A Pilot Study to Assess WATCHMAN FLX™ Implants by Cardiac Computed Tomography, Magnetic Resonance Imaging and Transesophageal Echocardiography: WATCHMAN FLX™ CT
Phase: NA
Conditions: The Focus of the Study is to Reduce the Risk of Stroke and Life-threatening Bleeding Events in Patients With Non-valvular Atrial Fibrillation
Sponsor: Boston Scientific Corporation

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A Pilot Study to Assess WATCHMAN FLX™ Implants by Cardiac 
Computed Tomography, Magnetic Resonance Imaging and 
Transesophageal Echocardiography: WATCHMAN FLX™ CT 
 
WATCHMAN FLX™ CT  
S2423 
CLINICAL INVESTIGATION PLAN 
 
National Clinical Trial (NCT) Identifier Number: NCT05324371 
 
 
Sponsor: 
Boston Scientific Corporation  
300 Boston Scientific Way 
Marlborough, MA 01752 USA 
International Representative  
Boston Scientific International SA 
2 Rue René Caudron, Bâtiment H 
78960 Voisins-le-Bretonneux, France 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should 
be held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 

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Contact Information 
Role 
Contact  
Clinical 
Contacts 
Nilou Zilinek, MS 
Clinical Trial Manager 
Interventional Cardiology – Structural Heart 
Boston Scientific Corporation  
100 Boston Scientific Way, M60 
Marlborough, MA 01752 
Peter Maurer, MPH 
Director, Clinical Trials 
Interventional Cardiology – Structural Heart  
Boston Scientific Corporation 
100 Boston Scientific Way, M60 
Marlborough, MA 01752  
Study 
Coordinating 
Principal 
Investigator 
Prof Jens Erik Nielsen-Kudsk, MD 
Department of Cardiology 
Aarhus University Hospital 
Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus N 
 
Vendors/Labs/ 
External 
Organizations 
A list of vendors/laboratories/external organizations involved in the trial 
is maintained by the sponsor. 
 
 
Original Release: 12-Apr-2022 
 
 
Revision History 
Revision Number 
Release Date 
Template Version 
Reason for Change 
A 
12-Apr-2022 
92120219 Rev/Ver G 
Not Applicable 
B 
20-Apr-2022 
92120219 Rev/Ver G 
• 
Removed Final Draft 
from header of several 
pages and yellow 
highlight on release 
date 
• 
Added procedural 
definitions within table 
17.2-1 Safety 
Definitions 
C 
02-Aug-2022 
92120219 Rev/Ver G 
• 
Identified the existing 
endpoint of tissue 

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Revision History 
Revision Number 
Release Date 
Template Version 
Reason for Change 
coverage assessment as 
the primary endpoint 
• 
Removed section 6.3 
as it’s not relevant to 
this study and 
endpoints are captured 
in section 6.2 
D 
14-Apr-23 
92120219 Rev/Ver G 
• 
Correction made to 
EC#3 in table 8.2-1 
• 
Update made 
throughout to increase 
the timeline for 
baseline imaging from 
7 days to 14 days to 
accommodate 
scheduling of patients 
 
 

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2. 
Protocol Synopsis 
A Pilot Study to Assess WATCHMAN FLX™ Implants by Cardiac 
Computed Tomography, Magnetic Resonance Imaging and 
Transesophageal Echocardiography: WATCHMAN FLX™ CT 
Study 
Objective(s) 
The primary objective of this study is to measure device tissue 
coverage post-implantation of the WATCHMAN FLX™ Left Atrial 
Appendage Closure (LAAC) Device (WATCHMAN FLX) using the 
serial advanced imaging modalities of cardiac computed tomography 
(CT) and transesophageal echocardiography (TEE) and assess its 
relationship, if any, to clinical events.  
Indication(s)  
for Use 
As per the product Instructions for Use (IFU), WATCHMAN FLX is 
intended to prevent thrombus embolization from the left atrial 
appendage and reduce the risk of life-threatening bleeding events in 
patients with non-valvular atrial fibrillation who are eligible for 
anticoagulation therapy or who have a contraindication to 
anticoagulation therapy. 
Commercial 
Device(s) 
Applied as 
Standard of 
Care and Sizes 
Commercially available WATCHMAN FLX™ Left Atrial 
Appendage Closure Device sizes 20mm, 24mm, 27mm, 31mm, and 
35mm 
Note 1: The WATCHMAN FLX LAAC Device comes preloaded on 
the WATCHMAN FLX Delivery Catheter. The preloaded delivery 
system is used in conjunction with a commercially available 
WATCHMAN® Access System (access sheath and dilator). 
Study Design 
WATCHMAN FLX™ CT is a prospective, single-arm, single-
center, post-market investigation to assess device tissue coverage in 
subjects with non-valvular atrial fibrillation (AF) who receive the 
WATCHMAN FLX device to reduce the risk of stroke. Serial 
advanced imaging modalities such as CT and TEE will be used. A 
core laboratory will independently assess select results. 
A subject is considered enrolled in the study when the subject or the 
subject’s legally authorized representative signs an Informed 
Consent Form (ICF) approved by the Independent Ethics Committee 
(IEC). Up to 25 subjects in whom placement of a WATCHMAN 
device is attempted will be enrolled. 
A baseline assessment including TEE and/or CT imaging with 
optional cardiac magnetic resonance imaging (MRI) will be done 
within 14 days prior to the index procedure following core 

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A Pilot Study to Assess WATCHMAN FLX™ Implants by Cardiac 
Computed Tomography, Magnetic Resonance Imaging and 
Transesophageal Echocardiography: WATCHMAN FLX™ CT 
laboratory guidelines. Follow-up clinical assessment and imaging 
will occur at 14 days, 45 days, and 3 months post index procedure; 
only clinical assessment will be required at 12 months (unless an in-
person assessment is required based on other data). Subjects who are 
enrolled but not implanted with a WATCHMAN LAAC device will 
be followed for safety through 12 months after the initial attempted 
index procedure but will not undergo imaging assessments or 
evaluation of biochemical markers including measures of 
coagulation, platelet and endothelial activation and inflammation.  
The study design is summarized below. 
 
WATCHMAN FLX CT Study Design Overview 
Eligibility is determined per standard of care. Any additional study specific testing 
to verify inclusion/exclusion criteria must be done after the ICF is signed. 
Abbreviation: ICF=Informed Consent Form 
Planned 
Number of 
Subjects 
Up to 25 subjects in whom placement of a WATCHMAN device is 
attempted will be enrolled. 
Planned 
Number of 
Centers / 
Countries 
There will be 1 investigational center in western Europe. 
Primary 
Endpoint 
• Device surface morphology (inclusive of tissue coverage) post 
implant procedure as assessed over time using the serial advanced 
imaging modalities of cardiac computed tomography (CT) and 
transesophageal echocardiography (TEE) 
 

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A Pilot Study to Assess WATCHMAN FLX™ Implants by Cardiac 
Computed Tomography, Magnetic Resonance Imaging and 
Transesophageal Echocardiography: WATCHMAN FLX™ CT 
Additional 
Endpoints 
Endpoint measurements will be collected peri- and post-procedure, 
predischarge, and at 14 days, 45 days, 3 months, and 12 months after 
the implant procedure, unless otherwise specified below.  
• Endpoints adjudicated by an independent Clinical Events 
Committee (CEC): 
o All-cause mortality (cardiovascular/unknown and non-
cardiovascular) 
o Stroke (disabling and non-disabling; ischemic and 
hemorrhagic) 
Note 2: For subjects diagnosed with a neurological event (e.g., 
stroke, TIA), mRS and NIHSS should be performed after the event. 
It is recommended that the subject be contacted regarding mRS 
assessment at 90±14 days following any suspected stroke; the 
simplified mRS questionnairea may be used for this follow-up 
assessment. It is also recommended that imaging be performed 
after the event to screen for device related thrombus. If performed, 
imaging results should be sent to the core laboratory.  
 
o Systemic embolism 
o Bleeding: International Society on Thrombosis and 
Haemostasis (ISTH) major and non-major clinically 
significant 
 Procedural bleeding (≤7 days post-procedure) 
 Non-procedural bleeding (>7 days post-procedure) 
o Pericardial effusion/tamponade requiring pericardiocentesis 
or surgery 
• Endpoints not adjudicated by an Independent Clinical Events 
Committee (CEC): 
• Device success: defined as implantation of a WATCHMAN FLX 
device without in-hospital mortality 
• Assessments by serial imaging modalities (CT and TEE; cardiac 
MRI optional) at 14 days, 45 days, and 3 months; data will be 
evaluated by an independent core lab 
• Device seal post index implant procedure (see Note 3)  

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A Pilot Study to Assess WATCHMAN FLX™ Implants by Cardiac 
Computed Tomography, Magnetic Resonance Imaging and 
Transesophageal Echocardiography: WATCHMAN FLX™ CT 
• Device-related thrombus (including hypoattenuated thickening 
[HAT] per CT analysis)  
• Device surface morphology (inclusive of tissue coverage) post 
implant procedure as assessed over time 
Note 3: Results are classified as no leak, leak >0 and ≤5mm, or 
leak >5mm  
Note 4: TEE is required at 12 months if the 3-month TEE 
assessment suggests a leak > 5mm or the 3-month CT assessment 
suggests a leak > 3mm; results must be sent to the core laboratory.  
• 4D cardiac MRI flow analysis (if available) of the left atrium (LA) 
and LAA before and serially after device implant at 14 days, 45 
days, and 3 months; data will be evaluated by an independent core 
lab 
• Changes compared to baseline in measures of biochemical markers 
including coagulation, platelet and endothelial activation and 
inflammation at 14 days, 45 days, and 3 months post implant 
procedure; correlations with morphological findings from imaging 
assessment of the device surface will be examined 
a: Bruno A, et al. Stroke 2011;42:2276-2279 
Follow-up 
Schedule 
Follow-up for all subjects will occur post-implant on the procedure 
day, at predischarge, and at 14 days, 45 days, 3 months, and 
12 months post index procedure. Follow-up will include clinical 
assessments at all time points and imaging assessments at 14 days, 
45 days, and 3 months. Subjects who are enrolled but not implanted 
with a WATCHMAN FLX device in the correct position will be 
followed for safety through 12 months after the initial attempted 
index procedure but will not undergo imaging assessments or 
evaluation of biochemical markers including measures of 
coagulation, platelet and endothelial activation and inflammation. 
The study will be considered complete after all available subjects 
have finished the 12-month follow-up visit. 
Study 
Duration 
Subjects will be followed for 12 months after the index procedure. 

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A Pilot Study to Assess WATCHMAN FLX™ Implants by Cardiac 
Computed Tomography, Magnetic Resonance Imaging and 
Transesophageal Echocardiography: WATCHMAN FLX™ CT 
Enrollment is expected to take minimally 5 months; therefore, the 
total study duration from first subject enrolled to last subject follow-
up is estimated to be at least 17 months. 
Participant 
Duration 
The study duration for each subject is expected to be approximately 
12 months. 
Inclusion 
Criteria 
Inclusion criteria are listed below. 
IC1.  Subject is of legal age to participate in the study per the laws of 
their respective geography. 
IC2. 
Subject has documented non-valvular atrial fibrillation (i.e., 
atrial fibrillation in the absence of moderate or greater mitral 
stenosis or a mechanical heart valve). 
IC3. 
Subject is clinically indicated for a WATCHMAN FLX device. 
IC4. 
Subject is deemed suitable for the protocol-defined 
pharmacologic regimen. 
IC5. 
Subject or legal representative is able to understand and willing 
to provide written informed consent to participate in the study. 
IC6. 
Subject is able and willing to return for required follow-up 
visits and examinations. 
Exclusion 
Criteria  
 
Exclusion criteria are listed below. 
EC1.  Subject is currently enrolled in another investigational study, 
except if the subject is participating in a mandatory 
governmental registry, or a purely observational registry with 
no associated treatment. 
EC2. Subject has eGFR <30 mL/min (chronic kidney disease 
stage IV or stage V). 
EC3. Subject is contraindicated for TEE. 
EC4. Subject requires long-term anticoagulation therapy for reasons 
other than AF-related stroke risk reduction (e.g., due to an 
underlying hypercoagulable state). 
EC5. Subject had or is planning to have any cardiac or non-cardiac 
intervention or surgical procedure within 30 days prior to or 60 
days after implant (including, but not limited to, cardioversion, 
percutaneous coronary intervention, cardiac ablation, cataract 
surgery, etc.). 

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A Pilot Study to Assess WATCHMAN FLX™ Implants by Cardiac 
Computed Tomography, Magnetic Resonance Imaging and 
Transesophageal Echocardiography: WATCHMAN FLX™ CT 
EC6. Subject had a prior stroke (of any cause, whether ischemic or 
hemorrhagic) or transient ischemic attack (TIA) within the 30 
days prior to enrollment. 
EC7. Subject had a prior major bleeding event per ISTH definitions 
within the 30 days prior to enrollment. Lack of resolution of 
related clinical sequelae or planned and pending interventions 
to resolve bleeding/bleeding source are a further exclusion 
regardless of timing of the bleeding event. 
EC8. Subject has an active bleed. 
EC9. Subject has a reversible cause for AF or has transient AF. 
EC10. Subject has no LAA or the LAA is surgically ligated. 
EC11. Subject has had a myocardial infarction (MI) documented in 
the clinical record as either a non-ST elevation MI (NSTEMI) 
or as an ST-elevation MI (STEMI), with or without 
intervention, within 30 days prior to enrollment. 
EC12. Subject has a history of atrial septal repair or has an atrial 
septal defect/patent foramen ovale (ASD/PFO) device. 
EC13. Subject has a known contraindication to percutaneous 
catheterization procedure. 
EC14.  Subject has a cardiac tumor. 
EC15.  Subject has signs/symptoms of acute or chronic pericarditis. 
EC16.  Subject has an active infection. 
EC17.  There is evidence of tamponade physiology. 
EC18. Subject has New York Heart Association Class IV congestive 
heart failure at the time of enrollment. 
EC19. Subject is of childbearing potential and is, or plans to become, 
pregnant during the time of the study (method of assessment 
per study physician’s discretion). 
EC20. Subject has a documented life expectancy of less than 
6 months. 
Adjunctive 
Pharmacologic 
Therapy 
Subjects must be treated with single antiplatelet therapy (SAPT; 
aspirin or P2Y12 inhibitor) for at least 3 months following 
WATCHMAN FLX implantation.   

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A Pilot Study to Assess WATCHMAN FLX™ Implants by Cardiac 
Computed Tomography, Magnetic Resonance Imaging and 
Transesophageal Echocardiography: WATCHMAN FLX™ CT 
Multiple 
Interventions 
During Index 
Procedure 
No concomitant procedures are to be performed at the time of the 
WATCHMAN FLX implant procedure with the exception of 
implantable loop recorder implants/explants. This includes, but is 
not limited to, cardiac ablation procedures, transcutaneous valve 
procedures, cardioversions, coronary stent implantation, pacemaker 
or implantable cardioverter defibrillator generator change, etc. 
Statistical Methods 
Analysis Sets 
Analysis sets are listed below. 
- 
Intention-To-Treat (ITT): This population includes all subjects 
who sign an ICF and are enrolled in the study, regardless of 
whether the study device is implanted.  
- 
Implanted: This population includes all subjects who sign an ICF, 
are enrolled in the study, and are successfully implanted with the 
study device in the correct position. 
Statistical 
Hypothesis 
There is no formal statistical hypothesis for this observational, 
single-arm study. No statistical inference will be made in the study. 
Methods  
Outcomes in the overall treatment cohort will be summarized using 
descriptive statistics for continuous variables (mean, standard 
deviation, number of observations, minimum and maximum) and 
discrete variables (percentage and count/sample).  
 
 

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3. 
Table of Contents 
1. 
TITLE PAGE  .......................................................................................................................1 
2. 
PROTOCOL SYNOPSIS .........................................................................................................4 
3. 
TABLE OF CONTENTS .......................................................................................................11 
3.1. Table of Figures .....................................................................................................14 
3.2. Table of Tables ......................................................................................................14 
4. 
INTRODUCTION ................................................................................................................16 
4.1. Background ............................................................................................................16 
4.1.1. 
Atrial Fibrillation, Stroke, and the LAA ...................................................16 
4.1.2. 
WATCHMAN and LAAO .......................................................................16 
4.1.3. 
Cardiac Imaging ........................................................................................17 
4.2. Study Rationale .....................................................................................................18 
5. 
COMMERCIAL DEVICE DESCRIPTION (PART OF STANDARD OF CARE) ..........................18 
5.1. Overview of WATCHMAN FLX .........................................................................18 
5.2. Overview of the WATCHMAN Access System (Access Sheath and Dilator) .20 
5.3. Device Labeling .....................................................................................................21 
5.4. Required Procedures and Medications ...............................................................21 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................................21 
6.1. Study Objectives ....................................................................................................21 
6.2. Study Endpoints ....................................................................................................21 
7. 
STUDY DESIGN .................................................................................................................23 
7.1. Scale and Duration ................................................................................................23 
7.2. Treatment Assignment..........................................................................................24 
7.3. Justification for the Study Design ........................................................................24 
8. 
SUBJECT SELECTION ........................................................................................................25 
8.1. Inclusion Criteria ..................................................................................................25 
8.2. Exclusion Criteria .................................................................................................25 
9. 
SUBJECT ACCOUNTABILITY .............................................................................................26 
9.1. Point of Enrollment ...............................................................................................26 

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9.2. Withdrawal ............................................................................................................27 
9.3. Lost to Follow-Up ..................................................................................................27 
9.4. End-of-Study Definition .......................................................................................28 
9.5. Subject Status and Classification .........................................................................28 
10. STUDY METHODS .............................................................................................................29 
10.1. Data Collection ......................................................................................................29 
10.2. Study Candidate Screening ..................................................................................32 
10.3. Subject Informed Consent ....................................................................................32 
10.4. Baseline Assessments ............................................................................................33 
10.5. Pre-procedure Medications ..................................................................................34 
10.6. Index Procedure ....................................................................................................34 
10.7. Predischarge ..........................................................................................................35 
10.8. Follow-up ...............................................................................................................35 
10.8.1. 14-Day Follow-up (14 Days ±3 Days) .....................................................36 
10.8.2. 45-Day Follow-up (45±15 Days) and 3-Month Follow-up (90±30 Days)
 37 
10.8.3. 12-Months Follow-up (365±30 Days) ......................................................38 
10.9. Study Completion ..................................................................................................38 
10.10. 
Source Documents ..................................................................................38 
11. STATISTICAL CONSIDERATIONS ......................................................................................39 
11.1. Endpoints ...............................................................................................................39 
11.2. General Statistical Methods .................................................................................39 
11.2.1. Analysis Sets .............................................................................................39 
11.2.2. Control of Systematic Error/Bias ..............................................................40 
11.2.3. Number of Subjects per Investigative Center ...........................................40 
11.3. Data Analyses ........................................................................................................40 
12. DATA MANAGEMENT .......................................................................................................40 
12.1. Data Collection, Processing, and Review ............................................................40 
12.2. Data Retention .......................................................................................................41 
12.3. Core Laboratory....................................................................................................41 
13. DEVIATIONS .....................................................................................................................41 

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14. COMPLIANCE ....................................................................................................................42 
14.1. Statement of Compliance ......................................................................................42 
14.2. Investigator Responsibilities ................................................................................42 
14.2.1. Delegation of Responsibility ....................................................................44 
14.3. Independent Ethics Committee ............................................................................44 
14.4. Sponsor Responsibilities .......................................................................................45 
14.4.1. Role of Boston Scientific Corporation Representatives ...........................45 
14.4.2. Training .....................................................................................................46 
14.5. Insurance ................................................................................................................46 
15. MONITORING ....................................................................................................................46 
16. POTENTIAL RISKS AND BENEFITS ...................................................................................46 
16.1. Instructions for Use ...............................................................................................46 
16.2. Risks Associated with Participation in the Clinical Study ................................47 
16.3. Possible Interactions with Concomitant Medical Treatments ..........................47 
16.4. Risk Minimization Actions ...................................................................................47 
16.5. Anticipated Benefits ..............................................................................................48 
17. SAFETY REPORTING .........................................................................................................48 
17.1. Reportable Events by Investigational Center to Boston Scientific ...................48 
17.2. Definitions and Classification ..............................................................................49 
17.3. Relationship to Study Device(s), (Device Under Study) and/or Study 
Procedure ...............................................................................................................51 
17.4. Investigator Reporting Requirements .................................................................53 
17.5. Device Deficiencies ................................................................................................54 
17.6. Reporting to Regulatory Authorities / IECs / Investigators .............................55 
18. INFORMED CONSENT........................................................................................................55 
19. COMMITTEES ...................................................................................................................56 
19.1. Safety Monitoring Process ....................................................................................56 
19.1.1. Clinical Events Committee .......................................................................57 
20. SUSPENSION OR TERMINATION .......................................................................................57 
20.1. Premature Termination of the Study ..................................................................57 

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20.1.1. Criteria for Premature Termination of the Study ......................................57 
20.2. Termination of Study Participation by the Investigator or Withdrawal of IEC 
Approval ................................................................................................................58 
20.3. Requirements for Documentation and Subject Follow-up ................................58 
20.4. Criteria for Suspending/Terminating a Study Center .......................................58 
21. STUDY REGISTRATION AND RESULTS .............................................................................59 
21.1. Study Registration .................................................................................................59 
21.2. Clinical Investigation Report ...............................................................................59 
21.3. Publication Policy ..................................................................................................59 
22. BIBLIOGRAPHY .................................................................................................................59 
23. ABBREVIATIONS AND DEFINITIONS .................................................................................63 
23.1. Abbreviations and Acronyms ..............................................................................63 
23.2. Definitions ..............................................................................................................65 
 
3.1. 
Table of Figures 
Figure 5.1-1: WATCHMAN FLX .......................................................................................... 19 
Figure 7.1-1: WATCHMAN FLX CT Study Design Overview............................................. 24 
Figure 10.1-1: WATCHMAN FLX CT Study Event Schedule Summary Diagram .............. 32 
 
3.2. 
Table of Tables 
Table 5.1-1: WATCHMAN FLX Device Selection ............................................................... 19 
Table 5.1-2: WATCHMAN FLX Additional Features ........................................................... 20 
Table 8.1-1: Inclusion Criteria ................................................................................................ 25 
Table 8.2-1: Exclusion Criteria ............................................................................................... 25 
Table 9.5-1: Subject Status and Classification ....................................................................... 28 
Table 10.1-1: WATCHMAN FLX CT Study Event Schedule ............................................... 30 
Table 10.10-1: Source Documentation Requirements ............................................................ 39 
Table 17.2-1: Safety Definitions ............................................................................................. 49 

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Table 17.3-1: Criteria for Assessing Relationship of Study Device(s) (Device Under Study) 
or Procedure to Adverse Event ....................................................................... 51 
Table 17.4-1: Investigator Reporting Requirements ............................................................... 53 
Table 23.1-1: Abbreviations and Acronyms ........................................................................... 63 
Table 23.2-1: Definitions ........................................................................................................ 65 
 
 

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4. 
Introduction 
This protocol specifies procedures for and contains information relevant to the clinical study 
entitled “A Pilot Study to Assess WATCHMAN FLX™ Implants by Cardiac Computed 
Tomography, Magnetic Resonance Imaging and Transesophageal Echocardiography” 
(WATCHMAN FLX™ CT). The study will measure device tissue coverage post 
implantation of the WATCHMAN FLX™ Left Atrial Appendage Closure Device 
(WATCHMAN FLX) and assess its relationship, if any, to clinical events. Serial advanced 
imaging modalities to be used in the study include cardiac computed tomography (CT) and 
transesophageal echocardiography (TEE). Approximately 25 consented subjects will be 
enrolled. Data for subjects receiving the WATCHMAN FLX device will be collected over 
12 months.  
Additional information on the commercially available device can be found in Section 5. 
Additional information on study design can be found in Section 7.  
4.1. 
Background 
4.1.1. 
Atrial Fibrillation, Stroke, and the LAA 
Atrial fibrillation (AF) is a common abnormal cardiac rhythm disturbance characterized by 
an irregular and often fast heart rhythm that results in uncoordinated contraction of the atria. 
The Global Burden of Disease project estimated approximately 46.3 million individuals 
worldwide were affected by AF/atrial flutter in 20161. Its prevalence is age-dependent with a 
frequency exceeding 15% among individuals 80 years or older2. It is a major cause of sudden 
cardiovascular death and heart failure3 and a major risk factor for ischemic stroke, with a 
poor prognosis regarding survival and residual disability4-6. The prevalence of AF is expected 
to rise over time due to the aging worldwide population7-9.  
Thrombus formation from stagnant blood flow in AF can lead to thromboembolism and 
stroke10. Reports have suggested that up to 90% of thrombi in the left atria of patients with 
nonvalvular atrial fibrillation (NVAF) are located in the left atrial appendage (LAA)11-13. The 
relative stasis that occurs in the LAA due to its narrow entrance orifice and interior 
trabeculations contributes to the observed thrombogenicity14. In patients with NVAF, initial 
stroke reduction therapy includes systemic oral anticoagulation (OAC) with warfarin and/or 
direct oral anticoagulants (DOACs) such as abigatran, rivaroxaban, apixaban, and 
edoxaban15-18. Given the observed long-term OAC limitations such as increased risk of major 
bleeding, drug interactions, and patient non-compliance19,20, percutaneous LAA occlusion 
(LAAO) has been developed as a nonpharmacologic alternative9,21.  
4.1.2. 
WATCHMAN and LAAO 
As noted above, percutaneous occlusion of the LAA is an alternative treatment for AF 
patients who are at high risk of stroke and not eligible for long-term anticoagulation therapy. 
The WATCHMANTM Left Atrial Appendage Closure (LAAC) Device (WATCHMAN) is a 
permanent implantable device designed to seal off the LAA22. The implant includes a self-

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expanding nitinol frame structure with fixation anchors around the perimeter and a permeable 
polyester fabric (polyethylene terephthalate; PET) that covers the atrial-facing implant 
surface. The WATCHMAN device received Conformité Européenne (CE) mark in 2005 and 
United States Food and Drug Administration (FDA) approval in 2015. 
The safety and efficacy of WATCHMAN was assessed in two multicenter randomized 
controlled trials (RCT) comparing outcomes with the device versus warfarin in high-stroke-
risk NVAF patients intolerant of long-term anticoagulation. In PROTECT AF (N=463 
WATCHMAN, N=244 warfarin), WATCHMAN was noninferior to warfarin in terms of the 
primary efficacy endpoint of stroke, cardiovascular/unexplained death, and systemic 
embolism (SE)23. In the subsequent PREVAIL RCT (N=269 WATCHMAN, N=138 
warfarin), WATCHMAN was noninferior to chronic warfarin for the prevention of ischemic 
stroke and SE >7 days post procedure; the short-term complication rate that was observed in 
PROTECT AF was also reduced24. A meta-analysis of the two trials at 5-year follow-up 
showed similar rates for the combined stroke and SE endpoint but a significantly lower rate 
of hemorrhagic stroke, disabling stroke, non-procedural bleeding, and all-cause mortality 
with WATCHMAN25.  
The iterative WATCHMAN FLX™ LAAC Device (WATCHMAN FLX; see Section 5.1) 
was assessed in the prospective, nonrandomized, multicenter PINNACLE FLX study 
(N=400)26. The primary safety end point was the occurrence by hospital discharge or 7 days 
post procedure, whichever came later, of one of the following events: death, ischemic stroke, 
systemic embolism, device- or procedure-related events requiring cardiac surgery. The 
primary effectiveness end point was the incidence of effective LAA closure (peri-device flow 
≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. The 
primary safety endpoint was met with a rate of 0.5% and a 1-sided 95% upper confidence 
interval (CI) of 1.6%, which was significantly below the performance goal of 4.2% 
(P<0.0001). The primary effectiveness endpoint was met with a rate of 100% and a 1-sided 
95% lower CI of 99.1%, which met the performance goal of 97.0% (P<0.0001). 
WATCHMAN FLX received CE mark in 2015 and FDA approval in 202027. 
4.1.3. 
Cardiac Imaging  
Healing post LAAO includes endothelialization of the LAA device. In a preclinical canine 
model, the PET fabric membranes of implanted WATCHMAN devices showed an organized 
neoendocardial surface at 45 days with endothelialization well under way by 90 days28.  
Human necropsy hearts showed similar healing stages, though animal healing was faster28.   
In patients, pre-procedural anatomical assessment of the LAA with TEE, CT, or cardiac 
magnetic resonance imaging (MRI) is used to determine the technical feasibility and safety 
of LAA occlusion, including device sizing and optimal implant positioning. A multimodality 
integrated approach including angiography, TEE, and/or intracardiac echocardiography (ICE) 
provides intraprocedural guidance and confirmation of LAA closure29-31. After the procedure, 
imaging surveillance at follow-up allows assessment of device tissue coverage, peri-device 
leaks, and device-related thrombus (DRT), which has been observed with various LAAO 
devices and may be associated with late thromboembolic events32-37.  

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The current WATCHMAN FLX Instructions for Use (IFU) recommends use of TEE at 45 
days post device implant to check for the presence of intra-cardiac thrombus as well as to 
detect and measure any residual flow around the device. The objective of the WATCHMAN 
FLX CT study is to assess device endothelialization at several time points in addition to the 
recommended 45 days using serial CT and TEE and assess its relationship, if any, to clinical 
events.  
4.2. 
Study Rationale 
The purpose of the WATCHMAN FLX CT study is to evaluate the device tissue coverage 
post-implantation using serial advanced imaging modalities such as CT and TEE and assess 
its relationship, if any, to clinical events.  
5. 
Commercial Device Description (part of Standard of Care) 
As per the product Instructions for Use (IFU), the WATCHMAN FLX™ Left Atrial 
Appendage Closure Device (Boston Scientific Corporation, Marlborough, MA, USA) is 
intended to prevent thrombus embolization from the left atrial appendage (LAA) and reduce 
the risk of life-threatening bleeding events in patients with non-valvular atrial fibrillation 
who are eligible for anticoagulation therapy or who have a contraindication to 
anticoagulation therapy. Please see the product IFU for any contraindications. 
The commercially available WATCHMAN FLX LAA Closure Device comes preloaded on 
the WATCHMAN FLX Delivery Catheter (Section 5.1). In the WATCHMAN FLX CT 
study, this preloaded delivery system may be used in conjunction with any version of the 
commercially available WATCHMAN® Access System (access sheath and dilator; 
Section 5.3) to facilitate device placement in the LAA via femoral venous access and 
crossing of the inter-atrial septum into the left atrium. 
The study will only use commercial devices. Device tracking and disposition will be captured in 
the study database.  
5.1. 
Overview of WATCHMAN FLX  
The commercially available WATCHMAN FLX device has two main parts: a WATCHMAN 
FLX LAA Closure Device implant and a delivery catheter for implant introduction and 
placement.  
The delivery catheter (Panel A in Figure 5.1-1) consists of an inner core wire with a 
reinforced braided jacket that is connected to the deployment knob at the proximal end and a 
screw thread assembly at the distal end. The outer sheath has an overall profile of 12F.  
The implant (Panel B in Figure 5.1-1) consists of a self-expanding nitinol frame structure 
with fixation anchors around the perimeter and a permeable polyester fabric (polyethylene 
terephthalate) that covers the atrial-facing implant surface. Table 5.1-1 shows the 
five available implant sizes. Appropriate sizing is determined by LAA measurements using 
fluoroscopy and echocardiographic guidance.  

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Figure 5.1-1: WATCHMAN FLX  
A: Delivery Catheter; B: LAA Closure Device implant 
Abbreviations: LAA=left atrial appendage; PET=polyethylene terephthalate 
Table 5.1-1: WATCHMAN FLX Device Selection 
Maximum Left Atrial Appendage Ostium Width (mm)  
Closure Device Size (mm)  
14.0 – 18.0  
20  
16.8 – 21.6  
24  
18.9 – 24.3  
27  
21.7 – 27.9  
31  
24.5 – 31.5  
35  
 
The WATCHMAN FLX LAA Closure Device implant is pre-loaded on the delivery catheter 
and is constrained within the catheter until deployment in the LAA. The implant is 
introduced percutaneously via femoral venous access using conventional catheterization 
techniques and is placed in the LAA after crossing the inter-atrial septum. It is deployed by 
loosening the valve on the delivery catheter and retracting the outer sheath. The implant can 
be partially recaptured and redeployed if initial placement is too distal. If the initial implant 
placement is too proximal, it can be fully recaptured and redeployed. The device is designed 
to be permanently implanted at or slightly distal to the ostium of the LAA to trap potential 

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emboli before they exit the LAA. The placement procedure can be done under local or 
general anesthesia. More detailed product information can be found in the commercial IFU.  
The WATCHMAN FLX device offers additional features compared to the predicate 
WATCHMAN™ Left Atrial Appendage Closure Device with Delivery System, as described 
in Table 5.1-2. 
Table 5.1-2: WATCHMAN FLX Additional Features 
Feature  
Purpose 
Closed distal end 
Provides improved deployment stability and control, with atraumatic 
distal structure 
Fully recapturable and re-
deployable 
Decrease the number of devices used and sheath exchanges per case, 
which may reduce procedure time and complications associated with 
sheath exchange 
Decreased recapture force 
Improve user experience 
Increased conformability 
Create a better LAA seal due to the increased number of contact 
points around the LAA ostium, which was designed to promote short-
term healing 
Decreased exposed metal 
volume on proximal face 
May promote short-term healing 
Enhanced radiopacity 
Improve visibility under fluoroscopy 
Smaller and larger device sizes 
Allow for treatment of complex, shallow LAA anatomies 
Greater overlap in device sizing 
choices 
Allow for treatment of a wider range of appendage sizes 
Note 1: Additional features as compared to the predicate WATCHMAN™ device. 
Abbreviation: LAA=left atrial appendage 
 
5.2. 
Overview of the WATCHMAN Access System (Access Sheath and Dilator)  
Commercially available access systems to use with WATCHMAN FLX include the 
WATCHMAN® Access System, the WATCHMAN™ TruSeal™ Access System, and the 
WATCHMAN FXD Curve™ Access System. They all have a dilator and access sheath, 
which are used to gain access to the LAA once initial transseptal entrance into the left atrium 
has been established. The distal end of the access sheath is available in multiple curve styles 
for coaxial placement in the LAA. The distal tip contains a marker band for in situ 
visualization and sizing marker bands to facilitate appropriate sheath positioning in the LAA 
based on the WATCHMAN FLX device size selected.  
Once the access sheath is positioned in the left atrium and the dilator has been removed, the 
sheath serves as a conduit for the WATCHMAN FLX Delivery System. The delivery system 
is introduced into the access sheath and the components snap together to act as one during 
device implantation. Additional product information can be found in the associated Access 
System IFUs.  

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5.3. 
Device Labeling 
A basic description of the device and a comprehensive set of Instructions for Use are 
contained in each commercial product package. 
5.4. 
Required Procedures and Medications 
A commercial training program has been established for the WATCHMAN FLX™ Left 
Atrial Appendage Closure Device (Section 14.4.2). Please see Section 10 for additional 
information on study methods. 
6. 
Study Objectives and Endpoints 
6.1. 
Study Objectives 
The primary objective of this study is to measure device tissue coverage post-implantation of 
the WATCHMAN FLX™ Left Atrial Appendage Closure (LAAC) Device (WATCHMAN 
FLX) using the serial advanced imaging modalities of cardiac computed tomography (CT) 
and transesophageal echocardiography (TEE) as well as device seal based on TEE and assess 
their its relationship, if any, to clinical events.  
6.2. 
Study Endpoints 
Outcomes in WATCHMAN FLX CT will be assessed on an intention-to-treat (ITT) basis 
and an implanted basis. The ITT analysis set includes all subjects who sign an Informed 
Consent Form (ICF; see Section 18) approved by the Independent Ethics Committee (IEC) 
and are enrolled in the study (see Section 9.1 for point of enrollment), whether or not the 
WATCHMAN FLX device is implanted. The implanted analysis set includes ITT subjects 
who are successfully implanted with the study device in the correct position.  
Endpoints are listed below. Measurements will be collected peri- and post-procedure, 
predischarge, and at 14 days, 45 days, 3 months and 12 months after the implant procedure, 
unless specified otherwise.  
 
The primary endpoint is device surface morphology (inclusive of tissue coverage) post 
implant procedure as assessed over time using the serial advanced imaging modalities of 
cardiac computed tomography (CT) and transesophageal echocardiography (TEE). 
 
 
 
 
Additional endpoints will include the following:  

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• Endpoints adjudicated by an Independent Clinical Events Committee (CEC): 
o All-cause mortality (cardiovascular/unknown and non-cardiovascular) 
o Stroke (disabling and non-disabling; ischemic and hemorrhagic) 
o Note 1: For subjects diagnosed with a neurological event (e.g., stroke, transient 
ischemic attack [TIA]), mRS and NIHSS should be performed after the event. It is 
recommended that the subject be contacted regarding mRS assessment at 90±14 
days following any suspected stroke; the simplified mRS questionnaire38 may be 
used for this follow-up assessment. It is recommended that imaging be performed 
after the event to screen for device related thrombus (DRT). If performed, 
imaging results should be sent to the core laboratory. 
 
o Systemic embolism 
o Bleeding: International Society on Thrombosis and Haemostasis (ISTH) major and 
non-major clinically significant 
 Procedural bleeding (≤7 days post-procedure) 
 Non-procedural bleeding (>7 days post-procedure) 
o Pericardial effusion/tamponade requiring pericardiocentesis or surgery  
• Endpoints not adjudicated by an Independent Clinical Events Committee (CEC): 
• Device success: defined as implantation of a WATCHMAN FLX device without in-
hospital mortality 
• Assessments by serial imaging modalities (CT and TEE, optional cardiac magnetic 
resonance imaging [MRI]) at 14 days, 45 days, and 3 months (TEE optional at 3 months 
if there is no leak at 45 days). Data will be evaluated by an independent core lab. 
o Device seal at 45 days post index implant procedure (see Note 2) 
o Device-related thrombus (including hypoattenuated thickening [HAT] per CT 
analysis) 
o Device surface morphology (inclusive of tissue coverage) post implant procedure as 
assessed over time 
Note 2: Results are classified as no leak, leak >0 and ≤5mm, or leak >5mm 
Note 3: TEE should be performed at 12 months if the 3-month TEE assessment 
suggests a leak > 5mm or the 3-month CT assessment suggests a leak > 3mm; results 
must be sent to the core laboratory. 
• 4D MRI flow analysis (if available) of the left atrium (LA) and LAA before (14 days 
prior to the index procedure) and serially after device implant (at 14 days, 45 days, and 
3 months); data will be evaluated by an independent core lab 
• Changes compared to baseline in measures of biochemical markers including 
coagulation, platelet and endothelial activation and inflammation over time post implant 

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procedure (at 14 days, 45 days, and 3 months); correlations with morphological findings 
from imaging assessment of the device surface will be examined  
 
7. 
Study Design 
WATCHMAN FLX™ CT is a prospective, single-arm, single-center, post-market 
investigation to assess device tissue coverage in subjects with non-valvular atrial 
fibrillation (AF) who receive the WATCHMAN FLX device to reduce the risk of stroke. 
Serial advanced imaging modalities such as CT and TEE will be used. A core laboratory 
will independently assess select results. 
7.1. 
Scale and Duration 
Up to 25 subjects in whom placement of a WATCHMAN device is attempted will be 
enrolled in WATCHMAN FLX CT in 1 investigational center in western Europe. Eligibility 
for the study is determined per standard of care. Any additional study specific testing to 
verify inclusion/exclusion criteria (see Section 8 below) must be done after the ICF is signed.  
All subjects will be assessed at baseline and post-implant on the procedure day, at 
predischarge, and at 14 days, 45 days, 3 months, and 12 months post index procedure. 
Follow-up will include in-person clinical assessments at all time points except 12 months (in 
person [preferred] or by telephone). Follow-up imaging assessments will occur at 14 days, 
45 days, and 3 months. Additional imaging may be done at 12 months if required based on 
imaging data obtained at earlier time points.  
Subjects who are enrolled but not implanted with a WATCHMAN FLX device will be 
followed for safety through 12 months after the initial attempted index procedure but will not 
undergo imaging assessments or evaluation of biochemical markers including measures of 
coagulation, platelet and endothelial activation and inflammation. Figure 7.1-1 provides an 
overview of the study design.   

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Figure 7.1-1: WATCHMAN FLX CT Study Design Overview 
Eligibility for the study is determined per standard of care. Any additional study specific testing to verify 
inclusion/exclusion criteria must be done after the ICF is signed. 
Abbreviations: CT=computed tomography; ICF=Informed Consent Form 
Enrollment is expected to take minimally 5 months; therefore, the total study duration from 
first subject enrolled to last subject follow-up is estimated to be at least 17 months. The study 
duration for each subject is expected to be approximately 12 months. 
The WATCHMAN FLX CT study will be registered at www.ClinicalTrials.gov prior to 
enrollment of the first subject (see Section 21.1). 
7.2. 
Treatment Assignment 
WATCHMAN FLX CT is a post-market study. All subjects who meet all inclusion criteria 
and no exclusion criteria can be enrolled. A subject is considered enrolled in the study when 
the subject or the subject’s legally authorized representative signs an ICF approved by the 
IEC. See Section 5.1 for a detailed description of the device and information on device sizes. 
7.3. 
Justification for the Study Design 
WATCHMAN FLX CT is an observational post-market study designed to assess device 
tissue coverage with the use of serial advanced imaging modalities such as CT and MRI. To 
support the stated objectives of this study (see Section 6.1) while also limiting the potential 
exposure of study subjects to risk, approximately 25 subjects will be enrolled at 1 center. 
Device implantation will be done according to current indications and device labelling as 
described in the device IFU. Safety and effectiveness results will be reported on all enrolled 
subjects (see Section 17 for information on safety reporting). All subjects will be followed 
for up to 12 months post index procedure. To decrease the risk of thrombotic or 
thromboembolic complications, subjects will be treated with single antiplatelet therapy 
(SAPT) for at least 3 months following WATCHMAN FLX implantation. 

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8. 
Subject Selection  
Eligibility for this study is determined per standard of care. Any subject who meets all the 
inclusion criteria, does not meet any of the exclusion criteria, and who provides written 
informed consent may be considered for enrollment in the study (see Note 1 below). The 
subjects selected for participation may be from the Investigator’s general patient population. 
The investigator has the responsibility for screening all potential subjects and selecting those 
who meet study inclusion criteria and do not meet any of the exclusion criteria as described 
below. All subjects will have unique identification numbers. 
Note 1: Vulnerable subjects (see Table 23.2-1 for the definition of vulnerable subject) will 
not be enrolled in the WATCHMAN FLX CT study. 
8.1. 
Inclusion Criteria 
Subjects who meet all of the criteria in Table 8.1-1 may be given consideration for inclusion 
in this clinical investigation, provided no exclusion criterion (see Section 8.2) is met.  
Table 8.1-1: Inclusion Criteria 
IC1.  
Subject is of legal age to participate in the study per the laws of their respective geography. 
IC2. 
Subject has documented non-valvular atrial fibrillation (i.e., atrial fibrillation in the absence of 
moderate or greater mitral stenosis or a mechanical heart valve). 
IC3. 
Subject is clinically indicated for a WATCHMAN FLX device. 
IC4. 
Subject is deemed suitable for the protocol-defined pharmacologic regimen. 
IC5. 
Subject or legal representative is able to understand and willing to provide written informed consent 
to participate in the study. 
IC6. 
 Subject is able and willing to return for required follow-up visits and examinations. 
Abbreviation: IC=inclusion criterion 
 
8.2. 
Exclusion Criteria  
Exclusion criteria are shown in Table 8.2-1. Subjects who meet any one of these criteria will 
be excluded. 
Table 8.2-1: Exclusion Criteria  
EC1.  Subject is currently enrolled in another investigational study, except if the subject is participating in 
a mandatory governmental registry, or a purely observational registry with no associated treatment. 
EC2. 
Subject has eGFR <30 mL/min (chronic kidney disease stage IV or stage V). 
EC3. 
Subject is contraindicated for TEE. 
EC4. 
Subject requires long-term anticoagulation therapy for reasons other than AF-related stroke risk 
reduction (e.g., due to an underlying hypercoagulable state). 

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Table 8.2-1: Exclusion Criteria  
EC5. 
Subject had or is planning to have any cardiac or non-cardiac intervention or surgical procedure 
within 30 days prior to or 60 days after implant (including, but not limited to, cardioversion, 
percutaneous coronary intervention, cardiac ablation, cataract surgery, etc.). 
EC6. 
Subject had a prior stroke (of any cause, whether ischemic or hemorrhagic) or transient ischemic 
attack (TIA) within the 30 days prior to enrollment. 
EC7. 
Subject had a prior major bleeding event per ISTH definitions within the 30 days prior to enrollment. 
Lack of resolution of related clinical sequelae or planned and pending interventions to resolve 
bleeding/bleeding source are a further exclusion regardless of timing of the bleeding event. 
EC8. 
Subject has an active bleed. 
EC9. 
Subject has a reversible cause for AF or has transient AF. 
EC10. Subject has no LAA or the LAA is surgically ligated. 
EC11. Subject has had a myocardial infarction (MI) documented in the clinical record as either a non-ST 
elevation MI (NSTEMI) or as an ST-elevation MI (STEMI), with or without intervention, within 30 
days prior to enrollment. 
EC12. Subject has a history of atrial septal repair or has an atrial septal defect/patent foramen ovale 
(ASD/PFO) device. 
EC13. Subject has a known contraindication to percutaneous catheterization procedure. 
EC14.  Subject has a cardiac tumor. 
EC15.  Subject has signs/symptoms of acute or chronic pericarditis. 
EC16.  Subject has an active infection. 
EC17.  There is evidence of tamponade physiology. 
EC18. Subject has New York Heart Association Class IV congestive heart failure at the time of enrollment. 
EC19. Subject is of childbearing potential and is, or plans to become, pregnant during the time of the study 
(method of assessment per study physician’s discretion). 
EC20. Subject has a documented life expectancy of less than 6 months. 
Abbreviations: AF=atrial fibrillation; EC=exclusion criterion; eGFR=estimated glomerular filtration rate; 
ISTH=International Society on Thrombosis and Haemostasis; LAA=left atrial appendage; MRI=magnetic 
resonance imaging; TEE=transesophageal echocardiography 
 
9. 
Subject Accountability 
9.1. 
Point of Enrollment 
A subject is considered enrolled in the study when the subject or the subject’s legally 
authorized representative signs an ICF approved by the IEC. No study-specific tests, 
procedures, etc. can take place until the ICF is signed. A subject who is determined to not 
meet study specific clinical eligibility criteria after signing consent will be considered a 
screen failure (see Table 9.5-1) and will not count towards the enrollment ceiling. 

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9.2. 
Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study) 
shall be accounted for and documented. If a subject withdraws from the clinical investigation 
the reason(s) shall be reported. Reasons for withdrawal include but are not limited to 
physician discretion, subject choice to withdraw consent, or death. Reasons for study exit 
will be captured in the secure electronic data capture (EDC) system. If such withdrawal is 
due to problems related to device safety or performance, the investigator shall ask for the 
subject’s permission to follow his/her status/condition outside of the clinical study.   
While all efforts will be made to minimize attrition, subjects may withdraw from the study at 
any time, with or without reason, and without prejudice to further treatment. Withdrawn 
subjects will not undergo any additional study follow-up, nor will they be replaced. The 
investigator may discontinue a subject from participation in the study if the investigator feels 
that the subject can no longer fully comply with the requirements of the study or if any of the 
study procedures are deemed potentially harmful to the subject. Data that have already been 
collected on withdrawn subjects will be retained and may be used for analysis unless local 
regulations apply. No new data will be collected after subject withdrawal.   
All applicable case report forms up to the point of subject withdrawal and an “End of Study” 
form for the subject must be completed. If the withdrawal is due to investigator discretion, 
the investigator should follow-up with the subject per standard of care.  
9.3. 
Lost to Follow-Up 
All enrolled subjects will be followed for up to 12 months post-procedure.  
A subject will be considered lost to follow-up if he or she fails to be available for 
2 consecutive scheduled visits without due cause and is unable to be contacted by study 
center staff. The following actions will be taken if a subject fails to be available for a 
required study visit. 
• The center will attempt to contact the subject and reschedule the missed visit and 
counsel the subject on the importance of maintaining the assigned visit schedule and 
ascertain if the subject wishes to and/or should continue in the study 
• Before a subject is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, if 
necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts will be documented in the subject’s 
medical record or study file. 
• Should the subject continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 

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9.4. 
End-of-Study Definition  
This clinical study will be considered completed when subjects are no longer being examined 
or the last subject’s last study visit as outlined in the data collection schedule (Table 10.1-1 
below) has occurred. All enrolled subjects will be evaluated clinically post-implant on the 
procedure day, at predischarge, at 14 days, 45 days, 3 months, and 12 months post index 
procedure (preferably all in-person visits; see Table 10.1-1 for additional information). 
At the point of study completion and/or withdrawal, all open adverse events must be assessed 
by the investigator. These events must be closed or documented as ongoing. Events assessed 
as related to the device should be followed through resolution if possible and if consent has 
been provided by the subject for data collection on these events. 
9.5. 
Subject Status and Classification 
Table 9.5-1 describes subject status/classification and associated forms. 
Table 9.5-1: Subject Status and Classification 
Classification 
Description 
Screen Failure 
A subject who signs an ICF but does not meet clinical eligibility criteria is considered a 
screen failure. Screen failure subjects do not count towards the enrollment ceiling and will 
not be used for the primary analyses. Screen failure subjects should exit from the study 
immediately upon determining ineligibility. The original signed ICF must be maintained 
in the center’s subject file and the following forms must be completed for all information 
collected prior to determining the subject’s ineligibility. 
• Baseline forms such as, but not limited to, ICF, baseline information and other 
related forms 
• Adverse Event form(s) for any reportable event, as defined in Section 17, for any 
adverse event that occurs after signing the ICF, up to the point of subject exit 
Attempt 
A subject who signs an ICF, meets eligibility criteria, and has had a WATCHMAN 
Access Sheath inserted to implant the device, but eventually does not receive a 
WATCHMAN FLX device will be classified as “Attempt.” Attempt subjects will be 
followed for 12 months from the time of the implant attempt and adverse events will be 
collected. Attempt subjects count towards the enrolment ceiling and will be used for 
analyses of the endpoints. The original signed ICF must be maintained in the centre’s 
study file and the following forms must be completed. 
• eCRFs in the Baseline and Implant folders 
• First Follow-up Visit Form(s), except LAA imaging 
• Adverse Event forms and/or Device Deficiency forms for any reportable adverse 
event that occurs after signing the ICF 
• End of Study form for withdrawal 
The date of withdrawal should be indicated in the End of Study form as the point of 
subject withdrawal. 
Implant 
A subject who is successfully implanted with the WATCHMAN FLX device will be 
classified as “Implant.” Successfully implanted subjects are those defined as having 
device success, where the device has been deployed and implanted in the correct position. 
These subjects are followed in accordance with the follow-up schedule and data will be 

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Table 9.5-1: Subject Status and Classification 
Classification 
Description 
included in all study analyses. All applicable case report forms per the protocol must be 
completed. The original signed ICF and any relevant documentation must be maintained 
in the centre’s study file. 
Abbreviations: eCRF=electronic case report form; ICF=Informed Consent Form; LAA=left atrial appendage 
 
10. Study Methods 
10.1. Data Collection 
This section lists the data needed to fulfill the objectives of this clinical study.  
The data collection schedule is provided in Table 10.1-1 and summarized diagrammatically 
in Figure 10.1-1. Additional information, including recommended post-procedure medical 
therapy, is provided in Section 10.2 through Section 10.10. 

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Table 10.1-1: WATCHMAN FLX CT Study Event Schedule 
Assessment 
Baseline 
Index 
Procedure 
Predischarge 
14 Days a  
(± 3 Days) 
45 Days a  
(± 15 Days) 
3 Months a  
(90 ± 30 Days) 
12 Months a 
(365 ± 30 Days) 
Signed Informed Consent Form (date) 
X 
– 
– 
– 
– 
– 
– 
Demographics  
X 
– 
– 
– 
– 
– 
– 
Medical history and inclusion/exclusion criteria 
X 
– 
– 
– 
– 
– 
– 
Physical assessment 
X 
– 
– 
– 
X 
X 
O 
Risk factor assessmentsb 
X 
– 
– 
– 
– 
– 
– 
TEE of LAAc 
 Xc 
– 
– 
X 
X 
Xc 
 Od 
CT of LAAc 
 Xc 
– 
– 
X 
X 
X 
O 
MRI of LAAe 
O 
– 
– 
O 
O 
O 
O 
Labs ‒ biochemical markersf 
X 
– 
– 
X 
X 
X 
O 
NIHSS Stroke Scaleg 
X 
– 
– 
– 
– 
– 
– 
Modified Rankin Scale scoreg 
X 
– 
– 
– 
– 
– 
– 
Procedural ICEh 
– 
X 
– 
– 
– 
– 
– 
Medications 
X 
X 
X 
X 
X 
X 
X 
SAE, ADE, SADE, USADE, procedure-related 
AE and device deficienciesi 
– 
X 
X 
X 
X 
X 
X 
Note 1: X = should be performed; O=optional (unless required based on other data); – = not required 
Baseline assessments should be done within 30 days unless specified otherwise in the footnotes below. Eligibility for the study is determined per standard of care. Any 
additional study specific testing to verify inclusion/exclusion criteria must be done after the ICF is signed. 
a: 
All follow-up dates will be calculated from the date of the (attempted) index procedure. Subjects are considered enrolled in the study when the subject or the 
subject’s legally authorized representative signs an ICF approved by the Independent Ethics Committee. Clinical follow-up is in-person at 14 days, 45 days, and 3 
months. Follow-up at 12 months is in-person (preferred) or by telephone (unless an in-person assessment is required based on other data). Subjects who are enrolled 
but do not have a WATCHMAN FLX™ LAA Closure Device implanted in the correct position will be followed for safety through 12 months after the initial 
attempted index procedure but will not undergo imaging assessments or evaluation of biochemical markers.  
b: Risk factor assessments include HAS-BLED and CHA2DS2-VASc scores. 
c: Either TEE or CT must be done within 14 days prior to the index procedure (baseline assessment) following the core laboratory guidelines (see Section 12.3). CT at 
14 days, 45 days, and 3 months are required for all subjects who have a WATCHMAN FLX™ LAA Closure Device implanted in the correct position and should be 
performed per the core lab guidelines. TEE is required at 14 days, 45 days and optional at 3 months if there is no leak at 45 days, for all subjects who have a 
WATCHMAN FLX™ LAA Closure Device implanted in the correct position and should be performed per the core lab guidelines. Results must be sent to the core 
laboratory for independent analysis (see Section 12.3).  

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Table 10.1-1: WATCHMAN FLX CT Study Event Schedule 
Assessment 
Baseline 
Index 
Procedure 
Predischarge 
14 Days a  
(± 3 Days) 
45 Days a  
(± 15 Days) 
3 Months a  
(90 ± 30 Days) 
12 Months a 
(365 ± 30 Days) 
d: Repeat TEE should be done at 12 months if the 3-month TEE assessment suggests a leak > 5mm or the 3-month CT assessment suggests a leak > 3mm; results 
must be sent to the core laboratory. 
e: MRI imaging assessments are optional. If MRI assessment is done, core laboratory guidelines should be followed. Results must be sent to the core laboratory for 
independent analysis (see Section 12.3).   
f: Labs include biochemical markers including measures of coagulation, platelet and endothelial activation and inflammation. At baseline, these labs should be 
obtained within 30 days prior to the index procedure. Baseline serum creatinine is also required but may be obtained up to 180 days prior to consent. 
g: Baseline neurological assessments should be done within 30 prior to the index procedure. For subjects diagnosed with a neurological event (e.g., stroke, TIA), mRS 
and NIHSS should be performed after the event. It is recommended that the subject be contacted regarding an mRS assessment at 90±14 days following any 
suspected stroke; the simplified mRS questionnaire may be used for this follow-up assessment and may be collected by telephone. 
 
Note 2: If a subject has a stroke or other thromboembolic event, work-up should occur as per local standard of care. It is recommended that imaging be performed 
to screen for DRT. If performed, imaging results should be sent to the Core Laboratory. 
h: Procedural ICE data should be sent to the Core Laboratory. 
i: Safety events will be monitored and reported to Boston Scientific Corporation from the time of enrollment through 12-month follow-up. Please refer to Section 
17.1 for a list of events to be adjudicated by the CEC through completion of a subject’s participation in the study and Table 23.2-1 for definitions of these events, 
which specify data required for CEC adjudication. Reporting of device deficiencies will follow applicable regional post-market safety surveillance requirements. 
Abbreviations: ADE=adverse device effect; AE=adverse event; CEC=Clinical Events Committee; CHA2DS2-VASc=congestive heart failure, hypertension, age 
≥75 years, diabetes mellitus, stroke/TIA, vascular disease, age 65‒74 years, sex category; CT=computed tomography; DRT=device related thrombus; HAS-
BLED=hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly; ICE=intracardiac 
echocardiography; ICF=Informed Consent Form; LAA=left atrial appendage; MRI=magnetic resonance imaging; mRS=modified Rankin Scale; NIHSS=National 
Institutes of Health Stroke Scale; SADE=serious adverse device effect; SAE=serious adverse event; TEE=transesophageal echocardiography; TIA=transient ischemic 
attack; USADE=unanticipated serious adverse device effect 
 
 

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NIH Stroke Scale
* A subject is considered enrolled in the study when the subject or the subject’s legally authorized representative signs an ICF approved by the IEC.
^ Clinical follow-up is in-person at 14 days, 45 days, and 3 months and in-person (preferred) or by telephone at 12 months.
† Baseline CT or TEE must be done within 7 days prior to the index procedure.
‡ Repeat TEE should be done at 12 months if the 3-month TEE suggests a leak > 5mm or the 3-month CT assessment suggests a leak > 3mm.
Index 
Procedure 
Clinical & Anatomic 
Eligibility Criteria 
Assessment and 
Baseline Measurements
14d 
Subject 
meets
criteria
TEE†
Medications
Demographics, Medical History 
& Risk Factors
3m
12m
45d
Procedural 
Data Collection
Subject
Enrollment*
Approximately
25
Transesophageal Echocardiography 
(TEE)
Physical Assessment
Physical Assessment
Medications
Adverse Event/Device Deficiency Assessment
Clinical Follow-up ^
Modified Rankin Scale
Computed Tomography (CT)†
Computed Tomography (CT)
Magnetic Resonance Imaging (MRI)
Magnetic Resonance Imaging (MRI)
Informed Consent
Labs – Biochemical Markers
Labs – Biochemical Markers
Predischarge 
Physical 
CT
MRI
Labs
TEE‡
 
 
Figure 10.1-1: WATCHMAN FLX CT Study Event Schedule Summary Diagram 
Approximately 25 subjects will be enrolled. Dashed line indicates the assessment is optional unless required 
based on other data. Eligibility for the study is determined per standard of care. Any additional study specific 
testing to verify inclusion/exclusion criteria must be done after the Informed Consent Form is signed. 
Please see Table 10.1-1 for additional information.  
 
10.2. Study Candidate Screening 
Investigators are responsible for screening all subjects and selecting those who are 
appropriate for study inclusion as per the product IFU. The subjects selected for participation 
should be from the Investigator’s general patient population. No study-specified procedures 
or tests will be done prior to consent, though studies, tests, or procedures performed as part 
of the normal standard of care may be performed prior to consent. 
10.3. Subject Informed Consent 
Written informed consent (see Section 18) must be obtained for all qualified subjects who are 
potential study candidates prior to the subject’s index procedure.  
The Investigator/designee who has been trained on the protocol will explain the nature and 
scope of the study, the potential risks and benefits of participation, and will answer questions 
for the subject. If the subject agrees to participate, the IEC-approved ICF must be signed and 

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personally dated by the subject or his/her legally authorized representative. The 
Investigator/designee must sign the ICF prior to subject enrollment. Any additional persons 
required by the center’s IEC to sign the ICF must also comply. 
The original, signed document is to be kept with the subject’s file and a copy must be 
provided to the subject. The informed consent process must be documented by the person 
obtaining consent and the documentation must be placed in the subject’s file.  
10.4. Baseline Assessments 
The following assessments must be completed within 30 days prior to the index procedure, 
unless otherwise specified below. The study electronic case report forms (eCRFs) identify 
the specific data points to be collected. 
• Confirmation of eligibility criteria and contraindications per the IFU 
• Clinical assessments  
o Demographics, including age at time of consent and sex 
o Medical and cardiac history; includes cardiovascular diseases, AF type (paroxysmal, 
persistent, permanent), prior history of stroke/transient ischemic attack (TIA), 
previous cardiac procedures, history of bleeding and location, eligibility for oral 
anticoagulation, indication for LAA occlusion   
o Physical assessment 
o Risk factor assessments, including HAS-BLED and CHA2DS2-VASc scores39 
o Current antiplatelet, anticoagulation, and other cardiovascular medications 
o mRS score and NIHSS score 
Note 1: Neurological status as determined by the mRS score should also be 
determined following any suspected stroke; it is recommended that the subject be 
contacted regarding an mRS assessment at 90±14 days post-stroke; the simplified 
mRS questionnaire38 may be used for this follow-up assessment and may be collected 
by telephone. 
o Labs including baseline serum creatinine (may be obtained up to 180 days prior to 
consent) and biochemical markers including measures of coagulation, platelet and 
endothelial activation and inflammation 
• Imaging assessments  
o Either CT or TEE assessment of the LAA must be carried out within 14 days prior to 
the index procedure to confirm LAA size and to document that eligibility criteria 
have been met. Results must be sent to the core lab. This preprocedural imaging 
assesses appendage anatomy and device sizing and excludes the presence of a LAA 
thrombus. Suitability for attempted device implantation will be assessed as follows. 
 Using multiple imaging planes, LAA size/shape, number of lobes in the LAA, and 
location of lobes to ostium will be determined. 

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 Absence of thrombus will be confirmed. If an intracardiac thrombus is visualized, 
device implantation will not be attempted. Re-assessment may be scheduled per 
the physician’s discretion. 
 Measurements of the LAA ostium width and LAA depth will be recorded. The 
measured maximum LAA ostium width must be ≥ 14.0 mm and ≤ 31.5 mm to 
accommodate the available WATCHMAN FLX device sizes. 
o Cardiac MRI assessment (including 4D cardiac MRI flow analysis of the LA and 
LAA) is optional but if performed, the results must be sent to the core lab.  
o All protocol required pre-procedural imaging will be performed by trained individuals 
and in accordance with core lab instructions (see Section 12.3). Copies of the imaging 
results will be sent to the core lab for independent analysis. Additionally, copies of all 
LAA imaging will be saved to disk at the center and available to the sponsor upon 
request. The center and subject identification number should be clearly identified on 
the disks. 
10.5. Pre-procedure Medications 
Pre-procedure medications are listed below and should be recorded on the eCRFs. 
• Single antiplatelet therapy (aspirin or P2Y12 inhibitor) is recommended prior to device 
implantation. A loading dose should be administered the day before the implant 
procedure. Dosing should be per standard of care. The choice of loading dose 
medication is at the discretion of the treating physician but should be the same as the 
intended post-procedure antiplatelet therapy.  
• Anticoagulant therapy (e.g., unfractionated heparin) must be administered per local 
standard of care during the implant procedure, with a recommended target activated 
clotting time (ACT) of ≥250 seconds during the implantation procedure. 
• Prophylactic antibiotic therapy should be given according to local practice. The choice 
of antibiotic drug is left to the investigator’s discretion. 
10.6. Index Procedure 
The preparation of the subject for the transcatheter procedure will be performed following 
standard techniques. Refer to the WATCHMAN FLX LAA Closure Device IFU and the 
WATCHMAN® Access System IFU for detailed instructions regarding device use. 
The following information will be collected in the eCRF during the procedure. Additional 
data to be collected may be outlined in the eCRF.  
• Date of procedure 
• WATCHMAN FLX LAA Closure Device size used 
• Commercially available WATCHMAN Access System used 
• Procedural ICE data with results sent to the core laboratory 

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• Medications 
• Adverse event assessment (see Section 17) 
10.7. Predischarge 
The subject may be discharged from the hospital when clinically stable, at the Investigator’s 
discretion per local standard of care. Prior to discharge from the hospital, a complete safety 
event assessment must be done. The study eCRFs identify the specific data points to be 
collected. This includes evaluation of any procedure-related adverse event (AE), serious 
adverse event (SAE), adverse device effect (ADE), serious adverse device effect (SADE), 
unanticipated serious adverse device effect (USADE), and any device deficiency with 
associated treatment.  
Note 1: For subjects diagnosed with a neurological event (e.g., stroke, TIA), mRS and 
NIHSS should be performed after the event. It is recommended that the subject be contacted 
regarding an mRS assessment at 90±14 days post-neurological event; the simplified mRS 
questionnaire may be used for this follow-up assessment and may be collected by telephone. 
It is recommended that imaging be performed after the event to screen for DRT. If 
performed, imaging results should be sent to the core laboratory. 
Antiplatelet therapy post index procedure is recommended to reduce the risk of thrombotic or 
thromboembolic complications if there are no contraindications to these medications. 
Subjects must be treated with single antiplatelet therapy (SAPT; aspirin or P2Y12 inhibitor) 
for at least 3 months following WATCHMAN FLX implantation. Extended therapy may be 
administered per physician choice.  
Prior to discharge, clinical staff should review the study follow-up visit schedule with the 
subject to maximize follow-up compliance. 
10.8. Follow-up 
All subjects successfully implanted with a WATCHMAN FLX device will be evaluated at 
14 days, 45 days, 3 months, and 12 months post index procedure. Subjects who are enrolled 
but not implanted with a WATCHMAN FLX device in the correct position will be followed 
for safety through 12 months after the initial attempted index procedure but will not undergo 
imaging assessments or evaluation of biochemical markers including measures of 
coagulation, platelet and endothelial activation and inflammation. 
It is important that this schedule be maintained as closely as possible for all subjects. Boston 
Scientific Corporation (BSC) recognizes that subjects may not be able to return for all 
scheduled visits at precisely the date required, and therefore, a period of time in which each 
visit is allowed is indicated in Table 10.1-1. Required follow-up assessments and visits not 
completed will be considered missed visits and recorded as protocol deviations. Visits 
completed outside follow-up windows will be recorded as protocol deviations. Each follow-
up visit must be performed by trained study personnel. Data from collected tests and images 

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as well as medical assessments will be recorded in source documentation and captured in the 
eCRFs.  
In the event that study personnel learn of a subject’s hospitalization outside the study center, 
the center should make every effort to obtain copies of reports or results based on tests (e.g., 
echocardiogram) and/or procedures performed on the study subject.  
10.8.1. 14-Day Follow-up (14 Days ±3 Days) 
All enrolled subjects will be evaluated 14 days after the index procedure. The study eCRFs 
identify the specific data points to be collected as listed below.  
• Complete safety event assessment, including any SAE, ADE, SADE, USADE, device 
deficiency with associated treatment, and any CEC event regardless of seriousness and 
device relationship. 
Note 1: For subjects diagnosed with a neurological event (e.g., stroke, TIA), mRS and 
NIHSS should be performed after the event. It is recommended that the subject be 
contacted regarding an mRS assessment at 90±14 days following any suspected stroke; 
the simplified mRS questionnaire may be used for this follow-up assessment and may be 
collected by telephone. It is also recommended that imaging be performed to screen for 
DRT. If performed, imaging results should be sent to the core laboratory. 
• All antiplatelet medications, which should be administered in accordance with local 
standard of care. Subjects must be treated with SAPT (aspirin or P2Y12 inhibitor) for at 
least 3 months following WATCHMAN FLX implantation.  
• Assessment of biochemical markers including measures of coagulation, platelet and 
endothelial activation and inflammation. 
• TEE is required for all subjects who have a WATCHMAN FLX™ LAA Closure Device 
implanted in the correct position and should be performed per the core lab guidelines, 
including assessment of device seal and device surface morphology (inclusive of tissue 
coverage) post implant procedure. Results must be sent to the core lab for independent 
analysis. 
• CT is required for all subjects who have a WATCHMAN FLX™ LAA Closure Device 
implanted in the correct position and should be performed per the core lab guidelines, 
including assessment of device seal, device-related thrombus (including hypoattenuated 
thickening [HAT]) and device surface morphology (inclusive of tissue coverage) post 
implant procedure. Results must be sent to the core lab for independent analysis. 
• Cardiac MRI assessment, including 4D cardiac MRI flow analysis of the LA and LAA, 
is optional but if performed, the results must be sent to the core lab for independent 
analysis.   
Subjects who are enrolled but not implanted with a WATCHMAN FLX device in the correct 
position during the index procedure will be followed for safety through 12 months after the 
initial attempted index procedure but will not undergo imaging assessments or evaluation of 

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biochemical markers including measures of coagulation, platelet and endothelial activation 
and inflammation.  
 
10.8.2. 45-Day Follow-up (45±15 Days) and 3-Month Follow-up (90±30 Days)   
All enrolled subjects will be evaluated 45 days and 3 months after the index procedure. The 
study eCRFs identify the specific data points to be collected as listed below. 
• Complete safety event assessment, including any SAE, ADE, SADE, USADE, device 
deficiency with associated treatment, and any CEC event regardless of seriousness and 
device relationship. 
Note 1: For subjects diagnosed with a neurological event (e.g., stroke, TIA), mRS and 
NIHSS should be performed after the event. It is recommended that the subject be 
contacted regarding an mRS assessment at 90±14 days following any suspected stroke; 
the simplified mRS questionnaire may be used for this follow-up assessment and may be 
collected by telephone. It is also recommended that imaging be performed after the 
event to screen for DRT. If performed, imaging results should be sent to the core 
laboratory. 
• All antiplatelet medications, which should be administered in accordance with local 
standard of care. Subjects must be treated with SAPT (aspirin or P2Y12 inhibitor) for at 
least 3 months following WATCHMAN FLX implantation.  
• Physical assessment as per local standard of care 
 
• Biochemical markers including measures of coagulation, platelet and endothelial 
activation and inflammation. TEE is required for all subjects who have a WATCHMAN 
FLX™ LAA Closure Device implanted in the correct position at 45 days and should be 
performed per the core lab guidelines, including assessment of device seal and device 
surface morphology (inclusive of tissue coverage) post implant procedure. Results must 
be sent to the core lab for independent analysis. 
• TEE is optional at 3 months for subjects who have a WATCHMAN FLX™ LAA 
Closure Device implanted in the correct position if there is no leak at 45 days. However, 
if TEE is performed results must be sent to the core lab for independent analysis. 
• CT is required for all subjects who have a WATCHMAN FLX™ LAA Closure Device 
implanted in the correct position and should be performed per the core lab guidelines, 
including assessment of device seal, device-related thrombus (including HAT) and 
device surface morphology (inclusive of tissue coverage) post implant procedure. 
Results must be sent to the core lab for independent analysis. 
• Cardiac MRI assessment, including 4D cardiac MRI flow analysis of the LA and LAA, 
is optional but if performed, the results must be sent to the core lab for independent 
analysis.   

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Subjects who are enrolled but not implanted with a WATCHMAN FLX device in the correct 
position during the index procedure will be followed for safety through 12 months after the 
initial attempted index procedure but will not undergo imaging assessments or evaluation of 
biochemical markers including measures of coagulation, platelet and endothelial activation 
and inflammation. 
10.8.3. 12-Months Follow-up (365±30 Days)  
All subjects successfully implanted with a WATCHMAN FLX device will be evaluated at 
12 months after the index procedure. The study eCRFs identify the specific data points to be 
collected as listed below. 
• Complete safety event assessment, including any SAE, ADE, SADE, USADE, device 
deficiency with associated treatment, and any CEC event regardless of seriousness and 
device relationship. 
Note 1: For subjects diagnosed with a neurological event (e.g., stroke, TIA), mRS and 
NIHSS should be performed after the event. It is recommended that the subject be 
contacted regarding an mRS assessment at 90±14 days following any suspected stroke; 
the simplified mRS questionnaire may be used for this follow-up assessment and may be 
collected by telephone. It is also recommended that imaging be performed after the 
event to screen for DRT. If performed, imaging results should be sent to the core 
laboratory. 
• All antiplatelet and other cardiovascular medications should be administered in 
accordance with local standard of care. 
10.9. Study Completion 
All enrolled subjects will be followed for the duration of 12 months post procedure. A 
subject’s participation in the study will be considered complete after the 12-month follow-up 
visit. Subjects who are enrolled but not implanted with a WATCHMAN FLX device in the 
correct position during the index procedure will be followed for safety through 12 months 
after the initial attempted index procedure but will not undergo imaging assessments or 
evaluation of biochemical markers including measures of coagulation, platelet and 
endothelial activation and inflammation. 
 
10.10. Source Documents 
It is preferable that original source documents, when available, are maintained at the 
investigative center. In lieu of original source documents, certified copies are required to be 
maintained. A certified copy is a copy (irrespective of the type of media used) of the original 
record that has been verified (i.e., by a dated signature or by generation through a validated 
process) to have the same information, including data that describe the context, content, and 
structure, as the original. Source documentation includes but is not limited to those items 

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noted in Table 10.10-1. Source documentation provided to the Sponsor for 
assessment/adjudication will be deidentified per local law and regulations. 
Table 10.10-1: Source Documentation Requirements 
Requirement 
Disposition 
Printed, optical, or electronic document containing source data. Examples may include but 
are not limited to the following: hospital records; laboratory notes; device accountability 
records; photographic negatives; radiographs; records kept at the investigation center, at 
the laboratories and at the medico-technical departments involved in the clinical 
investigation. 
Retain at center 
Note 1: Please see Table 23.2-1 for definitions of “source data” and “source document.” 
 
11. Statistical Considerations 
11.1. Endpoints 
Procedural and post-procedure information will be collected as detailed in the clinical study 
schedule (Table 10.1-1) and will be summarized using descriptive statistics for continuous 
variables (e.g., mean, standard deviation, n, minimum, maximum) and frequency tables or 
proportions for discrete variables. The Kaplan-Meier product-limit method will be used to 
estimate rates for time-to-event endpoints. Adverse event and SAE rates will be reported. 
11.2. General Statistical Methods 
All statistical analyses will be performed using the SAS System software, version 9.2 or later 
(Copyright© 2000 SAS Institute Inc., SAS Campus Drive, Cary, North Carolina 27513, USA. 
All rights reserved).  
All statistical analyses will be conducted according to applicable Standard Operating 
Procedures, Work Instructions, and the study-specific statistical analysis plan. 
Statistical models that account for censored data will be employed in appropriate 
circumstances (e.g., for time-to-event outcomes). 
11.2.1. Analysis Sets 
Endpoints will be analyzed on an intention-to-treat (ITT) basis and an implanted basis. For 
ITT analyses, all subjects who sign the IEC-approved study ICF (see Section 10.3) and are 
enrolled (see Section 9.1) in the study will be included in the analysis, whether or not a study 
device was implanted. For implanted analyses, ITT subjects who had the study device 
implanted in the correct position during the index procedure will be included in the analysis.  

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11.2.2. Control of Systematic Error/Bias 
The selection of subjects will be made from the Investigator’s usual case load. The study 
center’s heart team assessments and imaging measurements before device placement will 
contribute to the determination of subject eligibility for the study. All subjects who have 
signed the ICF and are selected to receive a study device will be enrolled in the study (see 
Section 9.1 for point of enrollment).  
To control for inter-observer variability, data from an independent core laboratory (see 
Section 12) will be used for analysis at pre-specified time points. An independent CEC (see 
Section 19.1.1) will adjudicate study endpoint related clinical events (see Section 6.2).  
11.2.3. Number of Subjects per Investigative Center 
A single center may enroll up to 25 subjects. 
11.3. Data Analyses 
Baseline and outcome variables will be summarized using descriptive statistics for 
continuous variables (mean, standard deviation, number of observations, minimum and 
maximum) and discrete variables (percentage and count/sample). Study endpoints are listed 
in Section 6.2.    
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in an amended statistical analysis plan approved before performing the analyses. 
Changes from the planned statistical methods after performing the analyses will be 
documented in the clinical study report along with a reason for the deviation. 
12. Data Management 
12.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by BSC or its representative. The associated Rave software and database have been 
designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to BSC require a new electronic signature by the Investigator 
acknowledging and approving the changes. 

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Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the Medidata EDC system 
and will be issued to the center for appropriate response. Center staff will be responsible for 
resolving all queries in the database. 
All access to the clinical database will be changed to “Read Only” after all data are either 
“Hard Locked” or “Entry Locked.” Once acceptance of the final study report or finalization 
of publications (as applicable) is received, final database storage and archiving activities can 
begin. When all closeout activities are completed, a request to the BSC Information 
Technology department is submitted to have the database locked or decommissioned and all 
database access revoked. 
12.2. Data Retention 
The Principal Investigator or his/her designee or investigational center will maintain all 
essential study documents and source documentation that support the data collected on the 
study subjects in compliance with applicable regulatory requirements. 
The Principal Investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. If for any reason the Principal Investigator or 
his/her designee withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change. Centers are required to inform BSC in writing 
where paper or electronic files are maintained in case files are stored off site and are not 
readily available. 
12.3. Core Laboratory 
Echocardiography images, CT data, and MRI data (if applicable) will be evaluated by an 
independent core laboratory. Procedure guidelines for the required imaging assessments are 
provided by the core laboratory in the Manual of Operations. These analyses will minimize 
bias and inconsistencies by providing an independent interpretation of all measurements 
using standard techniques. 
13. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify 
BSC and the reviewing IEC of any deviation from the investigational plan to protect the life 
or physical well-being of a subject in an emergency, and those deviations which affect the 
scientific integrity of the clinical investigation. Such notice shall be given as soon as 
possible, but no later than 5 working days after the emergency occurred, or per prevailing 
local requirements, if sooner than 5 working days. 
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to BSC using the EDC CRF. Centers may also 

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be required to report deviations to the IEC and the regulatory authority, per local guidelines 
and government regulations. 
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IEC/Regulatory Authority notification, center re-
training, or center discontinuation/termination) will be put into place by BSC. 
The sponsor will not approve protocol waivers.  
14. Compliance 
14.1. Statement of Compliance 
This clinical investigation is financed by the study sponsor. Before an investigational center 
can be considered “Authorized to Enroll,” the investigational center must enter into a Clinical 
Study Agreement with the sponsor that details the financing of the study as well as the rights 
and obligations of the investigational center and the investigator. 
The WATCHMAN FLX CT study will be conducted in accordance with the International 
Standard ISO 14155 Clinical Investigation of Medical Devices for Human Subjects – Good 
Clinical Practice; relevant parts of the International Conference on Harmonisation (ICH) 
Guidelines for Good Clinical Practices (GCP); ethical principles that have their origins in the 
Declaration of Helsinki; and pertinent individual country/state/local laws and regulations. 
The study shall not begin until the required approval/favorable opinion from the IEC and/or 
regulatory authority has been obtained, if appropriate. Also, the study shall not begin prior to 
issuance of the center Authorization to Enroll, as provided by the sponsor. Any additional 
requirements imposed by the IEC or regulatory authority shall be followed, if appropriate. 
Boston Scientific Corporation considers data collected from clinical trial subjects to be 
personal data (see definitions of different data categories in Table 23.2-1) and compliance 
with privacy and data protection laws and regulations (for example, the General Data 
Protection Regulation [GDPR]) to be critically important. Data collection for this clinical 
study has been carefully considered to comply with data privacy laws. 
14.2. Investigator Responsibilities 
The Principal Investigator of an investigational center is responsible for ensuring that the 
study is conducted in accordance with the Clinical Study Agreement, the clinical 
investigation plan/protocol, ISO 14155 or ICH/GCP, ethical principles that have their origins 
in the Declaration of Helsinki, any conditions of approval imposed by the reviewing IEC, and 
prevailing local and/or country laws and/or regulations, whichever affords the greater 
protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following. 
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   

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• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Complete training requirements associated with the WATCHMAN FLX™ Left Atrial 
Appendage Closure Device. 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to BSC 
in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency. 
• Report to BSC, per the protocol requirements, all reportable events. 
• Report to the IEC and regulatory authorities any SAEs and device deficiencies that 
could have led to a SADE and potential/USADE, if required by applicable laws or 
regulations or this protocol or by the IEC, and supply BSC with any additional requested 
information related to the safety reporting of a particular event. 
• Allow BSC and its representatives to perform monitoring and auditing activities and be 
accessible to the clinical research monitor or auditor and respond to questions during 
monitoring visits or audit(s). 
• Allow and support regulatory authorities and the IEC when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol, and local IEC requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the ICF. 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 

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treatment, including decoding procedures for blinded/masked clinical investigations, as 
needed. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together 
with identification and compliance information for concomitant treatment measures 
(contact address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical 
investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation center team and facilities exist and are maintained 
and documented during the clinical investigation. 
All investigators will provide their qualifications and experience to assume responsibility for 
their delegated tasks through up-to-date curriculum vitae or other relevant documentation and 
disclose potential conflicts of interest, including financial, that may interfere with the conduct 
of the clinical study or interpretation of results. 
14.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training, so the delegate is competent to perform the tasks they have been 
delegated and adequate supervision of those to whom tasks are delegated. Where there is a 
sub-investigator at a center, the sub-investigator should not be delegated the primary 
supervisory responsibility for the center. The investigator is accountable for regulatory 
violations resulting from failure to adequately supervise the conduct of the clinical study.  
14.3. Independent Ethics Committee 
The investigational center will obtain the written and dated approval/favorable opinion of the 
IEC for the clinical investigation before recruiting subjects and implementing all subsequent 
amendments, if required. 
A copy of the written IEC and/or competent authority approval of the protocol (or permission 
to conduct the study) and ICF must be received by BSC before recruitment of subjects into 
the study. Prior approval must also be obtained for other materials related to subject 
recruitment or which will be provided to the subject. 
Any amendment to the protocol will require review and approval by the IEC before the 
changes are implemented in the study. All changes to the ICF will be IEC approved; a 

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determination will be made regarding whether a new ICF needs to be obtained from subjects 
who provided consent using a previously approved ICF.  
Annual IEC approval and renewals will be obtained throughout the duration of the study as 
required by applicable local/country laws or regulations or IEC requirements. Copies of the 
study reports and the IEC continuance of approval must be provided to BSC.  
14.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 
applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to, a contract research organization (CRO) will have access to this 
information. Authorized regulatory personnel have the right to inspect and copy all records 
pertinent to this study. Study data collected during this study may be used by BSC for the 
purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical 
research, and proposals for developing new medical products and procedures. All data used 
in the analysis and reporting of this study or shared with a third-party researcher will be 
without identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
14.4.1. Role of Boston Scientific Corporation Representatives 
Boston Scientific Corporation personnel (including field clinical engineers and specialists) 
who are trained in the use of the WATCHMAN FLX™ Left Atrial Appendage Closure 
Device will provide training and technical support to the investigator and other health care 
personnel (collectively HCP) as needed during implantation of the WATCHMAN FLX 
device. Boston Scientific Corporation has established a structured training program for the 
physicians and staff who will be involved in the peri-procedural care of subjects selected to 
receive the WATCHMAN FLX device. Support may include HCP training (Section 14.4.2), 
addressing HCP questions, or providing clarifications to HCPs concerning the operation of 
BSC equipment/devices.  
In addition, BSC personnel may perform certain activities to ensure study quality. These 
activities may include the following. 
• Observation of testing or medical procedures to provide information relevant to protocol 
compliance 
• Review of collected data and study documentation for completeness and accuracy 
Boston Scientific personnel will not do the following.  
• Practice medicine 
• Provide medical diagnosis or treatment to subjects 

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• Discuss a subject’s condition or treatment with a subject without the approval and 
presence of the investigator  
• Independently collect critical study data (defined as endpoint-associated data) 
• Enter data in electronic data capture systems or on paper case report forms 
14.4.2. Training 
Boston Scientific Corporation has established a structured training program for the 
physicians and staff who will be involved in the peri-procedural care of subjects treated with 
the WATCHMAN FLX Left Atrial Appendage Closure Device. This commercial training 
program is designed to provide the physicians and staff with the information and experience 
necessary to control user-associated risks when the device is used in accordance with the 
IFU.  
14.5. Insurance  
Where required by local/country regulation, proof of and type of insurance coverage by BSC 
for subjects in the study will be obtained. 
15. Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the clinical research monitor verifies that 
study records are adequately maintained, that data are reported in a satisfactory manner with 
respect to timeliness, adequacy, and accuracy, and that the Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The sponsor will put a plan in place to document the specific monitoring requirements. 
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
16. Potential Risks and Benefits 
16.1. Instructions for Use 
Please refer to the IFU(s) for an overview of anticipated adverse (device) effects, and risks 
associated with the commercial device(s). 

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16.2. Risks Associated with Participation in the Clinical Study 
Risks associated with the use of a left atrial appendage closure device or implantation 
procedure and with the WATCHMAN FLX Left Atrial Appendage Closure Device are listed 
in the IFU and in the ICF. There are no incremental risks associated with participation in this 
clinical study. 
The baseline assessments in this study may include a CT scan. Protocol-required CT scans 
will occur at the 14-day, 45-day, and 3-month visits. Generally, the dose of radiation from 2 
CT scans is about 20 mSv, or the equivalent of about an additional 10 years’ worth of natural 
radiation. The benefits from the study should be weighed against the possible effects of 
radiation. The contrast dye used during the image acquisition can cause medical problems 
such as allergic reactions and increase the risk of worsening kidney function or failure. 
16.3. Possible Interactions with Concomitant Medical Treatments 
Please see Section 10.7 for suggested medications, which constitute standard of care for use 
of a left atrial appendage closure device. Information regarding risks associated with use of 
antiplatelet therapy or oral anticoagulants should be referenced with the medications. These 
risks may include the following. 
• Increased bruising 
• Increased bleeding tendency 
• Gastrointestinal (GI) side effects including stomach pain, heartburn, nausea, vomiting 
and gross GI bleeding 
• Elevated hepatic enzymes, blood urea nitrogen and serum creatinine, hyperkalemia, 
proteinuria and prolonged bleeding time 
• Thrombotic thrombocytopenic purpura 
• Thrombocytopenia  
16.4. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 
Data will be monitored as they are submitted to BSC. Qualified employees of BSC, or a 
designee under contract, will conduct monitoring visits at the initiation of the study and at 
interim intervals described in the monitoring plan throughout the course of the study to 
evaluate protocol compliance and determine if there are any issues that could affect the safety 
or welfare of any subject in the study. A dynamic safety review process including CEC 
(Section 19.1) adjudication of specified events will support risk mitigation. 

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16.5. Anticipated Benefits 
The potential benefit of implanting the WATCHMAN FLX Device is its expected ability to 
prevent thromboembolic events originating in the LAA. The WATCHMAN FLX Device 
may protect against ischemic stroke and systemic thromboembolism. In subjects implanted 
with the device, the elimination of long-term anticoagulation therapy may reduce bleeding 
complications associated with long-term anticoagulation, such as hemorrhagic stroke or 
gastrointestinal major bleeding events. There are also economic and subject benefits related 
to the elimination of life-long compliance to anticoagulation therapy and the frequent blood 
tests and lifestyle changes associated with blood thinning medications. 
17. Safety Reporting 
17.1. Reportable Events by Investigational Center to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of the following categories, from point of enrollment through the 12 month follow-up 
visit for all enrolled subjects. 
• Serious adverse event (SAE) – see Note 1 below 
• Adverse event (AE) related to the WATCHMAN FLX study device and/or 
WATCHMAN FLX implant procedure 
• Device deficiency  
• Unanticipated serious adverse device effect (USADE) 
• Adverse event related to the protocol-required testing (LAA imaging and blood draw) 
• Adverse event where systemic embolism is suspected and/or confirmed, regardless of 
relationship to the WATCHMAN FLX device 
• All bleeding events regardless of relationship to the WATCHMAN FLX device 
• Strokes (regardless of cause) and TIAs regardless of relationship to the WATCHMAN 
FLX device 
• New findings/updates in relation to already reported events 
 Note 1: Planned hospitalization for a pre-existing condition, or a procedure required by the 
clinical investigational plan, without serious deterioration in health, is not considered a 
serious adverse event. 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an AE and/or device 
deficiency. 

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Any reportable event experienced by the study subject after informed consent, whether prior 
to, during or subsequent to the procedure, must be recorded in the eCRF. 
Underlying diseases and chronic conditions are not reported as AEs unless there is an 
increase in severity or frequency during the course of the investigation. Death should not be 
recorded as an AE but should only be reflected as an outcome of one (1) specific SAE (see 
Table 17.2-1 for AE definitions) unless the cause of death is unknown.  
Refer to the Instructions for Use for the known risks associated with the commercial device. 
The adverse events and/or safety endpoints (see endpoint definitions in Table 23.2-1) 
requiring adjudication by the independent CEC include the following. 
• Mortality (all-cause: cardiovascular/unknown and non-cardiovascular)  
• Stroke (disabling and non-disabling; ischemic and hemorrhagic) 
• Systolic embolism  
• Bleeding (ISTH major and non-major clinically significant; procedural and non-
procedural)40,41 
• Pericardial effusion/tamponade requiring pericardiocentesis or surgery 
• Other events, at the discretion of Boston Scientific 
Details on the CEC events and procedures are outlined in the CEC charter. Tests and images 
required to adjudicate these events are specified in the event definitions (see Table 23.2-1). 
17.2. Definitions and Classification 
Adverse event definitions are provided in Table 17.2-1. Administrative edits were made on 
the safety definitions from applicable regulations and guidance including (but not limited to) 
21 CFR Part 812, ISO 14155 and EU MDR 2017/745/MDCG 2020-10/1 Guidance on Safety 
Reporting in Clinical Investigations for clarification purposes. 
Table 17.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
 
 
Any untoward medical occurrence, unintended disease or injury, or any untoward 
clinical signs (including an abnormal laboratory finding) in subjects, users or 
other persons, in the context of a clinical investigation, whether or not related to 
the study medical device and whether anticipated or unanticipated.  
NOTE 1: This includes events related to the study medical device or comparator. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events related 
to the study medical device.  
Adverse Device Effect 
(ADE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1   
Adverse event related to the use of the study medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the implantation, the 
installation, the operation, or any malfunction of the study medical device. 

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Table 17.2-1: Safety Definitions 
Term 
Definition 
NOTE 2: This definition includes any event resulting from use error or from 
intentional misuse of the study medical device. 
NOTE 3: This includes ‘comparator’ if the comparator is a medical device. 
Serious Adverse Event 
(SAE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1   
Adverse event that led to any of the following: 
a) death, 
b)  serious deterioration in the health of the subject, users or other persons, as 
defined by either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, including 
chronic diseases, or 
3) in-patient hospitalization or prolongation of existing hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function 
c) fetal distress, fetal death, or a congenital abnormality or birth defect including 
physical or mental impairment. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a procedure 
required by the clinical investigational plan, without a serious deterioration in 
health, is not considered a serious adverse event.  
Serious Adverse 
Device Effect (SADE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Adverse device effect that has resulted in any of the consequences characteristic 
of a serious adverse event. 
 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1  
Serious adverse device effect which by its nature, incidence, severity, or outcome 
has not been identified in the current risk assessment. 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect which 
by its nature, incidence, severity or outcome has been identified in the risk 
assessment. 
Serious Health Threat 
 
Ref: ISO 14155 
 
Signal from any adverse event or device deficiency that indicates an imminent 
risk of death or a serious deterioration in the health in subjects, users or other 
persons, and that requires prompt remedial action 
for other subjects, users or other persons. 
NOTE 1: This would include events that are of significant and unexpected nature 
such that they become alarming as a potential serious health hazard or possibility 
of multiple deaths occurring at short intervals. 
Device Deficiency 
Ref: ISO 14155 
Ref: MDCG 2020-10/1  
An inadequacy of a medical device related to its identity, quality, durability, 
reliability, usability, safety or performance.  
NOTE 1: Device deficiencies include malfunctions, use errors, and inadequacy in 
the information supplied by the manufacturer including labelling. 
NOTE 2: This definition includes device deficiencies related to the device under 
study. 
The following definitions will be used for defining hospitalization or prolongation of hospitalization for SAE 
classification purposes. 

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Table 17.2-1: Safety Definitions 
Term 
Definition 
Hospitalizations  
Hospitalization does not include: 
• emergency room visit that does not result in in-patient admission 
NOTE 1: Although an emergency room visit does not itself meet the 
definition for hospitalization, it may meet other serious criteria (e.g., medical 
or surgical intervention to prevent permanent impairment or damage). 
• elective and pre-planned treatment/surgery for a pre-existing condition that is 
documented in the subject’s record at the time of consent/enrollment 
• admission for social reasons and/or respite care in the absence of any 
deterioration in the subject’s general condition (e.g., subject is homeless, 
caregiver relief) 
• pre-planned, protocol-specified admission related to the clinical study (e.g., 
procedure required by protocol) 
Prolongation of 
hospitalization  
In-patient admission to the hospital that is prolonged beyond the expected 
standard duration for the condition under treatment. 
NOTE 1: New adverse events occurring during the hospitalization are evaluated 
to determine if they prolonged hospitalization or meet another SAE criteria. 
Procedural Definitions 
• 
“Index and Implant Procedure” refer to the procedure that involves the 
use of the investigational device which is the subject of the clinical trial 
 
• 
“Study Procedure” refers to procedures required during the clinical trial, 
but do not involve the investigational device 
 
• 
“Additional/Other Procedure” refers to procedures not specifically 
required by the protocol, but ones the subject may undergo as part of 
standard of care or in response to an adverse event 
 
17.3. Relationship to Study Device(s), (Device Under Study) and/or Study Procedure 
The Investigator must assess the relationship of the reportable AE to the WATCHMAN FLX 
LAA Closure Device or study procedure. See criteria in Table 17.3-1. 
Table 17.3-1: Criteria for Assessing Relationship of Study Device(s) (Device Under 
Study) or Procedure to Adverse Event 
Classification 
Description 
Not Related 
Ref: MDCG 2020-10/1 
Relationship to the device, comparator, or procedures can be excluded when: 
• the event has no temporal relationship with the use of the study device, or the 
procedures related to the use of the study device; 
• the serious event does not follow a known response pattern to the medical 
device (if the response pattern is previously known) and is biologically 
implausible; 
• the discontinuation of medical device application or the reduction of the level 
of activation/exposure – when clinically feasible – and reintroduction of its use 

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Table 17.3-1: Criteria for Assessing Relationship of Study Device(s) (Device Under 
Study) or Procedure to Adverse Event 
Classification 
Description 
(or increase of the level of activation/exposure), do not impact on the serious 
event; 
• the event involves a body-site or an organ that cannot be affected by the device 
or procedure;  
• the serious event can be attributed to another cause (e.g., an underlying or 
concurrent illness/clinical condition, an effect of another device, drug, 
treatment or other risk factors); 
• the event does not depend on a false result given by the study device used for 
diagnosis, when applicable. 
In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Possibly Related 
Ref: MDCG 2020-10/1 
The relationship with the use of the study device or comparator, or the relationship 
with procedures is weak but cannot be ruled out completely. Alternative causes are 
also possible (e.g., an underlying or concurrent illness/clinical condition and/or an 
effect of another device, drug or treatment). Cases where relatedness cannot be 
assessed, or no information has been obtained should also be classified as possible. 
Probably Related 
Ref: MDCG 2020-10/1 
The relationship with the use of the study device, comparator, or the relationship 
with procedures seems relevant and/or the event cannot be reasonably explained by 
another cause. 
Causal Relationship 
Ref: MDCG 2020-10/1 
The serious event is associated with the study device, comparator or with 
procedures beyond reasonable doubt when: 
• the event is a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
• the event has a temporal relationship with the study device use/application or 
procedures; 
• the event involves a body-site or organ that 
- the study device or procedures are applied to; 
- the study device or procedures have an effect on; 
• the serious event follows a known response pattern to the medical device (if 
the response pattern is previously known); 
• the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure) impact on the serious event (when clinically feasible); 
• other possible causes (e.g., an underlying or concurrent illness/clinical 
condition and/or an effect of another device, drug or treatment) have been 
adequately ruled out; 
• harm to the subject is due to error in use; 
• the event depends on a false result given by the study device used for 
diagnosis, when applicable. 
In order to establish the relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedures and the serious event. 

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17.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 17.4-1. 
Table 17.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method 
Communication Timeline (post-market 
studies) 
(EU MDR 2017/745, MDCG 2020-10/1, 
MEDDEV 2.12/1 : GUIDELINES ON A 
MEDICAL DEVICE VIGILANCE SYSTEM) 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
Complete AE eCRF page 
with all available new and 
updated information.  
• Within 1 business day of first becoming 
aware of the event. 
• Terminating at the end of the study 
Provide all relevant source 
documentation (de-
identified/ 
pseudonymized) for 
reported event.  
• Upon request of Sponsor.  
Serious Adverse Event (SAE) 
and CEC Events 
Complete AE eCRF page 
with all available new and 
updated information.  
• Within 10 calendar days after becoming 
aware of the event or as per local/regional 
regulations.  
• Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-
identified/ 
pseudonymized) for 
reported event. 
• When documentation is available 
Serious Adverse Device 
Effects (SADE) and Serious 
Adverse Events related to the 
protocol-required testing 
(LAA imaging) 
Complete AE eCRF page 
with all available new and 
updated information. 
• Within 3 calendar days of first becoming 
aware of the event or as per local/regional 
regulations.  
• Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-
identified/ 
pseudonymized) for 
reported event.  
• When documentation is available 
Device Deficiencies 
(including but not limited to 
malfunctions, use errors and 
inadequacy in information 
Complete applicable CRF 
fields/forms with all 
available new and updated 
information.  
• Within 3 calendar days of first becoming 
aware of the event. 
• Reporting required through the end of the 
study 

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Table 17.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method 
Communication Timeline (post-market 
studies) 
(EU MDR 2017/745, MDCG 2020-10/1, 
MEDDEV 2.12/1 : GUIDELINES ON A 
MEDICAL DEVICE VIGILANCE SYSTEM) 
supplied by the manufacturer, 
including labelling) 
NOTE: Any device 
deficiency that might have led 
to a serious adverse event if 
appropriate action had not 
been taken, intervention had 
not occurred, circumstances 
had been less fortunate is 
considered a reportable event. 
Provide all relevant source 
documentation (de-
identified/ 
pseudonymized) for 
reported event. 
• Upon request of Sponsor  
Adverse Event (AE) including 
Adverse Device Effects 
(ADE)  
Complete AE eCRF page, 
which contains such 
information as date of AE, 
treatment of AE,  
resolution, assessment of 
seriousness and 
relationship to the device.  
• ADE (or other key events of interest): in a 
timely manner but not later than 30 
business days after becoming aware of the 
information 
• AE: in a timely manner (recommend 
within 30 business days) after becoming 
aware of the information 
• Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-
identified/pseudonymized) 
for reported event.  
• Upon request of Sponsor 
Abbreviations: AE=adverse event; CEC=Clinical Events Committee; eCRF=electronic case report form; 
LAA=left atrial appendage 
 
17.5. Device Deficiencies 
Device deficiencies for study devices (WATCHMAN FLX LAA Closure Device preloaded 
on the WATCHMAN FLX Delivery Catheter) will be documented and reported to BSC 
using the Device Deficiency eCRF. If possible, the device(s) under study should be returned 
to BSC for analysis. Instructions for returning the device(s) will be provided on an individual 
basis. Device deficiencies should also be documented in the subject’s source records. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency, would be recorded as an adverse event on the appropriate eCRF. 

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17.6. Reporting to Regulatory Authorities / IECs / Investigators 
Boston Scientific Corporation is responsible for reporting adverse event information to all 
participating Principal Investigators, IECs, and regulatory authorities, as applicable according 
to local reporting requirements.  
The Principal Investigator is responsible for informing the IEC and regulatory authorities of 
USADEs and SAEs as required by local/regional regulations. 
18. Informed Consent 
Subject participation in this clinical study is voluntary. Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any study devices, study-
required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority, as applicable. The ICF must be accepted 
by BSC or its delegate (e.g., Clinical Research Organization), and approved by the center’s 
IEC or central IEC, if applicable. 
Boston Scientific Corporation will provide a study-specific template of the ICF to 
investigators participating in this study. The ICF template may be modified to meet the 
requirements of the investigative center’s IEC. Any modification requires acceptance from 
BSC prior to use of the form. The ICF must be in a language understandable to the subject 
and if needed, BSC will assist the center in obtaining a written consent translation. Translated 
consent forms must also have IEC approval prior to their use. Privacy language shall be 
included in the body of the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations, and guidelines. 
• Be conducted by the Principal Investigator or designee authorized to conduct the 
process,  
• Include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• Avoid any coercion of or undue influence of subjects to participate, 
• Not waive or appear to waive subject’s legal rights, 
• Use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• Provide ample time for the subject to consider participation and ask questions, if 
necessary, 

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• Ensure important new information is provided to new and existing subjects throughout 
the clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations, and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs the ICF, the subject shall be asked to provide 
informed consent for continued participation as soon as his/her medical condition allows. 
The original signed ICF will be retained by the center and a copy of the signed and dated 
document and any other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements. Any violations of the informed consent process 
must be reported as deviations to the sponsor and local regulatory authorities (e.g., IEC), as 
appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IEC. The new version of the ICF must be approved by the 
IEC. Acceptance by Boston Scientific is required if changes to the revised ICF are requested 
by the center’s IEC. The IEC will determine the subject population to be re-consented. 
19. Committees 
19.1. Safety Monitoring Process 
To promote early detection of safety issues, the Clinical Events Committee (see 
Section 19.1.1) will provide evaluations of pre-specified safety events. Success of this 
program requires dynamic collection of unmonitored data as soon as the event is reported. 
This is expedited through BSC or its designee, which is responsible for coordinating the 
collection of information for the subject dossier from the centers and core laboratory.  
The BSC personnel from the Medical Safety and Safety Trial Operations group review safety 
data as they are reported by the centers throughout the duration of the study. During regularly 
scheduled monitoring activities, clinical research monitors further support the dynamic 
reporting process through their review of source documents and other data information. The 
BSC Medical Safety and Safety Trial Operations team includes physicians with expertise in 
cardiology and with the necessary therapeutic and subject matter expertise to evaluate and 
classify the events into the categories outlined above (Section 17). 

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19.1.1. Clinical Events Committee 
A Clinical Events Committee (CEC) will be used in this study. The CEC is an independent 
group of individuals with pertinent expertise, including cardiovascular interventional therapy, 
cardiovascular surgery, and neurology, which reviews and adjudicates important endpoints 
and relevant adverse events reported by study investigators. The CEC will review a safety 
event dossier, which may include copies of subject source documents provided by study 
centers and adjudicate study endpoint related clinical events. The responsibilities, 
qualifications, membership, and committee procedures of the CEC are outlined in the CEC 
Charter. 
The CEC will review the following events for this study. 
• All-cause mortality (cardiovascular/unknown and non-cardiovascular)  
• Stroke (disabling and non-disabling; ischemic and hemorrhagic)  
• Systemic embolism  
• Bleeding: ISTH major and non-major clinically significant bleeding including procedural 
(≤7 days post-procedure) and non-procedural (>7 days post-procedure) 
• Pericardial effusion/tamponade requiring pericardiocentesis or surgery 
• Other events, at the discretion of Boston Scientific 
20. Suspension or Termination 
20.1. Premature Termination of the Study 
Boston Scientific Corporation reserves the right to terminate the study at any stage but 
intends to exercise this right only for valid scientific or business reasons and reasons related 
to protection of subjects. Investigators, associated IECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of study termination. 
20.1.1. Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following: 
• Suspicion of an unacceptable risk, including serious health threat. In this case, the 
sponsor shall suspend the clinical investigation while the risk is assessed. The sponsor 
shall terminate the clinical investigation if an unacceptable risk which cannot be 
controlled is confirmed. 
• Instructions by the IEC or regulatory authorities to suspend or terminate the clinical 
investigation. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  

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• A decision on the part of BSC to suspend or discontinue development/marketing of the 
device. 
20.2. Termination of Study Participation by the Investigator or Withdrawal of IEC 
Approval 
Any investigator, or associated IEC or regulatory authority may discontinue participation in 
the study or withdraw approval of the study, respectively, with suitable written notice to 
BSC. Investigators, associated IECs, and regulatory authorities, as applicable, will be notified 
in writing in the event of these occurrences. 
20.3. Requirements for Documentation and Subject Follow-up 
In the event of premature study termination, a written statement as to why the premature 
termination has occurred will be provided to all participating centers by BSC. The IEC and 
regulatory authorities, as applicable, will be notified. Detailed information on how enrolled 
subjects will be managed thereafter will be provided.  
In the event an IEC terminates participation in the study, participating investigators, 
associated IECs, and regulatory authorities, as applicable, will be notified in writing. Detailed 
information on how enrolled subjects will be managed thereafter will be provided by BSC. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility, detailed information on how enrolled 
subjects will be managed thereafter will be provided by BSC. 
The Principal Investigator or his/her designee must return all study-related documents and 
devices, if supplied by BSC, unless this action would jeopardize the rights, safety, or welfare 
of the subjects. 
20.4. Criteria for Suspending/Terminating a Study Center 
Boston Scientific Corporation reserves the right to stop the inclusion of subjects at a study 
center at any time after the study initiation visit if no subjects have been enrolled for a period 
beyond 3 months after center initiation, or if the center has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of center participation, all devices and testing equipment, as 
applicable, will be returned to BSC unless this action would jeopardize the rights, safety, or 
well-being of the subjects. The IEC and regulatory authorities, as applicable, will be notified. 
Study participants will be contacted, as applicable, and be informed of changes to study visit 
schedule. 

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21. Study Registration and Results 
21.1. Study Registration 
To comply with applicable laws and regulations, the study will be registered on a publicly 
accessible database. 
21.2. Clinical Investigation Report  
Study results will be made available in accordance with the legal requirements and the 
recognized ethical principles, in accordance with the Boston Scientific Policy. A Clinical 
Investigation Report will be made available to all investigators, IECs, and regulatory 
authorities, as applicable in accordance with the Boston Scientific Policy and local 
requirements.  As applicable an abbreviated Clinical Investigation Report will be made 
available on a publicly accessible database 
21.3. Publication Policy 
Boston Scientific Corporation requires disclosure of its involvement as a sponsor or financial 
supporter in any publication or presentation relating to a BSC study or its results. Boston 
Scientific Corporation may submit study results for publication (regardless of study outcome) 
following the conclusion or termination of the study. Boston Scientific Corporation adheres 
to the Contributorship Criteria set forth in the Uniform Requirements of the International 
Committee of Medical Journal Editors (ICMJE; http://www.icmje.org). In order to ensure the 
public disclosure of study results in a timely manner, while maintaining an unbiased 
presentation of study outcomes, BSC personnel may assist authors and investigators in 
publication preparation provided the following guidelines are followed.  
• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy should 
be discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical study may be made available 
to other researchers in accordance with the Boston Scientific Data Sharing Policy 
(http://www.bostonscientific.com). 
22. Bibliography 
1. 
Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics-2019 
update: a report from the American Heart Association. Circulation 2019;139:e56-e528. 

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2. 
Di Carlo A, Bellino L, Consoli D, et al. Prevalence of atrial fibrillation in the Italian 
elderly population and projections from 2020 to 2060 for Italy and the European Union: 
the FAI Project. Europace 2019;21:1468-75. 
3. 
Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of 
atrial fibrillation developed in collaboration with EACTS. Europace 2016;18:1609-78. 
4. 
Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for 
stroke: the Framingham Study. Stroke 1991;22:983-8. 
5. 
Lamassa M, Di Carlo A, Pracucci G, et al. Characteristics, outcome, and care of stroke 
associated with atrial fibrillation in Europe: data from a multicenter multinational 
hospital-based registry (The European Community Stroke Project). Stroke 
2001;32:392-8. 
6. 
Alkhouli M, Alqahtani F, Aljohani S, Alvi M, Holmes DR. Burden of atrial fibrillation-
associated ischemic stroke in the United States. J Am Coll Cardiol EP 2018;4:618-25. 
7. 
Velleca M, Costa G, Goldstein L, Bishara M, Boo LM. A review of the burden of atrial 
fibrillation: understanding the impact of the new millennium epidemic across Europe. 
EMJ Cardiol 2019;7:110-8. 
8. 
Williams BA, Chamberlain AM, Blankenship JC, Hylek EM, Voyce S. Trends in atrial 
fibrillation incidence rates within an integrated health care delivery system, 2006 to 
2018. JAMA Netw Open 2020;3:e2014874. 
9. 
Jackson LR, 2nd, Jackson KP, Thomas KL. Percutaneous left atrial appendage 
occlusion: A review of current devices, clinical evidence, patient selection, and post 
procedural antithrombotic management. Prog Cardiovasc Dis 2021;66:92-100. 
10. Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial 
fibrillation: a Global Burden of Disease 2010 Study. Circulation 2014;129:837-47. 
11. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical 
patients with atrial fibrillation. Ann Thorac Surg 1996;61:755-9. 
12. Klein AL, Grimm RA, Murray RD, et al. Use of transesophageal echocardiography to 
guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001;344:1411-20. 
13. Cresti A, García-Fernández MA, Sievert H, et al. Prevalence of extra-appendage 
thrombosis in non-valvular atrial fibrillation and atrial flutter in patients undergoing 
cardioversion: a large transoesophageal echo study. EuroIntervention 2019;15:e225-
e30. 
14. Al-Saady NM, Obel OA, Camm AJ. Left atrial appendage: structure, function, and role 
in thromboembolism. Heart 1999;82:547-54. 
15. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with 
atrial fibrillation. N Engl J Med 2009;361:1139-51. 
16. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular 
atrial fibrillation. N Engl J Med 2011;365:883-91. 

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17. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients 
with atrial fibrillation. N Engl J Med 2011;365:981-92. 
18. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with 
atrial fibrillation. N Engl J Med 2013;369:2093-104. 
19. O'Brien EC, Simon DN, Allen LA, et al. Reasons for warfarin discontinuation in the 
Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). 
Am Heart J 2014;168:487-94. 
20. Lip GYH, Pan X, Kamble S, et al. Discontinuation risk comparison among 'real-world' 
newly anticoagulated atrial fibrillation patients: Apixaban, warfarin, dabigatran, or 
rivaroxaban. PLoS One 2018;13:e0195950. 
21. Alfadhel M, Nestelberger T, Samuel R, McAlister C, Saw J. Left atrial appendage 
closure - Current status and future directions. Prog Cardiovasc Dis 2021;doi: 
10.1016/j.pcad.2021.11.013. 
22. Holmes DR, Jr., Alkhouli M, Reddy V. Left atrial appendage occlusion for the unmet 
clinical needs of stroke prevention in nonvalvular atrial fibrillation. Mayo Clin Proc 
2019;94:864-74. 
23. Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial 
appendage versus warfarin therapy for prevention of stroke in patients with atrial 
fibrillation: a randomised non-inferiority trial. Lancet 2009;374:534-42. 
24. Holmes DR, Jr., Kar S, Price MJ, et al. Prospective randomized evaluation of the 
Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation 
versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol 2014;64:1-
12. 
25. Reddy VY, Doshi SK, Kar S, et al. 5-Year outcomes after left atrial appendage closure: 
from the PREVAIL and PROTECT AF trials. J Am Coll Cardiol 2017;70:2964-75. 
26. Kar S, Doshi SK, Sadhu A, et al. Primary outcome evaluation of a next-generation left 
atrial appendage closure device: results from the PINNACLE FLX trial. Circulation 
2021;143:1754-62. 
27. Radinovic A, Falasconi G, Marzi A, et al. Long-term outcome of left atrial appendage 
occlusion with multiple devices. Int J Cardiol 2021;344:66-72. 
28. Schwartz RS, Holmes DR, Van Tassel RA, et al. Left atrial appendage obliteration: 
mechanisms of healing and intracardiac integration. J Am Coll Cardiol Intv 
2010;3:870-7. 
29. Gianni C, Horton RP, Della Rocca DG, et al. Intracardiac echocardiography- versus 
transesophageal echocardiography-guided left atrial appendage occlusion with 
Watchman FLX. J Cardiovasc Electrophysiol 2021;32:2781-4. 
30. Akella K, Murtaza G, Turagam M, et al. Evaluating the role of transesophageal 
echocardiography (TEE) or intracardiac echocardiography (ICE) in left atrial 
appendage occlusion: a meta-analysis. J Interv Card Electrophysiol 2021;60:41-8. 

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31. Turagam MK, Neuzil P, Petru J, et al. Intracardiac echocardiography-guided 
implantation of the Watchman FLX left atrial appendage closure device. J Cardiovasc 
Electrophysiol 2021;32:717-25. 
32. Tzikas A, Shakir S, Gafoor S, et al. Left atrial appendage occlusion for stroke 
prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac 
Plug. EuroIntervention 2016;11:1170-9. 
33. Lempereur M, Aminian A, Freixa X, et al. Device-associated thrombus formation after 
left atrial appendage occlusion: a systematic review of events reported with the 
Watchman, the Amplatzer Cardiac Plug and the Amulet. Catheter Cardiovasc Interv 
2017;90:E111-e21. 
34. Saw J, Tzikas A, Shakir S, et al. Incidence and clinical impact of device-associated 
thrombus and peri-device leak following left atrial appendage closure with 
the Amplatzer Cardiac Plug. J Am Coll Cardiol Intv 2017;10:391-9. 
35. Dukkipati SR, Kar S, Holmes DR, et al. Device-related thrombus after left atrial 
appendage closure: Incidence, predictors, and outcomes. Circulation 2018;138:874-85. 
36. Fauchier L, Cinaud A, Brigadeau F, et al. Device-related thrombosis after percutaneous 
left atrial appendage occlusion for atrial fibrillation. J Am Coll Cardiol 2018;71:1528-
36. 
37. Saw J, Nielsen-Kudsk JE, Bergmann M, et al. Antithrombotic therapy and device-
related thrombosis following endovascular left atrial appendage closure. J Am Coll 
Cardiol Intv 2019;12:1067-76. 
38. Bruno A, Akinwuntan AE, Lin C, et al. Simplified modified Rankin scale 
questionnaire. Reproducibility over the telephone and validation with Quality of Life. 
Stroke 2011;42:2276-9. 
39. Lane DA, Lip GY. Use of the CHA(2)DS(2)-VASc and HAS-BLED scores to aid 
decision making for thromboprophylaxis in nonvalvular atrial fibrillation. Circulation 
2012;126:860-5. 
40. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of 
antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 
2005;3:692-4. 
41. Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Definition of clinically relevant 
non-major bleeding in studies of anticoagulants in atrial fibrillation and venous 
thromboembolic disease in non-surgical patients: communication from the SSC of the 
ISTH. J Thromb Haemost 2015;13:2119-26. 
42. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for 
cardiovascular clinical trials: a consensus report from the Bleeding Academic Research 
Consortium. Circulation 2011;123:2736-47. 

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43. Ndrepepa G, Schuster T, Hadamitzky M, et al. Validation of the Bleeding Academic 
Research Consortium definition of bleeding in patients with coronary artery disease 
undergoing percutaneous coronary intervention. Circulation 2012;125:1424-31. 
44. Tzikas A, Holmes DR, Jr., Gafoor S, et al. Percutaneous left atrial appendage 
occlusion: the Munich consensus document on definitions, endpoints, and data 
collection requirements for clinical studies. Europace 2017;19:4-15. 
45. Leon MB, Piazza N, Nikolsky E, et al. Standardized endpoint definitions for 
transcatheter aortic valve implantation clinical trials: a consensus report from the Valve 
Academic Research Consortium. J Am Coll Cardiol 2011;57:253-69. 
46. Kappetein AP, Head SJ, Genereux P, et al. Updated standardized endpoint definitions 
for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 
consensus document. J Am Coll Cardiol 2012;60:1438-54. 
23. Abbreviations and Definitions  
23.1. Abbreviations and Acronyms 
Abbreviations and acronyms are shown in Table 23.1-1.  
 
 
Table 23.1-1: Abbreviations and Acronyms 
Abbreviation/Acronym 
Definition 
ADE 
adverse device effect 
AE 
adverse event 
AF 
atrial fibrillation 
ASD 
atrial septal defect 
AV 
atrioventricular 
BSC 
Boston Scientific Corporation 
CE 
Conformité Européenne 
CEC 
Clinical Events Committee 
CHA2DS2-VASc 
congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, 
stroke/TIA, vascular disease, age 65‒74 years, sex category 
CI 
confidence interval 
CNS 
central nervous system 
CRF 
case report form 
CT 
computed tomography 
DOAC 
direct oral anticoagulant 
DRT 
device related thrombus 
EC 
exclusion criterion 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 

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Table 23.1-1: Abbreviations and Acronyms 
Abbreviation/Acronym 
Definition 
GDPR 
General Data Protection Regulation 
GI 
gastrointestinal 
HAT 
hypoattenuated thickening  
HAS-BLED 
hypertension, abnormal renal/liver function, stroke, bleeding history or 
predisposition, labile INR, elderly, drugs/alcohol concomitantly 
HCP 
health care personnel 
IC 
inclusion criterion 
ICE 
intracardiac echocardiography 
ICF 
Informed Consent Form 
IEC 
Independent Ethics Committee 
IFU 
Instructions for Use 
INR 
international normalized ratio 
ISTH 
International Society on Thrombosis and Haemostasis 
ITT 
intention-to-treat 
LA 
left atrium 
LAA 
left atrial appendage 
LAAC 
left atrial appendage closure 
LAAO 
left atrial appendage occlusion 
MI 
myocardial infarction 
MRI 
magnetic resonance imaging 
mRS 
Modified Rankin Scale score 
NIHSS 
National Institutes of Health Stroke Scale 
NOAC 
Non-VKA oral anticoagulant 
NSTEMI 
Non-ST elevation myocardial infarction 
NVAF 
nonvalvular atrial fibrillation 
OAC 
oral anticoagulant 
PET 
polyethylene terephthalate 
PFO 
patent foramen ovale 
RCT 
randomized controlled trial 
SADE 
serious adverse device effect 
SAE 
serious adverse event 
SAPT 
single antiplatelet therapy 
SE 
systemic embolism 
STEMI 
ST-elevation myocardial infarction 
TEE 
transesophageal Doppler echocardiography 
TIA 
transient ischemic attack 
UADE 
unanticipated adverse device effect 
USADE 
unanticipated serious adverse device effect 
VTE 
venous thromboembolic 
 

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23.2. Definitions 
Terms are defined in Table 23.2-1. See Table 23.1-1 for a list of abbreviations.  
Table 23.2-1: Definitions 
Term 
Definition 
ADVERSE DEVICE 
EFFECT (ADE) 
Adverse event related to the use of an investigational medical device 
Note 1: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or 
operation, or any malfunction of the investigational medical device.  
Note 2: This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
BLEEDING 40-43  
  
 
International Society on Thrombosis and Haemostasis (ISTH) Definitions 
Clinically Relevant Non-Major Bleeding (AF and non-surgical VTE studies) 
Any sign or symptom of hemorrhage (e.g., more bleeding than would be expected 
for a clinical circumstance, including bleeding found by imaging alone) that does 
not fit the criteria for the ISTH definition of major bleeding but does meet at least 
one of the following criteria. 
• Requiring medical intervention by a healthcare professional 
• Leading to hospitalization or increased level of care 
• Prompting a face to face (i.e., not just a telephone or electronic 
communication) evaluation 
ISTH Major Bleeding in Non-Surgical Patients  
Defined as having a symptomatic presentation and one or more of the following. 
• Fatal bleeding, AND/OR 
• Bleeding in a critical area or organ, such as intracranial, intraspinal, 
intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with 
compartment syndrome, AND/OR 
• Bleeding causing a fall in hemoglobin level of 20 g L-1 (1.24 mmol L-1) or 
more, or leading to transfusion of two or more units of whole blood or red 
cells  
Bleeding Academic Research Consortium (BARC) Definitions 
Type 0 
No bleeding 
Type 1 
Bleeding that is not actionable and does not cause the subject to seek unscheduled 
performance of studies, hospitalization, or treatment by a health-care professional; 
may include episodes leading to self-discontinuation of medical therapy by the 
subject without consulting a health-care professional. 
Type 2 
Any overt, actionable sign of hemorrhage (e.g., more bleeding than would be 
expected for a clinical circumstance, including bleeding found by imaging alone) 
that does not fit the criteria for type 3, 4, or 5 but does meet at least one of the 
following criteria. 
• Requiring nonsurgical, medical intervention by a health-care professional, 
AND/OR 
• Leading to hospitalization or increased level of care, AND/OR 
• Prompting evaluation 
Type 3 
• Type 3a 

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Table 23.2-1: Definitions 
Term 
Definition 
o Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL (provided 
hemoglobin drop is related to bleed) 
o Any transfusion with overt bleeding 
• Type 3b 
o Overt bleeding plus hemoglobin drop ≥5 g/dL (provided hemoglobin drop 
is related to bleed) 
o Cardiac tamponade 
o Bleeding requiring surgical intervention for control (excluding 
dental/nasal/skin/hemorrhoid) 
o Bleeding requiring intravenous vasoactive agents 
• Type 3c 
o Intracranial hemorrhage (does not include microbleeds or hemorrhagic 
transformation, does not include intraspinal) 
o Subcategories confirmed by autopsy or imaging or lumbar puncture 
o Intraocular bleed compromising vision 
Type 4 
• Coronary bypass graft-related bleeding 
• Perioperative intracranial bleeding within 48h 
• Reoperation after closure of sternotomy for the purpose of controlling 
bleeding 
• Transfusion of ≥ 5 U whole blood or packed red blood cells within a 48-h 
period 
• Chest tube output more than or equal to 2L within a 24-h period 
Type 5 
Fatal bleeding 
• Type 5a 
o Probable fatal bleeding; no autopsy or imaging confirmation but clinically 
suspicious  
• Type 5b 
Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation 
CARDIAC 
TAMPONADE 
Evidence of a new pericardial effusion associated with hemodynamic instability 
and clearly related to the index procedure. Clinical syndrome caused by the 
accumulation of fluid in the pericardial space, resulting in reduced ventricular 
filling and subsequent hemodynamic compromise. 
CLINICAL EVENTS 
COMMITTEE (CEC) 
EVENT 
For the WATCHMAN FLX CT study, CEC events include the following:  
• 
Mortality 
• 
Stroke 
• 
Bleeding (ISTH major and non-major clinically significant) 
• 
Systemic embolism 
• 
Pericardial effusion/tamponade requiring pericardiocentesis or surgery 
• 
Other events, at the discretion of Boston Scientific 
DATA CATEGORIES 
Data categories as defined by GDPR are listed below. 
Personal Data: 
GDPR defines “Personal Data” to be any information relating to an identified or 
identifiable natural person (‘data subject’); an identifiable natural person is one 
who can be identified, directly or indirectly, in particular by reference to an 
identifier such as a name, an identification number, location data, an online 

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Term 
Definition 
identifier or to one or more factors specific to the physical, physiological, genetic, 
mental, economic, cultural or social identity of that natural person. 
Sensitive Personal Data: 
GDPR defines “Sensitive Personal Data” as a subset of Personal Data, which, due 
to their nature have been classified as deserving additional privacy and security 
protections because their processing may create a risk for an individual’s 
fundamental right and freedom. This subset includes but is not limited to the 
following: racial, ethnic origin or ethnicity; political opinions; religious or 
philosophical beliefs; trade union membership; genetic data; biometric data for the 
purpose of uniquely identifying a natural person; health data (including gender, 
family medical history, etc.); sex life or sexual orientation; criminal records or 
allegations of crimes (requires an even higher standard of protection). 
Identifiers: 
“Identifiers” are Personal Data that can be used alone or in combination with other 
identifiers to identify an individual. Identifiers include but are not limited to the 
following:  
• All government-issued identification numbers (including but not limited to 
names, social security number, certificate/license numbers, passport, national 
ID) 
• All financial account numbers (including but not limited to bank account 
numbers, payment numbers, bank or credit card numbers)  
• All geographic subdivisions smaller than a state, including street address, 
city, county, precinct, ZIP code, and their equivalent geocodes, except for the 
initial three digits of the ZIP code if, according to the current publicly 
available data from the Bureau of the Census, the geographic unit formed by 
combining all ZIP codes with the same three initial digits contains more than 
20,000 people and/or the initial three digits of a ZIP code for all such 
geographic units containing 20,000 or fewer people is changed to 000 
• All elements of dates (except year) for dates that are directly related to an 
individual, including birth date, admission date, discharge date, death date, 
and all ages over 89 and all elements of dates (including year) indicative of 
such age, except that such ages and elements may be aggregated into a single 
category of age 90 or older 
• Telephone numbers 
• Fax numbers 
• Device identifiers and serial numbers 
• E-mail addresses 
• Web Universal Resource Locators (URLs) 
• Internet Protocol (IP) addresses 
• Medical record numbers 
• Biometric identifiers, including finger and voice prints 
• Health plan beneficiary numbers 
• Full-face photographs and any comparable images 
Any other unique identifying number, characteristic, or code (including subject ID 
number) 
DEATH  
 
Cardiovascular Death 
Any one of the following criteria is met. 

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• Death due to proximate cardiac cause (e.g., myocardial infarction, cardiac 
tamponade, worsening heart failure, endocarditis, etc.) 
• Death caused by noncoronary, non-CNS vascular conditions such as 
pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other 
vascular disease 
• Death from vascular CNS causes 
o Hemorrhagic stroke 
o Ischemic stroke 
• All-cause mortality during the index procedure, any procedure-related death 
within 30 days after the index procedure or during postoperative 
hospitalization for the index procedure (if >30 days), including those related 
to a complication of the procedure or treatment for a complication of the 
procedure 
• Unexplained death (see below)  
Non-cardiovascular Death 
• Any death in which the primary cause of death is clearly related to another 
condition (e.g., trauma, cancer, suicide) 
Unexplained Death 
• Sudden or unwitnessed death defined as a non-traumatic, unexpected fatal 
event occurring within one hour of the onset of symptoms in an apparently 
healthy subject. If death is not witnessed, the definition applies when the 
victim was in good health 24 hours before the event. 
• Death of unknown causes 
DEVICE 
DEFICIENCY  
 
Inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, safety, or performance.  
Note 1: Device deficiencies include malfunctions, use errors, and inadequate 
labeling. 
DEVICE 
EMBOLIZATION 
Defined as movement of the device during or after deployment such that it 
dislodges and entirely leaves the LAA or completely loses contact with the LAA. 
DEVICE MIGRATION 
Defined as shifting of the implant within the LAA to create an inadequate seal 
where the gap is greater than 5mm at 45 days or later and the physician must 
intervene (e.g., adjust patient’s anticoagulant regimen). 
DEVICE RELATED 
THROMBUS 
Thrombus formation on the atrial facing side of the device, possibly resulting in 
the need for anticoagulation and/or hospitalization. 
DEVICE SUCCESS 
Defined as implantation of a WATCHMAN FLX device without in-hospital 
mortality 
EMBOLISM 
Examples include a free-flowing blood clot or lesion material that is located in the 
systemic or pulmonary circulation. Embolism may be manifested by a 
neurological event or a noncerebral embolic event. 
GENERAL DATA 
PROTECTION 
REGULATION 
The General Data Protection Regulation (GDPR) is a legal framework that sets 
guidelines for the collection and processing of personal information of individuals 
within the European Union. 
MAJOR 
ENDOVASCULAR 
INTERVENTION 
Examples include events such as pseudoaneurysm repair, AV fistula repair, or 
other major endovascular repair.  
Note 1: Percutaneous catheter drainage of pericardial effusions, snaring of an 
embolized device, thrombin injection to treat femoral pseudoaneurysm and 

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nonsurgical treatments of access site complications are NOT considered major 
endovascular repairs. 
NEUROLOGICAL 
DEFICIT  
An acute episode of a focal or global neurological deficit with at least one of the 
following: 
• Change in the level of consciousness 
• Hemiplegia 
• Hemiparesis 
• One-sided numbness or sensory loss 
• Dysphasia or aphasia 
• Hemianopia 
• Amaurosis fugax 
• Any other neurological signs or symptoms consistent with stroke 
In addition, there are no other readily identifiable non-stroke causes for the 
clinical presentation (e.g., brain tumor, trauma, infection, hypoglycemia, 
peripheral lesion, pharmacologic influences), to be determined by or in 
conjunction with the designated neurologist. 
NON-VALVULAR 
ATRIAL 
FIBRILLATION 
Atrial fibrillation in the absence of moderate-to-severe mitral stenosis or in the 
absence of a mechanical heart valve. 
PERICARDIAL 
EFFUSION44 
Severity of pericardial effusion, with or without cardiac tamponade, is defined by 
the clinical therapy associated with the effusion. 
• Clinically non-relevant 
o Requiring no intervention 
o Treated pharmacologically 
• Clinically relevant 
o 
Treated with therapeutic pericardiocentesis 
o 
Treated with surgical intervention 
o 
Requiring blood transfusion 
o 
Resulting in shock and/or death 
PROCEDURE-
RELATED EVENTS 
Events occurring during or as a direct result of the index procedure.  
SERIOUS ADVERSE 
EVENT (SAE) 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3 
Adverse event that: 
• Led to death, 
• Led to serious deterioration in the health of the subject as defined by either: 
o a life-threatening illness or injury, or 
o a permanent impairment of a body structure or a body function, or 
o in-patient hospitalization or prolongation of existing hospitalization, or 
o medical or surgical intervention to prevent life-threatening illness or injury 
or permanent impairment to a body structure or a body function 
• Led to fetal distress, fetal death, or a congenital abnormality or birth defect. 
SERIOUS ADVERSE 
DEVICE EFFECT 
(SADE) 
Adverse device effect that has resulted in any of the consequences characteristic 
of a serious adverse event 

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SOURCE DATA 
(per ISO 14155:2011) 
All information in original records of clinical findings, observations, or other 
activities in a clinical investigation, necessary for the reconstruction and 
evaluation of the clinical investigation 
SOURCE 
DOCUMENT 
(per ISO 14155:2011) 
Printed, optical or electronic document containing source data. Examples: 
Hospital records, laboratory notes, device accountability records, photograhic 
negatives, radiographs, records kept at the investigation center, at the laboratories 
and at the medico-technical departments involvced in the clinical investigation.  
STROKE45,46  
 
Stroke Definition  
Stroke is defined by one of following. 
• Duration of a focal or global neurological deficit ≥24 h  
• Duration of a focal or global neurological deficit <24 h, if available 
neuroimaging documents a new hemorrhage or infarct 
• A neurological deficit resulting in death  
Stroke Classification 
• Ischemic Stroke 
o An episode of neurological dysfunction caused by focal cerebral, spinal, or 
retinal infarction.  
• Hemorrhagic Stroke  
o Intracerebral: Rapidly developing clinical signs of neurological 
dysfunction attributable to a focal collection of blood within the brain 
parenchyma or ventricular system that is not caused by trauma. 
o Subarachnoid: Rapidly developing signs of neurological dysfunction 
and/or headache because of bleeding into the subarachnoid space (the 
space between the arachnoid membrane and the pia mater of the brain or 
spinal cord), which is not caused by trauma. 
• Not Otherwise Specified  
o An episode of acute neurological dysfunction presumed to be caused by 
ischemia or hemorrhage, persisting ≥ 24 hours or until death, but without 
sufficient evidence to be classified as one of the above. 
Stroke Diagnostic Criteria  
• Rapid onset of a focal or global neurological deficit with at least one of the 
following: change in level of consciousness, hemiplegia, hemiparesis, 
numbness or sensory loss affecting one side of the body, dysphasia or aphasia, 
hemianopia, amaurosis fugax, or other neurological signs or symptoms 
consistent with stroke 
• Duration of a focal or global neurological deficit ≥24 h; OR <24 h, if 
therapeutic intervention(s) were performed (e.g., thrombolytic therapy or 
intracranial angioplasty); OR available neuroimaging documents a new 
hemorrhage or infarct; OR the neurological deficit results in death 
• No other readily identifiable non-stroke cause for the clinical presentation 
(e.g., brain tumor, trauma, infection, hypoglycemia, peripheral lesion, 
pharmacological influences) 
• Confirmation of the diagnosis by at least one of the following.  
o Neurology or neurosurgical specialist  
o Neuroimaging procedure (MRI or CT scan or cerebral angiography) 
o Lumbar puncture (i.e., spinal fluid analysis diagnostic of intracranial 
hemorrhage)  

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Stroke Definitions 
Diagnosis as above, preferably with positive neuroimaging study 
• Non-disabling: Modified Rankin Scale (mRS) score <2 at 90 days OR one 
that does not result in an increase of at least one mRS category from an 
individual’s pre-stroke baseline 
• Disabling: Modified Rankin Scale score ≥2 at 90 days AND an increase of at 
least one mRS category from an individual’s pre-stroke baseline  
Note 1: Modified Rankin Scale assessments should be made by qualified 
individuals according to a certification process.  
Note 2: Assessment of the mRS score should occur at baseline; mRS also should 
be performed after a stroke and at 90 days after the onset of any stroke. 
SYSTEMIC 
EMBOLISM 
Acute vascular insufficiency or occlusion of the extremities or any non-CNS 
organ associated with clinical, imaging, surgical/autopsy evidence of arterial 
occlusion in the absence of other likely mechanism (e.g., trauma, atherosclerosis, 
or instrumentation). When there is presence of prior peripheral artery disease, 
angiographic or surgical or autopsy evidence is required to show abrupt arterial 
occlusion. 
TRANSIENT 
ISCHEMIC ATTACK 
(TIA) 
Any neurological deficit not satisfying the criteria for stroke (see above for 
definition of stroke), specifically: 
• Duration of a deficit is <24 h; AND 
• Neuroimaging does not document a new hemorrhage or infarct 
Note 1: The difference between TIA and ischemic stroke is the presence of tissue 
damage or new sensory-motor deficit persisting >24 hours. By definition, TIA 
does not produce lasting disability. 
UNANTICIPATED 
SERIOUS ADVERSE 
DEVICE EFFECT 
(USADE) 
Serious adverse device effect which by its nature, incidence, severity, or outcome 
has not been identified in the current version of the risk analysis report  
Note 1: An anticipated serious adverse device effect is an effect which by its 
nature, incidence, severity, or outcome has been identified in the risk analysis 
report. 
VALVULAR ATRIAL 
FIBRILLATION 
Atrial fibrillation in the setting of moderate-to-severe mitral stenosis (potentially 
requiring surgical intervention) or in the presence of an artificial (mechanical) 
heart valve. 
VULNERABLE 
SUBJECT 
(per ISO 14155:2020) 
Vulnerable subjects are individuals who are unable to fully understand all aspects 
of the investigation that are relevant to the decision to participate, or who could be 
manipulated or unduly influenced as a result of a compromised position, 
expectation of benefits or fear of retaliatory response. 
Abbreviations: ADE=adverse device effect; AE=adverse event; CEC=Clinical Events Committee; 
CNS=central nervous system; CT=computed tomography; GDPR=General Data Protection Regulation; 
ISTH=International Society on Thrombosis and Haemostasis; LAA=left atrial appendage; MRI=magnetic 
resonance imaging; mRS=Modified Rankin Scale score; SADE=serious adverse device effect; SAE=serious 
adverse event; TIA=transient ischemic attack; USADE=unanticipated serious adverse device effect