Long-term Follow-up on LAA Exclusion Using AtriClip, VCLIP Post-Market Study, CLINICAL TRIAL PROTOCOL: CP-2021-03
Phase: NA
Conditions: Left Atrial Appendage Absent
Sponsor: AtriCure, Inc.

 
Protocol Number: CP-2021-03 
 
 
Page 1 of 62 
Protocol Name: V-CLIP Study 
                                                                                                                                          
Version: Rev B; Oct 15, 2021 
                                                                                                                         Form-582.B 
Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
AtriCure, Inc. 
7555 Innovation Way 
 
Mason, Ohio 45040 
 
 
Long-Term Follow-Up On LAA Exclusion Using AtriClip 
VCLIP POST-MARKET STUDY 
 
CLINICAL TRIAL PROTOCOL: CP-2021-03 
 
 
Revision Number 
B 
Date 
October 15, 2021 
National Principal 
Investigator/Lead Principal 
Investigator:                
Elias Zias, MD 
NYU Langone Health 
530 1st Ave, NY, NY 10016 
Elias.Zias@nyulangone.org 
Study Oversight Committee 
National PI(s) & AtriCure Medical Advisor 
Planned Number of Sites 
and Region(s) (US/OUS) 
Up to 170 subjects will be enrolled at up to 20 sites in the 
US, United Kingdom (UK) and/or Europe (EU). 
Clinical Investigation Type 
Retrospective-prospective, multi-center, non-randomized, 
unblinded, post-market study to evaluate the long-term 
performance and safety of AtriClip® FLEX-V LAA and 
PRO•V LAA Exclusion devices for exclusion of the left atrial 
appendage of the heart during concomitant cardiac 
procedures. 
AtriCure Medical Advisor 
Sydney Gaynor 
Medical Director of Clinical Education, Clinical 
AtriCure, Inc. 
7555 Innovation Way, Mason, OH  45040 
M. 513-560-5974 
SGaynor@atricure.com 
Sponsor 
Pam Simons 
VP, Clinical Affairs  
AtriCure, Inc. 
7555 Innovation Way, Mason, OH  45040 
O. 763-260-5267  
PSimons@atricure.com 
Electronic Data Capture 
Software 
Clindex® 
Core Laboratories 
NYU Langone Health, NY  
Independent Physician 
Adjudicator(s)  
To be Determined 
Protocol Author  
Rebecca Ikura, Senior Clinical Project Manager 
 

 
Protocol Number: CP-2021-03 
 
 
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Protocol Name: V-CLIP Study 
                                                                                                                                          
Version: Rev B; Oct 15, 2021 
                                                                                                                         Form-582.B 
Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
CONFIDENTIALITY STATEMENT 
The information in this document contains trade secrets and commercial information that are privileged or confidential to 
AtriCure, Inc. and may not be disclosed unless such disclosure is required by federal or state law or regulations.  Subject 
to the foregoing, this information may be disclosed only to those persons involved in the trial who have a need to know, 
but all such persons must be instructed not to further disseminate this information to others.  These restrictions on 
disclosure will apply equally to all future information supplied to you which is indicated as privileged or confidential. 
 
SPONSOR SIGNATURE PAGE 
Trial Name 
VCLIP Study 
Trial Number: 
CP-2021-03 
Title: 
Long-Term Follow-Up on LAA Exclusion using AtriClip 
Test Articles:  
 
AtriCure AtriClip® LAA Exclusion system comprised of: 
• Flex-V (ACHV) and PRO•V  
Approvals:  
Electronic approvals obtained via AtriCure’s Quality System (Master Control) are located at the end of 
this document. 
See MasterControl                                                    See MasterControl 
Pam Simons  
Date 
VP Clinical Affairs 
AtriCure, Inc. 
 
Sydney Gaynor, MD 
Date 
Medical Director of Clinical Education, Clinical 
AtriCure, Inc. 
 
See MasterControl 
 
 
See MasterControl 
Dennis Hong, JD, RAC 
Date 
VP, Regulatory Affairs  
AtriCure, Inc. 
 
Yashasvi Awasthi 
Date 
VP Global Scientific Affairs and Evidence Strategy 
AtriCure, Inc. 
 
See MasterControl 
 
 
See MasterControl 
Nfii Ndikintum 
Date 
VP Clinical Affairs & Biometrics 
AtriCure, Inc. 
 
Jesse Sheridan 
Date 
Pr. Clinical Database Programmer  
AtriCure, Inc. 
 
See MasterControl 
 
 
Rebecca Ikura  
Date 
Sr. Clinical Project Manager 
AtriCure, Inc. 
 
 
 
 

 
Protocol Number: CP-2021-03 
 
 
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Protocol Name: V-CLIP Study 
                                                                                                                                          
Version: Rev B; Oct 15, 2021 
                                                                                                                         Form-582.B 
Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
SITE INVESTIGATOR PROTOCOL SIGNATURE PAGE / INVESTIGATOR AGREEMENT 
 
 
I have read, understood, and agree to: 
 
 
• 
Ensure that the requirements for obtaining informed consent are met 
• 
Conduct the trial in accordance with this protocol, including applicable local/state laws 
and regulations 
• 
Provide a copy of the Financial Disclosure form that summarizes financial interest in 
AtriCure, Inc.  
• 
Complete all Case Report Forms and study documentation, and relevant assessments 
(as required) promptly to the Sponsor, AtriCure, Inc., or its authorized representatives 
• 
Adhere to the publication policy of AtriCure, as stated in the Clinical Study Agreement, 
for data collected during this trial 
• 
Ensure that all associates, colleagues, and employees of AtriCure assisting in the 
conduct of the trial(s) are informed of their obligations in meeting the above 
commitments 
• 
Propose to the sponsor any appropriate modification(s) of the protocol or investigational 
device, or of the use of the investigational device 
 
I will ensure that the IRB/EC review complies with governmental requirements and will be 
responsible for the initial and continuing review and approval of the clinical investigation.  I also 
agree to promptly report to the IRB/EC all changes in the research activity and all unanticipated 
problems involving risks to human subjects or others.  Additionally, I will not make any changes 
in the research without sponsor and IRB/EC approval of an amended protocol, except where 
necessary to eliminate apparent immediate hazards to human subjects. 
 
I have read and agree to adhere to the clinical investigation plan and all regulatory requirements 
applicable in conducting this clinical investigation. 
 
Site Principal-Investigator / Sub-Investigator 
 
Printed name: 
Signature: 
Date: 
 
Please return the signed form to your site assigned CRA 
AtriCure, Inc. (Sponsor) 
7555 Innovation Way 
Mason, Ohio 45040 

 
Protocol Number: CP-2021-03 
 
 
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Protocol Name: V-CLIP Study 
                                                                                                                                          
Version: Rev B; Oct 15, 2021 
                                                                                                                         Form-582.B 
Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
VCLIP PROTOCOL SYNOPSIS 
Regulatory 
Classification 
Post-Market Study 
Indication  
The AtriCure AtriClip LAA Exclusion system is indicated for the exclusion of the 
heart’s left atrial appendage, performed under direct visualization and in 
conjunction with other cardiac surgical procedures. 
Clinical 
Investigation 
Name and 
Number 
VCLIP Post-Market Study 
CP-2021-03 
Title 
Long-Term Follow-Up on LAA Exclusion using AtriClip 
Objective(s) 
The objective of this trial is to evaluate the long-term performance and safety of 
the AtriClip FLEX-V and PRO•V LAA Exclusion devices for exclusion of the left 
atrial appendage. 
Device(s) Under 
Investigation 
AtriCure AtriClip LAA Exclusion system comprised of: 
• Flex-V (ACHV) and PRO•V  
Rationale 
The study proposed herein is to gather clinical data on the long-term 
performance and safety of the AtriClip FLEX-V and PRO•V LAA Exclusion 
devices.  
Data from this study may be used for submission to regulatory authorities in the 
US, Europe, China and other geographies as needed, as well as for publication 
purposes. 
Number of 
Subjects/Sites  
Up to 170 subjects will be enrolled at up to 20 sites in the US, UK and/or EU. 
Clinical 
Investigation 
Design 
Retrospective-prospective, multi-center, non-randomized, unblinded, post-
market study to evaluate the long-term performance and safety of AtriClip 
FLEX-V LAA and PRO•V LAA Exclusion devices for exclusion of the left atrial 
appendage of the heart during cardiac procedures. 
Subject 
Population 
Subjects who have undergone designated non-emergent, cardiac surgical 
procedure(s), received an AtriClip implant (with devices under investigation) 
and who are willing to return for follow-up chest imaging to ascertain Left Atrial 
Appendage (LAA) exclusion will be eligible to participate based upon the 
inclusion and exclusion criteria. 
Subjects who had received chest imaging for other reasons, and if the imaging 
includes pertinent information to verify LAA exclusion, will also be eligible to 
participate if they meet eligibility criteria. 

 
Protocol Number: CP-2021-03 
 
 
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Protocol Name: V-CLIP Study 
                                                                                                                                          
Version: Rev B; Oct 15, 2021 
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Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
Justification of 
Sample Size and 
Performance Goal 
A minimum sample size of 170 subjects is required to evaluate the primary 
performance of LAA exclusion at 12-months using the following assumptions: 
Test basis: exact test for one proportion 
1-sided alpha: 0.025 
Power: 92% 
Performance Goal: 80% 
Expected closure rate: 90% 
Expected attrition rate: 16% 
Based on these assumptions, a minimum of 143 subjects are required before 
accounting for attrition. To account for an estimated attrition of 16% for subjects 
that consent but miss the imaging during follow-up, a total of 170 subjects will 
need to be enrolled.  
Performance goal: 
The 12-month LAA closure rate (No leak) for contemporary devices ranges from 
66 % - 89.5%. In-line with these rates, a PG of 80% is proposed for this study. 
 
In addition, based on a performance goal of 10.5% for safety at 30-days post 
AtriClip implantation, expected SAE rate of up to 5%, the sample size provides 
85.4% power to demonstrate primary safety success. 
Inclusion Criteria 
1. Subject is greater than or equal to 18 years of age. 
2. Subject who received the AtriClip FLEX-V or PRO•V implant during a non-
emergent cardiac surgical procedure  
3. Subject is willing and able to provide written informed consent  
4. Subject is willing and able to return for scheduled follow-up visit and 
imaging (CTA or TEE) 
Exclusion Criteria 
1. Inability, unwillingness, or contraindication to undergo TEE or CTA imaging 
2. Subjects who are pregnant or breast feeding  
3. Subjects with active COVID-19 infection 
Subject Follow-up 
Treated subjects will be assessed for long-term performance and safety at 12-
months or greater post-procedure (i.e., the last follow-up visit). 
Primary 
Endpoint(s) 
Primary Performance Endpoint 
1. Left Atrial Appendage exclusion defined as absence of residual 
communication (no leaks) between the left atrium (LA) and the LAA as 
assessed by CTA or TEE imaging at the last follow-up visit. The images will 
be reviewed by an independent core lab using a standardized imaging 
protocol. 
 
Primary Safety Endpoint 

 
Protocol Number: CP-2021-03 
 
 
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Protocol Name: V-CLIP Study 
                                                                                                                                          
Version: Rev B; Oct 15, 2021 
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Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
1. Incidence of the following serious adverse events within 30-days, if related 
to the device and/or implant procedure:  
• 
Death 
• 
Major Bleeding (BARC 3 and above) 
• 
Surgical site infection 
• 
Pericardial effusion requiring intervention 
• 
Clinical diagnosis of myocardial infarction 
 
The safety events will be adjudicated by an independent medical monitor 
(cardiac surgeon). 
Secondary 
Endpoints  
1. A residual LAA neck ≤10 mm as assessed by CTA or TEE imaging at the 
last follow-up visit 
2. Device or procedure related SAEs through the last follow-up visit 
 
These data will be descriptively summarized by reporting the counts and 
percentages of each event reported. 
 
 
 
 

 
Protocol Number: CP-2021-03 
 
 
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Protocol Name: V-CLIP Study 
                                                                                                                                          
Version: Rev B; Oct 15, 2021 
                                                                                                                         Form-582.B 
Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
 
TABLE OF CONTENTS 
 
VCLIP POST-MARKET STUDY ................................................................................................... 1 
SPONSOR SIGNATURE PAGE ................................................................................................... 2 
VCLIP PROTOCOL SYNOPSIS ................................................................................................... 4 
1 
INTRODUCTION ................................................................................................................. 12 
1.1 
Background and Rationale ........................................................................................... 12 
1.1.1 
Background ........................................................................................................... 12 
1.1.2 
Rationale for Conducting this Clinical Investigation............................................... 12 
2 
CLINICAL INVESTIGATION OVERVIEW ........................................................................... 13 
2.1 
Clinical Investigation Objective ..................................................................................... 13 
2.2 
Investigational Device(s) To Be Used in the Clinical Investigation ............................... 13 
2.2.1 
Name of the Device(s) Under Investigation .............................................................. 13 
2.2.2 
Indication for Use ...................................................................................................... 13 
2.2.3 
Description of the Device(s) Under Investigation ...................................................... 13 
2.2.4 
Device Handling ........................................................................................................ 13 
3 
CLINICAL INVESTIGATION DESIGN ................................................................................ 13 
3.1 
Clinical Investigation Procedures and Follow-up Schedule .......................................... 14 
3.2 
Measures Taken to Avoid and Minimize Bias ............................................................... 14 
3.3 
Suspension or Early Termination of the Clinical Investigation ...................................... 15 
4 
ENDPOINTS ........................................................................................................................ 15 
4.1 
Primary Safety Endpoint ............................................................................................... 15 
4.2 
Primary Performance Endpoint .................................................................................... 15 
4.3 
Secondary Endpoint ..................................................................................................... 16 
4.4 
Descriptive Endpoint(s) or Additional Data ................................................................... 16 
5 
SUBJECT SELECTION AND WITHDRAWAL ................................................................... 16 
5.1 
Subject Population ........................................................................................................ 16 
5.2 
Subject Screening and Informed Consent .................................................................... 16 
5.2.1 
Subject Screening ..................................................................................................... 16 
5.2.2 
Informed Consent ..................................................................................................... 17 
5.2.2.1 
Special Circumstances for Informed Consent ....................................................... 18 
5.3 
Eligibility Criteria ........................................................................................................... 18 

 
Protocol Number: CP-2021-03 
 
 
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Version: Rev B; Oct 15, 2021 
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Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
5.3.1 
General Eligibility Criteria .......................................................................................... 18 
5.3.2 
Inclusion Criteria ....................................................................................................... 18 
5.3.2.1 
General Inclusion Criteria ...................................................................................... 18 
5.3.3 
Exclusion Criteria ...................................................................................................... 19 
5.3.3.1 
General Exclusion Criteria ..................................................................................... 19 
5.4 
Subject Enrollment ....................................................................................................... 19 
5.4.1 
Historically Under-Represented Demographic Subgroups ....................................... 19 
5.5 
Subject Withdrawal ....................................................................................................... 19 
5.6 
Number of Subjects ...................................................................................................... 21 
5.7 
Total Expected Duration of the Clinical Investigation ................................................... 21 
6 
TREATMENT AND EVALUATION OF ENDPOINTS .......................................................... 21 
6.1 
Study Eligibility ............................................................................................................. 21 
6.2 
Retrospective Follow-up Assessments ......................................................................... 21 
6.2.1 
Baseline (within 30 days prior to index procedure) ................................................... 21 
6.2.3 
30-days Post-Procedure Visit, if done (+/- 7 days) ................................................... 22 
6.3 
Prospective Follow-up Assessments ............................................................................ 22 
6.3.1 
12-Month Post-Procedure Visit (≥ 12months) ........................................................... 22 
6.3.2 
Study Exit .................................................................................................................. 22 
6.3.3 
Schedule of Events ................................................................................................... 23 
6.4 
Requirement for Clinical Laboratories .......................................................................... 24 
7 
ADVERSE EVENTS ............................................................................................................ 24 
7.1 
Definition ....................................................................................................................... 24 
7.1.1 
Adverse Event ........................................................................................................... 24 
7.1.2 
Serious Adverse Event ............................................................................................. 24 
7.1.3 
Device Deficiency/Device Malfunction ...................................................................... 25 
7.2 
Pre-Existing Conditions Versus Adverse Events .......................................................... 25 
7.3 
Severity of Adverse Events .......................................................................................... 25 
7.4 
Device Relationship ...................................................................................................... 26 
7.4.1 
Unanticipated (Serious Adverse) Device Effect [U(S)ADE] ...................................... 27 
7.5 
Adverse Event and Device Deficiency/Device Malfunction Reporting .......................... 27 
7.5.1 
AE/ADE/UADE Reporting ......................................................................................... 27 
7.5.2 
SAE/USADE Reporting ............................................................................................. 27 
7.5.3 
Device Deficiency/Malfunction Reporting ................................................................. 28 

 
Protocol Number: CP-2021-03 
 
 
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Version: Rev B; Oct 15, 2021 
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Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
7.5.4 
Adverse Event Reporting to Country Regulatory Authorities by the Sponsor ........... 29 
7.6 
Expected Morbidity/Procedural Complications Reporting ............................................ 29 
7.7 
Product Complaints ...................................................................................................... 30 
7.7.1 
Reporting Product Complaints .................................................................................. 30 
7.7.2 
Reporting Product Complaints with Non-Investigational Device Products ................ 31 
7.7.3 
Non-AtriCure Product Complaints ............................................................................. 31 
7.7.4 
Reporting Product Complaints for Global Compliance ............................................. 31 
8 
STATISTICAL CONSIDERATIONS .................................................................................... 31 
8.1 
Analysis Populations .................................................................................................... 31 
8.2 
Statistical Analyses ....................................................................................................... 31 
8.2.1 
Primary Performance Endpoint Analysis .................................................................. 32 
8.2.2 
Primary Safety Endpoint Analysis ............................................................................. 32 
8.2.3 
Secondary Endpoint Analyses .................................................................................. 32 
8.2.4 
Long-Term Safety Analyses ...................................................................................... 33 
8.3 
Sample Size Calculation and Assumptions .................................................................. 33 
8.4 
Timing of Analysis ........................................................................................................ 34 
8.5 
Subgroup Analysis ........................................................................................................ 34 
8.6 
Multiplicity ..................................................................................................................... 34 
8.7 
Pooling Strategy ........................................................................................................... 34 
8.8 
Procedures for Accounting for Missing Data ................................................................ 34 
8.9 
Statistical Criteria for Termination ................................................................................ 34 
8.10 
Success Criteria ........................................................................................................... 34 
8.11 
Deviations from Statistical Plan .................................................................................... 34 
9 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ...................................................... 34 
10 
QUALITY CONTROL AND QUALITY ASSURANCE ..................................................... 35 
10.1 
Selection of Clinical Sites and Investigators ................................................................. 35 
10.2 
Clinical Investigation Finances and Agreements .......................................................... 35 
10.3 
Protocol Amendments .................................................................................................. 35 
10.4 
Training ......................................................................................................................... 35 
10.4.1 
Site Training .............................................................................................................. 35 
10.5 
Monitoring ..................................................................................................................... 36 
10.6 
Protocol Deviations ....................................................................................................... 36 
10.7 
Quality Assurance Audit ............................................................................................... 37 

 
Protocol Number: CP-2021-03 
 
 
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Protocol Name: V-CLIP Study 
                                                                                                                                          
Version: Rev B; Oct 15, 2021 
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Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
10.8 
Committees .................................................................................................................. 37 
10.8.1 
Study Oversight Committee ...................................................................................... 37 
10.8.2 
Publications Committee ............................................................................................ 38 
10.8.3 
Independent Physician Adjudicator (IPA) ................................................................. 38 
11 
DATA HANDLING AND RECORD KEEPING ................................................................. 38 
11.1 
Protection of Personally Identifiable Information .......................................................... 39 
11.2 
Data Management Plan ................................................................................................ 40 
11.3 
Source Documentation ................................................................................................. 40 
11.4 
Case Report Form Completion ..................................................................................... 40 
11.5 
Record Retention .......................................................................................................... 40 
11.6 
Investigational Devices Accountability .......................................................................... 41 
12 
ETHICAL CONSIDERATION .......................................................................................... 41 
12.1 
Institutional Review Board/Medical Ethics Committee Review and Approval ............... 41 
13 
CLINICAL INVESTIGATION CONCLUSION .................................................................. 42 
14 
PUBLICATION POLICY .................................................................................................. 42 
15 
RISK ANALYSIS ............................................................................................................. 42 
15.1 
Anticipated Clinical Benefits ......................................................................................... 42 
15.2 
Foreseeable Adverse Events and Anticipated Adverse Device Effects ........................ 42 
15.3 
Residual Risks Associated with the Device Under Investigation, as Identified in the 
Risk/Quality Management Report ........................................................................................... 43 
15.4 
Risks Associated with Participation in this Clinical Investigation .................................. 43 
15.5 
Steps Taken to Control or Mitigate Risks ..................................................................... 43 
15.6 
Risk to Benefit Rationale .............................................................................................. 43 
APPENDIX I: REFERENCES ..................................................................................................... 44 
APPENDIX II: ABBREVIATIONS AND ACRONYMNS ............................................................. 45 
APPENDIX III: DEFINITIONS ..................................................................................................... 47 
APPENDIX IV: FORSEEABLE ADVERSE EVENTS ................................................................. 58 
APPENDIX V: INFORMED CONSENT FORM ........................................................................... 60 
APPENDIX VI: SITE CONTACT INFORMATION ...................................................................... 61 
APPENDIX VII: REVISION HISTORY ........................................................................................ 62 
 

 
Protocol Number: CP-2021-03 
 
 
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Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
COMPLIANCE STATEMENT 
 
This clinical investigation will be conducted in accordance with this Clinical Investigation Plan, 
the Declaration of Helsinki, applicable Good Clinical Practices and regulations (e.g., US 21 CFR 
Part 50, 21 CFR Part 56, 21 CFR Part 812 and OUS ISO14155:2020) and any other appropriate 
local regulations(s). The most stringent requirements, guidelines or regulations must always be 
followed. The conduct of the clinical investigation will be approved by the appropriate 
Institutional Review Board (IRB)/Ethics Committee (EC) of the respective investigational site 
and by the applicable regulatory authorities prior to study enrollment. 
 
This clinical investigation will be financed by AtriCure. Investigational sites will be compensated 
by AtriCure for participation in the clinical investigation per the conditions of Clinical Trial 
Agreement (CTA) between the Sponsor and the Investigational site. 
 

 
Protocol Number: CP-2021-03 
 
 
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Version: Rev B; Oct 15, 2021 
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CONFIDENTIAL 
 
 
 
1 
INTRODUCTION 
This clinical investigation will be conducted in accordance with this Clinical Investigational Plan 
(CIP), also referred to herein as the “Protocol”. All investigators involved in the conduct of the 
clinical investigation will be qualified by education, training, or experience to perform their tasks 
and the training will be documented appropriately. The investigator will create and maintain 
source documents throughout the clinical investigation and make them available as requested 
during monitoring visits or audits, as well as maintain documentation of the type and location of 
these source documents. The investigator will also determine the cause and implement 
appropriate corrective and preventative actions to address any significant noncompliance that 
arise during the conduct of the study/trial. 
 
1.1 
Background and Rationale 
 
1.1.1 Background 
Exclusion or excision of the left atrial appendage (LAA) has been performed since the late 
1940s. Left atrial appendage suture-enabled exclusion/excision is intended to prevent thrombi 
that are developed in the heavily trabeculated LAA from migrating outside of the LAA. In 
patients with AF >90% of thrombi are generated in LAA. These thrombi can dislodge from left 
atrium and migrate to other parts of the body and can cause ischemic events hence it is 
important to close or exclude LAA to avoid thrombus from escaping.  
Various surgical techniques include:  epicardial suture occlusion (ligation), endocardial suture 
occlusion, stapling, and surgical excision. These techniques are associated with incomplete 
LAA closure rates of 40% to 60% and the technique can be difficult, adding significant cross 
clamp time.1-6 
Results of the randomized control pilot Left Atrial Appendage Occlusion Study (LAAOS) were 
reported by Healy et al.7 The LAAOS study assessed the safety and efficacy of LAA exclusion 
performed at the time of coronary artery bypass grafting (CABG) using sutures or a stapling 
device.   It   was   shown   that   among   patients having   a   postoperative   transesophageal 
echocardiogram (TEE), complete exclusion of the LAA was achieved in 45% of cases using 
sutures and in 72% using a stapler.  Given the low rate of exclusion with these techniques there 
is a need to exclude LAA using the device that provides an improved rate of closure. 
1.1.2 Rationale for Conducting this Clinical Investigation 
This study is proposed herein is to gather clinical data on the long-term performance and safety 
of the AtriClip FLEX-V and PRO•V LAA Exclusion devices.  
Data from this study may be used for submission to regulatory authorities in the US, Europe, 
China and other geographies as needed, as well as for publication purposes.  

 
Protocol Number: CP-2021-03 
 
 
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Protocol Name: V-CLIP Study 
                                                                                                                                          
Version: Rev B; Oct 15, 2021 
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Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
2 
CLINICAL INVESTIGATION OVERVIEW 
2.1 
Clinical Investigation Objective 
The primary objective of this study is to demonstrate the long-term performance and safety of 
the AtriClip FLEX-V and AtriClip PRO•V devices to successfully exclude the LAA with absence 
of residual communication between the LA and the LAA at the last follow-up visit post AtriClip 
implant. 
2.2 
Investigational Device(s) To Be Used in the Clinical Investigation 
The subject device for this study will be the AtriCure AtriClip LAA Exclusion system, which has 
been cleared under the 510 (k) process by the FDA and is approved in the UK and EU for 
commercial use. It is therefore not an investigational device.  
 
The AtriCure AtriClip LAA Exclusion system is comprised of: 
• Flex-V (ACHV) and PRO•V  
2.2.1 Name of the Device(s) Under Investigation 
Please refer to the IFU for additional information regarding the device used in this clinical 
investigation. 
2.2.2 Indication for Use 
The AtriCure AtriClip LAA Exclusion system is indicated for the exclusion of the heart’s left atrial 
appendage (LAA), performed under direct visualization and in conjunction with other cardiac 
surgical procedures. 
 
Direct visualization in this context, requires that the surgeon was able to see the heart directly, 
with or without assistance from a camera, endoscope, etc., or any other appropriate viewing 
technology.  
2.2.3 Description of the Device(s) Under Investigation 
Please refer to the IFU for additional information regarding the device used in this clinical 
investigation. 
2.2.4 Device Handling 
Subjects enrolled in this study will already have been treated with commercial devices; 
therefore, device accountability is not required.  
3 
CLINICAL INVESTIGATION DESIGN 
This is a retrospective-prospective, multi-center, non-randomized, unblinded, post-market study 
sponsored by AtriCure, Inc. This study will evaluate the long-term performance and safety of the 
AtriClip FLEX-V LAA and PRO•V LAA Exclusion Systems for exclusion of the LAA of the heart 
during concomitant cardiac procedures. Specifically, the implanted clip (AOD2) for both the 
AtriCure FLEX-V and PRO•V devices will be evaluated. This study will be conducted in the US, 
EU and UK under a single protocol approved by an IRB/EC for each site prior to study 
enrollment at the site. The Principal Investigators (PIs) acknowledges the responsibilities 
described in the Protocol Signature Page.  

 
Protocol Number: CP-2021-03 
 
 
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Property of AtriCure, Inc. Not to be reproduced without permission of AtriCure, Inc. 
CONFIDENTIAL 
 
 
 
 
The PIs at the sites are cardiac surgeons, qualified by education, experience, and training to 
assume responsibility for the conduct of this study. Up to 20 sites will participate in the study.  
 
Up to 170 subjects will be enrolled as part of the study. Treated subjects will be assessed for 
long-term performance and safety at 12-months or greater post-procedure.  
An independent Core Lab will be utilized for evaluation of the CTA and TEEs. All prospective 
assessments should be performed in accordance with the Core Labs recommended protocol. 
 
An Electronic Data Capture (EDC) system will be utilized by study site personnel to transfer study 
data from source records (medical records and/or source document worksheets) onto common 
electronic case report forms (eCRFs). This system is a web-based, secure electronic software 
application, (Clindex®), developed and maintained by Fortress Medical Systems in a manner that 
is compliant with national and international GCP data protection/data privacy and electronic 
record/electronic signature (e.g., 21 CFR Part 11) regulatory requirements. 
 
Adverse Events and medical device performance issues (for medical devices used during the 
procedure), including potential and actual device-related adverse events, certain malfunctions 
and user errors suspected to be associated with the use of a Food and Drug Administration (FDA) 
regulated drug, biologic, medical device or dietary supplement used during the course of this 
study will be reported by the PI to applicable authorities including the: 1) Sponsor (AtriCure); 2) 
IRB/EC; 3) respective manufacturer(s); and/or 4) FDA via MedWatch Online Voluntary Reporting 
Process or Medical Device Reporting as appropriate. 
 
Critical decisions related to the design and execution of the study will be managed by the National 
PI and AtriCure’s Medical Advisor. 
 
The clinical investigation has been designed to involve as little pain, discomfort, fear, and any 
other foreseeable risk as possible for subjects. Refer to the Risks Analysis section of this 
protocol for details. 
 
3.1 
Clinical Investigation Procedures and Follow-up Schedule 
Clinical investigation sites that have treated subjects with either the AtriClip FLEX-V or PRO•V 
device will be approached to determine if they are resourced and willing to consent subjects 
treated at least 12-months post procedure for LAA closure imaging (CTA or TEE). The follow-up 
assessment data will be entered into the electronic data system developed for the study. 
Documentation and reason for screen failure (i.e., inability to consent, refused consent, did not 
meet inclusion exclusion criteria, death or major morbidity such as stroke, etc. will be secured 
on a screening log within EDC.  
3.2 
Measures Taken to Avoid and Minimize Bias 
This is a single-arm study. All enrolled subjects would have been treated with either the AtriClip 
FLEX-V or PRO•V device. Study data will be monitored against relevant source documents. An 

 
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CONFIDENTIAL 
 
 
 
independent physician will adjudicate the SAEs reported in the study and LAA closure imaging 
will also be adjudicated by a core lab. Furthermore, to mitigate temporal bias, enrollment in the 
trial will be based on random selection of treated subjects. The sequence with which treated 
subjects will be screened and invited to participate in the trial will be randomly generated by the 
sponsor and provided to each site.  
 
3.3 
Suspension or Early Termination of the Clinical Investigation 
The Sponsor reserves the right to discontinue the clinical investigation at any stage with suitable 
written notice to the investigator. Possible reason(s) may include, but are not limited to: 
• 
A Study Oversight Committee (e.g., National PI(s) & AtriCure Medical Advisor) 
makes a recommendation to stop or terminate the clinical investigation.  
 
Should the clinical investigation be discontinued by the Sponsor, subjects will be followed per 
routine hospital standard of care with device-related AEs reported to the Sponsor as per 
vigilance/commercial reporting requirements. All applicable clinical investigation documents 
shall be subject to the same retention policy as detailed in [Section 11.5] of the Protocol.  
 
A Principal Investigator, IRB/EC or regulatory authority may suspend or prematurely terminate 
participation in the clinical investigation at the investigational site(s) for which they are 
responsible. The investigators will follow the requirements specified in the Clinical Trial 
Agreement.  
 
If the Sponsor suspends or prematurely terminates the clinical investigation at an individual site 
in the interest of safety, the Sponsor will inform all other sites and Principal Investigators. 
 
If suspension or premature termination occurs, the Principal Investigator or authorized designee 
will promptly inform the enrolled subjects at his/her site, if appropriate, and return subjects to 
their standard of care medical treatment. 
4 
ENDPOINTS 
4.1 
Primary Safety Endpoint 
This endpoint is defined as the incidence of the following serious adverse events (SAEs) within 
30-days, if related to the device and/or implant procedure:  
• 
Death 
• 
Major Bleeding (BARC 3 and above) 
• 
Surgical site infection 
• 
Pericardial effusion requiring intervention 
• 
Clinical diagnosis of myocardial infarction 
Refer to Appendix III for definitions of each of the events. 
4.2 
Primary Performance Endpoint 
This endpoint includes LAA exclusion defined as absence of residual communication (i.e. no 
leak) between the left atrium and the LAA, assessed by CTA or TEE imaging at the last follow-
up visit. 

 
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CONFIDENTIAL 
 
 
 
4.3 
Secondary Endpoint 
Key Secondary Endpoints include: 
1. A residual LAA neck ≤10 mm as assessed by CTA or TEE imaging at the last follow-up 
visit 
2. Device or procedure related SAEs through the last follow-up visit 
 
These data will be descriptively summarized by reporting the counts and percentages of 
each event reported. 
 
4.4 
Descriptive Endpoint(s) or Additional Data  
If necessary, additional analyses and endpoints will be defined in a separate Statistical Analysis 
Plan (SAP) prior to database lock. 
5 
SUBJECT SELECTION AND WITHDRAWAL  
5.1 
Subject Population 
This clinical investigation will enroll subjects who have undergone designated non-emergent, 
cardiac surgical procedure(s) and received an AtriClip implant (with the devices under 
investigation), and who are willing to return for follow-up chest imaging to ascertain LAA 
exclusion. Subjects must meet all eligibility criteria and provide written informed consent prior to 
collection of study data.  
Subjects who had received chest imaging for other reasons and the image includes pertinent 
information to verify LAA exclusion, will also be eligible to participate if they meet eligibility 
criteria. 
 
5.2 
Subject Screening and Informed Consent 
5.2.1 Subject Screening 
Potential patients presenting at the clinical sites will be fully informed about the clinical 
investigation, following the established Informed Consent process (described in [Section 5.2.2]).  
 
Subjects must be screened for clinical investigation eligibility by a member of the site’s clinical 
investigation team trained to the protocol, and if applicable will be entered into a site-specific 
screening log. 
 
In case the subject does not meet all inclusion criteria or meets any of the exclusion criteria, the 
subject is considered a screening failure. The Principal Investigator or the delegated clinical 
investigation personnel will record the reasons for screen failure (e.g., inability to consent, 
refusal to consent, did not meeting inclusion/exclusion criteria, death or major morbidity (e.g., 
stroke) etc. on a screening log within the EDC as required. 
 

 
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CONFIDENTIAL 
 
 
 
Patients meeting general inclusion criteria and no exclusion criteria will be asked to sign an 
Informed Consent form if they wish to participate in the clinical investigation. These patients will 
also be entered into the screening log. 
 
Subject data will be collected following enrollment into the clinical investigation and will be based 
on random selection of treated subjects. 
 
5.2.2 Informed Consent 
The Informed Consent Form (ICF) must have the approval of the IRB or favorable opinion of the 
EC. While some institutions may request modification of the ICF to satisfy specific institutional 
requirements, the use of a modified or unique ICF is permitted if it meets the requirement of 21 
CFR Part 50 and ISO 14155:2020 and is approved by the Sponsor. 
The Investigator or his/her authorized designee will conduct the Informed Consent process, as 
required by applicable regulations and the center’s IRB/EC. This process will include a verbal 
discussion with the subject on all aspects of the clinical investigation that are relevant to the 
subject’s decision to participate, such as details of clinical investigation procedures, anticipated 
benefits, and potential risks of clinical investigation participation. Subjects must be informed 
about their right to withdraw from the clinical investigation at any time and for any reason 
without sanction, penalty or loss of benefits to which the subject is otherwise entitled. 
Withdrawal from the clinical investigation will not jeopardize their future medical care or 
relationship with the investigator.  
 
During the discussion, the Principal Investigator or his/her authorized designee will avoid any 
improper influence on the subject and will respect subject’s legal rights. Financial incentives will 
not be given to the subject. Subjects may be compensated for time and travel directly related to 
the participation in the clinical investigation. The subject shall be provided with the Informed 
Consent form written in a language that is understandable to the subject and has been 
approved by the center’s IRB/EC. The subject shall have adequate time to review, ask 
questions, and consider participation. The Principal Investigator or his/her authorized designee 
will make efforts to ensure that the subject understands the information provided. If the subject 
agrees to participate, the Informed Consent form must be signed and dated by the subject and 
thereafter by the person obtaining the consent prior to any clinical investigation-specific 
procedures. The signed original will be filed in the subject’s hospital or research charts, and a 
copy will be provided to the subject. 
 
Failure to obtain Informed Consent from a subject prior to clinical investigation enrollment 
should be reported to Sponsor within 5 working days and to the reviewing center’s IRB/EC 
according to the IRB’s/ EC’s reporting requirements. 
 
If, during the clinical investigation, new information becomes available that can significantly 
affect a subject's future health and medical care, the Principal Investigator or his/her authorized 
designee (if applicable) will provide this information to the subject. If relevant, the subject will be 
asked to confirm their continuing Informed Consent in writing. 
 

 
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CONFIDENTIAL 
 
 
 
The ICF will clearly stipulate that the duration of the study is approximately 1.5 years, and the 
implications of this commitment will be reviewed and discussed with the subjects prior to 
enrollment in the study. 
 
5.2.2.1 Special Circumstances for Informed Consent  
For eligible subjects in the U.S. an authorization for use and disclosure of the subject’s protected 
health information, in accordance with the Health Insurance Portability and Accountability Act 
(HIPAA), must be obtained from the subject or their legally acceptable representative.  
For subjects outside of the U.S. (OUS), a separate GDPR consent may be required if not already 
included within the ICF. 
 
In addition,  
• Individuals under the age of 18 or age of legal consent are excluded from the study 
population. 
• Pregnant or breastfeeding women are excluded from the study population. 
 
Incapacitated individuals, defined as persons who are mentally ill, mentally handicapped, or 
individuals without legal authority, are excluded from the study population. 
For individuals unable to read or write, Informed Consent will be obtained through a supervised 
oral process. An independent witness will be present throughout the Informed Consent process. 
The written Informed Consent form and any other information will be read aloud and explained to 
the prospective subject or his/her legally acceptable representative and either will sign and 
personally date the Informed Consent form. The witness will also sign and personally date the 
Informed Consent form attesting that the information was accurately explained, and that Informed 
Consent was freely given. 
 
5.3 
Eligibility Criteria 
5.3.1 General Eligibility Criteria 
Assessment for general eligibility criteria is based on medical records at the site and interview 
with a candidate subject. Subjects must meet ALL of the inclusion criteria to be considered for 
the clinical investigation. If ANY of the exclusion criteria are met, the subject is excluded from 
the clinical investigation and cannot be enrolled. 
 
5.3.2 Inclusion Criteria 
5.3.2.1 General Inclusion Criteria 
All subjects recruited for study participation must meet all of the following inclusion criteria to be 
enrolled in the study:  
1. Subject is greater than or equal to 18 years of age 
2. Subject who received the AtriClip FLEX-V or PRO•V implant during a non-emergent 
cardiac surgical procedure 
3. Subject is willing and able to provide written Informed Consent  

 
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CONFIDENTIAL 
 
 
 
4. Subject is willing and able to return for scheduled follow-up visit and imaging (CTA or 
TEE) 
5.3.3 Exclusion Criteria 
5.3.3.1 General Exclusion Criteria 
Potential subjects required for study participation must not meet any of the following exclusion 
criteria to be enrolled in the study:  
1. Inability, unwillingness, or contraindication to undergo TEE or CTA imaging  
2. Subjects who are pregnant or breast feeding 
3. Subjects with active COVID-19 infection. 
5.4 
Subject Enrollment 
Subjects will be provided the IRB/EC approved ICFs and will have the opportunity to read, 
understand, and have their questions answered prior to signing the ICFs. If the subject agrees to 
participate in the study and signs consent, the ICF process will be completed. The subject must 
sign and date the ICF prior to collection of study data. The person reviewing the ICF with the 
subject will also sign and date the ICFs.  The subject will be given a copy of the signed ICF for 
their personal records.  
Upon entering subject enrollment information into Clindex, each subject will be assigned a unique 
identification (ID) number sequentially in ascending order.  All subjects who sign the ICFs will be 
documented in a Screening and Enrollment Log. For subjects who sign the ICF but are ineligible 
to participate, minimum baseline characteristics (e.g., age, gender, race, screening date and 
screen failure reason, etc.) will be captured in Clindex. 
A subject is considered enrolled in the clinical investigation from the moment the subject provides 
written Informed Consent and has been confirmed to meet all inclusion criteria and none of the 
exclusion criteria.  
5.4.1 Historically Under-Represented Demographic Subgroups 
AtriCure will take the following steps to ensure adequate representation of women and racial or 
ethnic minorities in this clinical investigation:  
• 
as appropriate and necessary, AtriCure will train sites on the importance of recruiting and 
retaining subjects in the clinical investigation 
• 
approach sites without bias or consideration for specific demographic subgroups  
• 
have Informed Consent materials in alternative languages and will work with sites and 
IRBs/ECs on recruitment materials.  
5.5 
Subject Withdrawal 
Each enrolled subject shall remain in the clinical investigation until completion of the required 
follow-up period; however, a subject’s participation in any clinical investigation is voluntary and 
the subject has the right to withdraw at any time without penalty or loss of benefit. Conceivable 
reasons for discontinuation may include, but not be limited to, the following: 
• 
Subject death 
• 
Subject voluntary withdrawal  

 
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CONFIDENTIAL 
 
 
 
• 
Subject lost-to follow-up as described below  
• 
Subject’s follow-up is terminated due to site/study termination 
 
The Sponsor must be notified by the site of the reason(s) for subject discontinuation and record 
a reason for termination in the case report form (CRF). Investigators must also report this to their 
respective IRB/EC as defined by their institution’s procedure(s).  
 
Investigator Decision 
If the subject experiences an adverse event and the Principal Investigator or Medical Advisor 
believes it is in their best interest to discontinue participation in the study, they will be withdrawn 
from the study.  
 
Lost to follow-up 
If the subject misses their scheduled follow-up and the attempts at contacting the subject detailed 
below are unsuccessful, then the subject is considered lost-to-follow-up. Site personnel shall 
make all reasonable efforts to locate and communicate with the subject (and document these 
efforts in the source documents), including the following, at each contact time point: 
• 
A minimum of two telephone calls on different days and times should be recorded in the 
source documentation, including date, time and initials of site personnel trying to make 
contact. 
• 
If these attempts are unsuccessful, a letter (certified if applicable) should be sent to the 
subject. 
 
Withdrawal of consent 
The subject withdraws consent for participation in the study.  Any method of contact with the 
subject in which they state they no longer want to participate in the study specific activities 
constitutes withdrawal of consent.  When possible, the reason for withdrawal will be documented. 
 
Death: Subject expires after enrollment into the study. 
 
Site Termination or Study Termination 
A site or the study may be terminated. When this occurs all subjects at the site will be withdrawn 
and documented as early termination. Reasons for site or study termination may include, but are 
not limited to the following:  
• 
Administrative concerns (e.g., inadequate subject enrollment, Investigator/institution non-
compliance, change of business strategy, etc.);  
• 
Safety issues, including those due to non-compliance, which substantially affect the risk 
to benefit ratio of the study subjects at a site or for the study as a whole; 
• 
Regulatory body mandate(s). 
 
Other (which may include) 
• 
Protocol deviation, noncompliance, or violation; 
• 
Investigator/Sponsor recommendation; 
 
Follow-up for Early Terminated Subjects 

 
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CONFIDENTIAL 
 
 
 
Given the nature of the study procedures, there are situations where subjects may terminate 
from the study early that are not described above. No additional follow–up will be required or 
data recorded from subjects once withdrawn from the clinical investigation, except for the status 
(deceased/alive). The investigator can use existing data and ask for the subject's permission to 
collect follow-up data about his/her status/condition including information about device clinical 
performance or safety. If permission is obtained, the relevant data shall be included in the 
clinical investigation report. 
5.6 
Number of Subjects  
Up to 170 subjects will be enrolled at up to 20 sites in the US, UK and/or EU. 
 
5.7 
Total Expected Duration of the Clinical Investigation 
The expected duration of the study is approximately 21 months. Enrollment will be closely 
monitored and AtriCure will work directly with the sites to clearly understand the enrollment 
challenges they might be facing, retrain as needed and pursue other strategies to address any 
enrollment lapse. Subjects will be exited from the trial at the conclusion of their primary 
performance follow-up visit occurring at least 12-months post-procedure.  
6 
TREATMENT AND EVALUATION OF ENDPOINTS 
6.1 
Study Eligibility 
All subjects recruited for study enrollment must meet all study enrollment criteria prior to being 
enrolled in the study. The clinical investigation site will review all subjects treated with either the 
AtriClip FLEX-V or PRO•V device. Once the initial chart review indicates that the subject meets 
the study inclusion / exclusion criteria, the subject will be approached for their interest in the study, 
including willingness to return for their follow-up visit. 
6.2 
Retrospective Follow-up Assessments 
Once the subject is consented, the following data will be collected by reviewing the 
subjects’ medical records retrospectively. For retrospective visits that fall outside of the 
required windows, please refer to section 10.6 (Protocol Deviations).  
 
6.2.1 Baseline (within 30 days prior to index procedure) 
• 
Inclusion/Exclusion criteria 
• 
Demographic information (Age, Sex, Race, Ethnicity) 
• 
Review of Medical and Cardiac history, including CHADS, CHADSVASC, and 
HASBLED scores, if available  
• 
Vital Signs (BMI, Blood Pressure, Heart Rate) 
• 
NYHA Classification 
• 
Medication history (e.g., Anticoagulants, antihypertensives, etc.,). Medication 
information should include: 
o Name 
o Dosage with units 
6.2.2 Start Index Procedure 

 
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CONFIDENTIAL 
 
 
 
• 
Evaluation of any adverse events AEs/SAEs that occur up to discharge 
• 
Concomitant surgical procedure 
• 
Intra-op TEE pre-clip placement for thrombus, if done (e.g., LA Size) 
 
6.2.3 30-days Post-Procedure Visit, if done (+/- 7 days) 
• 
NYHA Classification 
• 
Evaluation of any AEs/SAEs 
 
6.3 
Prospective Follow-up Assessments 
6.3.1 12-Month Post-Procedure Visit (≥ 12months) 
Subjects will be asked to return to the clinic for a final 12-month post procedure evaluation. The 
follow-up visit assessment will include: 
• 
Vital Signs (BMI, Blood Pressure, Heart Rate) 
• 
NYHA Classification  
• 
LAA Closure Imaging [CTA or TEE] * 
• 
Evaluation of AEs/SAEs  
• 
Medications Review (Anticoagulants, antihypertensives, etc), including any 
adjustments 
 
*Prospective imaging (CTA/TEE) to be completed at or after the 12-month visit from the time of 
AtriClip implant. Retrospectively collected CTA or TEE may be submitted to the Core lab for 
review. Imaging that meets the quality of the Core Lab’s acquisition protocol may be used in lieu 
of prospective imaging.  
 
6.3.2 Study Exit 
Once study subjects have completed their last follow-up visit, and TEE closure imaging has 
been obtained, the subject will be exited from the study.  

 
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6.3.3 Schedule of Events 
 
 
 
Note: Medications administered during the post-operative period do not need to be captured in the eCRF. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
Trial Activity 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Baseline 
(Within 30 days of index 
procedure) 
Index Procedure 
30-days Post-Procedure 
(Within 23-37 days of 
index procedure) 
12-months Post-Procedure 
(≥ 12-months from index 
procedure) 
Informed Consent & Inclusion/Exclusion 
X 
 
 
 
Demographics (Age, Sex, Race, Ethnicity) 
X 
 
 
 
Vital Signs (BMI, BP, Heart Rate) 
X 
 
 
X 
Medical/Surgical/Cardiac History (CHADS, CHADSVASC, 
HASBLED scores) 
X 
 
 
 
NYHA Classification 
X 
 
X 
X 
Intra-Op TEE, if done 
 
X 
 
 
CTA or TEE Imaging 
 
 
 
X 
Cardiac Medications/Adjustment Review 
X 
 
 
X 
Adverse Events (AEs/SAEs) 
 
X 
X 
X 
Surgical Procedure 
 
X 
 
 

 
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CONFIDENTIAL 
 
 
 
6.4 
Requirement for Clinical Laboratories 
An independent Core Laboratory will be utilized for assessment LAA exclusion defined by the 
absence of residual communication (no leaks) and residual pocket (≤10 mm) ) between the LA 
and LAA. Imaging for subjects include:  
• 
CTA or TEE imaging at last follow-up visit (12-months or greater post-procedure visit) 
 
All closure imaging submitted should be performed in accordance with the Core Laboratory’s 
recommended protocol. 
7 
ADVERSE EVENTS 
7.1 
Definition 
7.1.1 Adverse Event 
Adverse Event (AE) is defined as any undesirable clinical occurrence or change from subject’s 
baseline (or pre-device procedure) condition, whether it is considered device related or not. An 
AE is also defined by the International Organization for Standardization (ISO) as an untoward 
medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal 
laboratory findings) in subjects, users or other persons, whether or not related to the 
investigational medical device and whether anticipated or unanticipated. 
Adverse Event Identification: a condition that is one of the following: 
1. 
A unique symptom or event that is a change from the subject’s baseline status. 
2. 
A series of symptoms or events that can be categorized as a single entity based on 
definitions found herein. 
3. 
A specific diagnosis responsible for a clinical change. 
4. 
A worsening or exacerbation of a pre-existing condition. 
7.1.2 Serious Adverse Event 
If the AE meets any of the criteria below, it is regarded as a SAE.  
a) Led to a death, 
b) Led to a serious deterioration in health of the subject, that either resulted in  
1. Life-threatening illness or injury, or 
2. Hospitalization (initial or prolonged) or 
3. Disability or permanent impairment of a body structure or a body function 
4. Congenital anomaly (physical or mental)/birth defect/fetal distress/fetal death 
5. Chronic disease  
6. Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
c) Other Serious (important Medical Events). 
 
Events qualifying as SAEs as defined in section 4.1 include:  
• 
Death 
• 
Major bleeding (BARC 3 and above) 
• 
Surgical site infection 

 
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CONFIDENTIAL 
 
 
 
• 
Pericardial effusion requiring intervention 
• 
Clinical diagnosis of myocardial infarction 
 
Any condition that was recorded as pre-existing is not a SAE unless there is a change in the 
nature, severity, or degree of the condition.  
 
Note: A planned hospitalization for pre-existing condition, or a procedure required by the protocol, 
without a serious deterioration in health, is not considered to be an SAE. 
Note: “Death” should not be reported as an adverse event.  The cause of death should be reported 
as an adverse event.  The only exception is “Sudden Death” when the cause is unknown. 
7.1.3 Device Deficiency/Device Malfunction 
Device Deficiency is defined as an inadequacy of a medical device related to its identity, quality, 
usability, durability, reliability, safety or performance, such as malfunction, misuse or use error 
and inadequate labeling. This includes the failure of the device to meet its performance 
specifications or otherwise perform as intended. Note: Performance specifications include all 
claims made in the labeling of the device. 
 
A device malfunction is the failure of a device to meet its performance specifications or otherwise 
perform as intended. 
 
All device deficiencies of the AtriClip LAA exclusion device shall be documented throughout the 
clinical investigation and managed by the sponsor in accordance with written procedures for the 
control of a non-conforming product. The sponsor shall take, where applicable, appropriate 
corrective and preventative actions to protect the safety of subjects, users, and other persons. 
Device deficiencies of the comparator, if applicable, shall be documented. Where applicable, the 
analysis of used or explanted investigational devices shall be included as supportive information. 
 
7.2 
Pre-Existing Conditions Versus Adverse Events 
A pre-existing condition is defined as a medical condition that is present before the index 
procedure and is to be reported as part of the subject’s medical history. It must be reported as a 
new AE if the intensity, frequency, or the character of the condition worsens during the study 
treatment and the AE was determined to have the relationship to the study procedures and/or 
study devices. 
To avoid confusing pre-existing conditions with AEs during data analysis, the study sites must 
make all attempts to provide start dates for all baseline medical conditions. Any pre-existing 
condition that now meets the stated criteria as an AE should be recorded on the AE CRF as an 
exacerbation of the pre-existing condition and the start date will be recorded as the time when the 
exacerbation occurred. 
7.3 
Severity of Adverse Events 
It is the Investigator’s responsibility to assess the severity of an AE.  A change in severity may 
constitute a new reportable AE. 

 
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CONFIDENTIAL 
 
 
 
The following guideline should be used to determine the severity of each adverse event: 
• 
MILD:  Awareness of experience, but easily tolerated. No medical intervention required 
• 
MODERATE: Enough discomfort to interfere with usual activities. Medical intervention 
required 
• 
SEVERE: Inability to carry out usual activities. Medical/surgical intervention (including 
hospitalization or prolongation of hospitalization) required. 
 
7.4 
Device Relationship 
Determination of whether there is a reasonable possibility that an investigational product or device 
under investigation caused or contributed to an AE is to be determined by the Investigator and 
recorded on the appropriate CRF form. Determination should be based on assessment of 
temporal relationships, evidence of alternative etiology, medical/biologic plausibility, and subject 
condition (pre-existing condition). 
It is the Investigator’s responsibility to assess the relationship of an AE to the study procedure 
and/or device. 
Adverse events will be assigned an attribution according to the Investigator’s believed primary 
cause.  Events will be categorized by relationship to the investigational device(s) listed in this 
protocol or ancillary device, surgical ablation procedure, general cardiac surgical procedure or 
subsequent intervention, concomitant medications, pre-existing condition, intercurrent condition, 
intercurrent intervention, or unknown.   
The following guidelines should be used in determining the relationship of an adverse event to 
the study device or procedure: 
• 
Unknown: A clinical event (including abnormal laboratory result) that cannot be 
determined to be related or unrelated to device/procedure/drug given information 
provided. 
• 
Device Related Adverse Event:  An adverse event, that in the judgment of the 
Investigator, resulted from use or placement of the AtriCure AtriClip LAA Exclusion System 
and may have caused or contributed to the AE. 
• 
Procedure Related Adverse Event:  An adverse event which, in the judgment of the 
Investigator, results as a consequence of the procedure (surgical procedure or general 
cardiac surgical procedure, subsequent intervention) and is not specifically related to the 
use of the AtriCure AtriClip LAA Exclusion System. 
• 
General Surgery Related Adverse Event: An adverse event which, in the judgement of 
the Investigator, results as a consequence of general cardiac surgical procedural 
complications and/or subsequent interventions. 
• 
Concomitant Medication-Related Adverse Event:  An adverse event is considered to 
be concomitant medication related when, in the judgment of the Investigator, it is 
reasonable to believe that the event is associated with concomitant medications used in 
conjunction with the AtriClip device and is not otherwise specific to the AtriClip device (e.g. 
bleeding associated with anticoagulation medication). 
• 
Intercurrent Condition: It is reasonable to believe that the event is directly associated 
with an intercurrent condition/co-morbidity. 

 
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• 
Intercurrent Intervention: It is reasonable to believe that the event is directly associated 
with an intercurrent intervention which was performed for reasons other than to address a 
device or general cardiac surgical procedure related complication. 
7.4.1 Unanticipated (Serious Adverse) Device Effect [U(S)ADE] 
Unanticipated serious adverse device effect (USADE) refers to any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects. 
 
7.5 
Adverse Event and Device Deficiency/Device Malfunction Reporting 
7.5.1 AE/ADE/UADE Reporting 
General AE Reporting 
Safety surveillance and reporting starts as soon as the subject is enrolled in the clinical 
investigation. Safety surveillance and reporting will continue until the 12-Month follow-up visit has 
been performed, the subject is deceased, the subject concludes participation in the clinical 
investigation, or the subject withdraws from the clinical investigation. Except for those events 
listed in Section 7.6 all adverse event data potentially related to device or implant procedure, 
including deaths and device deficiency data, thromboembolic events, or events related to the 12-
month TEE/CTA will be collected throughout the time period defined above and will be reported 
to the Sponsor on the eCRF. Additional information with regard to an adverse event should be 
updated within the appropriate CRF.  
 
Standard medical terminology should be used when recording AEs.  
In addition, the following information should be recorded: 
• 
Onset Date 
• 
Resolution date or date of death 
• 
Intensity of the event  
• 
Action Taken 
• 
Outcome of the event 
• 
Relationship of AE  
• 
Indication of whether the event is serious 
 
7.5.2 SAE/USADE Reporting 
The investigator (or designee) must report all SAE/USADEs to the Sponsor via the Adverse Event 
CRF as soon as possible but no later than outlined below.  
 

 
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Clinical 
Site 
Reporting timelines 
All Sites 
SAEs must be reported to the Sponsor no later than 10 calendar days from 
the day the site personnel became aware of the event or as per the 
investigative site’s local requirements, if the requirement is more stringent 
than those outlined. 
 
An event determined by the Investigator to be life-threatening or to have 
led to death must be reported within 24 hours. 
 
The date the site staff became aware the event met the criteria of an SAE must be recorded in 
the eCRF and ensure relevant source documents are collected.  The Investigator will further 
report the SAE to the local IRB/EC according to the institution’s IRB/EC reporting requirements. 
In the event of system outages or technical difficulties, serious and any unanticipated adverse 
events may be submitted via e-mail to SAEInbox@AtriCure.com.  Upon availability of the system 
or resolution of the technical difficulties, the event will be recorded in the Adverse Event eCRF. 
The Investigator (or designee) shall send a written report including a narrative description of the 
serious and/or unanticipated adverse event to AtriCure or their designee within three (3) working 
days of the initial report.  The Investigator should follow all unresolved serious adverse events 
until the events are resolved, or the subject has exited the study, or the adverse event is otherwise 
explained. 
AtriCure, Inc., or their designee, in cooperation with the Investigator, will assess all serious 
adverse events considered device-related for potential report-ability to the FDA as an 
Unanticipated Adverse Device Effect (UADE) in accordance with 21 CFR Part 812.46(b). 
If a UADE determination is made, the Investigator and Sponsor will comply with UADE reporting 
requirements per 21 CFR Part 812.150.  The Sponsor shall report the results of such evaluation 
to FDA and to all reviewing IRBs/ECs and participating Investigators within thirty (30) working 
days after the Sponsor first receives notice of the UADE.  Thereafter the Sponsor shall submit 
such additional reports concerning the effect as FDA requests.  Similarly, the Investigator shall 
submit to their reviewing IRB a report of any UADE as soon as possible, but in no event later than 
ten (10) working days, (or per local IRB requirements) after the Investigator first learns of the 
effect.  The Investigator (or designee) shall provide documentation of the UADE report/notification 
sent to their IRB to AtriCure (or designee). 
Note: It is also the responsibility of the Investigator to inform their IRB of other SAEs (i.e. non-
UADEs) as required by their IRB/EC procedures and in conformance with FDA requirements. 
If the subject reports any device or procedure related adverse events that are potentially serious 
during the follow-up evaluation period, the subject should return to the investigator’s facility for 
further evaluation of the event. 
7.5.3 Device Deficiency/Malfunction Reporting 
All device deficiencies/malfunctions should be reported on the appropriate CRF.  

 
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The investigator should report all device deficiencies/malfunctions to the Sponsor as soon as 
possible but no later than outlined below.  
Clinical Sites 
Reporting timelines 
All Sites 
Device deficiencies/malfunctions must be reported to the Sponsor no 
later than 10 calendar days from the day the site personnel became 
aware of the event or as per the investigative site’s local requirements, 
if the requirement is more stringent than those outlined. 
 
7.5.4 Adverse Event Reporting to Country Regulatory Authorities by the Sponsor  
The Sponsor will report SAEs and reportable device deficiencies/malfunctions to the country 
regulatory authority, per local requirements.  
 
Clinical investigation SAEs and device deficiencies/malfunctions reportable per MedDEV 2.7/3 
regulations will be submitted to European Competent Authorities by the Sponsor’s Clinical 
Product Safety & Surveillance Group.  
 
7.6 
Expected Morbidity/Procedural Complications Reporting 
For purposes of this study, the following events occurring within 48 hours of study procedures are 
not considered reportable (not recorded on eCRF but recorded in source documents) as they are 
normally expected to occur in conjunction with surgical treatment procedures or are associated 
with customary, standard care of subjects undergoing cardiac surgery: 
• 
Chest pain without associated ECG changes 
• 
Post-operative/post-procedure pain 
• 
Post-anesthesia emesis, nausea, or headache (within 24 hours of procedure) 
• 
Electrolyte imbalance without clinical sequelae following procedure, even if requiring    
correction 
• 
Low grade temperature increase (101°F or 38.5°C) 
• 
Dizziness: Imprecise term commonly used to describe various symptoms such as 
faintness, giddiness, imbalance, lightheadedness, unsteadiness or vertigo. 
• 
Elevated white blood count, outside the standard laboratory normal value, without signs 
and symptoms of infection 
• 
Post-operative hematocrit decreases from baseline measured in the OR, prior to the first 
incision, not associated with hemodynamic changes, remaining above 25% and 
requiring < 2 units PRBC’s 
• 
Minor, localized tenderness, swelling, induration, oozing, etc. at surgical site. 
• 
Sinus bradycardia/tachycardia that does not require treatment or intervention 
• 
Systolic or diastolic blood pressure changes that do not require treatment or intervention. 
• 
Any blood transfusions during preplanned operative procedures and unrelated to an 
adverse event. 
• 
Thrombocytopenia: does not become an AE until treatment is administered. 

 
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• 
Atelectasis - collapse of lung tissue affecting part or all of one lung; the alveoli are 
deflated. This is not considered to be an AE unless treatment other than chest PT is 
required or it prolongs hospitalization. 
• 
Hyperglycemia - The use of insulin in the post-operative period does not constitute 
hyperglycemia if during the same hospitalization. An elevated blood sugar of less than 
250 mg/dl during the first 48 hours post-operative does not constitute hyperglycemia. 
• 
Pleural effusion is not an event unless treatment with thoracentesis or chest tube 
insertion is required 
• 
Pericardial effusion without hemodynamic compromise or treatment 
• 
Atrial Fibrillation /Atrial Flutter/Atrial Tachycardia with or without cardioversion.  
• 
Junctional Rhythm requiring temporary pacing 
Note:  Treated subjects will have received general anesthesia and therefore will also be 
subject to general anesthesia-associated complications and morbidity. These are also not 
considered reportable (recorded on eCRF) adverse events. 
Note: This listing of events is intended to provide guidance to the Investigator and 
investigational site for the purpose of adverse event reporting. The Investigator should utilize 
his/her own clinical judgment in evaluating adverse experiences and may decide that the 
above events should be reported as adverse events based on the IRB/EC reporting 
requirements or the subject clinical situation. 
7.7 
Product Complaints 
A product complaint is any written electronic or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, usability safety, or performance of a device 
after it is release for distribution (a medical device that has been released from the organization’s 
control or related to a service that affects the performance of such medical devices). Product 
complaints may or may not be associated with an AE.   
7.7.1 Reporting Product Complaints 
All product complaints (as defined above) related to an investigational product (shall be 
documented throughout the clinical investigation and appropriately managed by the sponsor. All 
reported device observations, malfunctions or failures for the AtriClip LAA Exclusion system are 
required to be documented in the EDC within 10 days of observation of the Product Complaint 
and sent via e-mail to pcomplaints@atricure.com by the PI or study staff.  
If the AtriClip LAA Exclusion system or component is involved in a complaint, the device should 
be returned to AtriCure (e.g., product is damaged or use results in an AE).  If this occurs, sponsor 
representatives will send a Used Product Return Kit to study site personnel for packaging the 
product; which (depending on the product) may be sent to the appropriate facility for 
decontamination and further investigation of the complaint. 

 
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7.7.2 Reporting Product Complaints with Non-Investigational Device Products 
All reported device observations, malfunctions or failures for AtriCure Non-Investigational (i.e. 
Marketed Products) are required to be documented in the Clindex database on the device 
observation eCRF and emailed to pcomplaints@atricure.com within 10 days of the observation 
by the PI or study staff.  
If an event involving an AtriCure device is subject to reporting under the Medical Device Reporting 
Regulation (MDR), AtriCure shall submit to the FDA the appropriate reports required by MDR 
within the timeframes identified in 21 CFR Part 803.  
7.7.3 Non-AtriCure Product Complaints 
In compliance with the requirements of 21 CFR Part 803.30 (MDR), the study site (user facility) 
will be instructed to report any SAEs associated with the use of other (non-AtriCure) marketed 
products/devices in this study to the respective manufacturer and, if the SAE involves a death, 
the complaint should be reported to the manufacturer. 
7.7.4 Reporting Product Complaints for Global Compliance 
If a Product Complaint is reported in conjunction with a SAE/UADE, reporting guidelines will be 
the same as those listed in Section 7.5.4. 
 
8 
STATISTICAL CONSIDERATIONS 
The following section describes the statistical methods for the clinical investigation. Additional 
details on statistical analyses, including justification of clinical investigation design, sensitivity 
analyses, pool-ability analyses, subgroup analyses etc., may be maintained in a separate 
Statistical Analysis Plan. 
 
8.1 
Analysis Populations 
Intention-to-Treat Population: 
The Intention-to-Treat (ITT) population consists of the subjects with AtriClip implant. This is the 
primary population for performance endpoints. 
Protocol Population: 
The Per-Protocol (PP) study population is defined by the ITT population but without any major 
protocol deviations, that is, those that could potentially bias the results. This population is defined 
for the primary performance endpoints. 
8.2 
Statistical Analyses  
The primary goal of the study is to demonstrate safety and performance of the Flex-V and 
PRO•V device. For the study to be successful, the safety and performance endpoints must be 
statistically significant relative to their respective performance goals. 
 
Standard descriptive statistics will be used to summarize numeric variables, including the number 
of observed values, mean, standard deviation, median, minimum and maximum values. 

 
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Summaries of categorical variables will include the number and percentage of observed values, 
at each level of the categorical variable. Baseline and demographic information, including age, 
gender, race, ethnicity, BMI, and medical history will be summarized with standard descriptive 
statistics. 
Two-sided 95% and 90% confidence intervals will be provided for point estimates as appropriate.  
8.2.1 Primary Performance Endpoint Analysis 
The primary performance endpoint is further defined in section 4.1 of the protocol. 
Subjects meeting the primary performance endpoint (success LAA exclusion at least 12-months 
post AtriClip implant) will be labeled as “responders”, and the proportion of responders will be 
compared to a performance goal (PG) of 80%.  
An exact binomial test will be conducted at a one-sided α = 0.025 level of significance to test the 
following hypothesis that the proportion of performance successes is significantly higher than the 
PG: 
H0: p ≤ 80% 
HA: p > 80% 
where p is the responder rate at last follow-up visit occurring at least 12-months post-procedure. 
The ITT population will be the primary population for this analysis.  
8.2.2 Primary Safety Endpoint Analysis 
The primary safety endpoint is the proportion of subjects free from SAEs, as described in section 
4.1 of the protocol, through 30-days post AtriClip implantation. The SAE rate will be compared 
against a PG of 10.5%. 
An exact binomial test will be conducted at a one-sided α = 0.05 level of significance to test the 
following hypothesis that the proportion of MAEs is significantly lower than the PG: 
The hypothesis test for the safety endpoint is: 
H0: q ≥ 10.5% 
HA: q < 10.5% 
where q is the proportion of subjects with MAEs through 30-days AtriClip implantation in the safety 
population. The ITT population will be the primary population for this analysis.  
8.2.3 Secondary Endpoint Analyses 
The secondary endpoints are described in section 4.3 of the protocol.  
All analyses will be conducted using appropriate statistical methods as described in Section 8.2 
and for the primary performance endpoint, as applicable. These will include analyses of the 
populations and subgroups as specified in this protocol and may also include additional endpoints, 
populations and/or subgroups. 

 
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8.2.4 Long-Term Safety Analyses 
Serious events related to the index procedure (such as LAA tears, tissue injury or bleeding which 
requires intervention) will be reported. Descriptive statistics will be provided. No formal hypothesis 
testing will be done. 
8.3 
Sample Size Calculation and Assumptions 
Performance Endpoint 
The 12-month LAA closure rate (No leak) for contemporary devices ranges from 66 % - 89.5%. 
(Kar, 2021) In-line with these rates, a PG of 80% is proposed for this study. 
 
Based on the performance goal of 80% success and an expected success rate of 90%, a sample 
size of 143 subjects provides 92% power using a one-sided Exact test, with α = 0.025 level of 
significance to demonstrate primary performance success. Assuming an attrition rate of 16% at 
the last follow-up visit post procedure, a total of 170 subjects will be enrolled. 
 
The lowest primary performance endpoint that would meet the PG is 86.7% (that is, 124 out of 
143 subjects are responders). 
 
Safety Endpoint 
Minimal to no missing data are expected for the primary safety. Based on a PG of 10.5%, and an 
expected population MAE rate of up to 5%, a sample size of 170 subjects will have 85.4% power 
using a one-sided Exact test, with at a one-sided α = 0.05 level of significance. 
 
The highest primary safety endpoint that would meet the PG would be 6.5% (that is, 11 out of 170 
subjects experience at least one MAE). 
 
Watchman FLX device is CE approved and improved safety when compared to previous iterations 
of this device (1) reported a safety rate of 5% (20/400) [95% one-sided upper confidence limit of 
7%] reported within similar timeframe (45 days) after the device implant. The safety performance 
goal of 10.5% is based on 1.5 times the UCL of 7%. 

 
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8.4 
Timing of Analysis 
The primary performance endpoint analysis will be conducted when all subjects have completed 
at least their 12-months post-procedure visit. The expected duration of the study is approximately 
21 months. 
8.5 
Subgroup Analysis 
No subgroup analyses are planned for this clinical investigation. However primary safety and 
performance endpoints will be summarized by sex, race and other subgroups as needed. 
8.6 
Multiplicity 
No alpha multiplicity adjustments are planned for the exploratory and supporting secondary 
endpoints and analysis populations defined in the study. 
 
8.7 
Pooling Strategy  
For this study, data will be pooled from multiple study sites.  The justification for pooling will be 
made on a clinical basis considering three factors: (1) the study sites must implement one 
common protocol, (2) the Sponsor must closely monitor study site compliance with the protocol, 
and (3) the study site must use common data collection procedures.  
 
8.8 
Procedures for Accounting for Missing Data 
As applicable, several sensitivity analyses will be performed to evaluate the effect of the missing 
data on the primary performance and safety endpoints, including multiple imputation, last 
observation carried forward (LOCF) and a tipping point analysis. Details will be provided in the 
SAP prior to database lock. 
 
8.9 
Statistical Criteria for Termination 
There are no statistical criteria for termination of this clinical investigation. 
 
8.10 Success Criteria 
For the trial to be successful, the performance endpoints must be statistically significant relative 
to their respective performance goals and that the hypotheses are met. If the null effectiveness 
hypothesis is rejected, the treatment will be considered beneficial.  
 
8.11 Deviations from Statistical Plan 
Any major changes to the statistical plan will be documented in an amendment to the statistical 
plan. Less significant changes to the planned analyses will be documented in the final report.   
 
9 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The investigator/institution will permit direct access to source data/documents for the purpose of 
performing clinical investigation-related monitoring, audits, IRB/EC review and regulatory 
inspections. 

 
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Subjects providing Informed Consent are agreeing to allow clinical investigation monitors or 
regulatory authorities including foreign countries to review, in confidence, any records identifying 
the subjects in this clinical investigation. This information may be shared with regulatory agencies; 
however, Sponsor undertakes not to otherwise release the subject's personal and private 
information. 
10 QUALITY CONTROL AND QUALITY ASSURANCE 
10.1 Selection of Clinical Sites and Investigators 
The Sponsor will select investigators qualified by training and experience to participate in the 
clinical investigation. Sites will be selected based upon review of a recent site assessment, if 
applicable, and the qualifications of the investigators who will participate in the clinical 
investigation. 
 
10.2 Clinical Investigation Finances and Agreements 
The clinical investigation will be financed by AtriCure.  Investigational sites will be compensated 
by AtriCure for participation in the clinical investigation per the conditions of agreement between 
the Sponsor and the Investigational site. 
 
10.3 Protocol Amendments  
Approved protocol amendments will be provided to the Investigators by the Sponsor prior to 
implementing the amendment. The Principal Investigator is responsible for notifying the IRB/EC 
or equivalent committee of the protocol amendment (administrative changes) or obtaining 
IRB’s/EC’s approval of the protocol amendment (changes in subject care or safety), according 
to the instructions provided by the Sponsor with the protocol amendment.   
 
Acknowledgement/approval by the IRB/EC of the protocol amendment must be documented in 
writing prior to implementation of the protocol amendment. Copies of this documentation must 
also be provided to the Sponsor. 
 
The protocol and all subsequent amendments to the protocol are prepared by the Sponsor, 
agreed upon between the Sponsor and the National Principal Investigator, accepted by all 
Principal investigators, and are recorded with a justification for each amendment. 
 
10.4 Training 
10.4.1 Site Training 
All Investigators and clinical investigation personnel are required to attend Sponsor training 
sessions, which may be conducted at an Investigator's meeting, an onsite initiation visit, a virtual 
site initiation visit or other appropriate training sessions. Over-the-phone or self-training may take 
place as required. Training of Investigators and clinical investigation personnel will include, but is 
not limited to, the protocol requirements, investigational device usage, electronic case report form 
completion and clinical investigation personnel responsibilities.  
 

 
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All Investigators and clinical investigation personnel that are trained must sign a training log (or 
an equivalent) upon completion of the training. Prior to signing the training log, Investigators and 
clinical investigation personnel must not perform any protocol-related activities that are not 
considered standard of care at the site.  
 
10.5 Monitoring 
 
Sponsor and/or designee will monitor the clinical investigation over its duration according to the 
protocol specific monitoring plan which will include the planned extent of source data verification.  
 
Prior to initiating any procedure, the Sponsor monitor (or delegate) will ensure that the following 
criteria are met:  
 
• 
The Investigator understands and accepts the obligation to conduct the clinical 
investigation according to the protocol and applicable regulations, and has signed Clinical 
Study Agreement  
• 
Source documentation (including original medical records) must be available to 
substantiate proper Informed Consent procedures, adherence to protocol procedures, 
adequate reporting and follow-up of adverse events, accuracy of data collected on case 
report forms, and device information.  
• 
The Investigator/site will permit access to such records. A monitoring visit sign-in log will 
be maintained at the site. The Investigator will agree to dedicate an adequate amount of 
time to the monitoring process. The Investigator and/or research coordinator will be 
available for monitoring visits. It is expected that the Investigator will provide the monitor 
with a suitable working environment for review of clinical investigation-related documents. 
This study will be monitored by the sponsor to ensure: 
• 
The rights and well-being of the subjects are protected; 
• 
The reported study data is accurate, complete, and verifiable from source documents; 
• 
The conduct of the study is in compliance with the currently approved protocol and 
amendment(s), applicable GCPs, and with applicable local and regional regulatory 
requirements. 
 
10.6 Protocol Deviations 
Protocol deviations are events occurring during the conduct of the study which are not in 
compliance with the protocol and for which an amendment has not been granted. The Investigator 
should not deviate from the protocol for any reason except in cases of medical emergencies when 
the deviation is necessary to protect the rights, safety and well-being of the subject or eliminate 
an apparent immediate hazard to the subject. In that event, the Investigator will notify Sponsor 
immediately by phone or in writing.  
 
For retrospective data collection, it is possible that subject visits post-procedure will vary based 
on institutional standard of care. For the purposes of this study individual protocol deviation 
waivers will not be required for the following: 
• 
any retrospective subject visit that falls outside of the protocol defined visit window 
will not be documented as a protocol deviation; and 

 
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• 
Vital signs, Intra-Op TEE, or NYHA classifications that were not retrospectively 
performed will not be documented as a protocol deviation.  
 
All deviations must be reported to the Sponsor using the Deviation CRF. The occurrence of 
protocol deviations will be monitored by the Sponsor for evaluation of investigator compliance to 
the protocol and regulatory requirements and dealt with according to written procedures. 
Investigators will inform their IRB/EC or equivalent committee of all protocol deviations in 
accordance with their specific IRB/EC or equivalent committee reporting policies and procedures.  
 
In the event of repeated non-compliance, as determined by the Sponsor, a Sponsor’s monitor or 
company representative will attempt to secure compliance by one or more of the following (and 
not limited to):  
• 
Visiting the Investigator and/or delegate 
• 
Telephoning the Investigator and/or delegate 
• 
Corresponding with the Investigator and/or delegate 
 
Repeated non-compliance with the signed agreement, the protocol or any other conditions of the 
clinical investigation may result in further escalation in accordance with the Sponsor’s written 
procedures, including securing compliance or, at its sole discretion, Sponsor may terminate the 
Investigator's participation in the clinical investigation.  
 
10.7 Quality Assurance Audit 
A Sponsor representative or designee may request access to all clinical investigation records, 
including source documentation, for inspection during a Quality Assurance audit.  
 
In the event that an Investigator is contacted by a Regulatory Agency in relation to this clinical 
investigation, the Investigator will notify Sponsor immediately. The Investigator and Research 
Coordinator must be available to respond to reasonable requests and audit queries made during 
the audit process. The Investigator must provide Sponsor with copies of all correspondence that 
may affect the review of the current clinical investigation (e.g., Form FDA 483, Inspectional 
Observations, Warning Letters, Inspection Reports, etc.). The Sponsor may provide any needed 
assistance in responding to regulatory audits. 
 
10.8 Committees  
The Sponsor shall ensure oversight of any clinical investigation-related duties and functions. 
The outsourcing of duties or functions to external organizations, including subcontractors of the 
Sponsor's CRO(s)/Committees, shall be addressed by the Sponsor in accordance with written 
procedures for control of suppliers and/or charters as applicable. Additionally, records of 
transfer of duties and functions shall be maintained where applicable. 
 
10.8.1 Study Oversight Committee 
 
The Study Oversight Committee is comprised of the National PI and Sponsor Medical Advisor. 
The Chairman of the Core laboratories and other Sponsor personnel may also participate in the 

 
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Committee meetings if appropriate. Meeting minutes from this committee will be filed with the 
sponsor. 
 
The Study Oversight Committee is responsible for overseeing the scientific and operational 
aspects of the clinical investigation.  
 
Specifically, the committee with participate and/or advise on the following: 
• 
Review of the study protocol  
• 
Review of the training material for the sites as applicable 
• 
Study operations and safety  
• 
Discussion of study related issues with the sites, as needed 
• 
Regulatory communication, as needed 
 
10.8.2 Publications Committee 
 
A Publication Committee may be established to oversee clinical investigations publications, 
including publication planning and authorship determinations. Publication Committee 
membership may include the National PI(s), Site Principal Investigators, a representative of the 
Sponsor and a statistician. The Publication Committee will determine policy and strategies 
regarding individual presentations and/or publications arising from clinical investigation generated 
data. The committee will also review all external requests for accessing clinical investigation-
related data and strategies aligning with the Sponsor’s presentation and publication team 
expectations.  
 
10.8.3 Independent Physician Adjudicator (IPA) 
An independent, non-investigator physician(s) will function as the adjudicator(s) under the 
direction of AtriCure, Inc. The physician(s) will be responsible for the review and adjudication of 
the following:  
1. All Serious Adverse Events listed under the primary endpoint; 
2. All Unanticipated Device Effects; 
3. All Adverse Events that are potentially related to the procedure or any of the AtriCure 
AtriClip devices used in the study; 
In addition, all primary endpoints and other adverse events determined by the adjudicator(s) to 
be relevant, will be adjudicated until the subject exits the study. 
11 DATA HANDLING AND RECORD KEEPING 
The Sponsor and/or its affiliates will maintain documentation of the systems and procedures used 
in data collection for the duration of the clinical investigation.  
 
CRF data collection will be performed through a secure web portal and only authorized personnel 
will access the Electronic Data Capture (EDC) system using a unique username and password 
to enter, review or correct data. Passwords and electronic signatures will be strictly confidential.   
 

 
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The data will be subjected to consistency and validation checks within the EDC system and 
supplemental review by the Sponsor.    
 
At the conclusion of the clinical investigation, completed CRF images with the date-and-time 
stamped electronic audit trail indicating the user, the data entered, and any reason for change (if 
applicable) will be provided to the investigational sites.  
 
For the duration of the clinical investigation, the Investigator will maintain complete and accurate 
documentation including, but not limited to, medical records, clinical investigation progress 
records, laboratory reports, CRFs, signed ICFs, correspondence with the IRB/EC and clinical 
investigation monitor/Sponsor, adverse event reports, and information regarding subject 
discontinuation or completion of the clinical investigation. 
 
The Investigator shall assure the accuracy, completeness, legibility and timelines of the data 
reported to the sponsor on the CRFs and in all required reports. All copies of the retained original 
source documents shall be certified, as indicated by a dated signature by a member of the 
investigation site team unless generated through a validated process. 
 
11.1 Protection of Personally Identifiable Information 
The Sponsor respects and protects personally identifiable information collected or maintained for 
this clinical investigation.  
 
The Sponsor implements technical and physical access controls to ensure that Personal 
Information is accessible only to and processed only on a ‘need to know’ basis, including periodic 
review of access rights, and revocation of access when an individual’s employment is terminated 
or the individual transitions to a role that does not require access to Personal Information, and 
appropriate restrictions on physical access to premises, facilities, equipment, and records 
containing Personal Information. 
 
The Sponsor requires the investigational sites to transfer into Sponsor’s data management 
systems only pseudonymous Personal Information necessary to conduct the Clinical 
Investigation, such as the subject’s medical condition, treatment, dates of treatment, etc. The 
Sponsor discloses as part of the clinical investigation Informed Consent process that some 
Sponsor representatives still may see Personal Information at the participating sites for technical 
support of the participating physicians on the procedures, monitoring and quality control purposes. 
Confidentiality of Personal Information will be observed by all parties involved at all times 
throughout the clinical investigation. The privacy of each subject and confidentiality of his/her 
information will be preserved in reports and when publishing any data. 
 
The Sponsor data management systems and processes were designed, developed, and tested 
according to industry standards to appropriately safeguard Confidential Information (including any 
Personal Information) against unauthorized access and/or interference by third parties, intrusion, 
theft, destruction, loss or alteration. Clinical Investigation data are encrypted in transit and at rest.  
 

 
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11.2 Data Management Plan 
A Data Management Plan (DMP) will describe procedures used for data review, data cleaning, 
and issuing and resolving data discrepancies. If appropriate, the DMP may be updated 
throughout the duration of the clinical investigation. All revisions will be tracked and document 
controlled. 
 
11.3 Source Documentation 
 
Regulations and GCP require the Investigator to maintain information in the subject’s original 
medical records that corroborates data collected on the CRFs. In order to comply with these 
regulatory requirements/GCP, the following information should be included in the subject record 
at a minimum and if applicable to the clinical investigation: 
• 
Medical history/physical condition of the subject before involvement in the clinical 
investigation sufficient to verify protocol entry criteria 
• 
Dated and signed notes on the day of entry into the clinical investigation referencing 
the Sponsor, protocol number, subject ID number and a statement that Informed 
Consent was obtained 
• 
Dated and signed notes from each subject visit (for specific results of procedures 
and exams) 
• 
Adverse events reported and their resolution, including supporting documents, such 
as discharge summaries, catheterization laboratory reports, ECGs, and lab results 
including documentation of site awareness of SAEs and of investigator assessment 
of device relationship for SAEs. 
11.4 Case Report Form Completion 
 
Primary data collection based on source-documented hospital and/or clinic chart reviews will be 
performed clearly and accurately by site personnel trained on the protocol and CRF completion. 
The investigator will ensure accuracy, completeness, legibility and timeliness of the data 
reported to the Sponsor on the CRFs and in all required reports. 
 
CRF completion guidelines may also be developed to provide instructions to the site for accurate 
completion, correction and signature of CRFs along with expectations on handling clinical 
investigation deviations and unknown data, thus reducing the need of sponsor data queries. Only 
authorized site personnel will be permitted to enter the CRF data through the EDC system 
deployed by the Sponsor. An electronic audit trail will be used to track any subsequent changes 
of the entered data. 
 
11.5 Record Retention 
The Sponsor and Investigator/Site will archive and retain all documents pertaining to the clinical 
investigation as per the applicable regulatory record retention requirements.  
 
If custody of the records is transferred, notice of such a transfer should be given to the Sponsor 
no later than ten (10) working days after the transfer occurs. 
The Investigator should retain copies of all documents pertaining to this clinical investigation 
(including source documentation, the Informed Consent document, and any other documents to 

 
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identify the subjects) for at least 2 years after this clinical investigation is completed.  In addition, 
if the Clinical Investigator moves/retires, etc., he/she should provide AtriCure Inc. the name and 
address of the person who will look after and be responsible for the subjects’ clinical investigation 
related records. 
11.6 Investigational Devices Accountability 
Subjects enrolled in this study will already have been treated, therefore device accountability is 
not required.  
12 ETHICAL CONSIDERATION 
12.1 Institutional Review Board/Medical Ethics Committee Review and Approval 
Institutional Review Board (IRB)/ Ethics Committee (EC) approval for the protocol and ICF/other 
written information provided to the subject will be obtained by the Principal Investigator at each 
investigational site prior to consenting and enrolling subjects in this clinical investigation. The 
approval letter must be received prior to the start of this clinical investigation and a copy must 
be provided to the Sponsor.  
 
The IRB/EC may require a draft of the Clinical Study Agreement and proposed compensation to 
the investigation site or Principal Investigator be provided, including a letter of the Sponsor 
confirming outsourcing of duties and functions and CVs of the investigational site team. 
 
Any amendments to the protocol as well as associated ICF changes will be submitted to the 
IRB/EC and written approval obtained prior to implementation, according to each institution’s 
IRB/EC requirements.  
 
No changes will be made to the protocol or ICF or other written information provided to the 
subject without appropriate approvals, including IRB/EC, the Sponsor, and the regulatory 
agencies (if applicable).  
 
Until the clinical investigation is completed, the Investigator will advise his/her IRB/EC of the 
progress of this clinical investigation, per IRB/EC requirements. Written approval must be 
obtained from the IRB/EC yearly to continue the clinical investigation, or according to each 
institution’s IRB/EC requirements.  
 
No investigative procedures other than those defined in this protocol will be undertaken on the 
enrolled subjects without the written agreement of the IRB/EC and the Sponsor. 
 
In accordance with the Declaration of Helsinki, a description of the clinical investigation shall be 
registered in a publicly accessible database before the start of recruitment activities and the 
content shall be updated throughout the conduct of the clinical investigation and the results 
entered at completion of the clinical investigation. Note:  National regulations can apply 
concerning the timing of registration or updating the contents. 

 
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13 CLINICAL INVESTIGATION CONCLUSION 
The clinical investigation will be concluded when: 
• 
All sites are closed AND 
• 
The final report has been provided to investigators or the Sponsor has provided formal 
documentation of clinical investigation closure.  
14 PUBLICATION POLICY 
The data and results from the clinical investigation are the sole property of the Sponsor. The 
Sponsor shall have the right to access and use all data and results generated during the clinical 
investigation. The Investigators will not use this clinical investigation-related data without the 
written consent of the Sponsor for any purpose other than for clinical investigation completion or 
for generation of publication materials, as referenced in the Clinical Study Agreement. Single-
center results are not allowed to be published or presented before the multi-center results. Any 
proposals for publications or presentations by the investigators must be reviewed and approved 
by the Sponsor in a timely manner to enable Sponsor review in compliance with the Sponsor’s 
publication policy set forth in the Clinical Study Agreement. 
 
The Sponsor will be responsible for determining whether to register the clinical investigation on 
www.clinicaltrials.gov or any other clinical trials, in accordance with the International Committee 
of Medical Journal Editors guidelines, or any other applicable guidelines. In the event Sponsor 
determines that the clinical investigation should be registered, Sponsor shall be responsible for 
any such registration and results posting as required by the ClinicalTrials.gov website. Institution 
and/or Principal Investigator(s) shall not take any action to register the clinical investigation. 
15 RISK ANALYSIS 
Surgical cardiac procedures are commonly performed and LAA exclusion is a well-accepted 
treatment, with a well-established risk profile.  The primary objective of this study is to evaluate 
the long-term performance and safety of the AtriClip FLEX-V and PRO•V LAA Exclusion devices 
for exclusion of the left atrial appendage. 
15.1 Anticipated Clinical Benefits 
The potential benefit to study subjects outweighs the risks of participation in this study. The 
benefits may include but are not limited to, the following: 
• 
Overall advancement of medical and scientific knowledge that may benefit future subjects 
with similar conditions may be gained through this clinical study.  
There may also be other benefits that are unforeseen at this time. 
 
15.2 Foreseeable Adverse Events and Anticipated Adverse Device Effects 
Complications that could specifically have occurred at any time during the procedure, post 
procedure or may be possible during the follow-up period with the AtriCure AtriClip LAA Exclusion 
System. Refer to Appendix IV for a listing of foreseeable adverse events. 

 
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15.3 Residual Risks Associated with the Device Under Investigation, as Identified in the 
Risk/Quality Management Report 
Subjects enrolled in this trial have already been treated, however risk analyses and evaluations 
of the device hazards and product design, application, and process have been conducted for 
the AtriClip LAA Exclusion System devices.   
Upon review of the risk documentation for the AtriClip LAA Exclusion System, all individual 
residual risks were controlled and reduced to as far as possible. An acceptable level per the risk 
acceptability criteria set forth in the risk management plan was achieved.  
15.4  Risks Associated with Participation in this Clinical Investigation 
The clinical investigation has been designed to involve as little pain, discomfort, fear, and any 
other foreseeable risk as possible for subjects.  
 
15.5 Steps Taken to Control or Mitigate Risks 
In-depth recommendations and special precautions are included in the IFU. Risks associated 
with this clinical investigation are minimized through investigator selection and training, pre-
specified subject eligibility requirements, and study monitoring to ensure adherence to the 
protocol. All adverse events and device deficiencies will be reported to the Sponsor and will be 
monitored internally for safety surveillance purposes. 
 
15.6 Risk to Benefit Rationale 
The cumulative effect of all residual risks have been evaluated to ensure the overall residual risk 
of the product is acceptable and that the benefits of the device outweigh the overall residual 
risk.  
 
 
 
 
 

 
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APPENDIX I: REFERENCES 
1. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused 
update of the ESC Guidelines for the management of atrial fibrillation: an update of the 
2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special 
contribution of the European Heart Rhythm Association. Eur Heart J 2012;33:2719–47. 
doi:10.1093/eurheartj/ehs253 
2. Ailawadi, Gorav et al. “Exclusion of the left atrial appendage with a novel device: early 
results of a multicenter trial.” The Journal of thoracic and cardiovascular surgery vol. 142,5 
(2011): 1002-9, 1009.e1. doi:10.1016/j.jtcvs.2011.07.052 
3. Calkins, Hugh et al. “HRS/EHRA/ECAS expert consensus statement on catheter and 
surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures 
and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on Catheter and 
Surgical Ablation of Atrial Fibrillation developed in partnership with the European Heart 
Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in 
collaboration with the American College of Cardiology (ACC), American Heart Association 
(AHA), and the Society of Thoracic Surgeons (STS). Endorsed and approved by the 
governing bodies of the American College of Cardiology, the American Heart Association, 
the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the 
Society of Thoracic Surgeons, and the Heart Rhythm Society.” Europace : European 
pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on 
cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European 
Society of Cardiology vol. 9,6 (2007): 335-79. doi:10.1093/europace/eum120 
4. Caliskan, Etem et al. “Epicardial left atrial appendage AtriClip occlusion reduces the 
incidence of stroke in patients with atrial fibrillation undergoing cardiac surgery.” Europace 
: European pacing, arrhythmias, and cardiac electrophysiology : journal of the working 
groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the 
European 
Society 
of 
Cardiology vol. 
20,7 
(2018): 
e105-e114. 
doi:10.1093/europace/eux211  
5. Ueberham, Laura et al. “Pharmacological and Non-pharmacological Treatments for Stroke 
Prevention in Patients with Atrial Fibrillation.” Advances in therapy vol. 34,10 (2017): 
2274-2294. doi:10.1007/s12325-017-0616-6 
6. van Laar, Charlotte et al. “Thoracoscopic Left Atrial Appendage Clipping: A Multicenter 
Cohort 
Analysis.” JACC. 
Clinical 
electrophysiology vol. 
4,7 
(2018): 
893-901. 
doi:10.1016/j.jacep.2018.03.009 
7. Healey, Jeff S et al. “Left Atrial Appendage Occlusion Study (LAAOS): results of a 
randomized controlled pilot study of left atrial appendage occlusion during coronary 
bypass surgery in patients at risk for stroke.” American heart journal vol. 150,2 (2005): 
288-93. doi:10.1016/j.ahj.2004.09.054 
8. Kar et al. Primary outcomes evaluation of a next-generation left atrial appendage closure 
device. Results form PINNACLE FLX Trial. Circulation Volume 143, Issue 18, 4 May 
2021; Pages 1754-1762 
 
 
 

 
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APPENDIX II: ABBREVIATIONS AND ACRONYMNS 
Acronyms/Abbreviation 
 Terms 
AAD 
 
 
Antiarrhythmic Drug 
ACC 
 
 
American College of Cardiology 
ACT 
 
 
Activated Clotting Time 
ADE 
 
 
Adverse Device Effect 
AE 
 
 
 
Adverse Event 
AEF 
 
 
 
Atrio-esophageal Fistula 
AHA 
 
 
 
American Heart Association 
ANC 
 
 
 
Absolute Neutrophil Count 
ARDS  
 
 
Acute Respiratory Distress Syndrome 
AV 
 
 
 
Atrioventricular 
AVNRT 
 
 
Atrioventricular Nodal Reentry Tachycardia 
BARC  
 
 
Bleeding Academic Research Consortium 
BMI 
 
 
 
Body Mass Index 
CEC 
 
 
 
Clinical Events Committee 
CFR 
 
 
 
Code of Federal Regulations 
CABG  
 
 
Coronary Artery Bypass Graft 
CTA 
 
 
 
Computed Tomography Angiogram 
CVA 
 
 
 
Cerebrovascular Accident 
DCCV  
 
 
DC Cardioversion 
DOE 
 
 
 
Dyspnea on Exertion 
DVT 
 
 
 
Deep Vein Thrombosis 
ECG 
 
 
 
Electrocrdiography 
EDC 
 
 
 
Electronic Data Capture 
eCRF  
 
 
Electronic Case Report Form 
ECAS  
 
 
European Cardiac Arrythmia Society 
EC 
 
 
 
Ethics Committee 
EHRA  
 
 
European Heart Rhythm Association 
EP 
 
 
 
Electrophysiology 
ESC 
 
 
 
European Society of Cardiology 
FDA 
 
 
 
Food and Drug Administration 
GCP 
 
 
 
Good Clinical Practice 
GFL 
 
 
 
Glomerular filtration rate 
GI 
 
 
 
Gastrointestinal  
HCT 
 
 
 
Hematocrit 
HIPAA  
 
 
Health Insurance Portability and Accountability Act 
HIT 
 
 
 
Heparin Induced Thrombocytopenia 
HRS 
 
 
 
Heart Rhythm Society 
ICD 
 
 
 
Implantable cardioverter-defibrillator 
ICF 
 
 
 
Informed Consent Form 

 
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ICH 
 
 
 
International Conference on Harmonization 
IDE 
 
 
 
Investigational Device Exemption 
ILR 
 
 
 
Implantable Loop Recorder 
INR 
 
 
 
International Normalized Ratio 
IRB 
 
 
 
Institutional Review Board 
ISO 
 
 
 
International Organization for Standardization 
ITT 
 
 
 
Intent to Treat 
LA 
 
 
 
Left atrium 
LAA 
 
 
 
Left Atrial Appendage 
LVEF  
 
 
Left Ventricular Ejection Fraction 
MAE 
 
 
 
Major Adverse Event 
MDR  
 
 
Medical Device Reporting 
MI 
 
 
 
Myocardial Infarction 
OAC 
 
 
 
Oral Anticoagulant 
PE 
 
 
 
Pulmonary Embolism  
PI 
 
 
 
Principal Investigator 
PP 
 
 
 
Per Protocol 
PHI 
 
 
 
Personal Health Information 
PPM 
 
 
 
Permanent Pacemaker 
PRBC  
 
 
Packed Red Blood Cells 
SAE 
 
 
 
Serious Adverse Event 
SAP 
 
 
 
Statistical Analysis Plan 
SMP 
 
 
 
Safety Monitoring Plan 
SOB 
 
 
 
Shortness of Breath 
SOC 
 
 
 
Standard of Care 
TEE 
 
 
 
Transesophageal Echocardiogram (graphy) 
TIA 
 
 
 
Transient Ischemic Attack 
TTE 
 
 
 
Transthoracic Echocardiogram (graphy) 
UADE  
 
 
Unanticipated Adverse Device Effect 
ULN 
 
 
 
Upper Limit of Normal 
USADE 
 
 
Unanticipated Serious Adverse Device Effect 

 
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APPENDIX III: DEFINITIONS 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
 
Severe anemia: Hematocrit below 25%.  Generally, an accepted value to consider the need for 
transfusion of red blood cells.  This is not in the setting of acute persistent bleeding. 
 
Coagulopathy: Bleeding in the presence with abnormal clotting studies. 
 
Hemodilutional Anemia: Anemia associated with fluid volume overload as a result of 
cardiopulmonary bypass. 
 
HIT (Heparin Induced Thrombocytopenia): Low blood platelet count as a result of the 
medication heparin. Must have lab evidence of HIT +. 
 
Leukopenia: Leukopenia is defined as leukocyte count of < 3.5 x109/liter for more than 3 days. 
 
Neutropenia: Neutropenia is defined as ANC <1000 per mm3 for more than 3 days. 
 
Thrombocytopenia: A persistent decrease in the number of blood platelets. This is not 
considered to be an AE until treated. 
 
CARDIAC DISORDERS  
Arrhythmias  
Bradycardia: Abnormally low heart rate (<60 bpm) requiring treatment (implantation of a 
temporary or permanent pacemaker, or medication). 
 
SVT: Tachycardia in which QRS is narrow and P waves are present and associated. In certain 
SVT’s the QRS may be wide (>120msec) when it is aberrant and in some the P wave may be 
invisible as it maybe superimposed on the QRS (AV Nodal Reentrant Tachycardia). 
 
Ventricular tachycardia (VT): A regular heart rhythm originating from the ventricle with a  heart 
rate of greater than 100 bpm for at least 30 seconds or requiring termination due to hemodynamic 
compromise.    
Ventricular fibrillation (VF): A rapid irregular ventricular rhythm due to multiple reentrant 
activities associated with essentially zero cardiac output. 
 
Atrioventricular (AV) Block: 
• 
2nd degree: Second-degree (AV) block is characterized by interruption of impulse 

 
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conduction through the AV node. This may take the form of progressive prolongation of 
the P-R interval until there is a non-conducted beat with no QRS (Mobitz I or Wenckebach) 
or intermittent non-conducted P waves without preceding prolongation of the P-R interval 
or subsequent shortening of the interval (Mobitz II). This excludes block due to premature 
atrial beats 
• 
3rd degree: Third-degree AV block (complete heart block) exists when more P waves than 
the QRS complexes exist and no relationship exists between them (no conduction). 
 
Angina: A tight or heavy feeling in the chest, discomfort which spreads from the chest to the arm, 
back, neck, jaw, or stomach, numbness or tingling in the shoulders, arms or wrists, shortness of 
breath, and nausea. 
 
Atrial thrombus: Thrombus formation or detection within the atrium. 
 
Cardiac Arrest: Absent or inadequate contraction of the left ventricle of the heart that immediately 
causes body wide circulatory failure. 
 
Cardiac Tamponade: See Cardiac Tamponade/Perforation definition. 
 
Cardiac Tamponade/Perforation: Cardiac tamponade/perforation is defined as a complication 
of AF ablation if the development of a significant pericardial effusion occurs during or within 30 
days of undergoing an AF Ablation procedure. A significant pericardial effusion is one which 
results in hemodynamic compromise, requires elective or urgent pericardiocentesis, or results in 
a pericardial effusion of 1 cm or more (by echocardiography). Cardiac tamponade/perforation 
should be classified as “early” or “late” depending on whether it is diagnosed during or following 
initial discharge from the hospital. 
 
Cardiogenic Shock: Subject exhibits cardiogenic shock (systolic pressure < 80mm Hg and 
PCWP > 20mm Hg or cardiac index <1.8 liters/minute/m2 or intra-aortic balloon pump or 
intravenous inotropes are needed to maintain a systolic pressure>80 mm Hg) for any time within 
24 hours prior to index procedure. 
 
Congestive Heart Failure: Documentation of one of the following: 
• 
Paroxysmal nocturnal dyspnea (PND) 
• 
Dyspnea on exertion (DOE) due to heart failure 
• 
Elevated PCW with associated SOB or x-ray consistent with congestion. 
• 
May be related to fluid overload in the presence of underlying cardiovascular disease.  
 
Heart Failure: A clinical syndrome resulting from a cardiac disease which comprises ventricular 
systolic or diastolic function or both. Heart failure results when the heart is unable to generate a 
cardiac output sufficient to meet the demands of the body without unduly increasing diastolic 
pressure. Heart failure may be manifested by symptoms of poor tissue perfusion alone (i.e., 
fatigue, poor exercise tolerance, confusion) or by both symptoms of poor tissue perfusion and 

 
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congestion of vascular beds (e.g., dyspnea, chest rales, pleural effusion, pulmonary edema, 
distended neck veins, congested liver, peripheral edema). We will not distinguish between 
congestive and chronic heart failure for purposes of this protocol. 
 
Myocardial Infarction in the context of surgical AF Ablation: The presence of any one of the 
following criteria:  
1. Detection of ECG changes indicative of new ischemia (new ST-T changes), which may 
persist for more than one hour;  
2. Development of new pathological Q waves on an ECG;   
3. Imaging evidence of new loss of viable myocardium or new regional wall abnormality.  
 
Myocardial Perforation: See Cardiac Tamponade/Perforation definition. 
 
Pericardial effusion: Fluid detected in the pericardial space by standard imaging techniques 
(e.g., echocardiography). 
 
Pericarditis: Irritation or inflammation of the pericardium associated with pain on inspiration and 
shortness of breath. Clinical signs may include shallow respiration, pericardial friction rub and 
ECG changes (ST elevation across the precordial leads). 
 
Sick sinus syndrome: also called sinus node dysfunction, is a group of abnormal heart rhythms 
(arrhythmia) presumably caused by a malfunction of the sinus node, the heart's primary 
pacemaker. 
 
Unstable Angina: Angina which increases in frequency, intensity, or duration, which occurs at 
rest, or which is new in onset. Unstable angina is a syndrome that is intermediate between stable 
angina and myocardial infarction: it is characterized by an accelerating or "crescendo" pattern of 
chest pain that lasts longer than instable angina, occurs at rest or with less exertion than instable 
angina, or is less responsive to medication.  Unstable angina and myocardial infarction are 
considered acute coronary syndromes. 
 
GASTROINTESTINAL/GENITOURINARY DEFINITIONS 
 
Atrioesophageal Fistula: A connection between the atrium and the lumen of the esophagus. 
Evidence supporting this diagnosis includes documentation of esophageal erosion combined with 
evidence of a fistulous connection to the atrium such as an air embolus, an embolic event, or 
direct observation at the time of surgical repair.  A CT scan or MRI scan are the most common 
methods of documentation of an atrial esophageal fistula.  Esophagoscopy should NOT be 
performed as it may result in air insufflation into the left Atrium. 
 
Aortoesophageal Fistula: Abnormal passage from aorta communicating with the esophagus (for 
the purposes of the protocol - likely resulting from an esophageal perforation or burn). 
Presentation of aortoesophageal fistula may include hematemesis (possibly massive). Diagnosis 

 
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may be obtained with a contrast CT scan, aortography, esophagoscopy, or barium swallow.  A 
possible outcome of aortoesophageal fistula is sepsis, which may be diagnosed with blood 
cultures. 
 
Esophageal Dyskinesia: diffuse spasms of the esophagus which may occur as the result of 
vagal nerve injury  
Esophageal Injury: Any evidence of a mild complication such as erosion or ulceration or a major 
complication such as puncture, dissection, or perforation to the esophagus.   
Hernia: an anatomical part (such as section of the intestine) protrudes through an opening, tear, 
or weakness in the abdominal wall musculature.  
Gastric Motility Disorders: multiple gastric disorders may occur post AF ablation such as 
constipation, atony, weight loss, early satiety, diarrhea or GI disturbance.  
Gastroparesis: delayed gastric emptying resulting in paresis of the stomach.  As the vagus nerve 
controls the contractions of the stomach, this may occur when the vagus nerve is damaged and 
the muscles of the stomach and intestines do not work normally.  
Renal Complications: 
• 
Renal Failure: Inability of the kidneys to filter toxins resulting in a serum creatinine 
increase to > 2.0 mg/dl and one of the following: 
o increase of 2.0 mg/dl in serum creatinine over any previous value 
o 50% or greater increase in creatinine over baseline procedural value 
requirement for dialysis 
• 
Renal failure that requires dialysis: a significant decrease in renal function requiring 
dialysis. 
• 
Renal Insufficiency: An increase in serum creatinine of ≥1.0 mg/dl over previous value. 
 
Vomiting: The ejection of matter from the stomach in retrograde fashion through the esophagus 
and mouth. 
 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
 
Atypical Chest Pain: Located under the sternum, left chest, abdomen, back, or arm and is 
fleeting or sharp. It is unrelated to exercise, not relieved by rest or the administration of 
nitroglycerin. 
 
Drug Reactions: An unwanted or harmful side effect experienced following the administration of 
a drug or combination of drugs and is suspected to be related to the drug. 
 

 
Protocol Number: CP-2021-03 
 
 
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Fatigue/Malaise: Weariness, tiredness, or lack of energy.  Generalized feeling of discomfort, 
illness, or lack of well-being. 
 
Fever: A temperature > 101°F not related to a culture positive infection. 
 
General Discomfort: Physical or psychosocial signs or symptoms commonly associated with 
hospitalization that are investigated and determined to require minor (i.e., aspirin, non-narcotic 
medication) or no treatment. 
 
Medication Reaction: An unwanted or harmful side effect experienced following the 
administration of drug or combination of drugs and is suspected to be related to the drug. 
 
Multi-organ failure: Failure of more than one organ due to shock or sepsis. This requires volume 
and inotropic support and has a high incidence of death. 
 
Nausea: The unsettling feeling in the stomach that accompanies the urge to vomit. 
 
Non-ischemic Chest Pain: Any discomfort in the chest, shoulder, back or chest wall for which a 
cardiac ischemic origin is ruled out or not suspected. May be cardiac (for example pericardial) or 
non-cardiac (for example gastrointestinal) in origin. 
 
 
Pain: Reports of pain, ranging from mild discomfort to acute agony, may be generalized or 
localized, requiring treatment or intervention. 
 
Peripheral Edema: is the swelling of tissues, usually in the lower limbs, due the accumulation of 
fluids. 
 
Reoperation: A repeat operation for the same condition in the same subject or to resolve an 
adverse event resulting from the initial operation. Reoperation is not an adverse event – it is an 
outcome – the reason for reoperation is the adverse event. 
 
Sudden Death: Cardiac arrest which is unexpected and occurs within minutes of the onset of 
symptoms. 
 
Death: All-cause mortality. Death is not an adverse event, it is an outcome.  The Adverse Event 
is what caused the death. 
 
HEPATOBILIARY DISORDERS 
 
Hepatic Failure: A clinical condition that results from severe and extensive damage of liver cells 
leading to failure of the liver to function normally and can induce mental confusion of various 

 
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CONFIDENTIAL 
 
 
 
degrees. Liver failure is described as the combination of hyperbilirubinemia (total Bilirubin > 2), 
coagulopathy with INR level greater than the upper limits of normal (in the absence of Warfarin 
(Coumadin) treatment) and hypoalbuminemia (Albumin < 3). 
 
IMMUNE SYSTEM DISORDERS 
 
Allergic Reaction: A reaction to a foreign protein characterized by rash, nausea, vomiting, upper 
respiratory congestion, urticaria, shortness-of-breath, or general collapse (anaphylaxis). 
 
INFECTIOUS/INFLAMMATORY DEFINITIONS 
Bacteremia: Presence of viable bacteria in the circulating blood without systemic manifestation 
(sepsis). 
 
Endocarditis: An infection for which no source is identified associated with classic signs of 
endocarditis (positive blood cultures, fever, red blood cell casts in urine, splinter hemorrhages in 
finger nails, roof of mouth, lesions on retina, etc.) associated with a vegetation inside the atrium 
or on a valve which may be confirmed in echocardiography. 
 
Infection: The following are the categories for infections: 
 
• 
Deep Sternal: involving muscle, bone, and/or mediastinum 
• 
Deep Sternal Wound Infection: Infection involving the sternum and/or mediastinum as 
documented by clinical examination and culture which may require reoperation with 
sternal debridement and/or sternal rewiring. 
• 
Lung: involving airways associated with intubation or other respiratory causes 
• 
Leg: involving a leg vein harvest site. 
• 
Major: Including the chest wall, heart valves, mediastinum, etc., culture proven infection 
or presumptive treatment with antibiotics for clinically diagnosed infection 
• 
Minor: Temperature > 101°F /38.5°C or higher and a positive culture (e.g., tissue, urine, 
etc.) 
• 
Or Systemic Infection: Bloodstream infection caused by bacteria. 
 
Mediastinitis: The diagnosis requires at least one of the following: (1) an organism isolated from 
culture of mediastinal tissue or fluid; (2) evidence of mediastinitis seen during an operation; (3) 
one of the following conditions: chest pain, sternal instability, or fever (>38 ◦ C), in combination 
with either purulent discharge from the mediastinum or an organism isolated from blood culture 
or culture of mediastinal drainage. 
 
Pneumonia: Pneumonia diagnosed by one of the following: Positive cultures of sputum, blood, 
pleural fluid, emphysema fluid, transtracheal fluid or transthoracic fluid; consistent with the 
diagnosis and clinical findings of pneumonia.  Should include chest x-ray diagnostic of pulmonary 
infiltrates. 
 

 
Protocol Number: CP-2021-03 
 
 
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CONFIDENTIAL 
 
 
 
Sepsis: Culture-proven blood infection manifested by severe systemic symptoms (e.g. fever, 
hyperventilation, tachycardia, confusion). 
 
Septic Shock: Sepsis with hypotension despite adequate fluid resuscitation. In addition, two or 
more of the following must be present: 
• 
tachycardia 
• 
temperature < 36° or > 38°C 
• 
hyperventilation 
• 
WBC < 4000 or > 12000 
 
Urinary Tract Infection: Positive urine cultures requiring antibiotic therapy. 
 
Viral Illness: Diseases caused by a virus, including Bronchitis, Sinusitis, Cellulitis, and Upper Respiratory 
Infection. 
 
INJURY, POISONING AND PROCEDURAL COMPLICATIONS 
 
Atrial Tear: Any evidence of a tear or damage to the two upper chambers of heart/atrium 
 
Cardiac Valve Injury: Damage to any cardiac valve resulting from the index hybrid surgical 
procedure. 
 
Coronary Artery Injury: Damage to the artery caused during surgery requiring repair. 
 
Dissections: Presence of angiographically evident intimal disruption (e.g., linear luminal density 
or luminal staining or linear intraluminal filling defect) which requires treatment. 
 
Ventricular Perforation or Rupture: Any evidence of puncture/dissection/perforation or damage 
to the ventricle. 
 
Pseudoaneurysm: Compartmentalized blood contiguous with arterial lumen documented by 
ultrasound or visualized at repair. 
 
Skin Burns:  
 
• 
Second degree burns manifest as erythema with superficial blistering of the skin. Level 
of pain is dependent upon the level of nerve involvement. 
 
• 
Third-degree burns: occur when the epidermis is lost with damage to the subcutaneous 
tissue. This burn may exhibit charring and extreme damage of the epidermis, and 
sometimes hard eschar will be present. 
 
Wound dehiscence/delayed wound healing: not associated with infection. 

 
Protocol Number: CP-2021-03 
 
 
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CONFIDENTIAL 
 
 
 
 
METABOLISM DISORDERS 
 
Hyperglycemia: The use of insulin in the post op period does not constitute hyperglycemia if 
during the same hospitalization. An Elevated blood sugar ≥ 250 in the post-operative constitutes 
hyperglycemia. 
 
Hypoglycemia: Low blood glucose or low blood sugar, occurs when blood glucose drops below 
normal levels (50mg/dL). 
 
NERVOUS SYSTEM DISORDERS 
 
Headache: a term used to describe aching or pain that occurs in one or more areas of the head, 
face, mouth, or neck. Headache can be chronic, recurrent, or occasional. 
 
Recurrent Laryngeal Nerve Injury: Symptomatic hoarseness with documented laryngoscopy 
showing paralyzed or impaired laryngeal cord movement, beyond 30 days post procedure.  
Phrenic Nerve Paralysis:  Phrenic nerve paralysis is defined as absent phrenic nerve 
function as assessed by a sniff test. A phrenic nerve paralysis is considered to be permanent 
when it is documented to be present at 12 months or longer following ablation.  
Seizures: sudden, uncontrolled muscle spasms with or without loss of consciousness resulting 
from brain electrical activity 
 
Stroke: 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 neurological deficit lasting ≥ 24 hours, or 
lasting <24 hours if therapeutic intervention(s) were performed (i.e. thrombolytic therapy or 
intracranial angioplasty; or available neuro imaging documents a new hemorrhage or infarct or 
the neurological deficit results in death. Confirmation of the diagnosis by at least one of the 
following; neurology or neurosurgical specialist, neuro imaging study showing tissue injury or 
lumbar puncture demonstrating intracranial hemorrhage.   
 
Stroke diagnosis will be performed preferably with positive neuroimaging study. The stroke will 
be assessed as Minor or Major based on the following: 
• 
Minor—Modified Rankin (mRS) score <2 at 30 and 90 days 
• 
Major—Modified Rankin (mRS) score >2 at 30 and 90 days 
 
May be further categorized as: 
• 
Ischemic Stroke: Neurologic deficit attributed to thromboembolic event. 

 
Protocol Number: CP-2021-03 
 
 
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CONFIDENTIAL 
 
 
 
• 
Hemorrhagic Stroke: Neurologic deficit meeting the study definition for Stroke that is 
attributed to bleeding into brain tissue, epidural, subdural, or subarachnoid space; or a 
combination of these sites 
 
Systemic Embolism: The obstruction of blood flow in a vessel by an embolus (which may include 
a thrombus or an air bubble), in the pulmonary or peripheral arterial circulation. Diagnosis must 
be confirmed on imaging study, and interventional treatment performed to address condition. 
Does not include neurologic events (See Stroke definition). 
Transient Ischemic Attack (TIA): Neurological deficit lasting less than 24 hours and, if an 
imaging study is performed, shows no evidence of infarction. 
 
Vagal Nerve Injury: see esophageal dyskinesia and gastroparesis 
Vasovagal Reaction: Reflex stimulation of the vagus nerve causing slowing of the heartbeat, 
decreased blood pressure, etc. and requires treatment consisting of any of the following: (a) > 1 
liter of IV fluids; (b) postural changes; (c) pacing intervention; or (d) administration of atropine. 
 
PSYCHIATRIC DISORDERS 
 
Anxiety: A psychiatric disorder causing feelings of mental discomfort, for example, panic 
disorder, post-traumatic stress disorder or depression. 
 
RESPIRATORY/PULMONARY 
 
Acute respiratory distress syndrome (ARDS): A failure of the respiratory system characterized 
by fluid accumulation within the lung that causes the lung to stiffen. This condition must be 
confirmed by radiological evidence, or lung biopsy, or the need for prolonged positive pressure 
ventilation. 
 
Atelectasis: (post-surgical) is a collapse of lung tissue affecting part or all of one lung; the alveoli 
are deflated. This is an AE when treatment other than Chest PT is required or it prolongs 
hospitalization. 
 
Diaphragmatic paralysis: may be unilateral or bilateral.  Usually caused by injury to the phrenic 
nerve as a result of trauma to the thoracic cage. Findings include decreased air flow, dullness to 
percussion, and absence of diaphragmatic excursion on the ipsilateral side. Diagnosis may be 
made with fluoroscopy in which a quick “sniff” (i.e. subject inspiration) results in observation of 
paradoxical elevation of the ipsilateral diaphragm.  Often causes shortness of breath on activity. 
 
Hemoptysis: A cough that produces bloody sputum. 
 

 
Protocol Number: CP-2021-03 
 
 
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CONFIDENTIAL 
 
 
 
Pleural Effusion: Accumulation of fluid in the pleural space evidenced by x-ray, 
echocardiography, CT Scan or other appropriate diagnostic technique and which requires 
drainage. 
 
Pneumothorax: Air in the thoracic cavity associated with partial collapse of a lung with chest tube 
drainage required. 
 
Pulmonary Edema: Pulmonary edema is present if there is fluid accumulation in the lungs 
caused by backpressure in the lung veins. This condition must be confirmed by radiological 
evidence or lung water measurements. 
 
Pulmonary Embolism: Pulmonary embolism diagnosed by study such as V/Q scan or angiogram 
or spiral CT or clinical symptoms consistent with PE in the absence of these studies that result in 
treatment. 
 
Pulmonary Hypertension: Subject has mean pulmonary artery pressure that is greater than 25 
mmHg at rest and/or greater than 30 mmHg during exercise as measured by right heart 
catheterization. 
 
Pulmonary vein stenosis: Defined as 70% diameter stenosis of one pulmonary vein or 50% 
diameter stenosis of more than one vessel. PV stenosis is manifest as dyspnea at rest, may be 
associated with hemoptysis and must be confirmed by imaging studies of the pulmonary veins 
(using CT or MRI). 
 
Respiratory failure: Need for mechanical ventilation beyond 48 hours of completion of surgical 
procedure(s), or the need for re-intubation and ventilator support occurring at any time within 30 
days of the surgical procedure, outside the setting of an additional operation. 
 
Respiratory insufficiency: Deterioration of subject’s respiratory efforts that require supportive 
or medical treatment. 
 
VASCULAR DEFINITIONS 
 
Atrial Embolism: Angiographic evidence of embolic occlusion in any arterial distribution. 
 
Arterial Occlusion/Thrombosis at Access Site: Angiographic or ultrasonographic evidence of 
occlusion at the access site, 
 
Arteriovenous Fistula: A traumatic communication between an artery and vein documented by 
ultrasound or angiography 
 

 
Protocol Number: CP-2021-03 
 
 
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Deep Vein Thrombosis (DVT): Angiographic or ultrasonographic evidence of thromboembolic 
occlusion in the lower extremities.   
 
Embolism (including air emboli and thromboemboli): The blockage of an artery by an 
embolus, which can include a thrombus or an air bubble. 
 
Hematoma: Development of a collection of blood > 5 cm under the skin requiring compression or 
additional treatment to resolve. 
 
Major Bleeding: The following will constitute major bleeding events: 
• 
Fatal bleeding OR 
• 
Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial 
necessitating pericardiocentesis, or intramuscular with compartment syndrome OR  
• 
Bleeding causing hypovolemic shock or severe hypotension requiring surgery OR  
• 
Overt source of bleeding with drop in hemoglobin ≥5 g/dL or whole blood or packed red 
blood cells (RBCs) transfusion ≥4 units 
 
Hypertension: Systolic BP > 140 mmHg, or diastolic > 90 mmHg, or requiring specific medical 
therapy. 
 
Hypotension: Any prolonged systolic blood pressure < 80 mmHg associated with symptoms and 
requiring intravenous vasopressor medications. 
 
Limb Ischemia: Limb ischemia is manifested by pain in an extremity at rest, associated with non-
healing wounds and gangrene. Limb ischemia should be confirmed by diagnostic imaging studies. 
 
Peripheral Ischemia: Deficient supply of blood to the blood vessels outside the heart and brain 
that is due to obstruction of the inflow of arterial blood. 
 
Thromboembolism: Formation of a thrombus (masses composed of insoluble fibrin, deposited 
platelets, accumulating WBCs, and entrapped RBCs) that obstructs vascular blood flow locally 
and detaches and embolizes to occlude blood flow downstream. Diagnostic confirmation should 
be made with angiography or ultrasound. 
 
Thrombophlebitis: Inflammation of a vein with formation of a thrombus. 
 
Thrombus: Blood clot that obstructs a blood vessel. 
 
 
 

 
Protocol Number: CP-2021-03 
 
 
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CONFIDENTIAL 
 
 
 
APPENDIX IV: FORSEEABLE ADVERSE EVENTS 
Adverse Events that may be anticipated in this clinical study are believed to be consistent with 
those associated with other invasive surgical and cardiac procedures. 
 
Complications that may have occurred at any time during the procedure, post procedure or that 
are possible during the follow-up period with the AtriCure AtriClip LAA Exclusion System include, 
but are not limited to the following: 
 
• 
Air embolism 
• 
Allergic reaction to implant materials 
• 
Anesthesia risks 
• 
Aneurysm  
• 
Angina 
• 
Arrhythmia needing medical treatment (new onset) 
• 
Arterial or venous dissection and/or perforation  
• 
Arterial rupture  
• 
Arterial spasm  
• 
Arteriovenous fistula  
• 
Atelectasis (major lung tissue collapse with significant symptoms such as cyanosis, 
extreme shortness of breath, dyspnea, and/or stabbing pain on the affected side)  
• 
Atrial rupture  
• 
AV block requiring permanent pacemaker (new onset) 
• 
Bleeding requiring intervention to repair or which requires > 2 units of blood products 
• 
Blood vessel damage 
• 
Cardiac perforation 
• 
Cardiac tamponade (if either open chest or catheter drainage is required) 
• 
Coronary artery injury 
• 
Cardiac valve injury   
• 
Cerebrovascular accident (CVA)/stroke (ischemic or hemorrhagic) 
• 
Circumflex artery impingement 
• 
Conduction disturbances (SA/AV node) 
• 
Congestive heart failure (new onset or exacerbation) 
• 
Death                                                       
• 
Diaphragmatic paralysis (unilateral or bilateral)   
• 
Drug Reaction (significant reaction to any study related medications requiring treatment, 
including allergic reaction and anaphylactic shock)  
• 
Emergency during the operation requiring change in the planned surgical access  
• 
Endocarditis (bacterial) 

 
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• 
Pain and discomfort  
• 
Extension of cardiopulmonary/extracorporeal bypass 
• 
Esophageal rupture  
• 
Extravasation of contrast media  
• 
Fever 
• 
Gastro-intestinal bleed  
• 
Gastric motility disorders 
• 
Hematoma 
• 
Hematuria  
• 
Hemothorax  
• 
Hypertension  
• 
Hypotension 
• 
Iatrogenic lung injury (e.g., chest tube placement)  
• 
Infection requiring treatment 
• 
Injury to the heart, a blood vessel, or other part of the body due to the investigational 
device, possibly requiring intervention  
• 
Ischemia  
• 
Myocardial infarction (MI)  
• 
Nerve Injury (phrenic, laryngeal, thoracic, etc.)  
• 
Pericarditis  
• 
Persistent chest pain (post discharge surgical incision pain, not angina)  
• 
Pericardial effusion  
• 
Pleural effusion 
• 
Pneumothorax (requiring intervention)  
• 
Postoperative embolic complications 
• 
Pseudoaneurysm  
• 
Pulmonary edema  
• 
Pulmonary embolism 
• 
Renal insufficiency or failure  
• 
Respiratory distress or failure (breathing problems)   
• 
Sepsis  
• 
Sinus Node Dysfunction (new onset) 
• 
Thrombus and/or thromboembolism (including a deep vein thrombosis)  
• 
Transient ischemic attack (TIA)  
• 
Tracheal esophageal trauma 
• 
Unanticipated device effects 
• 
There may also be other risks that are unforeseen at this time. 
 
 

 
Protocol Number: CP-2021-03 
 
 
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CONFIDENTIAL 
 
 
 
APPENDIX V: INFORMED CONSENT FORM 
A copy of the Sponsor Informed Consent Form Template can be obtained upon request from 
the Sponsor Clinical Project Manager for the clinical investigation and will be provided to study 
sites for IRB/EC approval. 
 
 
 
 
 

 
Protocol Number: CP-2021-03 
 
 
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CONFIDENTIAL 
 
 
 
APPENDIX VI: SITE CONTACT INFORMATION 
A copy of contact information for each participating site can be obtained upon request from the 
Sponsor Clinical Project Manager for the clinical investigation. 
 
 
 
 
 

 
Protocol Number: CP-2021-03 
 
 
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CONFIDENTIAL 
 
 
 
 
APPENDIX VII: REVISION HISTORY 
 
 
Amendment 
Number 
Version / 
Revision 
Details 
Not Applicable 
RCS-036 
rev. A 
Initial Release per DCN-2021-0640. 
Not Applicable 
CP-2021-
03 rev. B 
See redlines on DCN-2021-0738 for all changes. Changes 
include: 
• 
Protocol number changed from RCS-036 to CP-2021-03 
to match CP number in other literature. 
• 
Protocol revised due to a need to change performance 
goals to better reflect contemporary literature for LAA 
closure rates.