Clinical Study for Safety and Acute Performance Evaluation of the THERMOCOOL SMARTTOUCH® SF-5D System Used With Fast Ablation Mode in Treatment of Patients With Paroxysmal Atrial Fibrillation.
Phase: NA
Conditions: Paroxysmal Atrial Fibrillation
Sponsor: Biosense Webster, Inc.

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QDOT – FAST  
Clinical Study for Safety and Acute Performance Evaluation of the 
THERMOCOOL SMARTTOUCH® SF-5D System used with Fast 
Ablation Mode in Treatment of Patients with Paroxysmal Atrial 
Fibrillation. 
 
 
Protocol Number:  
 BWI_2017_02  
 
Sponsor: 
Biosense Webster, Inc., a division of Johnson & Johnson with registered office at 
33 Technology Drive, Irvine, CA 92618 
 
Operating Company:  
Johnson & Johnson Medical NV/SA with registered office at Leonardo Da 
Vincilaan 15, 1831 Diegem, Belgium, represented by Nathalie Macours. 
 
Funded by: 
Biosense Webster, Inc., part of the Johnson & Johnson family of companies. 
 
Version: 
v.1.0  
 
Date: 
21 December 2017 
 
History of Changes: 
Version – Date  
Description 
 
V1.0 – 21 DEC 2017 
Original document 
 
The THERMOCOOL SMARTTOUCH® SF-5D catheter and system is for investigational device use only and is 
not commercially available anywhere in the world. QDOT MICRO™ catheter (THERMOCOOL 
SMARTTOUCH® SF-5D catheter) is an internal Biosense Webster name and other than as used in the 
present clinical investigation, is not intended for any other external use. The final commercial or trade 
name of the THERMOCOOL SMARTTOUCH® SF-5D catheter and system may be different. 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
1. BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
......................................................... 14 
1.1. 
BACKGROUND I
NFORMATION 
............................................................................................................... 14 
1.2. 
RATIONALE FOR DESIGN OF THE CLINICAL INVESTIGATION 
..................................................................... 14 
1.2.1. Previous Experience with the THERMOCOOL® SMARTTOUCH® SF catheter 
........................ 15 
1.2.2. Previous Experience with THERMOCOOL SMARTTOUCH® SF-5D catheter 
........................... 15 
1.3. 
ANIMAL STUDY THIGH PREP LESION MODEL 
........................................................................................ 16 
1.3.1. Animal Study Thigh Prep Lesion Model 
....................................................................................... 16 
1.3.2. Animal Testing: Endocardial Study 
.............................................................................................. 17 
1.4. 
POTENTIAL RISK AND BENEFIT ............................................................................................................ 18 
1.4.1. Known Potential Risks 
................................................................................................................. 18 
1.4.2. Minimization of Risk 
..................................................................................................................... 21 
1.4.3. Known Potential Benefits 
............................................................................................................. 22 
2. OBJECTIVES ........................................................................................................................................... 23 
3. STUDY DESIGN AND ENDPOINTS 
........................................................................................................ 23 
3.1. 
DESCRIPTION OF THE STUDY DESIGN 
.................................................................................................. 23 
3.2. 
STUDY ENDPOINTS 
............................................................................................................................. 23 
3.2.1. Primary Endpoint(s) 
..................................................................................................................... 23 
3.2.2. Secondary Endpoint(s) ................................................................................................................ 24 
4. STUDY POPULATION 
............................................................................................................................. 24 
4.1. 
PARTICIPANT I
NCLUSION CRITERIA ...................................................................................................... 24 
4.2. 
PARTICIPANT EXCLUSION CRITERIA 
..................................................................................................... 25 
4.3. 
PARTICIPANT WITHDRAWAL OR TERMINATION ...................................................................................... 26 
4.3.1. Reasons for Withdrawal or Termination ...................................................................................... 26 
4.3.2. Handling of Participant Withdrawals or Termination 
.................................................................... 26 
4.4. 
SUBJECT ENROLLMENT DISPOSITION 
................................................................................................... 26 
5. RESPONSIBILITIES 
................................................................................................................................. 27 
5.1. 
I
NVESTIGATOR RESPONSIBILITIES 
........................................................................................................ 27 
5.2. 
SPONSOR RESPONSIBILITIES 
............................................................................................................... 28 
6. STUDY DEVICE DESCRIPTION 
.............................................................................................................. 29 
6.1. 
DEVICE ACQUISITION 
.......................................................................................................................... 29 
6.2. 
DEVICE STORAGE AND STABILITY 
........................................................................................................ 29 
6.3. 
DEVICE PREPARATION 
........................................................................................................................ 29 
6.4. 
I
NSTRUCTIONS FOR USE ..................................................................................................................... 29 
6.5. 
DEVICE DESCRIPTION 
......................................................................................................................... 29 
6.5.1. THERMOCOOL SMARTTOUCH® SF-5D Catheter 
.................................................................... 29 
6.5.2. nMARQ™ Multi-Channel RF Generator 
...................................................................................... 32 
6.5.3. TGA mode 
...................................................................................................................................... 33 
6.6. 
EQUIPMENT 
........................................................................................................................................ 34 
6.6.1. System Components and Setup 
.................................................................................................. 34 
6.6.2. Required Study Devices .............................................................................................................. 35 
7. STUDY MEDICATION 
.............................................................................................................................. 35 
8. STUDY SCHEDULE 
................................................................................................................................. 36 
8.1. 
SCREENING AND I
NFORMED CONSENT 
................................................................................................. 36 
8.2. 
BASELINE EVALUATION AND PROCEDURES 
........................................................................................... 37 
8.2.1. Pre-Procedure/Baseline Assessments 
........................................................................................ 37 
8.2.2. Study Ablation Procedure Guidelines 
.......................................................................................... 38 
8.2.3. Data collection during study ablation procedure 
.......................................................................... 41 
8.2.4. Pre-Discharge Assessments ....................................................................................................... 42 
8.2.5. Repeat Ablation Procedures 
........................................................................................................ 43 
8.3. 
POST-ABLATION FOLLOW-
UP SCHEDULE ............................................................................................. 43 

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8.4. 
FINAL STUDY VISIT ............................................................................................................................. 44 
8.5. 
EARLY TERMINATION VISIT 
.................................................................................................................. 44 
8.6. 
UNSCHEDULED VISIT 
........................................................................................................................... 44 
8.7. 
CORE LABORATORY FOR EVALUATION 
................................................................................................. 44 
8.8. 
SCHEDULE OF EVENTS TABLE 
............................................................................................................. 45 
9. ASSESSMENT OF SAFETY 
.................................................................................................................... 46 
9.1. 
SPECIFIC SAFETY PARAMETERS 
.......................................................................................................... 46 
9.1.1. Definition of Adverse Events (AE) ............................................................................................... 46 
9.1.2. Definition of Serious Adverse Event (SAE).................................................................................. 46 
9.1.3. Primary Adverse Event (PAE)...................................................................................................... 47 
9.1.4. Adverse Device Effect (ADE) / Serious Adverse Device Effect (SADE) ..................................... 49 
9.1.5. Unanticipated (Serious) Adverse Device Effect (UADE/USADE) 
................................................ 49 
9.1.6. Study Device Deficiency, Failure or Malfunction ......................................................................... 49 
9.2. 
CLASSIFICATION OF AN ADVERSE EVENT ............................................................................................. 49 
9.2.1. Severity of Event 
.......................................................................................................................... 49 
9.2.2. Relationship to Study Device 
....................................................................................................... 50 
9.2.3. Outcome....................................................................................................................................... 50 
9.2.4. Expectedness .............................................................................................................................. 51 
9.3. 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-
UP 
........................................... 53 
9.4. 
REPORTING PROCEDURES 
.................................................................................................................. 53 
9.4.1. Adverse Event Documentation and Reporting Requirements 
..................................................... 53 
9.4.2. Serious Adverse Events Reporting 
.............................................................................................. 54 
9.4.3. Unanticipated Device Effect Reporting 
........................................................................................ 54 
9.4.4. Events of Special Interest 
............................................................................................................ 55 
9.5. 
SAFETY OVERSIGHT ........................................................................................................................... 55 
10. 
ADMINISTRATIVE RESPONSIBILITIES ............................................................................................ 55 
10.1. ETHICS COMMITTEE AND COMPETENT AUTHORITY APPLICATION 
........................................................... 55 
10.2. AUDITS AND I
NSPECTIONS 
................................................................................................................... 56 
11. 
DEVIATIONS FROM THE CLINICAL STUDY PLAN 
.......................................................................... 56 
12. 
INVESTIGATIONAL PRODUCT ACCOUNTABILITY 
......................................................................... 56 
12.1. USE OF THE I
NVESTIGATIONAL DEVICE AND I
NVESTIGATOR EXPERIENCE 
............................................... 56 
12.2. MATERIALS......................................................................................................................................... 57 
12.3. DEVICE ACQUISITION AND ACCOUNTABILITY 
......................................................................................... 57 
12.4. DEVICE RETURNS 
............................................................................................................................... 58 
12.5. DEVICE LABELING 
............................................................................................................................... 58 
13. 
CLINICAL MONITORING .................................................................................................................... 58 
14. 
STATISTICAL METHODOLOGY 
......................................................................................................... 59 
14.1. STUDY DESIGN 
................................................................................................................................... 59 
14.2. TREATMENT ASSIGNMENT 
................................................................................................................... 59 
14.3. I
NTERVAL WINDOWS 
........................................................................................................................... 59 
14.4. PRIMARY AND SECONDARY ENDPOINTS,
 AND ASSOCIATED HYPOTHESES 
.............................................. 59 
14.4.1. Primary Endpoints and Associated Hypotheses ..................................................................... 59 
14.4.2. Secondary Endpoints and Associated Hypotheses ................................................................ 59 
14.5. LEVELS OF SIGNIFICANCE ................................................................................................................... 60 
14.6. ANALYSIS SETS 
.................................................................................................................................. 60 
14.7. SAMPLE SIZE JUSTIFICATION 
............................................................................................................... 60 
14.8. ANALYSES TO BE CONDUCTED 
............................................................................................................. 61 
14.8.1. General Conventions 
............................................................................................................... 61 
14.8.2. Disposition of Study Subjects 
.................................................................................................. 61 
14.8.3. Demographic and Baseline Characteristics ............................................................................ 61 
14.8.4. Primary and Secondary Endpoint Analyses 
............................................................................ 61 
14.8.4.1. Analyses of Primary Safety Endpoint 
...................................................................................... 61 
14.8.4.2. Analyses of Primary Effectiveness Endpoint 
........................................................................... 61 
14.8.4.3. Analyses of Secondary and Additional Endpoints 
................................................................... 61 
14.8.5. Handling of Missing Data 
......................................................................................................... 61 

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14.8.6. Subgroup Analyses ................................................................................................................. 62 
15. 
ETHICS AND PROTECTION OF HUMAN SUBJECTS 
...................................................................... 62 
15.1. ETHICAL STANDARD 
............................................................................................................................ 62 
15.2. I
NFORMED CONSENT PROCESS 
........................................................................................................... 63 
15.3. PARTICIPANT AND DATA CONFIDENTIALITY 
........................................................................................... 64 
15.3.1. Research use of Stored Data 
.................................................................................................. 64 
16. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
................................... 64 
17. 
QUALITY ASSURANCE AND QUALITY CONTROL ......................................................................... 65 
18. 
DATA HANDLING AND RECORD KEEPING 
..................................................................................... 65 
18.1. DATA COLLECTION AND MANAGEMENT RESPONSIBILITY 
....................................................................... 65 
18.1.1. Data Collection ........................................................................................................................ 65 
18.1.2. Data Reporting ........................................................................................................................ 66 
18.1.3. Data Verification and Review .................................................................................................. 66 
18.1.4. Final Data Analysis 
.................................................................................................................. 67 
18.2. STUDY RECORD RETENTION AND ARCHIVING 
....................................................................................... 67 
19. 
STUDY SUSPENSION OR TERMINATION ........................................................................................ 67 
20. 
DATA AND PUBLICATION POLICY 
................................................................................................... 68 
21. 
DOCUMENT FILING 
............................................................................................................................ 68 
22. 
APPENDIX A: QMODE 
........................................................................................................................ 69 
22.1. I
NTRODUCTION QMODE ALGORITHM 
.................................................................................................. 69 
22.2. USE OF THE THERMOCOOL SMARTTOUCH® SF-5D Q-
MODE ALGORITHM 
..................................... 69 
22.2.1. Recommended ablation parameters 
............................................................................................ 70 
23. 
SCIENTIFIC REFERENCES 
................................................................................................................ 73 
 
 
 
 

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List of Tables 
Table 1 Summary of Subject Assessments........................................................................................... 
13 
Table 2 Required Study Devices 
........................................................................................................... 
35 
Table 3 Summary of Subject Assessments........................................................................................... 
45 
Table 4 Primary Adverse Events .......................................................................................................... 
47 
Table 5 Intensity or Severity Definitions 
.............................................................................................. 
49 
Table 6 Adverse Event Causality Classifications .................................................................................. 
50 
Table 7 Adverse Event Outcome Classifications 
.................................................................................. 
50 
Table 8 A provides a comprehensive list of anticipated AEs. 
.............................................................. 
51 
Table 9 AE Reporting Requirements 
.................................................................................................... 
54 
Table 10 Responsibilities for Preparing and Submitting Reports 
........................................................ 
66 
Table 11 Ablation parameters for - Q-mode ....................................................................................... 
70 
 
List of Figures 
Figure 1 Overview of the THERMOCOOL SMARTTOUCH® SF-5D Catheter with Bi-directional Tip 
Deflection 
............................................................................................................................................. 
30 
Figure 2 THERMOCOOL SMARTTOUCH® SF-5D tip Section D-1395-05-SI 
........................................... 
30 
Figure 3 THERMOCOOL SMARTTOUCH® SF-5D tip with Thermocouples (6), µElectrodes (3) and angled 
irrigation ports 
..................................................................................................................................... 
31 
Figure 4 Contact Force Sensor – External View 
................................................................................... 
32 
Figure 5 Ablation Screen: THERMOCOOL SMARTTOUCH SF 5D Catheter 
........................................... 
33 
Figure 6 Connectivity Diagram 
............................................................................................................. 
34 
 
 
 

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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 
33 Technology Drive,  
Irvine, CA 92618 
USA 
Tel: +1 800-729-9010 
 
CONTACTS:   
Clinical Franchise Research Manager CSS, EMEA 
Carmen Rousseeuw 
Johnson & Johnson Medical NV  
Leonardo Da Vincilaan 15 
1831 Diegem - Belgium 
Tel: +32 479 96 22 97 
E-mail: croussee@its.jnj.com 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
Whereas, the Clinical Study is sponsored by Biosense Webster Inc., Johnson and Johnson Medical NV/SA with 
registered offices at 
Leonardo Da Vincilaan 15, 1831 Diegem, Belgium, has been duly appointed by the Sponsor 
to conduct the Clinical Study on its behalf. 
 
The sponsor maintains an updated list of principal investigators, sites, institutions and Contract Research 
Organizations (CRO) (if applicable). The definitive list shall be integrated into the study report. 
 
 

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• Confirmation of PVI with Lasso® or Pentaray® (or other at investigators 
discretion) 
• Confirmation of entrance block with adenosine/isoproterenol challenge 
In this study protocol, TGA mode is to be used as the primary mode for pulmonary vein 
isolation. Only after the investigator deems TGA mode unable to achieve PVI should 
the study catheter in Q-mode be used to complete the procedure.   
Primary Endpoint 
Acute Safety: 
The primary safety endpoint is the incidence of Primary Adverse Events (PAEs) 
(within seven (7) days of the initial mapping and ablation procedure). PAEs include 
the following AEs: 
Atrio-Esophageal Fistula* 
Phrenic Nerve Paralysis 
Cardiac Tamponade/perforation 
Pulmonary Vein Stenosis* 
Death* 
Stroke/CVA 
Major Vascular Access 
Complication/Bleeding 
Thromboembolism 
Myocardial Infarction 
TIA 
* Device or procedure related death, pulmonary vein stenosis and atrio-esophageal fistula 
that occur greater than one week (7 days) post-procedure are considered and analyzed as 
primary AEs. 
 
Acute Effectiveness: 
Acute Procedural Success defined as confirmation of entrance block in all targeted 
PVs after adenosine and/or isoproterenol challenge. 
The use of a non-study catheter for PVI will be considered an effectiveness failure. 
Secondary Endpoints 
Safety 
- Incidence of Serious Adverse Device Effects (SADEs)  
- Incidence of Serious Adverse Events (SAEs) within 7 days (early-onset), >7-30 
days (peri-procedural) and >30 days (late onset) of initial ablation procedure 
- Incidence of non-serious adverse events  
- Incidence of pre-and post-ablation asymptomatic and symptomatic cerebral 
emboli as determined by MRI evaluations 
- Incidence of new or worsening neurological deficits compared to baseline 
- Summary of NIHSS, mRS and MoCA scores at baseline and follow-up 
timepoints 
 
Effectiveness 
- PVI achieved with TGA mode only among all targeted veins and by subject 
- PVI achieved with combined use of TGA and Q-mode among all targeted 
veins and by subject 
- Ablation of acute reconnection (touch-up) among all targeted veins and by 
subject 
- Ablation by a non-study catheter among all targeted veins and by subject 
- Touch-up applications with TGA, Q-mode and non-study catheter 
applications 
 
Additional analyses on procedural data, including but not limited to: 
- Use of QDOT Micro™ catheter ablation outside the PV area 
- Use of a non-study catheter for ablation outside the PV area 
- Total procedure time, mapping time, PV ablation time, total ablation time, 
RF application time, LA dwell time 
- Total number of RF applications, % TGA applications and % Q-mode 
applications 
- Anatomical location of touch-up applications 
- Temperature, power, contact force, impedance 

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- Total Fluoroscopy time/dose 
 
Inclusion Criteria 
Subjects must meet ALL the following inclusion criteria to be eligible for participation 
in this clinical investigation: 
1. Age 18 or older. 
2. Signed the Patient Informed Consent Form (ICF). 
3. Diagnosed with symptomatic PAF 
4. Selected for catheter ablation through pulmonary vein isolation.  
5. Able and willing to comply with all pre-, post-, and follow-up testing and 
requirements (e.g. patient not confined by a court ruling). 
Exclusion Criteria 
Subjects who meet ANY of the following exclusion criteria are not eligible for 
enrollment: 
1. Atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or 
reversible or non-cardiac cause. 
2. Previous surgical or catheter ablation for atrial fibrillation. 
3. Previously diagnosed with persistent, longstanding AF and/or continuous AF 
>7 days, or >48 hrs. terminated by cardioversion. 
4. Documented Left Atrial thrombus on baseline/pre-procedure imaging.  
5. Any carotid stenting or endarterectomy. 
6. Left atrial (LA) size >50mm. 
7. Left Ventricular ejection fraction (LVEF) <40%. 
8. Uncontrolled heart failure or New York Heart Association (NYHA) function 
class III or IV. 
9. History of blood clotting or bleeding abnormalities  
10. Contraindication to anticoagulation  
11. History of a documented thromboembolic event (including transient 
ischemic attack (TIA)) within the past 12 months. 
12. Previous percutaneous coronary intervention (PCI) or myocardial Infarction 
(MI) within the past 2 months. 
13. Coronary artery bypass grafting (CABG) in conjunction with valvular surgery, 
cardiac surgery (e.g. ventriculotomy, atriotomy) or valvular cardiac (surgical 
or percutaneous) procedure. 
14. Rheumatic Heart Disease 
15. Awaiting cardiac transplantation or other cardiac surgery within the next 12 
months. 
16. Unstable angina. 
17. Significant pulmonary disease (e.g. restrictive pulmonary disease, 
constrictive or chronic obstructive pulmonary disease) or any other disease 

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or malfunction of the lungs or respiratory system that produces chronic 
symptoms. 
18. Acute illness, active systemic infection, or sepsis. 
19. Presence of atrial myxoma, interatrial baffle or patch  
20. Presence of intramural thrombus, tumor or other abnormality that precludes 
catheter introduction or manipulation. 
21. Presence of a condition that precludes vascular access. 
22. Presence of implanted pacemaker or implantable cardioverter-defibrillator 
(ICD). 
23. Presence of IVC filter 
24. Significant congenital anomaly or a medical problem that in the opinion of 
the investigator would preclude enrollment in this trial. 
25. Currently enrolled in an investigational study evaluating another device, 
biologic, or drug. 
26. 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. 
27. Life expectancy or other disease processes likely to limit survival to less than 
12 months. 
28. Presenting contra-indication for the devices used in the study, as indicated in 
the respective instructions for use. 
29. Categorized as vulnerable population and requires special treatment with 
respect to safeguards of well-being 
30. Contraindication to use of contrast agents for MRI such as advanced renal 
disease, etc. (at PI discretion)  
31. Presence of iron-containing metal fragments in the body  
32. Unresolved pre-existing neurological deficit.  
Statistical Analysis 
All data will be summarized by descriptive analyses. No formal statistical inference 
will be made. Sub-analyses will be done for subjects where TGA was the only 
application mode used and for subjects where applications were done through a 
mixture of TGA and Q-mode. 
Interim Analysis 
Analysis of acute outcomes may be done prior to completion of the study FU period 
and after completion of all study procedures. 
Safety Monitoring 
Safety review will be performed by the medical safety officer as described by Safety 
Management Plan. 
Time and Events 
Schedule 
See table 1 below 
 
 

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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.
1,5 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.”
4 
Creation of transmural, continuous, and durable RF lesions is the objective of PVI. Conventional 
parameters of radiofrequency (RF) ablation with irrigated catheters involves 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%.9,10 
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.11,12 
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.13  
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.14,15 This can be achieved by delivering a large 
current for a short duration.  
 
 
1.2. Rationale for Design of the clinical investigation 
 
The Biosense Webster THERMOCOOL SMARTTOUCH® SF-5D 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.   
 

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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. 
 
A
 
 
 
 
    
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
   
 
 
 
1.2.1. 
Previous Experience with the THERMOCOOL® SMARTTOUCH® SF catheter 
 
The THERMOCOOL® SMARTTOUCH® SF catheter, approved in the European Union, features a porous 
electrode tip (56 small holes) in contrast to the predecessor THERMOCOOL®SMARTTOUCH® device, 
which featured 6 larger holes at the distal electrode tip.  In subjects with paroxysmal AF, the 
THERMOCOOL® SMARTTOUCH® SF catheter with Surround Flow (SF) technology was as successful as 
the predecessor catheter in achieving PV isolation, with delivery of similar amounts of RF energy. 
 
Moreover, the saline volume administered by the catheter was reduced when compared to the 
SMARTTOUCH® Catheter.
31 Procedural efficiency was also enhanced; time to PV isolation and total RF 
duration,32,33 as well as saline irrigation volume,
33,34 were diminished in paroxysmal AF subjects who 
underwent ablation with the SMARTTOUCH® SF catheter compared to the THERMOCOOL® 
SMARTTOUCH® catheter without SF technology. 
 
 
 
1.2.2. 
Previous Experience with THERMOCOOL SMARTTOUCH® SF-5D catheter 
 
This clinical feasibility study will be the first experience using THERMOCOOL SMARTTOUCH SF-5D
 in conjunction with the nMARQ™ Multi-Channel RF Generator (
 
, including TGA mode. 
 

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Bench and animal testing has been performed using the THERMOCOOL SMARTTOUCH SF-5D Catheter 
and the nMARQ™ Multi-channel RF Generator.  Please refer to the Investigator Brochure for detailed 
summaries of the test protocols and corresponding reports.  A synopsis of the In Vivo animal studies 
is presented below. 
 
1.3. 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 

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• 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
  
 
 
1.4. Potential Risk and Benefit 
 
RF catheter ablation has been used for over 20 years, and the risks and complications are well 
understood.  A summary of risks associated with catheter ablation, including analysis of and plans to 
minimize these risks is provided below: 
 
1.4.1. 
Known Potential Risks 
 
Known Potential Risks associated with catheter RF ablation procedure  
 
The risk of pulmonary adverse events (e.g., PV stenosis, thrombus and cardiac perforation) 
associated with an AF ablation procedure targeting the pulmonary veins is considered small 
(<4%).
16-22 
 
Arterial or venous injury, including arterial dissection, thrombosis, occlusion or hemorrhage at the 
catheter insertion sites or at other sites along the vessels can occur (risk <1%).23,24 These types of 
injuries may cause hemorrhage, hematoma or ischemic injury to an extremity or major organ. 
 
RF current may cause occlusion of a coronary artery, either by direct thermal damage, spasm, or 
thrombosis. Experience at numerous clinical sites/centers suggests that the risk of coronary 
occlusion is less than 0.5%.
23,24 Coronary arterial occlusion could produce myocardial infarction 
(MI), angina or death. 
 
The application of RF 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. 
 
A thrombus may form on the ablation electrode during the application of RF current, usually 
indicated by an impedance rise; however, this can also occur in the absence of an impedance rise. 
The thrombus could become dislodged and embolize to produce a stroke, myocardial infarction 
(MI), or other ischemic injury. The possible embolic sources include thrombus formation on the 
ablation catheter tip and sheath, debris from steam pop and charring, preexisting thrombus in the 
heart and air embolus. The risk of an embolus is reduced by quickly terminating the application of 

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current after an impedance rise, which limits the size of the coagulum on the electrode.  Probably 
the most important aspect of the THERMOCOOL® family of catheters is the absence or very low 
likelihood of thrombus formation during RF. 
 
Thrombus formation on the endocardium following ablation may produce an arterial or 
pulmonary embolus. This risk may be reduced using aspirin or other anticoagulant therapy, at the 
discretion of the investigator. 
 
Cardiac perforation may result from catheter manipulation or application of RF current. Published 
risks of cardiac perforation range from <1% to 2.5%.
25,8,26-29 This may result in cardiac tamponade 
and may require percutaneous pericardial drainage or surgical repair.  In a recent study using the 
THERMOCOOL SMARTTOUCH® Catheter with contact force sensing technology, there were 4 
(2.48%, 4/161) reported incidents of tamponade.
8,26 Additionally, in the SMART-SF study using a 
new investigational catheter with contact force sensing technology the observed incidence of 
tamponade was 1.3% (2/159). 
 Significant hemodynamic compromise can result 
in neurologic 
injury 
or death.  An increased risk of cardiac perforation during ablation may be associated with the use 
of saline-irrigated electrode catheter due to its ability to create a larger, deeper lesion. 
 
Using the standard RF power settings, i.e. between 25 to 45 watts, at current application duration, 
such as at 30 s, it could deliver up to 1200 J to atrial tissue and provide the potential risk of 
overheating.
14 The risk of cardiac perforation is even higher in thin walled, smooth muscle tissue 
and veins with the conventional approach, when each ablation stays longer on the same spot. In 
current clinical practice, RF application duration parameter becomes a crucial biophysical timer to 
monitor the safety threshold.  In this protocol, the novel high power and short duration algorithm 
reduces the application duration significantly. It has the potential to deliver less energy and to 
generate uniform lesions without collateral damages, in particular in a thin walled atrial chamber.   
 
Peri-esophageal vagal nerve injury or pyloric spasm after left atrial catheter ablation of AF can 
occur when RF energy 
is applied to the posterior wall of the LA.4 
While these complications are rare 
(approximately < 1%), they can potentially compromise the clinical outcome severely, requiring 
surgical treatment.
30,31 While there is no established method to prevent injury to the vagal nerves, 
the risk may be reduced by using the same techniques used to avoid an AEF (atrial esophageal 
fistula). 
4 
 
Injury to a cardiac valve may result from catheter manipulation or the application of RF current 
(risk <1%).
23,24   This may produce valvular insufficiency and possibly require surgical valve 
replacement. 
 
The application of RF energy along the posterior left atrium can result in thermal injury to the 
esophagus and the formation of an atrio-esophageal fistula.  This is a rare (0.04%) but severe 
complication of RF ablation requiring surgical intervention or that may result in permanent 
impairment.
25,28 Reducing power at sites in close proximity to and/or avoiding sites directly over 
the esophagus may reduce the risk of thermal injury. 
 
Injury to the phrenic nerve may occur as a result of RF application in the region of right pulmonary 
veins.  The reported incidence of phrenic nerve injury varies from 0% to 0.48% when RF energy is 
used for catheter ablation.32,33 Prior to ablation in the region of the right superior pulmonary vein, 
precautionary measures are recommended to be performed by investigators to evaluate proximity 
to the phrenic nerve, such as pacing maneuvers. 
 

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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%).
34-
36 
 
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%).
37-41 
Hemorrhage could occur as a result of anticoagulation (risk <0.5%), which may require 
transfusion.
23,24  
 
The percutaneous procedure carries risk of infection, either at the catheter insertion site or 
systemically, including endocarditis and septic emboli (risk <0.5%).23,24 This risk can be minimized 
by using standard aseptic technique and, when indicated, by the use of antibiotic agents. 
 
Investigational device related risks  
THERMOCOOL SMARTTOUCH® SF-5D catheter and nMARQ Multi-Channel RF generator with TGA 
mode 
Although the risks are low, anticipated risks /major complications associated with the catheter 
ablation procedure in general could still occur during the procedure.   During the TGA design phase 
(ref RBA section 6.1.1), systematic proactive risk analyses concluded that no new hazards and harms 
associated with TGA (FAST mode) have been identified to cause any foreseeable risks.  At this 
juncture, no new complications are anticipated concerning the TGA ablations.  
 
The nMARQ™ Multi-Channel RF Generator (D-1341-07) (SW version 2.3.1) was CE marked on Oct 
25, 2013. 
 In order to allow for an 
interface with the THERMOCOOL SMARTTOUCH® SF-5D Catheter, 
the software was modified to SW version 3.0.1.  As a result of the software modification, the 
nMARQ™ Multi-Channel RF Generator will be designated as an investigational device.   Further 
reference can be made to the User manual and addendum, for more information.  Enhanced 
versions of the SW v3.0.1 might be released and used during the course of this study. A protocol 
Amendment will be submitted for approval if any additional significant risks would be identified in 
newly released software versions. 
 
The software with TGA mode using the investigational catheter has been validated in both bench 
top and animal testing at the system level. The design of the software has been independently 
validated to perform against functional requirements. Accuracy of the generator as it relates to: 
temperature and power was 
identified to be the highest risk related to the device. 
 Therefore, 100% 
testing of generator power, temperature and impedance is included in the lot release protocol, 
prior to the release to the study. 
 
Robust testing of the devices from the component and the system level, within simulated clinical 
conditions, 
including certain up 
limits & extreme clinical scenarios, was determined to be successful 
with no adverse events identified. 
 
For SW V3.0.1 there are no anticipated potential direct risks to the subject, the risk is mitigated by 
the temp cutoff setting of the generator and the optimization of the target temperature.  Further 
reference can be made to the pre-clinical testing reports and Investigator Brochure for more 
information. 
 
 
 
 
 

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1.4.2. 
Minimization of Risk 
 
The criteria for subject selection, methods, personnel, facilities, and training that have been 
specified 
in this study are 
intended to minimize the risk to subjects undergoing this procedure.  
 
Patient selection: Subjects will be screened carefully prior to enrollment 
in the study to ensure 
compliance with the inclusion and exclusion criteria.  The exclusion criteria have been 
developed to exclude subjects with a medical history or condition that increases their risk of 
adverse events (refer to Section 4.2 for the Exclusion Criteria).   
 
Pre-procedure imaging: All subjects will have pre-procedure imaging as described in section 
8.2 
to screen for the presence of LA thrombus, which 
is 
intended to decrease the potential for 
thromboembolic complications.    
 
Within procedure safeguard: Investigators will undergo training on the use of the 
THERMOCOOL SMARTTOUCH® SF-5D technology prior to subject enrollment.  Investigators 
skilled in intracardiac mapping and ablation of AF with the use of RF ablation catheters 
containing contact force technology will be selected for participation in the study.  All
 
investigators are required to receive the training prior the enrollment. AF ablation procedures 
will be performed in electrophysiology laboratories with the assistance of skilled nurses and 
technicians. The detailed 
workflow for the procedure 
is provided 
in the protocol, 
including the 
target temperature, the cut-off temperature, the range of the contact force, the stability using 
Visitag, Respiratory compensation and Automatic tags. To proactively manage the four big 
“watch-out” complications (Atrio-Esophageal Fistula, PV stenosis, Phrenic nerve paralysis and 
cerebral embolism) for a RF ablation procedure, the protocol proposes the following: 
• In order to prevent esophageal injury, intraluminal esophageal monitoring is required 
for the study  
• The risk of
 cerebral lesions will be monitored by pre-post cerebral MRI examination 
monitoring for cerebral embolism. 
• The risk of PV stenosis will be minimized by monitoring that RF energy applications are 
at least 1 to 2 cm outside the PV ostium to isolate the left and right-sided PVs; Subjects 
presenting suggestive symptoms for PV stenosis, should undergo the cardiac CT/MRI;  
• The risk of PNP will be minimized by monitoring the PN with pacing maneuvers before the 
ablation. High output pacing is recommended at vulnerable sites and avoid ablations 
at the area that stimulate the PN 
 
Post-procedural 
management: 
In 
accordance 
with 
the 
2017 HRS expert consensus statement4, 
all subjects will be recommended to be maintained on systemic oral anticoagulation therapy 
for at least two months post-procedure, beginning within 6 hours post-procedure. After two- 
months post-procedure, a decision regarding continuation of systemic anti-coagulation 
agents will be based on the patient risk for thromboembolism. Systemic oral anticoagulation 
will be recommended to be continued beyond two-months post-ab
lat
ion in patients with 
CHA2DS2-VASc 
score 
≥2. 
 
Safety data during enrollment and follow-up will be c
losely mon
itored and evaluated per the 
specific safety management plan for the study. Also, refer to safety section 9 for more 
information 
on 
safety 
management. 
 
 
 
 

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1.4.3. 
Known Potential Benefits 
 
The Biosense Webster THERMOCOOL SMARTTOUCH® SF-5D 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 improved contact force information and temperature feedback in any tip tissue 
orientation, the new THERMOCOOL SMARTTOUCH® SF-5D 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 THERMOCOOL SMARTTOUCH® SF-5D Ablation System: nMARQ™ 
Multi-Channel RF Generator (D-1341-07, SW version 3.0.1) 
and 
THERMOCOOL SMARTTOUCH® 
SF-5D catheter may improve safety and efficiency.  The System may potentially: 
 
• 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 high-power for a short duration, giving that catheter instability in a 
constantly mobile heart and tissue edema remains problematic for the effective lesions 
using the conventional ablation technique. 
• 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. 
• Reduce the amount of fluid loading of the patient as compared to a focal ablation 
catheter. 
 
Further reference can be made to the Risk-Benefit Analysis (RBA) for more information.  
 

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2. Objectives  
 
The primary objective of this clinical investigation is to assess the safety and acute performance 
of the 
THERMOCOOL SMARTTOUCH® SF-5D system 
used with the TGA algorithm, 
in the 
isolation of the atrial 
pulmonary veins in treatment of patients diagnosed with Paroxysmal Atrial Fibrillation (PAF). 
Specifically, to demonstrate: 
o Safety based on the incidence of early onset Primary Adverse Events (PAEs) (within seven (7) 
days of the initial ablation procedure). 
o Acute system performance based on acute procedural success defined as confirmation of 
entrance block in all targeted PVs after adenosine and/or isoproterenol challenge. 
Secondary objectives of the study relate to further evaluation of safety with regards to (serious) 
adverse events and neurological incidents up to 3 months following procedure. Secondary 
evaluation of effectiveness and workflow will be done through characterization of the TGA and Q-
mode use for PVI, assessment of acute reconnection during the procedure and through description 
of procedural parameters.  
 
3. Study Design and Endpoints 
 
3.1. Description of the Study Design 
 
The QDOT-FAST study is a prospective, multi-center, non-randomized clinical study to evaluate the 
safety and acute performance of the THERMOCOOL SMARTTOUCH® SF-5D system with the TGA 
algorithm in patients diagnosed with Paroxysmal Atrial Fibrillation (PAF). 
 
The study population will consist of 
up to 
50 
subjects with PAF as an 
indication for radiofrequency (RF) 
ablation. PAF is defined as AF that terminates spontaneously or with intervention within 7 days of 
onset. Episodes may recur with variable frequency (HRS ACC guidelines, 2017).
4 
 
The study will be conducted at up to 10 sites 
in Europe. Follow-up will be conducted at 7 days, 1 month 
and 3-month post-ablation procedure. 
 
3.2. Study Endpoints 
 
3.2.1. 
Primary Endpoint(s) 
 
Acute Safety  
 
The primary safety endpoint is the incidence of Primary Adverse Events (PAEs) (within seven (7) days 
of the initial mapping and ablation procedure). Primary Adverse Events are one of the following 
adverse events listed below. (refer to section 9.1.3 for a complete list and description/criteria). 
 
Atrio-Esophageal Fistula (AEF)* 
Phrenic Nerve Paralysis (PNP) 
Cardiac Tamponade/perforation 
Pulmonary Vein Stenosis* 
Death* 
Stroke/CVA 
Major Vascular Access Complication/Bleeding 
Thromboembolism 
Myocardial Infarction 
TIA 
* Device or procedure related death, pulmonary vein stenosis and atrio-esophageal fistula, that occur 
greater than one week (7 days) post-procedure are considered and analyzed as primary AEs. 

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Acute Effectiveness  
 
Acute procedural success 
defined as confirmation of entrance 
block 
in all targeted PVs after adenosine 
and/or isoproterenol challenge. 
 
 
3.2.2. 
Secondary Endpoint(s) 
 
Safety 
- Incidence of Serious Adverse Device Effects (SADEs)  
- Incidence of Serious Adverse Events (SAEs) within 7 days (early-onset), >7-30 days (peri-
procedural) and >30 days (late onset) of initial ablation procedure 
- Incidence of non-serious adverse events  
- Incidence of pre-and post-ablation asymptomatic and symptomatic cerebral emboli as 
determined by MRI evaluations 
- Incidence of new or worsening neurological deficits compared to baseline 
- Summary of NIHSS, mRS and MoCA scores at baseline and follow-up timepoints 
 
Effectiveness 
- PVI achieved with TGA mode only among all targeted veins and by subject 
- PVI achieved with combined use of TGA and Q-mode among all targeted veins and by subject 
- Ablation of acute reconnection (touch-up) among all targeted veins and by subject 
- Touch-up applications with TGA, Q-mode and non-study catheter applications 
- PV ablation by a non-study catheter among all targeted veins and by subject 
 
Additional analyses on procedural data, including but not limited to: 
- Use of QDOT Micro™ catheter ablation outside the PV area 
- Use of a non-study catheter for ablation outside the PV area 
- Total procedure time, mapping time, PV ablation time, total ablation time, RF application time, 
LA dwell time 
- Total number of RF applications, % TGA applications and % Q-mode applications 
- Anatomical location of touch-up applications 
- Temperature, power, contact force, impedance 
- Total Fluoroscopy time/dose 
 
 
4. Study Population 
 
4.1. Participant Inclusion Criteria 
Subjects must meet ALL the following inclusion criteria to be eligible for participation in this clinical 
investigation: 
1. Age 18 or older. 
2. Signed the Patient Informed Consent Form (ICF). 
3. Diagnosed with symptomatic PAF 
4. Selected for catheter ablation through pulmonary vein isolation.  
5. Able and willing to comply with all pre-, post-, and follow-up testing and requirements (I.e. 
patient not confined by a court ruling). 

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4.2. Participant Exclusion Criteria 
Subjects who meet ANY of the following exclusion criteria are not eligible for enrollment: 
1. Atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or reversible or non-
cardiac cause. 
2. Previous surgical or catheter ablation for atrial fibrillation. 
3. Previously diagnosed with persistent, longstanding AF and/or continuous AF >7 days, or >48 
hrs. terminated by cardioversion. 
4. Documented Left Atrial thrombus on baseline/pre-procedure imaging.  
5. Any carotid stenting or endarterectomy. 
6. Left atrial (LA) size >50mm. 
7. Left Ventricular ejection fraction (LVEF) <40%. 
8. Uncontrolled heart failure or New York Heart Association (NYHA) function class III or IV. 
9. History of blood clotting or bleeding abnormalities  
10. Contraindication to anticoagulation  
11. History of a documented thromboembolic event (including transient ischemic attack (TIA)) 
within the past 12 months. 
12. Previous percutaneous coronary intervention (PCI) or myocardial Infarction (MI) within the 
past 2 months. 
13. Coronary artery bypass grafting (CABG) in conjunction with valvular surgery, cardiac surgery 
(e.g. ventriculotomy, atriotomy) or valvular cardiac (surgical or percutaneous) procedure. 
14. Rheumatic Heart Disease 
15. Awaiting cardiac transplantation or other cardiac surgery within the next 12 months. 
16. Unstable angina. 
17. Significant pulmonary disease (e.g. restrictive pulmonary disease, constrictive or chronic 
obstructive pulmonary disease) or any other disease or malfunction of the 
lungs or respiratory 
system that produces chronic symptoms. 
18. Acute illness, active systemic infection, or sepsis. 
19. Presence of atrial myxoma, interatrial baffle or patch  
20. Presence of intramural thrombus, tumor or other abnormality that precludes catheter 
introduction or manipulation. 
21. Presence of a condition that precludes vascular access. 
22. Presence of implanted pacemaker or implantable cardioverter-defibrillator (ICD). 
23. Presence of IVC filter 
24. Significant congenital anomaly or a medical problem that in the opinion of the investigator 
would preclude enrollment in this trial. 
25. Currently enrolled in an investigational study evaluating another device, biologic, or drug. 
26. 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. 
27. Life expectancy or other disease processes likely to limit survival to less than 12 months. 
28. Presenting contra-indication for the devices used in the study, as indicated in the respective 
instructions for use. 
29. Categorized as vulnerable population and requires special treatment with respect to 
safeguards of well-being 
30. Contraindication to use of contrast agents for MRI such as advanced renal disease, etc. (at PI 
discretion)  
31. Presence of iron-containing metal fragments in the body  
32. Unresolved pre-existing neurological deficit.  
 

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4.3. Participant Withdrawal or Termination 
 
4.3.1. 
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 3-months follow-up period. 
 
4.3.2. 
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 should follow the subject 
until the AE/SAE has resolved or is considered stable. 
 
If a subject is unable to return for an office/clinic visit or cannot be contacted by telephone, 3 
separate 
telephone calls 
should 
be 
made 
to obtain 
subject related safety 
information. All attempts 
should 
be documented 
in the 
source documents. 
If the subject 
does not 
respond to the 
3 telephone 
calls, 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 will not count for the enrollment goal of 50 subjects. Excluded 
subjects can be replaced with new enrolled subjects for the study to reach a total of 50 evaluable 
study-subjects.  
 
4.4. 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. Excluded subjects will only be followed between ICF signature and exclusion for 
event reporting. 

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• Evaluable Subjects:  All enrolled subjects who have the study catheter inserted.  
• Discontinued Subjects: Enrolled subjects who have the study catheter inserted but do not 
undergo ablation (i.e., no RF energy is delivered with the study catheter).  Discontinued 
subjects will remain in follow-up for 30 days. 
• Lost to Follow-up Subjects:  Evaluable subjects of which contact is lost after most recent visit 
(despite 3 documented attempts to contact the subject). 
• Withdrawn / Early Termination Subjects:  Subjects who withdraw consent for study 
participation or are withdrawn by the investigator, are terminated from the study prior to 
completion of all follow-up visits. 
• Completed Subjects:  Enrolled subjects who have not been excluded, discontinued, 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 
• Prov
iding 
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 comp
liance by site 
personnel 
with 
the 
prov
is
ions 
of 
the 
protocol 
• Comp
leting the appropr
iate training on the device (ab
lating investigators only) and 
the 
study 
protocol 
pr
ior 
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) 
EC 
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 pertain
ing to the pu
lmonary 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 
monitor
ing 
or 
auditing 
duties 
• Maintain 
records 
and 
prov
ide 
reports 
according 
to 
prevailing 
regulatory 
requirements 
• Share 
relevant 
study-related 
information 
with 
delegated 
study 
staff 

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• Inform the appropriate entities (e.g., Sponsor, 
CA, EC) in a timely manner regarding 
the 
occurrence 
of 
AEs 
and/or 
product 
malfunctions. 
• Making 
sufficient 
effort 
to 
maintain 
contact 
with 
treated 
subjects 
who 
fail 
to 
comply 
with 
the 
follow-up 
requirements 
• Maintain study records for at least 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. 
• Comp
lying 
with 
EC 
and 
Sponsor 
annual 
report 
requirements, 
including 
the 
final 
report. 
 
5.2. Sponsor Responsibilities 
 
The 
Sponsor 
(Biosense 
Webster, 
Inc.) 
will 
be 
responsib
le 
for 
the 
following: 
• Conduct 
of 
pre-study 
s
ite 
assessment 
and 
approval. 
• Preparation and modification (if applicable) of study documents including but 
not limited 
to 
the 
protocol, 
CRFs 
and 
informed 
consent 
• Selection of appropr
iately qualified and trained ind
iv
iduals, inc
lud
ing mon
itors, 
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/hosp
itals, 
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 
summar
izing 
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 
Clin
ical 
Study 
Protocol/Investigational 
Plan 
to the 
competent 
authority. 
 
 
 
 
 
 

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6. Study Device Description 
 
6.1. Device Acquisition 
 
After obtaining a fully executed clinical trial agreement and appropriate EC approvals, the sponsor will 
initiate shipment(s) of investigational devices to the site. The Sponsor will keep records of all 
investigational devices shipped to the site. Approved investigational devices will be shipped directly 
to the site and will be received by the site. Investigators are responsible for appropriate logging of the 
devices received, verification of packing slip 
information (i.e., 
lot numbers and quantity shipped), date 
and identity that each device was used in the study, disposition information regarding disposal or 
return to the Sponsor. 
 
6.2. Device Storage and Stability 
 
Devices are to be stored in a secure/locked location and in accordance with the IFU. Do not use this 
device after the “Use By” date. 
 
6.3. Device Preparation 
 
Information related to device preparation can be found in the Instruction for Use. 
 
6.4. Instructions for Use 
 
A comprehensive set of IFU/User manual for the Study Devices (Catheter and Generator) and all 
accessory cables/interface cables is contained in each product package and is also available upon 
request.   
  
 
6.5. Device Description 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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o Adenosine: A bolus (i.e. 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 
 
Subjects presenting to the institution with symptomatic PAF and considered for an RF ablation 
procedure 
should 
be 
screened 
by 
the 
investigator 
or 
designated 
member 
of 
the 
research 
team for 
study 
eligibility 
per 
the 
protocol 
inclusion 
and 
exclusion criteria. 
Sites 
will 
be 
instructed 
to screen all subjects 
who require a documented RF ablation procedure for symptomatic PAF without regard to sex or 
race. 
 
The study investigator or designated member of the research team will obtain written informed 
consent from the subject. The patient informed consent procedure must be done within 60 days 
before the actual study procedure takes place. The background of the proposed study and the 
potential benefits and risks of the study should be explained to the subject. The subject or legal 
representative must sign the consent form prior to any study-specific exams or tests are provided 
to them that fall outside of the standard of care. The consent form used must have prior approval 
from 
the regulatory 
authorities 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. 
 
Each subject screened for enrollment in the clinical investigation 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. 
 
 
 
 

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8.2. Baseline Evaluation and Procedures 
 
8.2.1. 
Pre-Procedure/Baseline Assessments 
 
Below pre-procedure assessments and data collection must be performed prior to the ablation 
procedure  
 
- Patient Information and Consent (procedure must be done within 60 days of consent) 
- Demographics (age, gender, etc.). 
- Medical history, including but not limited to arrhythmia, heart disease, thromboembolic 
events, lung/respiratory problems. 
- AF history (first evidence of AF, number of episodes, symptoms, etc.). 
- Medication history: Medication history (cardiac medication, AAD medication, 
anticoagulation regimen and any other clinically significant medication history) shall be 
gathered by interview or from medical records following enrolment but prior to the 
ablation procedure and should be recorded in the eCRF. 
- Anticoagulation therapy: Uninterrupted systemic anticoagulation therapy is 
recommended for at least 3 weeks prior to the AF ablation procedure.  
- CHA2DS2 VASc Score: Subjects will be scored against the CHA2DS2 VASc.  
- NYHA Functional Class Scale. 
- Pregnancy test must be done on all women of childbearing age and potential, within 1 
week prior to the procedure and documented in the subject’s medical chart. 
- Transthoracic Echo (TTE) to determine the atrial size and LVEF% should be completed 
within 30 days prior to the study ablation procedure, unless the subject has undergone an 
imaging procedure within 6 months prior where the atrial size was assessed. 
- Imaging for detection of left atrial thrombus or other structural contraindications to an 
ablation procedure is mandatory the day before or the day of the ablation procedure. 
Presence 
of 
a 
thrombus 
will 
require 
postponement 
of 
the 
ablation 
procedure 
or 
may 
even 
lead to exclusion of the subject from further study involvement. The imaging method to 
be used for atrial thrombus detection is transesophageal echocardiography (TEE), 
intracardiac Echocardiography 
(ICE), Computed Tomography (CT) 
or Magnetic Resonance 
Imaging (MRI). 
- Electrocardiogram (12-Lead ECG). Data from 12-lead ECG recordings will be collected if 
available. 
- Adverse Events must be collected from the time the subject signs the informed consent 
onwards 
- Cerebral MRI, Neurological Exam and Neurological Evaluation using the Montreal 
Cognitive Assessment (MoCA), NIH Stroke Scale (NIHSS) and Modified Rankin Scale 
(mRS) are required to be performed within 72- hours pre-procedure to evaluate the 
neurological condition and presence of neurological deficits of the subjects before 
undergoing study ablation procedure. A certified/qualified physician expert must 
perform neurologic exams at pre- and post-ablation and possibly at other follow-up 
visits, pending previous findings of micro-emboli/neurologic 
deficits. 
 
 
 
 
 

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8.2.2. 
Study Ablation Procedure Guidelines 
 
8.2.2.1 Recommended Ablation Parameters 
 
In this study protocol, TGA RF energy application mode  
) is to be used as the 
primary mode for circumferential pulmonary veins isolation.  Only after the investigator 
deems TGA unable to achieve PVI should the study catheter in Q-mode be used to complete 
the procedure. 
 
 
 
 
 
 
Note: The above-mentioned parameters are user-adjustable, in case the investigator deems 
appropriate.  
 
 
 
Caution: The parameters provided in this section are based on data obtained from animal 
studies. Use clinical judgment when using this catheter paying careful attention to initial 
impedance, impedance drop, electrogram reduction, time of RF application, and with 
consideration of individual patient conditions. 
 
Recommendation for CoolFlow® Irrigation Pump Setting and RF Power-delivery 
 
 
 
 
 
 
 
 
Recommended Contact Force (CF) Settings 
 
 
   
 
 
 
 
8.2.2.2 Esophageal monitoring  
 
REQUIRED: An appropriate strategy to minimize risk of esophageal injury MUST be used to ensure 
the physician has accurate information about the location of the esophagus relative to intended 
sites of ablation.  The method used to localize the esophagus will be collected in the CRFs. 
 
At least one of the following methods MUST be used for esophageal monitoring:  
- Use of an esophageal temperature probe  
- Esophageal visualization with CARTOSOUND® and/or ICE  
- Esophageal visualization using barium swallow 
- Esophageal displacement during RF application 
 

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8.2.2.3 Study 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 for this study should follow this sequence: 
- Transseptal puncture 
- Mapping (left atrial anatomical map) is required prior to the ablation procedure.  
Note: An anatomical map is not required for triggers outside the left atrium (e.g. 
SVC/CS etc.) 
- Ensure Esophageal monitoring 
- Confirmation of target ACT 300-400 PRIOR to insertion of the study catheter into the left 
atrium and maintain throughout the procedure 
- Introduction of the study catheter 
- Complete PV encirclement with TGA mode as the primary mode for ablation (refer to 
NOTE 1 below). Q-mode can be used where the investigator deems TGA mode unable to 
achieve PVI. 
- Confirmation of PV isolation in all targeted PV’s 
- Waiting period (20 minutes) and Isoproterenol/adenosine challenge 
- Confirmation of entrance block in all targeted PV’s 
 
 
8.2.2.4 Study Ablation Procedure Guidelines 
In this study protocol, TGA mode is to be used as the primary mode for pulmonary vein isolation 
(refer to NOTE 1 below). Only after the investigator deems TGA mode unable to achieve PVI should 
the study catheter 
in Q-mode be used to complete the procedure. 
(refer to appendix A for Q-mode) 
The circumferential anatomical approach will be used to isolate all PVs. To minimize the risk of 
PV stenosis, it is recommended that RF energy applications are at least 1 to 2 cm outside the PV 
ostium to isolate the left and right-sided PVs. Confirmation of entrance block in all targeted PVs is 
REQUIRED. 
 
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 (see section 8.2.2.2 for required esophageal 
monitoring instructions) 
- 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 
 
Electrophysiology Study, Mapping and Ablation procedure  
 
- Anesthesia or sedation should be delivered per standard EP lab procedure. 
- Placement of diagnostic catheters: 
- Coronary sinus catheter in the CS for pacing purposes  
- Other catheters may be placed at the discretion of the investigator 
- Mandatory use of an esophageal monitoring method to minimize risk of esophageal injury. 
- Administration of heparin bolus prior to transseptal puncture 
- Transseptal puncture 

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- Following successful transseptal puncture, an anatomic map can be performed, utilizing 
Lasso® or Pentaray® (or other at investigator discretion) 
- Confirm target ACT 300s-400s. Systematic Anticoagulation with heparin should be 
administrated with ACT level checked to target ACT of 300-400 seconds throughout the 
procedure 
- Introduce the study catheter (if not yet used for mapping purposes) 
- Perform respiratory training 
- Use the AUTOTAG feature 
in Carto to tag each TGA mode ablation point after each application 
- Display Visitag prior to the ablation to ensure stability 
- A pre-ablation flow rate delay of minimal 2 seconds will occur before every RF application  
- Ablation: RF power application 
 (TGA-mode) 
- A post-ablation flow rate delay of minimal 4 seconds will occur after every RF application  
- TGA mode should be used for full PV encirclement (refer to NOTE 1 below). Only in case the 
investigator deems TGA mode unable to achieve PVI should the study catheter in Q-mode be 
used to complete the procedure. 
- Move the catheter to a new location (~4mm) if clinically effective ablation is achieved (refer 
to NOTE 2 below)  
- At the new location ensure catheter stability before commencing RF application. 
- Continue RF applications and catheter movement until the circumferential PVI is completed. 
- Precautions: 
- If the temperature increases above the temperature cutoff 
 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, initiate a 20-min waiting period (ref. section verification of ablation 
procedure). 
- Map 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.  
- Perform additional applications (touch-up), if required 
- Confirmation of entrance block of all targeted PV’s 
 
NOTE 1:  The recommendations provided in this section are based on data obtained from 
animal studies. Use clinical judgment when using this catheter paying careful attention to 
initial impedance, impedance drop, electrogram reduction, time of RF application, and with 
consideration of individual patient conditions when selecting settings 
 
NOTE 2: At the end of a TGA ablation ( 
 a second  
 RF application can be made at the 
same ablation spot if clinically effective ablation did not occur.  A 4-sec waiting period before a 
new TGA RF application at the same site is required.  
 
 
 
 
 
 

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Ablation outside the PV Ostia 
- Prophylactic ablation of empirical sites outside the PV Ostia is discouraged for this protocol 
- CFAE ablation is not allowed per protocol 
- In the event of typical AFL/ AT, the placement of linear lesions in the cavotricuspid isthmus 
(CTI) is at the discretion of the investigator 
- If linear lesions are placed, bidirectional block should be confirmed as demonstrated by 
mapping and/or pacing maneuvers  
 
Verification of ablation procedure 
- Verification of isolation of the targeted PVs by demonstrating entrance block into each 
targeted PV is required. To verify entrance block, analyze electrograms in sinus and/or atrial 
paced rhythm to confirm that no PV potentials are present. 
- After initial PVI confirmation, apply a 20-minute waiting period. The time of initial PVI 
confirmation must be documented in the medical record as source documentation.  
- Mapping the ablation lines during the 20-minute waiting period should occur per standard 
practice.  If conduction is noted during mapping, additional RF applications should be 
applied. 
- After the 20-minute waiting period, administer one of the below to rule out dormant 
conduction: 
- Isoproterenol (to achieve a ≥ 20 beats per minute increase in heart rate; 
recommended dose range is 2-20 mcg/min) 
OR 
- Adenosine (i.e. bolus of 24 mg to confirm PV isolation) 
- In case of acute reconnection being identified, apply touch-up applications until entrance 
block is re-confirmed 
- Final demonstration of entrance block MUST be confirmed and documented by Lasso® or 
PentaRay® catheter (or other at investigators discretion) 
- The ablation procedure is considered complete when confirmation of entrance 
block/isolation of the pulmonary veins is confirmed and documented after the 20-minute 
waiting period and isoproterenol/adenosine challenge. 
 
 
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® data files for study analysis. 
At the completion of the study ablation procedure two back-up copies of the CARTO 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. 
 
 

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The information collected during the procedure will include, but will not be limited to, the list 
below. 
- RF application-mode per lesion (TGA-mode/Q-mode/other) 
- Number of RF applications with QDot catheter (total/Q-mode/TGA-mode) and with non-
study catheter 
- Duration of RF applications with QDot catheter (total/Q-mode/TGA-mode) and with non-
study catheter 
- 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: location, temperature, impedance, power, 
contact force, RF duration, ablation index, lesion information on CARTO® 
- Ablation number on the generator for first RF application and last RF application per 
target (left PV targets, right PV targets and for targets outside the PV area) 
- Ablation parameters for touch-up applications (location, RF application-mode, amount of 
touch-up applications, duration and associated generator file number) 
- Total procedure time (from first femoral puncture to last catheter removal) 
- Atrial mapping time 
- Fluoroscopy time and dose 
- 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 
- 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 
• 
Endoscopy: imaging of the esophagus for the detection of esophageal injury within 72 
hours post-procedure; prior to discharge. 
• 
Transthoracic echocardiogram (TTE) to assess the pericardium.  In the event of a 
significant pericardial effusion is identified, subjects should be followed until the condition 
resolves. 
• 
Adverse events, if any 
• 
Occurrence of AF or other arrhythmias, if any 
• 
Cerebral MRI (within 72hours post procedure), Neurological exam and Neurological 
Evaluation using the NIH stroke Scale (NIHSS) within 72- hours post procedure, prior to 
discharge. A certified/qualified physician expert must perform neurological exams. 
 
 
 

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8.2.5. 
Repeat Ablation Procedures 
 
Repeat ablation procedures and management of arrhythmia recurrences during follow-up may be 
performed at the discretion of the investigator. Repeat procedures during follow up may be 
managed per investigator discretion using a commercially approved and available ablation 
catheter. It’s recommended to perform repeat ablations with the THERMOCOOL SMARTTOUCH® 
SF-5D system. The follow-up schedule will remain based on the initial ablation procedure. 
 
 
8.3. Post-Ablation Follow-up Schedule 
 
The subject will be required to complete follow up visits through 3 months post initial ablation 
procedure. Follow-up will be done at 7 days (phone call or clinic visit), 1 month (if applicable) and 3 
months (clinic visits). 
 
Discharged subjects will receive a telephone call or have a clinic visit at 7 days (7D, day 6-8) post 
ablation procedure to assess cardiac medication AFL/AF/AT occurrences and occurrence of (Primary) 
Adverse Events. 
 
The subject will be required to complete follow up through 3 months post initial ablation procedure. 
The follow-up visits are 1 month ± 7 days (1M, day 23-37) (if applicable) and 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. 
 
• If findings of micro-emboli/neurologic deficits/ CVA or TIA events identified at a prior 
evaluation (i.e. pre-discharge) a 1 month follow up visit will be performed with the following 
assessment: 
o Cerebral MRI, Neurological Exam and NIH Stroke Scale (NIHSS), MoCA and mRS 
assessments.  Subjects with findings of micro-emboli/neurologic deficits/CVA/TIA will 
undergo additional MoCA/mRS through 3M follow-up 
 
• At the 3 months post ablation procedure visit (clinic 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 NYHA Functional Class Scale. 
o ECG in case of standard of care 
o Adverse events, if any 
o AFL/AT/AF occurrence and repeat ablation 
o Cerebral MRI, Neurological Exam and NIH Stroke Scale (NIHSS) and MoCA/mRS 
assessments will be performed in case observations findings of micro-
emboli/neurologic deficits were noted during previous assessments. A 
certified/qualified physician must perform neurologic exams at pre-and post-ablation 
and possibly at other follow-up visits, pending findings of micro-emboli/neurological 
deficits. 
o End of Study Follow up 
 
 
 
 

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8.4. Final Study Visit 
 
The Final Study visit for each participant will be conducted 3 months ± 14 days post ablation 
procedure. 
 
 
 
8.5. Early Termination Visit 
 
If early termination of the study is required due to safety concerns, each site will undergo a 
monitoring visit to conclude any outstanding issues, collect all outstanding CRF information, verify 
device accountability, and discuss any other items relevant to the conclusion of the study. Any 
enrolled 
subjects 
will 
continue 
to 
be 
followed 
per 
the 
study 
protocol 
requirements. 
 
 
8.6. Unscheduled visit 
 
If subject returns for a potential study related cardiovascular or neurological visit outside of the 
protocol-defined visit schedule provided in Table 4, the visit will be considered “unscheduled” 
(UNS). An investigator may request an unscheduled visit in the presence of a new or worsened 
cardiovascular condition or neurological deficit. If the unscheduled visit is for a repeat ablation 
procedure, the protocol follow-up schedule is based on the index ablation procedure. For all 
unscheduled 
visits, 
an unscheduled visit 
eCRF 
must 
be 
completed and 
the 
subject 
must 
also 
return 
for 
their 
next 
scheduled 
study 
visit per 
clinical 
investigational plan. 
 
 
8.7. Core Laboratory for Evaluation 
No core lab will be used during this study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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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 
investigational 
medical device. 
 
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: 
• Minor pericarditis attributable to the ablation procedure defined as pleuritic chest 
discomfort with or without pericardial rub and ECG changes. 
• AF/AFL/AT recurrence requiring pharmacological or synchronized electrical cardioversion 
during the hospitalization for the index ablation procedure, or throughout the duration of 
the study.  However, 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 
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. 

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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 
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. 
 
 
 

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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 
SAE must be recorded in the eCRF. 
 
 
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 
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. 

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9.4.4. 
Events of Special Interest 
 
All study device failure/malfunction must be reported to the Sponsor, via eCRF, as soon as possible 
within 72 hours by the study site personnel.  If a device failure is detected or suspected, it should 
be documented on the eCRF and the device returned according to the Sponsor’s instructions. 
 
The investigational device should be sent to appropriate R&D team or designated Quality 
engineer and should be reported to the medical safety lead. Complaints related to non-
investigational products manufactured and/or distributed by Biosense Webster, used during the 
procedure related to other devices (other than the study device under investigation), are to be 
reported according to current Biosense Webster procedures and 
other policies as necessary (i.e., 
institutional policies, EC policies, and local regulations), investigators are instructed to return 
devices in accordance with current company procedures and other relevant regulations. 
 
Event 
reporting 
to relevant competent 
authorities in accordance with the 
jurisdictional regulations 
will occur by the sponsor and/or by the investigator, depending upon the local requirements and 
will be done in EU per MEDDEV 2.12/1 guidelines for CE-marked devices manufactured by 
Biosense Webster and per MEDDEV 2.7/3 guidelines for non-CE-marked devices manufactured 
by Biosense Webster. 
 
A device deficiency related to a medical device not manufactured by Biosense Webster should be 
reported by the investigator to their respective manufacturer as per relevant regulation. 
Complaints related to non-Biosense Webster, Inc. products must be handled according to 
institutional policies, EC policies, and local regulations. 
 
 
9.5. Safety Oversight 
 
Safety oversight will be conducted as described in the safety management plan. Aggregate safety 
data will be reviewed during enrollment by the study safety lead in order to promptly identify new 
issues or trends which may have an impact on the conduct of the study and/or subject safety. Under 
the rules of an approved study-specific charter, safety events will 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 the Ethical Committee (EC) and Competent Authorities (CA) 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 approval letters addressed to the 
investigator must be submitted to Biosense Webster certifying study approval prior to subject 
enrollment. Biosense Webster and the EC must approve, in writing, any 
changes 
to 
the 
protocol 
that 
affect 
the 
rights 
safety 
and/or 
welfare 
of 
the 
subjects, 
or 
may adversely 
affect 
the 
validity 
of 
the 
study. 
 
In addition, Biosense Webster, Inc. is responsible for notifying the relevant CA of the intention to 
perform a clinical investigation under this protocol and ensure to get the official response/ approval 
before starting the clinical investigation. 
 

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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 
 
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 GCP. 
 
A protocol deviation is defined as an instance of failure to follow, intentionally or unintentionally, the 
requirements of the protocol (e.g. missed test or procedure, visit out of window, non-adherence to 
inclusion/exclusion criteria). Investigators are not allowed to deviate from the protocol. 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 
 
12.1. Use of the Investigational Device and Investigator Experience 
 
In addition to the clinical protocol training (i.e. during the site initiation visit), all investigators who 
will be performing the ablation procedures for this study will be required to attend both a didactic 
session, which includes detailed reviews of the study catheter (specifications, parameters, 
etc.) 
and the results of the preclinical studies completed. Ablating physicians with no prior in human 
experience with multi-ablation catheter will also receive hands-on training using the THERMOCOOL 
SMARTTOUCH® SF-5D catheter. The combination of the didactic and hands-on (in-vitro and/or in-
vivo) portions of the documented device training will provide the investigator with the experience 
necessary to perform the protocol specified procedures for the study. 
 

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Investigators selected will be highly skilled in intracardiac mapping and AF ablation with RF ablation 
catheters. 
 
12.2. Materials 
 
Biosense Webster, Inc., Irwindale, CA USA, has manufactured the catheters to be used in this study. 
The investigational devices were built in a clean room environment, and sterilized using EtO gas, in a 
manner similar to standard, commercially approved Biosense Webster products.  
 
Complete manufacturing records of every lot of catheter manufactured for human use during this 
study are maintained at Biosense Webster, Inc. Each lot of catheters is released for human use under 
a Confirmation of Conformity from Regulatory Affairs 
that will certify that the 
investigational catheters 
conforms to the Essential Requirements for product release apart from those features that are being 
investigated in this clinical investigation. And that, with regard to these aspects, every precaution has 
been taken to protect the health and safety of the patient. 
 
 
12.3. Device Acquisition and Accountability 
 
After obtaining a fully executed clinical trial agreement and appropriate competent authority 
(CA)/ethical committee (EC) approvals, the study site will receive the necessary amount of study-
related materials prior to commencement. Study-related devices (investigational ‘THERMOCOOL 
SMARTTOUCH® SF-5D catheters’ and non-investigational devices) will be shipped to the site upon 
completion of required documentation.  
 
Investigational Study Devices will be labeled as “Investigational Device” and are only to be used for 
subjects enrolled in this clinical study.  
 
The Sponsor will keep records of all investigational devices shipped to the site.  
 
Investigational site personnel is responsible for appropriate logging of devices received, verification 
of packing slip information (i.e. lot numbers and quantity shipped) and date, and identifying that each 
device was used in the study and disposition information completed when returned to the Sponsor. 
The Sponsor will label all investigational devices as “Investigational device” in a prominent location.  
 
The Investigational Device Accountability Log shall record the following information: 
• Date of receipt 
• Person in receipt of the devices 
• Quantity received 
• Catalog number for catheters 
• Serial/lot numbers 
• Expiry Date 
• Date devices was used 
• Subject ID on whom device was used 
• Date of return 
 
 
 
 
 

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12.4. Device Returns 
 
All investigational devices ‘THERMOCOOL SMARTTOUCH® SF-5D catheters’ (used and unused) will be 
returned to the Sponsor’s attention at the below address. Any suspected malfunctioning device or 
device associated with an adverse event (device related or possibly device related) will undergo a 
thorough complaint analysis and must be properly documented on the electronic case report form 
(eCRF).  
 
All returned devices must be properly labeled with the subject identification number, date of issue, 
identified as a defective return, non-defective return, or adverse event (as applicable).  
 
All tracking 
information 
must be retained 
in the event the package has been 
lost and requires tracking. 
All investigational devices should be returned to:  
 
ATTN: Complaints Lab 
Biosense Webster, Inc.  
15715 Arrow Highway 
Irwindale, CA 91706 USA 
 
12.5. Device Labeling 
 
Sample labels are included in the package approved by the Regulatory/Competent Authorities. All 
labeling clearly identifies the product as investigational.  
 
13. Clinical Monitoring 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of 
the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with 
applicable regulatory requirement(s). Each site will undergo periodic monitoring of the study, which 
involves a visit from a Sponsor representative, qualified to perform such visit.  
 
Monitoring visits may include, but are not limited to, the following: 
• 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. 
 
Further details on clinical monitoring are provided in the study specific monitoring plan.  
 
 

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14. Statistical Methodology 
 
14.1. Study Design 
The QDOT-FAST study is a prospective, multi-center, non-randomized, interventional clinical study. 
 
14.2. Treatment Assignment 
All subjects in the study will be treated with the THERMOCOOL SMARTTOUCH® SF-5D Catheter (D-
1395-05-SI).  
 
14.3. Interval Windows 
See Section 8.8. 
 
14.4. Primary and Secondary Endpoints, and Associated Hypotheses 
 
14.4.1. Primary Endpoints and Associated Hypotheses 
 
The primary safety endpoint is acute safety defined as the Primary Adverse Events (PAEs) within the 
first 7 days. PAEs include the following AEs: 
 
Atrio-Esophageal Fistula* 
Phrenic Nerve Paralysis 
Cardiac Tamponade/perforation 
Pulmonary Vein Stenosis* 
Death* 
Stroke/CVA 
Major Vascular Access Complication/Bleeding Thromboembolism 
Myocardial Infarction 
TIA 
*Device or procedure related death, pulmonary vein stenosis and atrio-esophageal fistula that occur greater 
than one week (7 days) post-procedure are considered and analyzed as primary AEs. 
 
The primary effectiveness endpoint is acute procedural success defined as achieving confirmation of 
entrance block in all targeted PVs after adenosine and/ or isoproterenol challenge.  The use of non-
study catheter for PVI will be considered as an effectiveness failure.  
 
No formal statistical hypotheses will be formulated and performed for the primary endpoints. 
 
14.4.2. Secondary Endpoints and Associated Hypotheses 
 
No formal statistical hypotheses will be formulated and performed for the secondary endpoints. The 
secondary safety and procedural endpoints are listed below. 
 
Safety 
- Incidence of Serious Adverse Device Effects (SADEs)  
- Incidence of Serious Adverse Events (SAEs) within 7 days (early-onset), >7-30 days (peri-
procedural) and >30 days (late onset) of initial ablation procedure 
- Incidence of non-serious adverse events  
- Incidence of pre-and post-ablation asymptomatic and symptomatic cerebral emboli as 
determined by MRI evaluations 
- Incidence of new or worsening neurological deficits compared to baseline 
- Summary of NIHSS, mRS and MoCA scores at baseline and follow-up timepoints 
 
 

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Effectiveness 
- PVI achieved with TGA mode only among all targeted veins and by subject 
- PVI achieved with combined use of TGA and Q-mode among all targeted veins and by subject 
- Ablation of acute reconnection (touch-up) among all targeted veins and by subject 
- Touch-up applications with TGA, Q-mode and non-study catheter applications 
- PV ablation by a non-study catheter among all targeted veins and by subject 
 
Additional analyses on procedural data, including but not limited to: 
- Use of QDOT Micro™ catheter ablation outside the PV area 
- Use of a non-study catheter for ablation outside the PV area 
- Total procedure time, mapping time, PV ablation time, total ablation time, RF application time, 
LA dwell time 
- Total number of RF applications, % TGA applications and % Q-mode applications 
- Anatomical location of touch-up applications 
- Temperature, power, contact force, impedance 
- Total Fluoroscopy time/dose 
 
14.5. Levels of Significance 
There are no formal hypothesis tests for this study. All confidence intervals will use two-sided 95% 
confidence unless otherwise stated. 
 
14.6. Analysis Sets 
 
The following analysis populations will be used to complete the analyses of data: 
 
- Safety Population: The safety population will include all enrolled subjects who have the 
investigational device inserted, regardless if RF energy is delivered. 
- Effectiveness Population: The effectiveness population will include all enrolled subjects who 
have had the investigational device inserted and underwent ablation with the study catheter 
used in conjunction with TGA mode for PVI. The subjects without any TGA mode application for 
PVI will be excluded from the effectiveness population.  
- Neurological Assessment Evaluable (NAE) Population: The NAE Population will include all 
enrolled subjects who meet the eligibility criteria, have been treated with the study catheter 
and had any post-ablation neurological assessment.  Assessment of incidence of new lesions or 
deficits requires availability of the associated pre-procedural assessment.  
 
 
14.7. Sample Size Justification 
This is a clinical feasibility study for evaluation of safety and acute performance of THERMOCOOL 
SMARTTOUCH® SF-5D system 
with TGA mode application for PVI. This clinical 
investigation 
is 
intended 
to provide preliminary estimates of workflow and acute outcomes.  Enrollment in the clinical 
investigation will be 50 subjects, distributed over up to 10 centers in Europe. Minimum attrition is 
expected for safety assessment.  No more than 10% attrition is expected to assess effectiveness 
outcomes.  
 
Because this study is a feasibility study, there is no statistical power calculation and no hypothesis to 
be tested.  50 subjects are deemed sufficient to clinically characterize safety and acute outcomes. 
 
 

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14.8. Analyses to be conducted  
 
  All data will be summarized by descriptive analyses. No formal statistical inference will be made. 
 
 
14.8.1. General Conventions 
 
Standard descriptive summaries for continuous data include the number of observations with 
data, mean, standard deviation, median, minimum, and maximum values. For categorical data, 
the count and percent will be provided. Percentages will be based on the number of subjects 
without missing data. 
 
14.8.2. Disposition of Study Subjects 
 
Subject disposition will be summarized for all 
enrolled 
subjects by summary tables and listings. 
 
14.8.3. Demographic and Baseline Characteristics  
 
All demographic 
and baseline characteristics, procedural, and immediate post-operative details will 
be summarized and listed overall in the safety population. 
 
14.8.4. Primary and Secondary Endpoint Analyses 
 
14.8.4.1. Analyses of Primary Safety Endpoint 
 
• Primary Safety Endpoint: Primary safety outcome will be reported as primary adverse events 
(within 7 days of catheter ablation, with exception for PV stenosis and AEF). The number of 
events and the number and percentage of subjects experiencing primary adverse events will be 
reported. The Primary Safety analysis will be performed on the Safety Population. 
 
14.8.4.2. Analyses of Primary Effectiveness Endpoint 
 
• Acute Procedural Success: Acute success 
is defined as achieving confirmation of entrance block 
in all targeted PVs after adenosine and/ or isoproterenol challenge. The number and 
percentage of subjects who have reached acute success will be summarized. Primary 
Effectiveness analysis will be performed on the Effectiveness Population. 
 
14.8.4.3. Analyses of Secondary and Additional Endpoints 
 
No formal statistical hypotheses and inferential statistics will be formulated and performed for the 
secondary and additional endpoints. Details of analyses methods for secondary and additional 
endpoints will be provided in SAP. 
 
Secondary Safety analysis for SADEs and AEs will be performed on the Safety Population. The 
neurological assessment related endpoints will be analyzed in the NAE population.  Secondary 
Effectiveness (including Procedural Data) will be performed on the Effectiveness Population. 
 
 
14.8.5. Handling of Missing Data 
 
Missing data will be queried for reasons and handled on an individual basis. 

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14.8.6. Subgroup Analyses 
 
The results of the primary and secondary safety endpoints will be presented for the following 
subgroups: 
• Sub-analysis on subjects where only TGA-mode was used for the procedure 
• Sub-analysis on subjects where both TGA- and Q-mode were used for the procedure 
 
The results of the primary and secondary effectiveness endpoints will be presented for the following 
subgroups.  
• Sub-analysis on subjects where only TGA-mode was used for PVI  
• Sub-analysis on subjects where both TGA- and Q-mode were used for PVI  
 
 
15. Ethics and Protection of Human Subjects 
 
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 MDD 93/42/EC and the local government. The Sponsor will also maintain 
compliance with Good Clinical Practice (ICH version 4 du 1 May 1996), the European standard EN ISO 
14155:2011 (Clinical Investigation of Medical Devices for Human Subjects), 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 
investigational plan. Based on outcome of evaluation process, Biosense Webster will select 
qualified investigators, ship devices only to participating investigators, obtain a signed 
Investigator’s Agreement and provide the investigators with the information necessary to 
conduct the study. 
 
• Supplemental Applications  
As appropriate, Biosense Webster will submit changes in the clinical investigational plan to 
the investigators to obtain all applicable re-approvals. 

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• Maintaining Records  
Biosense Webster will maintain copies of correspondence, data, adverse device effects and 
other records related to the study. Biosense Webster will maintain records related to the 
signed Investigator Agreements. 
 
• Submitting Reports  
Biosense Webster will submit any required regulatory reports identified in this section of the 
regulation. This may include 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 
 
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 
maintain 
confidentiality 
of 
the 
medical 
records 
at 
all 
times. 
 
The ICF will be written in a native, non-technical, language that is understandable to the 
subject and is to be approved by the applicable EC prior to enrolling subjects. The subject or 
designee will be provided with ample time to read and understand the ICF and to consider 
participation in the study. Informed consent will be requested prior to enrollment and must 
be personally signed and dated by the subject, or subject’s legal representative, prior to 
performance of any study related activity or procedure. If a subject is unable to read or write, 
informed consent shall be obtained through the aid of an independent witness who will be 
present 
throughout 
the 
process. 
The 
written 
ICF 
and 
any 
other 
information 
shall 
be 
read 
aloud 
and explained to the prospective subject and, whenever possible, subject shall sign and date 
the ICF. The witness must also sign and date the ICF attesting that the information was 
accurately explained and that informed consent was freely given. The point of enrollment 
corresponds with the time that 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 
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satisfaction of the patient or the representative. Failure to provide written informed consent 
renders the subject ineligible for the study. If new information becomes available that can 
significantly affect a subject’s future health and/or medical care, this information shall be 
provided to the subject(s) affected in written form. If relevant, all affected subjects shall be 
asked to confirm their continuing informed consent in writing by dating and signing the 
amended ICF. 
 
 
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. 
 
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 
European Union but Sponsor will take all reasonable steps to ensure a sufficient level of data 
protection. All data used in the analysis and reporting of this evaluation will exclude identifiable 
reference to the subject. 
 
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, 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. 

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• 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. 
 
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 investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
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 

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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 
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 EC). If the study is prematurely terminated or suspended, the PI will promptly inform the 
EC and will provide the reason(s) for the termination or suspension.  
 
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 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  
 

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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, investigational medical device, sponsor operations, patent 
application, manufacturing processes, and basic scientific data supplied by the sponsor to the 
investigator and not previously published, are considered confidential and remain the sole property of 
the sponsor. 
 
 
21. Document Filing 
 
A copy of all approved versions of the Investigation Protocol will be kept, by the site, in the Investigator 
Site File and in the Sponsor Trial Master File. 
 
 
 
 

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23. Scientific References 
 
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45. Ejima K,  Arai K, Suzuki T, et al. (2014) Long-term outcome and preprocedural predictors of 
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