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.

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

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

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

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

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

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 3 months: N = 979 Death: N = 21 Withdrawals: N = 5 study population Prof. M.W. Bergmann 2016

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%

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

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

EWOLUTION: procedural 3 months Prof. M.W. Bergmann 2016

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

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 – ± 2 20 – ± 5 28 – ± P-value<

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

EWOLUTION: safety 3 months Prof. M.W. Bergmann 2016

EWOLUTION: SAE 3 months Prof. M.W. Bergmann 2016

EWOLUTION: 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 puncture site 52.5%40.4% Genito-urinary52.5%30.3% Cancer42.0%40.4%

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

EWOLUTION peri-procedural drug regimen Prof. M.W. Bergmann 2016 AnticoagulationPre-implant (%)Post-implant (%) Nothing Single APT Dual APT NOAC Warfarin

SAE stratified for post-implant drug regimen Prof. M.W. Bergmann 2016 P = P = P = P = P = 0.763

LAA closure with WATCHMAN: conclusion 3 months Prof. M.W. Bergmann 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 3 months -dual antiplatelet therapy and NOAC feasible and safe during the first 3 months