timing Eggebrecht H, et al, EuroIntervention 2012, 8: 129-138 Stortecky et al., Eurointervention 2012;8:62-70 • Procedural stroke (<24 h): 1.5±1.4%. • Overall 30-day stroke/ TIA: 3.3±1.8% • First year after TAVI stroke/TIA: 5.2±3.4%. PD Dr. U. Schäfer

6. Cerebrovascular Accident Timing of Embolization during TAVI New lesions found in vast majority of diffusion-weighted MR images (DW-MRI) of the brain following TAVR Kahlert P, et al, Circulation 2012;126:1245-1255 Daneault et al, JACC 2011;58: 2143-50 PD Dr. U. Schäfer

7. Cerebral Protection Devices PD Dr. U. Schäfer

8. Claret Sentinel™ Cerebral Protection System Distal Filter Proximal Filter • The only dual, independent filter (proximal and distal) embolic protection device with visible embolic capture • The 3rd generation of the first commercially available CE Marked embolic protection device • Universal size and shape • Deflectable compounded curve sheath to facilitate cannulation of LCC • Ergonomically designed handle PD Dr. U. Schäfer

9. Montage- Heterogeneity of Captured Debris Van Mieghem et al, Circulation 2013;127:2194-2201. PD Dr. U. Schäfer

10. Claret Montage Debris Capture Methods 1 • n=45 patients were scheduled for various TAVI procedures. • - used Transcatheter Heart Valves: • ESV (n=30); MCV (n=9); Jena (n=2); Centera (n=1); Portico (n=3) • - various approaches: • transfemoral (n=36); transapical (n=8); transaxillary (n=1) • - different pathologies: • native AS (n=37); ViV (n=7); AR (n=1) • The Claret Montage™ (Claret Medical, Inc. Santa Rosa, CA, USA) cerebral protection device was placed via the right radial artery prior to TAVI and was removed after the procedure. • Stable Device placement/success, hemodynamic TAVI-data, and clinical events were recorded during the entire hospital stay. PD Dr. U. Schäfer

11. Claret Montage Debris Capture Methods 2 • all Filters were sent to Renu Virmani MD at CVPath Institute fixed • in 10% neutral buffered formalin. • Photographed and the aspirate measured and then filtered through a 40 micron nylon cell strainer. • The material was embedded in paraffin and serially cut at 4 to 5 microns • Theywere stained with Hematoxylin & Eosin (H&E) and Movat Pentrachrome (MP). • Histology analysis were evaluated for the presence of • Acute and organized thrombus • Valve leaflet • Arterial Wall • Calcified debris • Foreign material „only data of the first n=30 treated patients (60 filters) available“ PD Dr. U. Schäfer

12. Claret Montage Debris Capture Baseline characteristics 1.) different THVs ESV n=16 MCV n=8 Jena n=2 Centera n=1 Portico n=1 2.) various approaches transfemoral n=24 transapical n=5 transaxillary n=1 3.) different pathologies native AS n=22 ViV n=7 pure AR n=1 PD Dr. U. Schäfer

13. Claret Montage Debris Capture Results PD Dr. U. Schäfer

14. Claret Montage Debris Capture Results PD Dr. U. Schäfer

15. Claret Montage Debris Capture procedural data TAVI/TMVI • * one patient had post implant AR grade II • ** TIA after 48hours post TAVI completely resolving within the subsequent 24 hours PD Dr. U. Schäfer

16. Claret Montage Debris Capture transvalvular hemodynamics Invasive hemodynamics of n=22* patients with native aortic valvular stenosis *n=1 with pure aortic regurgitation #n=1 ptient with PVL >=2+ Invasive hemodynamics of n=5 patients with degenerated aortic bioprosthesis ## 2 ptients with AR 3+ Invasive hemodynamics of n=2 patients with degenerated mitral bioprosthesis # # # 2 ptients severe mitral stenosis PD Dr. U. Schäfer

17. <= 48 h > 48 h Claret Montage Clinical Data n=45 n=1 TIA at day 3 after TAVI completely resolving after 36 hours n=1 device with both filters could‘t be deployed n=1 distal filter embolized during the procedure n=30 prox. filter Claret Montage Debris Capture dist. filter any filter Histopathology R.Virmani CV Path PD Dr. U. Schäfer

18. Claret Montage Debris Capture Results from St. George Kilnik, Hamburg all patients (n=30) 1.) any debris in 100% 2.) „thrombus and tissue“ was most prevalent ≈ 90% 3.) trend to more debris in the proximal filter 4.) captured calcium was found in 40% Histopathology R.Virmani CV Path PD Dr. U. Schäfer

19. Claret Montage Debris Capture Valve-in-Valve (ViV) patients (n=7) 1.) any debris in 100% 2.) „thrombus and tissue“ was most prevalent ≈ 85% 3.) trend to more debris in the proximal filter 4.) captured calcium was found in 16% Histopathology R.Virmani CV Path PD Dr. U. Schäfer

20. Claret Montage Debris Capture without Valve-in-Valve (ViV) patients (n=23) 1.) any debris in 100% 2.) „thrombus and tissue“ was most prevalent ≈ 90% 3.) trend to more debris in the proximal filter 4.) captured calcium was found in 50% Histopathology R.Virmani CV Path PD Dr. U. Schäfer

21. Claret Montage Debris Capture 1.) recaptured debris is not associated with the severity of valvular stenosis 2.) captured calcium is idependent from valvular calcification 3.) trend to more „tissue“ in severe calcification Histopathology R.Virmani CV Path PD Dr. U. Schäfer

22. Claret Montage Debris Capture 1.) more tissue with ESV 2.) trend to more „tissue“ with porcelain aorta 3.) trend to more debris with post-ballooning 4.) no association to gender Histopathology R.Virmani CV Path PD Dr. U. Schäfer

23. SUMMARY and CONCLUSION Limitations: The study contains a high heterogenity of patients treated by: 1.) different valves (ESV n=16; MCV n=8; Jena n=2; Centera n=1; Portico n=1) 2.) various approaches (transfemoral n=24; transapical n=5; transaxillary n=1) 3.) with different pathologies (native AS n=22; ViV n=7; AI n=1) Claret Montage clinical data (n=45) • successful device placement in 96.7% • no acute TIA/stroke in 45 patients • n=1 TIA at day 3 after TAVI => feasibility & safety seems to be documented in that single center study PD Dr. U. Schäfer

24. SUMMARY and CONCLUSION Claret Montage histopathology data (n=30) • any debris capture rate 100% • prevalence rate: thrombus > tissue > calcium > foreign material • no significant difference between ViV and non-ViV patients • no association between load of debris and severity of aortic stenosis • trend to more debris with post-ballooning • no significant difference according to THV-type, gender or presence/absence of a porcelain aorta => embolic protection seems to be an unmet clinical need and should be investigated in larger patient cohorts PD Dr. U. Schäfer