1. EWOLUTION: 3-months outcome of Left Atrial Appendage Closure with the WATCHMAN device in Europe Thrombus at the device, leakage at follow-up, device embolisation, post-procedural drug regimen and impact of center experience data from the prospective 1025 patients EWOLUTION Registry M. W. Bergmann 1, B. Schmidt 2, T. Betts 3, E. Teiger 4, C. Tamburino 5, E. Pokushalov 6, S. Kische 7, T. Schmitz 8, H. Ince 9, H. Sievert 10, L.V.A. Boersma 11 – (1) Cardiologicum Hamburg, Germany (2) Cardiology Centre Bethanien (CCB), Frankfurt, Germany (3) John Radcliffe Hospital, Oxford, United Kingdom (4) University Hospital Henri Mondor, Creteil, France (5) Ferrarotto Hospital, Catania, Italy (6) State Research Institute of Circulation Pathology, Novosibirsk, Russian Federation (7) Vivantes Klinikum Friedrichshain, Berlin, Germany (8) Elisabeth Krankenhaus Essen, Germany (9) Vivantes Klinikum Urban, Berlin, Germany (10) CardioVascular Center Frankfurt, Germany (11) St Antonius Hospital, Nieuwegein, Netherlands.

2. Potential conflicts of interest Speaker's name: Martin W. Bergmann  I have the following potential conflicts of interest to report: Consultant: Biosense Webster, BOSTON SCIENTIFIC Honorarium: BAYER PHARMA AG, BIOTRONIK, Boehringer Ingelheim, DAIICHI SANKYO and ELI-LILLY, Novartis, ST. JUDE MEDICAL

3. Topics EWOLUTION study design & population EWOLUTION results @ 3 months Open question: impact of center experience? Open question: impact of post-implant drug regimen? Conclusions Prof. M.W. Bergmann 2016

4. EWOLUTION study design & population Prof. M.W. Bergmann 2016

5. EWOLUTION study design & population Top 10 enrolling centers # pts enrolled Berlin, Germany (Atmowihardjo/Ince)86 Berlin, Germany (Kische)68 Hamburg, Germany (Meincke/Bergmann)55 Novosibirsk, Russia (Pokushalov)51 Essen, Germany (Schmitz)48 Frankfurt, Germany (Schmidt)40 Dublin, Ireland (Foley)37 Mainz, Germany (Gori)33 Krasnoyarsk, Russia (Protopopov)29 N = 1025 Prof. M.W. Bergmann 2016

6. EWOLUTION study design & population Prof. M.W. Bergmann 2016 Boersma LVA et al. Catheter Cardiovasc Interv 2015 EWOLUTION: design of a registry to evaluate real-world clinical outcomes in patients with AF and high stroke risk-treated with the WATCHMAN left atrial appendage closure technology N = 5 N = 15 N = 1005

7. EWOLUTION: patient flow up to 3 months Informed consent obtained: N = 1025 Implant of WATCHMAN: N = 1020 Unsuccessful Implant: N = 15 Patients with Watchman implant: N = 1005 Anatomy considered not suitable at prescreening: N = 5 Patients with Watchman implant @ 3 months: N = 979 Death: N = 21 Withdrawals: N = 5 study population Prof. M.W. Bergmann 2016

8. EWOLUTION: patient baseline characteristics Prof. M.W. Bergmann 2016 CharacteristicPercentage Male Gender60% History of Ischemic Stroke20% Previous Hemorrhagic Stroke15% Prior Major or predisposition to bleeding39% CHA 2 DS 2 -VASc score ≥ 549% HAS-BLED ≥ 340% Contra-indication for oral anticoagulation72% Age ≥ 80 years26% Hypertension (uncontrolled or history of hypertension)86% Congestive heart failure34% Type II diabetes29% Vascular disease42% Abnormal renal function16% Abnormal liver function4%

9. Topics EWOLUTION study design & population EWOLUTION results @ 3 months Open question: impact of center experience? Open question: impact of post-implant drug regimen? Conclusions Prof. M.W. Bergmann 2016

10. EWOLUTION: device sizing Prof. M.W. Bergmann 2016 18%21%17%16%15% Mean Compression (%) mean

11. EWOLUTION: procedural results @ 3 months Prof. M.W. Bergmann 2016

12. Topics EWOLUTION study design & population EWOLUTION results @ 3 months Open question: impact of center experience? Open question: impact of post-implant drug regimen? Conclusions Prof. M.W. Bergmann 2016

13. Effect of center experience - procedural Prof. M.W. Bergmann 2016 Enrolment Quartile Subjects (Mean ± SD Min – Max) First Device Release Successful (%) First Device Size correct (%) Complete Seal or Jet Size ≤ 5 mm at implant (%) Complete Seal or Jet Size ≤ 5 mm at First FU (%) 1 11 ± 5 1 – 18 65.288.6100.099.1 2 23 ± 2 20 – 27 70.492.5100.099.0 3 33 ± 5 28 – 40 65.092.399.699.1 4 63 ± 18 48 - 86 84.498.899.298.2 P-value<0.0001 0.35450.8332

14. Effect of center experience – SAEs @ 3 Mo Prof. M.W. Bergmann 2016

15. EWOLUTION: safety results @ 3 months Prof. M.W. Bergmann 2016

16. EWOLUTION: SAE distribution @ 3 months Prof. M.W. Bergmann 2016

17. EWOLUTION: safety @ 3 mo. Other SAEs Prof. M.W. Bergmann 2016 Other SAEs # SAEs (N = 199) % SAEs # pts (N = 1020) % pts Heart Failure199.5%181.8% Pulmonary136.5%121.2% Arrhythmias105.0%90.9% Systemic Infection73.5%70.7% Peripheral Vascular Disease63.0%50.5% Vascular damage @ puncture site 52.5%40.4% Genito-urinary52.5%30.3% Cancer42.0%40.4%

18. Topics EWOLUTION study design & population EWOLUTION results @ 3 months Open question: impact of center experience? Open question: impact of post-implant drug regimen? Conclusions Prof. M.W. Bergmann 2016

19. EWOLUTION peri-procedural drug regimen Prof. M.W. Bergmann 2016 AnticoagulationPre-implant (%)Post-implant (%) Nothing27.56.6 Single APT22.17.1 Dual APT20.359.6 NOAC14.611.1 Warfarin15.515.6

20. SAE stratified for post-implant drug regimen Prof. M.W. Bergmann 2016 P = 0.768 P = 0.275 P = 0.498 P = 0.792 P = 0.763

21. LAA closure with WATCHMAN: conclusion EWOLUTION @ 3 months Prof. M.W. Bergmann 2016 -high success rate in european centers -low periprocedural event rate despite high risk, mostly oral anticoagulation contraindicated patient population -centers with less experience same high success rates with low complication rate compared to more experienced centers -bleeding itself is the issue with the highest event rate @ 3 months -dual antiplatelet therapy and NOAC feasible and safe during the first 3 months