Clinical Evaluation of Intracardiac Ultrasound With the NUVISION NAV Ultrasound Catheter
Phase: NA
Conditions: Scar-related Atrial Tachycardia, Persistent Atrial Fibrillation, Paroxysmal Atrial Fibrillation, Ventricular Tachycardia, Premature Ventricular Complex
Sponsor: Biosense Webster, Inc.

NUVISION NAV Study 
 
Version 2.0 
Protocol # BWI202104 
 
17 Apr 2023 
 
Biosense Webster, Inc. 
CONFIDENTIAL 
     Page 1 of 55 
 
 
 
 
Clinical Evaluation of Intracardiac Ultrasound  
with the NUVISION™ NAV Ultrasound Catheter.  
“NUVISION NAV Study” 
 
 
Protocol Number:  
BWI202104 
 
Sponsor: 
Biosense Webster, Inc., a division of Johnson & Johnson with registered office 
at 31 Technology Drive, Suite 200 Irvine, CA 92618, USA  
 
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:  
2.0 
Date: 
17 Apr 2023 
 
Eudamed number 
CIV-23-04-042835 
 
 History of Changes: 
Version — Date 
Description 
 
V 1.0 – 7 Nov 2022 
Original Document 
 
V 2.0 – 7  Apr 2023 
Updated 
 
Updated 
 
 
 
 
 
The NUVISION™ NAV Ultrasound Catheter and the NUVISION™ Connector Cable are approved and 
licensed in the USA but not yet approved in Europe and Israel, and thus considered investigational 
device for use in this study. 
 
 

NUVISION NAV Study 
 
Version 2.0 
Protocol # BWI202104 
 
17 Apr 2023 
 
Biosense Webster, Inc. 
CONFIDENTIAL 
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1. Table of Contents 
1. 
TABLE OF CONTENTS ....................................................................................................................................... 2 
2. 
LIST OF FIGURES AND TABLES ......................................................................................................................... 5 
3. 
LIST OF ACRONYMS AND ABBREVIATIONS ...................................................................................................... 6 
4. 
KEY ROLES AND RESPONSIBLE PARTIES ........................................................................................................... 8 
5. 
PROTOCOL SUMMARY .................................................................................................................................. 10 
6. 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ......................................................................... 16 
6.1 BACKGROUND INFORMATION...................................................................................................................................... 16 
6.2 PREVIOUS EXPERIENCE WITH THE INVESTIGATIONAL CATHETER .......................................................................................... 17 
6.2.1 Investigational catheter animal testing ....................................................................................................... 17 
6.3 RATIONALE FOR DESIGN OF THE CLINICAL INVESTIGATION ................................................................................................. 17 
6.4 POTENTIAL RISK AND BENEFIT ..................................................................................................................................... 17 
6.4.1 Known Potential Risks .................................................................................................................................. 17 
6.4.2 Minimization of Risk .................................................................................................................................... 18 
6.4.3 Anticipated Clinical Benefits ........................................................................................................................ 19 
7. 
OBJECTIVES AND PURPOSE ........................................................................................................................... 19 
7.1 OBJECTIVE............................................................................................................................................................... 19 
7.2 PURPOSE ................................................................................................................................................................ 20 
8. 
STUDY DESIGN AND ENDPOINTS ................................................................................................................... 20 
8.1 DESCRIPTION OF THE STUDY DESIGN ............................................................................................................................ 20 
8.2 STUDY ENDPOINTS .................................................................................................................................................... 20 
8.2.1 Primary Endpoints ....................................................................................................................................... 20 
8.2.2 Secondary Endpoints ................................................................................................................................... 20 
8.2.3 Additional Endpoints.................................................................................................................................... 20 
9. 
STUDY POPULATION ..................................................................................................................................... 21 
9.1 PARTICIPANT INCLUSION CRITERIA ............................................................................................................................... 21 
9.2 PARTICIPANT EXCLUSION CRITERIA ............................................................................................................................... 21 
10. 
PARTICIPANT WITHDRAWAL OR TERMINATION ........................................................................................... 22 
10.1 REASONS FOR WITHDRAWAL OR TERMINATION ............................................................................................................ 22 
10.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION ........................................................................................ 22 
10.3 SUBJECT DISPOSITION.............................................................................................................................................. 23 
11. 
RESPONSIBILITIES ......................................................................................................................................... 23 
11.1 INVESTIGATOR RESPONSIBILITIES ............................................................................................................................... 23 
11.2 SPONSOR RESPONSIBILITIES ...................................................................................................................................... 24 
12. 
STUDY DEVICE DESCRIPTION ......................................................................................................................... 25 
12.1 DEVICE ACQUISITION............................................................................................................................................... 25 
12.2 DEVICE STORAGE AND STABILITY ............................................................................................................................... 25 
12.3 DEVICE PREPARATION ............................................................................................................................................. 25 
12.4 INSTRUCTIONS FOR USE ........................................................................................................................................... 25 
12.5 DEVICE DESCRIPTION AND SPECIFIC CONSIDERATIONS ................................................................................................... 25 
12.6 ADDITIONAL EQUIPMENT ......................................................................................................................................... 27 
12.6.1 System Components and Setup ................................................................................................................. 27 
12.6.2 Required Study Devices .............................................................................................................................. 28 
13. 
STUDY MEDICATION ..................................................................................................................................... 28 
14. 
STUDY SCHEDULE .......................................................................................................................................... 28 
14.1 SCREENING AND INFORMED CONSENT ........................................................................................................................ 28 

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14.2 BASELINE EVALUATION AND PROCEDURES ................................................................................................................... 29 
14.2.1 Pre-Procedure/Baseline Assessments ........................................................................................................ 29 
14.2.2 Study Procedure ......................................................................................................................................... 30 
14.2.3 Collection of Procedure Data for Post-Analysis (non-SOC) ........................................................................ 31 
14.2.4 Data Collection during Study Ablation Procedure ..................................................................................... 31 
14.2.5 Pre-Discharge Assessments ....................................................................................................................... 31 
14.3 POST-PROCEDURE FOLLOW-UP SCHEDULE ................................................................................................................... 31 
14.4 EARLY TERMINATION VISIT ....................................................................................................................................... 31 
14.5 UNSCHEDULED VISIT ............................................................................................................................................... 32 
14.6 CORE LABORATORY FOR EVALUATION ......................................................................................................................... 32 
14.7 SCHEDULE OF EVENTS TABLE .................................................................................................................................... 32 
15. 
ASSESSMENT OF SAFETY ............................................................................................................................... 33 
15.1 SPECIFIC SAFETY PARAMETERS ....................................................................................................................... 33 
15.1.1 Definition of Adverse Events (AE) .............................................................................................................. 33 
15.1.2 Definition of Serious Adverse Event (SAE) .................................................................................................. 33 
15.1.3 Adverse Device Effect / Serious Adverse Device Effect .............................................................................. 33 
15.1.4 Unanticipated (Serious) Adverse Device Effect .......................................................................................... 34 
15.1.5 Study Device Deficiency ............................................................................................................................. 34 
15.2 CLASSIFICATION OF AN ADVERSE EVENT ...................................................................................................................... 34 
15.2.1 Severity of Event ........................................................................................................................................ 34 
15.2.2 Relationship to Study Device ..................................................................................................................... 34 
15.2.3 Outcome .................................................................................................................................................... 35 
15.2.4 Expectedness (Anticipatedness)................................................................................................................. 35 
15.3 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP ........................................................................ 37 
15.4 REPORTING PROCEDURES ......................................................................................................................................... 38 
15.4.1 Adverse Event Documentation and Reporting Requirements ................................................................... 38 
15.4.2 Serious Adverse Events Reporting ............................................................................................................. 39 
15.4.3 Unanticipated Device Effect Reporting ...................................................................................................... 39 
15.4.4 Events of Special Interest ........................................................................................................................... 39 
15.5 SAFETY OVERSIGHT ................................................................................................................................................. 40 
16. 
ADMINISTRATIVE RESPONSIBILITIES ............................................................................................................. 40 
16.1 ETHICS COMMITTEE AND COMPETENT AUTHORITY APPLICATION ..................................................................................... 40 
16.2 AUDITS AND INSPECTIONS ........................................................................................................................................ 40 
17. 
DEVIATIONS FROM THE CLINICAL INVESTIGATIONAL PLAN .......................................................................... 41 
18. 
INVESTIGATIONAL PRODUCT ........................................................................................................................ 41 
18.1 USE OF THE INVESTIGATIONAL DEVICE AND INVESTIGATOR EXPERIENCE ............................................................................. 41 
18.1.1 Training ...................................................................................................................................................... 41 
18.1.2 Materials ................................................................................................................................................... 41 
18.2 DEVICE ACQUISITION AND ACCOUNTABILITY ................................................................................................................ 42 
18.3 DEVICE RETURNS .................................................................................................................................................... 42 
19. 
CLINICAL MONITORING ................................................................................................................................. 43 
20. 
STATISTICAL METHODOLOGY ........................................................................................................................ 43 
20.1  
LEVELS OF SIGNIFICANCE ................................................................................................................................... 43 
20.2  
SAMPLE SIZE JUSTIFICATION ............................................................................................................................... 44 
20.3  
ANALYSIS SETS ................................................................................................................................................ 44 
20.4 
ANALYSES TO BE CONDUCTED ............................................................................................................................. 44 
20.4.1 General Conventions .................................................................................................................................. 44 
20.4.2 Subgroups .................................................................................................................................................. 44 
20.4.3 Subject Disposition..................................................................................................................................... 44 
20.4.4 Demographic and Baseline Characteristics ............................................................................................... 44 
20.4.5 Medical History .......................................................................................................................................... 45 
20.4.6 Analysis for Primary Endpoints .................................................................................................................. 45 
20.4.7 Analyses of Secondary Endpoints .............................................................................................................. 46 

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20.4.9 Handling of Missing Data .......................................................................................................................... 47 
21. 
ETHICS AND PROTECTION OF HUMAN SUBJECTS .......................................................................................... 47 
21.1 ETHICAL STANDARD ................................................................................................................................................ 47 
21.2 INFORMED CONSENT PROCESS .................................................................................................................................. 48 
21.2.1 Informed Consent Procedure and Documentation .................................................................................... 48 
21.3 PARTICIPANT AND DATA CONFIDENTIALITY .................................................................................................................. 49 
21.3.1 Research Use of Stored Data ..................................................................................................................... 49 
22. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ........................................................... 49 
23. 
QUALITY ASSURANCE AND QUALITY CONTROL ............................................................................................. 50 
24. 
DATA HANDLING AND RECORD KEEPING ...................................................................................................... 50 
24.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITY ................................................................................................ 50 
24.1.1 Data Collection .......................................................................................................................................... 50 
24.1.2 Data Reporting .......................................................................................................................................... 50 
24.1.3 Data Verification and Review .................................................................................................................... 51 
24.1.4 Final Data Analysis .................................................................................................................................... 51 
24.2 STUDY RECORD RETENTION AND ARCHIVING................................................................................................................ 51 
25. 
STUDY COMPLETION, SUSPENSION OR TERMINATION ................................................................................. 52 
26. 
DATA AND PUBLICATION POLICY .................................................................................................................. 53 
27. 
DOCUMENT FILING ....................................................................................................................................... 53 
28. 
SCIENTIFIC REFERENCES ................................................................................................................................ 54 
 
 
 
 

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2. List of Figures and Tables 
FIGURE 1: OVERVIEW INVESTIGATIONAL STUDY DEVICES............................................................................................. 26 
FIGURE 2: CONNECTIVITY DIAGRAM FOR SYSTEM SET-UP ............................................................................................ 27 
 
TABLE 1: REQUIRED STUDY DEVICES .............................................................................................................................. 28 
TABLE 2: SUMMARY OF SUBJECT VISITS AND ASSESSMENTS ........................................................................................ 32 
TABLE 3: INTENSITY OR SEVERITY DEFINITIONS ............................................................................................................. 34 
TABLE 4: ADVERSE EVENT CAUSALITY CLASSIFICATIONS ............................................................................................... 35 
TABLE 5: ADVERSE EVENT OUTCOME CLASSIFICATIONS ............................................................................................... 35 
TABLE 6: COMPREHENSIVE LIST OF ANTICIPATED ADVERSE EVENTS ............................................................................ 36 
TABLE 7: AE REPORTING REQUIREMENTS ..................................................................................................................... 38 
TABLE 8: RESPONSIBILITIES FOR PREPARING AND SUBMITTING REPORTS ................................................................... 51 
 
 

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3. List of Acronyms and Abbreviations 
Acronym/ 
Abbreviation 
Expanded Term 
ACC 
American College of Cardiology 
ACT 
Activated Clotting Time 
AE 
Adverse Event 
AF 
Atrial Fibrillation 
ASIC 
Application-Specific Integrated Circuit 
AT 
Atrial Tachycardia 
CA 
Competent Authority 
CABG 
Coronary Artery Bypass Graft  
CIP 
Clinical Investigational Plan 
CRF 
Case Report Form 
CRO 
Clinical Research Organization 
CT 
Computed Tomography 
CTA 
Clinical Trial Agreement 
CVA 
Cerebrovascular Accident or Stroke 
DD 
Device Deficiency 
EC 
Ethics Committee 
ECAS 
European Cardiac Arrhythmia Society 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EHRA 
European Heart Rhythm Association 
EMEA 
Europe, Middle East and Africa 
EP 
Electrophysiology 
ESC 
European Society of Cardiology 
EtO 
Ethylene Oxide 
FAM  
Fast Anatomical Mapping  
FDA 
Food and Drug Administration 
F 
French 
FU 
Follow-Up 
GCP 
Good Clinical Practices 
GLP 
Good Laboratory Practice 
HRS 
Heart Rhythm Society 
IB 
Investigator’s Brochure 
ICE 
Intracardiac Echocardiography 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IFU 
Instruction for Use 
LA 
Left Atrium 

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Acronym/ 
Abbreviation 
Expanded Term 
LAA 
Left Atrial Appendage 
LAAO 
Left Atrial Appendage Occlusion 
LAT 
Local Activation Time 
LV 
Left Ventricle 
LVEF 
Left Ventricular Ejection Fraction 
MDD 
Medical Device Directive 
MDR 
Medical Device Regulation 
MRI 
Magnetic Resonance Imaging 
NYHA 
New York Heart Association 
PAF 
Paroxysmal Atrial Fibrillation 
PI 
Principal Investigator 
PIU 
Patient Interface Unit 
PP 
Per Protocol 
PsAF 
Persistent Atrial Fibrillation 
PTCA 
Percutaneous Transluminal Coronary Angioplasty 
PV 
Pulmonary Vein 
PVCs 
Premature Ventricular Complex 
PVI 
Pulmonary Vein Isolation 
QC 
Quality Control 
RA 
Right Atrium 
RF  
Radiofrequency  
RV 
Right Ventricle 
SADE  
Serious Adverse Device Effect  
SAE  
Serious Adverse Event  
SOC 
Standard Of Care 
SPU 
Signal Processing Unit 
TEE 
Transesophageal Echocardiography 
TIA 
Transient Ischemic Attack 
TRUEref 
Tightly Referenced Unipolar Electrode reference 
TTM 
TransTelephonic Monitor 
TTE 
Transthoracic Echocardiography 
UADE 
Unanticipated Adverse Device Effect 
ULS 
UltraSound 
UM 
User Manual 
USADE 
Unanticipated Serious Adverse Device Effect 
VT 
Ventricular Tachycardia 
 
 
 

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4. 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:   
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
Whereas, the Clinical Study 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 Study on its behalf. 
 
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 PIs at 
each site, roles and responsibilities and qualifications of each respective investigator, institutions and 

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Contract Research Organizations (if applicable). The definitive list shall be integrated into the study 
report. 
 
The current protocol has been developed based on regulations applicable in Europe and Israel, for 
other countries outside Europe a country specific version of this study protocol may be developed, 
further defining regional regulations, if applicable. 
 
 

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5. Protocol Summary 
 
 
Full Title 
Clinical Evaluation of Intracardiac Ultrasound with the NUVISION™ NAV 
Ultrasound Catheter. 
Short Title 
NUVISION NAV Study 
Protocol Number 
BWI202104 
Eudamed 
number 
CIV-23-04-042835 
Sponsor 
Biosense Webster, Inc. 
Indication 
Intra-cardiac and intra-luminal visualization of cardiac and great vessel 
anatomy and physiology as well as visualization of other devices in the heart 
during cardiac interventional percutaneous procedures.  
Description of 
Investigational 
Devices 
The investigational NUVISION™ NAV Ultrasound Catheter (D-1426-01-SI), is a 
sterile, single use, disposable, diagnostic ultrasound imaging catheter designed 
for intracardiac use. It is built around the core design and technology of the 
existing NUVISION™ Ultrasound Catheter, 10 Fr (D-1423-01-S).  
 
 
 
 
 
 
 
 
  
 
 
The investigational NUVISION™ Connector Cable 
(FG10594) is used to connect the catheter to the GE Ultrasound System. The 
multipin SOUNDSTAR™ eco Cable is used to connect the catheter to the 
CARTO™ 3 System.  
Premarket or 
Post market 
Premarket 
Study Design 
Prospective, single arm, non-randomized, open-label, multi-center 
Primary 
Objective 
• 
Assess performance of the NUVISION™ NAV Ultrasound Catheter when 
used during study procedures 

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• 
Assess safety of the NUVISION™ NAV Ultrasound Catheter when used 
during study procedures 
Secondary 
Objective 
• 
Characterize 
physician 
feedback 
regarding 
the 
deployment, 
maneuverability, navigational features and imaging quality acquired with 
the NUVISION™ NAV Ultrasound Catheter during study procedures 
Primary 
Endpoints  
• 
Performance: Completion of imaging required for the study procedure 
with the NUVISION™ NAV Ultrasound Catheter without resort to a non-
study ultrasound device 
• 
Safety: Occurrence of serious adverse events within 7 days of index 
procedure related to the NUVISION™ NAV Ultrasound Catheter 
Secondary 
Endpoints 
• 
Physician assessment of deployment, maneuverability, navigational 
features and imaging quality acquired with the NUVISION™ NAV 
Ultrasound Catheter during the study procedures 
• 
Occurrence of all other serious adverse events within 7 days of index 
procedure (not related to the NUVISION™ NAV Ultrasound Catheter) 
• 
Occurrence of non-serious adverse events within 7 days of index 
procedure related to the NUVISION™ NAV Ultrasound Catheter 
Study Population 
Subjects who are scheduled to undergo an imaging process during an 
interventional cardiac ablation procedure for management of the following: 
1) Scar-related Atrial Tachycardia (AT; includes atypical atrial flutter), 
procedures resulting from previous atrial fibrillation ablation; 
2) Persistent Atrial Fibrillation (PsAF); 
3) Paroxysmal Atrial Fibrillation (PAF); 
4) Ventricular Tachycardia (VT): ischemic and non-ischemic VT, 
cardiomyopathy and idiopathic VT; 
5) Premature Ventricular Complex (PVC); 
Sample Size 
Up to 30 subjects will be enrolled in the study. 
Geographic areas 
to be included 
Europe and Israel 
Study Duration 
Approximately 5 months enrollment and 7-day follow-up per subject.   
Visit Intervals 
Baseline/procedure, 7-day follow-up phone call or clinic visit after study 
procedure 
Procedure(s) 
description 
 
During study procedures, investigators will use the investigational catheter 
instead of the institution’s standard ultrasound catheter (e.g. SOUNDSTAR™ 
ultrasound catheter). 

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The use of the investigational catheter is mandatory for thrombus detection, 
imaging for volume measurements, during transseptal puncture and as 
navigational ultrasound (ULS) catheter throughout the procedure. 
Any use of a non-investigational ultrasound device will be considered a failure 
of the primary effectiveness endpoint. 
Statistical 
Analysis 
There will be no formal hypothesis testing on outcomes in this study.  The 
safety and performance data below will be summarized with descriptive 
statistics. 
 
Analysis for these endpoints will be performed overall and per procedure type 
(atrial ablation/ventricular ablation). 
 
Analysis for Primary Endpoints:  
 
Performance 
- 
The number and proportion of subjects in whom imaging is performed 
successfully with the investigational catheter without resort to a non-
study ultrasound device.   
 
Safety 
- 
Serious Adverse Events related to the investigational catheter during 
the 7-day follow-up period  
 
Analysis for Secondary and Additional Endpoints:  
 
Physician Feedback  
- 
Physician feedback on the catheter deployment, maneuverability, 
navigational features and imaging quality acquired with the 
investigational catheter will be collected and summarized by using a 
physician-completed survey with a Likert scale of 1 to 7 (1=poor and 
7=excellent). 
 
Procedural data, including, but not limited to: 
- 
Anatomical structures assessed 
- 
Whether imaging for Left Atrium (LA) and Left Ventricle (LV) volume 
measurements was done 
- 
Total fluoroscopy time 
- 
Total procedure duration 
 
Safety 
- 
All other SAEs during the 7-day follow-up period (not related to the 
investigational catheter) 
- 
All investigational catheter related non-serious Adverse Events during 
the 7-day follow-up period 
 
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for 
participation in this clinical investigation. 

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1. Diagnosed with and candidate for clinically-indicated cardiac ablation 
procedure for the management of ventricular tachycardia, premature 
ventricular complex, scar-related atrial tachycardia or atrial fibrillation 
(patients having undergone a previous ablation procedure may be 
included). 
2. Age 18 years or older. 
3. Signed Patient Informed Consent Form (ICF). 
4. Able and willing to comply with all pre-, post-, and follow-up testing and 
requirements. 
Exclusion Criteria 
Subjects who meet any of the following exclusion criteria are not eligible for 
enrollment. 
1. Structural heart defect which can only be repaired by cardiac surgery   
2. Pericarditis within 6 months  
3. LVEF ≤ 25% for VT patients 
4. LVEF ≤ 40% for patients with atrial arrhythmia 
5. History of chronic gastro-intestinal medical problems involving the 
esophagus, stomach and/or untreated acid reflux 
6. History of abnormal bleeding and/or clotting disorder.  
7. Clinically significant infection or sepsis 
 
8. History of stroke or TIA within the past 6 months of enrollment 
9. Uncontrolled heart failure or NYHA function class IV 
10. Implanted with a pacemaker or intracardiac cardiac defibrillator within 
the past 6 weeks (42 days) 
11. Implanted with a mechanical valve 
12. Diagnosed atrial or ventricular myxoma, interatrial baffle or patch, tumor 
or other abnormality that precludes catheter introduction or 
manipulation. 
13. Any of the following within 6 months (182 days) of enrollment 
a. Major surgery except for the index procedure 
b. Myocardial infarction 
c. Unstable angina 
d. Percutaneous coronary intervention (e.g. CABG or PTCA) 
14. Patients with any other significant uncontrolled or unstable medical 
condition 
(such 
as 
uncontrolled 
bradyarrhythmia’s, 
ventricular 
arrhythmias, hyperthyroidism, or significant coagulation disorder) 
15. Significant congenital anomaly or medical problem that in the opinion of 
the investigator would preclude enrollment in this study. 
16. Women who are pregnant (as evidenced by pregnancy test if pre-
menopausal), lactating, or who are of childbearing age and plan on 
becoming pregnant during the course of the clinical investigation.  
17. Categorized as vulnerable population and requires special treatment with 
respect to safeguards of well-being. 
18. Concurrent enrollment in an investigational study evaluating another 
device or drug. 
Time and Events 
Schedule 
Pre-Procedure/Baseline 
• 
Informed consent documentation 
• 
Demographics 
• 
Medical history assessment 

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• 
Transthoracic echocardiogram for assessment of ejection fraction (not 
required if the subject has undergone an imaging procedure within the 
last 6-months where the requested values were assessed) 
• 
Cardiac computed tomography (CT) for assessment of cardiac anatomy 
(not required if the subject has undergone a CARTOMERGE™ 
compatible cardiac CT within 60 days of the procedure) 
• 
Pregnancy test for women of child-bearing potential (within 1-week 
before the procedure) 
• 
Adverse events 
Procedure 
• 
Use of the NUVISION™ NAV Ultrasound Catheter to confirm absence 
of thrombus 
• 
Procedural parameters 
• 
Use of the NUVISION™ NAV Ultrasound Catheter 
1. Imaging for LA and LV volume measurements 
2. During transseptal puncture 
3. Navigational feature throughout the procedure   
• 
Adverse events and procedural complications 
• 
Device deficiency 
• 
Physician survey 
Discharge  
• 
Adverse events 
7-Day Follow-Up visit  
• 
Adverse events 
 

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Assessments1 
Screening / 
Baseline 
(Clinic Visit) 
Study 
Procedure 
Discharge 
7-day  
Follow-up  
(Clinic Visit 
or Phone 
call) 
Informed 
Consent2 
 
 
 
 
Demographics 
 
 
 
 
Medical and 
Cardiac 
History3 
 
 
 
 
Transthoracic 
Echo (TTE)4, 8 
 
 
 
 
Cardiac CT5, 8 
 
 
 
 
Pregnancy 
Test6, 8 
 
 
 
 
Thrombus 
detection7 
 
 
 
 
Adverse 
Events9 
 
 
 
 
1. Standard of care assessments can be performed before ICF signature 
2. Informed consent to be signed within the 60 days prior to procedure  
3. Medical history-including but not limited to arrhythmia, heart disease and 
thromboembolic events 
4. TTE to determine the LVEF % within the 60 days prior to procedure (if the 
subject has undergone imaging in the last 6 months where the requested 
values were assessed, the assessment is not required) 
5. Cardiac CT for assessment of cardiac anatomy within 7 days prior to 
procedure (if the subject has undergone a CARTOMERGE™ compatible CT 
within 60 days of the procedure, the assessment is not required) 
6. Pregnancy tests for women of child-bearing potential only within the 7 days 
prior to procedure 
7. Thrombus detection, to rule out the presence of thrombus – mandatory to 
be performed with the investigational catheter during the study procedure 
8. Assessment should not be repeated for the study if already done per standard 
of care within the protocol defined time limits.   
9. AEs must be collected from the time the subject signs the informed consent 
onward. 
 
 

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6. Background Information and Scientific Rationale 
6.1 Background Information 
Intracardiac Echocardiography (ICE) is a common imaging modality used to visualize the various 
heart chambers during percutaneous interventional and electrophysiological procedures. For 
years, two-dimensional (2D) ICE was a widely used imaging technology in the electrophysiology 
(EP) and catheterization labs as alternative for Transesophageal Echocardiography (2D and real 
time (RT) 3D TEE) in both adults and children [1, 2, 3, 4, 5, 6].  
Recently, ICE has moved from 2D echo to 3D and 4D echo imaging capabilities, with 4D being 
high-quality 3D moving images. This has greatly improved device guidance visualization and 
allows real-time assessment of cardiac anatomy [7, 8]. The usage of ICE imaging is now also 
increasing for Left Atrial Appendage Occlusion (LAAO) procedures for which TEE imaging was 
the gold standard [9, 10]. Various articles have been published demonstrating that ICE catheters 
can help physicians to guide and localize devices in the heart, guide transseptal puncture, LAAO 
and ablation procedures and, can be used as an adjunct with other imaging modalities such as 
fluoroscopy to aid in placement of devices. ICE can also be used to exclude procedural 
complications such as a pericardial effusion or thrombus formation [10, 11, 12, 13].   
 
The introduction of the 4D NUVISION™ ICE Catheter Into the interventional cardiology and 
cardiac electrophysiology segments was successful and the product is routinely used by leading 
centers in the US. 
The First-in-Human Experience With Novel 4D ICE Catheter For Catheter Ablation and Left Atrial 
Appendage (LAA) Closure Procedures- HRS 2021 late-breaking study shows the utility of 3D/4D 
intracardiac echo image guidance for EP procedures [14]. 
 
This study will focus on a Navigational 4D ICE Ultrasound Catheter NUVISION™ NAV developed 
by Biosense Webster including the CARTO™ 3 interface which will enable electrophysiologists, 
structural heart cardiologists, and other physicians to image the heart on the CARTO™ 3 
mapping windows in conjunction with other navigational devices for diagnostic, device 
placement guidance and mapping.  
 
The NUVISION™ NAV Ultrasound Catheter is a single use, disposable, diagnostic ultrasound 
imaging catheter designed for intracardiac echo use. It is built around the core design and 
technology of the existing NUVISION™ ICE Catheter, 10 Fr (D-1423-01-SI) and will integrate the 
handling, mechanical performance, and imaging capability of his predecessor the NUVISION ICE 
catheter. 
 
 
 
 
  
 
Those features will support electrophysiologists in intra-cardiac and intra-luminal visualization 
of cardiac and great vessel anatomy and physiology as well as visualization of other devices in 
the heart. The catheter is intended for imaging guidance only, not treatment delivery, during 
cardiac interventional percutaneous procedures.  
 
 
 
 

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- 
 
 
6.2 Previous Experience with the Investigational Catheter 
6.2.1 Investigational catheter animal testing 
This study is the first in human study with the investigational catheter. Refer to the 
Investigator’s Brochure (IB) for a detailed description of the preclinical testing performed.  
 
 
 
 
 
 
  
 
6.3 Rationale for Design of the Clinical Investigation 
The study is a first in human study with the investigational catheter. Clinical experience in 30 
subjects, in various chambers of the heart, operated by multiple physicians in different hospitals 
will allow for initial characterization of the performance and safety of the investigational 
catheter. The selected physicians have experience with similar products and/or pre-clinical 
experience with the investigational catheter.  
 
Further knowledge regarding the performance and safety of the investigational catheter will be 
gathered during the External Evaluation in the US (FDA 510(k) clearance received on 16-Feb-
2023). 
 
The sample size was selected based on previous experience with similar design in first in human 
assessments of diagnostic catheters. This study is meant to characterize the catheter’s ability to 
perform safely in various types of procedures. No clinical claims of effectiveness or patient 
outcomes will be made from this study.  
 
Therefore, the study is designed as a prospective, multicenter, single arm clinical study. Only 
descriptive analysis will be performed. 
 
6.4 Potential Risk and Benefit 
6.4.1 Known Potential Risks 
The identified potential risks and hazards are common to the use of Intracardiac 
Echocardiography (ICE) catheters during cardiac mapping and ablation procedures: 
 
• 
Arrhythmia: The possible arrhythmia associated with the use of ICE catheters (risk is <0.2%) 
could occur by manipulation in unintended locations, or locations of high probability for 
arrhythmia such as atrial appendages or ventricular walls.  
The added CARTOSOUND™ sensor in this catheter will allow easier catheter orientation and 
location identification, what is expected to assist the operator in avoiding arrhythmogenic 
regions of the heart. 
• 
Heart injury (heart injury, cardiac perforation): Heart injury may result from catheter 

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manipulation when appropriate visualization is unavailable (risk is ≤0.002%). Cardiac 
perforation may result in pericardial effusion or cardiac tamponade which requires 
percutaneous pericardial drainage or surgical repair [15]. To prevent heart injury, the 
investigational catheter should be used as instructed. 
The CARTOSOUND™ capability allows the operator to map the intended region/chamber 
without physically entering the chamber with the catheter. This will reduce catheter 
manipulation and avoid regions of the heart susceptible to injury. 
• 
Burn: as for all electrical equipment, improper use and/or defects may lead to a short circuit, 
leading to skin burns (risk <0.02%). 
• 
Chest injury (esophageal injury): this catheter is contraindicated for use as TEE. When used as 
TEE esophageal injury may occur (risk ≤0.002%)  
• 
Thromboembolism or embolus: Intracardiac ultrasound catheters are not irrigated, a thrombus 
could form (risk ≤0.002%). Embolization of thrombus could produce stroke, myocardial 
infarction, or other ischemic injury. To prevent this injury, The Activated Clotting Time (ACT) 
should be maintained above the minimum level of 300 seconds while the investigational 
catheter is in the heart.   
• 
Hypersensitivity (allergic reaction, anaphylactic reaction): to the local anesthetic, sedatives, X-
ray dye, heparin, protamine, or other agents administered during the procedure (risk <1%) 
[16, 17, 18, 19, 20]. 
• 
Infection (sepsis, wound infection): The percutaneous procedure carries risk of infection, either 
at the catheter insertion site or systemically, including endocarditis and septic emboli (risk 
<0.5%) [21, 22]. This risk can be minimized by using standard aseptic technique and, when 
indicated, by the use of antibiotic agents. 
• 
Arterial or venous injury: including arterial dissection, thrombosis, occlusion or hemorrhage at 
the catheter insertion sites or at other sites along the vessels (risk < 1%) [21, 22]. These types 
of injuries may cause hemorrhage, hematoma, or ischemic injury to an extremity or major 
organ. Hemorrhage as a result of anticoagulation (risk < 0.5%), which may require transfusion 
[21, 22]. This risk can be minimized by using clinical standards of care, and a compatible sheath. 
• 
Entanglement and/or entrapment: When the investigational catheter is within the proximity 
of the tricuspid valve or mitral valve, caution needs to be applied to avoid entanglement and/or 
entrapment in cardiac tissue or vascular structure (risk <0.02%) [23]. 
• 
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%) [17, 21, 22, 24, 25, 26, 27, 28]. 
 
A Comprehensive List of Anticipated Adverse Events for standard cardiac RF ablation 
procedures can be found in chapter 15.2.4, table 6 
 
There are no anticipated potential direct risks to the patient related to the investigational 
connection cable. 
 
6.4.2 Minimization of Risk 
The criteria for subject selection, methods, personnel, facilities, and training that are specified 
in this study are intended to minimize the risk to subjects undergoing this procedure.  
 

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Patient selection:  Subjects will be prescreened 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 
adverse events (refer to Section 9.2 for the Exclusion Criteria).  
 
Imaging for thrombus detection: Subjects will be screened for the presence of thrombus with 
the investigational ultrasound catheter, which is intended to decrease the potential for 
thromboembolic complications. 
 
Within procedure safeguards: Investigators highly skilled in intracardiac mapping and 
ablation procedures will be selected for participation in the study.  These procedures will be 
performed in electrophysiology laboratories with the assistance of skilled nurses and 
technicians. Study investigators will undergo training prior to performing procedures with the 
investigational catheter. 
 
Post-procedural management: Investigators will be encouraged to follow recommended 
guidelines for systemic oral anticoagulation therapy for a given subject after their procedure.  
 
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 “Assessment of Safety” in section 
15.0 for more information on safety management. 
 
6.4.3 Anticipated Clinical Benefits 
For ablation procedures, the investigational devices (catheter and connection cable) are 
expected to contribute to the improvement of workflow and procedural efficiency by: 
• 
Supporting real-time 2D, 3D and 4D ultrasound imaging options controlled by user as 
well as pulsed and continuous wave color flow doppler in each imaging mode. 
• 
Allowing customized ultrasound image preparation and presentation to suit user 
clinical needs. 
• 
Combining ultrasound imaging with the CARTO™ 3 Navigation System to provide 
accurate magnetic navigation for electro-anatomical mapping and better image 
quality. 
• 
Having the ability to visualize internal cardiac structures in real time in conjunction 
with static cardiac CARTO maps. 
• 
Minimizing fluoroscopy usage (reduced fluoroscopy dose and time) which reduces the 
radiation exposure. 
The potential effectiveness and efficiency gains stated above are expected to provide benefit 
to patients by shorter procedure times and better clinical outcomes. 
 
7. Objectives and Purpose  
7.1 Objective 
The primary objective of this study is to assess the performance and safety of using the 
investigational catheter. 
 
A secondary objective is to gather physician assessment of deployment, maneuverability, 
navigational features and imaging quality acquired with the investigational catheter. 
 

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7.2 Purpose 
The purpose of this study is to evaluate the safety and feasibility of the NUVISION™ NAV 
Ultrasound Catheter performance for further product development. 
 
8. Study Design and Endpoints 
8.1 Description of the Study Design 
This study is a prospective, single arm, non-randomized, open-label, multi-center study.  Up to 
30 subjects will be enrolled. 
 
Subjects meeting the inclusion / exclusion criteria and who sign the informed consent form (ICF) 
will be enrolled in this study. The clinical investigation is targeting approximately 4 sites in 
Europe and Israel.  
 
This study will serve to characterize the performance and safety of using the investigational 
catheter in procedures for subjects in up to five different subgroups (scar-related AT, PsAF, PAF, 
VT and PVC). Subjects will be treated per investigator’s standard of care and followed until 7 
days post-procedure. 
 
Planned analyses are described in the Statistical Analysis section 20.0 of this clinical 
investigational plan. 
 
8.2 Study Endpoints 
8.2.1 Primary Endpoints 
Performance 
Completion of imaging required for the study procedure with the NUVISION™ NAV 
Ultrasound Catheter without resort to a non-study ultrasound device. 
Safety 
Occurrence of serious adverse events within 7 days of index procedure related to the 
NUVISION™ NAV Ultrasound Catheter.  
 
8.2.2 Secondary Endpoints 
Physician feedback 
Physician assessment of deployment, maneuverability, navigational features and imaging 
quality acquired with the NUVISION™ NAV Ultrasound Catheter during the study 
procedures. 
Safety 
- Occurrence of all other serious adverse events within 7 days of index procedure 
(excluding NUVISION™ NAV Ultrasound Catheter related SAE’s) 
- Occurrence of non-serious adverse events within 7 days of index procedure related to 
the NUVISION™ NAV Ultrasound Catheter 
 
8.4.3 
Additional Endpoints  
− 
Additional procedural data, including but not limited to: 
- 
Anatomical structures assessed 

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- 
Whether imaging for Left Atrium (LA) and Left Ventricle (LV) volume measurements 
was done 
- 
Total fluoroscopy time 
- 
Total procedure duration. 
 
− 
Additional safety data 
All non-serious adverse events not related to investigational catheter. 
 
9. Study Population 
The study population consists of subjects scheduled to undergo an imaging process for an 
interventional cardiac ablation procedure for management of the following: 
1) Scar-related Atrial Tachycardia (AT; includes atypical atrial flutter), procedures resulting from 
previous atrial fibrillation ablation; 
2) Persistent Atrial Fibrillation (PsAF); 
3) Paroxysmal Atrial Fibrillation (PAF). 
4) Ventricular Tachycardia (VT): ischemic and non-ischemic VT, cardiomyopathy and idiopathic 
VT. 
5) Premature Ventricular Complex (PVC) 
 
9.1 Participant Inclusion Criteria 
Candidates for this study must meet ALL of the following criteria: 
1. Diagnosed with and candidate for clinically-indicated cardiac ablation procedure for 
the management of ventricular tachycardia, premature ventricular complex, scar-
related atrial tachycardia or atrial fibrillation (patients having undergone a previous 
ablation procedure may be included). 
2. Age 18 years or older. 
3. Signed Patient Informed Consent Form (ICF). 
4. Able and willing to comply with all pre-, post-, and follow-up testing and 
requirements. 
 
9.2 Participant Exclusion Criteria 
Candidates will be excluded if ANY of the following criteria apply: 
1. Structural heart defect which can only be repaired by cardiac surgery   
2. Pericarditis within 6 months  
3. LVEF ≤ 25% for VT patients 
4. LVEF ≤ 40% for patients with atrial arrhythmia 
5. History of chronic gastro-intestinal medical problems involving the esophagus, 
stomach and/or untreated acid reflux 
6. History of abnormal bleeding and/or clotting disorder.  
7. Clinically significant infection or sepsis  
8. History of stroke or TIA within the past 6 months of enrollment 
9. Uncontrolled heart failure or NYHA function class IV 
10. Implanted with a pacemaker or intracardiac cardiac defibrillator within the past 6 
weeks (42 days) 
11. Implanted with a mechanical valve 
12. Diagnosed atrial or ventricular myxoma, interatrial baffle or patch, tumor or other 
abnormality that precludes catheter introduction or manipulation. 

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13. Any of the following within 6 months of enrollment 
a) 
Major surgery except for the index procedure 
b) 
Myocardial infarction 
c) 
Unstable angina 
d) 
Percutaneous coronary intervention (e.g. CABG or PTCA) 
14. Patients with any other significant uncontrolled or unstable medical condition (such 
as uncontrolled bradyarrhythmia’s, ventricular arrhythmias, hyperthyroidism, or 
significant coagulation disorder) 
15. Significant congenital anomaly or medical problem that in the opinion of the 
investigator would preclude enrollment in this study. 
16. Women who are pregnant (as evidenced by pregnancy test if pre-menopausal), 
lactating, or who are of childbearing age and plan on becoming pregnant during the 
course of the clinical investigation.  
17. Categorized as vulnerable population and requires special treatment with respect to 
safeguards of well-being. 
18. Concurrent enrollment in an investigational study evaluating another device or drug. 
 
10. Participant Withdrawal or Termination 
10.1 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 
protocol required follow-up period. 
 
10.2 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). If the subject withdraws 
consent PRIOR to insertion of the study catheter, the subject can be replaced. 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 or until the participant has been deemed lost to follow-up after 
demonstration of due diligence of follow-up efforts.   
 
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 
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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. 
All applicable case report forms up to the point of subject withdrawal must be completed. Data 
collected up to the point of subject withdrawal may be used, unless local regulations apply.  
10.3 Subject Disposition 
• 
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. 
• 
Discontinued Subjects: Enrolled subjects who have the study catheter inserted but no 
assessments are performed with it.  Discontinued subjects will remain in follow-up for 7 
days for safety evaluation.   
• 
Lost to Follow-up Subjects: Enrolled subjects of which contact is lost after most recent 
visit (despite 3 documented attempts to contact the subject). 
• 
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. 
 
11. Responsibilities 
11.1 Investigator Responsibilities 
Investigators at each participating clinical site will have the following responsibilities: 
• 
Assuring compliance by site personnel with the provisions of the protocol 
• 
Providing the Sponsor with: 
o Signed, dated Investigator Agreement 
o Written Ethics Committee (EC) approval letters and EC-approved consent 
forms 
o Signed, dated Financial Disclosure form for each participating investigator 
o 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 protocol 
• 
Completing the appropriate training on the device and the Clinical Study Protocol/ 
Investigational Plan prior to enrolling and using the catheter in subjects 
• 
Maintain accurate and current logs for the study such as:  
o Subject log, Device Accountability Log 

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• 
Obtain initial and amendment (if applicable) EC approval and annual review/approval 
thereafter for the study protocol and informed consent as applicable 
• 
Obtain ICF and enroll patients 
• 
Perform medical procedures 
• 
Order tests required by the study protocol 
• 
Follow subjects until the end of the study protocol 
• 
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 
• 
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 final 
report. 
 
11.2 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 Clinical Study Protocol/Investigational Plan, CRFs and informed consent  
• 
Selection of appropriately qualified and trained individuals, including monitors, to 
conduct the study  
• 
Conduct protocol and device training for investigators and research personnel as 
applicable 
• 
Set-up of study-specific committees (if applicable). 
• 
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 

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• 
Report (including AE’s and DDs) to study investigators and regulatory agencies, as 
required 
• 
Have relevant safety information reviewed by the Study Safety Lead, as required 
• 
Communications with the CA 
• 
Submission of any amendments to the Clinical Study Protocol/Investigational Plan to 
the CA. 
• 
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. 
 
12. Study Device Description 
12.1 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 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. 
 
12.2 Device Storage and Stability 
Devices are to be stored in a secure/locked location and in accordance with the catheter and 
cable IFU. Do not use the (disposable) devices after the “Use By” date.  
 
12.3 Device Preparation 
Information related to device preparation can be found in the IFU. 
 
12.4 Instructions for Use 
A comprehensive set of IFU for the study devices and all accessory cables/interface cables is 
contained in each product package and is also available upon request.   
 
12.5 Device Description and Specific Considerations 
The investigational study devices are indicated in Figure 1. 
 
 
 
 
 
 
 
 
 
 
 
 

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12.6 Additional Equipment 
12.6.1 System Components and Setup 
 
 
 
 
 
 
 
 
 
The following devices, which may be CE marked by other companies, may also be required for 
the procedure: 
− 
 
 
  
 
 
  
 
 
  
 
  
 
  
 
 
 
Figure 2: Connectivity diagram for system set-up 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 

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12.6.2 Required Study Devices 
These devices must be used for the study procedure and are required per protocol. 
 
Table 1: Required Study Devices 
 
  
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
13. Study Medication 
Medications in this protocol are at physician discretion and should reflect the center’s standard 
of care for the procedure type.  Anticoagulation therapy should be administered at a dose 
sufficient to meet a minimum ACT level of 300 seconds prior to insertion of the investigational 
catheter and throughout the procedure. 
 
14. Study Schedule  
14.1 Screening and Informed Consent 
Candidates presenting to the institution with a cardiac arrhythmia in scope of the protocol, and 
considered for an ablation procedure, should be screened by the investigator or designated 
member of the research team for study eligibility per the protocol inclusion and exclusion 

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criteria. Sites will be instructed to screen all subjects who require a documented ablation 
procedure for a cardiac arrhythmia in scope of the protocol, 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. Failure to obtain informed consent renders the 
subject ineligible for participation in the study. 
 
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) 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.   
 
14.2 Baseline Evaluation and Procedures 
14.2.1 Pre-Procedure/Baseline Assessments 
Below pre-procedure assessments and data collection must be performed prior to the ablation 
procedure.   
 
Within 60 days prior to the study procedure: 
• Baseline Medical, Cardiac History (including findings from TTM, ECG, Holter monitor, 
etc.)  
• Transthoracic Echocardiogram (TTE) – imaging to assess ejection fraction  
Note: Available imaging within 6 months prior to the procedure (TTE or other acceptable 
equivalent cardiac imaging – i.e. CT/MRI) can be used to assess the LVEF. In case the 
imaging assessment is older than 6 months LVEF shall be re-assessed prior to insertion of 
the study catheter. In case the re-measurements before study catheter insertion fail to 
meet the LVEF criteria, the subject will be considered as not meeting eligibility and will be 
excluded.   
 
Within 7 days prior to the study procedure: 
Cardiac CT – imaging to assess the cardiac anatomyNote: An available Cardiac CT, 
obtained within 60 days prior to the procedure, with a segmentable LA and LV compatible 
with CARTOMERGE™ can be used as reference when analyzing the CARTO™ and GE 
Vivid™ S70N data. In case the CT data is older than 60 days, or not compatible with 
CARTOMERGE™, a new CT should be obtained prior to the start of the study procedure. 

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• Pregnancy Test – only performed on women of child-bearing potential  
 
All adverse events observed/reported after enrollment (ICF signed) should be collected and 
reported to the sponsor and ethics committee, as appropriate.  
 
14.2.2 Study Procedure 
Subjects will arrive to the electrophysiology laboratory for their study procedure and will 
undergo preparation for the procedure per the hospital’s standard protocol (discretion of 
investigator) 
 
Overall Use of the Investigational Device 
During study procedures, investigators will use the investigational catheter instead of the 
institution’s standard ultrasound catheter choice (e.g. SOUNDSTAR™). Any use of a non-
investigational ultrasound device will be considered a failure of the primary performance 
endpoint. 
The use of the investigational NUVISION™ NAV Ultrasound Catheter is mandatory for: 
- 
Thrombus detection and LA/LV imaging for volume measurement at the start of the 
procedure; 
- 
During transseptal puncture; 
- 
And as navigational ULS catheter throughout the procedure. 
Imaging guidance for LA/LV volume measurements: 
- 
Capture preferably the full chamber in one ULS volumetric segment, if needed several 
segments can be taken. 
- 
For capturing of the LA: 
 
Capture 4D ULS clip (full 90°x90°) of the LA (with PVs and LAA) taken from the 
RA.     
 
Repeat the acquisition from 3-6 slightly different positions, where the LA 
volume is partial. 
Note: Capture 4D ULS clip before transseptal and insertion of any other 
catheters to the LA, by using the default ULS settings, and without using the 
“zoom” function.  
 
Place the investigational NUVISION™ NAV Ultrasound Catheter near the 
interatrial septum and make sure to capture the ENTIRE left atrium. 
 
Confirm by seeing both anterior-posterior and Roof to Mitral valve planes. 
 
Make sure to allow sufficient ULS depth by visualizing the distal LAA. 
- 
For capturing of the LV: 
 
The catheter can be positioned either in the RA near the inferior septum or in 
the right ventricle (RV) near the interventricular septum. 
 
Make sure to allow sufficient ULS depth by visualizing the entire chamber 
from the Mitral valve to the distal apex. 
 
Investigators should use the CARTO™ 3 system to “bookmark” instances of abnormal study 
catheter “imaging noises”. This will allow for further analysis of the data. 
 
 
 
 
 

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Standard of Care Ablation Procedure 
Treatment will be per institution’s standard of care (SOC). 
 
14.2.3 Collection of Procedure Data for Post-Analysis (non-SOC) 
At the completion of the study procedure, two back-up copies of the CARTO™ 3 and GE Vivid™ 
S70N Ultrasound Console system files will be made. One copy should be kept at the site within 
the investigator site or patient binders, and one anonymized copy will be provided to/collected 
by the Sponsor. Also, an anonymized copy of cardiac CT images will be collected to be used as 
reference when analyzing the CARTO™ and GE Vivid™ S70N data. 
 
14.2.4 Data Collection during Study Ablation Procedure 
Procedural parameters collected during the procedure include but are not limited to: 
- 
Anatomical structures assessed 
- 
Imaging for Left Atrium (LA) and Left Ventricle (LV) volume measurements 
- 
Total fluoroscopy time 
- 
Total procedure duration. 
 
Following each procedure, physician feedback on the investigational catheter and associated 
software used will be collected, using a 7-point Likert-scale survey; it will include feedback on 
deployment, maneuverability, navigational features and imaging quality acquired.  The survey 
will be entered into the eCRF for analysis.  
 
14.2.5 Pre-Discharge Assessments 
Once the investigator has achieved desired treatment results, the subject will be monitored as 
per the institution standard of care (post procedure practice) and subject will be discharged 
from the hospital in accordance with the hospitals standard procedures. 
 
Before hospital discharge, any adverse events that have occurred since the procedure should 
be documented, entered into the eCRF, and reported, as appropriate. 
 
14.3 Post-procedure Follow-up Schedule 
All subjects will be contacted 7-days post-procedure via telephone call or by attending a clinic 
visit to assess for any adverse events.  The window for this remote or in-clinic visit is +2 days (7-
9 days). Alternative contact methods are allowed in case a telephone call or clinic visit is not 
feasible (e.g. telemedicine or mail contact). The method of contact should be documented in 
the eCRF.  
 
At the 7-day follow-up visit, the following assessment will be performed: 
- 
Adverse events (from the time of the procedure up until the visit) 
 
14.4 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.  
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of early termination due to safety concerns, reporting to EC and CA may be required per local 
regulations. 
 
14.5 Unscheduled Visit 
If a subject returns for a potential study related cardiovascular visit outside of the protocol-
defined visit schedule provided in table 2, the visit will be considered “unscheduled” (UNS).  An 
investigator may request an unscheduled visit in the presence of a new or worsened 
cardiovascular condition. For this study, unscheduled visits are recorded in the eCRF linked to 
the next scheduled study visit per clinical investigational plan. 
 
14.6 Core Laboratory for Evaluation 
No core labs will be used for this study. 
 
14.7 Schedule of Events Table 
Table 2 displays the required schedule for subject treatments and evaluations.  
 
Table 2: Summary of Subject Visits and Assessments 
Assessments1 
Screening / 
Baseline 
(Clinic Visit) 
Study 
Procedure 
Discharge 
7-day Follow-up  
(Clinic Visit or 
Phone call) 
Informed Consent2 
 
 
 
 
Demographics 
 
 
 
 
Medical and Cardiac 
History3 
 
 
 
 
Transthoracic Echo 
(TTE)4,8 
 
 
 
 
Cardiac CT 5,8 
 
 
 
 
Pregnancy Test6,8 
 
 
 
 
Thrombus detection7 
 
 
 
 
Adverse Events9 
 
 
 
 
1. Standard of care assessments can be performed before ICF signature 
2. Informed consent to be signed within the 60 days prior to procedure  
3. Medical history-including but not limited to arrhythmia, heart disease and thromboembolic events 
4. TTE to determine the LVEF % within the 60 days prior to procedure (if the subject has undergone 
imaging in the last 6 months where the requested values were assessed, the assessment is not 
required) 
5. Cardiac CT for assessment of cardiac anatomy within 7 days prior to procedure (if the subject has 
undergone a CARTOMERGE™ compatible CT within 60 days of the procedure, the assessment is 
not required)  
6. Pregnancy tests for women of child-bearing potential only within the 7 days prior to procedure 
7. Thrombus detection, to rule out the presence of thrombus – mandatory to be performed with 
the investigational catheter during the study procedure 
8. Assessment should not be repeated for the study if already done per standard of care within the 
protocol defined time limits. 
9. AEs must be collected from the time the subject signs the informed consent onward.  
 
 

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15. Assessment of Safety  
15.1 Specific Safety Parameters  
15.1.1 Definition of Adverse Events (AE) 
An AE is any untoward medical occurrence in a subject whether or not related to the 
investigational device. 
 
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.  
 
Arrhythmia recurrence by itself is considered a recurrence of disease (pre-existing condition), 
and, therefore, does not meet the definition of an AE.   
 
15.1.2 Definition of Serious Adverse Event (SAE) 
A SAE is any event that meets one or more of the following criteria: 
• 
Leads to death 
• 
Leads to a serious deterioration in the health of a subject that resulted in: 
- 
A life-threatening illness or injury 
- 
An injury or permanent impairment of a body structure or a body function 
- 
In-patient hospitalization or prolongation of an existing hospitalization* 
- 
Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to body structure or a body function 
- 
Chronic disease  
• 
Leads to fetal distress, fetal death or a congenital abnormality 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. 
 
15.1.3 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. 
 
 

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A Serious Adverse Device Effect is an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE. 
 
15.1.4 Unanticipated (Serious) Adverse Device Effect 
An Unanticipated Adverse Device Effect (UADE) or 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, or degree of occurrence in the 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 6 for a comprehensive list of foreseeable and anticipated 
AEs. 
 
15.1.5 Study Device Deficiency 
A device deficiency means any inadequacy in the identity, quality, durability, reliability, 
usability, safety or performance, including of an investigational device, including  
 
Malfunction (failure to perform in accordance to its intended purpose when used in 
accordance with the IFU/Clinical Investigational Plan (CIP)/IB),  
 
Use errors, 
 
Inadequacy in information supplied by the manufacturer.  
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 0 AE documentation and reporting 
requirements. 
 
15.2 Classification of an Adverse Event 
15.2.1 Severity of Event 
The intensity or severity of each AE must be assessed according to the following classifications: 
Table 3: Intensity or Severity Definitions 
Mild 
Awareness of signs, symptoms, or events that are otherwise easily tolerated that 
may result in minimal transient impairment of a body function or damage to a 
body structure, but do not require intervention other than monitoring. 
Moderate 
Any event that results in moderate transient impairment of a body function or 
damage to a body structure that causes interference with usual activities, or that 
warrants possible intervention, such as the administration of medication, to 
prevent permanent impairment of a body function or damage to a body structure. 
Severe 
Any event that is incapacitating (an inability to do usual activities) or is life-
threatening and results in permanent impairment of a body function or damage 
to a body structure, or requires intervention, such as major surgery, to prevent 
permanent impairment of a body function or damage to a body structure. 
 
 
15.2.2 Relationship to Study Device 
For all collected AEs, the clinician who examines and evaluates the participant will determine 
the AEs causality based on temporal relationship and his/her clinical judgment. The degree of 
certainty about causality will be graded using the categories below as described per Medical 
Device Regulation (MDR) 
 

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Table 4: Adverse Event Causality Classifications 
Caused By 
Relation 
Definition of Relation 
Device 
Definitely 
(Causal 
Relationship) 
The event is associated with the investigational device beyond 
reasonable doubt  
Probable 
The relationship with the use of the investigational device seems 
relevant and/or the event cannot be reasonably explained by 
another cause, but additional information may be obtained  
Possibly 
The relationship with the use of the investigational device is 
weak but cannot be ruled out completely. Cases where 
relatedness cannot be assessed, or no information has been 
obtained should also be classified as possible 
Not related  
Relationship to the investigational device can be excluded  
Study 
Procedure 
Definitely 
(Causal 
Relationship) 
The event is associated with the study procedure beyond 
reasonable doubt  
Probable 
The relationship with the study procedure seems relevant 
and/or the event cannot be reasonably explained by another 
cause, but additional information may be obtained  
Possibly 
The relationship with the study procedure is weak but cannot be 
ruled out completely. Cases where relatedness cannot be 
assessed, or no information has been obtained should also be 
classified as possible 
Not related  
Relationship to the procedure can be excluded  
 
15.2.3 Outcome  
The outcome of each AE must be assessed according to the following classifications: 
 
Table 5: Adverse Event Outcome Classifications 
Classification 
Definition 
Resolved without sequelae 
Subject fully recovered with no observable residual effects 
Resolved with sequelae 
Subject recovered with observable residual effects 
Ongoing 
Improved 
Subject’s condition improved, but residual effects remain 
Unchanged 
AE is ongoing without changes in the overall condition 
Worsened 
Subject’s overall condition worsened 
Death 
Subject died as a result of the AE (whether or not the AE is related to 
the device or procedure) 
 
15.2.4 Expectedness (Anticipatedness) 
An anticipated AE is an effect which by nature, occurrence, severity or outcome has been 
identified as a possible complication associated with the investigational medical device and/or 
intervention procedure. 
 

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Potential AEs that are reasonably anticipated to occur during the cardiac EP procedure are 
listed in table 6. These events should be reported via EDC as anticipated AEs. Anticipated AEs 
are to be reported to the sponsor via EDC as indicated in section 0.  
 
Table 6: Comprehensive List of Anticipated Adverse Events 
 
Anticipated Adverse Events 
(Acute) renal failure 
Hypoxia 
(Aspiration) pneumonia 
Increased phosphokinase level 
(Skin) laceration 
Infection, localized  
(Vascular) bleeding 
Infection, systemic 
Acute Respiratory Distress Syndrome (ARDS) 
Ischemia 
Air embolism 
Local Hematoma/ecchymosis 
Allergic reaction to contrast media 
Localized skin reaction 
Allergic skin reaction 
Mitral Insufficiency 
Altered Mental Status Confusion; Altered Level of 
Consciousness;  
Myocardial infarction with or without ST 
elevation 
Anemia 
Nausea 
Anesthesia complications/reactions  
Palpitations 
Anoxic or hypoxic encephalopathy  
Papillary Muscle tear/injury 
Aortic Puncture 
Pericardial effusion resulting in tamponade  
Apnea - sedation induced 
Pericardial effusion without tamponade 
Arrhythmia (new or worsening of pre-existing 
arrhythmia) 
Pericarditis 
Asymptomatic Cerebral Emboli 
(Periesophageal) vagal nerve injury 
Atelectasis 
Peripheral nerve injury 
Atrial fibrillation 
Phlebitis 
Atrial Septal Defect (acquired) 
Phrenic nerve damage/injury 
Atrio-Esophageal fistula and/or injury 
Pleural effusion 
AV fistula 
Pneumothorax 
Back Pain 
Post- and perioperative pain 
Bronchial fistula, Broncho-pericardium fistula 
Post Procedural Hematuria 
Cardiac arrest 
Pseudoaneurysm 
Cardiac pacemaker insertion or replacement 
Pulmonary edema 
Cardiac perforation  
Pulmonary embolism 
Cardiac Tissue Injury 
Pulmonary hypertension 
Cardiac Valve Rupture/Damage 
Pulmonary toxicity, like acute pulmonary 
syndrome 
Cardiogenic Shock 
Pulmonary vein dissection 
Cerebro-Vascular accident (CVA)/Stroke 
Pulmonary vein stenosis 
Chest pain/discomfort 
Renal Artery Stenosis 
Complete or incomplete heart block 
Respiratory arrest 
Conduction block 
Respiratory depression 
Coronary Artery Stenosis 
Respiratory failure 
Coronary artery thrombosis 
Respiratory infection 
Death 
Retinal Artery Embolism 

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Deep venous thrombosis 
Retroperitoneal bleeding 
Diaphragmatic paralysis 
Sepsis 
Dislodgement/Malfunction of 
pacemaker/defibrillator leads 
Sinus bradycardia 
Disseminated Intravascular Coagulation 
Sinus tachycardia 
Dizziness, presyncope, vertigo 
Skin burn or necrosis 
Dysphagia 
Skin edema 
Dyspnea 
Skin or soft tissue (radiation) injury/tear 
Endocarditis 
ST segment changes 
Epigastric Distress 
Subclavian artery puncture 
Epistaxis 
Temperature elevation / Fever 
Esophageal injury / perforation 
Thrombocytopenia 
Fatigue 
Thromboembolism 
Fluid overload 
Thrombosis 
Gastric hypomotility 
Transient extremity numbness 
Gastroesophageal reflux 
Transient Ischemic attack (TIA) 
Gastrointestinal disorders 
Urinary Retention Postoperative 
Gastrointestinal diverticulosis 
Urinary tract injury or infection related to the 
urinary catheter 
Gastroparesis 
Valvular damage/insufficiency 
Headache 
Vascular (access) dissection (including 
coronary arteries) 
Heart failure (acute or chronic) 
Vascular Injury 
Heart injury 
Vascular occlusion 
Heart valve insufficiency 
Vascular Perforation 
Hemoptysis 
Vasovagal reactions 
Hemorrhage 
Ventricular Fibrillation 
Hemothorax 
Vessel damage/trauma 
High/increased creatine phosphokinase (CPK) 
Vessel perforation 
Hypertension 
Vessel spasm (including coronary arteries) 
Hypervolemia 
Visual disturbance 
Hypotension 
Worsening of pre-existing pulmonary disease  
Hypovolemia 
Wound healing disturbance 
*Recurrence 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. 
 
15.3 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. 
 

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15.4 Reporting Procedures 
15.4.1 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 protocol (section 0). 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 must be included on the appropriate eCRFs. 
 
The Sponsor is responsible for the classification of AEs and ongoing safety evaluation of the 
study and shall review the investigator’s assessment of all AEs. The sponsor will determine 
and document in writing their seriousness and relationship to the investigational device. In 
case of disagreement between the sponsor and the PIs, the sponsor shall communicate both 
opinions to the concerned parties. 
 
Biosense Webster will ensure that investigators are instructed to return devices suspected of 
causing an AE or SAE (i.e., linked to device-related AE) 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, the 
Sponsor will determine whether the risk analysis needs to be updated and whether corrective 
or preventative action is required. 
 
Timing for reporting the different types of AEs is described in table 7. 
 
Table 7: AE Reporting Requirements 
Type of Adverse Event 
Reporting Requirements 
Serious Adverse Events  
Report to Sponsor immediately upon 
awareness of event but no later than 72 hours 
USADE & SADE 
Report to Sponsor immediately upon 
awareness of event but no later than 72 hours 
Study device deficiency associated with 
an AE  
Report both study device failure and AE to 
Sponsor immediately upon awareness of 
event but no later than 72 hours 

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Study device deficiency that could have 
led to a SAE * 
Report to Sponsor immediately upon 
awareness of event but no later than 72 hours 
All other Adverse Events 
Report to Sponsor immediately upon 
awareness of event but no later than 2 weeks     
* If a) suitable action had not been taken, or b) intervention had not been made or,  
   c) if circumstances had been less fortunate. 
 
15.4.2 Serious Adverse Events Reporting 
All  
- SADEs 
- Investigational DD that might have led to a SAE if  
a) suitable action had not been taken or  
b) intervention had not been made or  
c) if circumstances had been less fortunate, whether or not they are related to 
the device or procedure,  
- new findings/updates in relation to already reported events. 
must be reported to the Sponsor, via eCRF, immediately upon awareness of event but no 
later than 72 hours by the study site personnel.  
 
The sponsor will ensure that investigators are instructed to return devices suspected of 
causing an AE or SAE (i.e., 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, 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 (by the principal investigator) as per national or site-specific 
requirements. 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.  
 
15.4.3 Unanticipated Device Effect Reporting 
All UADE/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 UADE occurring during an investigation 
according to EC requirements. 
 
15.4.4 Events of Special Interest 
All study device deficiencies 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 

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local regulations). Investigators are instructed to return devices in accordance with current 
company procedures and other relevant regulations.  
 
Event reporting to relevant CAs 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 for European sites 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 2020-10/1). For Israeli sites, the event 
reporting will be sent to the applicable MOH inbox ct_compliance@MOH.GOV.IL or 
dsur@MOH.GOV.IL, as indicated per local country requirements.   
 
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. 
 
15.5 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.  
 
16. Administrative Responsibilities 
16.1 Ethics Committee and Competent Authority Application 
The study protocol (or amendment[s]), ICF, and other applicable study related documents 
must be approved by the EC and CAs before enrollment of subjects. 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 validity of the study. 
 
In countries with a centralized submission process, a single submission will be 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 protocol and ensure to get the official response/ 
approval before starting the clinical investigation. 
 
16.2 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. 

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17. Deviations from the Clinical Investigational Plan 
The investigator is responsible for ensuring that the clinical investigation is conducted in 
accordance with the procedures and evaluations described in this protocol. The study 
monitors shall verify that the conduct of the study is in compliance with the currently 
approved protocol 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 protocol deviations; failure 
to obtain proper informed consent; non-conformance to EC requirements; failure to report 
AEs, product malfunctions and other product issues; and other non-conformance to GCP. 
 
A protocol deviation is defined as an instance of failure to follow, intentionally or 
unintentionally, the requirements of the protocol (e.g. missed test or procedure, visit out of 
window, non-adherence to inclusion/exclusion criteria). Investigators are not allowed to 
deviate from the protocol. Waivers are prohibited for this clinical study. Protocol deviations 
will be monitored closely and will be reported per EC/CA requirement.  
 
Under emergency circumstances, deviations from the protocol 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 study protocol 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 protocol. Administrative changes (do not affect 
subject’s benefits/risks ratio) may be inserted with abbreviated approval. All amendments will 
be distributed to all original protocol recipients. 
 
18. Investigational Product  
18.1 Use of the Investigational Device and Investigator Experience 
18.1.1 Training 
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.  
Investigators selected to participate in the study will be experienced in intracardiac mapping 
and ablation.  
 
To ensure uniform data collection and protocol compliance, the Sponsor will conduct a 
training session that will include reviewing the protocol, eCRF and data collection process, and 
the AE reporting process. The sponsor will reinforce the training or provide clarification 
throughout the study, as needed. 
 
18.1.2 Materials 
Biosense Webster, Inc., is the legal manufacturer of the NUVISION™ NAV Ultrasound catheters 
to be used in this study. The investigational catheters are 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 Investigator Brochure. 

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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 is 
released for human use under a Confirmation of Conformity from Regulatory Affairs that will 
certify that the investigational catheters conform to the General Safety and Performance 
Requirements for product release apart from those features, that are being investigated in 
this clinical investigation.  And that, with regards to these aspects, every precaution has been 
taken to protect the health and safety of the patient. 
 
Nuvera Medical is the legal manufacturer of the NUVISION™ Connection Cables to be used in 
this study. The non-sterile investigational cables are built on a validated production line. 
Further detail of cable components and production process are described in the Investigator 
Brochure. 
 
18.2 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 study.  
 
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, 
…)  
 
18.3 Device Returns 
All investigational devices (used and unused) will be returned to the Sponsor’s attention and 
per Sponsor’s Instructions. Device deficiencies should be properly documented on the eCRF. 
Any suspected malfunctioning device or device associated with an AE (device related AE) 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. 

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19. 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 
protocol/amendment(s), with ICH-GCP, and with applicable regulatory requirement(s).  
 
The sponsor will use a combination of remote contact and on-site monitoring. Each site will 
undergo periodic monitoring of the study, which involves a visit from a Sponsor 
representative, qualified to perform such visit.  On-site monitoring visits will be performed as 
frequently as necessary. The monitor will record dates of the visits in a study site visit log that 
will be kept at the study site. The first post-initiation visit will be made as soon as possible 
after enrollment has begun. 
 
Monitoring visits may include, but are not limited to, the following: 
- 
Protocol adherence 
- 
Source documentation verification and accuracy of the eCRFs  
- 
Safety events documentation and reporting 
- 
Verification that informed consent is being obtained for all subjects participating in the 
study in accordance with requirements described in the study protocol 
- 
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. 
 
The sponsor expects that, during monitoring visits, the relevant study site personnel will be 
available, the source documents will be accessible, and a suitable environment will be 
provided for review of study-related documents. In addition to on-site monitoring visits, 
remote contacts can occur to follow-up on outstanding items. It is expected that during these 
remote contacts, study site personnel will be available to provide an update on the progress 
of the study at the site. 
 
Data are to be submitted promptly via e-CRF after collection. Missing or unclear data will be 
corrected as necessary throughout the trial. The nature and location of all source documents 
will be identified to ensure that all sources of original data required to complete the eCRF are 
known to the sponsor and study site personnel and are accessible for verification by the 
sponsor study site contact. Biosense Webster will request further documentation such as 
physician and/or cardiac EP lab procedure notes when complications or malfunctions are 
observed and reported. 
 
20. Statistical Methodology 
This section represents the Statistical Analysis Plan for this protocol. All analyses and subsequent 
details are described below. 
 
20.1  
Levels of Significance 
All data will be summarized by descriptive analyses. No formal hypothesis testing will be 
performed. All confidence intervals will use the two-sided 95% confidence level unless 
otherwise stated. 

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20.2  
Sample Size Justification 
A sample size of 30 subjects will be enrolled to characterize the performance and safety of the 
Investigational catheter.  
 
The sample size is selected based on previous experience with similar design in first in human 
assessments of multi-electrode mapping catheters. This study is meant to characterize the 
catheter’s ability to perform safely in various types of arrhythmias. No clinical claims of 
effectiveness or patient outcomes will be made from this study.  
 
 
 
20.3  
Analysis Sets 
Safety Analysis Set: The Safety Analysis Set will consist of all enrolled subjects who have 
undergone insertion of the NUVISION™ NAV Ultrasound catheter. 
Per Protocol (PP) Analysis Set: The PP Analysis Set will include all enrolled subjects who met 
the study eligibility criteria and in whom assessments were performed with the NUVISION™ 
NAV Ultrasound catheter. 
 
20.4 
Analyses to be conducted 
20.4.1 General Conventions 
Standard descriptive summaries for continuous data include the number of observations with 
data, mean, standard deviation (SD), median, minimum, and maximum values. These will be 
referred to as “continuous summaries”. 
 
For categorical data, the count and percent will be provided. Percentages will be based on the 
number of subjects without missing data. For adverse event and device effects data, 
percentages will be based on the number of subjects in the analysis population being used in 
the analysis. This will be referred to as “categorical summaries”. 
 
20.4.2 Subgroups 
Subjects may be further classified into the five subgroups if appropriate:  
1. Scar-related Atrial Tachycardia  
2. Persistent Atrial Fibrillation (PsAF) 
3. Paroxysmal Atrial Fibrillation (PAF) 
4. Ventricular Tachycardia (VT) 
5. Premature Ventricular Complex (PVC) 
 
20.4.3 Subject Disposition 
Subject disposition will be summarized and listed for the subject categories defined in 
protocol section 10.3 for all subjects. Subject disposition will be summarized using categorical 
summaries. The number and percent of patients who are enrolled in the study, fail 
inclusion/exclusion criteria, are included in the safety, and per-protocol analysis sets, complete 
the study, and prematurely discontinue from the study will be presented. Patients who are 
prematurely discontinued will be summarized by primary reason for discontinuation. 
 
20.4.4 Demographic and Baseline Characteristics 

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Demographic variables will include age and sex. Baseline characteristics will include the 
primary study arrhythmia/procedure and the number of previous ablation procedures.  All 
demographic and baseline characteristics will be summarized using categorical and continuous 
summaries, as appropriate, for the Safety Analysis Set. A listing of subject demographic and 
baseline characteristics will be generated. 
 
20.4.5 Medical History 
Medical history will be presented using the Safety Analysis Set. 
 
Cardiovascular (CV) and Thromboembolic/Cerebrovascular medical history will be collected 
and summarized using categorical summaries.  Each subject will be counted once under each 
type of CV and/or thromboembolic/cerebrovascular medical history they have experienced.  
 
The number of subjects with TTE performed and those with pericardial effusion will be 
presented using categorical summaries.  The left ventricle ejection fraction and the maximum 
dimension of pericardial effusion will be presented in continuous summaries.  
 
The number of subjects with an exam performed to assess the presence of thrombus and 
whether a thrombus is present will be summarized. 
 
Other medical history, including NYHA class, occurrence of diabetes, and history of bleeding 
will be summarized similarly.  
 
20.4.6 Analysis for Primary Endpoints 
Primary Performance Endpoint is defined as the completion of imaging required for the study 
procedure with the NUVISION™ NAV Ultrasound Catheter without resort to non-study 
ultrasound device(s).  
 
The number of subjects who successfully completed the procedure without resort to a non-
study ultrasound device will be summarized overall and per procedure type (atrial 
ablation/ventricular ablation) for the PP Analysis Set. 
 
A listing of the primary performance endpoint will be provided. 
 
Primary Safety Endpoint is defined as the occurrence of serious adverse events related to the 
Investigational catheter within 7 days of index procedure.  An SAE will be counted as related 
to the investigational catheter if the relationship to a study catheter is anything other than 
‘Not Related’.     
 
The number of subjects with SAEs related to the investigational catheter will be summarized 
in the Safety Analysis Set overall and per procedure type (atrial ablation/ventricular ablation) 
by System Organ Class and Preferred Term and level of relationship.  All tables will present 
summaries both by subject and by event. If a subject has multiple occurrences of an event 
within a level of summarization, then for the by-subject summaries only a single occurrence 
will be counted at each level of summarization at the highest level of severity/relationship; for 
the by-event summary all events will be counted.  
 
All investigational catheter related SAEs will be listed by System Organ Class and Preferred 
Term, severity, causality (defined as possible, probable or having a causal relationship to the 
device and/or procedure), anticipation and outcome.   

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20.4.7 Analyses of Secondary Endpoints 
Secondary Safety Endpoints will be analyzed using the Safety Analysis Set: 
− 
All Serious Adverse Events, excluding investigational catheter related SAE, during the 
7-day follow-up period.  
− 
All non-serious Adverse Events related to the investigational catheter during the 7-
day follow-up period   
 
The number of subjects experiencing serious adverse events excluding investigational 
catheter related SAE and the number of serious adverse events excluding investigational 
catheter related SAE will be summarized in the Safety Analysis Set overall and per procedure 
type (atrial ablation/ventricular ablation) using categorical summaries similar to the primary 
safety endpoint.   
  
The number of subjects experiencing non-serious adverse events related to the investigational 
catheter and the number of non-serious adverse events related to the investigational catheter 
will be summarized in the Safety Analysis Set overall and per procedure type (atrial 
ablation/ventricular ablation) using categorical summaries similar to the primary safety 
endpoint.   
  
All SAEs excluding investigational catheter related SAE and all non-serious AEs related to 
investigational catheter will be listed by System Organ Class and Preferred Term, severity, 
causality (defined as possible, probable or having a causal relationship to the device and/or 
procedure), anticipation and outcome.   
 
A listing of device deficiencies including the category and timing of the device deficiency will 
also be provided.  Each deficiency will indicate whether it results in an adverse event.  
 
Physician feedback on deployment, maneuverability, navigational features and imaging 
quality acquired with the investigational catheter will be analyzed using the PP Analysis Set. A 
post-procedure survey will be administered.  Each question/sub-question will be answered by 
the physician using a Likert scale of 1 to 7 (1=poor and 7=excellent) and will be summarized.  
The summary results of each question will be presented overall and per procedure type (atrial 
ablation/ventricular ablation) using continuous summaries.  A by subject listing including all 
feedback results will be provided.  
 
20.4.8 Additional Endpoints 
Additional Procedural Data will be analyzed overall and per procedure type (atrial 
ablation/ventricular ablation) using the PP Analysis Set and include the following parameters:  
- 
Whether Imaging for Left Atrium (LA) and Left Ventricle (LV) volume measurements was 
done; 
- 
Total fluoroscopy time; 
- 
Total duration of the procedure.  
   
For each of the above procedural data, the denominator will be the number of subjects where 
assessments with the study device are performed. 
Listings will be provided.  
 
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All non-serious AEs not related to the investigational catheter will be listed by System Organ 
Class and Preferred Term, severity, causality (defined as possible, probable or having a causal 
relationship to the device and/or procedure), anticipation and outcome.   
 
20.4.9 Handling of Missing Data 
No missing data will be imputed in this study.  All analyses will be performed using observed 
data. 
 
21. Ethics and Protection of Human Subjects 
21.1 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 regulatory requirements of the 
Food and Drug Administration (FDA), applicable European medical device regulation and the 
local government. For study under MDR, MDR2017/745 will be applicable, amending Directive 
2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing 
Council Directives 90/385/EEC and 93/42/EEC. 
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. 
 
• 
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 protocol.   
 
• 
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. 
 

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• 
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 include UADEs, withdrawal of EC approval, current 
investigators list, annual progress reports, recall information, final reports and 
protocol deviations.  
 
21.2 Informed Consent Process 
21.2.1 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 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 the subject signs the informed consent. 
 
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 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 

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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. 
 
21.3 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. 
 
21.3.1 Research Use of Stored Data 
• 
Intended Use: Data collected under this protocol 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. 
 
22. 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 and ultrasound system).  If unique study 
parameters are not documented on 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 protocol selection criteria (if not already present). 

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• 
Dated and signed notes from the day of entry into the study including the study 
Sponsor (Biosense Webster), protocol 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 protocol-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, 
local government authorities, or the FDA, acting in their official capacities, will have access to 
these confidential files. 
 
23. 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 protocol, 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. 
 
24. Data Handling and Record Keeping 
24.1 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. 
 
24.1.1 Data Collection 
eCRFs will be used to collect all subject data during this clinical investigation. eCRFs have been 
developed to capture the information outlined in this clinical investigation Plan. Modification 
to the eCRF will only be made if deemed necessary by the sponsor. Data on these eCRFs will 
be monitored (source verified) and the monitor will ask the site representative to correct if 
necessary, to match the source documents. All changes made to the data will be tracked in 
the electronic audit trail. The investigator will be required to sign designated eCRFs as 
verification that they have been reviewed and the data entered are correct. Data from these 
eCRFs will be used to provide analysis of this clinical investigation.  
 
24.1.2 Data Reporting 

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The investigator, or a designated individual, is responsible for ensuring that clinical 
investigation data are timely and properly recorded on each subject’s eCRF and related 
documents. The investigator, or a designated individual, is required to electronically sign the 
eCRF on the appropriate pages to verify that he/she has reviewed and attests to the 
correctness of the recorded data. Completed eCRF will be reviewed and monitored by the 
sponsor personnel, or an appropriately qualified and trained designee, throughout the clinical 
investigation. To this end, the Investigator and institution must permit inspection of the trial 
files and subject eCRFs by such representatives and/or responsible government agencies. 
 
Investigators are required to prepare and submit accurate and timely reports on this study to 
the governing EC and Biosense Webster. 
 
Table 8: Responsibilities for Preparing and Submitting Reports 
Type of Report 
Prepared by 
Investigator For 
Time of Notification 
Subject withdrawal 
Biosense Webster 
Should report within 5 working days 
Withdrawal of EC approval 
Biosense Webster 
Should report within 5 working days 
Final report 
Biosense Webster, EC 
Will prepare a final report for the 
clinical investigation as required per 
national regulations. 
Informed consent not 
obtained from subject 
Biosense Webster, EC 
Should report within 5 working days 
 
It is recommended that all eCRF data be entered by the designated site personnel as soon as 
possible. For AE reporting, refer to the Adverse Event Reporting Requirements and timelines 
noted within this clinical investigation protocol. 
 
24.1.3 Data Verification and Review 
Biosense Webster will track the amount of missing data and contact sites as appropriate to 
instruct them on steps to minimize missing data and remain compliant with protocol required 
assessments. Missing or unclear data will be queried as necessary throughout the trial. 
Biosense Webster will request further documentation such as physician and/or cardiac EP lab 
procedure notes when complications or device malfunctions/complaints are observed and 
reported. Biosense Webster will be responsible for auditing the database and confirming the 
overall integrity of the data. 
 
24.1.4 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. 
 
24.2 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. This documentation must be accessible 
upon request by the CAs, the sponsor, or a designee. The sponsor must approve archiving, 

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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. 
 
25. Study Completion, Suspension or Termination 
The study end shall be deemed to coincide with the last visit of the last subject. 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.  
 
This study 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 
protocol compliance goals, site suspension by EC). If the study is prematurely terminated or 
suspended, the PI will promptly inform the EC and will provide the reason(s) for the 
termination or suspension. The sponsor will inform within 15 days the responsible CA and 
provide a justification in accordance with MDR Article 77.   
 
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 
study. Any enrolled subjects will continue to be followed per the study protocol 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. The sponsor will inform within 
24 hours the responsible CA and provide a justification in accordance with MDR Article 77.   
  
Circumstances that may warrant termination or suspension include, but are not limited to:  
• 
Determination of unexpected, significant, or unacceptable risk to participants  
• 
Demonstration of efficacy that would warrant stopping  
• 
Insufficient compliance to protocol requirements  
• 
Data that are not sufficiently complete and/or evaluable  
• 
Determination of futility  
 
Study may resume once concerns about safety, protocol compliance, data quality is addressed 
and satisfy the sponsor, EC and regulatory agency. 
 

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A clinical study report will be submitted within one year of the study end or within three 
months of the suspension or premature termination.  
 
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 141155: 2020 paragraph 5.4. a description of this clinical investigation will be 
registered in publicly accessible database (http://www.ClinicalTials.gov) and content shall 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 Investigation Protocol 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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