Safety and Effectiveness Evaluation of the OMNYPULSE Catheter With the TRUPULSE Generator for Treatment of Paroxysmal Atrial Fibrillation (PAF)
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Biosense Webster, Inc.

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Safety and Effectiveness Evaluation of the OMNYPULSE™ Catheter with 
the TRUPULSE™ Generator for treatment of Paroxysmal Atrial Fibrillation 
(PAF) 
Omny-IRE
Clinical Investigation Plan 
(CIP) Number:  
BWI202201 
Sponsor: 
Biosense Webster, Inc., a division of Johnson & Johnson with registered office 
at 31 Technology Drive, Suite 200 Irvine, CA 92618  
Operating Company: 
Johnson & Johnson Medical NV/SA with registered office at Leonardo Da 
Vincilaan 15, 1831 Diegem, Belgium, represented by 
Funded by: 
Biosense Webster, Inc., part of the Johnson & Johnson family of companies. 
Version: 
3.0 
Date: 
25/JUL/2025 
Eudamed number 
CIV-23-06-043176
 History of Changes: 
Version— Date 
Description 
V 1.0 —03APR2023 
Original Document 
V 2.0 – 23MAY2023 
Final Original Document for submission 
V 3.0 – 25JUL2025 
Administrative change to endpoints 
The Biosense Webster OMNYPULSE™ Bi-Directional Catheter 
(D-1430-05-SI), Sterile Interface Cable (D-1422-03-SI) and TRUPULSE™ Generator (D-1417-01-IC) are for 
investigational device use only and are not commercially available anywhere in the world. “OMNYPULSE™ Bi-
Directional Catheter”, “Sterile Interface Cable” and “TRUPULSE™ Generator” are internal Biosense Webster project 
names and are not intended for any other external use. The final commercial or trade name of the investigational 
system (OMNYPULSE™ Bi-Directional Catheter and TRUPULSE™ Generator) may be different. 
PPD
NCT05971693

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1 
Table of Contents 
1 
TABLE OF CONTENTS .................................................................................................................................... 2 
2 
LIST OF ACRONYMS AND ABBREVIATIONS .................................................................................................... 6 
3 
KEY ROLES AND RESPONSIBLE PARTIES ......................................................................................................... 9 
4 
CLINICAL INVESTIGATION PLAN SUMMARY ................................................................................................ 11 
5 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ........................................................................ 21 
5.1 
BACKGROUND INFORMATION ............................................................................................................................. 21 
5.2 
PREVIOUS EXPERIENCE WITH THE OMNYPULSE™ CATHETER .................................................................................. 22 
5.2.1 
Pre-Clinical Experience with the OMNYPULSE™ Catheter and TRUPULSE™ Generator ......................... 22 
5.2.2 
Previous Clinical Evaluations with the TRUPULSE™ Generator .............................................................. 22 
5.3 
RATIONALE FOR DESIGN OF THE CLINICAL INVESTIGATION ........................................................................................ 23 
5.4 
POTENTIAL RISK AND BENEFIT ............................................................................................................................ 23 
5.4.1 
Known Potential Risks and Mitigation ................................................................................................... 24 
5.4.2 
Known Potential Benefits ....................................................................................................................... 27 
6 
OBJECTIVES AND PURPOSE ......................................................................................................................... 28 
6.1 
OBJECTIVE ...................................................................................................................................................... 28 
6.2 
ADDITIONAL OBJECTIVE ..................................................................................................................................... 29 
7 
STUDY DESIGN AND ENDPOINTS................................................................................................................. 29 
7.1 
DESCRIPTION OF THE STUDY DESIGN .................................................................................................................... 29 
7.2 
ROLL-IN PHASE ............................................................................................................................................... 29 
7.3 
STUDY SUBSETS ............................................................................................................................................... 30 
7.3.1 
Neurological Assessment (NA) subset .................................................................................................... 30 
7.3.2 
Esophageal Endoscopy (EE) Subset ........................................................................................................ 30 
7.3.3 
Cardiac CT/MRA subset .......................................................................................................................... 31 
7.3.4 
PVI Durability Subset .............................................................................................................................. 31 
7.4 
STUDY ENDPOINTS ........................................................................................................................................... 31 
7.4.1 
Primary Hypothesized Endpoints ............................................................................................................ 31 
7.4.2 
Secondary Hypothesized Endpoints ........................................................................................................ 32 
7.4.3 
Additional Effectiveness Endpoints ........................................................................................................ 32 
7.4.4 
Additional Safety Endpoints ................................................................................................................... 34 
7.4.5 
Additional Procedural Endpoints ............................................................................................................ 34 
8 
STUDY POPULATION .................................................................................................................................. 34 
8.1 
PARTICIPANT INCLUSION CRITERIA ....................................................................................................................... 35 
8.2 
PARTICIPANT EXCLUSION CRITERIA ...................................................................................................................... 35 
9 
PARTICIPANT WITHDRAWAL OR TERMINATION .......................................................................................... 36 
9.1 
REASONS FOR WITHDRAWAL OR TERMINATION ..................................................................................................... 36 
9.2 
HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION ................................................................................. 37 
10 
RESPONSIBILITIES ....................................................................................................................................... 37 
10.1 
INVESTIGATOR RESPONSIBILITIES ......................................................................................................................... 37 
10.2 
SPONSOR RESPONSIBILITIES ............................................................................................................................... 38 
11 
STUDY DEVICE DESCRIPTION ...................................................................................................................... 38 
11.1 
DEVICE ACQUISITION ........................................................................................................................................ 38 
11.2 
DEVICE STORAGE AND STABILITY ......................................................................................................................... 39 
11.3 
DEVICE PREPARATION ....................................................................................................................................... 39 
11.4 
INSTRUCTIONS FOR USE..................................................................................................................................... 39 
11.5 
DEVICE DESCRIPTION AND SPECIFIC CONSIDERATIONS ............................................................................................. 39 
11.5.1 TRUPULSE™ Generator ........................................................................................................................... 39 

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11.5.2 The OMNYPULSE™ Bi-Directional Catheter ............................................................................................ 40 
11.5.3 Investigational Accessory Devices .......................................................................................................... 42 
11.5.4 System Components and Setup .............................................................................................................. 42 
12 
STUDY MEDICATION ................................................................................................................................... 46 
13 
STUDY SCHEDULE ....................................................................................................................................... 46 
13.1 
SCREENING AND INFORMED CONSENT .................................................................................................................. 46 
13.2 
BASELINE EVALUATION AND PROCEDURES ............................................................................................................ 47 
13.2.1 Pre-Procedure/Baseline Assessments .................................................................................................... 47 
13.3 
STUDY ABLATION PROCEDURE GUIDELINES ........................................................................................................... 48 
13.3.1 Ablation Selections ................................................................................................................................. 48 
13.3.2 Flow Settings .......................................................................................................................................... 49 
13.3.3 Study Ablation Procedure Sequence & Guidelines ................................................................................. 49 
13.3.4 Collection of Ablation Procedure Data for Post-Analysis (non-SOC) ...................................................... 52 
13.3.5 Data Collection during Study Ablation Procedure .................................................................................. 52 
13.3.6 Pre-Discharge Assessments .................................................................................................................... 53 
13.4 
REPEAT ABLATION PROCEDURES ......................................................................................................................... 54 
13.5 
POST-ABLATION FOLLOW-UP SCHEDULE .............................................................................................................. 54 
13.5.1 Seven (7) day follow-up visit ................................................................................................................... 54 
13.5.2 Monthly follow-up visit .......................................................................................................................... 55 
13.6 
EARLY TERMINATION VISIT ................................................................................................................................ 56 
13.7 
UNSCHEDULED VISIT ......................................................................................................................................... 56 
13.8 
CORE LABORATORY FOR EVALUATION .................................................................................................................. 56 
13.9 
SCHEDULE OF EVENTS TABLE .............................................................................................................................. 57 
14 
ASSESSMENT OF SAFETY............................................................................................................................. 58 
14.1 
SPECIFIC SAFETY PARAMETERS ............................................................................................................................ 58 
14.1.1 Definition of Adverse Events (AE) ........................................................................................................... 58 
14.1.2 Definition of Serious Adverse Event (SAE) .............................................................................................. 59 
14.1.3 Primary Adverse Event ........................................................................................................................... 60 
14.1.4 Adverse Device Effect / Serious Adverse Device Effect ........................................................................... 63 
14.1.5 Unanticipated Serious Adverse Device Effect ......................................................................................... 63 
14.1.6 Study Device Deficiency, Failure or Malfunction .................................................................................... 63 
14.1.7 Serious Public Health Threat .................................................................................................................. 63 
14.2 
CLASSIFICATION OF AN ADVERSE EVENT ............................................................................................................... 64 
14.2.1 Severity of Event ..................................................................................................................................... 64 
14.2.2 Relationship to Study Device .................................................................................................................. 64 
14.2.3 Outcome ................................................................................................................................................. 66 
14.2.4 Anticipated Adverse Event ..................................................................................................................... 66 
14.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP ................................................................. 67 
14.4 
REPORTING PROCEDURES .................................................................................................................................. 67 
14.4.1 Adverse Event Documentation and Reporting Requirements ................................................................ 67 
14.4.2 Serious Adverse Events Reporting .......................................................................................................... 68 
14.4.3 Unanticipated Serious Device Effect Reporting ...................................................................................... 69 
14.4.4 Events of Special Interest ....................................................................................................................... 70 
14.5 
SAFETY OVERSIGHT .......................................................................................................................................... 70 
15 
ADMINISTRATIVE RESPONSIBILITIES ........................................................................................................... 70 
15.1 
ETHICS COMMITTEE AND COMPETENT AUTHORITY APPLICATION ............................................................................... 70 
15.2 
AUDITS AND INSPECTIONS .................................................................................................................................. 71 
16 
DEVIATIONS FROM THE CLINICAL INVESTIGATION PLAN ............................................................................. 71 
17 
INVESTIGATIONAL PRODUCT ...................................................................................................................... 72 
17.1 
USE OF THE INVESTIGATIONAL DEVICE AND INVESTIGATOR EXPERIENCE ...................................................................... 72 
17.1.1 Training .................................................................................................................................................. 72 
17.1.2 BWI Investigational Materials ................................................................................................................ 72 
17.2 
DEVICE ACQUISITION AND ACCOUNTABILITY .......................................................................................................... 73 
17.3 
DEVICE RETURNS ............................................................................................................................................. 73 

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18 
CLINICAL MONITORING .............................................................................................................................. 74 
19 
STATISTICAL METHODOLOGY ..................................................................................................................... 74 
19.1 
LEVELS OF SIGNIFICANCE ................................................................................................................................... 74 
19.2 
SAMPLE SIZE JUSTIFICATION ............................................................................................................................... 75 
19.3 
ANALYSIS SETS ................................................................................................................................................ 75 
19.4 
GENERAL CONVENTIONS ................................................................................................................................... 76 
19.5 
SUBJECT DISPOSITION ....................................................................................................................................... 76 
19.6 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ................................................................................................... 77 
19.7 
ENDPOINTS AND ASSOCIATED HYPOTHESES ........................................................................................................... 77 
19.7.1 Primary Safety Endpoint: ........................................................................................................................ 77 
19.7.2 Primary Effectiveness Endpoint: ............................................................................................................. 77 
19.7.3 Secondary Effectiveness Endpoint: ......................................................................................................... 77 
19.8 
ANALYSES TO BE CONDUCTED. ............................................................................................................................ 78 
19.8.1 Primary Safety Endpoint ......................................................................................................................... 78 
19.8.2 Primary Effectiveness Endpoint .............................................................................................................. 78 
19.8.3 Secondary Effectiveness Endpoint .......................................................................................................... 78 
19.8.4 Subgroup Analyses ................................................................................................................................. 79 
19.8.5 Additional Endpoint Analyses ................................................................................................................. 79 
19.9 
HANDLING OF MISSING DATA ............................................................................................................................ 81 
20 
ETHICS AND PROTECTION OF HUMAN SUBJECTS ......................................................................................... 81 
20.1 
ETHICAL STANDARD .......................................................................................................................................... 81 
20.2 
INFORMED CONSENT PROCESS ........................................................................................................................... 82 
20.2.1 Informed Consent Procedure and Documentation ................................................................................. 82 
20.3 
PARTICIPANT AND DATA CONFIDENTIALITY ............................................................................................................ 83 
20.3.1 Research Use of Stored Data .................................................................................................................. 83 
21 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .......................................................... 83 
22 
QUALITY ASSURANCE AND QUALITY CONTROL ........................................................................................... 84 
23 
DATA HANDLING AND RECORD KEEPING .................................................................................................... 84 
23.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITY .......................................................................................... 84 
23.1.1 Data Collection ....................................................................................................................................... 85 
23.1.2 Data Reporting ....................................................................................................................................... 85 
23.1.3 Data Verification and Review ................................................................................................................. 85 
23.1.4 Final Data Analysis ................................................................................................................................. 86 
23.2 
STUDY RECORD RETENTION AND ARCHIVING ......................................................................................................... 86 
24 
STUDY SUSPENSION OR TERMINATION ...................................................................................................... 86 
25 
STUDY COMPLETION .................................................................................................................................. 87 
26 
DATA AND PUBLICATION POLICY ................................................................................................................ 87 
27 
DOCUMENT FILING ..................................................................................................................................... 87 
28 
SCIENTIFIC REFERENCES .............................................................................................................................. 88 
29 
APPENDIX 1................................................................................................................................................ 92 
30 
APPENDIX 2................................................................................................................................................ 93 
 
 
 
 

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FIGURE 1: PICTURE OF THE GENERATOR CONSOLE ....................................................................................................... 40 
FIGURE 2: PICTURE OF THE OMNYPULSE™ BI-DIRECTIONAL CATHETER ....................................................................... 41 
FIGURE 3: CONNECTIVITY DIAGRAM (FRONT VIEW) FOR SYSTEM SET-UP .................................................................... 44 
FIGURE 4: CONNECTIVITY DIAGRAM (BACK VIEW) FOR SYSTEM SET-UP ...................................................................... 44 
FIGURE 5: VISITAG™ SETTINGS  ...................................................................................................................................... 51 
 
 
TABLE 1: SUBJECT TREATMENT AND FOLLOW-UP SCHEDULE ....................................................................................... 18 
TABLE 2: REQUIRED STUDY DEVICES .............................................................................................................................. 42 
TABLE 3: RECOMMENDED FLOW SETTINGS ……………………………………………………………………………………………………………..49 
TABLE 4: SUMMARY OF SUBJECT VISITS AND ASSESSMENTS ........................................................................................ 57 
TABLE 5: PRIMARY ADVERSE EVENTS ............................................................................................................................ 60 
TABLE 6: INTENSITY OR SEVERITY DEFINITIONS ............................................................................................................. 64 
TABLE 7: ADVERSE EVENT CAUSALITY CLASSIFICATIONS (REF. MDCG 2020-10/1 GUIDANCE) ..................................... 64 
TABLE 8: ADVERSE EVENT OUTCOME CLASSIFICATIONS ............................................................................................... 66 
TABLE 9: THE INCIDENCE OF THE COMPLICATIONS OF AF ABLATION ........................................................................... 66 
TABLE 10: AE REPORTING REQUIREMENTS ................................................................................................................... 68 
TABLE 11: RESPONSIBILITIES FOR PREPARING AND SUBMITTING REPORTS ................................................................. 85 
TABLE 12: COMPREHENSIVE LIST OF ANTICIPATED ADVERSE EVENTS .......................................................................... 93 
 
 

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2 
List of Acronyms and Abbreviations 
Acronym/ 
Abbreviation 
Expanded Term 
AAD 
Antiarrhythmic Drug 
ACC/AHA 
American College of Cardiology/American Heart Association 
ACE 
Asymptomatic Cerebral Emboli 
ACL 
Advanced Catheter Location 
ACT 
Activated Clotting Time 
AE 
Adverse Event 
AEF 
Atrio Esophageal Fistula 
AF 
Atrial Fibrillation 
AFEQT 
Atrial Fibrillation Effect on Quality of Life 
AFL 
Atrial Flutter 
AT 
Atrial Tachycardia 
BWI 
Biosense Webster Inc. 
CA 
Competent Authority 
CABG 
Coronary Artery Bypass Graft 
CEC 
Clinical Events Committee 
CF 
Contact Force 
CHF 
Congestive Heart Failure 
CIP 
Clinical Investigation Plan 
CIV-ID 
Clinical Investigation - Identification 
COPD  
Chronic Obstructive Pulmonary Disease  
CPK 
Creatinine Phosphokinase 
CRF 
Case Report Form 
CRO 
Clinical Research Organization 
CS 
Coronary Sinus  
CIR 
Clinical Investigation Report 
CIU 
Connection Interface Unit 
CT 
Computed Tomography 
CTI 
Cavotricuspid Isthmus 
CVA 
Cerebrovascular Accident or Stroke 
DD 
Device Deficiency 
DMC  
Data Monitoring Committee  
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EDEL 
Endoscopically detected thermal esophageal lesion 
EE 
Esophageal Endoscopy 
EHRA AF 
European Heart Rhythm Association Atrial Fibrillation 

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Acronym/ 
Abbreviation 
Expanded Term 
EMEA 
Europe, Middle East and Africa 
EP 
Electrophysiology 
ESC 
European Society of Cardiology 
FAM  
Fast Anatomical Mapping  
FDA 
Food and Drug Administration 
Fr 
French 
FU 
Follow-Up 
GCP 
Good Clinical Practices 
GERD  
Gastroesophageal Reflux Disease  
HM 
Holter Monitoring 
HRS/EHRA/ECAS 
Heart Rhythm Society / European Heart Rhythm Association / European 
Cardiac Arrhythmia Society 
IB 
Investigator Brochure 
ICE 
Intracardiac Echocardiography 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IFU 
Instruction for Use 
IRE 
Irreversible Electroporation 
ITT 
Intention to Treat 
LA 
Left Atrium 
LBBB 
Left Bundle Branch Block 
LV 
Left Ventricle 
LVEF 
Left Ventricular Ejection Fraction 
MDD 
Medical Device Directive 
MDR 
Medical Device Regulation 
MI 
Myocardial Infarction 
mITT 
Modified Intent to Treat 
MMSE 
Mini Mental State Examination 
MRA 
Magnetic Resonance Angiogram 
MRI 
Magnetic Resonance Imaging 
mRS 
Modified Rankin Scale 
NA 
Neurological Assessment  
NIHSS 
National Institute of Health Stroke Scale 
NYHA 
New York Heart Association 
PAF 
Paroxysmal Atrial Fibrillation 
PCI 
Percutaneous Coronary Intervention 
PFA 
Pulsed Field Ablation 
PF energy 
Pulsed Electric Field Energy 
PI 
Principal Investigator 
PN 
Phrenic Nerve 

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Acronym/ 
Abbreviation 
Expanded Term 
PNP 
Phrenic Nerve Paralysis 
PP 
Per Protocol 
PPI 
Proton Pump Inhibitors 
PsAF 
Persistent Atrial Fibrillation 
PV 
Pulmonary Vein 
PVI 
Pulmonary Vein Isolation 
QA 
Quality Assurance 
QC 
Quality Control 
QoL 
Quality of Life 
RF  
Radiofrequency  
RV 
Right Ventricle 
SADE  
Serious Adverse Device Effect  
SAE  
Serious Adverse Event  
SAP 
Statistical Analysis Plan 
SDV  
Source Data Verification  
SOC 
Standard Of Care 
SP  
Safety Population  
STSF 
THERMOCOOL SMARTTOUCH Surroundflow 
SVC 
Superior Vena Cava 
TEE 
Transesophageal Echocardiography 
TIA 
Transient Ischemic Attack 
TRUEref 
Tightly Referenced Unipolar Electrode reference  
TS 
Transseptal 
TTE 
Transthoracic Echocardiography 
UM 
User Manual 
USADE 
Unanticipated Serious Adverse Device Effect 

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3 
Key Roles and Responsible Parties 
SPONSOR:   
Cardiovascular & Specialty Solutions (CSS) 
Biosense Webster Inc., part of the Johnson & Johnson family of companies 
31 Technology Drive, Suite 200 
 Irvine, CA 92618 - USA 
Tel: +1 800-729-9010 
 
The Sponsor will finance the study, and a clinical trial agreement (CTA) will manage the relationship 
between the sponsor, the investigator and the institution. Including but not limited to description and 
acknowledgment of responsibilities, terms of collaboration, indemnification, requirements for 
payment, publication and intellectual property terms and guidelines for dispute resolution. 
 
CONTACTS:   
Clinical Research Manager, EMEA 
 
Johnson & Johnson Medical NV  
Leonardo Da Vincilaan 15 
1831 Diegem, Belgium 
Tel: 
 
E-mail: 
 
 
Senior Director of Preclinical Research, Medical Affairs 
 
31 Technology Drive, Suite 200  
Irvine, CA 92618 - USA 
Tel : 
 
E-mail : 
 
 
Senior Director Clinical Research BW, EMEA 
Authorized Legal Representative 
 
Johnson & Johnson Medical NV  
Leonardo Da Vincilaan 15 
1831 Diegem - Belgium 
Tel: 
 
E-mail: 
 
 
Whereas the Clinical Investigation is sponsored by Biosense Webster Inc., Johnson and Johnson 
Medical NV/SA with registered offices at Leonardo Da Vincilaan 15, 1831 Diegem, Belgium, has 
been duly appointed by the Sponsor to conduct the Clinical Investigation on its behalf. 
 
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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The sponsor maintains an updated list of Principal Investigators (PIs), the coordinating investigator 
(if appointed), address details of each investigational site, emergency contact details for the PI’s at 
each site, roles and responsibilities and qualifications of each respective investigator, institutions, 
core labs (if applicable) and Contract Research Organizations (if applicable). The definitive list shall 
be integrated into the clinical investigation report. 
 
The current clinical investigation plan has been developed based on regulations applicable in 
Europe. For countries outside Europe, a country specific version of this clinical investigation plan 
may be developed, further defining regional regulations, if applicable. 
 
 

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Assessment (NA) subset, a Cardiac Computed Tomography (CT) or Magnetic 
Resonance Angiogram (MRA) image subset, an Esophageal Endoscopy (EE) subset 
and a Pulmonary Vein Isolation (PVI) durability subset in a prospective manner. 
These subsets are intended to delineate safety and assess lesion durability at 2-3 
months following ablation.  The same subjects will participate in all four (4) subsets.  
 
All subjects will be followed for 12 months and scheduled for evaluation at 7 days, 
1-, 3-, 6- and 12-month following index ablation procedure. 
 
Study Population 
Patients scheduled to have a clinically indicated ablation procedure for the 
management of their PAF. 
 
Geographic areas 
to be included 
Up to 14 sites in Europe and Canada. 
Anticipated 
Study Timeline  
Estimated 20-22 months total study duration: 
- 
Enrollment: Approximately 8-10 months 
- 
Primary endpoint evaluation: 3 months post procedure 
- 
Effectiveness evaluation: 12-months post procedure 
 
Procedure(s) 
description 
Subjects will arrive at the electrophysiology (EP) laboratory for their ablation 
procedure and will undergo preparation for the procedure per the hospital’s 
standard protocol (discretion of investigator). 
 
The AF ablation procedure will follow below sequence: 
 
1. 
Anatomical mapping of the Left Atrium (LA). 
2. 
Pulmonary Vein (PV) Isolation with PF energy using the study catheter 
and generator. 
3. 
Confirmation of PV Isolation (entrance block) with 
adenosine/isoproterenol challenge. 
4. 
If necessary, treatment of acute reconnections with additional 
applications of PF energy. 
5. 
Confirmation of entrance block of all targeted PVs at the end of 
procedure. 
 
All subjects will undergo PV ablation with the investigational device until PVI is 
achieved and confirmed via entrance block. If PVI cannot be achieved with the 
investigational device, a commercially approved Biosense Webster (RF) catheter and 
compatible commercially available RF generator can be used to complete the 
procedure.   
 
A right atrial Cavotricuspid Isthmus (CTI) linear ablation is allowed only in cases with 
documented typical atrial flutter (AFL) either prior to or during the index ablation 
procedure. The CTI line should be completed with a commercially approved and 
compatible Biosense Webster (RF) catheter and (RF) generator.   
 
Major Objective 
The major objective of this clinical investigation is to demonstrate safety and 
effectiveness of the ablation system (OMNYPULSE™ Bi-Directional Catheter and 
TRUPULSE™ Generator) when used for isolation of the atrial PVs in treatment of 
subjects with PAF.  

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Acute safety and acute effectiveness will be evaluated through hypothesized 
primary endpoints and 12-month effectiveness will be evaluated through a 
hypothesized secondary endpoint. 
Additional 
objectives 
The additional objectives of this clinical investigation are to evaluate procedural 
data, quality of life and the incidence of (procedure and/or device related) serious 
adverse events during and after index ablation procedure up to 12 months.   
Primary  
Hypothesized 
Endpoints 
 Safety 
The primary safety endpoint is the occurrence of Primary Adverse Events (PAEs) 
within seven (7) days of the index ablation procedure where the investigational 
OMNYPULSE™ Bi-Directional Catheter and TRUPULSE™ Generator are used per 
clinical investigation plan.  
PAEs include the following Adverse Events (AEs): 
Atrio-Esophageal Fistula* 
Phrenic Nerve Paralysis  
Cardiac Tamponade/perforation** 
Pulmonary Vein Stenosis* 
Device or procedure related death* 
Stroke/Cerebrovascular Accident (CVA) 
Major Vascular Access 
Complication/Bleeding 
Thromboembolism 
Myocardial Infarction 
Transient Ischemic Attack (TIA) 
Pericarditis 
Heart Block 
Pulmonary Edema (Respiratory 
Insufficiency) 
Vagal Nerve Injury/Gastroparesis 
* Device or procedure related death, pulmonary vein stenosis and atrio-esophageal fistula 
that occur greater than one week (7 days) and less than or equal to 90 days post-
procedure are considered and analyzed as PAEs. 
** Cardiac Tamponade/Perforation occurring up to 30 days post AF ablation process 
procedure will be considered a PAE. 
 
Acute Effectiveness 
The acute effectiveness endpoint is the electrical isolation of clinically relevant 
targeted PVs which is evidenced by confirmation of entrance block after 
adenosine/isoproterenol challenge at the end of the index ablation procedure. Use 
of a non-study device to achieve PVI is considered an acute procedural failure. 
 
Secondary 
Hypothesized 
Endpoint 
12-month Effectiveness 
Freedom from documented (symptomatic and asymptomatic) atrial arrhythmia 
(Atrial Fibrillation (AF), Atrial Tachycardia (AT) or Atrial Flutter (AFL) of unknown 
origin*) episodes based on electrocardiographic data (≥30 seconds on arrhythmia 
monitoring device) during the effectiveness evaluation period (day 91-day 365) on 
or off antiarrhythmic therapy. Acute procedural failure (i.e., failure to achieve 
entrance block with the study device in any of the clinically relevant targeted PVs) 
will also be deemed a 12- month effectiveness failure. 
 
*AFL of unknown origin is defined as all AFL except those CTI dependent AFL as 
confirmed by 12-lead electrocardiogram (ECG) or entrainment maneuvers in an EP 
study. 
 
Additional 
Effectiveness 
Endpoints 
• 
PVI Durability (for PVI Durability Subset) 
- 
Sustained isolations of PVs that are targeted in the index ablation 
procedure, which is evidenced by the confirmation of isolation via the 

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electroanatomical mapping 75 days (+/- 15 days) post index ablation 
procedure. 
• 
Single Procedural Success: defined as freedom from documented symptomatic 
atrial arrhythmia (AF, AT or AFL of unknown origin*) episodes based on 
electrocardiographic data (≥30 seconds on arrhythmia monitoring device) 
during the effectiveness evaluation period (day 91-day 365) following a single 
index ablation procedure.   
• 
Freedom from documented symptomatic atrial arrhythmia (AF, AT or AFL of 
unknown origin*) episodes based on electrocardiographic data (≥30 seconds on 
arrhythmia monitoring device) during the effectiveness evaluation period (day 
91-day 365). Acute procedure failure will also be considered failure of the 12-
month symptomatic recurrence free endpoint.  
• 
Freedom from documented (symptomatic and asymptomatic) atrial 
arrhythmia (AF, AT or AFL of unknown origin*) episodes based on 
electrocardiographic data (≥30 seconds on arrhythmia monitoring device) 
during the effectiveness evaluation period (day 91-day 365) with extra failure 
modes. A subject who meets any of the following criteria will also be deemed 
an effectiveness failure:  
- 
Failure to achieve acute procedural success.  
- 
Taking a new Antiarrhythmic Drug (AAD) (Class I / Class III) for atrial 
tachyarrhythmia (AF, AT or AFL of unknown origin*) or taking a 
previously failed Class I/III AAD at a greater than the highest ineffective 
historical dose for AF/AFL/AT during the effectiveness evaluation period 
(day of 3-month visit – day 365). 
- 
Greater than 1 repeat ablation for AF/AT or AFL of unknown origin in 
the blanking period or any repeat ablation for AF/AT or AFL of unknown 
origin* during the effectiveness evaluation period. 
• 
Use of a non-study device for the purpose of  
- 
PVI (i.e., touch-up) among all clinically relevant targeted PVs during the 
index procedure.   
- 
Ablation of left atrial non-PV AF targets (i.e., posterior wall) during 
index ablation procedure or for repeat procedures during blanking 
period. 
• 
Acute reconnection identified by adenosine/isoproterenol challenge among all 
clinically relevant targeted PVs.  
• 
Repeat ablation procedures for left atrial arrhythmia (AF, AT or AFL of 
unknown origin*) within the 12-month FU period. 
• 
Quality of Life (QoL): the change of QoL assessed by comparing the Atrial 
Fibrillation Effect on Quality-of-Life (AFEQT™) scores before and at 3, 6 and 12- 
months after the ablation procedure. 
• 
Hospitalization for cardiovascular events through 12 months follow-up 
compared to 12 months prior to baseline.  
 
*AFL of unknown origin is defined as all AFL except those CTI dependent AFL as 
confirmed by 12-lead electrocardiogram (ECG) or entrainment maneuvers in an EP 
study. 
 
Additional 
Safety 
Endpoints  
Safety  
- 
Occurrence of Serious Adverse Device Effects (SADEs) 
- 
Occurrence of Unanticipated Serious Adverse Device Effects (USADEs) 

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Total Sample size: 
 
the roll-in phase is anticipated to 
be 30-50 subjects. A total of 135 evaluable subjects will be included in the main 
study. Each of the four (4) subsets (NA, CT/MRA, EE and PVI durability) will consist 
of 30 subjects and will be integrated within the main study.   
 
Inclusion Criteria 
1. Diagnosed with Symptomatic Paroxysmal AF defined as AF that terminates 
spontaneously or with intervention within 7 days of onset. This PAF is 
considered to be symptomatic if symptoms related to AF are experienced by 
the patient.  
2. Selected for AF ablation procedure by PVI. 
3. Age 18 -75 years.  
4. Willing and capable of providing consent. 
5. Able and willing to comply with all pre-, post-, and follow-up testing and 
requirements. 
Exclusion Criteria 
1. Previously known AF secondary to electrolyte imbalance, thyroid disease, or 
reversible or non-cardiac cause (e.g., documented obstructive sleep apnea, 
acute alcohol toxicity, morbid obesity (Body Mass Index >40 kg/m²), renal 
insufficiency (with an estimated creatinine clearance < 30 mL/min/1.73 m2), 
…). 
2. Previous LA ablation or surgery. 
3. Patients known to require ablation outside the PV region (e.g., atrioventricular 
reentrant tachycardia, atrioventricular nodal re-entry tachycardia, atrial 
tachycardia, ventricular tachycardia and Wolff-Parkinson-White).  
4. Previously diagnosed with persistent AF (> 7 days in duration). 
5. Severe dilatation of the LA (LAD >50mm antero-posterior diameter in case of 
Transthoracic Echocardiography (TTE)). 
6. Presence of LA thrombus.  
7. Severely compromised Left Ventricular Ejection Fraction (LVEF <40%). 
8. Uncontrolled heart failure or New York Heart Association (NYHA) Class III or IV.  
9. History of blood clotting, bleeding abnormalities or contraindication to 
anticoagulation (heparin, warfarin, or dabigatran). 
10. History of a documented thromboembolic event (including TIA) within the past 
6 months.  
11. Previous Percutaneous Coronary Intervention (PCI) / Myocardial Infarction 
(MI) within the past 2 months. 
12. Previous Coronary Artery Bypass Grafting (CABG) in conjunction with valvular 
surgery, cardiac surgery (e.g., ventriculotomy, atriotomy) or valvular cardiac 
(surgical or percutaneous) procedure. 
13. Unstable angina pectoris within the past 6 months. 
14. Anticipated cardiac transplantation, cardiac surgery, or other major surgery 
within the next 12 months. 
15. Significant pulmonary disease (e.g., restrictive pulmonary disease, constrictive 
or chronic obstructive pulmonary disease) or any other disease or malfunction 
of the lungs or respiratory system that produces severe chronic symptoms. 
CCI
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16. Known significant PV anomaly that in the opinion of the investigator would 
preclude enrollment in this study. 
17. Prior diagnosis of pulmonary vein stenosis. 
18. Pre-existing hemi diaphragmatic paralysis. 
19. Acute illness, active systemic infection, or sepsis. 
20. Presence of intracardiac thrombus, myxoma, tumor, interatrial baffle or patch 
or other abnormality that precludes catheter introduction or manipulation. 
21. Severe mitral regurgitation.  
22. Presence of implanted pacemaker or Implantable Cardioverter-Defibrillator 
(ICD) or other implanted metal cardiac device that may interfere with the 
pulsed electric field energy. 
23. Presence of a condition that precludes vascular access (such as inferior vena 
cava (IVC) filter). 
24. Significant congenital anomaly or a medical problem that in the opinion of the 
investigator would preclude enrollment in this study. 
25. Categorized as vulnerable population and requires special treatment with 
respect to safeguards of well-being. 
26. Current enrollment in an investigational study evaluating another device or 
drug. 
27. Women who are pregnant (as evidenced by pregnancy test if pre-
menopausal), lactating, or who are of child-bearing age and plan on becoming 
pregnant during the course of the clinical investigation. 
28. Life expectancy less than 12 months. 
29. Presenting contra-indications for the devices used in the study, as indicated in 
the respective Instructions For Use (IFU). 
 
Additional exclusion criteria for Neurological Assessment (NA) subjects: 
30. Known contraindication for MRI such as use of contrast agents due to 
advanced renal disease, claustrophobia etc. (at PI discretion)  
31. Presence of iron-containing metal fragments in the body  
32. Known unresolved pre-existing neurological deficit. 
 
Additional exclusion criteria for Esophageal Endoscopy (EE) subjects: 
33. Known uncontrolled significant Gastroesophageal Reflux Disease (GERD) 
 
Statistical 
Analysis  
 
Primary Safety Endpoint:   
The primary adverse event rate will be compared to a pre-specified threshold of 
12%.   
𝐻𝐻0: PS ≥ 0.12 vs. 𝐻𝐻𝐴𝐴: PS < 0.12, 
where PS denotes the rate of primary adverse event 
 
An exact binomial test will be performed to compare the PAE rate against the 
performance goal of 12%. The analysis will be performed in the modified Intent To 
Treat (mITT) analysis set. 
 
 
 
Primary Effectiveness Endpoint:   

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The acute effectiveness success rate of confirmation of entrance block of all 
targeted PVs at the end of the index ablation procedure will be compared to a pre-
specified threshold of 90%.  
 
𝐻𝐻0: PE ≤ 0.90 vs. 𝐻𝐻𝐴𝐴: PE > 0.90, 
where PE denotes the rate of acute effectiveness success. 
 
An exact binomial test will be performed to compare acute effectiveness success 
rate against the performance goal of 90%. The analysis will be performed in the Per 
Protocol (PP) analysis set. 
 
Secondary Effectiveness Endpoint: 
The rate of effectiveness success at 12 months, will be compared to a pre-specified 
threshold of 50%. 
 
𝐻𝐻0: P1 ≤ 0.50 vs. 𝐻𝐻𝐴𝐴: P1 > 0.50, 
where P1 denotes the proportion of freedom from primary effectiveness failures at 12 
months post the initial ablation procedure 
 
The 12-Month effectiveness endpoint will be evaluated using the Kaplan-Meier 
estimate. The proportion for freedom from effectiveness failure events at 12-
month, along with the two-sided 95% confidence interval, will be estimated. The 
lower bound of the two-sided 95% confidence interval confidence interval will be 
compared to the performance goal of 50%. The analysis will be performed in the PP 
analysis set. 
 
If study success is achieved based on the primary endpoint analyses results, then 
the hypotheses testing of the secondary endpoint analyses will be performed with 
full follow-up data. 
 
Primary Endpoint 
Analysis 
A primary endpoint analysis will be performed when all subjects completed their 3-
month follow-up. This primary endpoint analysis report will be part of the CE mark 
application dossier. 
 
Independent 
Committees/Revi
ewers 
A Data Monitoring Committee (DMC) and Clinical Events Committee (CEC) will be 
established for this study. 
 
- 
DMC will assess clinical safety data on regular intervals and make 
recommendations on study adaptations. 
- 
CEC will adjudicate primary safety endpoint events.  
 
Independent Core Laboratories will conduct objective evaluations of remote 
arrhythmia monitoring and ECG tracings for presence of atrial arrhythmia and will 
perform an independent analysis of collected images (Cerebral MRI, Endoscopy, 
CT/MRA) for evaluation of safety.  
 
Time and Events 
Schedule 
See  
Table 1 below 
 
Table 1: Subject Treatment and Follow-up Schedule 

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11. AEs must be collected from the time the subject signs the informed consent onward.  
12. Patient questionnaires will only be used in countries with validated languages. 
13. For all subjects: CT/MRA to be completed within 6 months prior to the index ablation procedure. Post procedure: for 
CT/MRA subset to be repeated at 3M FU, for all subjects CT/MRA to be repeated post procedure in case subject 
presents with PV stenosis symptoms. 
14. For PV Durability subset: an electro anatomical map, activation and voltage map is to be performed during the index 
ablation procedure (pre and post ablation) and to be repeated at 75 days post procedure (+/- 15 days). 
15. For Endoscopy subset: Endoscopy preferable between 1 day to 3 days (72hours) post procedure. For procedures on 
Friday a window of a maximum of 96 hours is justified.  
16. If observations are noted on the post-procedure MRI, the subject must have follow-up MRI at the next follow-up 
visit(s) until observations are resolved. 
17. A certified/qualified physician expert must perform neurologic exams at pre-and post-ablation and possibly at other 
follow-up visits, pending previous findings of micro-emboli/neurologic deficits. 
18. To be completed within 72-hours pre-procedure. For procedures on Monday a window of a maximum of 96 hours is 
justified. 
19. To be completed within 72-hours post-procedure. For procedures on Friday a window of a maximum of 96 hours is 
justified. 
20. Full neurological follow-up to be undertaken if neurologic symptoms and/or cerebral ischemic lesions identified in a 
prior evaluation.  
21. If subject returns for a potential study related cardiovascular or neurological visit outside of the CIP-defined visit 
schedule as deemed required per investigators discretion. 
22. Assessments should not be repeated for the study if already done per standard of care within CIP defined time limits. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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5 
Background Information and Scientific Rationale 
5.1 
Background Information 
Atrial Fibrillation (AF) is the most common sustained arrhythmia in humans.  It affects anywhere from 
0.4% to 1% of the general population, and increases in prevalence with age to approximately 8% in 
patients over 80 years of age.1, 2 The primary clinical benefit of AF ablation is improvement in Quality 
of Life (QoL) resulting from the elimination of arrhythmia-related symptoms such as palpitations, 
fatigue, or effort intolerance. In recognition of this, the elimination of symptomatic atrial arrhythmias 
was recommended by the 2017 HRS/EHRA/ECAS Consensus on Catheter and Surgical Ablation of Atrial 
Fibrillation.3 The opinion of the ESC as expressed in their 2020 AF Management Guidelines is that 
“Catheter ablation of symptomatic Paroxysmal Atrial Fibrillation (PAF) is recommended to improve AF 
symptoms in patients who have symptomatic recurrences of AF on Antiarrhythmic Drug (AAD) therapy 
and who prefer further rhythm control therapy, when performed by an electrophysiologist who has 
received appropriate training and is performing the procedure in an experienced center.”1, 4, 5  
 
The 2017 HRS/EHRA/ECAS consensus statement states that electrical isolation of the Pulmonary Veins 
(PVs) from the Left Atrium (LA) is the “cornerstone for most AF ablation procedures” and that 
“complete electrical isolation of all PVs should be the goal.3 Point-by-point ablation with 
radiofrequency (RF) catheters has provided positive results for treating many types of supraventricular 
arrhythmias6, 7, including PAF.6-12  
 
Multiple studies have shown that a contact force (CF) guided ablation protocol aiming to enclose the 
veins with stable, contiguous and optimized RF lesions is associated with a high incidence of successful 
PVI, high single-procedure arrhythmia-free survival at 1 year, marked reduction in arrhythmia burden, 
and a high likelihood of finding four isolated veins at repeat ablation.13, 14 Contact-Force catheters (e.g. 
the Biosense Webster THERMOCOOL SMARTTOUCH™ SF) provide real-time measurement of CF 
between the catheter tip and heart wall, as well as location information, when used with the CARTO™ 
3 Navigation System and have been associated with increased acute and long-term procedural success 
in the paroxysmal AF population. 
 
Most of the catheter ablation systems are thermal energy-based and use either heat or cold energy 
to destroy arrhythmogenic tissues. The ablation has been connected with arrhythmia recurrences due 
to incomplete lesion creation. It is also associated with severe complications such as pulmonary vein 
(PV) stenosis, phrenic nerve damage, coronary artery damage, atrio-esophageal fistula, steam pop, 
cardiac perforation and pericardial tamponade.3, 15, 16 
 
In the past decades, extensive research on alternative energy forms for ablation has been conducted 
to improve ablation efficiencies and reduce ablation-related complications. One of the new 
technologies for lesion creation is based on electroporation by pulsed field (PF) ablation. 
Electroporation is a process in which an electric field is applied to the cell/tissue for a short period of 
time that results in pore formation in the cell membrane and a subsequent increase in cell 
permeability.17 The electric field strength and duration could cause reversible or irreversible 
permeabilizations.18 At low electric field strength and a short duration, the cell membrane forms 
nanosized pores, allowing small or medium sized molecules, such as drug and DNA, flow across the 
lipid bilayer. The pore formation is transient and reversible. The affected cells are able to survive from 
this reversible electroporation. At medium electric field strengths, the density of pore formation in 
the membrane increases to a certain level such that the process becomes irreversible. Free flows of 
water and ions in and out of the cell membrane result in the loss of cellular homeostasis, ultimately 
triggering cell apoptosis.  
 

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This irreversible aspect of the process is called “irreversible electroporation” or IRE.15, 17 Finally, at high 
electric field strengths, the cell membrane quickly undergoes fragmentation resulting in necrotic cell 
death.17  
 
The PFA system generally consists of an electric field generator and electric current applicators. The 
electric field required for IRE  can be delivered by applying a high voltage or direct current (DC) across 
electrodes in contact with cardiac tissues.17 Different kinds of electric currents, such as DC, alternate 
current (AC), pulsed DC, or a combination of these were used to generate the electric field for IRE in 
preclinical and clinical studies.19 Pulsed DC was the most commonly used energy source in preclinical 
and clinical studies.20, 21 Early studies found that the strength of the electric field delivered by pulsed 
DC is dictated by pulse shape, pulse duration, pulse height, pulse polarity, pulse interval, number of 
pulses per application or pulse train, number of pulse trains delivered, and interval between pulse 
train deliveries.17, 18, 22  
 
The influence of PF energy on adjacent structures has been previously studied. Of the well described 
complications in RF ablation techniques, the tissue specificity of IRE has been considered as a major 
advantage.23 The IRE effect on the phrenic nerve has been described to be recoverable , suggesting 
that permanent damage can be avoided with IRE.24-27 A rare but dangerous complication of RF 
ablation, namely development of lethal Atrio-Esophageal Fistula (AEF), might be minimized with IRE 
as it’s suggestive that the risk with IRE would only be limited to the muscular layer of the esophagus.28 
 
5.2 
Previous Experience with the OMNYPULSE™ Catheter 
5.2.1 
Pre-Clinical Experience with the OMNYPULSE™ Catheter and TRUPULSE™ Generator 
Bench and animal testing was performed using the OMNYPULSE™ Catheter and TRUPULSE™ 
Generator. The animal testing validates the use of the OMNYPULSE™ Catheter and TRUPULSE™ 
Generator at the targeted ablation locations and met the acceptance criteria of safety and efficacy 
assessment. Refer to the Investigator Brochure (IB) for detailed description and outcomes of the 
testing performed.  
 
5.2.2 
Previous Clinical Evaluations with the TRUPULSE™ Generator    
The TRUPULSE™ Generator is capable of controlling the delivery of Pulsed Field (PF) and 
Radiofrequency (RF) energy to the THERMOCOOL SMARTTOUCH TM SF Catheter and the delivery of PF 
energy to the OMNYPULSE™ Catheter.  The TRUPULSE™ Generator to support the OMNYPULSE™ 
Catheter in this clinical investigation is a modified version of the TRUPULSE™ Generator that is used 
in the SmartfIRE clinical investigation.   
 
Safety and Effectiveness Evaluation of the THERMOCOOL SMARTTOUCH™ SF Catheter with the 
TRUPULSE™ Generator for treatment of Paroxysmal Atrial Fibrillation (PAF), the SmartfIRE clinical 
study (BW202202). 
 
The ‘SmartfIRE’ clinical study (CIV-22-11-041528, NCT05752487) is a prospective, single arm, multi-
center, pre-market clinical evaluation utilizing the THERMOCOOL SMARTTOUCH™ SF (STSF) Catheter 
and the TRUPULSE™ Generator. The objective of the clinical investigation is to demonstrate safety and 
effectiveness of the ablation system (THERMOCOOL SMARTTOUCH™ SF (STSF) Catheter and the 
TRUPULSE™ Generator) in the isolation of atrial pulmonary veins in treatment of symptomatic 
paroxysmal atrial fibrillation. This study is conducted in Europe. Enrollment commenced on 27th 
February 2023 in Europe and is currently ongoing.    

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5.3 
Rationale for Design of the Clinical Investigation 
The Sponsor has carefully considered the most appropriate study design for the assessment of the IRE 
Ablation system.  The 2017 HRS/EHRA/ECAS Expert Consensus29 Statement on Catheter and Surgical 
Ablation of Atrial Fibrillation addressed the appropriateness and concerns of randomized control (non-
inferiority) studies– “…the possibility of a downward “creep” in acceptable effectiveness (if each 
device is numerically inferior but statistically equivalent to the prior comparator device).  In the future, 
we expect that devices designed to treat patients with symptomatic PAF might alternatively be 
evaluated in nonrandomized trials, comparing prespecified performance goals or objective 
performance criteria (OPC), if uniformly established and applied.” Similar concerns may be extended 
to the evaluation of safety given the rapid pace of technology development in this arena. This is 
balanced by the establishment of the treatment of PAF by catheter ablation as a safe procedure with 
pulmonary vein isolation (PVI) as the cornerstone of treatment.  
 
Data published from many recent prospective multi-center clinical trials30-33 for ablation devices 
demonstrate that the safety and effectiveness rates for similar primary endpoints are comparable 
across the varied technologies in a well-defined PAF patient population, further supporting acute PVI 
as a reliable treatment in reducing long-term recurrence of PAF. Accordingly, this study is designed to 
be multicenter and single arm with comparison to rigorously determined performance goals for both 
safety and effectiveness.  
 
The planned performance goal for 12-month effectiveness is 50%, based on the minimum chronic 
acceptable success rate for paroxysmal AF at 12-month follow-up as recommended in the 2017 
HRS/EHRA/ECAS Expert Consensus Statement29 on Catheter and Surgical Ablation of AF. Data from 
large multicenter pre- and post-market clinical trials of AF ablation devices which were published 
between 2014 to 2019 were reviewed as a first step to deriving the performance goal for the safety 
endpoint. A meta-analysis approach was taken to estimate the average composite endpoint rate. The 
following trials were reviewed: Fire & Ice30, Heartlight31, 34, TOCCASTAR32, ZERO-AF35, and SMART-AF33.  
These trials are representative of different catheter designs and energy sources. Since the definition 
of the safety composite varies across the studies reviewed, individual complication rates were 
reviewed and utilized to derive composite rates from each trial that are more closely aligned with the 
proposed primary safety composite endpoint definition. This clinical investigation is intended to 
characterize safety and effectiveness of the investigational devices in scope. The study is not designed 
to include a comparator/control group since it is not intended to prove superiority.  
 
5.4 
Potential Risk and Benefit 
The overall risks posed by use of the OMNYPULSE™ Bi-Directional Catheter, with the TRUPULSE™ 
Generator are expected to be comparable to those anticipated during routine use of radio frequency 
(RF) catheter ablation systems and use of AAD therapy according to current AF management 
guidelines and are mentioned below. The OMNYPULSE™ Bi-Directional Catheter IFU and TRUPULSE™ 
User Manual warn users of all potential risks associated with the use of PF energy, list all 
contraindications (i.e., myxoma, prosthetic valves, history of myocardial infarction, implanted (metal) 
device, active systemic infection, pregnancy), and provides the user with precautionary measures 
when using the devices for general risk mitigation. Additional specific mitigations are described with 
the associated risk below. 
 
 
 
 

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5.4.1 
Known Potential Risks and Mitigation 
Pericarditis: According to HRS guidelines 2017, the incidence of pericarditis incidence varies from 0%-
50% as a complication of AF ablation.  Pericarditis can occur due to mechanical or thermal irritation of 
the myocardium. This tends to be underreported as it is usually transient and resolves without invasive 
intervention.3 The risk for pericarditis will be further minimized by the use of PF energy, which is 
minimal thermal.   
 
Phrenic Nerve Palsy (PNP): Although injury to the Phrenic Nerve (PN) is rare for RF (<1%) and not 
expected with the PF energy provided,  stimulation of the phrenic nerve that resolves acutely has been 
noted in the literature.24 Prior to ablation in the region of the RSPV, investigators are encouraged to 
perform precautionary measures such as evaluation of proximity to the phrenic nerve and pacing 
maneuvers.3 Additionally, no new ablations should be delivered on or near the PN if evidence of PN 
impairment is observed and the catheter should be repositioned.  
 
Atrio-Esophageal Fistula (AEF): AEF is a rare (0.02%-0.11%)29 but catastrophic complication of AF 
ablation that can occur due to the anatomical proximity of the esophagus to the posterior wall of the 
LA and is associated with a high mortality rate.36 In patients, the application of traditional RF energy 
along the posterior LA can result in thermal injury to the esophagus and the formation of an AEF.3 As 
PF energy is non-thermal, AEF is not an expected outcome and has not been reported in literature to 
date .28, 37 Per CIP the risk will be minimized due to usage of, PF energy on the posterior wall. Many 
investigators attempt to mitigate esophageal damage by monitoring endoluminal temperature during 
the ablation procedure. 
 
Gastric Hypomotility and Periesophageal Vagal Nerve Injury:  Injury to the vagal anterior esophageal 
plexus can occur with traditional thermal energy such as RF energy being applied to the posterior wall 
of the LA, which can cause acute pyloric spasm and gastric hypomotility. Vagal injury is unlikely with 
PF ablation and has not been reported in published data to date. The risk for vagal nerve injury will be 
prevented by the PFA technology itself.  
 
Pulmonary vein stenosis: Pulmonary vein stenosis (PVS) is a well-known complication of thermal 
catheter ablation of atrial fibrillation. In RF procedures, the risk of PV stenosis is small (<1%)29. The risk 
of pulmonary stenosis associated with a pulsed field energy ablation procedure is expected to be 
unlikely and to date has not been reported following pulsed field applications. PVS can be prevented 
by delivering energy outside the pulmonary vein ostium and by using a wide circumferential 
technique. 
 
Thrombus formation: The incidence of thromboembolism associated with AF ablation is reported to 
be between 0% and 7%29. Thrombus generated during the ablation procedure may pose a serious and 
even life-threatening risk to the patient. Embolization of thrombus could produce stroke, Myocardial 
Infarction (MI), or other ischemic injury. The possible embolic sources include thrombus formation on 
the ablation catheter tip and sheath, debris from steam pop and charring, preexisting thrombus in the 
heart and air embolus. Thrombus could form due to temperature / impedance rise at the catheter-
tissue region, insufficient level of anti-coagulation or lack of irrigation. The study catheter is irrigated 
and irrigation settings per the catheter’s Instructions for Use should be maintained throughout the 
procedure. The CIP describes the pre-, peri- and -post procedural anticoagulation regimen to be 
followed. Imaging on the LA prior to the procedure to check on existing thrombus is a mandatory 
assessment in this CIP. These measurements in the CIP workflow should minimize the risk for 
thrombus formation.  
 
 

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Cardiac perforation/ Pericardial effusion/ Cardiac tamponade: Cardiac perforation may result from 
catheter manipulation or prolonged application of energy (risk is <1% for RF ablation and unknown for 
PF energy). Cardiac perforation may result in pericardial effusion or cardiac tamponade which requires 
percutaneous pericardial drainage or surgical repair.3  Cardiac tamponade is a known complication of 
AF ablation and has a reported incidence of 0.2%-5%29.  The occurrence of cardiac tamponade with PF 
technology is unknown. Physicians will be instructed to manipulate the catheter carefully in order to 
avoid cardiac damage (such as mitral valve incompetence, valve injury), perforation or tamponade. In 
addition, the amount of power and force at any one location should be limited.  
 
Cerebral ischemic lesions:  An Asymptomatic Cerebral Emboli (ACE) is defined as an occlusion of a 
blood vessel in the brain due to an embolus that does not result in any acute clinical symptoms and is 
therefore ‘silent’. Emboli can result from thrombus, gas, air, tissue, or fat. Source of micro-emboli 
include thrombi, which can develop on sheaths, materials, air introduction through sheath or during 
catheter exchange. Additionally, the hazard of microbubble formation in pulsed field ablation, leads 
to an unknown level of risk of ACE.38 According to HRS guidelines, 2017, incidence of ACE is expected 
in 2%-15% as a complication to AF ablation.3, 29 However, literature on asymptomatic cerebral lesions 
after existing ablation modalities for AF (RF, Cryo) reports large variations between publications with 
rates that range from 2-40%.3, 39-46 Recent publications on detection of asymptomatic brain lesions 
when using PF energy for AF ablation show a similar trend and present rates from 3-40%.47-50 With 
either energy modality, the risk of ACE will be minimized by implementing an anti-coagulation regimen 
prior to catheter introduction into the LA and during procedure to avoid thrombi/emboli. To minimize 
the risk of air introduction, investigators will be trained on proper sheath handling, including removing 
air bubbles prior to insertion and will be instructed to minimize catheter exchange during the 
procedure. 
  
Coronary Artery Spasm:  Limited clinical data publications raised the potential for complication of 
coronary arterial spasm during ablation near the coronary arteries.51-53  Coronary artery spasm may 
lead to coronary artery stenosis/occlusion, heart attack (ventricular tachycardia) and or chest pain.3, 
52, 54, 55  Energy application near the coronary arteries should be avoided to prevent coronary spasm. 
Administration of nitroglycerin, intravenous or intracoronary has been shown to be highly effective in 
attenuating the vasospasm.  In this CIP, PF energy will be used for Pulmonary Vein Isolation which is 
more remote from the coronary arteries and further reducing the risk for any coronary artery spasm. 
 
Heart block: The application of PF energy close to the atrioventricular (AV) node or HIS bundle could 
damage or destroy the normal AV conduction system, producing complete heart block and requiring 
implantation of a permanent pacemaker.  As per Instructions for Use, PF energy should not be used 
in close proximity to the AV node and extreme caution should be taken when delivering RF/PF energy 
in close proximity to the normal conduction system. The physician will be trained to closely monitor 
AV conduction during energy delivery and immediately terminate energy delivery if partial or 
complete AV block is observed, which will mitigate the risk for heart block.   
 
Vascular access / bleeding complication: Vascular access complication, femoral arteriovenous fistula, 
hematoma, and pseudoaneurysm are commonly reported in procedures requiring femoral access. 
Arterial or venous injury, including arterial dissection, thrombosis, occlusion or hemorrhage at the 
catheter insertion sites or at other sites along the vessels occur in rare circumstances (risk <1%). These 
types of injuries may cause hemorrhage, hematoma or ischemic injury to an extremity or major organ.  
Hemorrhage could occur as a result of anticoagulation (risk <0.5%), which may require transfusion.3 
The risk of vascular access complication can be minimized by using a compatible sheath, vascular 
access techniques, ultrasound-guided access and appropriate anticoagulation management.  
 
 

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Radiation exposure: Radiation exposure during the fluoroscopic imaging of the catheters may result 
in an increase in the lifetime risk of developing a fatal malignancy (0.1%) or a genetic defect in offspring 
(0.002%).56-58 The use of X-ray during the study procedure should be minimized or eliminated.   
 
Infection: The percutaneous procedure carries risk of infection, either at the catheter insertion site or 
systemically, including endocarditis and septic emboli (risk <0.5%).59, 60 Risk can be minimized by using 
standard aseptic technique and, when indicated, by the use of antibiotic agents.3 
 
Allergic, Anaphylactic and Toxic Reaction: A patient could develop an allergic reaction and/or 
inflammation due to the local anesthetic, sedatives, x-ray dye, heparin, protamine, or other agents 
administered during the procedure (risk <1%).58, 61-65  If an allergic reaction occurs, typical standard of 
care precautions should be taken. The product (s) should not be used where the packaging has been 
compromised, or already used, or reprocessed. 
 
Ventricular Tachycardia, Ventricular Fibrillation or other arrythmia: The literature suggests that in 
some instances PF energy could induce ventricular tachycardia, ventricular fibrillation (ventricular rate 
usually >300 bpm), or another arrythmia induced by vagal response.66-69 Vagal responses (VRs) such 
as brady cardia, sinus arrest, and atrioventricular block frequently occur, and are known to happen 
(0.1%-0.4%) with both RF and PF technologies.70-72 Vagal responses may be associated with 
simultaneous modification of intrinsic cardiac autonomic nervous system expression. Extreme vagal 
response resulting in prolonged asystole should be treated using clinical standards of care.  Risk for 
ventricular tachycardia has been minimized by the design of the catheter and generator, which uses 
bipolar energy with very short duration of pulses. Care should be taken to thoroughly monitor the 
patient’s ECG recordings throughout the procedure. Physicians will be instructed to be extra cautious 
when ablating near other anatomical structures such as ganglia. 
 
Muscular Nerve Injury: Pulse field ablations have been associated with muscular contraction in the 
literature.73, 74 These contractions can cause acute or post procedural patient discomfort. Patient 
comfort should be maintained through proper administration of pharmaceuticals and through local 
pain management standards of care.  
 
Hypervolemia/Fluid Overload: The study catheter is an irrigated catheter. Excessive use of irrigation 
could cause hemodynamic imbalance. The risk of hypervolemia will be mitigated when irrigation 
settings are used per its instructions for use.  
 
Risk due to Arcing: The hazard of arcing75 of energy creates a risk for patient injuries including cardiac 
arrest, burns, papillary muscle rupture, valve rupture, or cardiac perforation. To prevent such harms, 
the physician should use the catheter and generator per their intended directions for use. The 
likelihood for arcing has been mitigated by the specific design of the study devices. To further prevent 
the associated risks from arcing, do not operate the device in patients with metal cardiac implants or 
having metal in the same cardiac chamber with the ablation catheter. 
 
Pulmonary injury: Pulmonary injuries, such as pneumothorax, may be caused by thermal injury during 
traditional RF ablation.76 As PF is a minimally thermal modality, this injury is not expected to occur. 
However, to keep the risk of pulmonary injuries low, energy delivery should be halted after ECG signals 
have been sufficiently attenuated.3  
 
 
 
 
 

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In addition to the information in the IFU/UM and specific mitigation strategies for above mentioned 
potential risks, the criteria for subject selection, methods, personnel, facilities and training of the 
physicians are intended to minimize the risks to subjects undergoing this procedure.  
 
Appropriate measures have been outlined in this study protocol to minimize the risk to subjects, while 
still providing the possible benefits (including but not limited to safety/effectiveness) of the treatment 
options to be studied.  
 
Patient selection:  Subjects will be screened carefully prior to enrollment in the study to 
ensure compliance with the inclusion and exclusion criteria.  The exclusion criteria have been 
developed to exclude subjects with a medical history or condition that increases their risk of 
AEs (refer to section 8.2 for the Exclusion Criteria).77 
 
Pre-procedure 
imaging: 
Subjects 
must 
have 
a 
pre-procedure 
Transesophageal 
Echocardiogram (TEE) or other imaging technique to screen for the presence of LA thrombus, 
which is intended to decrease the potential for thromboembolic complications.   
 
Within procedure safeguards: Investigators highly skilled in intracardiac mapping and AF 
ablation with ablation catheters will be selected for participation in the study.  AF ablation 
procedures will be performed in EP laboratories with the assistance of skilled nurses and 
technicians. Ablating investigators will undergo training, prior to enrolling subjects (refer to 
section 17.1.1). 
 
Post-procedural management: In accordance with the 2020 ESC AF Management 
Guidelines78, all subjects will be recommended to be maintained on systemic oral 
anticoagulation therapy for at least two months post-procedure.  After two- months post-
procedure, a decision regarding continuation of systemic anti-coagulation agents will be 
based on the patient risk for thromboembolism. Systemic oral anticoagulation will be 
recommended to be continued beyond two-months post-ablation in patients with CHA2DS2-
VASc score ≥2. 
 
Safety data during enrollment and follow-up will be closely monitored and evaluated per the 
specific safety management plan for the study. Also, refer to safety section (section 14) for 
more information on safety management.   
 
DMC and CEC:  A Data Monitoring Committee (DMC) will assess subjects’ data for safety on 
regular intervals and make recommendations on study adaptations as described in the DMC 
Charter. A Clinical Events Committee (CEC) will adjudicate primary safety endpoint events. The 
CEC will operate as described in the CEC Charter. 
 
5.4.2 
Known Potential Benefits 
In patients with AF, elimination of or a reduction in symptoms is a major driving force for therapy. The 
primary clinical benefit of cardiac ablation of AF is an improvement in QoL resulting from the 
elimination of arrhythmia-related symptoms such as palpitations, fatigue, or effort intolerance.3  
 
 
 
 
 

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Published animal and human studies demonstrate the potential for PF to be a safe and efficacious way 
to deliver energy for ablation via a non-thermal ablative modality.38, 79 Influence on adjacent structures 
has been previously studied. The additional benefit of tissue selectivity of PF energy reduces the risk 
of collateral tissue injury38 Of the well described complications in RF ablation techniques, the tissue 
specificity of IRE has been considered as a major advantage.23  
 
The OMNYPULSE™ Bi-Directional Catheter is a large tip catheter with force-sensing technology that 
provides a real-time measurement of contact force (CF) between the catheter tip and the heart.   CF 
sensing technology include feedback to the user on tissue contact to prevent inappropriate energy 
applications and enhances efficient lesion formation.33, 80 Additional benefit of confirmed tissue 
contact includes efficient creation of 3D anatomical maps with the CARTO™ 3 system and may 
translate to reduction of mapping fluoroscopy and procedure time. 
 
In the base of the distal tip of the catheter there is a local unipolar reference electrode (TRUEref™ 
electrode) for enhanced clarity during sensing and electrogram recording in the CARTO™ 3 System. 
The use of the close unipolar electrode allows for enhanced mapping capabilities by removing 
additional far-field signals providing more localized information during mapping. 
 
The TRUPULSE™ Generator provides a novel approach for the treatment of cardiac arrythmias by using 
pulsed field (PF) energy to produce targeted intracardiac lesions and achieve the intended therapeutic 
effect. The novel investigational device system is intended to treat atrial fibrillation with the 
theoretical potential while minimizing thermal collateral damage.  
 
Further reference can be made to the Risk Management Documentation for more information. 
 
6 
Objectives and Purpose 
6.1 
Objective 
The major objective of this clinical investigation is to demonstrate safety and effectiveness of the 
OMNYPULSE™ Bi-Directional Catheter when used in conjunction with the Guiding Sheath and the 
TRUPULSE™ Generator for Pulmonary Vein Isolation (PVI) in the treatment of subjects with Paroxysmal 
Atrial Fibrillation (PAF).  
Specifically: 
- 
To demonstrate safety based on early-onset Primary Adverse Events (PAEs) (within 7 days 
following the ablation procedure). 
- 
To demonstrate the acute effectiveness based on the achievement of entrance block on 
targeted PVs. 
- 
To demonstrate 12-month effectiveness based on the freedom from documented 
(symptomatic and asymptomatic) atrial arrhythmia (Atrial Fibrillation (AF), Atrial Tachycardia 
(AT) or Atrial Flutter (AFL)) episodes based on electrocardiographic data (≥30 seconds on 
arrhythmia monitoring device) during the effectiveness evaluation period (day 91-day 365). 
 
Acute safety and acute effectiveness will be evaluated through hypothesized primary endpoints and 
12- month effectiveness will be evaluated through a hypothesized secondary endpoint. The results of 
the primary endpoint analysis will provide evidence to support CE-mark registration of these devices.  
 
 
 
 
 

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6.2 
Additional Objective 
The additional objectives of this study are to evaluate procedural data, quality of life and the incidence 
of (procedure and/or device related) serious adverse events during and after procedure up to 12 
months.  
 
7 
Study design and Endpoints 
7.1 
Description of the Study Design 
The study will be carried out as an interventional, prospective, multicenter, single-arm safety and 
effectiveness evaluation using the OMNYPULSE™ Bi-Directional Catheter in conjunction with the 
guiding sheath and the TRUPULSE™ Generator.  
 
The study will enroll subjects with symptomatic PAF who are candidates for catheter ablation.   
Subjects who sign the Informed Consent Form (ICF) and who meet all eligibility criteria will be enrolled 
and treated with the OMNYPULSE™ Catheter and the TRUPULSE™ Generator.   
 
The first two subjects for each ablating physician will be considered a roll-in subject to verify consistent 
workflow of study device components and to minimize any learning curve effects. The roll-in phase 
will include up to 50 subjects.  A maximum sample size of 135 evaluable subjects is planned in the 
main study.  All study subjects will be followed-up for 12 months after study procedure.  
 
For the purpose of characterization of safety and to provide an assessment of lesion durability of the 
investigational ablation system, four (4) subsets will be embedded in the main study; the Neurological 
Assessment (NA), a Cardiac Computed Tomography (CT) or Magnetic Resonance Angiogram (MRA) 
imaging (CT/MRA), an Esophageal Endoscopy evaluation (EE) and a PVI durability subset in a 
prospective manner. Each subset will consist of the same 30 subjects, who will undergo the index 
ablation procedure and additional neurological, PV, esophageal and PVI durability assessments. The 
same subjects will participate in all four (4) subsets.  
 
All subjects will be evaluated prior to the procedure, prior to discharge, and post procedure at 7 days 
(day 7-9), 1 month (day 23-37), 3 months (day 76-104), 6 months (day 166-194), and 12 months (day 
335-379). 
 
Planned statistical analyses of the endpoints and analysis populations are described in the Statistical 
Analysis section (section 19) of this clinical investigational plan and in the Statistical Analysis Plan 
(SAP). The results for the roll-in phase will be analyzed and presented separately from the main study 
phase. 
 
7.2 
Roll-In Phase 
New devices often require operators to scale a learning curve. The inclusion of a roll-in phase in the 
study will allow learning for the operators, and an evaluation of safety and effectiveness of the device 
that is not diminished by the early learning curve. In addition to a requirement for investigational 
system/device training for ablating physicians, further experience within the context of this clinical 
investigational plan will serve to generate a clearer perspective of the effectiveness of the 
investigational system in treating PAF subjects.  
 
 

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Therefore, the first two subjects treated by an ablating physician with the study catheter will be 
prospectively assigned as roll-in subjects to minimize the learning curve effect. It is estimated to have 
15-25 ablating physicians to allow for a wide range of physician skill level. Because roll-in subjects are 
prospectively enrolled at the ablating physicians’ level, some physicians at a site may complete their 
roll-in subjects and move to the main study phase while other physicians at the site are still in the roll-
in phase. A subject who is excluded or discontinued (i.e., without energy delivery via the study devices) 
will not count towards the roll-in subjects. Roll-in subjects will not be included in the subsets. Roll-in 
subjects will be followed for 12 months post index procedure.  
 
7.3 
Study Subsets 
7.3.1 
Neurological Assessment (NA) subset 
A focused neuropathological evaluation will be integrated within the study. This subset of subjects will 
represent the neurological assessment (NA) subgroup. Subjects will be assessed for incidences of post-
ablation cerebral emboli with either an absence (asymptomatic) or presence (symptomatic) of 
neurological symptoms. Specifically, an asymptomatic cerebral embolism is defined as an occlusion of 
a blood vessel in the brain due to an embolus that does not result in any acute clinical symptoms. The 
presence (symptomatic) or absence (asymptomatic) of neurological symptoms will be determined by 
the site neurologist of the participating hospitals.  The Cerebral MRI data will be analyzed by an 
independent Core Laboratory. 
 
A total of 30 subjects will be prospectively included in this subset at sites with accessible MRI 
capabilities and a certified neurologist available to participate in the study. All subjects enrolled in the 
NA subset will meet all inclusion and exclusion criteria, including the additional exclusion criteria 
specific for the NA subset.  
 
NA subset subjects will, in addition to the general follow-up schedule, undergo additional assessments 
including Cerebral MRI, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), 
Mini Mental State Examination (MMSE), and general neurological assessments for evaluation of 
neurological incidences.  NOTE: Patient questionnaires will only be used in countries with validated 
languages. 
 
7.3.2 
Esophageal Endoscopy (EE) Subset 
A subset of study subjects will be enrolled in the EE subgroup and will, in addition to the general 
follow-up schedule, undergo an esophageal endoscopy within 1 to 3 days post ablation procedure to 
assess the presence of endoscopically detected thermal esophageal lesions (EDEL) in the region of the 
contact area between esophagus and LA. The presence or absence of EDEL post ablation will be 
determined by independent gastroenterologists of the Core Laboratory.  
 
These 30 subjects will be prospectively included by sites with accessible endoscopy capabilities and a 
certified gastroenterologist available to participate in the study.  All subjects who are enrolled in the 
EE subset will meet all inclusion and exclusion criteria, including the additional exclusion criteria 
specific for the EE subset.  
 
 
 
 
 
 

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7.3.3 
Cardiac CT/MRA subset 
An additional subset of study subjects will be enrolled in the cardiac CT/MRA subset and undergo a 3-
month CT/MRA in addition to the baseline CT/MRA (all subjects will have a baseline CT/MRA) to assess 
incidence of post-ablation PV stenosis.  A total of 30 subjects will be included in the CT/MRA subset at 
sites that have the appropriate equipment for CT/MRA imaging.    
 
In addition to this subset, any subjects with signs or symptoms of PV stenosis will undergo a post 
ablation CT/MRA. These subjects will not be included in the CT/MRA subset analysis. If severe PV 
stenosis is present, it will be reported as adverse event. The CT/MRA data will be analyzed for PV 
stenosis by an independent Core Laboratory. 
 
7.3.4 
PVI Durability Subset 
A subset of 30 study subjects will be enrolled in the PVI durability subset and will, in addition to the 
index ablation procedure and general follow-up schedule, undergo an electro-anatomical re-map 
procedure at 75 days (+/- 15 days) post index ablation procedure. The re-map is intended to evaluate 
the durability of the pulmonary vein isolation generated at the index ablation procedure. The 
assessment of lesion durability will be done by the physician at the participating sites.   
 
7.4 
Study Endpoints 
Main phase subject data will be used for the purpose of primary and secondary hypothesis testing.  
Roll-in subject data will be separately analyzed (not part of the primary hypothesis testing), further 
described in the statistical section of this protocol (section 19). 
 
7.4.1 
Primary Hypothesized Endpoints 
 
Safety  
 
The primary safety endpoint is the occurrence of Primary Adverse Events (PAEs) (within seven (7) days 
of the index ablation procedure where the investigational OMNYPULSE™ Catheter and TRUPULSE™ 
Generator are used per clinical investigation plan).  
 
PAEs include the following Adverse Events (AEs): 
Atrio-Esophageal Fistula* 
Phrenic Nerve Paralysis  
Cardiac Tamponade/perforation** 
Pulmonary Vein Stenosis* 
Device or procedure related death* 
Stroke/Cerebrovascular Accident (CVA) 
Major Vascular Access Complication/Bleeding 
Thromboembolism 
Myocardial Infarction 
Transient Ischemic Attack (TIA) 
Pericarditis 
Heart Block 
Pulmonary Edema (Respiratory Insufficiency) 
Vagal Nerve injury/Gastroparesis 
*Device or procedure related death, pulmonary vein stenosis and atrio-esophageal fistula that 
occur greater than one week (7 days) and less than or equal to 90 days post-procedure are 
considered and analyzed as PAEs. 
** Cardiac Tamponade/Perforation occurring up to 30 days post AF ablation process procedure will 
be considered a PAE. 
 

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Acute Effectiveness: 
 
The acute effectiveness endpoint is the electrical isolation of clinically relevant targeted PVs which is 
evidenced by confirmation of entrance block after adenosine/isoproterenol challenge at the end of 
the index ablation procedure. Use of a non-study device to achieve PVI is considered an acute 
procedural failure. 
 
NOTE: Subjects who have the study catheter inserted but do not undergo ablation due to study device 
(OMNYPULSE™ Bi-Directional Catheter and TRUPULSE™ Generator) related reasons will be considered 
acute effectiveness failures; subjects who are discontinued due to non-study device related reasons 
(e.g., pump, other equipment or anatomy that precludes treatment with the OMNYPULSE™ Bi-
Directional Catheter and TRUPULSE™ Generator or a commercially available device) will be considered 
as missing outcome of the acute effectiveness endpoint as entrance block would not be achieved by 
the study device. 
 
7.4.2 
Secondary Hypothesized Endpoints 
 
12-Month Effectiveness 
 
Freedom from documented (symptomatic and asymptomatic) atrial arrhythmia (AF, AT or AFL of 
unknown origin*) episodes based on electrocardiographic data (>30 seconds on arrhythmia 
monitoring device) during the effectiveness evaluation period (day 91-day 365) on or off 
antiarrhythmic therapy. Acute procedural failure (i.e., failure to achieve entrance block with the study 
device in any of the clinically relevant targeted PVs) will also be deemed a 12-month effectiveness 
failure. 
 
*AFL of unknown origin is defined as all AFL except those CTI dependent AFL as confirmed by 12-lead 
electrocardiogram (ECG) or entrainment maneuvers in an EP study. 
 
Further refer to Appendix 1 for definitions on effectiveness terms. 
 
7.4.3 
Additional Effectiveness Endpoints 
 
PVI Durability (for PVI Durability subset): defined as a sustained isolations of PVs that are targeted in 
the index ablation procedure, which is evidenced by the confirmation of isolation via the 
electroanatomical mapping 75 days (+/- 15 days) post index ablation procedure.  
Single Procedural Success: defined as freedom from documented symptomatic atrial arrhythmia (AF, 
AT or AFL of unknown origin*) episodes based on electrocardiographic data (>30 seconds on 
arrhythmia monitoring device) during the effectiveness evaluation period (day 91-day 365) following 
a single index ablation procedure.   
Freedom from documented symptomatic atrial arrythmia (AF, AT or AFL of unknown origin*) 
episodes based on electrocardiographic data (>30 seconds on arrythmia monitoring device) during the 
effectiveness evaluation period (day 91-day 365). Acute procedural failure will also be considered 
failure of 12-month symptomatic recurrence free endpoint.  
 
 

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Freedom from documented (symptomatic and asymptomatic) atrial arrhythmia (AF, AT or AFL of 
unknown origin*) episodes based on electrocardiographic data (>30 seconds on arrhythmia 
monitoring device) during the effectiveness evaluation period (day 91-day 365) with extra failure 
modes. A subject who meets any of the following criteria will also be deemed an effectiveness failure:  
- 
Failure to achieve acute procedural success.  
- 
Taking a new Antiarrhythmic Drug (AAD) (Class I / Class III) for atrial tachyarrhythmia (AF, 
AT or AFL of unknown origin*) or taking a previously failed Class I/III AAD at a greater than 
the highest ineffective historical dose for AF/AFL/AT during the effectiveness evaluation 
period (day of 3-month visit – day 365). 
- 
Greater than 1 repeat ablation for AF/AT or AFL of unknown origin* in the blanking period 
or any repeat ablation for AF/AT or AFL of unknown origin* during the effectiveness 
evaluation period. 
Use of a non-study device for the purpose of: 
- 
PVI (i.e., touch-up) among all clinically relevant targeted PVs during index ablation 
procedure.    
- 
Ablation of left atrial non-PV AF targets (i.e., posterior wall) during index ablation 
procedure or for repeat procedures during blanking period. 
Acute reconnection identified by adenosine/isoproterenol challenge among all clinically relevant 
targeted PVs.  
Repeat ablation procedures for left atrial arrhythmia (AF, AT or AFL of unknown origin*) within the 
12-month FU period. 
- 
Percentage of subjects with repeat ablation during blanking period (≤90 days post index 
ablation procedure). 
- 
Percentage of subjects with repeat ablation after blanking period (day 91 – 365 post index 
ablation procedure). 
- 
Percentage of PV reconnection observed during repeat ablation procedures by targeted 
PVs treated at index ablation procedure and by subject. 
- 
Percentage of subjects with repeat ablations due to non-PV targets. 
 
Quality of Life (QoL): the change of QoL assessed by comparing the Atrial Fibrillation Effect on Quality-
of-Life (AFEQT™) scores before and at 3, 6 and 12- months after the ablation procedure. 
Hospitalization for cardiovascular events through 12 months follow-up compared to 12 months prior 
to baseline.  
*AFL of unknown origin is defined as all AFL except those CTI dependent AFL as confirmed by 12-lead 
electrocardiogram (ECG) or entrainment maneuvers in an EP study. 
 
 
 
 
 
 
 
 
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7.4.4 
Additional Safety Endpoints  
Safety  
- 
Occurrence of Serious Adverse Device Effects (SADEs) 
- 
Occurrence of Unanticipated Serious Adverse Device Effects (USADEs) 
- 
Occurrence of Serious Adverse Events (SAEs) within 7 days (early-onset), 8 to 30 days (peri-
procedural) and >30 days (late onset) of index ablation procedure 
- 
Occurrence of non-serious adverse events (non-SAEs)  
 
Neurological Assessment Subset 
- 
Occurrence of new asymptomatic and symptomatic cerebral emboli observed post-ablation as 
determined by Magnetic Resonance Imaging (MRI) evaluations. 
- 
Occurrence of new or worsening neurological deficits post-ablation and during follow-up. 
- 
Summary of Mini Mental State Examination (MMSE), National Institute of Health Stroke Scale 
(NIHSS) and Modified Rankin Scale (mRS) at baseline, post-ablation and during follow-up (if 
lesions were identified in prior evaluation) 
 
CT/MRA Subset 
- 
Occurrence of PV stenosis up to 3 months post-ablation as determined by Computed 
Tomography (CT)/ Magnetic Resonance Angiogram (MRA) evaluations. 
 
Esophageal Endoscopy Subset 
- 
Occurrence of endoscopically detected esophageal thermal lesions in the region of the contact 
area between esophagus and LA as determined by post procedure endoscopy.  
 
7.4.5 
Additional Procedural Endpoints  
Procedural data, including but not limited to 
- 
Total procedure time, PVI time, PF application time and mapping time.  
- 
Number of PF applications by left and right PV and by subject. 
- 
Total fluoroscopy time. 
- 
Total study catheter left atrial dwell time.  
- 
Ablation settings used. 
 
8 
Study Population 
Patients scheduled to have a clinically indicated ablation procedure for the management of their PAF 
will be screened for enrollment per the study’s inclusion and exclusion criteria. The “investigation 
population” (meeting all inclusion and exclusion criteria) represents the “target population” 
(symptomatic PAF subjects) indicated for catheter ablation per consensus guidelines. In addition, the 
criteria listed below ensure mitigation of risks (as per instructions for use and user manual) associated 
with the patients’ health status at the time of screening and contraindications for study assessments. 
 
 
 
 
 
 
 

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8.1 
Participant Inclusion Criteria 
Candidates for this study must meet ALL of the following criteria: 
1. 
Diagnosed with Symptomatic Paroxysmal AF defined as AF that terminates spontaneously or 
with intervention within 7 days of onset. This PAF is considered to be symptomatic if 
symptoms related to AF are experienced by the patient. 
2. 
Selected for AF ablation procedure by PVI. 
3. 
Age 18-75 years.  
4. 
Willing and capable of providing consent. 
5. 
Able and willing to comply with all pre-, post- and follow-up testing and requirements. 
 
8.2 
Participant Exclusion Criteria 
Candidates will be excluded if ANY of the following criteria apply: 
1. 
Previously known AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-
cardiac cause (e.g., documented obstructive sleep apnea, acute alcohol toxicity, morbid 
obesity (Body Mass Index >40 kg/m²), renal insufficiency (with an estimated creatinine 
clearance < 30 mL/min/1.73 m2) ….). 
2. 
Previous LA ablation or surgery. 
3. 
Patients known to require ablation outside the PV region (e.g., atrioventricular reentrant 
tachycardia, atrioventricular nodal re-entry tachycardia, atrial tachycardia, ventricular 
tachycardia and Wolff-Parkinson-White).  
4. 
Previously diagnosed with persistent AF (> 7 days in duration). 
5. 
Severe dilatation of the LA (LAD >50mm antero-posterior diameter in case of Transthoracic 
Echocardiography (TTE)). 
6. 
Presence of LA thrombus. 
7. 
Severely compromised Left Ventricular Ejection Fraction (LVEF <40%). 
8. 
Uncontrolled heart failure or New York Heart Association (NYHA) Class III or IV.  
9. 
History of blood clotting, bleeding abnormalities or contraindication to anticoagulation 
(heparin, warfarin, or dabigatran). 
10. History of a documented thromboembolic event (including TIA) within the past 6 months.  
11. Previous Percutaneous Coronary Intervention (PCI) / Myocardial Infarction (MI) within the 
past 2 months. 
12. Previous Coronary Artery Bypass Grafting (CABG) in conjunction with valvular surgery, cardiac 
surgery (e.g., ventriculotomy, atriotomy) or valvular cardiac (surgical or percutaneous) 
procedure. 
13. Unstable angina pectoris within the past 6 months. 
14. Anticipated cardiac transplantation, cardiac surgery, or other major surgery within the next 
12 months. 
15. Significant pulmonary disease (e.g., restrictive pulmonary disease, constrictive or chronic 
obstructive pulmonary disease) or any other disease or malfunction of the lungs or respiratory 
system that produces severe chronic symptoms. 
16. Known significant PV anomaly that in the opinion of the investigator would preclude 
enrollment in this study. 
17. Prior diagnosis of pulmonary vein stenosis. 
18. Pre-existing hemi diaphragmatic paralysis. 
19. Acute illness, active systemic infection, or sepsis. 
20. Presence of intracardiac thrombus, myxoma, tumor, interatrial baffle or patch or other 
abnormality that precludes catheter introduction or manipulation. 
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22. Presence of implanted pacemaker or Implantable Cardioverter-Defibrillator (ICD) or other 
implanted metal cardiac device that may interfere with the pulsed electric field energy.  
23. Presence of a condition that precludes vascular access (such as Inferior Vena Cava (IVC) filter) 
24. Significant congenital anomaly or a medical problem that in the opinion of the investigator 
would preclude enrollment in this study. 
25. Categorized as vulnerable population and requires special treatment with respect to 
safeguards of well-being. 
26. Current enrollment in an investigational study evaluating another device or drug. 
27. Women who are pregnant (as evidenced by pregnancy test if pre-menopausal), lactating, or 
who are of child-bearing age and plan on becoming pregnant during the course of the clinical 
investigation. 
28. Life expectancy less than 12 months.  
29. Presenting contra-indications for the devices used in the study, as indicated in the respective 
Instructions For Use (IFU). 
 
Additional exclusion criteria for Neurological Assessment (NA) subjects:  
30. Known contraindication for MRI such as use of contrast agents due to advanced renal disease, 
claustrophobia etc. (at PI discretion).  
31. Presence of iron-containing metal fragments in the body.  
32. Known unresolved pre-existing neurological deficit. 
 
Additional exclusion criteria for Esophageal Endoscopy (EE) subjects:  
33. Known uncontrolled significant GastroEsophageal Reflux Disease (GERD) 
 
9 
Participant Withdrawal or Termination 
9.1 
Reasons for Withdrawal or Termination 
Participants are free to withdraw from participation in the study at any time upon request without 
penalty or loss of benefits to which they may otherwise be entitled. Participants will be informed prior 
to study entry that they are free to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by a physician or the institution. 
 
An investigator may terminate a subject’s participation in the study if:  
- 
Any clinical AE, laboratory abnormality, or other medical condition or situation occurs such that 
continued participation in the study would not be in the best interest of the participant.  
- 
Withdrawal is in the subjects’ best interest. 
- 
Subject withdraws consent. 
- 
Subject is lost to follow-up. 
 
Every subject should be encouraged to remain in the study until they have completed the CIP required 
follow-up period. 
 
 
 
 
 
 
 
 

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9.2 
Handling of Participant Withdrawals or Termination 
 
If a subject is removed or withdraws from the study, the date and reason for withdrawal will be 
recorded on the appropriate electronic Case Report Form (eCRF) and the applicable on-site source 
documentation. If the subject is withdrawn due to an AE or SAE, the investigator should follow the 
subject until the AE/SAE has resolved or is considered stable.   
 
If a subject is unable to return for an office/clinic visit or cannot be contacted by telephone, 3 separate 
telephone calls should be made to obtain subject related safety information. All attempts should be 
documented in the source documents. If the subject does not respond to the 3 telephone calls, the 
investigator must perform a final documented attempt (e.g., send a certified letter to the subject, ...).  
If the subject does not respond to the letter, then the subject will be considered “lost to follow-up” 
for the study.   
 
Subjects who have signed the ICF but are later found not to be eligible PRIOR to insertion of the study 
catheter can be replaced. Replacement subjects will be recruited and enrolled following the same 
procedures as non-replacement subjects. 
 
10 Responsibilities 
10.1 Investigator Responsibilities 
 
Investigators at each participating clinical site will have the following responsibilities: 
- 
Assuring compliance by site personnel with the provisions of the CIP  
- 
Providing the Sponsor with: 
• 
Signed, dated Investigator Agreement. 
• 
Written Ethics Committee (EC) approval letters and EC-approved consent forms. 
• 
Signed, dated Financial Disclosure form for each participating investigator. 
• 
Curriculum vitae for each investigator 
- 
Maintain an accurate and current Delegation of Authority log which identifies individuals 
authorized to perform work for the study and assuring compliance by site personnel with the 
provisions of the CIP. 
- 
Completing the appropriate training on the device (ablating investigators only) and the CIP 
prior to enrolling and treating subjects 
- 
Maintain accurate and current logs for the study such as:  
• 
Subject log, Device Accountability Log 
- 
Obtain initial and amendment (if applicable) EC approval and annual review/approval 
thereafter for the CIP and informed consent as applicable. 
- 
Obtain ICF and enroll patients. 
- 
Perform medical procedures. 
- 
Order tests required by the CIP.  
- 
Review pre-procedure imaging pertaining to the PV size prior to treatment. 
- 
Follow subjects until the end of the CIP.  
- 
Accurately complete and sign eCRFs in a timely manner 
- 
Maintain relevant source documentation and allow Sponsor direct access to perform 
monitoring or auditing duties.  
- 
Maintain records and provide reports according to prevailing regulatory requirements. 
- 
Share relevant study-related information with delegated study staff. 

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- 
Inform the appropriate entities (e.g., Sponsor, Competent Authority (CA), EC) in a timely 
manner regarding the occurrence of AEs and/or product malfunctions. 
- 
Making sufficient effort to maintain contact with treated subjects who fail to comply with the 
follow-up requirements. 
- 
Maintain study records for at least 10 years or as specified per country specific record 
retention requirements after the study is completed and or terminated. The Sponsor will 
notify the Investigator of either of these events. 
- 
Complying with EC and Sponsor annual report requirements, including the clinical 
investigation report. 
 
10.2 Sponsor Responsibilities 
 
The Sponsor (Biosense Webster, Inc.) will be responsible for the following: 
- 
Conduct of pre-study site assessment and approval. 
- 
Preparation and modification (if applicable) of study documents including but not limited to 
the CIP, CRFs and informed consent.  
- 
Selection of appropriately qualified and trained individuals, including monitors, to conduct the 
study.  
- 
Conduct CIP and device training for investigators and research personnel as applicable. 
- 
Set-up of study-specific committees. 
- 
Obtain signed study contracts from investigators/hospitals, Clinical Research Organizations 
(CROs) and other involved parties. 
- 
Ship study devices to each site. 
- 
Monitor sites for the duration of the study. 
- 
Maintain study database. 
- 
Inform investigator of his/her responsibilities.  
- 
Submit and obtain approval for study from applicable regulatory agencies. 
- 
Preparation of reports summarizing the status of the study no less than annually.  These 
reports will be supplied to the PI at each site. 
- 
Update Report of Priors, IFU, IB, and Risk Analyses, as applicable. 
- 
Update investigators on safety issues, if needed. 
- 
Report (including AE’s and DDs) to study investigators and regulatory agencies, as required. 
- 
Have relevant safety information reviewed by the study-specific committees, as required. 
- 
Communications with the CA. 
- 
Substantial modifications to the study will be submitted to CAs and/or ECs for approval before 
implementation. A response of no objections will be awaited as per ISO 14155, MDR article 
75. Non-substantial modifications will be notified to the CAs and/or ECs but do not require a 
formal approval before implementation.  
- 
Maintain study records for at least 10 years or as specified per country specific record 
retention requirements after the study is completed and/or terminated. 
 
11 Study Device Description 
11.1 Device Acquisition 
 
After obtaining a fully executed clinical trial agreement and appropriate approvals, the sponsor will 
initiate shipment(s) of investigational devices to the site. The Sponsor will keep records of all 
investigational devices shipped to the site. Approved investigational devices will be shipped directly 
to the site and will be received by the site. Investigators are responsible for appropriate logging of the 

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devices received, verification of packing slip information (i.e., lot numbers and quantity shipped), date 
and identity that each device was used in the study, disposition information regarding disposal or 
return to the Sponsor. 
 
11.2 Device Storage and Stability 
Devices are to be stored in a secure/locked location and in accordance with the catheter IFU and 
generator User Manual (UM). Do not use the (disposable) devices after the “Use By” date. Hardware 
should not be used past its preventative maintenance date.  
 
11.3 Device Preparation 
Information related to device preparation can be found in the catheter IFU and generator UM. 
 
11.4 Instructions for Use 
A comprehensive set of IFU and UM for the study system and all accessory cables/interface cables is 
contained in each product package and is also available upon request.   
 
11.5 
 
11.5.1 
  
 
CCI
CCI
CCI
CCI

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SMARTABLATE™ Irrigation Tubing Sets 
(SAT001) 
Delivers heparinized saline to the catheter  
Patient Interface Unit (PIU) of the CARTO™ 3 
system 
 
The EP recording system should be connected to the 
CARTO 3 System PIU to transfer ECG  
BWI multi-electrode mapping catheter 
• 
Pre-ablation recording and mapping of the atria of 
the heart with the CARTO™ 3 System. 
• 
Confirmation of entrance block 
Tx Eco Cable 
 
Connector between the OMNYPULSE™ catheter and 
the system (CIU/PIU) for information of location and 
contact force.  
 
The following devices, CE marked by other companies, are also required for the procedure: 
- 
Electrophysiology (EP) Recording System 
- 
Stimulator 
- 
Body Surface Electrocardiogram (ECG) Patches and Leads  
- 
Indifferent electrode patch(es)  
- 
Fluoroscopy/X-Ray System 
- 
Cardiac Defibrillator 
- 
Intracardiac Ultrasound (Investigator preference, not required) 
- 
Esophageal Temperature Monitoring Device (OPTIONAL) 
 
11.5.4.2 System Connectivity 
 
Each site will have CIP specified devices required for study participation. These devices must be used 
during the study to perform ablation procedures. Device set-up must be complete per the IFU and 
User Manual.  
 
Below figures displaying a connectivity diagram from the front view (Figure 3) and back view (Figure 
4) for system set up and a description of the connectivity respectively.  

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12 Study Medication 
The following medications are applicable for this CIP: 
  
PRIOR to the procedure 
- Uninterrupted anticoagulation therapy should be in place at least 3 weeks prior to ablation 
procedure.   
• 
Recommended: anticoagulation with Warfarin/Coumadin (INR≥ 2.0), a factor Xa 
inhibitor, or direct thrombin inhibitor is recommended for at least 3 weeks before and 
at least 4 weeks after ablation regardless of the CHA2DS2-VASc score or the method 
(electrical or pharmacological) used to restore sinus rhythm. 
- Anticoagulation therapy should not be interrupted or stopped prior to the procedure (this means 
no doses should be missed or omitted) and daily regimen should be continued. One dose can be 
omitted on the evening prior- or day of procedure as per standard of care.  
- AAD therapy and administration of Proton Pump Inhibitors (PPI) should be managed as per the 
institution’s standard of care. 
 
DURING the procedure, provided in the Study Ablation Procedure Guidelines (section 13.3.3) 
 
FOLLOWING the procedure 
- Anticoagulation therapy is strongly recommended for at least 2 months following ablation.  
- Decisions regarding continuation of systemic anticoagulation beyond 2 months post ablation 
should be based on the subject’s stroke risk profile.  
- Per HRS3 guidance systemic anticoagulation is recommended be continued beyond two months 
post-procedure in subjects with a CHA2DS2-VASc score of ≥ 2 (unless deemed contraindicated 
based on clinical considerations). 
- PPI administration for at least 6 weeks following the procedure is MANDATORY if an endoscopy 
is performed post procedure. 
- AAD management during the study will be at the discretion of the investigator. 
- Additional medications needed to treat clinical indications are at the discretion of the clinical 
investigation physician.  
 
13 Study Schedule  
13.1 Screening and Informed Consent 
Candidates presenting to the institution with symptomatic PAF and considered for an ablation 
procedure should be screened by the investigator or designated member of the research team for 
study eligibility per the CIP inclusion and exclusion criteria. Sites will be instructed to screen all subjects 
who require a documented ablation procedure for symptomatic PAF without regard to sex or race. 
 
The study investigator or designated member of the research team will obtain written informed 
consent from the subject. The patient informed consent procedure must be done within 60 days 
before the actual study procedure takes place. The background of the proposed study and the 
potential benefits and risks of the study should be explained to the subject. The subject or legal 
representative must sign the consent form prior to any study-specific exams or tests are provided to 
them that fall outside of the standard of care. The consent form used must have prior approval from 
the CAs and study site's EC or jointly given approval from CAs and independent EC. Failure to obtain 
informed consent renders the subject ineligible for participation in the study. 
 

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The investigator and/or designee must also clearly document the process of obtaining informed 
consent in the subject’s source documents. The voluntary process of informed consent confirms the 
subject’s willingness to participate in the study. It’s the investigator’s responsibility to ensure that the 
informed consent process is performed in accordance with International Conference on 
Harmonization-Good Clinical Practices (ICH-GCP), the Declaration of Helsinki, and with applicable local 
and national regulations. If new information becomes available that can significantly affect a subject’s 
future health and/or medical care, this information shall be provided to the subject(s) affected in 
written form. If relevant, all affected subjects shall be asked to confirm their continuing informed 
consent in writing by dating and signing an amended ICF. 
 
Each subject screened for enrollment in the clinical investigation who signs the patient ICF will be 
enrolled into the study. No subject should undergo any clinical investigation specific tests or 
examinations that fall outside the standard of care without first signing the patient ICF for this clinical 
investigation.   
 
13.2 Baseline Evaluation and Procedures 
13.2.1 Pre-Procedure/Baseline Assessments 
Below pre-procedure assessments and data collection must be performed prior to the ablation 
procedure.   
- 
Patient Information and Consent (procedure must be done within 60 days of consent) 
- 
Demographics (age, gender, etc.). 
- 
Medical history, including but not limited to arrhythmia, heart disease, thromboembolic events, 
lung/respiratory problems. 
• 
AF history (first evidence of AF, number of episodes, symptoms, etc.). 
• 
NYHA Functional Class Scale. 
• 
CHA2DS2 VASc Score Subjects will be scored against the CHA2DS2 VASc.  
• 
Vital signs (Height, weight, etc.) 
• 
Cardiovascular hospitalization history: information on hospitalization for 
cardiovascular reason (including arrhythmia, cardioversion, …) from 12 months prior 
to enrollment will be collected from medical records and recorded in the eCRF. 
• 
Medication history: Medication history (cardiac medication, AAD medication, 
anticoagulation regimen and any other clinically significant medication history) shall 
be gathered by interview or from medical records following enrolment but prior to 
the ablation procedure and should be recorded in the eCRF.  
- 
Anticoagulation therapy: Uninterrupted anticoagulation therapy should be in place at least 3 
weeks prior to ablation procedure for each subject (mandatory).  
• 
For subjects on Warfarin/Coumadin therapy, the subject shall be maintained on 
Warfarin/Coumadin for at least 3 weeks prior to ablation procedure with an INR ≥2. 
• 
Any INR <2 within 3 weeks prior to ablation will lead to exclusion of the patient or 
postponement of the study procedure. The results must be available prior to start of 
the procedure. 
• 
INR value ≥2 is to be confirmed maximum 48 hours pre-procedure. 
 
 
 
 

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- 
Pregnancy test must be done on all women of childbearing age and potential within 72-hours 
prior to the procedure and documented in the subjects medical chart. 
- 
Imaging (TTE or other acceptable equivalent cardiac imaging – i.e., CT/MRA) within 6 months 
prior to procedure to assess the LA and LVEF. Must be collected within 6 months prior to 
procedure, in case of the imaging assessment is older than 6 months LA/LVEF, dimensions shall be 
re-measured during the index ablation procedure prior to insertion of the study catheter. In case 
of re-measurements before study catheter insertion fail to meet the LA and/or LVEF criteria, the 
subject will be considered as not meeting eligibility and will be excluded.  
- 
Imaging for detection of left atrial thrombus or other structural contraindications to an ablation 
procedure is mandatory the day before or on the day of the ablation procedure. Presence of a 
thrombus will require postponement of the ablation procedure or may even lead to exclusion of 
the subject from further study involvement. The imaging method to be used for atrial thrombus 
detection is TEE, Intracardiac Echocardiography (ICE), Cardiac CT or MRI 
- 
Electrocardiogram (12-Lead ECG). Data from 12-lead ECG recordings will be collected.   
- 
Adverse Events must be collected from the time the subject signs the informed consent onwards. 
- 
Quality of life via the Atrial Fibrillation Effect on Quality-of-Life (AFEQT™) questionnaire (non-
Standard of Care). NOTE: Patient questionnaires will only be used in countries with validated 
languages.  
- 
Cardiac CT/MRA is required to be performed for all subjects within 6 months prior to the ablation 
procedure to assess the structure and size of the PVs and the left atrial anatomy. 
 
- 
Additional Assessments for NA subset subjects: Cerebral MRI, Neurological Exam and 
Neurological Evaluation using the MMSE, NIHSS and mRS (non-SOC) are required to be 
performed within 72-hours pre-procedure (for procedures on Monday a window of a maximum 
of 96 hours is justified) to evaluate the neurological condition and presence of neurological deficits 
of the subjects before undergoing study ablation procedure. A certified/qualified physician expert 
must perform neurologic exams at pre-and post-ablation and possibly at other follow-up visits, 
pending previous findings of micro-emboli/neurologic deficits. Pre-and post-ablation cerebral 
MRIs will be analyzed by a central core lab to determine the frequency, size, and anatomical 
location of cerebral micro-emboli, if any. NOTE: Patient questionnaires will only be used in 
countries with validated languages. 
 
13.3 Study Ablation Procedure Guidelines 
13.3.1 Ablation Selections  
The TRUPULSE™ Generator is capable of controlling the delivery of PF energy to the OMNYPULSE™ 
Catheter. The generator includes a touch screen that allows the user to start and stop ablation. The 
start button contains a drag feature. Each ablation occurs in under a second, which requires caution 
prior to start an ablation. After the start button is dragged or the pedal is pressed, there is a 
countdown until ablation begins. When the stop button is pressed or the pedal is released, the delivery 
of energy is terminated. For more general operation of the TRUPULSE™ Generator, refer to the user 
manual for detailed information. 
 
 
 
 
 

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MAPPING prior to the ablation procedure: 
 
- 
REQUIRED FOR ALL SUBJECTS: Creation of a left atrial anatomical map, including PV anatomy 
prior to ablation: 
• 
Recommended to use the OMNYPULSE™ Bi-Directional Catheter, possible substituted 
by the use of a BWI multi-electrode mapping catheter or 3D rotational angio (at 
investigator discretion) 
- 
Additional imaging techniques such as 3D rotational angiography (at investigator discretion), 
or CT integration can be used to supplement the map. 
- 
A pre-ablation paced activation and bi-polar voltage map may be created at physician 
discretion and if SOC. 
- 
Pace the phrenic nerve prior to ablation in the region of the right sided PV’s in order to 
evaluate the proximity.  NOTE: in case of deep sedation a fluoroscopic evaluation of the 
diaphragm may be used.  
 
ABLATION Procedure: 
 
- 
REQUIRED: Confirmation of ACT ≥350 seconds PRIOR to start ablation with investigational 
catheter and systematic anticoagulation with heparin should be administrated.  
• 
ACT must be targeted to be maintained ≥350 seconds throughout the ablation. 
• 
ACT level must be checked on regular basis while investigational device is in the left 
atrium.  
• 
If ACT is below 350 seconds, systematic anticoagulation with heparin should be 
administrated to ensure an ACT target of 350 seconds without pausing ablation 
procedure.  
- 
Introduction of the compatible 10 F guiding sheath, if not used for mapping. Before inserting 
the sheath into the patient, flush the sheath with heparinized normal saline to remove air 
bubbles. 
- 
Introduce the investigational OMNYPULSE™ Bi-Directional Catheter as per IFU. 
- 
NOTE: Usage of a diagnostic catheter or any metal device in the same chamber during ablation 
is strictly prohibited, and diagnostic catheter should be disconnected from the CARTO™ 3 
system prior to starting ablation. 
- 
When position is satisfactory, commence energy delivery with the investigational catheter per 
recommended workflow.  
- 
NOTE: In the situation that the CARTO™ system shuts down, the connection configuration will 
not allow the OMNYPULSE™ catheter to pace. An alternative method (e.g., CS catheter) must 
be in place in order to pace in case of emergency. 
 
 
 
 
 
 
 
 
 
 
 
 

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Pulmonary Vein Isolation (PVI)  
 
- 
Use point-by-point ablation to obtain a contiguous lesion set for ipsilateral PV isolation.  
- 
Create VISITAG™ settings in order to segment the left atrium during the procedure according to 
below image (Figure 5). 
 
 
Figure 5: VISITAG™ settings  
 
- 
All subjects will undergo PV ablation with the investigational device until PVI is achieved in all 
targeted PV’s:  
• 
ONLY after investigator deems unable to achieve PVI with the investigational device, 
a commercial and compatible BWI (RF) catheter and generator can be used to 
complete the procedure (PVI only).  
- 
REQUIRED: Confirmation of entrance block (exit block is optional) / PVI of all clinically relevant 
targeted PVs  
• 
To verify entrance block, analyze electrograms in coronary sinus and/or atrial paced 
rhythm to confirm that no PV potentials are present.  
 
Post Pulmonary Vein Isolation: 
 
- 
Administer adenosine/isoproterenol for each clinically relevant targeted PV to rule out dormant 
conduction.  
• 
If any, treat reconnected PV regions by reviewing remaining signals on reconnection 
location and deliver energy in corresponding locations.  
- 
REQUIRED: Confirmation and documentation of final entrance block (exit block is optional) / PVI 
of all clinically relevant targeted PVs  
• 
To verify entrance block, analyze electrograms in coronary sinus and/or atrial paced 
rhythm to confirm that no PV potentials are present.  

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• 
Use a BWI multi-electrode mapping catheter for confirmation per investigators 
choice. 
- 
The ablation procedure is considered complete when confirmation of entrance block in all 
clinically relevant targeted PVs is confirmed. 
- 
REQUIRED: after last application or confirmation of final entrance block at the right sided PVs, 
evaluate diaphragmatic capture while pacing the phrenic nerve. NOTE: in case of deep sedation a 
fluoroscopic evaluation of the diaphragm might be used. 
- 
A post paced activation and bipolar voltage map may be created at physician discretion and if SOC. 
- 
REQUIRED for roll-in and PVI durability subset:  
• 
REQUIRED: creation of paced activation map and bipolar voltage map, using a BWI 
multi-electrode mapping catheter.  
• 
The OMNYPULSE™ Bi-Directional Catheter can be substituted (investigator discretion) 
prior to leave the LA. 
 
 
Ablation outside the PV region 
- 
A right atrial CTI linear ablation is allowed only in cases with documented typical atrial flutter 
identified either prior to or during the procedure. The CTI line should be completed with a BWI 
commercially approved and compatible (RF) catheter and (RF) generator.   
- 
Prophylactic ablation outside the PV region (in example SVC, PW, roofline) is NOT allowed.  
- 
If an arrhythmia is requiring ablations outside the PV: 
• 
Prior to insertion of the study catheter (consistent with exclusion criteria) investigators will 
be required to switch to the commercial setup using a commercially available Biosense 
Webster catheter used with a commercially available RF generator. The subject will be 
considered a screen failure (<ICF signature) or excluded from the study (> ICF signature). 
• 
After insertion of the study catheter, the subject will undergo PVI with study set up followed 
by ablation with a commercially approved BWI (RF) catheter and compatible RF generator to 
complete the procedure for the treatment of arrhythmia outside PV region. The subject will 
be evaluable for acute success and followed till 3-months post procedure. NOTE: Ongoing 
AE(s) at 3 months shall be followed up until resolution (with or without sequelae) 
 
13.3.4 Collection of Ablation Procedure Data for Post-Analysis (non-SOC) 
At the completion of the study ablation procedure, two back-up copies of the CARTO™ and 
generator system log files will be made. One copy should be kept at the site within the 
investigator site or patient binders, and one fully anonymized copy will be provided 
to/collected by the Sponsor.  
 
13.3.5 Data Collection during Study Ablation Procedure 
The following information will be collected during the procedure, including but not limited to: 
 
Technical parameters are collected via CARTO™ datafiles and TRUPULSE™ generator files, including 
but not limited to: 
- 
Number of PF applications.  
- 
Energy delivered.  
- 
PF application time. 
- 
Ablation settings used. 
- 
Contact force values. 

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Other procedural parameters are collected via Electronic Data Capture (EDC), including but not 
limited to: 
- 
Use of a non-study catheter for PVI. 
- 
Number of PF applications per left and right PV and by subject.  
- 
Number of RF applications required with a non-study catheter. 
- 
Use of a non-study multi-electrode catheter for mapping. 
- 
PVI confirmed with BWI multi-electrode mapping catheter.  
- 
PV acute reconnection. 
- 
Procedure time (from first femoral puncture to last catheter out). 
- 
Mapping time (start mapping – end mapping). 
- 
Total fluoroscopy time. 
- 
Total study catheter LA dwell time (from first study catheter insertion in LA until study catheter 
removal from LA). 
- 
ECG data. 
- 
Total fluid delivered via study catheter. 
- 
Total fluid delivered via intravenous line (if captured). 
- 
Fluid output (if captured). 
- 
Device deficiency information (if applicable). 
- 
Procedural medication (paralytics, ...). 
- 
Use of paralytics and type of anesthesia. 
 
 
13.3.6 Pre-Discharge Assessments 
 
Prior to hospital discharge, the following assessments should be performed: 
- 
Medication regimen (Cardiac, anti-coagulation, PPIs) 
- 
Imaging assessment of pericardial fluid presence 
- 
AEs  
- 
12- Lead -ECG (as per SOC) 
- 
Additional Assessments for NA subset subjects (non-SOC):  Cerebral MRI, neurological exam 
and neurological evaluation using the NIH stroke scale within 72-hours post procedure, 
preferable prior to discharge.  A certified/qualified physician expert must perform neurologic 
exams at pre-and post-ablation and possibly at other follow-up visits, pending previous 
findings of micro-emboli/neurologic deficits. For procedures on Friday a window of maximum 
96 hours is justified. Cerebral MRI images will be transmitted to an independent core 
laboratory. NOTE: Patient questionnaires will only be used in countries with validated 
languages. 
- 
Additional assessments for EE subset subjects (non-SOC): Endoscopy to check for any 
esophageal lesions and/or damage will be performed preferable prior to discharge and no 
later than 72- hours after procedure (for procedures on Friday a window of a maximum of 96 
hours is justified). Endoscopy images will be transmitted to an independent core laboratory.  
 
 
 
 
 
 
 

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13.4 Repeat Ablation Procedures 
Repeat procedures may be performed at the discretion of the investigator. It is highly recommended 
to collect arrhythmia documentation (in example documented recurrences) before performing a 
repeat procedure.  
 
During the blanking period: 
 
• 
Repeat procedures during the blanking period (≤ 90 days post index ablation procedure) must 
be conducted with the investigational device, with or without focal touch-up, if the arrhythmia 
is due to PV triggers. ONLY after investigator deems unable to achieve PVI with the 
investigational device, a commercial and compatible BWI (RF) system can be used to complete 
the procedure (PVI only).  
 
• 
If the arrhythmia is due to non-PV triggers and the subject is treated with a commercially 
available ablation catheter and generator, the subject will be excluded from the long- term 
effectiveness cohort.  
 
• 
Procedures for newly CTI dependent flutter in the follow up period are not considered repeat 
procedures per CIP and will be treated with a commercially available ablation catheter and 
generator.  
  
After the Blanking period:  
 
Repeat procedures performed after the blanking period (91- 365 days post index ablation procedure) 
may be managed per investigator discretion using a commercially available ablation catheter and 
generator. 
 
For the repeat procedures, the investigator must collect and provide information on location of 
reconnections of PVs and in case of atrial flutter recurrence, confirm if CTI dependent flutter or not. 
The follow-up schedule will remain based on the index ablation procedure. 
 
13.5 Post-Ablation Follow-up Schedule 
The subjects will be required to complete follow-up visits through 12 months post index ablation 
procedure. Follow-up will be done at 7 days (phone call or clinic visit), 1, 3, 6 and 12 months (clinic 
visit).  Follow-up visits should be scheduled according to the following timeframes: 1 month (1M 23-
37), 3 months (3M, day 76-104), 6 months (6M, day 166-194) and 12 months (12M, day 335-379). 
Follow-up visit schedule should be based on the date of the index ablation procedure and will not 
reset if subject undergoes a repeat AF ablation procedure. 
 
13.5.1 Seven (7) day follow-up visit  
Discharged subjects will receive a telephone call or have a clinic visit at 7 days (7d, day 7-9) post 
ablation procedure to assess any occurrence of Adverse Events and any change in medication 
regimen. If subject is coming for a clinic visit at day 7, data from 12 lead ECG will be collected. 
 
 
 
 

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13.5.2 Monthly follow-up visit 
At 1, 3, 6 and, 12-month follow-up visits, the following assessments will be performed: 
 
- 
Medical evaluation: 
• 
AEs 
• 
Cardiac and anti-coagulation medication regimen 
• 
Cardiac related hospitalization and cardioversions 
• 
12 Lead-ECG  
 
- 
As from 1-month: Atrial arrhythmia monitoring (non-SOC) 
• 
Remote Monitoring: subjects will be provided with a remote monitoring device at the 1M FU 
visit and asked to record and transmit a minimum of 1 transmission (≥ 30 seconds) every 
week through the end of the month 5 of FU. Starting at month 6 of FU, subjects will be asked 
to record and transmit a minimum of 1 transmission (≥ 30 seconds) every month until the 
effectiveness evaluation period is completed (12 months post index ablation procedure). 
Subjects will also be asked to transmit any symptom-triggered episode that occurs from the 
time they receive the remote monitoring device through the 12M FU visit. Remote 
monitoring will be conducted as follows:  
• 
Distribution and start by month 1. 
• 
<6M: Weekly transmission of at least 1 scheduled recording.  
• 
≥6M: Monthly transmission of at least 1 scheduled recording. 
• 
Conduct and transmit recording whenever symptoms are present.  
• 
24 Hour Holter Monitoring: per CIP a Holter monitor will be used at the 3-, 6- and 12-months 
follow-up visit to monitor the subjects ‘heart rhythm for 24 hours continuously. Following the 
24h Holter, subjects will be contacted by the site to verify if symptoms are experienced during 
24h Holter. An independent core laboratory will be used to evaluate and assess the remote 
and 24h Holter monitoring tracings.  
 
- Additional Assessments for Cardiac CT/MRA subset subjects: A cardiac CT/MRA is required to be 
performed at the 3M FU (non-SOC) visit or any other point in time when the subject presents 
with symptoms of PV stenosis.  For other subjects, a cardiac CT/MRA is only required to be 
performed if the subject presents with symptoms of PV stenosis. 
 
- Additional Assessments for NA subset subjects (non-SOC): A Cerebral MRI, Neurological Exam 
and Neurological Evaluation using the MMSE, NIHSS and mRS are required to be performed if 
any neurological symptoms and/or cerebral ischemic lesions were identified at a prior evaluation. 
NOTE: Patient questionnaires will only be used in countries with validated languages. 
 
- Additional Assessments for PVI Durability subset subjects (non-SOC): 
• 
A repeat electro anatomical creation of a paced activation map and bipolar voltage map will 
be performed at 75 days (+/-15days) post index ablation procedure to verify isolation 
durability of the treated pulmonary vein during the index ablation procedure. 
• 
A BWI multi-electrode mapping catheter should be used for the remap procedure. It is 
REQUIRED to use the same mapping catheter that was used during the index ablation 
procedure. 
• 
If reconnections are identified in the remap procedure, additional ablations may be 
performed at the discretion of the investigator with the investigational ablation system. If 
the additional ablations cannot be achieved with the investigational system, a commercially 
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- Quality of life via the Atrial Fibrillation Effect on Quality-of-Life (AFEQT™) questionnaire (non-
SOC), at Month 3, 6 and 12. NOTE: Patient questionnaires will only be used in countries with 
validated languages.  
 
13.6 Early Termination Visit 
If early termination of the study is required due to safety concerns, each site will undergo a monitoring 
visit to conclude any outstanding issues, collect all outstanding CRF information, verify device 
accountability, and discuss any other items relevant to the conclusion of the study.  Any enrolled 
subjects will continue to be followed per the CIP requirements. In case of early termination due to 
safety concerns, reporting to EC and CA may be required per local regulations. 
 
13.7 Unscheduled Visit 
If a subject returns for a potential study related cardiovascular or neurological visit outside of the CIP 
defined visit schedule provided in Table 4, the visit will be considered “unscheduled” (UNS).  An 
investigator may request an unscheduled visit in the presence of a new or worsened cardiovascular 
condition or neurological deficit. If the unscheduled visit is for a repeat ablation procedure, the CIP 
follow-up schedule is based on the index ablation procedure.  For all unscheduled visits, an 
unscheduled visit eCRF must be completed and the subject must also return for their next scheduled 
study visit per clinical investigational plan. 
 
13.8 Core Laboratory for Evaluation 
Independent central core laboratories and/or expert physician(s) will conduct objective evaluations of 
remote arrhythmia monitoring tracings, ECGs, Holter, Cerebral MRI, endoscopy and will evaluate PV 
stenosis of all subjects requiring the applicable assessments per CIP.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11. AEs must be collected from the time the subject signs the informed consent onward.  
12. Patient questionnaires will only be used in countries with validated languages. 
13. For all subjects: CT/MRA to be completed within 6 months prior to the index ablation procedure. Post procedure: for CT/MRA 
subset to be repeated at 3M FU, for all subjects CT/MRA to be repeated post procedure in case subject presents with PV stenosis 
symptoms. 
14. For PV Durability subset: an electro anatomical map, activation and voltage map is to be performed during the index ablation 
procedure (pre and post ablation) and to be repeated at 75 days post procedure (+/- 15 days). 
15. For Endoscopy subset: Endoscopy preferable between 1 day to 3 days (72hours) post procedure. For procedures on Friday a 
window of a maximum of 96 hours is justified.  
16. If observations are noted on the post-procedure MRI, the subject must have follow-up MRI at the next follow-up visit(s) until 
observations are resolved. 
17. A certified/qualified physician expert must perform neurologic exams at pre-and post-ablation and possibly at other follow-up 
visits, pending previous findings of micro-emboli/neurologic deficits. 
18. To be completed within 72-hours pre-procedure. For procedures on Monday a window of a maximum of 96 hours is justified. 
19. To be completed within 72-hours post-procedure. For procedures on Friday a window of a maximum of 96 hours is justified. 
20. Full neurological follow-up to be undertaken if neurologic symptoms and/or cerebral ischemic lesions identified in a prior 
evaluation.  
21. If subject returns for a potential study related cardiovascular or neurological visit outside of the CIP defined visit schedule as 
deemed required per investigators discretion. 
22. Assessments should not be repeated for the study if already done per standard of care within CIP defined time limits. 
 
14 Assessment of Safety 
14.1 Specific Safety Parameters 
14.1.1 Definition of Adverse Events (AE) 
 
An Adverse Event (AE) means any untoward medical occurrence, unintended disease or injury or any 
untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other persons, 
in the context of a clinical investigation, whether or not related to the investigational device (MDR 
Article 2(57)) 
 
NOTE: 
a. This definition includes events that are anticipated as well as unanticipated events.  
b. This definition includes events occurring in the context of a clinical investigation related to the 
investigational device, the comparator or the procedures involved. 
 
Specifically, an AE is any undesirable experience (sign, symptom, illness, abnormal laboratory value, 
or other medical event) occurring to a subject during the course of the study, whether or not it is 
related to the investigational device or procedure.  Physical findings (including vital signs) observed at 
follow-up, or pre-existing physical findings that worsen compared to baseline are considered AEs. 
 
Any medical condition that is present at the time that the participant is screened will be considered 
as baseline and not reported as an AE. Such conditions should be added to background medical 
history, if not previously reported. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
 
 
 
 
 
 
 

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Following arrhythmia’s do not meet the definition of an AE: 
- 
AF recurrence by itself is considered a recurrence of disease (pre-existing condition) 
- 
Recurrence of pre-existing or underlying (treated during index ablation procedure) AFL/AT is 
considered as a recurrence of disease. 
- 
Onset of non-previously identified AFL/AT which was treated during the index ablation 
procedure as underlying arrhythmia (pre-existing condition) 
- 
Re-ablation for AF or any pre-existing AFL/AT, however any procedural complication is 
considered an AE and shall be reported within the applicable timelines. 
- 
Re-ablation for any non-pre-existing (underlying) AFL/AT, which was treated during the index 
ablation procedure, however any procedural complication is considered an AE and shall be 
reported within the applicable timelines. 
- 
Cardioversion (pharmacological or synchronized electrical) for AF/AFL/AT recurrence during the 
hospitalization for the index ablation procedure, or throughout the duration of the study. 
 
Following arrhythmia’s meet the definition of an AE: 
Onset of non-pre-existing AFL/AT which was not treated during the index ablation procedure. 
 
 
 
 
 
 
 
 
 
 
 
14.1.2 Definition of Serious Adverse Event (SAE) 
 
A SAE is any event that led to any of the following: 
• Death 
• Serious deterioration in the health of a subject that resulted in any of the following: 
- 
Life-threatening illness or injury 
- 
permanent impairment of a body structure or a body function 
- 
In-patient hospitalization or prolongation of patient hospitalization* 
- 
Medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to body structure or a body function. 
- 
Chronic disease 
• Fetal distress, fetal death or a congenital physical or mental impairment or birth defect. 
 
*Planned hospitalization for a condition present prior to the participant’s enrollment in the study will 
not meet the definition of an SAE. An AE would meet the criterion of “hospitalization” if the event 
necessitated an admission to a health care facility (e.g., an overnight stay).  Emergency room visits 
that do not result in admission to the hospital should be evaluated for one of the other serious 
outcomes. 
 
 

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14.1.4 Adverse Device Effect / Serious Adverse Device Effect 
 
An adverse device effect is an AE related to the use of the investigational medical device.  
 
NOTE 1- This includes any AE resulting from insufficiencies or inadequacies in the IFU, the deployment, 
the implantation, the installation, the operation, or any malfunction of the investigational medical 
device. 
NOTE 2- This includes any event that is a result of a use error or intentional abnormal use of the 
investigational medical device. 
 
A SADE is an adverse device effect that has resulted in any of the consequences characteristic of an 
SAE. 
 
14.1.5 Unanticipated Serious Adverse Device Effect 
 
An Unanticipated Serious Adverse Device Effect (USADE) is any SAE on health, safety, 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, outcome, or degree of incidence in the current 
investigational plan or risk analysis report, or any other unanticipated serious problem associated with 
a device that relates to rights, safety, or welfare of subjects. Refer to Table 3 for a comprehensive list 
of foreseeable and anticipated AEs. 
 
14.1.6 Study Device Deficiency, Failure or Malfunction 
 
A device deficiency means any inadequacy in the identity, quality, durability, reliability, usability, 
safety, or performance of an investigational device, including:  
- Malfunction (failure to perform on its intended purpose when used in accordance with the 
IFU/CIP/IB),  
- Use errors, 
- Inadequacy in information supplied by the manufacturer (including labelling).  
 
If a device failure is detected or suspected, it should be documented on the appropriate eCRF, and 
device failure and AE must be reported per section 14 AE documentation and reporting requirements. 
 
14.1.7 Serious Public Health Threat 
Signal from any adverse event or device deficiency that indicates an imminent risk of death, serious 
illness, or a serious deterioration in a person’s state of health in subjects, users or other persons, and 
that may require prompt remedial action for other subjects, users or other persons and that may cause 
significant morbidity or mortality in humans, or that is unusual or unexpected for the given place and 
time. 
 
NOTE:  This would include events that are of significant and unexpected nature such that they become 
alarming as a potential serious health hazard or possibility of multiple deaths occurring at short 
intervals. 
 
 

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- other possible causes (e.g., an underlying or concurrent illness/ clinical 
condition or/and an effect of another device, drug, or treatment) have 
been adequately ruled out.  
- harm to the subject is due to error in use,  
- the event depends on a false result given by the investigational device 
used for diagnosis, when applicable. 
 
Probable 
 
The relationship with the use of the investigational device or the relationship 
with procedures, seems relevant and/or the event cannot be reasonably 
explained by another cause.  
 
Possible 
 
The relationship with the use of the investigational device or the relationship 
with procedures, is weak but cannot be ruled out completely. Alternative causes 
are also possible (e.g., an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug, or treatment). Cases where 
relatedness cannot be assessed, or no information has been obtained should 
also be classified as possible.  
 
Not related  
 
Relationship to the device or procedures can be excluded when:  
- the event has no temporal relationship with the use of the 
investigational device, or the procedures related to application of the 
investigational device,  
- the serious adverse event does not follow a known response pattern to 
the medical device (if the response pattern is previously known) and is 
biologically implausible,  
- the discontinuation of medical device application or the reduction of 
the level of activation/exposure - when clinically feasible - and 
reintroduction 
of 
its 
use 
(or 
increase 
of 
the 
level 
of 
activation/exposure), do not impact on the serious adverse event,  
- the event involves a body-site or an organ that cannot be affected by 
the device or procedure,  
- the serious adverse event can be attributed to another cause (e.g., an 
underlying or concurrent illness/ clinical condition, an effect of another 
device, drug, treatment or other risk factors);  
- the event does not depend on a false result given by the investigational 
device used for diagnosis, when applicable,  
 
To establish the non-relatedness and/or relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedures and the serious adverse event. 
 
 
 
 
 
 
 
 

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Permanent phrenic nerve paralysis 
0% to 0.4% 
Pulmonary vein stenosis 
<1% 
Radiation injury 
<0.1% 
Stiff left atrial syndrome 
<1.5% 
Stroke and TIA 
0% to 2% 
Vascular complications 
0.2% to 1.5% 
* Data from 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and 
surgical ablation of atrial fibrillation3  
 
Anticipated AEs are to be reported to the sponsor via EDC as indicated in section 14. 
 
14.3 Time Period and Frequency for Event Assessment and Follow-up 
 
The investigator, or designated individual, will record all reportable events with start dates occurring 
any time after informed consent is obtained. At each study visit, the investigator will inquire about the 
occurrence of AEs/SAEs since the last visit.  
 
All AEs, especially SAE’s, need to be followed until the event is resolved (with or without sequelae), 
stabilization, or until the event is adequately explained. The medical monitor or designee of this 
clinical investigation will decide if more follow-up information is needed in case the event is not 
resolved at study completion. All required treatments and outcomes of the SAE must be recorded in 
the eCRF. 
 
14.4 Reporting Procedures 
 
14.4.1  Adverse Event Documentation and Reporting Requirements  
 
Subjects should be encouraged to report AEs spontaneously or in response to general, non-directed 
questioning (e.g., “How was your health been since last visit?”). Anytime during the study, the subject 
may volunteer information that resembles an AE. 
 
Each AE must be reported to the sponsor regardless of classification, seriousness, intensity, outcome 
or causality. The investigator is responsible for ensuring that all AEs observed by the investigator, or 
reported by the subject, that occur from the time that the subject has signed the informed consent 
through the end of the study are properly assessed, recorded, and reported as defined and described 
in the AEs, Adverse Device Effects and Device Deficiencies section of this CIP (section 14). All AEs must 
be documented by completing subject’s medical records (source documents) and appropriate eCRF 
by the investigator or study coordinator throughout the study and provided to the Sponsor.  All AEs 
will be monitored until they are adequately resolved or explained.   
 
Anonymized documentation pertaining to the AE (e.g., laboratory tests, consultation reports, post-
mortem reports, new information relating to a previously reported AE, correspondence with the local 
EC, etc.) will be provided by the investigator to the sponsor or designee in a timely manner, when 
requested.  Follow-up reports relative to the subject’s subsequent course must be submitted to the 
sponsor or designee until the event has resolved or, in case of permanent impairment, until the 
condition stabilizes.  If the subject is withdrawn from the study because of the AE, the information 
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14.4.2.2 Serious Adverse Events Reporting by the Sponsor to the CA/EC 
 
As per MDR (MDCG 2021-10/1), following events are considered reportable events: 
 
a. Any serious adverse event (SAE) that has a causal relationship with the investigational 
device, the comparator or the investigation procedure of where such causal relationship 
is reasonably possible. 
 
b. Any device deficiency that might have led to a serious adverse event if:  
 
Appropriate action had not been taken or 
 
Intervention had not occurred or 
 
If circumstances had been less fortunate 
 
c. Any new finding/updates in relation to any event referred to in point a) and b)  
 
Both the relationship between the occurrence of each adverse event and the use of the medical 
investigational device, and the relationship between the occurrence of each adverse event and the 
investigational procedure must be assessed and categorized (see section 14.2.2). Only causality level 
(not related) is excluded from reporting. If either the sponsor or the investigator has assigned a higher 
causality level than ‘not related’, the event will be reported. 
 
The sponsor will ensure that investigators are instructed to return devices suspected of causing an AE 
or SAE (i.e., definitely (causal relationship) device-related or possibly device-related) in accordance 
with relevant regulations and current company procedures. 
 
In the case of serious device effects and device deficiencies that could have led to SADEs or serious 
health threat, the Sponsor will determine whether the risk analysis needs to be updated and whether 
corrective or preventative action is required. 
 
The sponsor will report or ensure reporting all reportable events and updates to the reportable events 
to the EC and CA as per national, site-specific or EC specific requirements.  The reportable events will 
be reported through the Eudamed web form once fully functional. Until then, the template for the 
Clinical Investigation Summary Safety Report Form will be used (MDCG 2020-10/2 or its next 
revisions). Event reporting to relevant CAs for non-CE-marked devices will occur by the sponsor and if 
indicated per local country requirements by the investigator.  
 
14.4.3 Unanticipated Serious Device Effect Reporting 
 
All SADE/USADE must be reported to the Sponsor, via eCRF, immediately upon awareness of event 
but no later than 72 hours by the study site personnel.  An investigator shall submit to the reviewing 
EC a report of any USADE occurring during an investigation according to EC requirements. 
 
 
 
 
 
 
 

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14.4.4 Events of Special Interest 
 
All study device failure/malfunction must be reported to the Sponsor, via eCRF, as soon as possible, 
within 72 -hours by the study site personnel.  If a device failure is detected or suspected, it should be 
documented on the eCRF, and the device returned according to the Sponsor’s instructions.  
 
The investigational device should be sent to appropriate R&D team or designated Quality engineer. 
Complaints related to non-investigational products manufactured and/or distributed by Biosense 
Webster, used during the procedure related to other devices (other than the study device under 
investigation), are to be reported according to current Biosense Webster procedures and other 
policies as necessary (i.e., institutional policies, EC policies, and local regulations). Investigators are 
instructed to return devices in accordance with current company procedures and other relevant 
regulations.  
 
Event reporting to relevant CA’s in accordance with the jurisdictional regulations will occur by the 
sponsor and/or by the investigator, depending upon the local requirements and will be done in EU per 
MDR 2017/745. Event reporting will be done through the Eudamed web form once fully functional. 
Until then, the template for the Clinical Investigation Summary Safety Report Form will be used (MDCG 
2020-10/2 or next revisions) however this format will continue to be used for events which were 
initially reported in this format.  
 
A device deficiency related to a medical device not manufactured by Biosense Webster should be 
reported by the investigator to their respective manufacturer as per relevant regulation. Complaints 
related to non-Biosense Webster, Inc. products must be handled according to institutional policies, EC 
policies, and local regulations. 
 
14.5 Safety Oversight 
 
Safety oversight will be conducted as described in the Safety Management Plan. Aggregate safety data 
will be reviewed during enrollment by the study safety lead in order to promptly identify new issues 
or trends which may have an impact on the conduct of the study and/or subject safety. Under the 
rules as defined in the Safety Management Plan, safety events will be reviewed by the Safety 
Management Team which may recommend appropriate action(s) to ensure subject safety. 
 
15 Administrative Responsibilities 
 
15.1 Ethics Committee and Competent Authority Application 
 
The CIP (or amendment[s]), ICF, and other applicable study related documents must be approved by 
the EC and CAs before enrollment of subjects. The application shall be submitted by means of the 
electronic system referred to in Article 73 (MDR [EU - 2020/561]), which shall generate a Union-Wide 
unique single identification number for the Clinical Investigation. Any additional requirement imposed 
by the EC or CA shall be discussed, agreed upon, and followed. A signed copy of the EC and CA approval 
letters addressed to the investigator must be submitted to Biosense Webster certifying study approval 
prior to subject enrollment. Biosense Webster and the EC must approve, in writing, any changes to 
the protocol that affect the rights safety and/or welfare of the subjects or may adversely affect the 
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performed in order to obtain the joint opinion from EC and CA. This applies for the initial application 
and for substantial modifications. 
 
In addition, Biosense Webster, Inc. is responsible for notifying the relevant CA of the intention to 
perform a clinical investigation under this CIP and ensure to get the official response/ approval before 
starting the clinical investigation. For all relevant communication in relation to the clinical 
investigation the Union-Wide unique single identification number shall be used as a reference. 
 
15.2 Audits and Inspections 
 
The sponsor and/or designee and/or CAs may contact the participating institution to inform the 
investigator of an upcoming audit/inspection. The investigator should immediately notify the sponsor 
of any CA audits/inspection at the study site. The audit/inspection can include the review of 
documents, facilities, records, and any other resources deemed by the authorities to be related to 
study. 
 
16 Deviations from the Clinical Investigation Plan 
The investigator is responsible for ensuring that the clinical investigation is conducted in accordance 
with the procedures and evaluations described in this CIP. The study monitors shall verify that the 
conduct of the study is in compliance with the currently approved CIP and applicable regulations and 
shall identify any issues of non-compliance with regulations or guidelines. 
 
Issues of non-compliance include but are not limited to repeated CIP deviations; failure to obtain 
proper informed consent; non-conformance to EC requirements; failure to report AEs, product 
malfunctions and other product issues; and another non-conformance to GCP. 
 
A deviation to the CIP is defined as an instance of failure to follow, intentionally or unintentionally, 
the requirements of the CIP (e.g., missed test or procedure, visit out of window, non-adherence to 
inclusion/exclusion criteria). Unplanned pregnancy during the course of the study (after index 
procedure) is not warranting ineligibility of the subject. Investigators are not allowed to deviate from 
the CIP. Waivers are prohibited for this clinical study.  Deviations to the CIP will be monitored closely 
and will be reported per EC/CA requirement.  
 
Under emergency circumstances, deviations from the CIP to protect the rights, safety and well-being 
of a subject may proceed without prior approval of the sponsor and EC.  Such deviations shall be 
documented and reported to the sponsor and the EC as required. 
 
All instructions described in this CIP are to be followed. If an amendment is required, it must be made 
in written form and receive approval from all persons and authorities who approved the original CIP. 
Administrative changes (do not affect subject’s benefits/risks ratio) may be inserted with abbreviated 
approval. All amendments will be distributed to all original CIP recipients. 
 
 
 
 
 
 
 

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17 Investigational Product  
17.1 Use of the Investigational Device and Investigator Experience 
17.1.1 Training 
Investigators selected to participate in the study will be experienced in intracardiac mapping and AF 
ablation. The training of applicable clinical site personnel will be the responsibility of the Sponsor. 
Prior to initiating subject enrollment at a site, appropriate study training will be provided.  The study 
training in includes following:  
 
- 
All investigators who will be performing the ablation procedures for this study will be required 
to attend device and PF technology training in accordance with the physician training charter.  
Investigators will also undergo a didactic training, which includes detailed reviews of the study 
catheter and the results of preclinical studies completed. This training will occur prior to first 
treatment of the subject and will take 2 hours on average. 
 
- 
To ensure uniform data collection and CIP compliance, the Sponsor will conduct a training 
session that will include reviewing the CIP, eCRF and data collection process, and the AE 
reporting process. This training will occur during the site initiation visit, prior to site activation 
and will take on average 3 to 4 hours. The sponsor will reinforce the training or provide 
clarification throughout the study, as needed. 
 
 
17.1.2 BWI Investigational Materials 
 
TRUPULSE™ Generator 
Biosense Webster, Inc. USA, is the legal manufacturer of the generator to be used in this clinical 
investigation. The TRUPULSE™ Generator manufacturing processes consist primarily of Surface-Mount 
Technology (SMT) and manual assembly in a linear assembly process with inspection responsibility 
incorporated into the manufacturing steps.  
  
Complete manufacturing records of each generator manufactured for human use during this study 
are maintained at the respective manufacturing location. Each generator is inspected in-process for 
all safety and functionality (including essential performances). Prior to release for use in the 
investigation, the testing establishes conformance to performance and safety specifications. A 
Confirmation of Conformity from Regulatory Affairs that will certify that the investigational generator 
conforms to the Essential Requirements   And that, with regard to these aspects, every precaution has 
been taken to protect the health and safety of the patient. 
 
OMNYPULSE™ Bi-Directional Catheter  
Biosense Webster, Inc. USA, is the legal manufacturer of the catheters to be used in this clinical 
investigation. The investigational devices were built in a clean room environment, and sterilized using 
EtO gas, in a manner similar to standard, commercially approved Biosense Webster products. Further 
detail of catheter components coming into contact with the human body are described in the IB.  
 
 
 
 
 
 

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Complete manufacturing records of every lot of catheters manufactured for human use during this 
study are maintained at the respective manufacturing location. Each lot of catheters are inspected 
prior to release for use in the investigation with conformance to performance and safety 
specifications. A Conformation of Conformity from regulatory Affairs that will certify that the 
investigational catheters conform to the Essential Requirements. And that, with regard to these 
aspects, every precaution has been taken to protect the health and safety of the patient.  
 
Sterile Interface Cable 
Biosense Webster, Inc. USA, is the legal manufacturer of the Sterile Interface Cable to be used in this 
clinical investigation. The investigational devices were sterilized using EtO gas, in a manner similar to 
standard, commercially approved Biosense Webster products.  
 
Complete manufacturing records of every lot of cables manufactured for human use during this study 
are maintained at the respective manufacturing location. Each lot of cables are inspected prior to 
release for use in the investigation with conformance to performance and safety specifications. A 
Conformation of Conformity from regulatory Affairs that will certify that the investigational cable 
conforms to the Essential Requirements. And that, with regard to these aspects, every precaution has 
been taken to protect the health and safety of the patient.  
 
17.2 Device Acquisition and Accountability 
After obtaining a fully executed clinical trial agreement and appropriate CA/EC approvals, the study 
site will receive the necessary amount of study-related materials prior to commencement. Study-
related devices (investigational and non-investigational) will be shipped to the site upon completion 
of required documentation. Investigational Study Devices will be labeled as “Investigational Device” 
and are only to be used for subjects enrolled in this clinical investigation.  
 
The Sponsor will keep records of all investigational devices shipped to the site.  Investigational site 
personnel are responsible for appropriate logging of devices received, verification of packing slip 
information (i.e., lot numbers and quantity shipped) and date and identifying that each device was 
used in the study and disposition information completed when returned to the Sponsor.  
 
The Investigational Device Accountability Log shall record the following information: 
− 
Date of receipt. 
− 
Person in receipt of the devices. 
− 
Quantity received. 
− 
Catalog number.  
− 
Serial/lot numbers. 
− 
Expiry Date. 
− 
Date device was used. 
− 
Subject ID on whom device was used. 
− 
Date of return. 
− 
Reason for return (i.e., used without incident, malfunction, expired, end of study, …)  
 
17.3 Device Returns 
All investigational devices (used and unused) will be returned to the Sponsor’s attention and per 
Sponsor’s Instructions.  The used OMNYPULSE ™ Bi-Directional Catheter and the guiding sheaths with 
a suspicion of DD shall be returned to the below address. Device deficiencies should be properly 
documented on the eCRF. Any suspected malfunctioning device or device associated with an AE 

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(device related or probably/ possibly device related) will undergo a thorough complaint analysis. All 
returned devices must be properly labeled with the study name, the subject identification number, 
date of issue, identified as a defective return, non-defective return, or AE (as applicable). All tracking 
information must be retained in the event the package has been lost and requires tracking. All 
investigational devices should be returned to:  
 
ATTN: Complaints Lab 
C. G Laboratories, Inc. 
2449 Bob White Drive 
Granbury, TX 76049 USA 
 
18 Clinical Monitoring  
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct 
of the trial is in compliance with the currently approved CIP /amendment(s), with GCP, and with 
applicable regulatory requirement(s). Each site will undergo periodic monitoring of the study, which 
involves a visit from a Sponsor representative, qualified to perform such visit.  Monitoring visits may 
include, but are not limited to, the following: 
− 
Adherence to the CIP  
− 
Source documentation verification and accuracy of the eCRFs  
− 
Verification that informed consent is being obtained for all subjects participating in the study in 
accordance with requirements described in the CIP.  
− 
Verification of completeness of the site file 
− 
Verification of accuracy of all study logs such as the Delegation of Responsibility Log, etc.  
− 
Compliance with applicable regulations 
− 
Identification and action to resolve any issues or problems with the study. 
 
Data are to be submitted promptly via e-CRF after collection. Missing or unclear data will be corrected 
as necessary throughout the trial. Biosense Webster will request further documentation such as 
physician and/or cardiac EP lab procedure notes when complications or malfunctions are observed 
and reported.  Specific monitoring requirements are provided in the study specific monitoring plan. 
 
19 Statistical Methodology 
The Sponsor will be responsible for the overall analysis of data from this CIP. The Statistical Analysis 
Plan (SAP) will describe all planned analyses based on the statistical design of this study and the 
subsequent data collected. A brief statistical overview of key statistical analyses is provided below. 
 
19.1 Levels of Significance 
Significance levels and the type-I error will be controlled for the primary and secondary endpoints at 
a one-sided 2.5% level.  
 
 
 
 
 
 
 

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Roll-in Analysis Set:
 
  
 
Neurological Assessment (NA) Analysis Set: 
 
 
 
 
 
Esophageal Endoscopy (EE) Analysis Set: 
 
 
 
 
Cardiac CT/MRA Analysis Set: 
 
   
 
PVI Durability Analysis Set:
 
  
 
19.4 General Conventions 
Standard descriptive summaries for continuous data include the number of observations with data, 
mean, standard deviation, median, 25% percentile, 75% percentile, minimum, and maximum values. 
For categorical data, the count and percent will be provided. Percentages will be based on the number 
of subjects without missing data.  
 
19.5 Subject Disposition  
Disposition and accountability of the study subjects will be summarized descriptively for the subject 
categories defined as following,   
 
Enrolled Subjects: Patients who sign the ICF. 
 
Excluded Subjects: Subjects who are enrolled but never undergo insertion of the study catheter. 
Excluded subjects will be subjected to safety event reporting between ICF signature and date of 
exclusion. Subjects who signed the ICF but are found to be ineligible prior to insertion of the catheter 
are also considered as excluded. 
 
Evaluable Subjects: All enrolled subjects who have the study catheter inserted.  
 
Discontinued Subjects: Evaluable subjects who have the catheter inserted, but do not undergo 
ablation (i.e., no energy is delivered with the study catheter). 
- Discontinued subjects will remain in follow-up for 3- months post catheter insertion.  
- Discontinued subset subjects are not subjected to the additional subset assessments (esophageal, 
neurological, PV and PVI durability).  
- If an SAE is reported for a discontinued subject, the subject will be followed until event resolution 
(with or without sequelae), stabilization, or until the event is adequately explained. 
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Lost to Follow-up Subjects:  Evaluable subjects of which contact is lost after most recent visit (despite 
3 documented attempts to contact the subject and a final documented attempt (e.g., certified letter). 
 
Withdrawn / Early Termination Subjects:  Subjects who withdraw consent for study participation or 
are withdrawn by the investigator, are terminated from the study prior to completion of all follow-up 
visits. 
 
Completed Subjects:  Enrolled subjects who have not been excluded, discontinued, withdrawn, 
terminated early, or lost-to-follow-up from the study prior to the final study visit. 
 
19.6 Demographic and Baseline Characteristics 
Subject demographics, medical history, previously failed AADs (if any), active AAD use (still 
administered) and other baseline data will be summarized descriptively for all enrolled subjects. 
 
19.7 Endpoints and Associated Hypotheses 
19.7.1 Primary Safety Endpoint: 
To evaluate the primary safety objective of the study, the PAE rate will be formally compared against 
a performance goal of 12%.  
 
The null and alternative hypotheses are: 
 
𝐻𝐻0: PS ≥ 0.12 vs. 𝐻𝐻𝐴𝐴: PS < 0.12, 
where PS denotes the rate of early onset Primary Adverse Events 
 
19.7.2 Primary Effectiveness Endpoint: 
The null and alternative hypotheses are: 
 
𝐻𝐻0: PE ≤ 0.90 vs. 𝐻𝐻𝐴𝐴: PE > 0.90, 
 where PE denotes the rate of acute effectiveness success 
 
19.7.3 Secondary Effectiveness Endpoint:   
The null and alternative hypotheses are: 
 
𝐻𝐻0: P1 ≤ 0.50 vs. 𝐻𝐻𝐴𝐴: P1 > 0.50, 
where P1 denotes the proportion of freedom from secondary effectiveness failures at 12 months post the initial 
ablation procedure. 
 
 
 
 
 
 

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19.8 Analyses to be Conducted. 
19.8.1 Primary Safety Endpoint 
The number and percentage of primary safety events will be reported. The hypothesis testing of the 
primary safety endpoint will be based on 3-month follow-up data. The primary safety endpoint will 
be evaluated using an exact test for a binomial proportion at a one-sided significance level of 2.5%. If 
the upper bound of the exact two-sided 95% confidence interval of the primary safety endpoint rate 
is less than the performance goal of 12%, the study will be considered to have demonstrated safety. 
The primary safety endpoint analysis will be performed in the mITT analysis set. 
 
19.8.2 Primary Effectiveness Endpoint 
The number and percentage of acute effectiveness success will be reported. The acute effectiveness 
endpoint will be evaluated using the exact test for a binomial proportion at a one-sided significance 
level of 2.5%. If the lower bound of the exact two-sided 95% confidence interval of the acute 
effectiveness success rate is greater than the performance goal of 90%, the study will be considered 
to have demonstrated effectiveness. The primary effectiveness endpoint will be performed in the Per 
Protocol analysis set. 
 
The study will be declared a success if both primary safety and acute effectiveness endpoints are met. 
A CSR will be submitted when all subjects completing 3 months of follow-up. The hypothesis of the 
secondary endpoint will be tested based on the 12-month follow-up data, only if the primary 
endpoints are met. 
 
19.8.3 Secondary Effectiveness Endpoint  
The secondary effectiveness endpoint of 12-month recurrence-free rate will be evaluated using the 
Kaplan-Meier estimate. The proportion for freedom from effectiveness failure events at 12-month, 
along with the two-sided 95% confidence interval, will be estimated. If the lower bound of the 
confidence interval is greater than the performance goal of 50%, the study will be considered to have 
demonstrated long-term effectiveness of the study system. Acute procedural failure (i.e., failure to 
confirm entrance block with or without touch-up in all PVs except those that are silent and/or cannot 
be cannulated post procedure) will also be deemed an effectiveness failure. 
 
The 12-month effectiveness success analysis will be performed in the PP analysis set. However, per 
section 13.3 and 13.4, using a commercial RF device for the treatment of arrhythmia outside the PV 
region, such as for the ablation of a CTI line for documented typical AFL identified prior to or during 
the procedure, is allowed during index or within-blanking repeat ablation procedure. To filter out the 
potential effect of the commercial RF devices on the long-term effectiveness, these subjects will be 
censored at the time of using the commercial RF device for this 12-month effectiveness analysis. 
 
If success is achieved in both the primary safety and acute effectiveness endpoints, then the secondary 
effectiveness endpoint will be tested. The secondary hypothesis test will be performed after all 
subjects have completed their 12-month follow up. The testing of the hypothesis for the secondary 
effectiveness endpoint after the success of the primary endpoints are met ensures family-wise error 
rate is controlled at a 2.5% level.  
 
 
 

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19.8.4 Subgroup Analyses 
 
Subgroup analyses by clinically relevant factors will be performed and details will be provided in SAP. 
 
19.8.5 Additional Endpoint Analyses 
 
No formal statistical hypotheses will be formulated and performed for the additional endpoints. 
Additional safety endpoints will be analyzed in SP, and mITT analysis sets. Effectiveness endpoints and 
procedural data will be analyzed in the PP and mITT analysis sets respectively. NA, EE, CT/MRA, and 
PVI durability endpoints will be analyzed in the NA, EE, CT/MRA, and PVI durability analysis sets, 
correspondingly. All endpoints will also be analyzed for the roll-in analysis set separately. Details of 
the analyses will be elaborated in the SAP.  
 
• 
PVI Durability Rate (for PVI Durability subset) 
- 
Percentage of targeted PVs in the index ablation procedure being durably isolated as 
confirmed by the electroanatomical mapping 75 days (+/- 15 days) post index ablation 
procedure. 
- 
Percentage of subjects with durably isolated targeted PVs, as confirmed by the 
electroanatomical mapping at 75 days (+/- 15 days) post index ablation procedure.  
 
• 
Single Procedural Success: defined as freedom from documented symptomatic atrial arrhythmia 
(AF, AT or AFL of unknown origin*) episodes based on electrocardiographic data (>30 seconds on 
arrhythmia monitoring device) during the effectiveness evaluation period (day 91-day 365) 
following a single index ablation procedure. 
 
 
 
• 
Freedom from documented symptomatic atrial arrythmia (AF, AT or AFL of unknown origin *) 
episodes based on electrocardiographic data (>30 seconds on arrythmia monitoring device) during 
the effectiveness evaluation period (day 91-day 365). Acute procedural failure will also be 
considered failure of 12-month symptomatic recurrence free endpoint. The proportion of 
freedom from documented symptomatic atrial arrythmia at 12 months post the index ablation 
procedure will be evaluated using the Kaplan-Meier estimate. 
 
• 
Freedom from documented (symptomatic and asymptomatic) atrial arrhythmia (AF, AT or AFL 
of unknown origin*) episodes based on electrocardiographic data (>30 seconds on arrhythmia 
monitoring device) during the effectiveness evaluation period (day 91-day 365) with extra failure 
modes. A subject who meets any of the following criteria will also be deemed an effectiveness 
failure:  
- 
Failure to achieve acute procedural success.  
- 
Taking a new Antiarrhythmic Drug (AAD) (Class I / Class III) for atrial tachyarrhythmia (AF, 
AT or AFL of unknown origin*) or taking a previously failed Class I/III AAD at a greater than 
the highest ineffective historical dose for AF/AFL/AT during the effectiveness evaluation 
period (day of 3-month visit – day 365). 
- 
Greater than 1 repeat ablation for AF/AT or AFL of unknown origin* in the blanking period 
or any repeat ablation for AF/AT or AFL of unknown origin* during the effectiveness 
evaluation period. 
 
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The proportion of freedom from documented symptomatic atrial arrythmia and extra failure 
modes at 12 months post the index ablation procedure will be evaluated using the Kaplan-Meier 
estimate.  
 
• 
Use of a non-study device for the purpose of PVI (i.e., touch-up) among all clinically relevant 
targeted PVs during the index procedure and/or ablation of left atrial non-PV AF targets (i.e., 
posterior wall) during index ablation procedure or for repeat procedures during blanking period 
will be summarized descriptively by the purposes of use, timing of use, at the subject-level and at 
the vein-level, if applicable. 
 
• 
Acute reconnection identified by adenosine/isoproterenol challenge among all clinically relevant 
targeted PVs will be summarized descriptively at the subject-level and at the vein-level. 
 
• 
Repeat ablation procedures for left atrial arrhythmia (AF, AT or AFL of unknown origin*) within 
the 12-month FU period will be summarized descriptively for the following: 
- 
Percentage of subjects with repeat ablation during blanking period (≤90 days post index 
ablation procedure). 
- 
Percentage of subjects with repeat ablation after blanking period (day 91 – 365 post index 
ablation procedure). 
- 
Percentage PV reconnection observed during repeat ablation procedures by targeted PVs 
treated at index ablation procedure and by subject. 
- 
Percentage of subject with repeat ablations due to non-PV targets. 
 
• 
Quality of Life (QoL): the change of QoL assessed by comparing the Atrial Fibrillation Effect on 
Quality-of-Life (AFEQT™) scores before and at 3, 6 and 12- months after the ablation procedure 
will be summarized descriptively in subjects with non-missing data. 
 
• 
Hospitalization for cardiovascular events through 12 months follow-up compared to 12 months 
prior to baseline.  
 
 
 
The proportion of freedom from cardiovascular events-related hospitalization at 12 months post 
the index ablation procedure will be evaluated using the Kaplan-Meier estimate. The change of 
cardiovascular events-related hospitalization between 12-month before and after the index 
procedure will be summarized descriptively, in terms of the percent of subjects with event, 
average length of stay. 
 
• 
Safety  
- 
Occurrence of Serious Adverse Device Effects (SADEs) 
- 
Occurrence of Unanticipated Serious Adverse Device Effects (USADEs) 
- 
Occurrence of Serious Adverse Events (SAEs) within 7 days (early-onset), 8 to 30 days 
(peri-procedural) and >30 days (late onset) of index ablation procedure 
- 
Occurrence of non-serious adverse events (non-SAEs)  
 
 
 
 
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• 
Neurological Assessment Subset 
- 
Occurrence of new post-ablation asymptomatic and symptomatic cerebral emboli 
observed post-ablation as determined by Magnetic Resonance Imaging (MRI) evaluations 
will be summarized by the anatomical location. The size of the lesions will be listed for 
individual events.  
- 
Incidence of new or worsening neurological deficits post-ablation and at follow-up, 
compared to baseline. 
- 
Mini Mental State Examination (MMSE), National Institute of Health Stroke Scale (NIHSS) 
and Modified Rankin Scale (mRS) will be summarized descriptively for the evaluation at 
baseline, post-ablation and during follow-up (if lesions were identified in prior evaluation). 
 
• 
CT/MRA Subset 
- 
Occurrence of PV stenosis up to 3 months post-ablation as determined by Computed 
Tomography (CT)/ magnetic Resonance Angiogram (MRA) evaluations. 
 
• 
Esophageal Endoscopy Subset 
- 
Occurrence of endoscopically detected esophageal thermal lesions in the region of the 
contact area between esophagus and LA as determined by post procedure endoscopy. 
Note: *AFL of unknown origin is defined as all AFL except those CTI dependent AFL as confirmed by 12-lead 
electrocardiogram (ECG) or entrainment maneuvers in an EP study. 
 
19.9 Handling of Missing Data  
 
• 
 
 
 
  
 
• 
 
 
 
• 
To investigate the robustness of the analysis result for the primary endpoints, several sensitivity 
analyses will be performed. Details on these analyses will be provided in SAP. 
 
20 Ethics and Protection of Human Subjects 
20.1 Ethical Standard 
As the Sponsor of this study, Biosense Webster has the overall responsibility for the conduct of the 
study, including assurance that the study meets the applicable European medical device regulation 
and the local government. For this study, MDR2017/745 will be applicable. The Sponsor will also 
maintain compliance with GCP (ICH E6 (R2), 9 November 2016), the European standard EN ISO 14155 
(Clinical Investigation of Medical Devices for Human Subjects), the Declaration of Helsinki (Ethical 
Principles for Medical Research Involving Human Subjects, Fortaleza 2013), Sponsor general duties (21 
CFR 812.40), selection of investigators (21 CFR 812.43), monitoring (21 CFR 812.46), supplemental 
applications (21 CFR 812.35 [a] and [b]), maintaining records (21 CFR 812.140 [b]), and submitting 
reports (21 CFR 812.150 [b)]), and to local regulations where required. 
 
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- 
General Duties: Biosense Webster’s general duties consist of submitting the clinical investigation 
application to appropriate regulatory agencies, assuring that sites have received EC approvals 
prior to shipping the devices, selecting investigators, ensuring proper clinical site monitoring, and 
ensuring subject informed consent is obtained. 
- 
Data Quality and Reporting: Biosense Webster is responsible for providing quality data that 
satisfy federal regulations and informing proper authorities of serious unanticipated AEs and 
deviations from the CIP.   
- 
Selection of Investigators: All potential investigational sites will undergo an evaluation to ensure 
that the site has the appropriate facilities and personnel to conduct the study in compliance with 
the clinical investigational plan. Based on outcome of evaluation process, Biosense Webster will 
select qualified investigators, ship devices only to participating investigators, obtain a signed 
Investigator’s Agreement and provide the investigators with the information necessary to conduct 
the study. 
- 
Supplemental Applications: As appropriate, Biosense Webster will submit changes in the Clinical 
Investigational Plan to the investigators to obtain all applicable re-approvals. 
- 
Maintaining Records: Biosense Webster will maintain copies of correspondence, data, adverse 
device effects and other records related to the study. Biosense Webster will maintain records 
related to the signed Investigator Agreements. 
- 
Submitting Reports: Biosense Webster will submit any required regulatory reports identified in 
this section of the regulation.  This may includeUSADEs, withdrawal of EC approval, current 
investigators list, annual progress reports, recall information, final reports, and CIP deviations.  
 
20.2 Informed Consent Process 
20.2.1 Informed Consent Procedure and Documentation 
Subjects informed consent must be obtained and documented according to the principles of informed 
consent in the latest version of the Declaration of Helsinki (Fortaleza, 2013), ISO 14155, and approved 
by the reviewing CA and EC. 
 
Informed consent is mandatory and must be obtained from all subjects prior to their participation in 
the study. 
 
Prior to screening or performing any study related procedures that are solely for the purpose of 
determining eligibility for this study, any potential benefits and risks of the study must be explained 
to the subject. Subjects will be informed about aspects of the study that are relevant to the subject's 
decision to participate. Subjects should be made aware that by signing the ICF, they are granting 
approval for study personnel to review their medical records and to collect/analyze personal medical 
information. Subjects should also be informed that study personnel will maintain confidentiality of the 
medical records at all times. 
 
The ICF will be written in a native, non-technical, language that is understandable to the subject and 
is to be approved by the applicable EC prior to enrolling subjects. The subject or designee will be 
provided with ample time to read and understand the ICF and to consider participation in the study. 
Informed consent will be requested prior to enrollment and must be personally signed and dated by 
the subject, or subject’s legal representative, prior to performance of any study related activity or 
procedure. If a subject is unable to read or write, informed consent shall be obtained through the aid 
of an independent witness who will be present throughout the process. The written ICF and any other 

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information shall be read aloud and explained to the prospective subject and, whenever possible, 
subject shall sign and date the ICF. The witness must also sign and date the ICF attesting that the 
information was accurately explained, and that informed consent was freely given. The point of 
enrollment corresponds with the time that subjects sign the informed consent. The subject will receive 
one copy of the fully signed ICF. 
 
The investigator and/or designee must also clearly document the process of obtaining informed 
consent in the subject’s source documents and maintain the investigational site’s signed informed 
consent with the essential documents. The voluntary process of obtaining informed consent confirms 
the subject’s willingness to participate in the study. It’s the investigator’s responsibility to ensure that 
the informed consent process is performed in accordance with ICH-GCP and, where applicable, local 
and federal regulations. Subjects should not be coerced, persuaded, or unduly influenced to 
participate or continue to participate in the trial. Subjects or his/her legal representative must be given 
ample time and opportunity to inquire about details of the trial and all questions about the trial should 
be answered to the satisfaction of the patient or the representative. Failure to provide written 
informed consent renders the subject ineligible for the study. If new information becomes available 
that can significantly affect a subject’s future health and/or medical care, this information shall be 
provided to the subject(s) affected in written form. If relevant, all affected subjects shall be asked to 
confirm their continuing informed consent in writing by dating and signing the amended ICF. 
 
20.3 Participant and Data Confidentiality 
During this clinical investigation, all representatives of the Sponsor will comply with all in-country 
privacy laws and regulations regarding contact with subjects, their medical record information, 
copying of information, and protection of the subject identities. 
 
All information and data sent to Biosense Webster concerning subjects or their participation in this 
clinical investigation will be considered confidential. Only authorized Biosense Webster personnel or 
representatives (including contracted service providers, i.e. Core Lab, Clinical Research Associate, 
CRO, etc.), representatives of the FDA or CAs acting in their official capacities will have access to these 
confidential files upon request (including, but not limited to, laboratory test result reports, ECG 
reports, admissions/discharge summaries for hospital admission occurring during a patient’s study 
participation and autopsy reports for deaths occurring during the clinical investigation). Some of the 
countries to which the study subjects and investigators personal data may be transferred may not 
offer as comprehensive a level of protection of personal data as within the European Union but 
Sponsor will take all reasonable steps to ensure a sufficient level of data protection. All data used in 
the analysis and reporting of this evaluation will exclude identifiable reference to the subject. 
 
20.3.1 Research Use of Stored Data 
- 
Intended Use: Data collected under this CIP may be used to study AF. 
- 
Storage: Access to stored data will be limited. Data will be stored using codes assigned by the 
sponsor. Data will be kept in password-protected computers. Only investigators and the sponsor 
will have access to the data. 
 
21 Source Documents and Access to Source Data/Documents 
Data entered on to the eCRFs will be taken from source documentation, such as hospital procedure 
reports, admission and discharge summaries, other hospital or investigator office/clinic documents, 
and system data (CARTO™, generator system). If unique study parameters are not documented on 

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standard hospital or office reports, a worksheet may be developed to record this information.  The 
worksheet shall be signed by the PI or authorized designee and will serve as source document and as 
basis for monitoring the eCRFs.  Electronic subject records will be considered as source documents on 
the condition that the hospital’s database is a validated system. If this is not the case, electronic 
records should be printed and added to the subject’s paper file. A print-out of a completed eCRF 
cannot be used as source documentation.  
 
Investigators should maintain information in the subject’s medical records, which corroborate data 
collected on the eCRFs. In order to comply with these regulatory requirements, at minimum, the 
following is a list of information that should be maintained. 
- Medical history/physical condition of the study subject before involvement in the study sufficient 
to verify CIP selection criteria (if not already present). 
- Dated and signed notes from the day of entry into the study including the study Sponsor (Biosense 
Webster), CIP number, clinical site, subject number assigned and a statement that consent to 
participate in the study was obtained. 
- Dated and signed notes from each study visit with reference to the eCRFs for further information, 
if appropriate (for specific results of procedures and exams). 
- Reports on AEs and their resolution, including supporting documents such as discharge 
summaries, EP lab reports, ECGs, lab results. 
- Notes regarding CIP -required medication and prescription medications taken during the study 
(including start and stop dates). 
- Notes on subject’s condition upon completion of or withdrawal from the study. 
 
Only authorized Biosense Webster personnel or representatives, authorized site personnel and 
government authorities acting in their official capacities, will have access to these confidential files. 
 
22 Quality Assurance and Quality Control 
Quality Control (QC) procedures will be implemented beginning with the data entry system and 
ongoing QC checks will be run on the database. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. Following written SOPs, monitors will verify 
that the clinical trial is conducted, and data are generated, documented, and reported in compliance 
with the CIP, GCP, and the applicable regulatory requirements. If noncompliance is identified, Sponsor 
is required by regulation to implement measures to secure compliance. The investigational site will 
provide direct access to all trial related sites, source data/documents, and reports for the purpose of 
monitoring and auditing by the sponsor, and inspection by local and CAs. 
 
23 Data Handling and Record Keeping 
23.1 Data Collection and Management Responsibility 
The Sponsor will be responsible for all data management activities. These activities include 
development of an EDC system and utilizing a validated EDC system into which all study data will be 
entered. The Sponsor will be responsible for reviewing all data to ensure the overall integrity of the 
database. 
 
 
 
 
 
 

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23.1.4 Final Data Analysis 
All exported datasets for analyses will undergo a final data review before final database lock. Once all 
critical data are monitored and locked, the final analyses of clinical investigation data will be 
performed. 
 
23.2 Study Record Retention and Archiving 
Records and reports for the study will remain on file at the site for a minimum of 10 years or per 
country specific record retention requirements following notification by the sponsor that all 
investigations have been terminated or completed, or in the event that the device is subsequently 
placed on the market, at least 10 years after the last device has been placed on the market. This 
documentation must be accessible upon request by the CAs, the sponsor, or a designee. The sponsor 
must approve archiving, transfer, and destruction of the documentation, in writing, prior to the actual 
archiving, transfer, and destruction.  The investigator must notify the sponsor, in writing, of transfer 
location, duration, and the procedure for accessing the study documentation. 
 
If the investigator retires, relocates, or withdraws from assuming primary responsibility for keeping 
the study records, custody transfer per written notice must be submitted to the sponsor indicating 
the name and address of the person accepting primary responsibility. The EC must be notified in 
writing of the name and address of the new custodian. Record retention dates must be provided to 
all parties by the sponsor’s corporation. 
 
Each Member State shall require that this documentation is kept at the disposal of the competent 
authorities for the period referred to in the first section of the paragraph, in case the Sponsor, or its 
contact person or legal representative as referred to in Article 62 (2) (MDR [EU - 2020/561]) 
established within its territory, goes bankrupt or ceases its activity prior to the end of this period. 
 
24 Study Suspension or Termination 
This clinical investigation may be temporarily suspended or prematurely terminated at the discretion 
of the Sponsor. The Sponsor may also terminate a site prior to study completion if the Sponsor believes 
the site is no longer capable of participating (e.g., cannot fulfill subject enrollment or CIP compliance 
goals, site suspension by EC). If the CI is prematurely terminated or suspended, the PI will promptly 
inform the EC and will provide the reason(s) for the termination or suspension.  
 
If suspension or premature termination occurs, the terminating party shall justify its decision in writing 
and promptly inform the other parties with whom they are in direct communication. The PI and 
sponsor shall keep each other informed of any communication received from either the EC or the CA. 
 
If early termination of the study is required due to safety concerns, each site will undergo a monitoring 
visit to conclude any outstanding issues, collect all outstanding CRF information, verify device 
accountability, and discuss any other items relevant to the conclusion of the CI. Any enrolled subjects 
will continue to be followed per the CIP requirements. 
 
If, for any reason, the sponsor suspends or prematurely terminates the study at an individual study 
site, the sponsor shall inform the responsible CA as appropriate and ensure that the EC is notified, 
either by the PI or by the sponsor. If the suspension or premature termination was in the interest of 
safety, the sponsor shall inform all other PIs. 
  
 

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Circumstances that may warrant termination or suspension include, but are not limited to:  
- If suspicion of an unacceptable risk, including serious health threat, to subjects arises during 
the clinical investigation, or when so instructed by the EC or regulatory authorities, the 
sponsor shall suspend the clinical investigation while the risk is assessed. The sponsor shall 
terminate the clinical investigation if an unacceptable risk which cannot be controlled is 
confirmed.  
- Instructions by the EC or regulatory authority to suspend or prematurely terminate 
participation in a clinical investigation at the investigation sites for which they are responsible. 
- Demonstration of efficacy that would warrant stopping.  
- Insufficient compliance to CIP requirements.  
- Data that are not sufficiently complete and/or evaluable.  
- Determination of futility.  
 
The clinical investigation may resume once concerns about safety, CIP compliance, data quality is 
addressed and satisfy the sponsor, EC and regulatory agency. 
 
The Sponsor must notify the CA in case of a temporary halt or early termination of the clinical 
investigation. This notification must be made within 15 days of the temporary halt or early 
termination, providing a justification for the event. In the event that the sponsor has temporarily 
halted or terminated early the investigation on safety grounds, the CA must be informed within 24 
hours of the event. 
 
25 Study Completion 
The study end shall be deemed to coincide with the last visit of the last subject or last 12-month 
assessment date (i.e., Holter end date). The sponsor will inform the responsible CA within 15 days of 
the study end in a participating country. In addition, each CA will be notified within 15 days of the 
global study end.  
 
Within one year of the end of the clinical investigation, the full final clinical investigational report must 
be submitted to the CA.  A clinical investigation ends with the last visit of the last subject unless 
another endpoint is specifically set out in the clinical investigation plan. 
 
26 Data and Publication Policy 
Publications and/or presentation of clinical investigation results will be coordinated and governed 
between Biosense Webster, Inc., the clinical investigation author(s) and if applicable local law. 
Authorship will be determined prior to development of any manuscript. All information concerning 
the study, investigational medical device, sponsor operations, patent application, manufacturing 
processes, and basic scientific data supplied by the sponsor to the investigator and not previously 
published, are considered confidential and remain the sole property of the sponsor. As per ISO 
14155:2020 paragraph 5.4. a description of this clinical investigation will be registered in publicly 
accessible database (http://www.ClincialTrials.gov) and content will be updated throughout the study. 
Results will be entered at completion of the clinical investigation.   
 
27 Document Filing 
A copy of all approved versions of the Clinical Investigation Plan will be kept, by the site, in the 
Investigator Site File and in the Sponsor Trial Master File. 
 

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28 Scientific References 
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Dukkipati, S.R., et al., Pulmonary Vein Isolation Using the Visually Guided Laser Balloon: A 
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Chavez, P., et al., Atrioesophageal fistula following ablation procedures for atrial fibrillation: 
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Deneke, T., et al., Postablation asymptomatic cerebral lesions: long-term follow-up using 
magnetic resonance imaging. Heart Rhythm, 2011. 8(11): p. 1705-11. 

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14-21. 
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Atrial Fibrillation Undergoing Left Atrial Catheter Ablation in the Randomized AXAFA-AFNET 
5 Trial. Circulation, 2022. 145(12): p. 906-915. 
44. 
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13(10): p. e008192. 
45. 
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cerebral lesions comparing irrigated radiofrequency current ablation with the cryoballoon 
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29 Appendix 1 
 
Definitions on effectiveness terms are mentioned below. 
 
Term 
Definition 
Recurrent AF/AT/AFL 
Recurrent AF/AFL/AT is defined as AF/AFL/AT of at least 30 seconds’ 
duration that is documented by an ECG or device recording system and 
occurs following catheter ablation. Recurrent AF/AFL/AT may occur 
within or following the post ablation blanking period. Recurrent 
AF/AFL/AT that occurs within the post-ablation blanking period is not 
considered a failure of AF ablation. 
Early recurrence of AF/AFL/AT 
Early recurrence of AF/AFL/AT is defined as a recurrence of atrial 
fibrillation within three months of ablation. Episodes of atrial 
tachycardia or atrial flutter should also be classified as a “recurrence.” 
These are not counted toward the success rate if a blanking period is 
specified. 
Recurrence of AF/AT/AFL 
Recurrence of AF/AFL/AT post-ablation is defined as a recurrence of 
atrial fibrillation more than 3 months following AF ablation. Episodes 
of atrial tachycardia or atrial flutter should also be classified as a 
“recurrence.” 
 
Electrocardiographical occurrences of new onset non left atrial 
arrhythmia’s, if confirmed by entrainment maneuvers during 
electrophysiology testing, should not be considered an ablation failure 
or primary effectiveness endpoint. Examples are: 
• 
CTI dependant AFL. Cavotricuspid isthmus-dependent atrial flutter 
is easily treated with cavotricuspid isthmus ablation and is not an 
iatrogenic arrhythmia following a left atrial ablation procedure for 
AF. 
• 
Atrioventricular nodal reentry tachycardia (AVNRT) 
Off AAD  
As assessed from the end of the 3-month blanking period (Day 91 or 
Day of the visit whatever comes last) to 12 months following the 
ablation procedure. 
 
Class I and III antiarrhythmic drug therapy, same dose as before 
procedure is not considered as failure. 
Class I and III antiarrhythmic drug therapy, higher dose or newly 
prescribed after procedure is considered as failure. 
 
Class I and III antiarrhythmic drug therapy prescribed for other 
arrhythmia’s than AF/AT/AFL is not considered as failure 
 
 
 

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Deep venous thrombosis 
Rhabdomyolysis, including produced by body 
position or propofol 
Diaphragmatic paralysis 
Sedation induced CO2 retention with lethargy and 
cholecystitis 
Dislodgement/Malfunction of 
pacemaker/defibrillator leads 
Seizure 
Disseminated Intravascular Coagulation 
Sepsis 
Dizziness, presyncope, vertigo 
Sinus bradycardia 
Dysphagia 
Sinus tachycardia 
Dyspnea 
Skin burn or necrosis 
Endocarditis 
Skin discoloration 
Epigastric Distress 
Skin edema 
Epistaxis 
Skin or soft tissue (radiation) injury/tear 
Esophageal injury / perforation 
Subclavian artery puncture 
Expressive aphasia 
Temperature elevation / Fever 
Fatigue 
Thrombocytopenia 
Gastric hypomotility 
Thromboembolism 
Gastroesophageal reflux 
Thrombosis 
Gastrointestinal disorders 
Thyroid disorders 
Gastrointestinal diverticulosis 
Toxic reaction 
Gastroparesis 
Transient extremity numbness 
Headache 
Transient Ischemic attack (TIA) 
Heart failure (acute or chronic) 
Urinary Retention Postoperative 
Heart injury 
Urinary tract injury or infection related to the 
urinary catheter 
Heart valve insufficiency 
Valvular damage/insufficiency 
Hemoptysis 
Vascular (access) dissection (including coronary 
arteries) 
Hemorrhage 
Vascular occlusion 
Hemothorax 
Vasovagal reactions 
High/increased creatine phosphokinase (CPK) 
Ventricular Fibrillation 
Hypertension 
Vessel damage/trauma 
Hypervolemia 
Vessel perforation 
Hypotension 
Vessel spasm (including coronary arteries) 
Hypovolemia 
Visual disturbance 
Hypoxia 
Worsening of pre-existing pulmonary disease  
Increased phosphokinase level 
Wound healing disturbance 
Infection, localized  
  
*Atrial Fibrillation and exacerbation of an existing arrhythmia are anticipated adverse events.  
However, they will not be captured as such under this protocol, as they are considered recurrence of 
disease.