Dr. Lucas Boersma, MD/PhD/FESCSt. Antonius Hospital, Nieuwegein, The Netherlands

B. Schmidt Cardiology Centre Bethanien, Frankfurt Am Main, GermanyT. Betts John Radcliffe Hospital, Oxford, United KingdomE. Teiger Hospital Henri Modor, Creteil, FranceC. Tamburino Ferrarotto Hospital, Catania, ItalyI. Atmowihardjo Vivantes Klinikum am Urban, Berlin, GermanyS. Kische Vivantes Klinikum im Friedrichshain, Berlin, GermanyE. Pokushalov State Res Inst of Circ Path. Novosibirsk, Russian FederationH. Sievert CardioVascular Center Frankfurt, Frankfurt Am Main, GermanyM. W. Bergmann Cardiologicum Hamburg, Hamburg, Germany

Implant Success and Safety of Left Atrial Appendage Closure with the WATCHMAN device: peri-procedural outcomes from the EWOLUTION Registry

LAA closure for stroke prevention – PROTECT AF

WATCHMAN superior over VKA during long-term FU

Reddy, et al. JAMA 2014

Death, Stroke, Embolism

Registry on WATCHMAN Outcomes in Real-Life Utilization: EWOLUTION

EMEA WATCHMAN Registry

Study Objective: Collect real-world WATCHMAN LAAO experience outside of selected populations in prior RCT

Study Design: Prospective, single-arm, multi-center registry of the Watchman LAA Closure Technology

Primary Endpoint: Primary analysis includes procedural success and safety, incidence of stroke, bleeding, and death after 2 yr of FUInvestigator and Medical Safety Group for adjudication

Patient Population: >1000 patients

Number of Sites: 47 throughout Europe, Russia and Middle East

Enrollment: Started October 2013 - Completed May 2015

Follow-up:Standard practice at participating centers• Normally 1-3 months post-procedure• Annually thereafter for a total of 2 years

Inclusion criteria:1. Eligible for WATCHMAN LAAC per international/local guidelines and at

physicians discretion;2. willing and capable of providing informed consent, participating in all testing

associated with this clinical investigation at an approved clinical investigational center;

3. 18 years or above, or of legal age to give informed consent specific to state and national law;

Exclusion criteria:1. Current enrollment in another investigational study or registry that would directly

interfere with the current study;2. Women of childbearing potential who are, or plan to become, pregnant during the

time of the study;3. The subject is unable or not willing to complete follow-up visits and examination

for the duration of the study.

Centers were encouraged to enrol consecutive patients to represent real life practice and avoid selection bias

EWOLUTION - Study population

EWOLUTION - Flow ChartInformed consent obtained

LAA criteria met?

Implant of WATCHMAN*** subject is enrolled ***

Reassess per physician’s discretion

NOYES

Device implantedDevice not implanted

Follow-up according to center’s practiceWithdrawal (Attempt)

reimplant

Withdrawal (Intent)

Baseline patient characteristics - 1Characteristic All Pts (N=1021)Not eligible for OAC 61.8%

Age at time of consent (years) 73.4 ± 8.9 (range 39, 94)

Age ≥75 50.8%Female gender 40.1%Congestive Heart Failure 34.2%History of Hypertension 86.3%Diabetes 29.6%Vascular Disease 41.8%Abnormal Renal Function 15.6%Abnormal Liver Function 4.2%

Baseline patient characteristics - 2Characteristic All Pts (N=1021)History of TIA 10.7%History of Ischemic Stroke 19.7%Previous Hemorrhagic Stroke 15.0%Prior Major or Predisposition Bleeding 38.7%Labile INRs 17.0%Concomitant Use of Drugs 27.8%Alcohol Abuse 4.2%CHADS2 2.8 ± 1.3CHA2DS2-VASC 4.5 ± 1.6HAS-BLED 2.3 ± 1.2

CharacteristicPROTECT AF CAP PREVAIL CAP2 EWOLUTION

N=707 N=566 N=407 N=579 N=1021

CHADS2 Score 2.2 ± 1.2 2.4 ± 1.2 2.6 ± 1.0 2.7 ± 1.1 2.8 ± 1.3

CHA2DS2-VASc 3.4 ± 1.5 3.9 ± 1.5 4.0 ± 1.1 4.5 ± 1.3 4.5 ± 1.6

StudyPatients (%) with HAS-BLED Score

Low Risk Moderate Risk High Risk0 1-2 ≥3

PROTECT AF (N=707) 6.4 73.7 19.9

PREVAIL (N=407) 1.7 68.6 29.7

CAP (N=566) 2.8 61.0 36.2

CAP2 (N=579) 2.8 69.9 28.3EWOLUTION (N=1013) 4.4 55.3 40.3

EWOLUTION - Higher risk patients compared to prior WATCHMAN trials

• ESC guideline 2012: consider OAT ineligible pts• 62% of all subjects deemed unsuitable for OAT

based on co-morbidities and/or bleeding risk

• Post-implant 86% were on OAT or DAPT per instructions of use in Europe

EWOLUTION – Peri-procedural OAT

Anticoagulation Pre-implant Post-implantNothing 26.7% 6.1%Single APT 20.7% 7.4%Dual APT 21.7% 59.4%OAT 30.9% 27.0%

Measure % (N = 1019)Implant Success (deployment and release of the device into the left atrial appendage)

98.5% (1004/1019)

Implant Failure – device not implanted 1.5% (15/1019)- Release criteria not met – Position (too proximal) 6.7% (1/15)

- Release criteria not met – Anchor (stability) 13.3% (2/15)- Release criteria not met – Size (device too small or

too big)20.0% (3/15)

- LAA anatomy not suitable 46.7% (7/15)

- Other 13.3% (2/15)

EWOLUTION - Implant Success

Study Proportion % Fisher's Exact P-valueEWOLUTION 1004/1019 98.5% -PROTECT 408/449 90.9% p<0.001CAP 534/566 94.4% p<0.001PREVAIL 252/265 95.1% p=0.002CAP2 545/575 94.8% p<0.001

EWOLUTION – Highest Implant Success

EWOLUTION

98.5%

PROTECT AF

90.9%

PREVAIL

95.1%

CAP

94.4%

CAP2

94.8% Comparison of proportions between allstudies: p=<0.001

Days implant to deathAcute RV failure 0

Respiratory insufficiency 4Cardiac Arrest 6

Clostridium Difficile 10Major GI bleeding - hemorrhagic shock 12Major GI bleeding - hemorrhagic shock 15

Cerebral air embolism at implant *19

EWOLUTION - 30-Day MortalityN = 1019

Subject deaths 7Kaplan Meier Event Rate 0.8%Two-Sided 95% CI 0.3%, 1.5%

* procedure- or device-related

EWOLUTION – 30-Day SAE Listing

Kaplan-Meier Event rate 7.9%Two-Sided 95% CI 6.3%,9.8%

Procedure- or Device-relatedN = 34 (40%)

Unrelated

N = 50 (60%)

Major bleeding requiring transfusion 8 11Other bleeding (hematoma, hemoptysishematuria, anemia requiring transfusion) 2 4

Vascular damage at puncture site 5 -Pericardial Effusion 3 2Cardiac Tamponade 2 -Strokes 1 2Suspected TIA - 2Pulmonary Embolism - 1Air Embolism 3 -Device Embolization 2 -Miscellaneous 8 28

Population divided by CHADS2≥3, CHA2DS2-VASc ≥5, HAS-BLED≥3, OAT eligibility, OAT after implant

• Higher 30-day SAE rate if:

• Higher 30-day Bleeding rate if:

30-Day SAE rate – Subgroup analysis

Composite of vascular complications includes cardiac perforation, pericardial effusion with tamponade, ischemic stroke, device embolization, and other vascular complications1

All Prior WATCHMAN studies: 7-Day Procedure/Device Related SAEs

8.7%

4.1% 4.2%

Kaplan-MeierSAE rate

2.8%

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

% o

f Pat

ient

s

PROTECT AF CAP PREVAIL EWOLUTION

n=39

n=23 n=12

1Includes observed PE not necessitating intervention, AV fistula, major bleeding requiring transfusion, pseudoaneurysm, hematoma and groin bleeding

PROTECT AF/CAP: Reddy et al. Circulation 2011PREVAIL: Holmes et al. JACC 2014

n=26

The EWOLUTION real-world prospective registry:• Shows the highest LAA closure success rate of all

WATCHMAN studies so far• With the lowest peri-procedural risk, even in multi-

morbid patients, with high stroke and bleeding risk, and 62% unsuitable for OAT

- OAT ineligible pts had lower SAE rate- HASBLED ≥3 pts had higher bleeding rate

• Improvement in implantation techniques mayfurther boost the net clinical benefit of LAAC during long-term follow up

Conclusions

THANK YOU