Acute Performance Evaluation of the QDOT Micro™ Catheter Used With nGEN Generator in Treatment of Patients With Atrial Fibrillation.
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Biosense Webster, Inc.

QDOT-NGEN Study 
 
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QDOT – nGEN  
Acute Performance Evaluation of the QDOT Micro™ Catheter used with nGEN Generator in 
Treatment of Patients with Atrial Fibrillation. 
 
Protocol Number:  
 BWI_2019_09  
 
Sponsor/Company: 
Biosense Webster, Inc., a division of Johnson & Johnson with registered office at 
 
 
 
Funded by: 
Biosense Webster, Inc., part of the Johnson & Johnson family of companies. 
 
Version: 
v.4.0  
 
Date: 
 02 Mar 2021  
 
 
 
 

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TABLE OF CONTENTS 
1. 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ......................................................... 13 
1.1. 
BACKGROUND INFORMATION ............................................................................................................... 13 
1.2. 
RATIONALE FOR DESIGN OF THE CLINICAL INVESTIGATION ..................................................................... 14 
1.2.1. Previous Experience with QDOT MICRO™ Catheter and Rational ............................................ 14 
1.3. 
POTENTIAL RISK AND BENEFIT ............................................................................................................ 15 
1.3.1. Known Potential Risks ................................................................................................................. 15 
1.3.2. Minimisation of Risk ..................................................................................................................... 18 
1.3.3. Known Potential Benefits ............................................................................................................. 19 
2. 
OBJECTIVES ........................................................................................................................................... 21 
3. 
STUDY DESIGN AND ENDPOINTS ........................................................................................................ 21 
3.1. 
DESCRIPTION OF THE STUDY DESIGN .................................................................................................. 21 
3.2. 
STUDY ENDPOINTS ............................................................................................................................. 21 
3.2.1. Primary Endpoint(s) ..................................................................................................................... 21 
3.2.2. Additional Endpoints .................................................................................................................... 21 
4. 
STUDY POPULATION ............................................................................................................................. 22 
4.1. 
PARTICIPANT INCLUSION CRITERIA ...................................................................................................... 22 
4.2. 
PARTICIPANT EXCLUSION CRITERIA ..................................................................................................... 22 
4.3. 
CONTRAINDICATIONS .......................................................................................................................... 22 
4.4. 
PARTICIPANT WITHDRAWAL OR TERMINATION ...................................................................................... 22 
4.4.1. Reasons for Withdrawal or Termination ...................................................................................... 23 
4.4.2. Handling of Participant Withdrawals or Termination .................................................................... 23 
4.5. 
SUBJECT ENROLLMENT DISPOSITION ................................................................................................... 23 
5. 
RESPONSIBILITIES ................................................................................................................................. 24 
5.1. 
INVESTIGATOR RESPONSIBILITIES ........................................................................................................ 24 
5.2. 
SPONSOR RESPONSIBILITIES ............................................................................................................... 25 
6. 
STUDY DEVICE DESCRIPTION .............................................................................................................. 25 
6.1. 
DEVICE ACQUISITION .......................................................................................................................... 25 
6.2. 
DEVICE STORAGE AND STABILITY ........................................................................................................ 26 
6.3. 
DEVICE PREPARATION ........................................................................................................................ 26 
6.4. 
INSTRUCTIONS FOR USE ..................................................................................................................... 26 
6.5. 
DEVICE DESCRIPTION ......................................................................................................................... 26 
6.5.1. QDOT MICRO™ Catheter ........................................................................................................... 26 
6.5.2. Bi-directional Catheter Description (D-1395-XX-S) ..................................................................... 29 
6.5.3. Uni-directional Catheter Description (D-1394-XX-S) ................................................................... 29 
6.5.4. nGEN Generator (D-1384-01) ..................................................................................................... 29 
6.5.5. nGEN™ Pump (D-1397-01) ......................................................................................................... 31 
6.5.6. TX eco EXT Interface Cable (D-1357-03-S) ................................................................................ 31 
6.5.7. TX eco Cable Dongle (D-1401-02) .............................................................................................. 32 
6.5.8. CARTO® 3 (Version 6.0 or above) QDOT MICRO™™ Software Module .................................. 33 
6.5.9. 
Ablation Parameters for the QDOT MICRO™™ Catheter ............................................................... 36 
6.6. 
EQUIPMENT ........................................................................................................................................ 39 
6.7. 
SYSTEM COMPONENTS AND SETUP ..................................................................................................... 39 
7. 
STUDY MEDICATION .............................................................................................................................. 41 
8. 
STUDY SCHEDULE ................................................................................................................................. 42 
8.1. 
SCREENING AND INFORMED CONSENT ................................................................................................. 42 
8.2. 
BASELINE EVALUATION AND PROCEDURES ........................................................................................... 43 
8.2.1. Pre-Procedure/Baseline Assessments ........................................................................................ 43 
8.2.2. Study Ablation Procedure Guidelines .......................................................................................... 43 
8.2.3. Data Collection During Study Ablation Procedure ....................................................................... 46 
8.2.4. Pre-Discharge Assessments........................................................................................................ 46 

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8.3. 
POST-ABLATION FOLLOW-UP SCHEDULE AND FINAL STUDY VISIT ......................................................... 47 
8.4. 
EARLY TERMINATION VISIT .................................................................................................................. 47 
8.5. 
SCHEDULE OF EVENTS TABLE ............................................................................................................. 47 
9. 
ASSESSMENT OF SAFETY .................................................................................................................... 49 
9.1. 
SPECIFIC SAFETY PARAMETERS .......................................................................................................... 49 
9.1.1. Definition of Adverse Events (AE) ............................................................................................... 49 
9.1.2. Definition of Serious Adverse Event (SAE) .................................................................................. 49 
9.1.3. Adverse Device Effect (ADE) / Serious Adverse Device Effect (SADE) ..................................... 50 
9.1.4. Unanticipated (Serious) Adverse Device Effect (UADE/USADE) ................................................ 50 
9.1.5. Study Device Deficiency, Failure or Malfunction ......................................................................... 50 
9.2. 
CLASSIFICATION OF AN ADVERSE EVENT ............................................................................................. 50 
9.2.1. Severity of Event .......................................................................................................................... 51 
9.2.2. Relationship to Study Device ....................................................................................................... 51 
9.2.3. Outcome....................................................................................................................................... 52 
9.2.4. Anticipated Adverse Event ........................................................................................................... 52 
9.3. 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP ........................................... 54 
9.4. 
REPORTING PROCEDURES .................................................................................................................. 54 
9.4.1. Adverse Event Documentation and Reporting Requirements ..................................................... 54 
9.4.2. Incident Reporting ........................................................................................................................ 55 
9.4.3. Events of Special Interest ............................................................................................................ 56 
9.5. 
SAFETY OVERSIGHT ........................................................................................................................... 56 
10. 
ADMINISTRATIVE RESPONSIBILITIES ............................................................................................ 56 
10.1. 
ETHICS COMMITTEE AND COMPETENT AUTHORITY APPLICATION ........................................................... 56 
10.2. 
AUDITS AND INSPECTIONS ................................................................................................................... 56 
11. 
DEVIATIONS FROM THE CLINICAL STUDY PLAN .......................................................................... 56 
12. 
INVESTIGATIONAL PRODUCT ACCOUNTABILITY ......................................................................... 57 
13. 
CLINICAL MONITORING .................................................................................................................... 57 
14. 
STATISTICAL METHODOLOGY ......................................................................................................... 58 
14.1. 
LEVELS OF SIGNIFICANCE ................................................................................................................... 58 
14.2. 
ANALYSIS SETS .................................................................................................................................. 58 
14.3. 
SAMPLE SIZE JUSTIFICATION ............................................................................................................... 58 
14.4. 
ANALYSES TO BE CONDUCTED ............................................................................................................. 58 
14.4.1. 
General Conventions ............................................................................................................... 58 
14.4.2. 
Disposition of Study Subjects .................................................................................................. 59 
14.4.3. 
Demographic and Baseline Characteristics ............................................................................ 59 
14.4.4. 
Analysis for Primary Endpoint ................................................................................................. 59 
14.4.5. 
Analyses of Additional Endpoints ............................................................................................ 59 
14.4.6. 
Analyses of Secondary Safety Endpoints ............................................................................... 60 
14.4.7. 
Handling of Missing Data ......................................................................................................... 60 
15. 
ETHICS AND PROTECTION OF HUMAN SUBJECTS ...................................................................... 60 
15.1. 
ETHICAL STANDARD ............................................................................................................................ 61 
15.2. 
INFORMED CONSENT PROCESS ........................................................................................................... 61 
15.3. 
PARTICIPANT AND DATA CONFIDENTIALITY ........................................................................................... 62 
15.3.1. 
Research use of Stored Data .................................................................................................. 63 
16. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ................................... 63 
17. 
QUALITY ASSURANCE AND QUALITY CONTROL ......................................................................... 64 
18. 
DATA HANDLING AND RECORD KEEPING ..................................................................................... 64 
18.1. 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITY ....................................................................... 64 
18.1.1. 
Data Collection ........................................................................................................................ 64 
18.1.2. 
Data Reporting ........................................................................................................................ 64 
18.1.3. 
Data Verification and Review .................................................................................................. 65 
18.1.4. 
Final Data Analysis .................................................................................................................. 65 

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18.2. 
STUDY RECORD RETENTION AND ARCHIVING ....................................................................................... 65 
19. 
STUDY SUSPENSION OR TERMINATION ........................................................................................ 66 
20. 
DATA AND PUBLICATION POLICY ................................................................................................... 66 
21. 
DOCUMENT FILING ............................................................................................................................ 66 
22. 
SCIENTIFIC REFERENCES ................................................................................................................ 68 
 
 
List of Tables 
Table 1. Summary of Subject Assessments .................................................................................... 12 
Table 2. Standard equipment used for this study .......................................................................... 40 
Table 3.  RF and Flow Settings during RF applications .................................................................... 43 
Table 4.  Summary of Subject Assessments ................................................................................... 48 
Table 5.  Intensity or Severity Definitions ...................................................................................... 51 
Table 6.  Adverse Event Causality Classifications ........................................................................... 51 
Table 7.  Adverse Event Outcome Classifications ........................................................................... 52 
Table 8.  Comprehensive List of Anticipated AEs ........................................................................... 52 
Table 9.  AE Reporting Requirements ............................................................................................ 55 
Table 10. Responsibilities for Preparing and Submitting Reports ................................................... 65 
 
List of Figures 
Figure 1. Overview of the QDOT MICRO™ Catheter with Uni-directional and Bi-directional Tip 
Deflection ..................................................................................................................................... 27 
Figure 2. QDOT MICRO™ tip Section .............................................................................................. 27 
Figure 3. QDOT MICRO™ tip with Thermocouples (6), µElectrodes (3) and angled irrigation ports . 28 
Figure 4. Contact Force Sensor – External View ............................................................................. 28 
Figure 5: nGEN Generator ............................................................................................................. 30 
Figure 6: nGEN pump .................................................................................................................... 31 
Figure 7: TX eco EXT Connection Cable .......................................................................................... 32 
Figure 8. TX eco Cable (Dongle) with Extension Cable ................................................................... 33 
Figure 9. Block Diagram of the TX eco Cable (Dongle) Processing and Transfer Activities ............... 33 
Figure 10. Information Displayed on the CARTO® 3 System ........................................................... 34 
Figure 11. Temperature Distribution Display ................................................................................. 35 
Figure 12. Temperature Display for Perpendicular Catheter Tip Orientation ................................. 35 
Figure 13. Temperature display for Parallel Catheter Tip Orientation ............................................ 36 
Figure 14. CARTO® 3 GUI with RF generator in Unipolar Mode, QDOT MIDRO™ Catheter .............. 36 
Figure 15A-D: Graphs of the Generator Power over Time .............................................................. 38 
Figure 16. nGEN™ Generator System Connectivity Diagram .......................................................... 41 
 
 
 

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List of Acronyms and Abbreviations 
  
Acronym/ Abbreviation 
Expanded Term 
AAD 
Antiarrhythmic Drug 
ACC/AHA 
American College of Cardiology/American Heart Association 
ACT 
Activated clotting time 
AE 
Adverse Event 
AEF 
Atrio Esophageal Fistula 
AF 
Atrial Fibrillation 
AFL 
Atrial Flutter 
AT 
Atrial Tachycardia 
BP 
Blood Pressure 
CA 
Competent Authority  
CABG 
Coronary Artery Bypass Graft 
CE 
Conformite Européen 
CHF 
Congestive Heart Failure 
COPD 
Chronic Obstructive Pulmonary Disease 
CPK 
Creatinine Phosphokinase 
CRF 
Case Report Form 
CS 
Coronary Sinus  
CT 
Computed Tomography 
CVA 
Cerebrovascular Accident or Stroke 
DD 
Device Deficiency  
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EF 
Ejection Fraction 
EHRA AF 
European Heart Rhythm Association Atrial Fibrillation 
EMEA 
Europe, Middle East and Africa 
EOS 
End of Study  
EP 
Electrophysiology 
ER 
Emergency Room 
ESC 
European Society of Cardiology 
EU 
European Union 
FAM  
Fast Anatomical Mapping  
FU 
Follow-Up 
GCP 
Good Clinical Practices 
GI 
Gastro-Intestinal  
HRS/EHRA/ECAS 
Heart Rhythm Society / European Heart Rhythm Association / European Cardiac Arrhythmia Society 
IB 
Investigator Brochure 
ICD 
Implantable Cardioverter-Defibrillator 
ICE 
Intracardiac Echocardiography 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ID 
Identification  
IFU 
Instruction for Use 
ISO 
International Organization of Standardization  
ITT 
Intention to treat 
IV 
Intravenous 
LA 
Left Atrium 
LBBB 
Left Bundle Branch Block 
LV 
Left Ventricle 
LVEF 
Left Ventricular Ejection Fraction 
MEDDEV 
Medical Device Directive 

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Acronym/ Abbreviation 
Expanded Term 
MI 
Myocardial Infarction 
MOH 
Ministry of Health 
MRI 
Magnetic Resonance Imaging 
NOS 
Not Other Specified 
NSR 
Normal Sinus Rhythm 
NYHA 
New York Heart Association 
PAF 
Paroxysmal Atrial Fibrillation 
PsAF 
Persistent Atrial Fibrillation 
PE 
Primary Endpoint 
PI 
Principal Investigator 
PIU 
Patient Interface Unit 
PN 
Phrenic Nerve 
PNP 
Phrenic Nerve Paralysis 
PV 
Pulmonary Vein 
PVI 
Pulmonary Vein Isolation 
QA 
Quality Assurance 
QoL 
Quality of Life 
RA 
Right Atria 
RBA 
Risk-Benefit Analysis 
RF  
Radiofrequency  
RV 
Right Ventricle 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SDV 
Source Data Verification 
SVC 
Superior Vena Cava 
SW 
Software 
TEE 
Transesophageal Echocardiography 
TIA 
Transient Ischemic Attack 
TS 
Transseptal 
TTE 
Transthoracic Echocardiography 
UADE 
Unanticipated Adverse Device Effect 
UNS 
Unscheduled 
US 
United States 
USADE 
Unanticipated Serious Adverse Device Effect 
 
 
 
 

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Key roles and Responsible Parties 
SPONSOR:   
Cardiovascular & Specialty Solutions (CSS) 
Biosense Webster Inc., part of the Johnson & Johnson family of companies 
  
 
 
 
 
CONTACTS:   
 
Clinical Research Contact, US 
Bita Najimipour 
  
 
 
  
 
 
Medical Affairs 
Jack Wang, MD 
  
 
 
 
 
 
Clinical Research Contact, CANADA 
Swati Trivedi  
Johnson & Johnson Medical Products 
 
 
  
 
 
Whereas, the Clinical Study is sponsored by Biosense Webster Inc., Johnson and Johnson Medical with 
registered offices at CANADA, has been duly appointed by the Sponsor to conduct the Clinical Study on its 
behalf. 
 
The sponsor maintains an updated list of Sponsor study contacts, principal investigators, sites, institutions and 
Contract Research Organizations (CRO) (if applicable). The definitive list shall be integrated into the study 
report. 
 
 

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Statement of Compliance 
 
Study Title: 
Acute Performance Evaluation of the QDOT Micro™ Catheter used with nGEN 
Generator in Treatment of Patients with Atrial Fibrillation. 
 
History of Changes: 
Version – Date  
Description 
 
V1.0 – 08 JAN 2020 
Original document 
 
V2.0 – 27 JAN 2020 
Administrative changes – Protocol Title Update 
 
V3.0 – 27 APR 2020 
Add 3-Month Follow-up Visit 
 
V4.0 – 02 Mar 2021 
Product information update 
Visit assessments update due to COVID-19 
 
Study #: 
BWI_2019_09 
 
I have read this protocol and agree to conduct this clinical investigation in accordance with the design 
and specific provisions outlined herein. I understand the protocol, and I understand I am solely 
responsible to ensure the investigation is conducted in accordance with Good Clinical Practices (GCP), 
applicable country regulations the Declaration of Helsinki, the signed clinical study contract with 
Sponsor and with the protocol outlined herein. I will conduct this study as outlined therein and will 
make reasonable effort to complete the study within the time period designated by the Sponsor.    
I will provide copies of the protocol and all pertinent information to all individuals responsible to me 
who will assist in the conduct of this study. I will discuss this material with them to ensure they are 
fully informed regarding the device and the conduct of the study.  
I will fulfill the requirements of my Institutional Review Board (IRB)/Ethics Committee (EC), or other 
oversight committee, to ensure complete and continual oversight of this clinical investigation. I will 
use an Informed Consent Document approved by the Sponsor and my reviewing IRB/EC (where 
required).  
I agree to report all information or data in accordance with the protocol and, in particular, I agree to 
report any serious adverse events, device related adverse events, or procedure related adverse events 
as defined in this protocol to the Sponsor, and comply with all adverse event reporting requirements 
of my reviewing IRB/EC.  I agree to permit the Sponsor, its authorized representatives, my reviewing 
IRB/EC, and any regulatory authority/body access to all records relating to the clinical investigation. 
The below signature confirms I have read and understood this protocol and its associated amendments 
or attachments and will accept respective revisions or amendments provided by the Sponsor. 
 
____________________________   _____________________________  _______________ 
 Principal Investigator  
   
Signature 
 
 
   
Date 
 Name (PRINT) 
 
 
 

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Protocol Summary 
 
 
Full Title 
Acute performance evaluation of the QDOT Micro™ Catheter used with nGEN 
Generator in treatment of patients with Atrial Fibrillation. 
Protocol Number 
BWI_2019_09 
Short Title 
QDOT-NGEN 
Sponsor 
Biosense Webster, Inc. 
 
 
Indication 
Atrial Fibrillation (Paroxysmal and Early Persistent, diagnosed for ≤6 months) 
Study Article Description 
QDOT MICRO™ System, consisting of a radiofrequency ablation catheter combining 
microelectrodes, thermocouples, porous tip irrigation and contact force sensing with 
the nGEN Generator with conventional (QMODE) and QMODE+ modality software 
installed. The QMODE+ modality is designed to deliver very high power (90w) in a 
short ablation duration (up to 4 sec) under temperature control. 
The nGEN / QDOT Micro Ablation System 
• 
nGEN™ Generator (D-1384-01), (console software version 2.0.3 and above 
/monitor software version 2.0.0 and above)   
• 
nGEN™ pump (D-1397-01)  
• 
QDOT MICRO™ Catheter (D-1394-XX-S and D-1395-XX-S) 
o 
Dongle (D-1401-02) 
o 
TX eco EXT Cable (D-1357-03-S) 
CARTO® 3 Version 6.0 or above 
Study Design 
The purpose of this study is to evaluate the workflow of the nGEN system with the 
QDOT Micro™ catheter.  Criteria to be assessed: acute performance of the QDOT 
Micro™ Catheter with nGEN Generator used in the treatment of atrial fibrillation 
during standard electrophysiology mapping and RF ablation procedures. 
BWI developed the nGEN RF generator with the same electrical design and software 
algorithm as the nMARQ Generator for use with the QDOT Micro™ Catheter. 
Accordingly, the essential performance of the nGEN Generator, which include power 
output and accuracy, temperature accuracy and control to start and stop ablations, 
are the same or improved compared to the nMARQ Generator.  The nGEN Generator 
has undergone extensive software, hardware, system and preclinical testing to assure 
safety and effectiveness.  Based on the same algorithm and essential performance, 
the clinical performance equivalency, safety and effectiveness of the nGEN Generator 
to use with the QDOT Micro™ catheter are established. This study is to obtain 
additional confirmatory data in the electrophysiology laboratory setting with 
expanded users.  
 
The QDOT-nGEN study is a prospective, multi-center, non-randomized, interventional 
clinical workflow study. 

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Sample Size and  
Statistical Analysis 
Up to 50 subjects with a minimum of 30 subjects undergoing a study ablation 
procedure will be enrolled. 
This study is a workflow study, there is no statistical power calculation and no 
hypothesis will be tested. Descriptive statistics will be presented. Thirty subjects (30) 
undergoing an ablation procedure are deemed enough to characterize safety and 
acute performance. 
Study Population 
Subjects with AF who are scheduled to undergo a clinically indicated ablation 
procedure for management of their AF will be the target population for screening.  
Geographic areas to be 
included 
Up to 6 centers in Canada 
Study Duration 
Approximately 9 months 
Participant Duration 
Subjects will be followed until completion of the 3-month visit post-procedure 
Procedure Description 
Subjects will arrive to the electrophysiology laboratory for their ablation procedure and 
will undergo preparation for the procedure per the hospital’s standard protocol 
(discretion of investigator). 
The AF Ablation procedure will follow below sequence: 
• 
Esophageal monitoring to avoid injury is recommended when ablating near 
the esophagus 
• 
Anatomical mapping of the left atrium 
• 
Introduction of the study catheter 
• 
Circumferential Pulmonary Vein Isolation (PVI) primarily using QMODE+ 
mode  
• 
Confirmation of PVI with Lasso® or PentaRay® (or other at investigators 
discretion) 
• 
Confirmation of entrance block with adenosine/isoproterenol challenge 
In this study protocol, QMODE+ is to be used as the primary mode for pulmonary vein 
isolation. Only after the investigator deems QMODE+ is unable to achieve PVI should 
the study catheter in QMODE be used to complete the procedure.   
Additional RF ablation lesion outside the PVs can be made by either QMODE+ or 
QMODE at the discretion of the physician. 
Primary Endpoints 
Acute Performance: 
Acute Procedural Success defined as confirmation of entrance block in all targeted 
PVs after adenosine and/or isoproterenol challenge using the nGEN / QDOT Micro 
Ablation System 
 
Additional Data 
Collection 
Adverse events:  
- Adverse events will be collected and evaluated. All events will be reported to 
complaints handling unit.  
Procedural parameters 
- 
PVI achieved with QMODE+ only among all targeted veins and by subject 
- 
PVI achieved with combined use of QMODE+ and QMODE among all 
targeted veins and by subject 
- 
Need for ablation of acute PV reconnection (touch-up) among all targeted 
veins and by subject  
- 
Temperature, power, contact force, impedance  
- 
Functionality of nGEN RF generator during PVI assessed by the nGEN data 
files 
Additional analyses on procedural data, including but not limited to: 
- 
Use of QDOT Micro™ catheter ablation of targets outside the PV area 

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- 
Total procedure time, mapping time, PV ablation time, total ablation time, 
RF application time 
- 
Total number of RF applications, % QMODE+ applications and % QMODE 
applications 
- 
Anatomical location of touch-up applications using the QDOT catheter 
 
Subject population 
Subjects diagnosed with symptomatic paroxysmal or early persistent atrial fibrillation 
undergoing catheter ablation through pulmonary vein isolation 
Inclusion Criteria 
Subjects must meet ALL the following inclusion criteria to be eligible for participation 
in this clinical investigation: 
1. Subjects diagnosed with symptomatic paroxysmal or early persistent AF 
undergoing a catheter ablation procedure through pulmonary vein isolation. 
2. Age 18 or older. 
3. Signed the Patient Informed Consent Form (ICF). 
Exclusion Criteria 
Subjects who meet ANY of the following exclusion criteria are not eligible for 
enrollment. 
If a subject meets the following exclusion criteria, they will not be enrolled in the 
study:  
1. If the patient has had a ventriculotomy or atriotomy within the preceding 
twelve weeks. 
2. Presence of a myxoma or an intracardiac thrombus. 
3. Presence of prosthetic valves. 
4. Presence of active systemic infection  
5. Patient with an interatrial baffle or patch 
6. 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. 
Contraindications 
Do not use this catheter: 
1. If the patient has had a ventriculotomy or atriotomy within the preceding 
twelve weeks because the recent surgery may increase the risk of 
perforation. 
2. In patients with a myxoma or an intracardiac thrombus as the catheter could 
precipitate an embolus. 
3. In patients with prosthetic valves as the catheter may damage the 
prosthesis. 
4. In the coronary arterial vasculature due to risk of damage to the coronary 
arterial vasculature. 
5. In patients with an active systemic infection because this may increase the 
risk of cardiac infection. 
6. Via the transseptal approach in a patient with an interatrial baffle or patch 
because the opening could persist and produce an iatrogenic atrial shunt. 
7. Via the retrograde trans-aortic approach in patients who have had aortic 
valve replacement. 
8. With a long sheath or short introducer < 8.5 F in order to avoid damage to 
the catheter shaft. 
Safety Monitoring 
All data will be summarized by descriptive analyses. No formal statistical inference 
will be made. 
Time and Events 
Schedule 
See table 1 below 
 
 

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Table 1. Summary of Subject Assessments 
(to be completed 60 days prior to ablation procedure) 
 
Assessments 
Pre-ablation 
Procedure 
Pre-
discharge 
7D 
(D6-10) 
M3 
(D76-104) 
Clinic visit 
 
 
 
 
1 
Phone Call 
 
 
 
 1 
 
Patient Informed Consent2 
 
 
 
 
 
Demographics2 
 
 
 
 
 
Medical/AF history 
 
 
 
 
 
Cardiac and Anticoagulation Medications 
 
 
 
 
 
Ablation Assessment 
 
 
 
 
 
ECG 
 
 
5 
1,5 
1,5 
Pregnancy Test 
 3 
 
 
 
 
LA thrombus detection 
 2 
 
 
 
 
Adverse events/Device Deficiency4 
 
 
 
 
 
AF Recurrence 
 
 
 
 
 
1. 
May be conducted as a clinic visit (ECG performed if Clinic visit) or a telehealth visit. 
2. 
To be completed within 48 hours prior to ablation procedure  
3. 
In all women of childbearing age and potential. To be completed within one week prior to ablation procedure. 
4. 
Device Deficiency to be collected at ablation and pre-discharge 
5. 
If Completed At the investigator’s discretion. 
 
 
 
 

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1. 
Background Information and Scientific Rationale 
 
1.1. 
Background Information 
 
Atrial fibrillation (AF) is the most common sustained arrhythmia in humans. It affects anywhere from 
0.4% to 1% of the general population, and increases in prevalence with age, from < 1% in young adults 
to 8% in patients over 80 years of age [1-4].  
Radiofrequency (RF) catheter ablation has provided excellent results for treating many types of 
supraventricular arrhythmias [4, 5]. Its utility in treating paroxysmal AF has already been established; 
studies have shown high rates of elimination of the arrhythmia [6, 7].  In a non-randomized clinical 
trial evaluating the impact of contact force on successful outcomes, RF ablation with the 
THERMOCOOL SMARTTOUCH® SF catheter was associated with elimination of symptomatic atrial 
arrhythmias in 72.5% of patients at 1 year [8]. 
The 2017 HRS/EHRA/ECAS/APHRS/SOLAECE Consensus Statement states that electrical isolation of 
the pulmonary veins (PVs) from the left atrium is “the cornerstone for most AF ablation 
procedures.”[2] Creation of transmural, continuous, and durable RF lesions is the objective of PVI. 
Conventional parameters of radiofrequency (RF) ablation with irrigated catheters involve the delivery 
of moderate power (20-40W) for a relatively long duration (20-40sec) at a contact force range of 10-
20g.  Still, the incidence of acute PV reconnection remains frequent, occurring after PVI at a frequency 
15-22%.[8, 9] While the mechanisms underlying PV reconnection are not entirely understood, 
catheter instability, tissue edema, and reversible non-transmural injury have been suggested as major 
contributor [10, 11]. 
RF lesion formation results from two thermal heating phases; resistive and conductive heating.  
Resistive heating is highly dependent on RF power immediately creating a hot spot ~2mm from the 
tip.  This resistive heating phase creates a heat source that extends passively to deeper tissue layers 
during the conductive phase.  Conductive heating is time dependent, with heat conducted from the 
hot spot into the deeper layers of the myocardium [12]. 
Modification of the relationship between the resistive and conductive heating phases, by increasing 
the resistive heating phase to deliver immediate heating to the full thickness of the LA tissue 
circumferential to the PVs, may achieve uniform, transmural lesions. By reducing the conductive 
heating phase collateral tissue damage could be limited [13, 14]. This can be achieved by delivering a 
large current for a short duration.   
The Biosense Webster QDOT MICRO™ catheter is a steerable multi-electrode luminal catheter with a 
deflectable tip designed to facilitate electrophysiological mapping of the heart and to transmit 
radiofrequency (RF) current to the catheter tip electrode for ablation purposes.  In addition to force-
sensing technology, the catheter incorporates six thermocouple temperature sensors and three micro 
electrodes embedded in the 3.5 mm tip electrode. 
 
The measured temperature can be used by the operator to assess the efficiency of ablation in real 
time. The localized temperature measurement will provide a highly sensitive measure of catheter 
location stability and/or movement during RF application and may reduce the need for additional RF 
applications.   
 
The micro electrodes will provide high quality localized electrograms that will allow finer endocardial 
electrical mapping and a better assessment of possible conduction gaps in the ablation lesion sets 
used to isolate the pulmonary veins and determining bidirectional block of linear lesion sets.   

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Finally, the catheter tip has incorporated a new angled design of the irrigation ports.  This new design 
allows for reduced incidence/risk of charring and coagulum on the catheter increasing safety during 
the ablation procedure. 
 
The nGEN Generator is used by electrophysiology (EP) Physicians in conjunction with compatible 
catheters, to deliver RF energy to cardiac tissue to treat arrhythmia. An ablation catheter is connected 
via interface cables to nGEN Generator or through CARTO 3 System. The nGEN Pump is also connected 
to nGEN generator via pump/generator communication cable and the appropriate saline flow rate is 
automatically activated by the generator during ablation. The generator can be configured to support 
various BWI therapeutic ablation catheter families. The current version is configured for use with the 
QDOT MICRO Catheter. 
 
Delivery of very high power for short duration (90W, up to 4 seconds) achieves uniform transmural 
lesions, mainly relying on resistive heating [15, 16]. QMODE+ at 50-90W, up to 4 seconds may 
significantly shorten RF ablation time while maintaining the effectiveness and safety profile.  A 
temperature limit has been defined (maximal at 65°C) to maintain the ablation safety profile.  Ablation 
effectiveness may be improved since the physician is required to maintain catheter stability for a short 
duration. By reducing the conductive heating phase, QMODE+ may minimize the risk of collateral 
damage to adjacent structures.   
 
1.2. 
Rationale for Design of the clinical investigation 
 
1.2.1. 
Previous Experience with QDOT MICRO™ Catheter and Rational 
 
A series of In vivo and in vitro experiments, including thigh muscle preparation model and in vivo 
beating heart experiments, were conducted to determine an appropriate QMODE+ setting that could 
be demonstrated to be safe and deliver uniform transmural lesion near the PV circumference. The 
main objective was to identify and evaluate an optimal ablation setting that allows maximal power 
output at the shortest duration possible, without char or steam-pop formation.   A range of power (i.e. 
50-100W) and durations (3-15 seconds) were studied and analyzed.  The data from these evaluations 
suggests that using higher power to promote resistive heating while shortening the duration to limit 
the impact of conductive heating through adjacent tissue provides the optimal balance for efficiency, 
effectiveness and safety.  The conclusion from these studies has been implemented as the QMODE+ 
algorithm using ablation parameters of 90W for a duration of 4s (irrigation setting at 8ml/min). These 
parameters were used for validation of animal studies as summarized in the Investigator Brochure 
(IB). 
 
Two feasibility studies are conducted to assess the performance of the QDOT MICRO™ Catheter.  
The purpose of the QDOT-MICRO study (NCT02944968) was to evaluate the workflow and acute 
performance, during standard electrophysiology mapping and RF ablation procedures, of the QDOT 
MICRO™ Catheter with improved temperature sensing capabilities and micro electrodes used in 
combination with the CARTO®3 Navigation System with QDOT-MICRO Software Module. The 
CARTO®3 System (Health Canada Licenses 81053 and 91793) is an advanced imaging technology that 
utilizes electromagnetic technology to create real-time, 3D maps of a patient’s cardiac structures, 
designed to help electrophysiologists better navigate the heart. The CARTO® 3 EP Navigation System 
is intended for catheter-based atrial and ventricular mapping. The QDOT MICRO study was a 
prospective, multi-center, non-randomized, interventional clinical study with a target population of 
paroxysmal AF subjects who were scheduled to undergo a clinically-indicated ablation procedure for 
management of their paroxysmal AF and a follow up period of 3 months post procedure. In total 51 
subjects were enrolled. The conclusion of the study was that the QDOT MICRO™ Catheter and its 
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demonstrated a favorable acute device performance and safety profile.  In addition, based on 
investigator feedback the design of the catheter and software modalities have acceptable 
performance. 
 
A second feasibility study namely the QDOT-FAST study (NCT03459196) was previously conducted. 
The purpose of this feasibility study was to evaluate safety and acute performance of the QDOT 
Micro™ catheter used in combination with the nMARQ™ Multi-Channel RF Generator with QMODE+ 
mode in the treatment of Paroxysmal Atrial Fibrillation (PAF) during standard electrophysiology 
mapping and RF ablation procedures. This was a prospective, multi-center, non-randomized, 
interventional clinical study with a target population of paroxysmal AF subjects who are scheduled to 
undergo a clinically-indicated ablation procedure for management of their paroxysmal AF a follow up 
of 3 months post procedure. In total 54 subjects were enrolled. The conclusion of the study was that 
the QDOT-MICRO™ catheter used in combination with the nMARQ™ Multi-Channel RF Generator and 
QMODE+ ablation mode in treatment of patients with Paroxysmal Atrial Fibrillation has demonstrated 
an acceptable safety and acute effectiveness profile.  
 
This workflow study will further evaluate the acute performance of the QDOT MICRO™ catheter used 
in combination with nGEN Generator in a patient population within the indication for use, namely in 
patients with paroxysmal and persistent Atrial Fibrillation during standard electrophysiology mapping 
and RF ablation procedures. The main objectives of the study are acute device performance and acute 
safety. The study will enroll up to 50 subjects with a minimum of 30 subjects will be enrolled at 6 
centers in Canada. Subjects will be followed for 3 months post procedure. 
 
The QDOT MICRO™ Catheter was licensed on December 18, 2020  under License 105640, whereas the 
nGEN Generator which has been recently upgraded (console software version 2.0.3 and above 
/monitor software version 2.0.0 and above) is an investigational device since the upgraded version 
has not been licensed in Canada. 
 
1.3. 
Potential Risk and Benefit 
 
RF catheter ablation has been used for over 20 years, and the risks and complications are well 
understood.  Procedural risks posed by the QDOT MICRO™ catheter are expected to be comparable 
to these known anticipated risks [2, 3, 17]. Few, if any, additional risks that might occur during and 
following RF ablation of symptomatic PAF are anticipated for subjects enrolled in this study. 
 
A summary of risks associated with catheter ablation, including analysis of and plans to minimize these 
risks is provided below: 
 
1.3.1. 
Known Potential Risks 
 
Risks associated with catheter ablation 
Studies have reported low rates of major complications (0.8%)[21, 22] with major centers worldwide 
reporting rates <5% [23, 24] associated with catheter ablation. The most common complications 
associated with catheter ablation of AF include:  
 
Cardiac tamponade is reported at approximately 0.2 to 5% in catheter ablation of atrial fibrillation 
(AF) [2], comprising mainly pulmonary vein isolation (PVI) procedures. Data presented by recent 
meta-analysis of 34,943 ablation procedures by Michowitz et al reported incidence of 0.8% . Rates as 
low as 0.18% have also been reported in a recent study that reviewed complications among 2,750 
procedures [19].  

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The general incidence of pericardial effusion during AF ablation is around 1.2% to 1.3% 21-31. Cardiac 
perforation may result from catheter manipulation or application of radiofrequency current.  
Published risks of cardiac perforation range from <1%to 2.4% [21]. However the risk of perforation is 
decreased with advances in catheter technology [23]. This potentially life-threatening injury may 
result in cardiac tamponade and may require percutaneous pericardial drainage or surgical repair.  
Significant hemodynamic compromise can result in neurologic injury or death.  An increased risk of 
cardiac perforation may be associated with the use of a saline-irrigated electrode catheter due to its 
ability to create a larger, deeper RF lesion.  This risk is greatest in a thin walled chamber (i.e., RA, LA, 
appendage, or RV).  
 
Pulmonary vein stenosis: Pulmonary vein stenosis (PVS) is a well-known complication of 
radiofrequency catheter ablation of atrial fibrillation. Incidence of severe PVS (>70% diameter 
reduction) was found to be <1% in a recent study with 976 subjects [24]. Incidence of only 0.5% was 
reported in a large systematic review on complications of radiofrequency catheter ablation.  
 
Esophageal injury: Since the left atrium has close anatomical proximity to the esophagus, catheter 
ablation on the LA posterior wall may thermally damage the esophagus and eventually generate an 
esophageal ulcer with a prevalence of 5% [25]  that rarely progresses to an atrial esophageal fistula 
(AEF) with catastrophic consequences [26]. Esophageal injury by endoscopy has a prevalence 
between 2.2 to 21% [25]. Esophageal perforation is a serious complication of atrial fibrillation 
ablation that occurs in 0.02 to 11% [25, 27] of atrial fibrillation ablation procedures. Delayed 
diagnosis is associated with the development of atrial-esophageal fistula (AEF) and increased 
mortality. Complication rates for esophageal injury are quite varied, depending upon lesion location 
and type of lesion found (erythema, necrotic ulceration, perforation, or fistula formation). The 
incidence of AEF post-ablation of AF is approximately 0.1% [28]. Studies using luminal temperature 
monitoring to identify potentially dangerous heating of the esophagus during ablation have not been 
able to demonstrate reduction in incidence [29].  
 
Phrenic nerve paralysis: Currently, this complication has been reported in less than 0.5%, with 
permanent paralysis between 0% to 0.4% when the isolation of right PV is not obtained during PV 
antra isolation and RF ablation is performed inside at carina the right PVs [2, 29, 30]. A 2018 
published study reported very low rates of PNP of 0.04% among 2,750 procedures [19]. Prior to 
ablation in the region of the RSPV, investigators are encouraged to perform precautionary measures 
such as evaluation of proximity to the phrenic nerve and pacing maneuvers.  
 
Death is an uncommon complication associated with CA techniques. Overall incidence of death has 
been reported to be <0.1% to 0.4%[2]. A 2010-published global survey provided an overall mortality 
rate of 0.1%.  Another report from an international survey of AF ablation of 162 centers provided 
details on 32 deaths that occurred during or after AF ablation procedures in 32,569 patients (0.1%) 
[31, 32]. Among the most frequent causes of death were cardiac tamponade (25% of deaths), stroke 
(16%), atrio-esophageal fistula (16%) and massive pneumonia (6%) [31]. 
 
Radiofrequency current may cause occlusion of a coronary artery, either by direct thermal damage, 
spasm, or thrombus formation.  Acute coronary artery occlusion is a very rare but potentially life-
threatening complication of RFCA [33]. Experience at numerous centers suggests that the risk of 
coronary occlusion is less than 0.5% [34].  Coronary arterial occlusion could produce myocardial 
infarction (MI), angina or death.  Occlusion of a coronary artery can be treated by restoring coronary 
blood flow through pharmacological, catheter and/or surgical intervention as medically indicated.  
 

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The application of radiofrequency current close to the AV node or His bundle could damage or 
destroy the normal AV conduction system, producing complete heart block and requiring 
implantation of a permanent pacemaker.  
 
Thromboembolic events: Thrombus generation during the procedure may pose a serious and even 
life-threatening risk to the patient.  Thrombus may form on the ablation electrode during the 
application of radiofrequency current with or without any change in impedance.  The thrombus 
might become dislodged and embolize to produce an ischemic stroke, MI, or other occlusive injury. 
Although some observational studies have shown a relatively lower stroke rate after catheter 
ablation, whether catheter ablation can reduce the thromboembolic risk remains unclear.  
 
The mean incidence of thromboembolism associated with AF ablation was reported by Cappato et al 
in 2010 to be between 1% and 2% [21]. More recently, Fujii et al have reported incidence of 
thromboembolism in up to 5% of patients undergoing AF ablation despite perioperative 
anticoagulation [35]. Ischemic stroke events typically occur within 24 hours of the AF ablation 
procedure with the higher risk period covering for the first two weeks following ablation [36]. 
 
Pulmonary hemorrhage is a rare but severe complication of PVI. Late hemoptysis and pulmonary 
hypertension can occur secondary to pulmonary vein stenosis (PVS) after ablation. Acute pulmonary 
hemorrhage also has been reported[37]. Mechanical trauma from catheter manipulation is a 
possible mechanism for pulmonary hemorrhage 41 . 
 
Injury to a cardiac valve may result from catheter manipulation or the application of radiofrequency 
current (risk <1%) [38]42. This may produce valvular insufficiency and possibly require valve 
replacement surgery.  
 
Vascular access / bleeding complication: Arterial or venous injury, including arterial dissection, 
thrombosis, occlusion or hemorrhage at the catheter insertion sites or at other sites along the 
vessels (risk 0.2% to 1.5%) [2, 39, 40]. These types of injuries may cause hemorrhage, hematoma or 
ischemic injury to an extremity or major organ.   
Hemorrhage could occur as a result of anticoagulation (risk < 0.5%), which may require transfusion 
43,44.  
 
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%) [41-43]. 
 
Allergic Reaction: A patient could develop an allergic reaction to the local anesthetic, sedatives, x-
ray dye, heparin, protamine, or other agents administered during the procedure (risk < 1%) [44-48]. 
 
Infection: The percutaneous procedure carries risk of infection, either at the catheter insertion site 
or systemically, including endocarditis and septic emboli (risk < 0.5%) [39, 40]. This risk can be 
minimized by using standard aseptic technique and, when indicated, by the use of antibiotic agents. 
 
Additional contraindications: Additional contraindications for RF ablation include: hemodynamic 
instability, bacteremia, coagulopathy, prosthetic tricuspid valve, intra-atrial or venous thrombosis, 
and pregnancy. 
 
A review of the testing of the QDOT MICRO™ catheter verifies that risks associated with the designs 
are acceptable and not unacceptable (Intolerable) risks have been noted. Any testing deviations are 

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discussed within the body of the respective testing reports and all deviations were reviewed and 
considered to be acceptable. 
 
The designs of the QDOT MICRO™ catheter have been subjected to testing (bench top, thigh 
preparation, simulated clinical conditions via in vivo beating heart testing and EMC/Electrical Safety 
testing). The results of the various testing performed have verified the safety of the catheter when 
used in accordance with the Instructions for Use.  
 
Biocompatibility and Sterility Assessments for the applicable catheter have been performed and 
verify that the proposed design and packaging meet the existing requirements for both categories.   
 
A review of the risk assessment documents for the QDOT MICRO™ catheter have verified that there 
are no “Intolerable” ratings related to risks associated with the designs of the catheter.  All ratings 
are “As Low As Practical” (ALAP). 
 
1.3.2. 
Minimisation of Risk 
 
Although there are potential risks posed during a cardiac RF ablation procedure, the criteria 
for subject selection, methods, personnel, facilities, and training that have been specified for 
this study are intended to minimize the risk to subjects undergoing this procedure.   
 
Robust testing of the investigational devices at component and the system level, within 
simulated clinical conditions, was successful with no adverse events identified. During the 
QMODE+ design phase, systematic proactive risk analyses did not identify new hazards and 
harms. Minimization of Risk has been described per QDOT MICRO™ catheter IFUs within the 
section Warnings and Precautions for the QDOT MICRO™ Uni-Directional Catheter (M-5276-
1043A), which are the same as those listed in the QDOT MICRO™ Bi-Directional IFU (M-5276-
1042A) with the exception of the product name. The list of warnings and precautions entail 
pre-procedural and procedural precautions whereas postprocedural management is in 
accordance with the ACC/AHA/HRS 2017 Guidelines for the Management of Patients with 
Atrial Fibrillation. Additionally, the risk of potential adverse events is mitigated by the 
temperature cutoff setting of the generator and the optimization of the target temperature. 
 
Patient selection: Subjects will be screened carefully prior to enrollment in the study to 
ensure compliance with the inclusion and exclusion criteria.  Both criteria have been 
developed to reflect the population indicated for commercial use of the QDOT MICRO™ 
catheter. The exclusion criteria and contraindications have been developed to exclude 
subjects with a medical history or condition that relates to the contraindications per catheter 
IFUs and therefore their risk of (unanticipated) adverse events (refer to Section 4.2 for the 
Exclusion Criteria and the catheter IFUs). 
 
Procedure safeguard and post-procedural management: 
Investigators skilled in intracardiac mapping and ablation of AF with the use of RF ablation 
catheters containing contact force technology and qualified training experience with the use 
of the QDOT MICRO™ system will be selected for participation in the study.  AF ablation 
procedures will be performed in electrophysiology laboratories with the assistance of skilled 
nurses and technicians. The laboratory will contain sufficient resuscitative equipment and 
facilities to manage any potential complications.  Immediate access to cardiac surgical 
facilities, as well as a qualified cardiovascular surgeon, will be available during the ablation 
procedure in the event that surgical intervention becomes necessary. 
 

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To proactively manage serious and potentially life-threatening complications during an AF 
ablation procedure (Atrio-Esophageal Fistula, PV stenosis, Phrenic nerve paralysis and cerebral 
embolism), the following precautions are highly recommended: 
• 
When ablating near the esophagus (along the posterior wall of the left atrium), take 
precautions to avoid injuring the esophagus. These may include beginning the ablation 
with reduced RF power, reducing contact force, reducing application time, increasing 
the time interval between ablations, esophageal visualization, and/or intraluminal 
esophageal temperature monitoring. 
• 
When ablating near the phrenic nerve, take precautions to avoid injuring the phrenic 
nerve, including appropriately reducing RF power, and performing pacing maneuvers 
to identify the proximity of ablation electrode(s) to the nerve. 
• 
To prevent stenosis of the pulmonary veins, do not place the catheter in the pulmonary 
veins during the application of RF energy. 
• 
Inspect the saline within the irrigation tubing for air bubbles prior to its use in the 
procedure. Air bubbles in the irrigation saline may cause emboli. 
• 
To prevent thromboembolism, intravenous heparin (target ACT of ≥325 s) should be 
administered prior to or immediately following transseptal puncture during AF 
ablation procedures. The 2017 HRS/EHRA/ECAS/ AOHRS/SOLAECCE expert consensus 
statement on catheter and surgical ablation of atrial fibrillation recommends systemic 
anticoagulation with warfarin or a direct thrombin or factor Xa inhibitor for at least 2 
months following an AF ablation procedure. 
 
Safety data during enrollment and short follow-up will be routinely monitored by the Medical 
Safety group.   
 
1.3.3. 
Known Potential Benefits 
 
Current practice guidelines reflect extensive expert reviews of published risks and benefits 
among various treatment modalities and patient populations. All key published guidelines 
agree that the primary clinical benefit of catheter ablation for PAF is an improvement in quality 
of life, following abatement of arrhythmia-related symptoms. 
 
The role of catheter ablation as first-line therapy, prior to a trial of a Class I or III antiarrhythmic 
agent, has been suggested as an appropriate indication for catheter ablation of AF in patients 
with symptomatic paroxysmal or persistent AF by the HRS/EHRA/ECAS 2017 Consensus 
Statement [2]. In this circumstance, the benefits of catheter ablation outweigh the risks (Class 
IIa); however, the strength of evidence/data supporting this therapeutic modality (Level B) 
reflects a limited number of clinical studies. Not all expert bodies are in line with the 
aforementioned expert opinion.   
 
The 2016 ESC-published guidelines and recommendations for the management of AF 
suggested that in patients who experience symptomatic recurrences of AF despite 
antiarrhythmic drug therapy, catheter ablation shows better sinus rhythm maintenance with 
catheter ablation than on antiarrhythmic drugs [49]. However, the guidelines also present that 
randomized trials showed only modestly improved rhythm outcome with catheter ablation 
compared to antiarrhythmic drug therapy [49].  
 
Catheter ablation has been used for over two decades to treat AF patients to achieve PVI. 
Significant catheter design improvements (e.g., irrigated encircling catheters) focus upon 
improving physicians’ abilities to achieve finite entrance block following PVI, reducing damage 
to neighboring structures and improving procedural efficiency. 

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The QDOT MICRO™ catheter is a steerable multi-electrode luminal catheter with a deflectable 
tip designed to facilitate electrophysiological mapping of the heart and to transmit 
radiofrequency (RF) current to the catheter tip electrode for ablation purposes.  In addition to 
force-sensing technology, the catheter incorporates six thermocouple temperature sensors 
and three micro electrodes embedded in the 3.5 mm tip electrode.   
 
The measured temperature can be used by the operator to assess the efficiency of ablation in 
real time.  The localized temperature measurement will provide a highly sensitive measure of 
catheter location stability and/or movement during RF application and may reduce the need 
for additional RF applications.  
  
The micro electrodes will provide high quality localized electrograms that will allow finer 
endocardial electrical mapping and a better assessment of possible conduction gaps in the 
ablation lesion sets used to isolate the pulmonary veins and determining bidirectional block of 
linear lesion sets.   
 
Finally, the catheter tip has incorporated a new angled design of the irrigation ports.  This new 
design allows for reduced incidence/risk of charring and coagulum on the catheter increasing 
safety during the ablation procedure. 
 
With contact force information and improved temperature feedback in any tip tissue 
orientation, the QDOT MICRO™ catheter is designed to create durable lesions, in shorter time, 
with fewer ablation applications, and improved irrigation flow decreasing the opportunity for 
char and coagulum formation.   
 
The expected benefits of the QDOT MICRO™ System, consisting of a radiofrequency ablation 
catheter combining microelectrodes, thermocouples, porous tip irrigation and contact force 
sensing with the nGEN Generator with QMODE+ modality software installed may improve 
safety and efficiency. There are several types of clinical benefits for catheter ablation that are 
not specific to the subject device. These catheter ablation clinical benefits include impact of 
the procedure on clinical management, patient health, and patient satisfaction in the target 
population. 
 
The QDOT-MICRO™ System may potentially impact the procedure by the following: 
 
• 
Limit conductive heating and collateral damage to neighboring structures including non-
cardiac adjacent tissues. 
• 
Increase catheter stability and reduce tissue edema, therefore improve lesion to lesion 
consistency at very high power for a short duration, since catheter instability in a constantly 
beating heart and tissue edema remains problematic for the effective lesions using the 
conventional ablation techniques. 
• 
Contact force sensing capabilities and improved temperature feedback may aid in 
increasing the effectiveness of RF ablations by maintaining better control for a more 
effective lesion formation. 
• 
Reduce the procedural time related to ablating the pulmonary vein triggers in the left 
atrium and improve the PVI efficiency significantly. 
• 
Reduce fluoroscopy exposure for both the patient and the staff. 
• 
Microelectrodes may aid in better assessment of possible conduction gaps in the ablation 
lesion sets. 

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• 
Reduce the amount of fluid loading of the patient as compared to a focal ablation 
catheter. 
 
2. 
Objectives 
 
The objective of this study is to evaluate the workflow and acute performance of the QDOT MICRO™ 
catheter used in combination with the nGEN Generator with QDOT software module for the treatment 
of Patients with Atrial Fibrillation during standard electrophysiology mapping and RF ablation 
procedures. In this study, QMODE+ will be used as the primary mode for pulmonary vein isolation. If 
the investigator deems QMODE+ is unable to achieve PVI, the study catheter in QMODE will be used 
to complete the procedure.   
 
3. 
Study Design and Endpoints 
 
3.1. 
Description of the Study Design 
 
The QDOT-nGEN study is a prospective, multi-center, non-randomized, interventional clinical 
workflow study. The study population will consist of up to 50 subjects with minimum of 30 subjects 
who are scheduled to undergo a clinically indicated ablation procedure for the management of their 
AF. The study will be conducted at up to 6 centers in Canada. 
 
3.2. 
Study Endpoints 
 
3.2.1. 
Primary Endpoint(s) 
The primary endpoint is to confirm pulmonary vein isolation. This is defined as confirmation of 
entrance block in all targeted PVs after adenosine and/or isoproterenol challenge using the nGEN/ 
QDOT Micro Ablation System. 
 
3.2.2. 
Additional Endpoints  
The following additional data will be collected and analyzed as part of this study. These data will 
include but not limited to: 
- Adverse events will be collected and evaluated. All events will be reported to the Complaint 
Handling Unit (CHU).  
- Procedural data associated with  
o Catheter ablations outside the PV area 
o PVI achieved with QMODE+ only among all targeted veins and by subject 
o PVI achieved with combined use of QMODE+ and QMODE among all targeted veins 
and by subject 
o Need for ablation of acute PV reconnection (touch-up) among all targeted veins 
and by subject  
- Procedural parameters 
o Total procedure time  
o Mapping time 
o PV ablation time 
o Total ablation time 
o RF application time 
o Total Fluoroscopy time 
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- Anatomical location of touch-up applications using the QDOT catheter 
- Temperature, power, contact force, impedance during RF application 
- Confirmation of RF energy delivery from nGEN log files 
 
4. 
Study Population 
 
4.1. 
Participant Inclusion Criteria 
Subjects must meet ALL the following inclusion criteria to be eligible for participation in this 
study: 
1. Subjects diagnosed with symptomatic Paroxysmal or Early Persistent* AF undergoing a 
catheter ablation procedure through pulmonary vein isolation. 
2. Age 18 or older. 
3. Signed the Patient Informed Consent Form (ICF). 
 
*Definitions for paroxysmal and early persistent AF are based on the 2017 HRS consensus statement.  
 
4.2. 
Participant Exclusion Criteria 
Subjects who meet ANY of the following exclusion criteria are not eligible for enrollment. 
1. If the patient has had a ventriculotomy or atriotomy within the preceding twelve weeks. 
2. Presence of a myxoma or an intracardiac thrombus. 
3. Presence of prosthetic valves. 
4. Presence of active systemic infection  
5. Patient with an interatrial baffle or patch 
6. Women who are pregnant (as evidenced by pregnancy test if pre-menopausal), lactating, or 
who are of child bearing age and plan on becoming pregnant during the course of the 
clinical investigation. 
4.3. 
Contraindications 
The following contraindications are referenced in the IFU for study  
• 
If the patient has had a ventriculotomy or atriotomy within the preceding twelve 
weeks because the recent surgery may increase the risk of perforation. 
• 
In patients with a myxoma or an intracardiac thrombus as the catheter could 
precipitate an embolus. 
• 
In patients with prosthetic valves as the catheter may damage the prosthesis. 
• 
In the coronary arterial vasculature due to risk of damage to the coronary arterial 
vasculature. 
• 
In patients with an active systemic infection because this may increase the risk of 
cardiac infection. 
• 
Via the transseptal approach in a patient with an interatrial baffle or patch because 
the opening could persist and produce an iatrogenic atrial shunt. 
• 
Via the retrograde trans-aortic approach in patients who have had aortic valve 
replacement. 
• 
With a long sheath or short introducer < 8.5 F in order to avoid damage to the 
catheter shaft. 
 
4.4. 
Participant Withdrawal or Termination 
 

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4.4.1. 
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 adverse event (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 
• 
The participant no longer meets eligibility criteria or meets an exclusion criterion (either 
newly developed or not previously recognized) that precludes further study participation. 
• 
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 7-day follow-up period. 
 
4.4.2. 
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 is withdrawn due to 
an adverse event (AE) or serious adverse event (SAE), the Investigator will follow the subject 
until the AE/SAE has resolved or is considered stable. The local CHU will collect the resolution 
information of any reported SAEs.  
 
If a subject is unable to return for an office/clinic visit or cannot be contacted by telephone, 3 
separate telephone calls should be made to obtain subject related safety information. All attempts 
should be documented in the source documents. If the subject does not respond to the 3 telephone 
calls, then the investigator must send a certified letter to the subject. If the subject does not 
respond to the letter, then the subject will be considered “lost to follow-up” for the study. 
 
Subjects who have signed the ICF but are later found not to be eligible PRIOR to insertion of the 
study catheter will be excluded and might not count for the enrollment goal. Excluded subjects can 
be replaced with new enrolled subjects for the study to reach a total of the predefined  
evaluable study-subjects (up to 50).  
 
4.5. 
Subject Enrollment Disposition 
 
The following subject groups are defined:  
 
• 
Enrolled Subjects: Patients who sign the informed consent form. 
• 
Excluded Subjects: Subjects who are enrolled but never undergo insertion of the study 
catheter.  
• 
Discontinued Subjects: Enrolled subjects who have the study catheter inserted but do not 
undergo ablation (no RF energy is delivered with the study catheter and the nGEN 
generator).   

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• 
Lost to Follow-up Subjects:  Subjects for whom 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, expired, 
withdrawn, terminated early, or lost-to-follow-up from the study prior to the final study 
visit. 
 
5. 
Responsibilities 
 
5.1. 
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 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 (ablating investigators only) and 
the study protocol prior to enrolling and treating subjects 
• 
Maintain accurate and current logs for the study such as: 
o Subject log, Device Accountability Log 
• 
Obtain initial and amendment (if applicable) HC approval and annual review/approval 
thereafter for the study protocol and informed consent as applicable 
• 
Obtain informed consent form and enroll patients 
• 
Perform medical procedures 
• 
Order tests required by the study protocol 
• 
Review pre-procedure imaging pertaining to the pulmonary vein size prior to 
treatment 
• 
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, HC) in a timely manner regarding the 
occurrence of AEs and/or product malfunctions. 
• 
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with the follow-up requirements 
• 
Maintain study records for at least 5 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 HC and Sponsor annual report requirements, including the final 
report. 
 
5.2. 
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 protocol, 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 
• 
Obtain signed study contracts from investigators/hospitals, 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 Principal Investigator at each site. 
• 
Update Report of Priors, IFU, IB, and Risk Analyses, as applicable 
• 
Update investigators on safety issues, if needed 
• 
Report to study investigators and regulatory agencies, as required 
• 
Have AEs reviewed by the study-specific committees, as required 
• 
Communications with the competent authority 
• 
Submission of any amendments to the Clinical Study Protocol/Post market clinical 
follow up plan to the competent authority. 
 
 
6. 
Study Device Description 
 
6.1. 
Device Acquisition 
After obtaining a fully executed clinical trial agreement and appropriate HC approvals, the sponsor 
will initiate shipment(s) of the investigational device 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 

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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. 
 
6.2. 
Device Storage and Stability 
 
Devices are to be stored in accordance with the IFUs and User Manual. Do not use this device after 
the “Use By” date. 
 
6.3. 
Device Preparation 
 
Information related to device preparation can be found in the IFUs. 
 
6.4. 
Instructions for Use 
 
A comprehensive set of IFU/User manuals for the QDOT MICRO™ System, and all accessory 
cables/interface cables is contained in each product package and is also available upon request. 
 
6.5. 
Device Description 
 
6.5.1. 
QDOT MICRO™ Catheter 
The Biosense Webster QDOT MICRO™ Navigation Catheter (Uni-Directional and Bi-Directional) and 
related accessory devices are indicated for catheter-based cardiac electrophysiological mapping 
(stimulating and recording) and, when used in conjunction with a compatible radiofrequency 
generator (including the nGEN Generator, D-1384-01), for cardiac ablation. The Biosense Webster 
QDOT MICRO™ Uni-Directional and Bi-Directional Navigation Catheter provides a real-time 
measurement of temperature and contact force between the catheter tip and heart wall, as well 
as location information when used with the CARTO™ 3 System. 
The catheter has a high-torque shaft with deflectable tip section containing an array of electrodes 
which includes a 3.5 mm tip dome with three microelectrodes. All of the electrodes may be used 
for recording and stimulation purposes. The tip electrode serves to deliver RF energy from the RF 
generator to the desired ablation site. The tip electrode and ring electrodes are made from noble 
metals. 
The catheter incorporates six thermocouple temperature sensors that are embedded in the 3.5 
mm tip electrode.   
At the proximal end of the catheter, a saline input port with a standard Luer fitting terminates from 
the open lumen. This saline port serves to permit the injection of normal saline to irrigate the tip 
electrode. During ablation, heparinized normal saline is passed through the internal lumen of the 
catheter and through the tip electrode, to irrigate and cool the ablation site as well as the electrode 
tip. An irrigation pump should be used to control the saline irrigation. 
 

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Figure 1. Overview of the QDOT MICRO™ Catheter with Uni-directional and Bi-
directional Tip Deflection 
 
 
 
Figure 2. QDOT MICRO™ tip Section 
 
  
 
SIDEARM 
LUER CONNECTOR 
HANDLE BARREL HOUSING 
34 PIN PCB 
CONNECTOR 
PISTON WITH 
THUMB KNOB 
PEBAX 
SHAFT 
QUAD LUMEN 
DEFLECTABLE TIP 
PALLADIUM/PLATINUM  TIP 
USABLE LENGTH 
115cm 

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Figure 3. QDOT MICRO™ tip with Thermocouples (6), µElectrodes (3) and angled 
irrigation ports 
 
 
An irrigation pump is used to control the saline irrigation. The catheter interfaces with standard 
recording equipment and a compatible RF generator via accessory extension cables with the 
appropriate connectors. 
This catheter features a location sensor embedded in the tip section that transmits location and 
contact force information to the CARTO® 3 (Version 6.0 or above) Navigation System (refer to 
Figure 4). An appropriate reference device is required for location reference position purposes. 
For information on using the catheter in mapping procedures and for information on appropriate 
reference devices, refer to the user manual for the CARTO® 3 (Version 6.0 or above) Navigation 
System. 
 
Figure 4. Contact Force Sensor – External View   
 
 
This catheter features a location sensor embedded in the tip section that transmits location and 
contact force information to the CARTO® 3 System. An appropriate reference device is required for 
location reference position purposes. The catheter connects to the CARTO® 3 Navigation System 
through an interface box called the Patient Interface Unit (PIU). The catheter interfaces with 
standard recording equipment and a compatible RF generator via accessory extension cables with 
the appropriate connectors. For use in mapping procedures, for information on appropriate 

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reference devices, and for further description of the operation of the CARTO® 3 Navigation System, 
refer to the CARTO® 3 Navigation System User Manual.  
For further information on the irrigation pump (nGEN® Pump), RF Generator (nGEN Generator), 
and required cables, refer to the respective Instructions for Use and/or User Manual. 
Refer to Section 6.6 (Required Study Equipment) for details on additional equipment required for 
this study.  
 
6.5.2. 
Bi-directional Catheter Description (D-1395-XX-S) 
The catheter has a high-torque shaft with a bi-directional deflectable tip section containing an array 
of electrodes which includes a 3.5 mm tip dome. All of the electrodes may be used for recording 
and stimulation purposes. The tip electrode serves to deliver RF energy from the generator to the 
desired ablation site. The tip electrode and ring electrodes are made from noble metals. The 
catheter incorporates six thermocouple temperature sensors and ECG electrodes that are 
embedded in the 3.5 mm tip electrode. A Rocker Lever is used to deflect the tip. The high-torque 
shaft also allows the plane of the curved tip to be rotated to facilitate accurate positioning of the 
catheter tip at the desired site. Additionally, a variety of curve types are available in symmetric or 
asymmetric combinations, providing two 180° opposed, single-planed curves. Five curve 
configurations designated “DD”, “FF”, “JJ”, “DF”, and “FJ” are available. 
 
6.5.3. 
Uni-directional Catheter Description (D-1394-XX-S) 
The catheter has a high-torque shaft with a uni-directional deflectable tip section containing an 
array of electrodes which includes a 3.5 mm tip dome. All of the electrodes may be used for 
recording and stimulation purposes. The tip electrode serves to deliver RF energy current from the 
generator to the desired ablation site. The tip electrode and ring electrodes are made from noble 
metals. The catheter incorporates six thermocouple temperature sensors and ECG electrodes that 
are embedded in the 3.5 mm tip electrode. A Rocker Lever is used to deflect the tip. The high-
torque shaft also allows the plane of the curved tip to be rotated to facilitate accurate positioning 
of the catheter tip at the desired site. Three curve types configurations designated “D,” “F,” and 
“J” are available. 
 
6.5.4. 
nGEN Generator (D-1384-01)  
 
The nGEN™ Generator is indicated for use in cardiac ablation. The generator is a highly specialized 
device used in conjunction with compatible cardiac ablation catheters and a dispersive pad (indifferent 
electrode) to create a closed electrical circuit capable of delivering specified doses of RF energy. The 
RF energy is delivered to cardiac tissue that forms unwanted electrical pathways that either drive or 
maintain arrhythmias. The RF energy heats the tissue so that it becomes denatured and no longer 
functional. This interrupts and/or destroys the unwanted electrical pathways, thereby restoring 
normal heart function. 
 
The nGEN Generator actively generates RF energy and continuously monitors, displays, and 
coordinates the amount of RF energy delivered, the temperature of the catheter’s ablation 
electrode(s), and the tissue impedance during ablation. Simultaneously, an impedance measurement 
mechanism measures the heart tissue impedance allowing detection of small tissue changes before, 
during, and after treatment. Before and during treatment, electrical signals generated by the heart 
are also detected and transmitted by the catheter through the generator to the connected CARTO® 3 
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The nGEN™ Generator consists of the following components: 
• 
Monitor: The monitor is a touch screen computer that contains the software. The monitor has 
a control knob and physical start and stop buttons. The monitor is supplied with a base which 
can be detached. An optional second monitor may also be used.  
• 
The monitor software includes a base software, which consists of all basic GUI screens 
required for the operation of the monitor software, and the configuration files, which are 
installed based on the catheter presets. 
• 
Console: The console produces and controls the delivery of RF energy. The console also 
connects to and communicates with therapeutic catheters and other devices. 
• 
Power Supply Unit (PSU): The PSU provides power to the console. 
• 
Pedal: The pedal is an alternate way to start and stop an ablation session. 
• 
Cables: The nGEN™ Generator is shipped with cables for connecting the generator 
components to each other and to other devices. 
 
 
 
Both the internal hardware and software design of the nGEN Generator incorporate a safety 
architecture that enables independent monitoring of critical parameters (e.g. RF time, power delivery, 
temperature, impedance). All safety-critical parameters, i.e. voltage and current measures, 
temperature measurements, and start/stop ablations, are implemented via two independent paths: 
a primary control path and a secondary safety monitoring path.  Since the start and stop commands 
can be initiated from various sources, the paths may include both digital and analog communications. 
This two-path design is intended to prevent common cause events that may lead to safety hazard. The 
continuous crosschecks of critical parameters between the console software and the monitor 
software mitigate systemic failures and enhance safety. 
 
When used with the irrigated catheters, the nGEN Generator is connected to the nGEN Pump by a 
communication interface that allows both the generator and the pump to be controlled from the 
touch screen on the monitor. The nGEN Pump is connected to the catheter irrigation port to provide 
irrigation during ablation for irrigated catheters.   
 
The generator can be configured to support various BWI therapeutic ablation catheter families. This 
nGEN Generator version (console software version2.0.3 and above /monitor software version 2.0.0 
and above) utilized in this clinical study is configured for use solely in combination with the QDOT 
MICRO Catheter in conventional intracardiac RF ablation procedures. 
 
Figure 5: nGEN Generator 
 
 

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6.5.5. 
nGEN™ Pump (D-1397-01) 
The nGEN™ Pump is a peristaltic pump designed for use by electrophysiology laboratory staff in 
cardiac electrophysiology procedures. The pump delivers irrigation solution from a connected 
irrigation solution bag via a compatible irrigation tubing set to a compatible irrigated catheter. 
 
When the pump is connected to the nGEN Generator, the generator automatically sets the irrigation 
flow rate based on the connected catheter type, changes the flow rate when the delivery of RF energy 
starts and stops, and monitors the flow rate. 
 
Only compatible accessories and devices provided by or recommended by Biosense Webster may be 
used with the nGEN™ Pump.  
 
This nGEN pump is compatible with nGEN generator and SMARTABLATE™ Irrigation Tubing Set.  
 
Figure 6: nGEN pump 
 
 
6.5.6. 
TX eco EXT Interface Cable (D-1357-03-S) 
The TX eco EXT Connection Cable (D-1357-03-S) is designed to connect the QDOT MICRO™ Catheter 
that interfaces the Patient Interface Unit (PIU) of the CARTO® 3 EP Navigation System via the dongle. 
The TX eco EXT Connection Cable consists of a gray connector which connects to the dongle and a 
black connector that connects to the catheter receptacle.  
 

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Figure 7: TX eco EXT Connection Cable 
 
 
 
6.5.7. 
TX eco Cable Dongle (D-1401-02) 
The Biosense Webster TX eco Cable (Dongle) (D-1401-02) is an accessory device primarily intended to 
provide a means for the QDOT MICRO™ Catheter to interface with the CARTO® 3 (Version 6.0  or 
above) EP Navigation System and to the nGEN generator. The TX eco Cable (Dongle) processes and 
transfers catheter location signals to the CARTO® 3 System. Additionally, the TX eco Cable (Dongle) 
contains integrated firmware that reads the temperature from each thermocouple (six total) within 
the QDOT MICRO™ Catheter tip. The highest temperature will be sent to the compatible RF Generator 
and all six temperatures will be sent to the CARTO®3 System for real-time visual display.  
 

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Figure 8. TX eco Cable (Dongle) with Extension Cable 
 
 
Refer to Figure 9 below which depicts a functional block diagram of the TX eco Cable (Dongle) signal 
processing and transfer activities. 
 
Figure 9. Block Diagram of the TX eco Cable (Dongle) Processing and Transfer 
Activities 
 
 
6.5.8. 
CARTO® 3 (Version 6.0 or above) QDOT MICRO™™ Software Module 
The QDOT MICRO™ software module is a software feature to the CARTO® 3 System to display and 
record ECG, temperature, location and contact force information when the QDOT MICRO™ Catheter 
is connected and the QDOT MICRO™ software module is enabled. The temperatures recorded by the 
6 thermocouples within the QDOT MICRO™ Catheter are transmitted to and displayed graphically on 
the CARTO® 3 System. The purpose of sending all six (6) temperature readings to the CARTO® 3 System 
is to provide two graphical displays to the physician on the CARTO® 3 System. 
 
Tip Temperature Display 
The CARTO® 3 System will display the temperature measured by the TX eco Cable in colored 2D and 
3D imaging format. The image on the left is the temperature distribution around the tip electrode.  The 
image on the right is the “bullseye” display. 
 

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Figure 10. Information Displayed on the CARTO® 3 System 
 
Colored catheter 
temperature distribution 3D 
display 
“Bulls eye” 2D display of 
values for each 
thermocouple reading 
 
The “bulls eye” display provides temperature information to the physician.  An optional numerical 
value of the temperature from the RF Generator is displayed on the “bulls eye” determined by the 
physician’s preference to display or not to display).  The colored graphic of the bulls eye provides 
relative tip to tissue interface temperature readings obtained from the 6 thermocouples. The colored 
tip graphic provides the physician with an indication as to which part of the catheter tip has contact 
with the tissue. In addition, it can also provide the physician with an indication of the catheter’s tip to 
tissue stability; if the catheter tip slips, the temperatures obtained from the thermocouples will 
change which will be visually displayed on the “bulls eye” as well as on the graphic of the tip of the 
catheter. The colors in the displays change as the temperature of the thermocouples change. The 
colors range from dark blue (minimum temperature) to dark red (maximum temperature) and the 
circular presentation allows the physician to visualize the relative temperatures of distal and proximal 
thermocouples in the tip (viewed from the center outward). The outer halo provides the orientation 
of the catheter tip in 3-dimensional space. 
 
The TX eco Cable is responsible for gathering the QDOT MICRO™ Catheter temperature and micro 
electrode signal information and transferring this data to the CARTO® 3 System for display. The 
temperature feedback display during ablation is described below. 
 
• 
Tip Temperature Distribution - monitor the maximum temperature measured and verify the 
proper response of the temperature distribution of the catheter tip during the RF session. In the 
figure below, the six small circles represent the 6 thermocouples: 3 distal and 3 proximal. The 
inner circle represents the tip electrode and the outer ring represents the tip sides. 
 

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Figure 11. Temperature Distribution Display 
 
 
 
Any change in the desired Ablation catheter tip orientation – from a perpendicular orientation to the 
tissue, would result in temperature rise of the corresponding part of the catheter tip electrode, as 
indicated by the red color the tip temperature distribution display as shown below. 
 
Figure 12. Temperature Display for Perpendicular Catheter Tip Orientation 
 
 
 
 
• 
Any change in the desired Ablation catheter tip orientation – from a parallel orientation to the 
tissue, would result in maximum temperature rise of the cylindrical part of the tip that is in 
contact with the tissue.  This is indicated by the red color at the tip temperature distribution 
display, as shown below. 
 

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Figure 13. Temperature display for Parallel Catheter Tip Orientation 
 
 
 
 
Figure 14. CARTO® 3 GUI with RF generator in Unipolar Mode, QDOT MIDRO™ 
Catheter 
 
 
 
 
6.5.9. 
Ablation Parameters for the QDOT MICRO™™ Catheter 
The ablation algorithm is designed to maximize RF lesion efficiency by using temperature feedback 
from the tip to adjust power and irrigation flow. The QMODE Temperature mode monitors the 
temperature rate of change in relationship to the set target temperature during RF application.  To 
maintain desired power levels at a safe temperature, the QMODE adjusts the irrigation flow rate as a 
first order of control.  A secondary control of power titration is also used if the temperature cannot 
be maintained with the increased irrigation flow rate alone.  Typical temperature control algorithms 
for mainstream commercial irrigation RF catheters rely purely on power titration to maintain the 
desired temperature.  By utilizing the irrigation flow rate first, the Q-dot catheter is able to deliver 
consistent power for efficient ablations without compromise of safety. 

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RF Energy Modulation:  
The RF energy application is separated into two distinct zones: 1-50W and 90W.  
 
For power settings from 1-50W, the approach is to modulate irrigation and then titrate power as 
needed to maintain the target temperature. As an example (see Figure 15A), the power delivery (e.g. 
35W) would start with the irrigation setting at 4 ml/min until it reaches a target temperature (e.g. 
50°C).  When the catheter reaches the target temperature, irrigation is then changed to 15 ml/min 
automatically by the generator algorithm.  This increase in irrigation flow rate cools the tip and allows 
the generator to maintain the delivered power.  If the temperature decreases, the pump irrigation 
flow rate is returned to the lower setting (i.e. 4mL). Under circumstances when increased irrigation 
flow does not sufficiently reduce the tip temperature, power delivery is automatically reduced. 
 
In a second example (see Figure 15B), the power delivery (e.g. 50W) starts with the irrigation setting 
at 15 ml/min until it reaches a target temperature (e.g. 50°C).  If the catheter is below the desired 
temperature initially, the irrigation is automatically reduced to 4ml/min by the generator algorithm to 
maximize the sensitivity to temperature.  Once the temperature sensed at the tip starts to rise, the 
generator automatically increases the irrigation flow back to 15 ml/min.  This cycle continues between 
low and high irrigation settings in order to maintain the target temperature.  Again, under 
circumstances where the tip temperature is above 50°C, the power delivery is automatically reduced.  
 
For power settings at 90W (Figures 15C and 15D), the maximum duration is 4 seconds. Therefore, the 
approach is to only titrate power.  At this setting, power delivery is delivered at a constant irrigation 
flow of 8 ml/min with no modulation given the short duration.   
 

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Figure 15A-D: Graphs of the Generator Power over Time 
A. RF Power Delivery at 35W  
 
 
B. RF Power Delivery at 50W  
 
 
C. RF Power Delivery at 90W 
 
 

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D. RF Power Delivery at 90W, power titration evident 
 
  
 
6.6. 
Equipment 
 
6.7. 
System Components and Setup 
Some devices and software used in this study are investigational and some are available 
commercially at the hospital. Table below shows the investigational and non-investigational 
equipment used in the study.  
 

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Table 2. Standard equipment used for this study 
Equipment 
Function or Specifics 
Investigational Equipment 
nGEN Generator (D-1384-01) 
Transmits RF energy to the Ablation Catheter 
Non-Investigational Equipment 
8.5 F compatible sheath 
Facilitate deployment of catheter into the atria. 
Lasso® or PentaRay® (optional) 
Pre-ablation recording and mapping of the atria 
of the heart with the CARTO® 3 system. 
SMARTABLATE™ Irrigation Tubing Set 
Delivers heparinized saline to the catheter for 
cooling during the RF energy application 
Esophageal temperature monitoring device 
Esophageal temperature monitoring 
EP lab recording equipment 
Records multiple intracardiac electrograms and 
signals from the RF generator (power, 
temperature, impedance) and performs 
electrical stimulation. 
Adhesive electrical dispersive pads / 
indifferent electrode 
Component of the RF current return path 
(Valley Lab required) 
Interface Cables 
Connection of choice 
CARTO® System Junction Box 
Provide the interface to the catheter, generator, 
and the CARTO® System. 
CARTO® 3 Version 6.0 or above 
For mapping and visualization information.  
nGEN Pump (Part Number D-1397-01) 
Works with compatible irrigation tubing set 
to deliver irrigation solution 
to compatible irrigated catheters. 
QDOT MICRO™™ Catheters 
D-1394-XX-S 
D-1395-XX-S 
Delivers RF energy to the target tissue. 
TX eco EXT Connection Cable 
(D-1357-03-S) 
Provides a means to interface the QDOT 
MICRO™ catheters with the Dongle 
TX eco Cable (Dongle) 
(D-1401-02) 
Provides a means to interface the QDOT 
MICRO™ catheters to the Multi-Channel RF 
Generator 
 
For RF ablation, the QDOT MICRO™ Catheter is connected to the CARTO 3 System Patient Interface 
Unit (PIU), which is connected to the RF generator. A Biosense Webster TX eco Cable (dongle) and 
compatible interface cable is required to achieve a proper generator interface. To complete the 
electrical circuit, an indifferent electrode must be connected to the indifferent electrode input on 
the generator. A schematic depiction of the QDOT MICRO Catheter system set up is provided in 
Figure 16. 
 

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Figure 16. nGEN™ Generator System Connectivity Diagram 
9
Patient’s 
Body
EP-Recording 
System 
Workstation
Control 
Room
CARTO® 3 System 
Workstation
Secondary 
nGEN™ Monitor
3
2
1
4
Operating 
Room
Primary nGEN™ 
Monitor
3
5
4
Monitor 
PSU
CARTO® 3 PIU
 nGEN™ Foot 
Pedal
nGEN™ Pump
Pump PSU
3
12
Infusion 
Bag
4
Indifferent Electrode
8
7
 nGEN™ Foot 
Pedal
Electric Splitter 
Cable
Medical Cart\ 
Table
2
2
2
nGEN™ System component
Non-nGEN™ System component
Connection to nGEN™ System component
Connection between non-nGEN™ System components
Irrigation connection
13
Qdot Dongle
Qdot Catheter 
Recording System 
Amplifier
Cardiac Stimulator
nGEN™ Console
511
6
10
10
10
 nGEN™ Foot 
Pedal
nGEN™ Monitor 
Desk base – 
Ethernet hub
Monitor 
PSU
nGEN™ PSU
9
14
nGEN™ Monitor 
Desk base – 
Ethernet hub
14
 
 
7. 
Study Medication  
For the purpose of this study, it is highly recommended to comply with the medication management as 
described per HRS consensus guidelines 2017.[2] 
 
The following medications are recommended for subjects undergoing a study catheter ablation for AF.  
 
• 
Before the AF Ablation procedure 
o Uninterrupted systemic anticoagulation therapy is recommended for at least 3 weeks 
prior to the AF ablation procedure. 
• 
If receiving warfarin/coumadin therapy, subjects must have an international 

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normalized ratio (INR) ≥ 2 for at least 3 weeks prior to treatment and the 
subject’s must be confirmed to be ≥ 2 within 48 hours pre-procedure.  
 
• 
During the AF Ablation procedure 
 
o Administer a heparin bolus PRIOR to transseptal puncture.  
o Target an ACT of at least ≥325 seconds, prior to or immediately following transseptal 
puncture and throughout the procedure.  
• 
It’s strongly recommended to check ACT levels on regular basis during the procedure 
to ensure an ACT target of at least ≥325 seconds 
o Adenosine or isoprotenerol challenge is mandatory for the purposes of this study 
unless the subject is contraindicated for one of these medications. 
o Adenosine: A (12 to 24 mg) to confirm PV isolation; rule out dormant conduction 
OR 
o Isoproterenol to achieve a ≥20 beats per minute increase in heart rate to induce 
AF upon completion of the ablation procedure is recommended if pacing 
maneuvers are not performed (recommended dose range is 2-20 mcg/min).  
 
• 
Following the AF Ablation procedure 
o Anticoagulation therapy is strongly recommended for at least 2 months following 
ablation. 
o Additional medications needed to treat clinical indications are at the discretion of the 
clinical investigation physician. 
o AAD management during the study will be at the discretion of the investigator 
 
 
8. 
Study Schedule 
8.1. 
Screening and Informed Consent 
 
All patients considered for RF ablation procedure for drug refractory recurrent symptomatic AF should 
be evaluated by the investigator or designated member of the research team for study eligibility per 
the protocol inclusion and exclusion criteria.  
 
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 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 regulatory authorities 
(as applicable) and study site's Ethics Committee. 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 ICH-GCP and with applicable 
local and federal 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. 

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Each subject screened for enrollment in the clinical study who signs the patient informed consent 
form 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 informed 
consent form for this clinical investigation. 
 
8.2. 
Baseline Evaluation and Procedures 
 
8.2.1. 
Pre-Procedure/Baseline Assessments 
 
Below pre-procedure assessments and data collection must be performed within 60 days prior to the 
ablation procedure  
 
- 
Patient Information and Consent  
- 
Demographics (age, gender, etc.). 
- 
Medical history, including but not limited to arrhythmia, heart disease, 
thromboembolic events, lung/respiratory problems. 
- 
AF history (first evidence of AF, number of episodes, symptoms, etc.). 
- 
Medication history: Medication history (cardiac medication, AAD medication, 
anticoagulation regimen and any other clinically significant medication history) shall 
be gathered by interview or from medical records following enrolment but prior 
to the ablation procedure and should be recorded in the eCRF. 
- 
Cardiac medication and anticoagulation regimen: Uninterrupted systemic 
anticoagulation therapy is recommended for at least 3 weeks prior to the AF ablation 
procedure.  
- 
Imaging for detection of LA thrombus: performed within 48 hours prior of the study 
procedure or day of ablation procedure. The following are allowable imaging modalities: 
▪ 
TEE 
▪ 
CT/MRI 
▪ 
Intracardiac Echocardiography (ICE) 
- 
Pregnancy Test: Pre-menopausal women only, performed within one week prior to the 
procedure. 
- 
Adverse Events must be collected from the time the subject signs the informed 
consent onwards 
 
8.2.2. 
Study Ablation Procedure Guidelines 
 
8.2.2.1 Recommended Ablation Parameters and irrigation pump settings 
 
In this study protocol, QMODE+ is to be used as the primary mode for pulmonary vein 
isolation. Only after the investigator deems that QMODE+ is unable to achieve PVI should 
the study catheter in QMODE be used to complete the procedure. 
 
Table 3.  RF and Flow Settings during RF applications 
 
 
 

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Power 
Target Temp* 
Cut-off Temp 
Nominal Irrigation 
Flow rate 
Range 
Maximum 
allowed 
Range 
Maximum 
allowed 
25-35 W 
40-50ºC 
50ºC 
50-
55ºC 
55ºC 
4mL** 
36-
50W*** 
40-50ºC 
50ºC 
50-
55ºC 
55ºC 
15mL** 
90W† 
40-60ºC 
60ºC 
60-
70ºC 
70ºC 
8mL** 
* Temperatures displayed on the RF generator do not represent tissue temperature or 
electrode tissue interface temperature. 
**A minimum flow rate of 2mL during mapping is recommended. 
*** RF applications at 36-50W should not exceed 60 sec. 
† The study recommends using this power setting for PVI as a primary ablation Strategy.  RF 
applications at this power setting are limited up to 4 sec. It is recommended to use lower 
target temperature setting for the posterior wall RF applications. 
 
Note: The QMODE and QMODE+ parameters, presented in Table A, are user-adjustable, in case the 
investigator deems appropriate.  
 
8.2.2.2 QDOT MICRO™ Contact Force (CF) Settings: 
When using the study catheter in both QMODE and QMODE+, operators should Target: 
• Target CF: 10g 
• CF Range:   5-30g  
 
8.2.2.3 Recommended AF Ablation Procedure Sequence 
 
Subjects will arrive to the electrophysiology laboratory for their ablation procedure and will 
undergo preparation for the procedure per the hospital’s standard protocol (discretion of 
investigator). 
 
The AF ablation procedure workflow is recommended to follow the sequence below: 
 
- 
Anesthesia or sedation should be delivered per standard EP lab procedure. 
- 
Placement of diagnostic catheters 
- 
Cardioversion if subject not in sinus rhythm (per investigator discretion) 
- 
CARTO® Respiratory Gating (unless using Jet Ventilation) 
- 
Administration of heparin bolus prior to transseptal puncture or immediately following 
transseptal puncture  
- 
Transseptal puncture 
- 
Following successful transseptal puncture, an anatomic map can be performed, utilizing 
Lasso® or PentaRay® (or other at investigator discretion) 
Note: An anatomical map is not required for triggers outside the left atrium (e.g. 
SVC/CS etc.) 
- 
Placement of esophageal temperature monitoring device (per investigator discretion) 

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- 
Confirmation of target ACT is ≥325 sec (but preferable 350 sec) prior or immediately after 
transseptal but no later than first ablation into the left atrium and maintain throughout 
the procedure 
- 
Introduction of the QDOT MICRO™ catheter 
o Use the AUTOTAG feature in CARTO® 3 (Version 6.0 or above) to tag each 
QMODE+ ablation point after each application 
o At the new location ensure catheter stability before commencing RF application. 
o A pre-ablation flow rate delay of minimal 2 seconds will occur before RF 
application  
o Ablation modality: RF power application of up to 90W for up to 4 seconds 
(QMODE+)  
o Move the catheter to a new location (~4mm) if clinically effective ablation is 
achieved  
o QMODE+ should be used for full PV encirclement. If the investigator deems that 
QMODE+ is unable to achieve PVI, the study catheter in QMODE should be used 
to complete the procedure  
o Continue RF applications and catheter movement until the circumferential PVI is 
completed. 
o Precautions:  
 
If the temperature increases above the temperature cutoff (default 
65°C), RF application will stop immediately (automatically) 
 
The decision to interrupt RF power delivery at any time during ablation 
should be guided by Clinical Investigator judgment and the monitoring of 
ablation effectiveness parameters commonly used such as EGM 
reduction and/or impedance changes. 
- 
All subjects will continue PV ablation until PVI is achieved and isolation is confirmed by 
Lasso® or PentaRay® (or other at investigator discretion). 
- 
After PVI is confirmed, it’s recommended to initiate a 20-min waiting period  
- 
Verify the ablation lines with a mapping catheter (Lasso® or PentaRay® or other at 
investigator discretion) 
- 
Perform additional applications, if required 
- 
Administer adenosine or isoproterenol for each targeted PV to rule out dormant 
conduction, mandatory unless subject is contraindicated for adenosine 
- 
Perform additional applications (touch-up), if required 
- 
Confirmation of entrance block of all targeted PVs 
 
8.2.2.4 Ablation Procedure Guidelines 
 
General Introduction of the Study Catheter 
When ablating near adjacent anatomical structures, take precautions to minimize collateral 
damage to the adjacent structures: 
- 
When ablating near the esophagus (along the posterior wall of the left atrium), take 
precautions to avoid injuring the esophagus  
- 
Prior to ablation in the region of the right superior PV, precautionary measures are 
recommended to evaluate proximity to the phrenic nerve, such as pacing maneuvers 
 
Ablation outside the PV Ostia 
The ablation procedure includes PVI, ablation of non-PV triggers and substrate modification.  For 
RF application outside the PV ostia QMODE+ and QMODE may be used at the discretion of the 
Investigator. 
 

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8.2.3. 
Data Collection During Study Ablation Procedure 
 
Procedural data collection will be done through generator files, CARTO® datafiles, procedural 
worksheets and subject medical files. Documentation of procedural data will be kept in the subject’s 
CRF, back-up generator files and back-up CARTO® log files for study analysis. 
At the completion of the study ablation procedure two back-up copies of the CARTO® 3 and 
generator log files will be made. One copy should be kept at the site within the investigator site or 
patient binders, and one fully anonymized copy will be sent to the sponsor, in a timely manner 
 
The Carto and Generator data (electronic raw data) collected during the Study Ablation procedure 
will be anonymized (or de-identified) prior to its transfer to the Sponsor. Data will be verified during 
this lifecycle (Data Transfer) to ensure the records are complete and are traceable to subjects within 
each clinical site. Data will be archived per the applicable policies and procedures as it relates to 
Data Extract process, Record Retention etc., and will be the source for data analysis. During data 
transfer, redundant copies will be stored at each critical stage of the transfer to safeguard adequate 
control over business continuity or disaster recovery of records. A copy of the electronic raw data 
will also be stored at each clinical site until receipt and storage by the sponsor has been confirmed. 
 
The information collected during the procedure will include, but will not be limited to, the list 
below. 
- 
RF application-mode per lesion (QMODE+ /QMODE) 
- 
Number of RF applications with QDOT MICRO™ catheter (total/QMODE+/QMODE) 
- 
Duration of RF applications with QDOT MICRO™ catheter (total/QMODE+/QMODE) 
- 
PVI ablation time (time between first RF application and last RF application on a PV before 
isolation confirmed and circumferential ablation achieved) 
- 
Subject PVI ablation time (time between first RF application and last RF application before 
all PVI complete) 
- 
Subject total ablation time (time between first RF application and last RF application in a 
subject) 
- 
Ablation parameters per RF application from the generator files 
- 
Touch-up applications  
- 
Total procedure time (from first femoral puncture to last catheter removal) 
- 
Mapping time 
- 
Fluoroscopy time 
- 
LA catheter dwell time (from ablation catheter LA insertion to ablation catheter removal 
from the LA)  
- 
ECG data 
- 
Total fluid delivered via ablation catheter and via intravenous line (if captured); fluid 
output and net fluid input (if captured) 
- 
Strategy used to minimize risk of esophageal injury, if any 
- 
Abnormal esophageal temperature rises (if captured) 
 
 
8.2.4. 
Pre-Discharge Assessments 
 
Prior to hospital discharge, the following assessments should be performed: 
• 
Cardiac medication and anticoagulation regimen (only cardiac related AADs, 
anticoagulation regimen, etc.) 
• 
ECG in case of standard of care 
• 
Adverse events, if any 

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• 
Occurrence of AF or other arrhythmias, if any 
 
 
8.3. 
Post-Ablation Follow-up Schedule and Final Study Visit 
 
The subject will be required to complete follow up visit at 7 days (phone call or clinic visit) post 
procedure. 
 
Discharged subjects will receive a telephone call or clinic visit at (7D, day -1 or +3) post ablation 
procedure to assess medication, AF occurrences and Adverse Events.  
 
The subject will be required to complete follow up through 3 months post initial ablation procedure. 
The follow-up visit is 3 months ± 14 days (3M, day 76-104) post ablation procedure. Follow-up visit 
schedule should be based on the date of the index study ablation procedure and will not reset if 
subject undergoes a repeat AF ablation procedure. 
 
• 
At the 3 months post ablation procedure visit (in-clinic or telehealth visits) the following 
assessments should be performed: 
o Cardiac medication and anticoagulation regimen (only cardiac related AADs, 
anticoagulation regimen, etc.) 
o Medical / Hospitalization History 
o ECG at the discretion of the investigator 
o Adverse events, if any 
o Assessment of AFL/AT/AF occurrence and repeat ablation 
o End of Study Follow up 
 
 
8.4. 
Early Termination Visit 
Subjects may withdraw from the clinical investigation at any time. The decision for the subject to 
withdraw informed consent must be made independently of influence by the investigator or site 
personnel. The subject’s decision will be documented in the source and eCRF. The investigator may 
also choose to withdraw a subject from the study if there are safety concerns. If a subject withdraws 
from the study, the date and reason for withdrawal will be recorded on the appropriate electronic 
case report form (eCRF).   
 
All data will be collected (as available) until the subject is withdrawn. If the subject is withdrawn due 
to an adverse event (AE) or serious adverse event (SAE), the investigator should follow the subject 
until the AE/SAE has resolved or is considered stable. The local CHU will collect the resolution 
information of any reported SAEs.  
 
8.5. 
Schedule of Events Table 
 
This table displays the required schedule for subject treatments and evaluations. Subjects should 
undergo procedure within 60 days of signing informed consent.  
 
 

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Table 4.  Summary of Subject Assessments 
Assessments 
Pre-
ablation 
Procedure 
Pre-
discharge 
7D 
(D6-10) 
M3 
(D76-104) 
Clinic visit 
 
 
 
 
1 
Phone Call 
 
 
 
 1 
 
Patient Informed Consent2 
 
 
 
 
 
Demographics2 
 
 
 
 
 
Medical/AF history 
 
 
 
 
 
Cardiac and Anticoagulation 
Medications 
 
 
 
 
 
Ablation Assessment 
 
 
 
 
 
ECG 
 
 
5 
1,5 
1,5 
Pregnancy Test 
 3 
 
 
 
 
LA thrombus detection 
 2 
 
 
 
 
Adverse events/Device Deficiency4 
 
 
 
 
 
AF recurrences 
 
 
 
 
 
1. 
May be conducted as a clinic visit (ECG performed if Clinic visit) or a telehealth visit.  
2. 
To be completed within 48 hours prior to ablation procedure  
3. 
In all women of childbearing age and potential. To be completed within one week prior to ablation procedure. 
4. 
Device Deficiency to be collected at ablation and pre-discharge 
5. 
If completed at the investigator’s discretion.  
 
 

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9. 
Assessment of Safety 
 
9.1. 
Specific Safety Parameters 
 
9.1.1. 
Definition of Adverse Events (AE) 
 
An AE is any untoward medical occurrence in a subject whether or not related to the medical device 
under study. 
 
Specifically, an adverse event (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 device or procedure.  Physical findings (including vital signs) 
observed at follow-up, or pre-existing physical findings that worsen compared to baseline, are 
considered adverse events.    
 
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.  
 
AF recurrence by itself is considered a recurrence of disease (pre-existing condition), and, 
therefore, does not meet the definition of an AE.  Recurrence of pre-existing AFL/ atrial 
tachycardia (AT) is also considered recurrence of disease and does not meet the definition of an 
AE. 
 
The following clinical events will not be considered an adverse event for this clinical study: 
• 
A trace / trivial pericardial effusion that is asymptomatic, requires no medical 
intervention, and does not extend hospitalization will not be considered an adverse 
event 
• 
AF/AFL/AT recurrence requiring pharmacological or synchronized electrical 
cardioversion during the hospitalization for the index ablation procedure 
• 
AF/AFL/AT recurrences throughout the duration of the study, as they will be reported as 
within the effectiveness analysis of early recurrences during the blanking period via 
arrhythmia monitoring data collection per consensus guidelines. 
• 
However, the development of a new atrial arrhythmia deemed as not an effect of the 
ablation procedure (in example new onset of left atrial flutter occurring post-ablation) is 
an AE.  
• 
Re-ablation for AF or preexisting AFL/AT itself is not an AE, however any procedural 
complication is considered an AE and shall be reported within the applicable timelines 
 
9.1.2. 
Definition of Serious Adverse Event (SAE) 
 
A serious adverse event (SAE) is ANY event that meets one or more of the following criteria: 
• 
Leads to a death 
• 
Leads to a serious deterioration in the health of a subject that resulted in: 
o A life-threatening illness or injury 
o An injury or permanent impairment of a body structure or a body function 

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o In-patient hospitalization or prolongation of an existing hospitalization* 
o Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to body structure or a body function 
• 
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 
(ER) visits that do not result in admission to the hospital should be evaluated for one of the other 
serious outcomes. 
 
 
9.1.3. 
Adverse Device Effect (ADE) / Serious Adverse Device Effect (SADE) 
 
An Adverse Device Effect (ADE) is an adverse event related to the use of the device under study.  
 
NOTE 1: This includes any adverse event resulting from insufficiencies or inadequacies in the 
instructions for use, the deployment, the implantation, the installation, the operation, or any 
malfunction of the medical device under study. 
NOTE 2: This includes any event that is a result of a use error or intentional abnormal use of the 
investigational device under study. 
 
A Serious Adverse Device Effects (SADE) is an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE. 
 
9.1.4. 
Unanticipated (Serious) Adverse Device Effect (UADE/USADE) 
 
An unanticipated adverse device effect (UADE) or unanticipated serious adverse device effect 
(USADE) is any serious adverse effect 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 incidence in the post market clinical follow up 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 8 for a comprehensive list of foreseeable and anticipated adverse events. 
 
9.1.5. 
Study Device Deficiency, Failure or Malfunction 
 
A device has failed if it does not perform according to the IFU or fails to meet the expectations of 
the device and/or investigator (i.e., related to appearance of the device, performance, durability, 
safety, effectiveness, quality, reliability, labeling, etc.).  If a device failure is detected or suspected, 
it should be documented on the appropriate eCRF and device failure and AE must be reported as 
soon as possible to the Sponsor per section 9.4. 
 
9.2. 
Classification of an Adverse Event 
 

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9.2.1. 
Severity of Event 
The intensity or severity of each AE must be assessed according to the following classifications: 
 
Table 5.  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. 
 
9.2.2. 
Relationship to Study Device 
 
For all collected AEs, the clinician who examines and evaluates the participant will determine the 
AE’s causality based on temporal relationship and his/her clinical judgment. The degree of certainty 
about causality will be graded using the categories below.   
 
Table 6.  Adverse Event Causality Classifications 
 
Caused By 
Relationship Definition of Relation 
Device 
 Causal 
The event is associated with the device under study beyond 
reasonable doubt  
Probable 
The relationship with the use of the device under study seems 
relevant and/or the event cannot reasonably explained by another 
cause, but additional information may be obtained  
Possibly 
The relationship with the use of the device under study is weak but 
cannot be ruled out completely  
Unlikely 
The relationship with the use of the device under study seems not 
relevant and/or the event can be reasonably explained by another 
cause, but additional information may be obtained  
Not Related  Relationship to the device under study can be excluded  
Study 
Procedure 
 Causal 
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  
Unlikely 
The relationship to the study procedure seems not relevant and/or 
the event can be reasonably explained by another cause, but 
additional information may be obtained  
Not Related  Relationship to the procedure can be excluded  
 
 

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9.2.3. 
Outcome  
 
The outcome of each AE must be assessed according to the following classifications: 
 
Table 7.  Adverse Event Outcome Classifications 
Classification 
Definition 
Recovered  
Resolved  
Subject fully recovered with no observable residual 
effects 
Resolved with 
sequelae 
Subject recovered with observable residual effects 
Recovering 
Resolving 
Adverse event has not resolved and additional 
change in condition is possible 
Not Recovered 
Not Resolved 
Subject didn’t recover from the AE and the observed 
AE effects are still present 
Fatal 
Subject died as a result of the AE (whether or not the 
AE is related to the device or procedure) 
 
 
9.2.4. 
Anticipated Adverse Event  
 
An anticipated Adverse Event is an effect which by nature, incidence, severity or outcome has 
been identified as a possible complication associated with the investigational medical device 
and/or intervention procedure. 
 
Potential adverse events that are reasonably anticipated to occur during the cardiac 
electrophysiology procedure are listed in Table 8. These events should be reported via EDC as 
anticipated AEs.  
 
Table 8.  Comprehensive List of Anticipated AEs 
Anticipated Adverse Events 
 
Acute Respiratory Distress Syndrome 
(ARDS) 
Air embolism 
Allergic reaction  
Allergic reaction to Anesthesia (e.g., 
hair loss) 
Anaphylactic shock 
Anemia 
Anesthesia reaction 
Apnea - sedation induced 
Arrhythmia: bradycardia 
Arrhythmia: pro-arrhythmias 
Arrhythmia: tachycardia 
Aspiration pneumonia 
Asthmatic attack 
Atelectasis 
Atelectasis 
Atrial fibrillation* 
Atrio-Esophageal fistula 
Atypical left atrial flutter 
AV fistula 
Bleeding complications 
Bleeding requiring transfusion 
Cardiac arrest 
Cardiac perforation  
Cardiac thrombo-embolism 
Cerebro-vascular accident (CVA) / stroke 
Chest pain/discomfort 
Complete heart block, temporary or 
permanent 
Conduction block: ongoing / resolved 

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Congestive Heart Failure 
Coronary artery dissection 
Coronary artery occlusion 
Coronary artery spasm 
Coronary artery Thrombosis 
Damage to the vascular system 
Death 
Deep venous thrombosis 
Diaphragmatic paralysis 
Dislodgement of permanent pacing 
leads 
Disseminated Intravascular Coagulation 
Dyspnoea 
Endocarditis 
Epistaxis 
Esophageal Injury 
Exacerbation of pre-existing 
arrhythmia* 
Expressive aphasia 
Fainting 
Fatigue 
Gastric reflux 
Gastrointestinal diverticulosis 
Gastro-intestinal NOS 
Heart Failure 
Hematoma (local) /ecchymosis 
Hemorrhage 
Hemothorax 
High / increased creatine phosphokinase 
(CPK) 
Hypotension 
Hypoxia 
Increase in frequency or duration of 
episodes of typical atrial flutter 
Increased phosphokinase level 
Infection, localized  
Infection, systemic 
Injury to skin, muscle, connective tissue 
due to body position, electrical 
cardioversion, etc. 
Laceration 
Leakage of air or blood into the lungs 
or other organs due to perforation 
Liver toxicity 
Mobile strands in Inferior Vena Cava 
Myocardial Infarction 
Nausea 
Neurological disorders (headache) 
Neurological disorders (poor 
coordination) 
Neurological disorders (tremor) 
Obstruction to the vascular system 
Palpitations 
Perforation to the vascular system 
Pericardial effusion without tamponade 
Pericardial effusion resulting in 
tamponade 
Peripheral embolus 
Pericarditis 
Peripheral thromboembolism 
Peripheral nerve injury 
Phrenic nerve damage  
Phlebitis 
Pneumothorax 
Pleural effusion 
Pulmonary edema 
Pseudoaneurysm 
Pulmonary hypertension 
Pulmonary embolism 
Pulmonary vein dissection 
Pulmonary toxicity, like acute 
pulmonary syndrome 
Pulmonary vein thrombus 
Pulmonary vein Stenosis 
Renal failure 
Pump failure 
Respiratory failure 
Respiratory depression 
Rhabdomyolysis, including produced by 
body position or propofol 
Retroperitoneal hematoma 
Seizure 
Sedation induced CO2 retention with 
lethargy and cholecystitis 
Skin burns (due to cardioversion, tape, etc) 
Sepsis 

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Skin injury / muscle or connective tissue 
injury due to body position, electrical 
cardioversion 
Skin discoloration 
Tamponade 
Skin rash 
Thrombocytopenia 
Temperature elevation 
Thrombosis 
Thromboembolism 
Transient extremity numbness 
Thyroid disorders 
Unintended complete or incomplete AV, 
Sinus node, or other heart block or damage 
Transient ischemic attack (TIA) 
Urinary tract injury or infection related to 
the urinary catheter 
Urinary retention 
Vasovagal reactions 
Valvular damage/insufficiency 
Volume overload 
Vision change 
X-ray radiation injury of skin, muscle and/or 
organ 
Worsening obstructive, restrictive, or 
other form of pulmonary disease 
*Atrial Fibrillation and exacerbation of an existing arrhythmia are anticipated adverse events.  
However, they will not be captured as such under this protocol, as they are considered recurrence of 
disease. 
 
9.3. 
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 AE/SAEs since the last visit.  
 
All AE/SAEs need to be followed until the event is resolved (with or without sequelae). 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 
(S)AE must be recorded in the eCRF.  Additional documentation may be requested by the Sponsor or 
designee, including but not limited to, a written subject narrative detailing the clinical course of the 
AE/incident, a copy of any correspondence with the local REB, hospital records, death certificate and 
autopsy report if available. The local CHU will collect the resolution information of any reported SAEs.  
 
 
9.4. 
Reporting Procedures 
 
9.4.1. 
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. All adverse events must be documented by completing subject’s medical records 
(source documents) and appropriate eCRF by the investigator or study coordinator throughout 

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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 principal investigator(s), 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., definitely device-related or possibly device-related) in accordance with 
relevant regulations and current company procedures. 
 
In the case of serious device effects and device deficiencies that could have led to serious adverse 
device effects, 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 9. 
 
Table 9.  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 
Primary AEs 
Report to Sponsor immediately upon awareness of event but no 
later than 72 hours 
Study device 
failure/malfunction 
associated with an AE 
Report both study device failure and AE to Sponsor immediately 
upon awareness of event but no later than 72 hours 
All other Adverse Events 
Report to Sponsor within 2 weeks upon awareness of the event  
 
 
9.4.2. 
Incident Reporting 
 
All Adverse Event will be reviewed by the Complaint Handling Unit (CHU) of the Sponsor, where 
the assessment will be made if the respective event is reportable as required by Health Canada. 
 
The sponsor will submit as per site specific requirements in a timely manner to all 
participating clinical investigators, a safety overview.  Pursuant to EN ISO 14155AEs will be fully 

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recorded and reported by the sponsor to Health Canada as well as the REB according to the 
requirements and deadlines in force. 
 
 
9.4.3. 
Events of Special Interest 
 
Event reporting to Health Canada in accordance with the jurisdictional regulations will occur by 
the sponsor and/or by the investigator, depending upon the local 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, HC policies, and local regulations. 
 
 
9.5. 
Safety Oversight 
 
Safety oversight will be conducted by the Medical Safety group. 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. As deemed 
applicable, under the rules of an approved study-specific charter, safety events might be 
reviewed by an established committee which may recommend appropriate action(s) to ensure 
subject safety. 
 
 
10. Administrative Responsibilities 
 
10.1. Ethics Committee and Competent Authority Application 
The study protocol (or amendment[s]), ICF, and other applicable study related documents must 
be approved by HC before enrollment of subjects. Any additional requirement imposed by the EC or 
regulatory authority shall be discussed, agreed upon, and followed. A signed copy of the EC and CA (if 
applicable) 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. 
 
 
10.2. Audits and Inspections 
 
The sponsor and/or designee and/or Regulatory Authorities may contact the participating institution 
to inform the investigator of an upcoming audit/inspection. The investigator should immediately notify 
the sponsor of any Regulatory Authority 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. 
 
 
11. Deviations from the Clinical Study Plan 
 

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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 Adverse 
Events, product malfunctions and other product issues; and other non-conformance to GCPs. 
 
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. 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. 
 
 
12. Investigational Product Accountability 
 
13. Clinical Monitoring 
 
Clinical site/remote (targeted) 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 
GCP, and with applicable regulatory requirement(s). Each site might undergo periodic monitoring of the 
study, which might involve a visit from a Sponsor representative, qualified to perform such visit.  
 
Monitoring contacts (visits or remote) may include, but are not limited to, the following: 
• 
Protocol adherence 
• 
Source documentation verification and accuracy of the eCRFs  
• 
Verification that informed consent is being obtained for all subjects participating in the study in 
accordance with requirements described in the 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. 
 
Data are to be submitted promptly via e-CRF after collection. Missing or unclear data will be 
corrected as necessary throughout the trial. Biosense Webster will request further documentation 
such as physician and/or cardiac EP lab procedure notes when complications or malfunctions are 
observed and reported. 
 

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Further details on clinical monitoring are provided in the study specific monitoring plan.  
 
 
14. Statistical Methodology 
 
The Sponsor will be responsible for the overall analysis of data from this protocol. This section 
represents the Statistical Analysis Plan for this protocol. All analyses and subsequent detail are 
described below. 
 
14.1. Levels of Significance 
All data will be summarized by descriptive analyses. No formal statistical inference will be made. 
 
14.2. Analysis Sets 
 
The following analysis populations will be used to complete the analyses of data: 
 
• 
Safety Analysis Set: The Safety Analysis Set will include all enrolled subjects who have the 
investigational device inserted, regardless if RF energy is delivered. 
 
• 
Effectiveness Analysis Set : The effectiveness analysis set will include all enrolled subjects who 
meet the study eligibility criteria, have the investigational device inserted and undergo an ablation 
procedure with the study catheter used in conjunction with QMODE+ and /or QMODE for PVI (RF 
energy is delivered). The subjects without any QMODE+ applications for PVI will be considered a 
failure.  
 
14.3. Sample Size Justification 
Since this study is a workflow study with no primary hypotheses to be tested, there are no statistical 
power calculations.  Evidence from between 30 to 50 prospectively enrolled subjects are deemed 
sufficient to characterize safety and performance of the Qdot-nGen ablation system.  
 
14.4. Analyses to be conducted  
 
 
14.4.1. 
General Conventions 
 
Standard descriptive summaries for continuous data include the number of observations with data, 
mean, standard deviation (SD), median, minimum, and maximum values. The mean and median will 
be rounded to one decimal place greater than in the raw data where applicable; the standard 
deviation will be rounded to two decimal places greater than in the raw data where applicable. In 
cases where this is not applicable (e.g., average time spent), the mean will be rounded to one 
decimal place; the standard deviation to two decimal places; the minimum and maximum to the 
nearest whole number. These will be referred to as “continuous summaries” in this document. 
 
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. When 
count data are presented, the percentage for zero counts will be suppressed in order to draw 
attention to the non-zero counts. Frequency counts will be presented as whole numbers and 

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percentages will be rounded to one decimal place. This will be referred to as “categorical 
summaries” in this document. 
 
Adverse events (AE) tables will be sorted by decreasing frequency of events, unless otherwise 
specified. 
 
14.4.2. 
Disposition of Study Subjects 
 
Subject disposition of will be summarized using categorical summaries. The number and percent of 
patients who were enrolled in the study, excluded from the study, included in the safety, and 
effectiveness analysis set, completed the study, and prematurely discontinued from the study will 
be presented. Patients who prematurely discontinued will be summarized by number and 
percentage by primary reason for discontinuation. 
 
A listing of subject disposition will be generated as well as flow diagrams. 
 
14.4.3. 
Demographic and Baseline Characteristics  
 
All demographic and baseline characteristics will be summarized using categorical and continuous 
summaries, as appropriate, for all the safety analysis set. 
 
A listing of subject demographic and baseline characteristics will be generated. 
 
14.4.4. 
Analysis for Primary Endpoint 
Acute procedural success will be summarized using categorical summaries for the effectiveness 
analysis set. 
 
A listing of the primary endpoint will be provided. 
 
14.4.5. 
Analyses of Additional Endpoints 
All analyses of additional endpoints will use the effectiveness analysis set. 
 
Procedural parameters (Total procedure time, Mapping time, PV ablation time, Total ablation time, 
RF application time, and Total Fluoroscopy time) will be analyzed using the safety analysis set using 
continuous summaries. 
 
Procedural data measures (Catheter ablations outside the PV area, PVI achieved with QMODE+ only 
among all targeted veins and by subject, PVI achieved with combined use of QMODE+ and QMODE 
among all targeted veins and by subject, Need for ablation of acute PV reconnection (touch-up) 
among all targeted veins and by subject, Total number of RF applications, % QMODE+ applications 
and % QMODE applications, Anatomical location of touch-up applications using the QDOT catheter, 
and Confirmation of RF energy delivery from nGEN log files) will be summarized using categorical 
summaries. 
 
Procedural details will be summarized as follows. Temperature, power, contact force, and 
impedance during RF application will be summarized using continuous summaries. Anatomical 
segment location per RF application will be summarized using categorical summaries. 
 
Listings of additional endpoints will be generated. 
 

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14.4.6. 
Analyses of Secondary Safety Endpoints 
Secondary safety endpoints will be analyzed using the safety analysis population. 
 
An adverse event (AE) is an event recorded on the Adverse Event CRF page with an onset on or after 
the study ablation procedure. AEs with onset prior to this date that worsen in severity (i.e., increases 
in severity) after a subject has signed informed consent OR have a missing onset date are also 
considered an AE. AEs will be summarized both by subject and event. If a subject has multiple 
occurrences of an AE, for the by-subject summary only a single occurrence will be counted and for 
the by-event summary each event will be counted. 
 
The overall incidence of AEs will be summarized by: 
• 
Any adverse event; 
• 
Serious adverse event; 
• 
Non-serious adverse event; 
• 
Device-related adverse event (defined as unlikely, possible, probable or having a causal 
relationship with the device); 
• 
Serious device-related adverse event;  
• 
Unanticipated device-related adverse event; 
• 
Serious unanticipated device-related adverse event; 
• 
Procedure-related adverse event (defined as unlikely, possible, probable or having a causal 
relationship with the procedure); 
• 
Adverse events leading to discontinuation. 
 
 
 
Serious AEs (SAE) and Non-Serious AEs (NSAE) will be summarized separately by overall incidence 
and adverse event term using categorical summaries.   
 
An adverse device effect (ADE) is any event recorded to have led to an AE on the Investigational 
device deficiency CRF. 
 
ADEs will be summarized by overall incidence, ADEs leading to an AE, ADEs leading to an SADE and 
unanticipated SADE (USADE), device, and time point during the procedure using categorical 
summaries.  
 
Serious Adverse ADEs (SADE) will be summarized by overall incidence, SADEs leading to an AE, SADEs 
leading to a USADE, device, and time point during the procedure using categorical summaries. 
 
ADEs, SADEs, and USADEs will be summarized by overall incidence and by adverse event term using 
categorical summaries in separate tables. 
 
Listings of adverse events and device effects will be generated as well as device deficiencies.  
 
 
14.4.7. 
Handling of Missing Data 
 
Missing data will not be imputed. All analyses will be performed using observed data. 
 
15. Ethics and Protection of Human Subjects 
 

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15.1. 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 and the local government (Health Canada). The Sponsor will also maintain compliance 
with Good Clinical Practice (ICH version 4 du 1 May 1996), the Declaration of Helsinki (Ethical Principles 
for Medical Research Involving Human Subjects, Tokyo 2004), 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 adverse events (SADE’s)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 post 
market clinical follow up 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 post market clinical follow 
up plan to the investigators to obtain all applicable re-approvals. 
 
• 
Maintaining Records  
Biosense Webster will maintain copies of correspondence, data, adverse device effects and 
other records related to the study. Biosense Webster will maintain records related to the 
signed Investigator Agreements. 
 
• 
Submitting Reports  
Biosense Webster will submit any required regulatory reports identified in this section of the 
regulation. This may include unanticipated adverse device effects, withdrawal of EC approval, 
current investigators list, annual progress reports, recall information, final reports and 
protocol deviations.  
 
 
15.2. Informed Consent Process 
 

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Subjects informed consent must be obtained and documented according to the principles of 
informed consent in the latest version of the Declaration of Helsinki (Brazil, 2013), ISO 
14155:2011, and approved by the reviewing Regulatory Authority 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 
Informed Consent Form (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 always maintain confidentiality of the medical records. 
 
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 subjects 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 
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. 
 
 
15.3. 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. 
 

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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 Competent Authorities 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 
Canada 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. 
 
15.3.1. 
Research use of Stored Data 
 
• 
Intended Use: Data collected under this protocol may be used to study Atrial Fibrillation. 
 
• 
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. 
 
16. 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® 3, generator).  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). 
• 
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. 
 

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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. 
 
 
17. Quality Assurance and 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 participating 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 
regulatory authorities. 
 
18. Data Handling and Record Keeping 
 
18.1. Data Collection and Management Responsibility 
 
The Sponsor will be responsible for all data management activities. These activities include 
development of an electronic data collection (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. 
 
18.1.1. 
Data Collection 
Electronic Case Report Forms (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.  
 
All CARTO® 3 (Version 6.0 or above) and nGEN Generator log files created during the procedure 
will be downloaded/ extracted and an anonymized copy provided to the sponsor for further 
evaluation. 
 
18.1.2. 
Data Reporting 
 
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 

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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 HC and Biosense Webster. 
 
Table 10. 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. 
 
18.1.3. 
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. 
 
18.1.4. 
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. 
 
18.2. Study Record Retention and Archiving 
 
Records and reports for the study will remain on file at the site for a minimum of five (5) years or per 
local and country specific record retention requirements following notification by the sponsor that 
all investigations have been terminated or completed. The sponsor must approve archiving, 
transfer, and destruction of the documentation, in writing, prior to the actual archiving, transfer, 
and destruction. The investigator must notify the sponsor, in writing, of transfer location, 
duration, and the procedure for accessing the study documentation. 
 
If the investigator retires, relocates, or withdraws from assuming primary responsibility for keeping 
the study records, custody transfer per written notice must be submitted to the sponsor indicating 
the name and address of the person accepting primary responsibility. The EC must be notified in 

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writing of the name and address of the new custodian. Record retention dates must be provided to 
all parties by the sponsor’s corporation. 
 
19. Study Suspension or Termination 
 
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 HC). 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.  
 
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 principal 
investigator and sponsor shall keep each other informed of any communication received from either 
the EC or the regulatory authority. 
 
If early termination of the study is required due to safety concerns or the occurrence of unanticipated 
adverse or device events, each site will undergo a monitoring visit or call 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 regulatory authority as appropriate and ensure that the 
EC is notified, either by the principal investigator or by the sponsor. If the suspension or premature 
termination was in the interest of safety, the sponsor shall inform all other principal investigators. 
 
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 are addressed and 
satisfy the sponsor, EC and/or regulatory agency.  
 
20. Data and Publication Policy 
 
Publications and/or presentation of clinical investigation results will be coordinated between Biosense 
Webster, Inc. and the clinical investigation author(s). Authorship will be determined prior to 
development of any manuscript.  
 
All information concerning the study, device under study, 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. 
 
 
21. Document Filing 
 

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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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22. Scientific References 
 
1. 
Cain, M.E., Atrial fibrillation--rhythm or rate control. N Engl J Med, 2002. 347(23): p. 1822-3. 
2. 
Calkins, H., et al., 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter 
and surgical ablation of atrial fibrillation: Executive summary. J Arrhythm, 2017. 33(5): p. 369-409. 
3. 
Fuster, V., et al., ACC/AHA/ESC 2006 guidelines for the management of patients with atrial 
fibrillation: full text: a report of the American College of Cardiology/American Heart Association Task 
Force on practice guidelines and the European Society of Cardiology Committee for Practice 
Guidelines (Writing Committee to Revise the 2001 guidelines for the management of patients with 
atrial fibrillation) developed in collaboration with the European Heart Rhythm Association and the 
Heart Rhythm Society. Europace, 2006. 8(9): p. 651-745. 
4. 
January, C.T., et al., 2014 AHA/ACC/HRS guideline for the management of patients with atrial 
fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on 
Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol, 2014. 64(21): p. e1-76. 
5. 
Jazayeri, M.R., et al., Selective transcatheter ablation of the fast and slow pathways using 
radiofrequency energy in patients with atrioventricular nodal reentrant tachycardia. Circulation, 
1992. 85(4): p. 1318-28. 
6. 
Pappone, C., et al., A randomized trial of circumferential pulmonary vein ablation versus 
antiarrhythmic drug therapy in paroxysmal atrial fibrillation: the APAF Study. J Am Coll Cardiol, 2006. 
48(11): p. 2340-7. 
7. 
Wilber, D.J., et al., Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation 
in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA, 2010. 303(4): p. 
333-40. 
8. 
Ullah, W., et al., Randomized trial comparing pulmonary vein isolation using the SmartTouch 
catheter with or without real-time contact force data. Heart Rhythm, 2016. 13(9): p. 1761-7. 
9. 
Kautzner, J., et al., EFFICAS II: optimization of catheter contact force improves outcome of pulmonary 
vein isolation for paroxysmal atrial fibrillation. Europace, 2015. 17(8): p. 1229-35. 
10. 
Andrade, J.G., et al., Pulmonary vein isolation using "contact force" ablation: the effect on dormant 
conduction and long-term freedom from recurrent atrial fibrillation--a prospective study. Heart 
Rhythm, 2014. 11(11): p. 1919-24. 
11. 
Anter, E., et al., Acute pulmonary vein reconnection is a predictor of atrial fibrillation recurrence 
following pulmonary vein isolation. J Interv Card Electrophysiol, 2014. 39(3): p. 225-32. 
12. 
Haines, D.E., The biophysics of radiofrequency catheter ablation in the heart: the importance of 
temperature monitoring. Pacing Clin Electrophysiol, 1993. 16(3 Pt 2): p. 586-91. 
13. 
Bhaskaran, A., et al., Five seconds of 50-60 W radio frequency atrial ablations were transmural and 
safe: an in vitro mechanistic assessment and force-controlled in vivo validation. Europace, 2017. 
19(5): p. 874-880. 
14. 
Kuck, K.H., et al., A novel radiofrequency ablation catheter using contact force sensing: Toccata 
study. Heart Rhythm, 2012. 9(1): p. 18-23. 
15. 
Ikeda, A.N., H; Sharma, T;  Govari, A; Datta, K; Joshi, H; Lifshitz, A; Wittkampf, F and Jackman, W, 
High Power - Short Radiofrequency Applications Rapidly Produce Shallow Lesions Of Equal Diameter 
Without Increasing Risk Of Thrombus Or Steam Pop, in Heart Rhythm Society. 2018: Boston, MA. 
16. 
leshem, E., Zilberman I, Tschabrunn C, et al, High-Power and Short-Duration Ablation for Pulmonary 
Vein Isolation Biophysical Characterization. JACC: Clinical Electrophysiology, 2018. In Press. 
17. 
Sandhu, R.K., et al., The epidemiology of atrial fibrillation in adults depends on locale of diagnosis. 
Am Heart J, 2011. 161(5): p. 986-992 e1. 
18. 
Lee, G., et al., Low risk of major complications associated with pulmonary vein antral isolation for 
atrial fibrillation: results of 500 consecutive ablation procedures in patients with low prevalence of 
structural heart disease from a single center. J Cardiovasc Electrophysiol, 2011. 22(2): p. 163-8. 

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19. 
Voskoboinik, A., et al., Low Rates of Major Complications for Radiofrequency Ablation of Atrial 
Fibrillation Maintained Over 14 Years: A Single Centre Experience of 2750 Consecutive Cases. Heart 
Lung Circ, 2018. 
20. 
Bohnen, M., et al., Incidence and predictors of major complications from contemporary catheter 
ablation to treat cardiac arrhythmias. Heart Rhythm, 2011. 8(11): p. 1661-6. 
21. 
Cappato, R., et al., Updated worldwide survey on the methods, efficacy, and safety of catheter 
ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol, 2010. 3(1): p. 32-8. 
22. 
Michowitz, Y., et al., Effects of sex on the incidence of cardiac tamponade after catheter ablation of 
atrial fibrillation: results from a worldwide survey in 34 943 atrial fibrillation ablation procedures. 
Circ Arrhythm Electrophysiol, 2014. 7(2): p. 274-80. 
23. 
Muthalaly, R.G., et al., Temporal trends in safety and complication rates of catheter ablation for 
atrial fibrillation. J Cardiovasc Electrophysiol, 2018. 
24. 
Teunissen C, V.B., Hassink, R, et.al, Incidence of Pulmonary Vein Stenosis After Radiofrequency 
Catheter Ablation of Atrial Fibrillation. JACC: Clinical Electrophysiology, 2017. 3(6): p. 589-598. 
25. 
Ha, F.J., et al., Prevalence and prevention of oesophageal injury during atrial fibrillation ablation: a 
systematic review and meta-analysis. Europace, 2018. 
26. 
Knopp, H., et al., Incidental and ablation-induced findings during upper gastrointestinal endoscopy in 
patients after ablation of atrial fibrillation: a retrospective study of 425 patients. Heart Rhythm, 
2014. 11(4): p. 574-8. 
27. 
Kapur, S., et al., Esophageal Injury and Atrioesophageal Fistula Caused by Ablation for Atrial 
Fibrillation. Circulation, 2017. 136(13): p. 1247-1255. 
28. 
Nair, K.K., et al., Atrioesophageal Fistula: A Review. J Atr Fibrillation, 2015. 8(3): p. 1331. 
29. 
Scanavacca, M.I., How to prevent, recognize and manage complications of AF ablation? Rev Port 
Cardiol, 2017. 36 Suppl 1: p. 43-49. 
30. 
Yong Ji, S., et al., Phrenic nerve injury: An underrecognized and potentially preventable complication 
of pulmonary vein isolation using a wide-area circumferential ablation approach. J Cardiovasc 
Electrophysiol, 2013. 24(10): p. 1086-91. 
31. 
Cappato, R., et al., Prevalence and causes of fatal outcome in catheter ablation of atrial fibrillation. J 
Am Coll Cardiol, 2009. 53(19): p. 1798-803. 
32. 
Haegeli, L.M. and H. Calkins, Catheter ablation of atrial fibrillation: an update. Eur Heart J, 2014. 
35(36): p. 2454-9. 
33. 
Funayama, N., et al., Acute right coronary artery occlusion after radiofrequency catheter ablation of 
cavotricuspid isthmus: Vascular response assessed by optical frequency domain imaging. 
HeartRhythm Case Rep, 2017. 3(10): p. 496-498. 
34. 
Rillig, A., et al., Catheter ablation within the sinus of Valsalva--a safe and effective approach for 
treatment of atrial and ventricular tachycardias. Heart Rhythm, 2008. 5(9): p. 1265-72. 
35. 
Fujii, S., J.R. Zhou, and A. Dhir, Anesthesia for Cardiac Ablation. J Cardiothorac Vasc Anesth, 2017. 
36. 
Liu, Y., et al., Incidence and outcomes of cerebrovascular events complicating catheter ablation for 
atrial fibrillation. Europace, 2016. 18(9): p. 1357-65. 
37. 
Bessiere, F. and P. Chevalier, Pulmonary vein hematoma after atrial fibrillation cryoablation: a new 
complication. Heart Rhythm, 2013. 10(9): p. 1359. 
38. 
De, S.C., et al., Direct Pulmonary Vein Ablation With Stenosis Prevention Therapy. J Cardiovasc 
Electrophysiol, 2015. 26(9): p. 1000-1006. 
39. 
Lin, A.C. and D. Wilber, Complications associated with radiofrequency catheter ablation, in 
Radiofrequency Catheter Ablation of Cardiac Arrhythmias: Basic Concepts and Clinical Applications, 
S.K.S. Huang and D.J. Wilber, Editors. 2000, Futura Publishing Company, Inc.: Grouponk, NY. p. 737-
746. 
40. 
Scheinman, M.M. and S. Huang, The 1998 NASPE prospective catheter ablation registry. Pacing Clin 
Electrophysiol, 2000. 23(6): p. 1020-8. 
41. 
Calkins, H., et al., Radiation exposure during radiofrequency catheter ablation of accessory 
atrioventricular connections. Circulation, 1991. 84(6): p. 2376-82. 

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42. 
Kovoor, P., et al., Risk to patients from radiation associated with radiofrequency ablation for 
supraventricular tachycardia. Circulation, 1998. 98(15): p. 1534-40. 
43. 
Nahass, G.T., Fluoroscopy and the skin: implications for radiofrequency catheter ablation. Am J 
Cardiol, 1995. 76(3): p. 174-6. 
44. 
Cox, B., M.E. Durieux, and M.A. Marcus, Toxicity of local anaesthetics. Best Pract Res Clin 
Anaesthesiol, 2003. 17(1): p. 111-36. 
45. 
Mertes, P.M. and M.C. Laxenaire, Allergic reactions occurring during anaesthesia. Eur J Anaesthesiol, 
2002. 19(4): p. 240-62. 
46. 
Morcos, S.K., et al., Prevention of generalized reactions to contrast media: a consensus report and 
guidelines. Eur Radiol, 2001. 11(9): p. 1720-8. 
47. 
Bick, R.L. and E.P. Frenkel, Clinical aspects of heparin-induced thrombocytopenia and thrombosis and 
other side effects of heparin therapy. Clin Appl Thromb Hemost, 1999. 5 Suppl 1: p. S7-15. 
48. 
Gruchalla, R.S., 10. Drug allergy. J Allergy Clin Immunol, 2003. 111(2 Suppl): p. S548-59. 
49. 
Kirchhof, P., et al., 2016 ESC Guidelines for the management of atrial fibrillation developed in 
collaboration with EACTS. Europace, 2016. 18(11): p. 1609-1678.