Evaluation of QDOT MICRO™ Catheter for Pulmonary Vein Isolation (PVI) in Subjects With PAF
Phase: NA
Conditions: Paroxysmal Atrial Fibrillation
Sponsor: Biosense Webster, Inc.

Q-fficiency 
 
Version 5.0 
Protocol# BWI_2017_07 
 
February 3, 2021 
 
Biosense Webster, Inc 
 
 
CONFIDENTIAL 
 
 
 
Evaluation of QDOT MICRO™ catheter 
for pulmonary vein isolation (PVI) in 
subjects with Paroxysmal Atrial 
Fibrillation (PAF)  
(Q-fficiency) IDE #G180176 
 
Clinical Study Protocol 
 
Protocol# BWI_2017_07 
 
 
Version 5.0 
February 3, 2021 
 
 
 
 
Sponsor: 
 
BIOSENSE WEBSTER, INC. 
33 Technology Dr 
Irvine, CA 92618  
USA

Q-fficiency  
 
Protocol# BWI_2017_07
 
 
 
 
Biosense Webster, Inc 
 
Version 5.0 – Feb 3, 2021 
CONFIDENTIAL 
Page 2 of 135 
Table of Contents 
1.0 
List of Acronyms and Abbreviations ........................................................................ 8 
2.0 
Key Roles and Responsible Parties........................................................................... 9 
3.0 
Statement of Compliance ........................................................................................ 10 
4.0 
Protocol Summary .................................................................................................. 11 
5.0 
Schematic of Study Design ..................................................................................... 21 
6.0 
Background Information and Scientific Rationale ................................................. 23 
6.1 
Background .................................................................................................................... 23 
6.2 
Previous Experience with the QDOT MICRO™ Catheter and nMARQ RF Generator 24 
6.2.1 
QMODE Animal Testing ........................................................................................ 24 
6.2.2 
QMODE+ Mode with the QDOT MICRO™ Catheter Animal Testing ................. 26 
6.2.3 
QDOT MICRO GLP Study .................................................................................... 29 
6.2.4 
QDOT FIM Studies................................................................................................. 30 
6.3 
Rationale......................................................................................................................... 31 
6.3.1 
Ablation Parameters for the QDOT MICRO™ Catheter ....................................... 32 
6.4 
Potential Risk and Benefit .............................................................................................. 36 
6.4.1 
Description and Analysis of Risks .......................................................................... 36 
6.4.2 
Minimization of Risks............................................................................................. 39 
6.4.3 
Precautions .............................................................................................................. 40 
6.5 
Known Potential Benefits............................................................................................... 40 
7.0 
Study Objectives and Purpose ................................................................................ 41 
7.1 
Purpose ........................................................................................................................... 41 
7.2 
Objectives ....................................................................................................................... 41 
8.0 
Study Design and Endpoints ................................................................................... 42 
8.1 
Description of the Study Design .................................................................................... 42 
8.1.1 
Cardiac CT/MRA Subset ........................................................................................ 43 
8.2 
Study Endpoints ............................................................................................................. 43 
8.2.1 
Primary Safety Endpoint ......................................................................................... 43 
8.2.2 
Primary Effectiveness Endpoint ............................................................................. 44 
8.2.3 
Secondary Endpoints(s) .......................................................................................... 45 
9.0 
Study Population ..................................................................................................... 47 
9.1 
Subject Selection ............................................................................................................ 47 
9.1.1 
Inclusion Criteria .................................................................................................... 47 
9.1.2 
Exclusion Criteria ................................................................................................... 47 

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Version 5.0 – Feb 3, 2021 
CONFIDENTIAL 
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9.2 
Strategies for Recruitment and Retention ...................................................................... 48 
9.3 
Subject Withdrawal/Early Termination ......................................................................... 49 
9.4 
Subjects Lost to Follow up ............................................................................................. 50 
9.5 
Subject Disposition ........................................................................................................ 50 
10.0 
Responsibilities ....................................................................................................... 51 
10.1 
Study Timelines .......................................................................................................... 51 
10.2 
Investigator Responsibilities....................................................................................... 51 
10.3 
Sponsor Responsibilities............................................................................................. 52 
10.4 
Training ...................................................................................................................... 53 
10.4.1 
Research Team .................................................................................................... 53 
10.4.2 
Investigator Training ........................................................................................... 53 
11.0 
Study Device Description ....................................................................................... 53 
11.1 
Device Acquisition ..................................................................................................... 53 
11.2 
Device Storage and Stability ...................................................................................... 54 
11.3 
Instructions for Use (IFU) .......................................................................................... 54 
11.4 
Device Description ..................................................................................................... 54 
11.4.1 
QDOT MICRO™ Catheter ................................................................................. 54 
11.4.2 
nMARQ® Multi-channel RF Generator (D-1341-07-I) ..................................... 57 
11.4.3 
TX eco EXT Interface Cable (D-1357-03-SI) ..................................................... 58 
11.4.4 
TX eco Cable Dongle (EM-5050-055F) ............................................................. 59 
11.4.5 
CARTO® 3 v6.0.60 QDOT MICRO™ Software Module ................................. 60 
11.5 
Required Study Devices and Equipment .................................................................... 63 
11.6 
System Components and Set-Up ................................................................................ 64 
12.0 
Study medications ................................................................................................... 65 
12.1 
Antiarrhythmic Drugs ................................................................................................. 65 
12.1.1 
Definitions ........................................................................................................... 65 
12.2 
Study specific anticoagulation requirements .............................................................. 66 
13.0 
Study Schedule, Procedures, and Assessments....................................................... 67 
13.1 
Screening and Informed Consent ............................................................................... 67 
13.1.1 
Patient Screening ................................................................................................. 67 
13.1.2 
Informed Consent ................................................................................................ 67 
13.2 
Pre-Procedure/Baseline Assessments, Evaluations and Procedures ........................... 68 
13.3 
Study Ablation Procedure ........................................................................................... 69 
13.3.1 
QMODE+ Recommended Ablation Parameters ................................................. 71 

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Version 5.0 – Feb 3, 2021 
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13.3.2 
General AF Procedure Guidelines for QMODE+ ............................................... 72 
13.3.3 
Esophageal Monitoring ....................................................................................... 74 
13.3.4 
Ablation Outside the PV Ostia ............................................................................ 74 
13.3.5 
QMODE Ablation Parameters and Workflow .................................................... 75 
13.4 
Post Ablation .............................................................................................................. 76 
13.5 
Data collection During the Study Procedure .............................................................. 77 
13.5.1 
Collection of Ablation Procedure data for post-analysis .................................... 78 
13.6 
Repeat Procedures ...................................................................................................... 78 
13.7 
Post Procedure Follow-up Assessments ..................................................................... 78 
13.8 
Standard Tests and Procedures ................................................................................... 81 
13.9 
Unscheduled visit ....................................................................................................... 84 
13.10 
Heart Rhythm Monitoring .......................................................................................... 84 
13.11 
Repeat AF Ablation Procedures ................................................................................. 84 
13.12 
Core Laboratory .......................................................................................................... 85 
14.0 
Assessment of Safety .............................................................................................. 85 
14.1 
Adverse Event Recording ........................................................................................... 85 
14.2 
Classification .............................................................................................................. 86 
14.2.1 
Primary Adverse Event ....................................................................................... 86 
14.3 
Serious AEs ................................................................................................................ 90 
14.4 
Non-Serious AEs ........................................................................................................ 90 
14.5 
Anticipated AEs .......................................................................................................... 90 
14.6 
Unanticipated Serious Adverse Device Effect ........................................................... 94 
14.7 
Clinical Investigation Device Failure/Malfunction/Deficiency ................................. 94 
14.8 
Reporting Requirements ............................................................................................. 94 
14.9 
Intensity or Severity.................................................................................................... 95 
14.10 
Outcome...................................................................................................................... 96 
14.11 
Causality ..................................................................................................................... 96 
14.12 
Documentation............................................................................................................ 97 
14.13 
Safety Oversight ......................................................................................................... 97 
14.14 
Clinical Events Committee (CEC) ............................................................................. 97 
15.0 
Deviations from Protocol and Good Clinical Practice ............................................ 97 
16.0 
Device Accountability ............................................................................................ 98 
16.1 
Device Accountability ................................................................................................ 98 
16.2 
Device Returns ........................................................................................................... 98 

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17.0 
Monitoring the Study .............................................................................................. 99 
17.1 
Early Termination Monitoring Visit ......................................................................... 100 
18.0 
Statistical Analysis Methods ................................................................................. 100 
18.1 
Study Design............................................................................................................. 100 
18.2 
Treatment Assignment .............................................................................................. 100 
18.3 
Interval Windows ..................................................................................................... 100 
18.4 
Primary and Secondary Endpoint(s), and Associated Hypotheses ........................... 100 
18.4.1 
Study Success .................................................................................................... 100 
18.4.2 
Primary Endpoint(s) and Associated Hypotheses ............................................. 101 
18.4.3 
Secondary Endpoints and Associated Hypotheses ............................................ 101 
18.4.4 
Other Endpoints................................................................................................. 102 
18.5 
Levels of Significance .............................................................................................. 102 
18.6 
Analysis Set .............................................................................................................. 102 
18.7 
Sample Size Justification .......................................................................................... 102 
18.8 
Data Monitoring Committee ..................................................................................... 103 
18.9 
Analyses to be Conducted ........................................................................................ 104 
18.9.1 
General Conventions ......................................................................................... 104 
18.9.2 
Disposition of Study Subjects ........................................................................... 104 
18.9.3 
Demographic and Baseline Characteristics ....................................................... 104 
18.9.4 
Analysis of Primary Endpoint Analyses ........................................................... 104 
18.9.5 
Analyses of Secondary and Additional Endpoints ............................................ 105 
18.9.6 
Plans for Interim Analysis ................................................................................. 106 
18.9.7 
Handling of Missing Data ................................................................................. 106 
18.9.8 
Sensitivity Analyses .......................................................................................... 107 
18.9.9 
Subgroup Analyses ............................................................................................ 107 
18.9.10 
Assessment of Site Homogeneity ...................................................................... 107 
19.0 
Ethics and Protection of Human Subjects ............................................................. 108 
19.1 
Ethics Review ........................................................................................................... 108 
19.2 
Patient Informed Consent ......................................................................................... 108 
19.3 
Confidentiality .......................................................................................................... 108 
19.4 
Subject Confidentiality/Record ................................................................................ 108 
20.0 
Data Management ................................................................................................. 109 
20.1 
Electronic Case Report Forms (CRFs) ..................................................................... 109 
20.2 
Data Reporting .......................................................................................................... 109 

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Biosense Webster, Inc 
 
Version 5.0 – Feb 3, 2021 
CONFIDENTIAL 
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20.3 
Data Review ............................................................................................................. 110 
20.4 
Procedural Data ........................................................................................................ 110 
20.5 
Source Documentation ............................................................................................. 110 
21.0 
Quality Assurance and Quality Control ................................................................ 110 
22.0 
Administrative Responsibilities ............................................................................ 111 
22.1 
Records and Reports ................................................................................................. 111 
22.1.1 
Records .............................................................................................................. 111 
22.1.2 
Record Retention ............................................................................................... 111 
22.1.3 
Investigator’s Final Report ................................................................................ 112 
23.0 
Termination of the Study ...................................................................................... 112 
24.0 
Data and Publication Policy .................................................................................. 112 
25.0 
Document Filing ................................................................................................... 112 
26.0 
References: ............................................................................................................ 113 
27.0 
Appendix A: Study Definitions ............................................................................ 116 
28.0 
Appendix B: QMODE .......................................................................................... 120 
28.1 
Use of the QDOT MICRO™ QMODE algorithm ................................................... 120 
28.2 
Recommended ablation parameters .......................................................................... 121 
29.0 
Appendix C:  Justification of Safety Performance Goal ....................................... 124 
30.0 
Appendix D Adaptive Design Main Study ........................................................... 127 
30.1 
Introduction .............................................................................................................. 127 
30.1.1 
Endpoints ........................................................................................................... 127 
30.2 
Adaptive Design ....................................................................................................... 127 
30.2.1 
Primary Analysis ............................................................................................... 127 
30.2.2 
Interim Analyses for Early Success .................................................................. 128 
30.2.3 
Longitudinal Modeling for Effectiveness ......................................................... 129 
30.3 
Simulation Scenarios ................................................................................................ 129 
30.3.1 
Effectiveness Profiles ........................................................................................ 129 
30.3.2 
Adverse Event Rate Profiles ............................................................................. 130 
30.3.3 
Enrollment Rates ............................................................................................... 131 
30.3.4 
Attrition Rate Profile ......................................................................................... 131 
30.4 
Operating Characteristics ......................................................................................... 131 
30.4.1 
Type I Error Control .......................................................................................... 131 
30.4.2 
Probability of Success ....................................................................................... 132 
30.4.3 
Sensitivity to Enrollment Rate .......................................................................... 134 

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31.0 
APPENDIX E ADAPTIVE DESIGN SECOND (VARIABL FLOW) STUDY
 
Error! Bookmark not defined. 
31.1 
Introduction ................................................................. Error! Bookmark not defined. 
31.1.1 
Endpoints .............................................................. Error! Bookmark not defined. 
31.2 
Adaptive Design .......................................................... Error! Bookmark not defined. 
31.2.1 
Safety and Effectiveness Analysis for the Second (Variable Flow) Study .. Error! 
Bookmark not defined. 
31.2.2 
Interim Analyses for Early Success ..................... Error! Bookmark not defined. 
31.2.3 
Modeling for Effectiveness .................................. Error! Bookmark not defined. 
31.3 
Simulation Scenarios ................................................... Error! Bookmark not defined. 
31.3.1 
The Effectiveness Endpoint ................................. Error! Bookmark not defined. 
31.3.2 
The Safety Endpoint ............................................. Error! Bookmark not defined. 
31.3.3 
Enrollment Rates .................................................. Error! Bookmark not defined. 
31.3.4 
Attrition Rate Profile ............................................ Error! Bookmark not defined. 
31.4 
Operating Characteristics for the Second (Variable Flow) Study .... Error! Bookmark 
not defined. 
31.4.1 
Type I Error Control ............................................. Error! Bookmark not defined. 
31.4.2 
Power .................................................................... Error! Bookmark not defined. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Q-fficiency  
 
Protocol# BWI_2017_07
 
 
 
 
Biosense Webster, Inc 
 
Version 5.0 – Feb 3, 2021 
CONFIDENTIAL 
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1.0 LIST OF ACRONYMS AND ABBREVIATIONS 
AAD 
Antiarrhythmic drug 
ICF 
Informed consent form 
ACC 
American College of Cardiology 
 
 
ACT 
Activated clotting time 
IEC 
Independent Ethics Committee  
AE 
Adverse event 
IFU 
Instructions for use 
AF 
Atrial fibrillation 
IRB 
Institutional Review Board 
 
 
ITT 
Intent-to-treat 
HIPAA 
Health Insurance Portability and 
Accountability Act 
AFL 
Atrial flutter 
AHA 
American Heart Association 
LA 
Left atrium 
ANOVA 
Analysis of variance 
MI 
Myocardial infarction 
AT 
Atrial tachycardia 
MRI 
Magnetic resonance imaging 
AV 
Atrioventricular 
MV 
Mitral valve 
BP 
Blood pressure 
 
 
CEC 
Clinical Events Committee 
PAF 
Paroxysmal atrial fibrillation 
CHF 
Congestive heart failure 
PCI 
Pecutaneous coronary intervention 
CF 
Contact force 
PIU 
Patient Interface Unit 
PP 
Per protocol 
CFAE 
Complex fractionated atrial electrogram 
PV 
Pulmonary vein 
CHADS 
Congestive heart failure, High blood 
pressure, Age 75+, Diabetes, previous Stroke 
or transient ischemic attack 
PVI 
Pulmonary vein isolation 
 
QOL 
 
Quality of life 
CPVI 
Complete pulmonary vein isolation 
CRF 
Case Report Form 
RA 
Right atrium 
CS 
Coronary sinus 
REB 
Review Ethics Board 
CT 
Computed tomography 
RF 
Radiofrequency 
CTI 
Cavotricuspid isthmus 
SADE 
Serious adverse device effect 
CVA 
Cerebrovascular accident 
SAE 
Serious adverse event 
ECAS 
European Cardiac Arrhythmia Society 
 
 
EPU 
External processing unit 
SAP 
Statistical analysis plan 
ESC 
European Society of Cardiology 
SF 
Surround Flow 
FDA 
Food Drug Administration 
SVC 
Superior vena cava 
GCP 
Good Clinical Practice 
TIA 
Transient ischemic attack 
ECG 
Electrocardiogram 
TEE 
Transesophageal echocardiogram 
EHRA 
European Heart Rhythm Association 
TTE 
Transthoracic echocardiogram 
HRS 
Heart Rhythm Society 
TTM 
Transtelephonic monitoring 
ICD 
Implantable cardioverter defibrillator 
UADE 
Unanticipated adverse device effect 
ICE 
Intracardiac echocardiography 
USADE 
Unanticipated serious adverse device effect 
 
 
VT 
Ventricular tachycardia  

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Protocol# BWI_2017_07
 
 
 
 
Biosense Webster, Inc 
 
Version 5.0 – Feb 3, 2021 
CONFIDENTIAL 
Page 9 of 135 
2.0 KEY ROLES AND RESPONSIBLE PARTIES 
SPONSOR:  
Biosense Webster, Inc.  
part of the Johnson & Johnson family of companies  
33 Technology Drive,  
Irvine, CA 92618  
USA  
 
 
CONTACTS:  
Clinical Research Manager   
  
33 Technology Drive,  
Irvine, CA 92618  
USA  
  
  
 
Franchise Medical Manager  
  
33 Technology Drive,  
Irvine, CA 92618  
USA  
   
  
 
 
CRO(S) AND CORE LAB(S):  
The sponsor maintains a list of CRO(s) and Core Lab(s) and their contact information.  
 
INVESTIGATORS:  
The sponsor maintains a list of study Investigators and their contact information. 
 
 
 
 
 
 
 

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Protocol# BWI_2017_07
 
 
 
 
Biosense Webster, Inc 
 
Version 5.0 – Feb 3, 2021 
CONFIDENTIAL 
Page 10 of 135 
3.0 STATEMENT OF COMPLIANCE 
Study Title: 
Evaluation of the QDOT MICRO™ Catheter for pulmonary vein isolation (PVI) 
in subjects with Paroxysmal Atrial Fibrillation (PAF) (Q-fficiency) 
Study #: 
BWI_2017_07 
Protocol Type 
Revision Rationale 
Effective Date 
Original 
#1 
Original submission 
July 17, 2018 
Amendment 
#2 
Changes made in response to the FDA deficiency letter 
September 29, 2018 
Amendment 
#3 
Changes made in response to the conditional approval 
from FDA 
November 19, 2018 
Amendment 
#4 
Inclusion of the second study in the clinical study 
September 10, 2019 
Amendment  
#5 
Administrative and COVID-19 study assessment 
updates  
February 3, 2021 
 
I have read this protocol and agree to conduct this clinical investigation in accordance with the 
design and specific provisions outlined herein. I understand the protocol, and I understand I am 
solely responsible to ensure the investigation is conducted in accordance with Good Clinical 
Practices (GCP), applicable country regulations the Declaration of Helsinki, the signed clinical 
study contract with Sponsor and with the protocol outlined herein. I will conduct this study as 
outlined therein and will make reasonable effort to complete the study within the time period 
designated by the Sponsor.    
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who will assist in the conduct of this study. I will discuss this material with them to ensure they 
are fully informed regarding the device and the conduct of the study.  
I will fulfill the requirements of my Institutional Review Board (IRB)/Ethics Committee (EC), or 
other oversight committee, to ensure complete and continual oversight of this clinical 
investigation. I will use an Informed Consent Document approved by the Sponsor and my 
reviewing IRB/EC (where required).  
I agree to report all information or data in accordance with the protocol and, in particular, I agree 
to report any serious adverse events, device related adverse events, or procedure related adverse 
events as defined in this protocol to the Sponsor, and comply with all adverse event reporting 
requirements of my reviewing IRB/EC.  I agree to permit the Sponsor, its authorized 
representatives, my reviewing IRB/EC, and any regulatory authority/body access to all records 
relating to the clinical investigation. 
The below signature confirms I have read and understood this protocol and its associated 
amendments or attachments and will accept respective revisions or amendments provided by the 
Sponsor. 
 
____________________________   _____________________________  _______________ 
 Principal Investigator  
   
Signature 
 
 
   
Date 
 Name (PRINT) 

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Protocol# BWI_2017_07
 
 
 
 
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Version 5.0 – Feb 3, 2021 
CONFIDENTIAL 
Page 11 of 135 
4.0 PROTOCOL SUMMARY 
Evaluation of QDOT MICRO™ Catheter for pulmonary vein isolation (PVI) in subjects 
with PAF (QDOT IDE# G180176) 
 
 
Full Title & Protocol Number 
Evaluation of QDOT MICRO™ Catheter for pulmonary vein isolation 
(PVI) in subjects with PAF 
Protocol #: BWI_2017_07 
Short Title 
Q-fficiency 
IDE/IND number  
  G180176 
Sponsor 
CSS/BWI 
Indication 
Atrial Fibrillation 
Study Article Description 
• QDOT MICRO™ Catheter (D-1394-XX-SI and D-1395-XX-SI) 
o Interface Cable (D-1357-03-SI) 
o Dongle (EM-5050-055F) 
• nMARQ Multi-Channel RF Generator v3.0.1 (D-1341-07I) 
o 
v3.0.1 – Main Study 
o 
v3.0.6 – Second (Variable Flow) Study 
• CARTO® 3 v6.0.60 QDOT MICRO™ Software Module 
Study Design 
Prospective, non-randomized, pre-market clinical evaluation of the QDOT 
MICRO™ Catheter to demonstrate the safety and effectiveness when 
compared to an historical control performance goal.  
The trial will have 2 studies:  
• 
The Main study includes subjects treated with nMARQ RF generator 
with constant flow rate (8mL/min) for QMODE+ RF applications.  
• 
The Second (variable flow) study will include subjects treated with 
the nMARQ RF generator with variable flow rate for QMODE+ RF 
applications.   
QMODE RF applications will use the same flow rates for both studies. 
To assess PV stenosis, embedded within the Study will be a Cardiac 
Computed Tomography (CT) or Magnetic Resonance Angiogram (MRA) 
image (CT/MRA) subset with consecutive enrollment (n=40).  
The Main study will enroll 185 subjects who are candidates for catheter 
ablation. Bayesian adaptive design will be used to assess early success at 
one interim analysis. The study will be considered successful if primary 
endpoints are met for Main study.  
A second (variable flow) study of subjects will enroll 92 subjects who are 
candidates for catheter ablation. Enrollment for the second study will begin 
after enrollment for the Main study is complete. The second study will use 
the same eligibility criteria and the same sites as the Main study. The 
success of the second (variable flow) study will be based on same endpoints 
and hypotheses formulated for the main study. 
 

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Biosense Webster, Inc 
 
Version 5.0 – Feb 3, 2021 
CONFIDENTIAL 
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Sample Size 
N = 277 subjects at up to 30 US sites with 185 subjects in the Main study 
of the study and 92 in the second study.  
Study Population 
Subjects undergoing electrophysiology mapping and RF ablation for 
treatment of Antiarrhythmic Drug (AAD) Refractory symptomatic 
paroxysmal AF with the QDOT MICRO™ catheter. 
Geographic areas to be included 
Geographic involvement will include the US  
Study Duration 
~18-20 months (including 6-8 months enrollment and 12 months follow up 
from LPI) for the Main study 
~ 18 months (including 6 months enrollment and 12 months follow up from 
LPI for Second (variable flow) study.  
Start Date:  4Q18 
End Date:4Q21 
Procedure(s) Description 
In this study protocol, QMODE+ (90W 4 sec) is the primary temperature 
control mode for pulmonary vein isolation. If the investigator deems 
QMODE+ unable to achieve PVI, the study catheter in QMODE 
temperature control mode (25-50W) should be used to complete the PVI 
procedure.  
In addition, QMODE+ and QMODE (25-50W) are to be used to treat non-
PV triggers, Linear ablation lines and the right atrial CTI line when atrial 
tachycardias are documented during the procedure or by medical history.  
 
QDOT MICRO™ Catheter Parameter Tables:  
 
For the Main study:  
 
Table A: RF and Flow Settings during RF applications 
Power 
Target Temp* 
Cut-off Temp 
Nominal 
Irrigation 
Flow rate 
Range 
Maximum 
allowed 
Range 
Maximum 
allowed 
25-35 W 
40-50ºC 
50ºC 
50-55ºC 
55ºC 
4mL** 
36-
50W*** 
40-50ºC 
50ºC 
50-55ºC 
55ºC 
15mL** 
90W† 
40-60ºC 
60ºC 
60-70ºC 
70ºC 
8mL** 
* Temperatures displayed on the RF generator do not represent tissue temperature 
or electrode tissue interface temperature. 
**A minimum flow rate of 2mL during mapping is recommended. 
*** RF applications at 36-50W should not exceed 60 sec. 
† The study recommends using this power setting for PVI as a primary ablation 
Strategy.  RF applications at this power setting are limited up to 4 sec. It is 
recommended to use lower target temp setting for the posterior wall RF 
applications. 
 
For the Second (variable flow) study:  
 
Table B: RF and Flow Settings during RF applications 
Power 
Target Temp* 
Cut-off Temp 
Nominal 
Irrigation 
Flow rate 
Range 
Maximum 
allowed 
Range 
Maximum 
allowed 
25-35 W 
40-50ºC 
50ºC 
50-55ºC 
55ºC 
4mL** 
36-
50W*** 
40-50ºC 
50ºC 
50-55ºC 
55ºC 
15mL** 
90W† 
40-60ºC 
60ºC 
60-70ºC 
70ºC 
4- 15 ml 
** 

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Protocol# BWI_2017_07
 
 
 
 
Biosense Webster, Inc 
 
Version 5.0 – Feb 3, 2021 
CONFIDENTIAL 
Page 13 of 135 
* Temperatures displayed on the RF generator do not represent tissue temperature 
or electrode tissue interface temperature. 
**A minimum flow rate of 2mL during mapping is recommended. 
*** RF applications at 36-50W should not exceed 60 sec. 
† The study recommends using this power setting for PVI as a primary ablation 
Strategy.  RF applications at this power setting are limited up to 4 sec. It is 
recommended to use lower target temp setting for the posterior wall RF 
applications. 
 
QDOT MICRO™ Ablation: 
The QDOT MICRO™ Catheter utilizes a temperature-controlled ablation 
(QMODE) designed to maximize RF lesion efficiency by using temperature 
feedback measured at the tip to adjust power and irrigation flow.  The 
QMODE temperature control mode monitors the temperature rate of change 
in relationship to the set target temperature during RF application.  To 
maintain desired power levels at a safe temperature, the QMODE 
temperature control mode utilizes changes in the irrigation flow rate as a 
first-order approach to maintain temperature. If the change in irrigation 
flow rate is not sufficient, the RF energy is also titrated to maintain 
temperature. 
Irrigation Titration for the main study: 
• For power settings, 35W or lower: The flow rate starts at low flow 
(4ml, lowest setting).  If the temperature approaches or exceeds the set 
target temperature (50°C), the generator changes the pump flow rate 
from low (4mL) to high flow (15 mL) to maintain the set maximum 
power at its setting.  Once the temperature decreases the pump 
irrigation flow rate is returned to low (4mL). 
• For power settings, greater than 35W: The flow rate starts at high flow 
(15ml). If the target temperature is not reached, the generator changes 
the pump from high (15 mL) to low (4mL) flow. Once the temperature 
increases the pump irrigation flow rate is returned to high (15mL).  
• For power settings up to 90W: The flow rate starts at moderate flow 
(8mL) and is maintained throughout the ablation.  The duration of the 
ablation is limited to 4 seconds at this power setting.  
• At any set power (1-90W), as the tip temperature approaches the 
selected target temperature (i.e. 50°C) the power level will also titrate 
down to not exceed the target temperature.  If the cut-off temperature 
is reached, the generator will stop the ablation. 
 
Irrigation Titration for the second (variable flow) study: 
• For power settings, 35W or lower: The flow rate starts at low flow 
(4ml, lowest setting).  If the temperature approaches or exceeds the set 
target temperature (50°C), the generator changes the pump flow rate 
from low (4mL) to high flow (15 mL) to maintain the set maximum 
power at its setting.  Once the temperature decreases the pump 
irrigation flow rate is returned to low (4mL). 
• For power settings, greater than 35W: The flow rate starts at high flow 
(15ml). If the target temperature is not reached, the generator changes 
the pump from high (15 mL) to low (4mL) flow. Once the temperature 
increases the pump irrigation flow rate is returned to high (15mL).  
• For power settings up to 90W: The flow rate starts at moderate flow 
(4mL) and is maintained throughout the ablation.  The duration of the 
ablation is limited to 4 seconds at this power setting.  
• At any set power (1-90W), as the tip temperature approaches the 
selected target temperature (i.e. 50°C) the power level will also titrate 

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down to not exceed the target temperature.  If the cut-off temperature 
is reached, the generator will stop the ablation 
Recommendation for CoolFlow® Irrigation Pump Setting and RF Power-
delivery 
• The CoolFlow® Irrigation Pump will deliver a continuous infusion of 
2 ml/min of room temperature heparinized saline (1 u heparin/1 ml 
saline) during mapping.  
• The nominal irrigation setting will start up to 2 seconds before the 
onset of RF energy delivery  
 
QDOT MICRO™ Contact Force (CF) Settings: 
 
When using the study catheter in both QMODE and QMODE+, operators 
should Target: 
• Target CF: 10g 
• CF Range:   5-30g  
 
Post procedure: 
20 minutes waiting period is required followed by adenosine/isoproterenol 
challenge 
 
Primary Objective 
The primary objective of this clinical investigation is to demonstrate the 
safety and 12-month effectiveness of the QDOT MICRO™ catheter for 
pulmonary vein isolation (PVI) in the treatment of subjects with paroxysmal 
atrial fibrillation.  
Specifically: 
• To demonstrate the safety based on the proportion of subjects with 
early-onset (within 7 days of ablation procedure) primary adverse 
events  
• To demonstrate the 12-month effectiveness based on the proportion of 
subject with freedom from documented left atrial arrhythmia (atrial 
fibrillation (AF), atrial tachycardia (AT) or atrial flutter (AFL)) 
episodes during the effectiveness evaluation period (Day 91-365)  
Secondary Objectives 
The major secondary objectives of this study are:  
Safety: 
• to evaluate the incidence of serious adverse events during and after 
procedure up to 3 months following procedure.  
Acute Effectiveness: 
• Acute Procedural Success as defined by:  
o The % of subjects with electrical isolation of PVs (entrance 
block) at the end of the procedure, and  
 The % of subjects with electrical isolation of PVs (entrance 
block) using QMODE+ as only ablation strategy 
 The % of subjects with electrical isolation of PVs (entrance 
block) at all power settings combined 
o The % of subjects with electrical isolation of PVs (entrance 
block) after waiting period and adenosine challenge   
 
Exploratory Objectives 
N/A 
Primary Endpoints & Follow-up 
Intervals 
Acute Safety:  
• Incidence of early onset primary adverse events (PAE) related to the 
device or procedure. Occurrence of Primary AEs within 7 days of an 

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ablation procedure. (refer to Appendix A for a comprehensive 
definition list of primary adverse events) 
12-Month Chronic Effectiveness: 
• Freedom from documented (Symptomatic and asymptomatic) atrial 
arrhythmia (atrial fibrillation (AF), atrial tachycardia (AT) or atrial 
flutter (AFL)) episodes during the effectiveness evaluation period 
(Day 91-365) 
 
Effectiveness Monitoring:  
Effectiveness monitoring will include event Monitoring (TTM). Each 
subject will be provided an event monitor (Transtelephonic monitor, TTM) 
no later than at the 3-month visit, episodes ≥ 30 secs on TTM or 
continuously recorded on the standard 12-leads ECG will be considered 
recurrence. Subjects will be expected to transmit asymptomatic recordings 
once every week starting no later than the month 3 visit until the month 6 
visit.  Starting from month 6, subjects will record and transmit once every 
month until the end of the 12-month follow-up period.   All symptomatic 
cardiac episodes should be recorded and transmitted soon after the event 
occurs during the Evaluation Period (Day 91-365). 
Secondary Endpoints & Follow-
up Intervals 
Secondary Safety Endpoints:  
• 
Incidence of Unanticipated Adverse Device Effects (UADEs) 
• 
Incidence of Serious Adverse Events (SAEs) within 7 days (early 
onset), >7 to 30 days (peri-procedural) and >30 days (late onset) of 
initial ablation 
• 
Incidence of bleeding complication: a) Major, b) clinically relevant 
non-major and c) minor bleeding as defined in the 2017 
HRS/EHRA/ECAS/APHRS /SOLAECE Consensus Statement 
Secondary Effectiveness Endpoints:  
• Acute Procedural success:  
o % of subjects with electrical isolation of all PVs (entrance block) at 
the end of the procedure  
 
The % of subjects with electrical isolation of PVs (entrance 
block) using QMODE+ as only ablation strategy 
o % of subjects with electrical isolation of all PVs (entrance block) 
after first encirclement (evaluated prior to the 20-minute waiting 
period and adenosine challenge)  
o % of subjects with electrical isolation of all PVs (entrance block) 
after first encirclement without acute reconnection, after waiting 
period and adenosine challenge   
o % of subjects and % of PVs with touch-up (ablation of acute 
reconnection) among all targeted veins and touch-up location  
o Anatomical location of acute PV reconnection after first 
encirclement 
• Repeat Ablation Procedures:  
o Incidence (%) of repeat ablation procedures during 12-months 
period post-procedure   
o % PVs re-isolated among all of the targeted PVs at repeat procedure  
o % repeat ablation procedures requiring new linear lesions and/or 
identifying new foci outside of initially isolated area among the 

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repeat ablation procedures 
• 12-Month Single Procedure Success 
o The 12-month single procedure success is defined as freedom from 
documented AF/AFL/AT recurrence (episodes > 30 secs) during 
the Evaluation Period after a single ablation procedure and off 
AADs. Any repeat ablation procedure or AAD therapy will be 
deemed effectiveness failure for this analysis 
Additional Endpoints: 
• 
Procedural data 
o 
total procedure time, PVI time, RF application time, mapping time, 
and RF application time per lesion 
o 
fluoroscopy time/dose 
o 
location of RF applications, number of RF applications 
o 
RF ablation parameters per application  
o 
Total fluid/irrigation delivered 
o 
Esophageal monitoring 
o 
VISITAG™ parameters will be collected in the CARTO® 3 system 
during the ablation procedures for generation of LA ablation maps 
o 
VISITAG SURPOINT™ values (Tag Index) per RF application  
• 
Quality of Life (QOL) status (AFEQT scores) 
• 
Cardiac CT/MRA Subset for PV Stenosis Assessment 
• 
HEMA  
o 
Incidence of hospitalizations post-index ablation procedure 
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for 
participation in this study:  
1. Symptomatic paroxysmal AF with one electrocardiographically 
documented AF episode within 6 months prior to enrollment ,a 
physician’s note indicating recurrent self-terminating AF within 7 
days. Documentation may include electrocardiogram (ECG); 
Transtelephonic monitoring (TTM), Holter monitor or telemetry 
strip.  
2. Failed at least one (1) antiarrhythmic drug (AAD) (class I or III) as 
evidenced by recurrent symptomatic AF, contraindicated or 
intolerable to the AAD.  
3. Age 18 years or older. 
4. Signed Patient Informed Consent Form (ICF). 
5. Able and willing to comply with all pre-, post-, and follow-up testing 
and requirements. 
Exclusion Criteria 
Subjects who meet any of the following exclusion criteria are not eligible 
for enrollment. 
1. Previous surgical or catheter ablation for atrial fibrillation.  
2. AF secondary to electrolyte imbalance, thyroid disease, or reversible 
or non-cardiac cause. 
3. Patient on amiodarone at any time during the past 3 months prior to 
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4. Previously diagnosed with persistent or long-standing persistent AF 
and/or Continuous AF lasting > 7 days 
5. CABG surgery within the past 6 months (180 days). 
6. Valvular 
cardiac 
surgical/percutaneous 
procedure 
(i.e., 
ventriculotomy, atriotomy, and valve repair or replacement and 
presence of a prosthetic valve). 
7. Any carotid stenting or endarterectomy within the last 6 months. 
8. Documented LA thrombus on imaging (within 48 hr prior of a study 
ablation procedure). 
9. Documented LA size > 50 mm (parasternal long axis view). 
10. Documented LVEF < 40%. 
11. Contraindication to anticoagulation (e.g. heparin) 
12. History of blood clotting or bleeding abnormalities 
13. MI/PCI within the past 2 months (60 days) 
14. Documented thromboembolic event (including TIA) within the past 
12 months (365 days) 
15. Rheumatic Heart Disease 
16. Uncontrolled heart failure or NYHA function class III or IV 
17. Severe mitral regurgitation (Regurgitant volume ≥ 60 mL/beat, 
Regurgitant fraction ≥ 50%, and/or Effective regurgitant orifice area 
≥ 0.40cm2) 
18. Awaiting cardiac transplantation or other major cardiac surgery 
within the next 12 months (365 days) 
19. Unstable angina 
20. active systemic infection or sepsis 
21. Diagnosed atrial myxoma or presence of an interatrial baffle or patch. 
22. Presence of implanted ICD/CRT-D. 
23. 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. 
24. Severe Gastroesophageal Reflux Disease (GERD; active requiring 
significant intervention not including OTC medication) 
25. Significant congenital anomaly or medical problem that in the 
opinion of the investigator would preclude enrollment in this study. 
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 study 
27. Enrollment in an investigational study evaluating another device, 
biologic, or drug. 
28. Presence of intramural thrombus, tumor or other abnormality that 
precludes vascular access, or manipulation of the catheter.  

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29. Presence of an inferior vena cava filter. 
30. Presenting contra-indication for the devices (e.g. TTE, CT, etc.) used 
in the study, as indicated in the respective instructions for use. 
31. Life expectancy less than 12 months 
Statistical Analysis  
For the Main study: 
Primary Safety Endpoint 
Sample Size and Power Calculations 
• 
Based on a performance goal of 14%, an anticipated rate of 7% for 
the primary safety endpoint, approximately 185 evaluable subjects 
will provide at least 80% power to declare success for the primary 
safety endpoint in the main study controlling one-sided alpha of 
2.5%, assuming a 5% attrition rate.  
Primary Effectiveness Endpoint 
Sample Size and Power Calculations 
• 
Based on a performance goal of 50%, and anticipated freedom 
from AF/AT/AFL recurrence rate of 65%, approximately 185 
evaluable subjects will be required to obtain at least 80% power 
to declare success for primary effectiveness endpoint in the main 
study controlling one-sided alpha of 2.5%, assuming a 12% 
attrition rate. 
The Final analyses for primary safety and effectiveness endpoints will apply 
Bayesian methods and use a beta-binomial model (assuming early success 
is not achieved for the primary effectiveness endpoint).  
 
For the Variable flow study: 
Primary Safety Endpoint 
Sample Size and Power Calculations 
• 
Based on a performance goal of 14%, an anticipated rate of 7% for 
the primary safety endpoint, with borrowing up to 91 subjects from  
the main study, the sample size of  92 subjects, will provide close to 
80% power for testing the primary safety endpoint controlling one-
sided alpha of 2.5%, assuming a 5% attrition rate in the variable flow 
study.  
Primary Effectiveness Endpoint 
Sample Size and Power Calculations 
• 
Based on a performance goal of 50%, and anticipated freedom 
from AF/AT/AFL recurrence rate of 65%, with borrowing  up to 
91 subjects  from the main study, the sample size of  92 subjects 
will be required to obtain at least 80% power to achieve success 
for primary effectiveness endpoint controlling one-sided alpha of 
2.5%, assuming a 12% attrition rate in the variable flow study. 
The analyses for primary safety and effectiveness endpoints will apply 
Bayesian methods and use a beta-binomial with data borrowing from the 
Main study using a propensity score-integrated power prior approach. 
Interim Analysis 
One early success claim interim analysis will be executed for main  study  
Determination if DMC/CEC 
required 
CEC will be convened to adjudicate the primary safety endpoint. Data 
Monitoring Committee (DMC) will be responsible for reviewing the study 
results. The same committees will be responsible for both studies. 

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Time and Events Schedule 
Subjects will be evaluated prior to the procedure, prior to discharge, and 
post procedure at 7 days (7-10 days), 1 month (23-37 days), 3 months (76-
104 days), 6 months (150-210 days), and 12 months (335-395 days) unless 
otherwise specified in the protocol. 
• Baseline 
o 
Demographics 
o 
Medical History 
 AAD Medication History 
 Arrhythmia History 
o 
Quality of Life Assessment  
 Quality of Life – Atrial Fibrillation Effect on Quality of life 
(AFEQT) 
o 
Device Interrogation (if applicable) 
o TTE or TEE evaluation 
• Ablation Procedure 
o 
Ablation procedure strategy outside of the pulmonary vein ostia 
will utilize QMODE +/ QMODE and Investigator’s Standard of 
Care 
 
Data Collection:  
o 
Catheter Information (Serial #, Lot #) 
o 
Dongle (Serial #) 
o 
RF Generator Information (Serial #) 
o 
Target sites for RF lesion application 
 
Target Sites 
 
Number of RF Applications per target 
 
total RF duration per application (sec) 
 
Fluoroscopy time/dose 
 
Esophageal temperature monitoring 
 
ICE usage, if used 
 
Procedure Times 
- 
Total procedure time 
- 
Total mapping time 
- 
Total RF time 
- 
Time to PVI 
 
Fluid delivered 
- 
From the Study Catheter 
- 
From IV (if applicable) 
o 
CARTO and modified RF Generator download for offline 
analysis   
 
Segmentation of LA ablation maps based on chosen CARTO 
tags 
 
Full Case backup [including complete VISITAG export] and 
CARTO Case recording 
 
RF Ablation parameters per application: Power, Impedance, 
Flow Rate, Temperature, and Time 
 
Contact force measurements and RF ablation parameters  
 
VISITAG SURPOINT™ value per application, if used 
 
Localized ECG Electrodes measurements for offline analysis 
o 
Acute Success (entrance and exit block PVI) 
o 
Adverse Events 
o 
Cardiac medications 
• Discharge 
o 
Recurrence of arrhythmia prior to discharge 
o 
Device Interrogation (if applicable) 

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o 
HEMA Billing information 
o 
Adverse Events 
• Follow-up Assessments Post Ablation* 
o 
7 Day phone Call 
o 
1-month  
o 
3-month 
o 
6-month 
o 
12-month  
Data to be collected during the study visits will include:  
• Adverse Events (since last visit) 
• Physical Exam 
• Medication update/changes 
• Quality of Life Assessment (at 3-, 6-, and 12-month visit) 
o 
Quality of Life – Atrial Fibrillation Effect on QualiTy of life 
(AFEQT)  
• Billing Information for all hospitalizations, ER visits and outpatient 
visits for economic analyses 
• ECG 
• Recurrence of Study Arrhythmia (each patient will be provided a TTM 
event monitor) 
• Repeat ablation procedures/subject during the follow-up period, repeat 
ablation procedure will be at the discretion of the investigator     
• Throughout the 12-month effectiveness follow-up period, arrhythmia 
status will be assessed by symptom-initiated event monitoring.   
 
Device Interrogation (if applicable) 
 
All symptomatic cardiac episodes will be documented   
*based on the initial ablation procedure 
QUALIFICATION AND 
ACTIVATION OF OPERATORS 
• Experience with Focal Catheters and AF ablation ≥100 cases 
• Operators – Investigator training is required for the Protocol and 
Investigational QDOT MICRO™ Catheter 
 

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5.0 SCHEMATIC OF STUDY DESIGN 
 
 
Study Enrollment (N=185) 
12-month post-ablation follow-up  
For all treated subjects 
Pre-Ablation: Obtain informed consent and then perform baseline 
assessments as described in the Section 14 of the Protocol. 
Procedure: Perform procedure as described in Section 14 of the Protocol. 
Pre-discharge: Perform Pre-discharge assessments as described in Section 14 
of the Protocol. 
7 Day Follow-up: Call subject 7 days (7-10 days) post procedure to assess 
adverse events as described in the Section 14 of the Protocol. 
1 Month Follow-up: Perform 1-month (23-37 days) post procedure 
assessments as described in Section 14 of the Protocol. 
3 Month Follow-up: Perform 3-month (76-104 days) post procedure 
assessments as described in Section 14 of the Protocol. 
6 Month Follow-up: Perform 6-month (150-210 days) post procedure 
assessments as described in Section 14 of the Protocol. 
12 Month Follow-up: Perform 12-month (335-395 days) post procedure 
assessments as described in Section 14 of the Protocol. 
  
NAE Subset  
(n  =40 )  
Cardiac CT/MRA Subset 
(n =40)
Study Enrollment (N=92) 
12-month post-ablation follow-up for all treated subjects 
Pre-Ablation: Obtain informed consent and then perform baseline 
assessments as described in the Section 14 of the Protocol. 
Procedure: Perform procedure as described in Section 14 of the 
Pre-discharge: Perform Pre-discharge assessments as described in 
Section 14 of the Protocol. 
7 Day Follow-up: Call subject 7 days (7-10 days) post procedure to 
assess adverse events as described in the Section 14 of the Protocol. 
1 Month Follow-up: Perform 1-month (23-37 days) post procedure 
assessments as described in Section 14 of the Protocol. 
3 Month Follow-up: Perform 3-month (76-104 days) post procedure 
assessments as described in Section 14 of the Protocol. 
6 Month Follow-up: Perform 6-month (150-210 days) post procedure 
assessments as described in Section 14 of the Protocol. 
12 Month Follow-up: Perform 12-month (335-395 days) post 
procedure assessments as described in Section 14 of the Protocol. 
Second Study 

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Evaluation of QDOT MICRO™ catheter for pulmonary vein isolation 
(PVI) in subjects with Paroxysmal Atrial Fibrillation (PAF) 
6.0 BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
6.1 Background 
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.  

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6.2 Previous Experience with the QDOT MICRO™ Catheter and nMARQ RF 
Generator 
6.2.1 
QMODE Animal Testing  
6.2.1.1 
QMODE with the QDOT MICRO™ Catheter Thigh Prep 
Animal testing was performed using the catheter and complete system per study 
protocol P-0022114 and test report TR-0022114, Verification of QDOT Micro-
Electrode Catheter with Q-mode Ablation Mode – Canine Thigh Preparation Test.  
Purpose: 
The purpose of this study was to evaluate the safety and performance of the QDOT 
MICRO™ electrode catheter using QMODE ablation mode (Test Catheter) when 
compared with STSF and ST catheters using power control mode (Control catheters) 
using a well-established canine thigh muscle model. 
Scope: 
The QDOT MICRO™ catheter is intended to be used clinically thus the primarily focus 
of this test was to assess the safety and performance of QDOT MICRO™ electrode 
catheter using QMODE ablation mode.  The following objectives were tested: 
• Char/coagulum and steam pop rate of QDOT MICRO™ catheter using QMODE 
ablation mode compared with STSF and ST catheters using power control mode.  
• Lesion dimensions (max depth, max diameter and surface diameter) comparison 
between test and control catheters.  
• Ablation parameters were collected for analysis for characterization purposes to 
understand the similarities and differences in their behavior when compared to 
control catheters: average power, maximum electrode temperature, Temperature 
Rise, Initial Impedance, Impedance Drop. 
Summary: 
The overall incidence of coagulum observed with the QDOT MICRO™ catheter in 
QMODE ablation mode was similar to STSF (Control Catheter) and significantly less 
compared to the ST (Control catheter). The overall incidence of Steam pops observed 
with the QDOT MICRO™ catheter in QMODE ablation mode was similar compared to 
the STSF and ST (Control catheters). The lesion characteristics were similar between 
the QDOT MICRO™ catheter and the control catheters. The overall performance of the 
QDOT MICRO™ catheter, in the QMODE ablation mode was similar or better 
compared to the control catheters (ST and STSF) in power control ablation mode. 
Conclusions: 
Based on the results of the canine thigh prep study, the overall safety and performance 
(Coagulum, Steam pops) of the QDOT MICRO™ catheter, when used in the QMODE 
ablation mode, is similar compared to the control catheters (STSF, ST) being used in 
power control mode. The maximum ablation parameters identified for the QDOT 

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MICRO™ catheter, in the QMODE ablation mode have been tested and assessed to be 
safe and effective based on the results of this canine thigh prep study. 
6.2.1.2 
QMODE with the QDOT MICRO™ Catheter In Vivo Animal Testing 
Animal testing was performed using the catheter and complete system per study 
protocol P-0023068 and test report TR-0023068, Evaluation of QDOT MICRO-
Electrode Catheter with Q-mode Ablation Mode - Beating Heart Animal Study. 
Purpose: 
The purpose of this acute study was to evaluate the safety and overall functional 
performance of the QDOT MICRO™ electrode catheter, in the QMODE ablation mode 
(nMARQ multichannel RF generator), when simulating a clinical pulmonary vein 
isolation (PVI) procedure. The overall safety and functional performance of the QDOT 
MICRO™ electrode catheter and QMODE ablation mode was compared to the control 
catheter (Smart Touch SF) being used in power control mode (Smart Ablate generator). 
Discussion: 
The QMODE Beating Heart study was conducted according to the study protocol design 
and its requirements.  
No char/coagulum observed on the test catheter (QDOT MICRO™). The overall 
incidence of steam pop observed with QDOT MICRO™ (0 in RA, 5/9 in the LV and 0 
in all other locations) was lower compared to the control STSF catheter (0 in RA, 3/36 
during PVI, 5/12 in LA wall, 5/6 in LV and 1/7 in RV). Of note, there were zero 
incidence of steam pop occurrence in both left and right atrial ablations using QDOT 
MICRO™ catheter with QMODE at the study settings.  
The QDOT MICRO™ ablation catheter used in conjunction with the QMODE ablation 
mode was able to: 
• Deliver RF energy at a target site  
• Demonstrate acute isolation of the pulmonary vein. 
• Demonstrate clinically acceptable signal quality which was comparable to control. 
• Pace from ring electrodes and microelectrodes during idle-state and during 
ablation. 
• Provide significantly better temperature feedback during ablation than control 
catheter. 
• Function effectively when used in conjunction with ancillary equipment like 
nMARQ multichannel RF generator, QDOT Dongle, CoolFlow pump and CARTO 
3 mapping system. 
The QDOT MICRO™ ablation catheter, when used with QMODE ablation mode, was 
able to produce effective electrogram signal attenuation and equivalent to (or better) 
lesions as compared to that with the STSF catheter in all four cardiac chambers. 

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The nMARQ generator was able to successfully modify the irrigation flow rate based 
on QDOT MICRO™ catheter electrode temperature response and power settings to 
maintain temperature limit when used in the QMODE ablation mode. 
Conclusions: 
The QDOT MICRO™ ablation catheter with QMODE ablation mode using the 
temperature target and flow rate settings as set forth by the protocol, meets all 
acceptance criteria as listed in protocol P-0023068.  
The overall functionality and the safety of the QDOT MICRO™ ablation catheter with 
QMODE ablation mode is equivalent to or better than that of the control STSF catheter. 
6.2.2 
QMODE+ Mode with the QDOT MICRO™ Catheter Animal Testing  
6.2.2.1 
QMODE+ Mode with the QDOT MICRO™ Catheter Thigh Prep 
Animal testing was performed using the catheter and complete system per study 
protocol P-0022211 and test report TR-0022211, Verification of QDOT Micro-
Electrode Catheter with QMODE+ Ablation Mode – Canine Thigh Preparation Tests. 
Purpose:  
The purpose of this study was to evaluate the safety and performance of the QDOT 
MICRO™ Catheter in QMODE+ (high power, short duration) ablation mode (90W/4s) 
using the nMARQ Multi-channel RF generator. The overall safety and performance of 
the QDOT MICRO™ catheter in the QMODE+ ablation mode was compared to the 
safety and performance of STSF catheter (Control catheter) in power control mode at 
two different settings (50W/10s or 30W/30s) using the Smart Ablate RF generator, 
using a well-established canine thigh muscle model. 
Scope:  
The QDOT MICRO™ catheter is intended to be used clinically thus the primarily focus 
of this test was to assess the safety and performance of QDOT MICRO™ electrode 
catheter using QMODE+ ablation mode.  The following objectives were tested: 
• Safety of QDOT MICRO™ catheter using QMODE+ ablation mode 
(char/coagulum and steam pop) compared with STSF catheter using power control 
mode.  
• Lesion dimensions (max depth, max diameter and surface diameter) comparison 
between test and control catheters.  
• The following ablation parameters were collected for analysis for characterization 
purposes only (no acceptance criteria) in order to understand the similarities and 
differences in their behavior when compared to control catheter: average power, 
maximum electrode temperature, Temperature Rise, Initial Impedance, Impedance 
Drop. 
Summary: 
There was no significant difference in the overall incidence of coagulum observed with 
the QDOT MICRO™ catheter in QMODE+ ablation mode compared to the STSF 

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(Control Catheter) in power control mode, when tested in both perpendicular and 
parallel orientations. A small Grade 1 (Grade 1: ≤1mm3) was observed with the Qdot 
catheter at 90W/4s with perpendicular orientation at 30g. Whereas one Grade 1(Grade 
1: ≤1mm3) observed with STSF catheter at 50W/10s with parallel orientation at 10g 
and one Grade 2 (Grade 2:>1mm3) was observed at 30W/30s with parallel orientation 
at 30g.  
No Steam pop was observed with the QDOT MICRO™ catheter in QMODE+ ablation 
mode in Perpendicular as well as Parallel orientation at 10g and 30g. One steam pop 
was observed with STSF catheter (Control Catheter) at 50W/10s with perpendicular 
orientation at 30g and two steam pops were observed at 30W/30s with parallel 
orientation at 30g.  
The lesion depth was significantly smaller with the QDOT MICRO™ in QMODE+ 
ablation mode than the STSF catheter in Power control mode for both perpendicular and 
parallel with 10g and 30g. The lesion diameter was greatest with the STSF catheter in 
power control mode for 30W/30s for both perpendicular and parallel orientation at 10g 
and 30g. However, lesion diameter of QDOT MICRO™ catheter in QMODE+ ablation 
mode (90W/4s) and STSF (50W/10s) in power control mode was similar. The overall 
safety of the QDOT MICRO™ catheter, in the QMODE+ ablation mode was similar or 
better compared to the control catheter (STSF) in power control ablation mode. 
Conclusion: 
Based on the results of the canine thigh prep study, the maximum ablation parameters 
identified for the QDOT MICRO™ catheter, in the QMODE+ ablation mode have been 
tested and assessed to be safe and effective. 
6.2.2.2 
QMODE+ Mode with the QDOT MICRO™ Catheter In Vivo Animal 
Testing 
Animal testing was performed using the catheter and complete system per study 
protocol P-0022212 and test report TR-0022212, Acute Canine Beating Heart Study for 
Validation of QMODE+ with QDOT MICRO™ Catheter. 
Purpose: 
The purpose of this study was to verify safety and effectiveness of the QDOT MICRO™ 
catheter using the QMODE+ mode (test group) as compared to the STSF catheter using 
the power control mode (control group) in a simulated clinical environment using the 
canine beating heart model. 
Scope: 
The test focused on the safety and effectiveness of the QDOT MICRO™ catheter with 
QMODE+ mode as compared with the STSF catheter using power control mode.  
• QMODE+ primary safety endpoints 
o Char, Coagulum and Steam pop 
o Primary adverse event: cardiac perforation, tamponade and death 
o Collateral damage in the heart and adjacent organ/tissues 

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• QMODE+ secondary effectiveness endpoints 
o Endocardial and epicardial surface diameters 
o Lesion depth and transmurality and PVI rate 
o Signal quality (M1-4 compared to control, μ1-3 qualitive measurements) 
 
Discussion: 
 
The QMODE+ Beating Heart study was conducted according to the study protocol 
design and its requirements.  
 
No char/coagulum observed on the test catheter (QDOT MICRO™). The overall 
incidence of steam pop observed with QDOT MICRO™ (0 in all locations) was lower 
compared to the control STSF catheter (1 in LA PVI). Of note, there were zero incidence 
of steam pop occurrence in the right atrial location and both the left and right ventricular 
locations using QDOT MICRO™ catheter with QMODE+ at the study settings. 
 
The QDOT MICRO™ ablation catheter used in conjunction with the QMODE+ mode 
was able to: 
• Deliver RF energy at a target site  
• Demonstrate acute isolation of the pulmonary vein. 
• Demonstrate clinically acceptable signal quality which was comparable to control. 
• Pace from ring electrodes and microelectrodes during idle-state and during 
ablation. 
• Provide significantly better temperature feedback during ablation than control 
catheter. 
• Function effectively when used in conjunction with ancillary equipment like 
nMARQ multichannel RF generator, QDOT MICRO Dongle, CoolFlow pump, and 
CARTO 3 mapping system. 
 
The QDOT MICRO™ ablation catheter, when used with QMODE+ mode, was able to 
produce effective electrogram signal attenuation with equivalent (or better) lesions as 
compared to those with the STSF catheter in all four cardiac chambers.  
 
Conclusions: 
 
The QDOT MICRO™ ablation catheter with QMODE+ ablation mode using the 
temperature target and flow rate settings as set forth by the protocol, meets all 
acceptance criteria as listed in protocol P-0022212.  
 
The overall functionality and the safety of the QDOT MICRO™ ablation catheter with 
QMODE+ mode is equivalent to or better than that of the control STSF catheter. 

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6.2.3 
QDOT MICRO GLP Study 
 
Purpose: 
 
This study was designed to evaluate overall safety of a new modified therapeutic micro-
electrode ablation catheter (QDOT MICRO™) and demonstrated that added catheter 
features do not introduce any new safety risks when compared to its predicate device 
Biosense Webster THERMOCOOL SMARTTOUCH® SF catheter.  
 
Results: 
 
Overall, The GLP study findings met all endpoints concerning the safety of the Test 
catheter: 
• Occurrence of thrombus and/or charring on the catheter tip: 
There was no evidence of thrombus and/or charring on any of the catheters used and 
examined, following delivery of RF energy. 
• Occurrence of mural thrombus in the treated heart chambers: 
There was no evidence of mural thrombus detected during the ablation or follow-up 
procedures using intracardiac echo or at the treatment sites that could be detected 
macroscopically or microscopically.   
• Pulmonary vein stenosis: 
There was no evidence of pulmonary vein stenosis in any of the animals regardless 
of treatment or group assignment. 
• Occurrence of collateral damage:  
Collateral damage to the adjacent tissues was rare, was occasionally observed at the 
hilus in the right lung lobes and in the pulmonary artery and aorta. These lesions 
were self-limited, did not disrupt the integrity of tissues involved and showed optimal 
healing through fibrosis. 
• Occurrence of device related mechanical injury: 
There was no pathologically meaningful procedural trauma in any of the treated sites 
with rare exceptions of minor endocardial tears that were fully healed at 30 days with 
no evidence of prior thrombosis.  
• Occurrence of peripheral thrombo-emboli: 
No thrombo-emboli or ischemic lesions were observed in downstream tissues: brain, 
myocardium, kidneys, liver, spleen and lungs based on screening through systematic 
bread-loafing with gross evaluation and systemic sampling for microscopic 
evaluation. 
 
Overall, The GLP study findings met all endpoints concerning efficacy of the Test 
catheter: 

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• Effectiveness of ablation in the left atrium  
Elimination of PV electrical potential could be confirmed immediately following 
ablations in all animals regardless of group assignment or treatment received. In 
addition, this study demonstrated long term effectiveness of pulmonary vein isolation 
using the Test or Control catheters as delayed conduction (only in Animal 1244, 
Group 2) or no electrical potential could be detected in the treated pulmonary veins 
at 35-36 days post isolation. 
• Effectiveness of ablation in the right atrium  
All ablations delivered to the right atrium regardless of ablation settings or ablation 
catheter use were found effective as a greater than 50% reduction in the electrogram 
amplitude.   
 
Conclusions: 
 
Biosense Webster QDOT MICRO™ ablation catheter met the safety and efficacy 
criteria set forth in the study protocol when used with nMARQ™ RF generator, Carto 
3 EP navigation system, CoolFlow irrigation pump, catheter interface cable, and 
standard pacing system for ablation in the beating heart of a chronic canine model 
without any significant device related clinical adverse events.  
 
In conclusion, this study demonstrated that added catheter features do not introduce any 
new safety risks when compared to its predicate device Biosense Webster 
THERMOCOOL SMARTTOUCH® SF catheter. 
6.2.4 
QDOT FIM Studies 
Two feasibility studies are underway to assess the performance of the QDOT Micro™ 
Catheter.  
6.2.4.1 
QDOT MICRO™ Workflow 
The purpose of QDOT MICRO™ Workflow study is to evaluate the workflow and acute 
performance, during standard electrophysiology mapping and RF ablation procedures, 
of the QDOT MICRO™ catheter. This study is a prospective, multi-center, non-
randomized, interventional clinical study. The target population are paroxysmal AF 
subjects who are scheduled to undergo a clinically-indicated ablation procedure for 
management of their paroxysmal AF. Subjects will be followed up at 7 days and 3-
month post-procedure.  
The main objectives of the study are acute device performance and acute safety. The 
study will enroll 50 subjects at 5 centers in Europe.  
 
6.2.4.2 
QDOT MICRO™ QMODE+ FIM 
The purpose of this feasibility study is to evaluate safety and acute performance of the 
QDOT Micro™ catheter used in combination with the nMARQ™ Multi-Channel RF 

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Generator with QMODE+ mode in the treatment of Paroxysmal Atrial Fibrillation (PAF) 
during standard electrophysiology mapping and RF ablation procedures. This a 
prospective, multi-center, non-randomized, interventional clinical study. 50 paroxysmal 
AF subjects who are scheduled to undergo a clinically-indicated ablation procedure for 
management of their paroxysmal AF will be enrolled at up to 10 centers in Europe. The 
subjects will be followed till 3-months post-procedure. 
6.3 Rationale 
The Biosense Webster QDOT MICRO™ Catheter is a steerable multi-electrode luminal 
catheter with a deflectable tip designed to facilitate electrophysiological mapping of the 
heart and to transmit radiofrequency (RF) current to the catheter tip electrode for 
ablation purposes.  In addition to force-sensing technology, the catheter incorporates six 
thermocouple temperature sensors and three micro electrodes embedded in the 3.5 mm 
tip electrode. 
The measured temperature can be used by the operator to assess the efficiency of 
ablation in real time. The localized temperature measurement will provide a highly 
sensitive measure of catheter location stability and/or movement during RF application 
and may reduce the need for additional RF applications.   
The micro electrodes will provide high quality localized electrograms that will allow 
finer endocardial electrical mapping and a better assessment of possible conduction gaps 
in the ablation lesion sets used to isolate the pulmonary veins and determining 
bidirectional block of linear lesion sets.   
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 series of In vivo and in vitro experiments, including thigh muscle preparation model 
and in vivo beating heart experiments, were conducted to determine an appropriate 
QMODE+ setting that could be demonstrated to be safe and deliver uniform transmural 
lesion near the PV circumference. The main objective was to identify and evaluate an 
optimal ablation setting that allows maximal power output at the shortest duration 
possible, without char or steam-pop formation.   A range of power (i.e. 50-100W) and 
durations (3-15 seconds) were studied and analyzed.  The data from these evaluations 
suggests that using higher power to promote resistive heating while shortening the 
duration to limit the impact of conductive heating through adjacent tissue provides the 
optimal balance for efficiency, effectiveness and safety.  The conclusion from these 
studies has been implemented as the QMODE+ algorithm using ablation parameters of 
90W for a duration of 4s (irrigation setting at 8ml/min). These parameters were used for 
validation of animal studies as summarized in this study protocol (refer to Sections 6.2.2 
and 6.2.3).  
Delivery of high RF power for short duration (90W, 4 seconds) achieves uniform 
transmural lesions, mainly relying on resistive heating [16-19] QMODE+ at up to 90W, 
4 seconds may significantly shorten RF ablation time while maintaining the 
effectiveness and safety profile.  A temperature limit has been defined to maintain the 
ablation safety profile.  Ablation effectiveness may be improved since the physician is 

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required to maintain catheter stability for a short duration. By reducing the conductive 
heating phase, QMODE+ may minimize the risk of collateral damage to adjacent 
structures.   
6.3.1 
Ablation Parameters for the QDOT MICRO™ Catheter 
The ablation algorithm is designed to maximize RF lesion efficiency by using temperature 
feedback from the tip to adjust power and irrigation flow. The QMODE Temperature mode 
monitors the temperature rate of change in relationship to the set target temperature during 
RF application.  To maintain desired power levels at a safe temperature, the QMODE 
adjusts the irrigation flow rate as a first order of control.  A secondary control of power 
titration is also used if the temperature cannot be maintained with the increased irrigation 
flow rate alone.  Typical temperature control algorithms for mainstream commercial 
irrigation RF catheters rely purely on power titration to maintain the desired temperature.  
By utilizing the irrigation flow rate first, the Q-dot catheter is able to deliver consistent 
power for efficient ablations without compromise of safety. 
 
RF Energy Modulation:  
The RF energy application is separated into two distinct zones: 1-50W and 90W.  
 
For power settings from 1-50W, the approach is to modulate irrigation and then titrate 
power as needed to maintain the target temperature. As an example (see Figure 7.3.1a), the 
power delivery (e.g. 35W) would start with the irrigation setting at 4 ml/min until it reaches 
a target temperature (e.g. 50°C).  When the catheter reaches the target temperature, 
irrigation is then changed to 15 ml/min automatically by the generator algorithm.  This 
increase in irrigation flow rate cools the tip and allows the generator to maintain the 
delivered power.  If the temperature decreases, the pump irrigation flow rate is returned to 
the lower setting (i.e. 4mL). Under circumstances when increased irrigation flow does not 
sufficiently reduce the tip temperature, power delivery is automatically reduced. 
 
In a second example (see Figure 7.3.1b), the power delivery (e.g. 50W) starts with the 
irrigation setting at 15 ml/min until it reaches a target temperature (e.g. 50°C).  If the 
catheter is below the desired temperature initially, the irrigation is automatically reduced 
to 4ml/min by the generator algorithm to maximize the sensitivity to temperature.  Once 
the temperature sensed at the tip starts to rise, the generator automatically increases the 
irrigation flow back to 15 ml/min.  This cycle continues between low and high irrigation 
settings in order to maintain the target temperature.  Again, under circumstances where the 
tip temperature is above 50°C, the power delivery is automatically reduced.  
 
Main Study 
For power settings at 90W (Figures 6.3.1C and 6.3.1D), the maximum duration is set to 4 
seconds. Therefore, the approach is to only titrate power.  At this setting, power delivery 
is delivered at a constant irrigation flow of 8 ml/min with no modulation given the short 
duration.   

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Figure 6.3.1A-D: Graphs of the Generator Power over Time 
A. RF Power Delivery at 35W  
 
 
B. RF Power Delivery at 50W  
 
 
C. RF Power Delivery at 90W 

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D. RF Power Delivery at 90W, power titration evident 
 
Second (Variable Flow) Study 
 
RF energy modulation for Variable Flow rate: 
 
The QDOT MICRO catheter is designed to work in a temperature control/power and 
irrigation modulation mode.  This is how the system works for QMODE (refer to Figures 
6.3.1A and Figure 6.3.1B above).  However, when making 90W RF applications with a 
constant irrigation flow (8 mL/min) the system only worked in power control mode.   
 
The purpose of the variable flow irrigation option is to improve the catheter tip 
temperature response during high power, short duration (Qmode+) ablations. This is 

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achieved by optimizing the flow rate (4-15 mL/min), which minimizes the impact of 
constant irrigation (8 mL/min) on the lack of catheter tip temperature response during 
short duration (4s) 90W RF applications (refer to Figure 6.3.2A and Figure 6.3.2B).  
 
For power settings at 90W (Figures 6.3.2A and 6.3.2B), the maximum duration is set to 4 
seconds. Therefore, the approach is to only titrate power.  At this setting, power delivery 
is delivered with a variable flow rate. Irrigation at 4 mL/min starts with the initiation of 
90W energy application.  The flow rate remains at 4 mL/min if the catheter tip 
temperature remains below the target energy cutoff temperature (refer to Figure 6.3.2A). 
If the catheter tip reaches the target temperature, irrigation is then changed to 15 ml/min 
automatically by the generator algorithm.  This increase in irrigation flow rate cools the 
tip and allows the generator to maintain the delivered power (refer to Figure 6.3.2B). 
 
Figure 6.3.2A-B: Graphs of the Generator Power over Time 
A. 
Example 1 at 90W: Temperature does not approach Target Temperature 
(flow rate 4mL/min) 
 
 
B. Example 2 at 90W: Temperature approaches Target Temperature (flow rate 
changes to 15 mL/min) 
 

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6.4 Potential Risk and Benefit 
After over two decades of intracardiac radiofrequency (RF) catheter ablation, the 
procedural risks and complications associated with routine RF ablation are well 
documented and understood.  Procedural risks posed by the QDOT MICRO™ catheter 
are expected to be comparable to these known anticipated risks.[3, 4, 20].  Few, if any, 
additional risks that might occur during and following RF ablation of symptomatic PAF 
are anticipated for subjects enrolled in this study. 
A summary of risks associated with catheter ablation, including analysis of and plans to 
minimize these risks is provided below: 
6.4.1 
Description and Analysis of Risks  
Risks associated with catheter ablation 
Studies have reported low rates of major complications (0.8%)[21, 22] with major centers 
worldwide reporting rates lower that <5%[23, 24] associated with catheter ablation.  
The most common complications associated with catheter ablation of AF include:  
 
Cardiac tamponade is reported at approximately 0.2 to 5% in catheter ablation of atrial 
fibrillation (AF)[4], comprising mainly pulmonary vein isolation (PVI) procedures. Data 
presented by recent meta-analysis of 34,943 ablation procedures by Michowitz et al 
reported incidence of 0.8%[25]. Rates as low as 0.18% have also been reported in a recent 
study that reviewed complications among 2,750 procedures[22].  
 
The general incidence of pericardial effusion during AF ablation is around 1.2% to 
1.3%[21, 23]. Cardiac perforation may result from catheter manipulation or application of 
radiofrequency current.  Published risks of cardiac perforation range from <1%to 
2.4%[23]. However the risk of perforation is decreased with advances in catheter 
technology[26]. This potentially life-threatening injury may result in cardiac tamponade 
and may require percutaneous pericardial drainage or surgical repair.  Significant 
hemodynamic compromise can result in neurologic injury or death.  An increased risk of 
cardiac perforation may be associated with the use of a saline-irrigated electrode catheter 
due to its ability to create a larger, deeper RF lesion.  This risk is greatest in a thin walled 
chamber (i.e., RA, LA, appendage, or RV).  
 
Pulmonary vein stenosis: Pulmonary vein stenosis (PVS) is a well-known complication 
of radiofrequency catheter ablation of atrial fibrillation. Incidence of severe PVS (>70% 
diameter reduction) was found to be <1% in a recent study with 976 subjects[27]. Incidence 
of only 0.5% was reported in a large systematic review on complications of radiofrequency 
catheter ablation.  
 
Esophageal injury: Since the left atrium has close anatomical proximity to the esophagus, 
catheter ablation on the LA posterior wall may thermally damage the esophagus and 
eventually generate an esophageal ulcer with a prevalence of 5% [28] that rarely may 
progresses to an atrial esophageal fistula (AEF) with catastrophic consequences[29]. 
Esophageal injury by endoscopy has a prevalence between 2.2 to 21%[28]. Esophageal 
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11% [28, 30] of atrial fibrillation ablation procedures. Delayed diagnosis is associated with 
the development of atrial-esophageal fistula (AEF) and increased mortality. Complication 
rates for esophageal injury are quite varied, depending upon lesion location and type of 
lesion found (erythema, necrotic ulceration, perforation, or fistula formation). The 
incidence of AEF post-ablation of AF is supposed to be around 0.1% of the procedures[31]. 
Studies using luminal temperature monitoring to identify potentially dangerous heating of 
the esophagus during ablation have not been able to  demonstrate reduction in 
incidence[32].  
 
Phrenic nerve paralysis: Currently, this complication has been reported in less than 0.5%, 
with permanent paralysis between 0% to 0.4% when the isolation of right PV is not 
obtained during PV antra isolation and RF ablation is performed inside at carina the right 
PVs [4, 32, 33]. A 2018 published study reported very low rates of PNP of 0.04% among 
2,750 procedures[22]. Prior to ablation in the region of the RSPV, investigators are 
encouraged to perform precautionary measures such as evaluation of proximity to the 
phrenic nerve and pacing maneuvers.  
 
Death is an uncommon complication associated with CA techniques. Overall incidence of 
death has been reported to be <0.1% to 0.4%[4]. A 2010-published global survey provided 
an overall mortality rate of 0.1%.  Another report from an international survey of AF 
ablation of 162 centers provided details on 32 deaths that occurred during or after AF 
ablation procedures in 32,569 patients (0.1%)[34, 35]. Among the most frequent causes of 
death were cardiac tamponade (25% of deaths), stroke (16%), atrio-esophageal fistula 
(16%) and massive pneumonia (6%)[35]. 
 
Radiofrequency current may cause occlusion of a coronary artery, either by direct thermal 
damage, spasm, or thrombus formation.  Acute coronary artery occlusion is a very rare but 
potentially life-threatening complication of RFCA[36]. Experience at numerous centers 
suggests that the risk of coronary occlusion is less than 0.5%[37].  Coronary arterial 
occlusion could produce myocardial infarction (MI), angina or death.  Occlusion of a 
coronary artery can be treated by restoring coronary blood flow through pharmacological, 
catheter and/or surgical intervention as medically indicated.  
The application of radiofrequency current close to the AV node or His bundle could 
damage or destroy the normal AV conduction system, producing complete heart block and 
requiring implantation of a permanent pacemaker.  
 
Thromboembolic events: Thrombus generation during the procedure may pose a serious 
and even life-threatening risk to the patient.  Thrombus may form on the ablation electrode 
during the application of radiofrequency current with or without any change in impedance.  
The thrombus might become dislodged and embolize to produce an ischemic stroke, MI, 
or other occlusive injury. Although some observational studies have shown a relatively 
lower stroke rate after catheter ablation, whether catheter ablation can reduce the 
thromboembolic risk remains unclear.  
 
The mean incidence of thromboembolism associated with AF ablation was reported by 
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incidence of thromboembolism up to 5% of patients undergoing AF ablation despite 
perioperative anticoagulation[38]. Ischemic stroke events typically occur within 24 hours 
of the AF ablation procedure with the higher risk period covering for the first two weeks 
following ablation[39]. 
 
Pulmonary hemorrhage is a rare but severe complication of PVI. Late hemoptysis and 
pulmonary hypertension can occur secondary to pulmonary vein stenosis (PVS) after 
ablation. Acute pulmonary hemorrhage also has been reported[40]. Mechanical trauma 
from catheter manipulation is a possible mechanism for pulmonary hemorrhage[41]. 
Injury to a cardiac valve may result from catheter manipulation or the application of 
radiofrequency current (risk <1%)[42]. This may produce valvular insufficiency and 
possibly require valve replacement surgery.  
 
Vascular access / bleeding complication: Arterial or venous injury, including arterial 
dissection, thrombosis, occlusion or hemorrhage at the catheter insertion sites or at other 
sites along the vessels (risk 0.2% to 1.5%).[4, 43, 44] These types of injuries may cause 
hemorrhage, hematoma or ischemic injury to an extremity or major organ.   
Hemorrhage could occur as a result of anticoagulation (risk < 0.5%), which may require 
transfusion.[43, 44] 
 
Radiation exposure: Radiation exposure during the fluoroscopic imaging of the catheters 
may result in an increase in the lifetime risk of developing a fatal malignancy (0.1%) or a 
genetic defect in offspring (0.002%).[45-47] 
 
Allergic Reaction: A patient could develop an allergic reaction to the local anesthetic, 
sedatives, x-ray dye, heparin, protamine, or other agents administered during the procedure 
(risk < 1%).[48-52] 
 
Infection: The percutaneous procedure carries risk of infection, either at the catheter 
insertion site or systemically, including endocarditis and septic emboli (risk < 0.5%).[43, 
44] This risk can be minimized by using standard aseptic technique and, when indicated, 
by the use of antibiotic agents. 
 
Additional contraindications: Additional contraindications for RF ablation include: 
hemodynamic instability, bacteremia, coagulopathy, prosthetic tricuspid valve, intra-atrial 
or venous thrombosis, and pregnancy. 
 
Investigational device related risks  
 
A review of the testing of the investigational devices verifies that risks associated with the 
designs are acceptable and no unacceptable (Intolerable) risks have been noted. Any testing 
deviations are discussed within the body of the respective testing reports and all deviations 
were reviewed and considered to be acceptable. 
 
The designs of the investigational devices have been subjected to testing (bench top, thigh 
preparation, simulated clinical conditions via in vivo beating heart testing and 

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EMC/Electrical Safety testing). The results of the various testing performed have verified 
the safety of the investigational devices when used in accordance with the Instructions for 
Use.  
 
Biocompatibility and Sterility Assessments for the applicable investigational devices have 
been performed and verify that the proposed design and packaging meet the existing 
requirements for both categories.   
 
A review of the risk assessment documents for the investigational devices has verified that 
there are no “Intolerable” ratings related to risks associated with the designs of the devices.  
All ratings are “As Low As Practical” (ALAP). 
6.4.2 
Minimization of Risks 
Appropriate measures have been outlined in the study protocol to minimize the risk to 
subjects, while still providing the possible benefits of the treatment options to be studied. 
Although there are potential risks posed during a cardiac RF ablation procedure, the criteria 
for subject selection, methods, personnel, facilities, and training that have been specified 
for this study are intended to minimize the risk to subjects undergoing this procedure.   
 
Robust testing of the investigational devices at component and the system level, within 
simulated clinical conditions, was successful with no adverse events identified. During the 
QMODE+ design phase, systematic proactive risk analyses did not identify new hazards 
and harms. Additionally, the risk of potential adverse events is mitigated by the temp cutoff 
setting of the generator and the optimization of the target temperature.  
 
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 
eliminate confounding co-morbidities that might interfere with study interpretation; to 
furnish a more homogenous study population that allows a focused characterization of the 
QDOT MICRO™ catheter for the treatment of PAF; exclude subjects with a medical 
history or condition that increases their risk of adverse events. Subjects will be evaluated 
for presence of left atrial thrombus prior to the procedure. Additionally, using esophageal 
monitoring techniques will be used while ablating the posterior wall, thus minimizing risk 
of injury. 
 
Participating investigators will be experienced and highly skilled in performing 
electrophysiology studies, intracardiac mapping and ablation of AF with the use of RF 
ablation catheters.  Each site’s Principal Investigator will have satisfied the established 
training criteria. Procedures will be performed in electrophysiology laboratories with the 
assistance of skilled nurses and technicians.  The laboratory will contain sufficient 
resuscitative equipment and facilities to manage any potential complication.  Immediate 
access to cardiac surgical facilities, as well as a qualified cardiovascular surgeon, will be 
available during the ablation procedure in the event that surgical intervention becomes 
necessary. 
 
 

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6.4.3 
Precautions 
Invasive electrophysiological evaluation and catheter ablation may impart some degree 
of risk to the subject. The risk of serious complications is generally related to the 
severity of cardiac disease. The degree of risk of the electrophysiological and catheter 
ablation procedures versus the potential benefit of the treatment of a paroxysmal or 
recurrent arrhythmia should be determined by a qualified physician. Cardiac 
catheterization and electrophysiological procedures should be performed by qualified 
and appropriately trained personnel in an electrophysiology laboratory. The laboratory 
should contain sufficient resuscitative equipment and facilities to manage most potential 
complications. Failure to observe the contraindications, warnings, and precautions in 
these instructions and the IFU may result in procedural complications. Immediate risks 
from ablation treatment may include: cardiovascular injury or perforation with or 
without cardiac tamponade, pulmonary embolus, tricuspid regurgitation, myocardial 
infarction, bleeding at the catheter insertion site, sepsis, and death.  
Contraindications for catheter ablation of arrhythmia include: existing hemodynamic 
instability, bacteremia, coagulopathy, prosthetic tricuspid valve, intra-atrial or venous 
thrombosis, and pregnancy. 
 
6.5 Known Potential Benefits 
Current practice guidelines reflect extensive expert reviews of published risks and benefits 
among various treatment modalities and patient populations. All key published guidelines 
agree that the primary clinical benefit of catheter ablation for PAF is an improvement in 
quality of life, following abatement of arrhythmia-related symptoms. 
 
The role of catheter ablation as first-line therapy, prior to a trial of a Class I or III 
antiarrhythmic agent, has been suggested as an appropriate indication for catheter ablation 
of AF in patients with symptomatic paroxysmal or persistent AF by the HRS/EHRA/ECAS 
2017 Consensus Statement[4]. In this circumstance, the benefits of catheter ablation 
outweigh the risks (Class IIa); however, the strength of evidence/data supporting this 
therapeutic modality (Level B) reflects a limited number of clinical studies. Not all expert 
bodies are in line with the aforementioned expert opinion.   
 
The 2016 ESC-published guidelines and recommendations for the management of AF 
suggested that in patients who experience symptomatic recurrences of AF despite 
antiarrhythmic drug therapy, catheter ablation shows better sinus rhythm maintenance with 
catheter ablation than on antiarrhythmic drugs[53]. However, the guidelines also present 
that randomized trials showed only modestly improved rhythm outcome with catheter 
ablation compared to antiarrhythmic drug therapy[53].  
 
Catheter ablation has been used for over two decades to treat AF patients to achieve PVI. 
Significant catheter design improvements (e.g., irrigated encircling catheters) focus upon 
improving physicians’ abilities to achieve finite entrance block following PVI, reducing 
damage to neighboring structures and improving procedural efficiency.  
 

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The QDOT MICRO™ Catheter is a steerable multi-electrode luminal catheter with a 
deflectable tip with the force-sensing technology also incorporates six thermocouple 
temperature sensors and three micro electrodes embedded in the 3.5 mm tip electrode.  
  
The measured temperature allows the operator to assess the efficiency of ablation in real 
time.  Thus providing a highly sensitive measure of catheter location stability and/or 
movement during RF application and potentially reducing the need for additional RF 
applications.  
  
The micro electrodes provide high quality localized electrograms that allow finer 
endocardial electrical mapping and 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.   
 
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 QDOT Micro™ catheter is 
designed to create durable lesions, in shorter time thus reducing the procedural time, and 
improved irrigation flow with reduction in the amount of fluid load in the patient as 
compared to a typical irrigation ablation catheter. The catheter also limits conductive 
heating and collateral damage to neighboring structures including non-cardiac adjacent 
tissues, improving safety during the procedure[14, 19, 54] 
7.0 STUDY OBJECTIVES AND PURPOSE 
7.1 Purpose 
The purpose of this study is to demonstrate the safety and 12-Month effectiveness of the 
QDOT MICRO™ catheter when used with the nMARQ™ RF generator in the treatment 
of drug refractory symptomatic paroxysmal atrial fibrillation (PAF) during standard 
electrophysiology mapping and RF ablation procedures. 
7.2 Objectives 
The primary objective of this clinical investigation is to demonstrate the safety and 12-
month effectiveness of the QDOT MICRO™ catheter when used with the nMARQ™ RF 
generator for pulmonary vein isolation (PVI) in the treatment of subjects with paroxysmal 
atrial fibrillation (PAF).  
• To demonstrate the safety based on the proportion of subjects with early-onset 
(within 7 days of ablation procedure) primary adverse events  
• To demonstrate the 12-month effectiveness based on the proportion of subject with 
freedom from documented atrial arrhythmia (atrial fibrillation (AF), atrial 
tachycardia (AT) or atrial flutter (AFL)) episodes during the effectiveness 
evaluation period (Day 91-365)  
The major secondary objectives of this study are:  

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• To evaluate the incidence of (serious) adverse events during and after procedure up 
to 3 months following procedure.  
• To evaluate Acute Procedural Success as defined by:  
o The % of subjects with electrical isolation of PVs (entrance block) at the end of 
the procedure, and  
 The % of subjects with electrical isolation of PVs (entrance block) using 
QMODE+ as the only ablation strategy 
 The % of subjects with electrical isolation of PVs (entrance block) at all 
power settings combined 
o The % of subjects with electrical isolation of PVs (entrance block) after first 
pass isolation, after waiting period and adenosine challenge   
 
8.0 STUDY DESIGN AND ENDPOINTS 
8.1 Description of the Study Design 
The QDOT study is a prospective, multicenter, non-randomized clinical evaluation of the 
QDOT MICRO™ catheter in treating subjects with symptomatic PAF who have failed at 
least one antiarrhythmic drug.  
 
Main Study 
Up to 185 subjects will be enrolled at up to 30 sites. A Cardiac CT/MRA image subset will 
be integrated within the Main Study. 
Second (Variable flow) Study 
Up to 92 subjects will be enrolled at up to 26 sites.   
Both Studies 
Effectiveness and safety endpoints have been defined and will be compared to 
predetermined performance goals. Subjects who sign informed consent are considered 
enrolled in the study. Enrolled subjects who satisfy all eligibility criteria will then 
undergo the ablation procedure with the QDOT MICRO™ catheter.  
After the study ablation procedure, subjects will enter a 3-Month blanking period (Day 
0-90).  
After the Blanking Period, subjects will enter the Evaluation Period (Days 91-365). 
Subjects having AF recurrence and/or receiving therapeutic interventions during the 
evaluation period will be considered effectiveness failures (refer to Section 8.2.2 for all 
effectiveness failure modes).  
All subjects will undergo follow up visits at defined intervals (refer to Table  13.8A 
Schedule of Treatments and Evaluations). Subjects complete the IDE study after the 12-
month follow up visit.  

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8.1.1 
Cardiac CT/MRA Subset 
Main Study 
At a subset of sites, subjects from the Main Study will be enrolled in the cardiac 
CT/MRA subset and will undergo a 3-month CT/MRA in addition to the baseline 
CT/MRA (all subjects will have a baseline CT/MRA) to assess incidence of post-
ablation severe PV stenosis. In order to be included in the cardiac CT/MRA population, 
the subject must have readable outcomes at baseline and 3 months. The first 40 subjects 
consecutively enrolled in the Main Study (included in the 185 total) at cardiac CT/MRA 
subset sites who have readable outcomes will be included in the CT/MRA subset (until 
sufficient CT/MRA subjects are accrued). The probability of observing at least one 
moderate/severe PV stenosis with 40 subjects is 87% assuming the event rate of 
moderate/severe PV stenosis is 5%. 
In addition to this subset, any subjects with signs or symptoms of PV stenosis will 
undergo a post ablation CT/MRA. These subjects will not be included in the CT/MRA 
subset analysis. If severe PV stenosis is present it will be reported as an adverse event.   
8.2 Study Endpoints 
8.2.1 
Primary Safety Endpoint 
The primary safety endpoint is the incidence of any primary adverse event occurring 
within 7 days of the AF ablation procedure (including the initial and repeat procedures), 
using the QDOT MICRO™ catheter per protocol, except atrio-esophageal fistula and 
PV stenosis, which may also be considered as primary adverse events if occurring 
greater than seven (7) days and up to 90 days post the ablation procedure.[55, 56] 
Primary adverse events include the following conditions (refer to Table 14.2.1A: 
Primary Adverse Events for detailed instructions for defining these adverse events): 
• Death 
• Atrio-esophageal fistula 
• Cardiac Tamponade*+/Perforation+ 
• Myocardial infarction (MI) 
• Stroke / Cerebrovascular accident 
(CVA) †, †† 
• Thromboembolism 
• Transient Ischemic Attack  
• Phrenic Nerve Injury/Diaphragmatic 
paralysis 
• Heart block 
• PV stenosis 
• Pulmonary 
edema 
(Respiratory 
Insufficiency)  
• Vagal Nerve Injury 
• Pericarditis 
• Major vascular access complication / 
bleeding 
 
* Hemodynamic compromise or instability is defined as Systolic BP < 80 mm Hg. 
+ Cardiac Tamponade/Perforation occurring within 30 days of the AF ablation process 
will be considered Primary AEs 
† Subjects with non-focal global encephalopathy will not be reported as a stroke without 
unequivocal evidence based upon neuroimaging studies. 
†† Modified Rankin score assessments should be made by certified individuals.  
 

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Data from recent clinical trials for devices similar to the device in the current study were 
reviewed as a first step to deriving the performance goal for the safety endpoint. A meta-
analysis approach was taken to estimate the average composite endpoint rate. Figure 8.2.1 
presents the results of the meta-analysis for combining the safety rates. Based on the plot, 
the upper bound of the 95% confidence interval was estimated to be equal to 9%. The 
proposed performance goal of 14% would reflect an approximately 50% increase in risk 
from the upper bound of the 95% CI. Details of the meta-analysis can be found in Appendix 
C.  
 
Figure 8.2.1 Meta-analysis results 
 
8.2.2 
Primary Effectiveness Endpoint 
The primary effectiveness endpoint is defined as the freedom from documented atrial 
fibrillation, atrial flutter and atrial tachycardia (AF/AFL/AT) (hereinafter collectively 
referred to as “atrial tachyarrhythmias") recurrence (episodes ≥ 30 secs on TTM or 
continuously recorded on the standard 12-leads ECG) during the evaluation period (Day 
91-365) and freedom from the following failure modes:  
• Acute procedural failure, including: 
o Failure to confirm entrance block in all pulmonary veins post-procedure,  
o Use of a non-study catheter to treat left atrial ablation targets and cavo-
tricuspid isthmus 
• Repeat ablation failure, including:  
o > 2 repeat ablation procedures with the study catheter during the 3-Month 
Blanking Period (Day 0-90) after the index ablation procedure. 
o Use of a non-study catheter to treat study arrhythmia ablation targets during 
the blanking period  
o Any repeat ablation procedure during the Evaluation Period. 
• AAD failure: Taking a new AAD for AF or a previously failed AAD at a 
greater than the highest ineffective historical dose for AF during the evaluation 
period (refer to section 13.1 for details). 
This study is designed to compare the primary effectiveness of the QDOT MICRO™ 
Catheter to a pre-determined performance goal of 50%, which is indicated as the 

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minimum acceptable success rate at 12 months for a paroxysmal AF population in the 
2017 HRS/EHRA/ECAS/APHRS/SOLAECE consensus statement.   
8.2.3 
Secondary Endpoints(s) 
The secondary endpoints will apply to both studies.   
8.2.3.1 
Secondary Safety Endpoints 
• Incidence of Unanticipated Adverse Device Effects (UADEs) 
• Incidence of Serious Adverse Events (SAEs) within 7 days (early onset), >7 to 
30 days (peri-procedural) and >30 days (late onset) of initial ablation  
• Incidence of bleeding complication (ISTH definitions): a) major, b) clinically 
relevant non-major and c) minor bleeding  
Refer to Section 14.3 for the definition of Serious Adverse Event.  Refer to Appendix A: 
Study Definitions for the ISTH bleeding complications definitions. 
8.2.3.2 
Secondary Effectiveness Endpoints 
• Acute Procedural Success 
Acute procedural success is defined as confirmation of entrance block in all PVs. 
o % of subjects with electrical isolation of PVs (entrance block) at the end of 
the procedure  
 The % of subjects with electrical isolation of PVs (entrance block) 
using QMODE+ as only ablation strategy 
o % of subjects with electrical isolation of PVs (entrance block) after first 
encirclement (evaluated prior to the 20-minute waiting period and 
adenosine challenge  
o % of subjects with electrical isolation of all PVs (entrance block) after first 
encirclement without acute reconnection, after waiting period and 
adenosine challenge 
o % of subjects and % of PVs with touch-up (i.e. touch-up is used to remove 
ablation of acute reconnection) among all targeted veins and touch-up 
location  
o Anatomical location of acute PV reconnection after first encirclement 
• Repeat ablation procedures during 12-month period post-procedure 
o Incidence (%) of repeat ablation procedures  
o % PVs re-isolated among all the targeted PVs at repeat procedure  
o % repeat ablation procedures requiring new linear lesions and/or 
identifying new foci outside of initially isolated area among the repeat 
ablation procedures 
• 12-Month Single Procedure Success 

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o The 12-month single procedure success is defined as freedom from 
documented AF/AFL/AT recurrence (episodes > 30 secs) during the 
Evaluation Period after a single ablation procedure and off AADs. Any 
repeat ablation procedure or AAD therapy will be deemed effectiveness 
failure for this analysis. 
8.2.3.3 
Additional Endpoints 
• Procedural Data: 
o Total procedure time, PVI time, RF application time, mapping time and RF 
application time per lesion  
o Total Fluoroscopy Time and Dose 
o Fluid delivered from the study catheter  
o Location of RF applications, number of RF applications 
o Repeat Ablation Rate 
o RF Ablation parameters per application  
o Device(s) utilized (per ablation) 
o VISITAG™ Settings 
o CF range 
o Power range 
o Tag Index Assessment per anatomical region 
NOTE: Tag Index data (Force, Power, and Time) will be collected in the 
CARTO® 3 System during the ablation procedures. The data will be 
processed to generate the Tag Index. 
• Quality of Life:  
o Quality of Life (QOL) status will be evaluated by assessing AFEQT 
• Cardiac CT/MRA Subset 
o Incidence of severe PV stenosis at 3 months post ablation in the CT/MRA 
subset assessment evaluation. The CT/MRA subset will be included in the 
main study only.  
8.2.3.4 
Health Economic Data 
The cost and frequency of health care utilization during hospitalization for the study index 
ablation procedure, as well as any additional hospitalizations during the study period will 
be collected. Because this data does not support the safety and efficacy of the QDOT 
MICRO™ catheter, it will not be provided to the Food and Drug Administration (FDA) as 
part of the IDE reporting.   
 
The hospitalization health care data to be collected may include but is not limited to: copies 
of the subject’s hospital bills (UB04) and/or itemized hospital bills.  Subject’s admission 

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date, discharge date, procedure date, ICD-10 and procedure code, Diagnosis Related Group 
(DRG) assignment and total cost for the hospitalization will be extracted from the forms. 
 
In addition, the sponsor will also collect health economic data associated with follow up 
care, including any repeat ablation procedure for treating arrhythmia, any inpatient or 
outpatient visit (including ER admissions) to address post-procedural complications or any 
procedure related condition and any inpatient or outpatient visit (including ER admissions) 
related to arrhythmia and cardiovascular conditions.   
 
9.0 STUDY POPULATION 
9.1 Subject Selection  
9.1.1 
Inclusion Criteria 
Candidates for this study must meet ALL of the following criteria: 
1. 
Symptomatic paroxysmal AF with one electrocardiographically documented AF episode 
within 6 months prior to enrollment and a physician’s note indicating recurrent self-
terminating AF within 7 days. Documentation may include electrocardiogram (ECG); 
Transtelephonic monitoring (TTM), Holter monitor or telemetry strip.  
2. Failed at least one (1) antiarrhythmic drug (AAD) (class I or III) as evidenced by recurrent 
symptomatic AF, contraindicated, or intolerable to the AAD.  
3. Age 18 years or older. 
4. Signed Patient Informed Consent Form (ICF). 
5. Able and willing to comply with all pre-, post-, and follow-up testing and requirements. 
9.1.2 
Exclusion Criteria 
Candidates for this study will be EXCLUDED from the study if ANY of the following 
conditions apply:  
1. Previous surgical or catheter ablation for atrial fibrillation.  
2. AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause. 
3. Patient on amiodarone at any time during the past 3 months prior to enrollment. 
4. Previously diagnosed with persistent or long-standing persistent AF and/or Continuous AF 
lasting > 7 days 
5. CABG surgery within the past 6 months (180 days). 
6. Valvular cardiac surgical/percutaneous procedure (i.e., ventriculotomy, atriotomy, valve 
repair or replacement and presence of a prosthetic valve). 
7. Any carotid stenting or endarterectomy within the last 6 months. 
8. Documented LA thrombus on imaging (within 48 hr prior to a study ablation procedure). 
9. Documented LA size > 50 mm (parasternal long axis view). 
10. Documented LVEF < 40%. 

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11. Contraindication to anticoagulation (e.g. heparin) 
12. History of blood clotting or bleeding abnormalities 
13. MI/PCI within the past 2 months (60 days) 
14. Documented thromboembolic event (including TIA) within the past 12 months 
(365 days) 
15. Rheumatic Heart Disease 
16. Uncontrolled heart failure or NYHA function class III or IV 
17. Severe mitral regurgitation (Regurgitant volume ≥ 60 mL/beat, Regurgitant fraction 
≥ 50%, and/or Effective regurgitant orifice area ≥ 0.40cm2) 
18. Awaiting cardiac transplantation or other major cardiac surgery within the next 12 
months (365 days) 
19. Unstable angina 
20. Active systemic infection or sepsis 
21. Diagnosed atrial myxoma or presence of an interatrial baffle or patch. 
22. Presence of implanted ICD/CRT-D. 
23. 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. 
24. Severe Gastroesophageal Reflux Disease (GERD; active requiring significant 
intervention not including OTC medication) 
25. Significant congenital anomaly or medical problem that in the opinion of the 
investigator would preclude enrollment in this study. 
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 study. 
27. Enrollment in an investigational study evaluating another device, biologic, or drug. 
28. Presence of intramural thrombus, tumor or other abnormality that precludes 
vascular access, or manipulation of the catheter.  
29. Presence of an inferior vena cava filter. 
30. Presenting contra-indication for the devices (e.g. TTE, CT, etc.) used in the study, 
as indicated in the respective instructions for use. 
31. Life expectancy less than 12 months 
 
9.2 Strategies for Recruitment and Retention 
Main Study 

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The QDOT MICRO™ IDE study seeks to enroll up to 185 subjects in the study at up to 30 
clinical sites in the US.  Once enrolled, each subject will participate in the study for 12 
Months.  
Centers will be selected for participation in the study based on experience with RF focal 
catheter technology, ablation experience, their capacity to screen and enroll a reasonable 
number of eligible patients, and ability to perform the required procedures, according to 
this protocol.  
Historically, women and minorities have been underrepresented in or excluded from 
many clinical studies, leading to a lack of information for women and their physicians 
regarding the risk and benefits of many medical treatments and diagnostic procedures. 
It is the Sponsor’s intent to apply the principles from FDA’s guidance titled Evaluation 
of Sex-Specific Data in Medical Device Clinical Studies in this clinical trial to ensure 
adequate representation of women and minorities. The Sponsor will take reasonable 
steps to ensure adequate representation of women and racial or ethnic minorities in this 
clinical trial: 
In order to reflect the gender ratio of the intended population, Sponsor plans to enroll 
approximately 70% males and 30% females in the study. The gender ratio (male: female 
= 7:3) undergoing ablation procedures in the AF population is estimated based on 
previous studies.[57]  
Sites will be instructed to screen all subjects who may be eligible for participation in the 
study without regard to sex or race. Statistical analysis of primary safety and 
effectiveness endpoints will be carried out to evaluate any interaction between treatment 
and gender. Subjects will be encouraged to remain in the study until they have 
completed the protocol required follow-up period.  
Sponsor will attempt to include a diversified group of research sites engaging a variety 
of academic and private institutions geographically located throughout the US and 
possibly other regions. To ensure generalizability of results and minimize the influence 
of any single site, no more than approximately 15% of the total enrollment will be 
allowed at a single site.  
Second (Variable Flow) Study 
Centers that have enrolled subjects in the main arm of the study will be allowed to enroll 
subjects into the second (variable flow) study.  The 15% site enrollment cap also applies 
to the second (variable flow) study. 
9.3 Subject Withdrawal/Early Termination  
Subjects may withdraw from the clinical investigation at any time. The decision for the 
subject to withdraw informed consent must be made independently of influence by the 
investigator or site personnel. The subject’s decision will be documented in the source 
and eCRF. The investigator may also choose to withdraw a subject from the study if 

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there are safety concerns. If a subject withdraws from the study, the date and reason for 
withdrawal will be recorded on the appropriate electronic case report form (eCRF).   
All data will be collected (as available) until the subject is withdrawn. If the subject is 
withdrawn due to an adverse event (AE) or serious adverse event (SAE), the investigator 
should follow the subject until the AE/SAE has resolved or is considered stable. 
9.4 Subjects Lost to Follow up  
Subjects should be encouraged to return for protocol required, clinic visits for evaluation 
during the study follow-up period. If a subject is unable to return for an office or clinic 
visit or unable to 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 requesting the subject’s continuation in the study 
or confirming the subjection desire to terminate from the study. 
If the subject does not respond to the phone telephone calls or letter, then the subject 
will be considered “lost to follow-up.”  
9.5 Subject Disposition 
A subject is considered enrolled when they sign the informed consent. Because the 
treatment assignment is the same for both studies the subject disposition does not change 
for the second (variable flow) study. 
• Enrolled Subjects: subjects who sign the informed consent. 
• Excluded Subjects: subjects that are enrolled but never undergo insertion of 
the study catheter. Excluded subjects will not be included in the safety 
evaluation of the study catheter. 
• Discontinued Subjects: subjects that have the study catheter inserted but are 
not treated with the study catheter (i.e., no RF energy applied). These 
discontinued subjects will be followed for 3 months and be part of the safety 
evaluation. 
• Evaluable Subjects: enrolled subjects who meet the eligibility criteria and 
undergo ablation with the study catheter. 
• Lost to Follow-up Subjects: subjects who are enrolled, but contact is lost after 
most recent follow-up visits (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 or are terminated 
from the study prior to completion of all follow-up visits. 
• Completed Subjects: enrolled subjects who completed the 12-month follow-
up visit and have not been excluded, discontinued, withdrawn, early 
terminated, expired or lost-to-follow-up from the study prior to the final study 
visit. 

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10.0 
RESPONSIBILITIES 
10.1 
Study Timelines 
Study Duration: The study is expected to last approximately 20 months (8-9 months for 
enrollment for main study and 5 months for the second study; 12 months of follow-up 
for primary endpoint for each study).  
10.2 
Investigator Responsibilities 
The Principal Investigator is responsible for supervision of all study activities and is 
ultimately responsible for overall compliance with protocol, GCP, local and regional 
regulations, and IRB/REB requirements. Many study activities may be formally 
delegated to support staff, but the Principal Investigator retains responsibility for 
supervision of all study activities. 
Specific responsibilities include:  
• Obtaining IRB/REB approval and renewals 
• Providing Sponsor with: 
o Written IRB/REB approval letters and IRB/REB-approved consent forms, 
o Signed, dated Investigator Agreement, 
o Signed and dated Financial Disclosure form at study outset and any time 
financial changes occur, for up to one year following completion of the study 
o Curriculum vitae for each Investigator and key research staff member 
• Maintaining an accurate and current Study Personnel Log which identifies all 
individuals authorized to perform work for the study at each site 
• Completing appropriate training on the study device and the study protocol 
prior to enrolling and treating subjects 
• Maintaining accurate and current logs for the study as requested by the study 
team, including but not limited to: 
o Subject screening log 
o Device Accountability log 
• Obtaining informed consent (including privacy language) from patients 
• Performing the ablation procedure 
• Complying with the clinical protocol 
• Notifying the Sponsor and IRB/REB of adverse events, deaths, and deviations 
as defined in this protocol and per IRB/REB requirements. 
• Notifying Sponsor promptly of withdrawal of IRB/REB approval 
• Complying with IRB/REB (as applicable) and Sponsor annual report 
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• Completing eCRFs accurately and as soon as possible after collection of data 
• Reviewing and signing designated eCRFs 
• Maintaining relevant source documentation to support future verification of 
data on the eCRFs. 
• Complete all subject follow-up visits, including efforts to maintain contact 
with subjects who fail to comply with the follow-up schedule. Before a subject 
may be classified as ‘lost to follow-up’, the Investigator or authorized 
personnel should document attempts to contact the subject.  
• Retaining study records as described in section 22.1. The Sponsor will notify 
the Investigator when records may be destroyed.  
• Preparing a final report and periodic IRB/REB updates as required 
10.3 
Sponsor Responsibilities 
The Sponsor (Biosense Webster) will be responsible for the following: 
• Preparing of study documents including but not limited to the protocol, eCRFs 
and template informed consent, if no local template is preferred 
• Completing pre-study site assessments and approvals 
• Obtaining approval from the FDA and regional Health Authorities (HAs)/ 
Regulatory Authorities (RAs)  
• Providing protocol training to investigators and research personnel 
• Instructing operators and technicians in the proper use and monitoring of study 
devices 
• Monitoring the study throughout the duration of the investigation 
• Securing investigator/site compliance with the protocol and applicable 
regulations 
• Creation and maintenance of eCRF database  
• Conducting all communications with HAs/RAs 
• Submitting study supplements for regulatory approval (as necessary), e.g., 
request for study expansion 
• Preparing reports summarizing the status of the clinical study no less often than 
annually, which will be supplied to the FDA and to other HAs/RAs as 
requested. Annual reports may also be provided to each HA/RA, and possibly 
to the Principal Investigator as requested 
• Report the results of an evaluation of an unanticipated adverse device effect to 
FDA within 10 working days after receiving notice of the adverse effect.  
• Access to clinical study data provides opportunities to conduct further research 
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ensure the data provided by research participants are used in the creation of 
knowledge and understanding. To this end, the study results on all pre-
specified outcomes, including negative outcomes, will be submitted to 
ClinicalTrials.gov no later than one year after completion of the primary 
endpoint (unless an extension has been approved via certification from the 
Secretary of Health and Human Services). Results submission could be 
delayed if an extension is granted to the results submission deadline; however, 
the release of all results on pre-specified outcomes will be hastened if the study 
is terminated early 
10.4 
Training 
10.4.1 
Research Team 
The training of appropriate clinical site personnel will be the responsibility of the 
Sponsor or the Sponsor’s representative. In some cases, training may be performed by 
an existing site staff member who has already been trained by the Sponsor (such as 
assigning a new CRC to the study). To insure uniform data collection and protocol 
compliance, the Sponsor will present a formal educational session to study site 
personnel that will include review of the Clinical Study Protocol, techniques for the 
identification of eligible subjects, instructions on in-hospital data collection, follow-up 
schedules, and regulatory requirements. Remote as well as on-site contacts will be used 
to monitor study performance indicators such as enrollment compliance, data 
submission rate, data errors, protocol questions, and GCP compliance.  
10.4.2 
Investigator Training  
QDOT MICRO™ Catheter Training:  
The training of applicable clinical site personnel will be the responsibility of the Sponsor. 
Prior to initiating subject enrollment at a site, appropriate study training will be provided. 
Investigators selected to participate in the study will be experienced in intracardiac 
mapping and AF ablation with focal ablation catheters. Investigators will undergo device 
training in accordance with the physician training charter. 
 
To ensure uniform data collection and protocol compliance, the Sponsor will conduct a 
training session that will include reviewing the protocol, eCRF and data collection 
process, and the adverse event reporting process. The sponsor will reinforce the training 
or provide clarification throughout the study, as needed. 
 
11.0 
STUDY DEVICE DESCRIPTION 
11.1 
Device Acquisition 
After obtaining a fully executed clinical trial agreement and appropriate approvals, the 
Sponsor may 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 investigator or 

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designee. Site study personnel are responsible for appropriate logging of the devices 
received, verification of packing slip information (i.e., lot numbers and quantity shipped), 
recording the date of use and subject ID for each device used in the study, and recording 
device disposition information regarding disposal or return to the Sponsor. 
 
11.2 
Device Storage and Stability 
Investigational Devices are to be stored in a secure/locked location. All devices are to be 
stored in accordance with the IFU. Do not use any devices after the “Use By” date. 
11.3 
Instructions for Use (IFU)  
A copy of the IFU for the QDOT MICRO™ catheters and interface cable is included in 
each product package. 
11.4 
Device Description 
11.4.1 
QDOT MICRO™ Catheter 
The Biosense Webster QDOT MICRO™ Catheters are 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. The catheter shaft measures 7.5 F with 8 F ring 
electrodes. For ablation, the catheter is used in conjunction with a compatible RF 
generator and a dispersive pad (indifferent electrode). The catheter has force-sensing 
technology that provides a real-time measurement of contact force between the catheter 
tip and the heart wall. 
The catheter has a high-torque shaft with deflectable tip section containing an array of 
electrodes which includes a 3.5 mm tip dome with three microelectrodes. All of the 
electrodes may be used for recording and stimulation purposes. The tip electrode serves 
to deliver RF energy from the RF generator to the desired ablation site. The tip electrode 
and ring electrodes are made from noble metals. 
The catheter incorporates six thermocouple temperature sensors that are embedded in 
the 3.5 mm tip electrode.   
At the proximal end of the catheter, a saline input port with a standard Luer fitting 
terminates from the open lumen. This saline port serves to permit the injection of normal 
saline to irrigate the tip electrode. During ablation, heparinized normal saline is passed 
through the internal lumen of the catheter and through the tip electrode, to irrigate and 
cool the ablation site as well as the electrode tip. An irrigation pump should be used to 
control the saline irrigation. 
 
Figure 11.4.1A Overview of the QDOT MICRO™ Catheter with both Uni-directional 
and Bi-directional Tip Deflection 

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Figure 11.4.1B QDOT MICRO™ tip Section 
 
  
 
SIDEARM 
LUER CONNECTOR 
HANDLE BARREL HOUSING 
34 PIN PCB 
CONNECTOR 
PISTON WITH 
THUMB KNOB 
PEBAX 
SHAFT 
QUAD LUMEN 
DEFLECTABLE TIP 
PALLADIUM/PLATINUM  TIP 
USABLE LENGTH 
115cm 

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Figure 11.4.1C QDOT MICRO™ tip with Thermocouples (6), µElectrodes (3) and 
angled irrigation ports 
 
 
 
An irrigation pump is used to control the saline irrigation. The catheter interfaces with 
standard recording equipment and a compatible RF generator via accessory extension 
cables with the appropriate connectors. 
This catheter features a location sensor embedded in the tip section that transmits 
location and contact force information to the CARTO® 3 v6 Navigation System (refer 
to Figure 11.4.1D). An appropriate reference device is required for location reference 
position purposes. For information on using the catheter in mapping procedures and for 
information on appropriate reference devices, refer to the user manual for the CARTO® 
3 v6 Navigation System. 
 
Figure 11.4.1D Contact Force Sensor – External View   
 
 

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This catheter features a location sensor embedded in the tip section that transmits 
location and contact force information to the CARTO® 3 System. An appropriate 
reference device is required for location reference position purposes. The catheter 
connects to the CARTO® 3 Navigation System through an interface box called the 
Patient Interface Unit (PIU). The catheter interfaces with standard recording equipment 
and a compatible RF generator via accessory extension cables with the appropriate 
connectors. For use in mapping procedures, for information on appropriate reference 
devices, and for further description of the operation of the CARTO® 3 Navigation 
System, refer to the CARTO® 3 Navigation System User Manual.  
For further information on the irrigation pump (COOLFLOW® Irrigation Pump) RF 
Generator (nMARQ RF Generator), and required cables, refer to the respective 
Instructions for Use and/or User Manual. 
Refer to Section 11.5 (Required Study Equipment) for details on additional equipment 
required for this study.  
11.4.1.1 
Bi-directional Catheter Description (D-1395-XX-SI) 
The catheter has a high-torque shaft with a bi-directional deflectable tip section 
containing an array of electrodes which includes a 3.5 mm tip dome. All of the 
electrodes may be used for recording and stimulation purposes. The tip electrode serves 
to deliver RF energy from the generator to the desired ablation site. The tip electrode 
and ring electrodes are made from noble metals. The catheter incorporates six 
thermocouple temperature sensors and ECG electrodes that are embedded in the 3.5 mm 
tip electrode. A Rocker Lever is used to deflect the tip. The high-torque shaft also allows 
the plane of the curved tip to be rotated to facilitate accurate positioning of the catheter 
tip at the desired site. Additionally, a variety of curve types are available in symmetric 
or asymmetric combinations, providing two 180° opposed, single-planed curves. Five 
curve configurations designated “DD”, “FF”, “JJ”, “DF”, and “FJ” are available. 
11.4.1.2 
Uni-directional Catheter Description (D-1394-XX-SI) 
The catheter has a high-torque shaft with a uni-directional deflectable tip section 
containing an array of electrodes which includes a 3.5 mm tip dome. All of the 
electrodes may be used for recording and stimulation purposes. The tip electrode serves 
to deliver RF energy current from the generator to the desired ablation site. The tip 
electrode and ring electrodes are made from noble metals. The catheter incorporates six 
thermocouple temperature sensors and ECG electrodes that are embedded in the 3.5 mm 
tip electrode. A Rocker Lever is used to deflect the tip. The high-torque shaft also allows 
the plane of the curved tip to be rotated to facilitate accurate positioning of the catheter 
tip at the desired site. Three curve types configurations designated “D,” “F,” and “J” are 
available. 
11.4.2 
nMARQ® Multi-channel RF Generator (D-1341-07-I) 
The nMARQ® Multi-channel RF generator software version 3.0.1 (main study) and 
version 3.0.6  (second [variable flow] study) are intended for cardiac ablation applications. 
Its purpose is to generate RF energy for delivery to a site in the heart via compatible RF 
ablation catheters. The generator includes functions for controlling ablation parameters at 

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the ablation electrodes of the catheter. Ablation parameters, such as power, impedance, 
ablation duration, and temperature are recorded and can be exported at the end of the 
procedure to a USB device. 
 
The generator consists of the following main components: 
• Console: The console contains the hardware that provides the delivery of RF 
energy. 
• Local Control Workstation (Local Monitor): The local monitor contains a touch 
screen user interface. The monitor contains the software that controls the generator 
and tells the console what function to perform. It also provides communication with 
the CARTO® 3 workstation and the Remote Control Workstation. The local 
monitor attaches directly to the console. 
• Remote Control Workstation (Remote Monitor, optional): The remote monitor 
is physically the same as the local monitor. The remote monitor connects to the 
local monitor via a connecting cable which allows the remote monitor to be used 
outside of the patient area. The only differences between the local and remote 
monitors are: 
o Log files can only be copied from the local monitor, not the remote monitor. 
o Technician settings are accessible only from the local monitor. 
o Only the local monitor communicates to the console. The remote monitor 
passes the user inputs to the local monitor that then passes the inputs to the 
console. Further, when the “Stop” button is pressed on the remote monitor, the 
signal is passed directly from the remote monitor to the console through the 
local monitor but without any intervention. 
• Foot Pedal: The foot pedal allows the user to start and stop ablation without 
pressing the Start and Stop buttons on the monitor. 
• Cart: The generator’s console and local monitor rest on the cart to facilitate 
movement of the equipment throughout the lab. 
• Connection Cables: Cables are used to provide an interface between the various 
components of the generator and to provide connection to an external energy source 
to allow operation of the generator. 
11.4.3 
TX eco EXT Interface Cable (D-1357-03-SI) 
The TX eco EXT Connection Cable (D-1357-03-SI) is designed to connect the QDOT 
MICRO™ Catheter that interfaces the Patient Interface Unit (PIU) of the CARTO® 3 EP 
Navigation System via the dongle. The TX eco EXT Connection Cable consists of a gray 
connector which connects to the dongle and a black connector that connects to the catheter 
receptacle.  
 

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Figure 11.4.3A: TX eco EXT Connection Cable 
 
 
 
11.4.4 
TX eco Cable Dongle (EM-5050-055F) 
The Biosense Webster TX eco Cable (Dongle) (EM-5050-055F) is an accessory device 
primarily intended to provide a means for the QDOT MICRO™ Catheter to interface with 
the CARTO®3 v6.0 EP Navigation System and to the nMARQ® RF generator. The TX 
eco Cable (Dongle) processes and transfers catheter location signals to the CARTO® 3 
System. Additionally, the TX eco Cable (Dongle) contains integrated firmware that reads 
the temperature from each thermocouple (six total) within the QDOT MICRO™ Catheter 
tip. The highest temperature will be sent to the compatible RF Generator and all six 
temperatures will be sent to the CARTO®3 System for real-time visual display.  
 

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Figure 11.4.4A: 
TX eco Cable (Dongle) with Extension Cable 
 
 
Refer to Figure 11.4.4B below which depicts a functional block diagram of the TX eco 
Cable (Dongle) signal processing and transfer activities. 
 
Figure 11.4.4B Block Diagram of the TX eco Cable (Dongle) Processing and Transfer 
Activities 
 
 
11.4.5 
CARTO® 3 v6.0.60 QDOT MICRO™ Software Module 
The QDOT MICRO™ software module is an add-on software feature to the CARTO® 3 
System to display and record ECG, temperature, location and contact force information 
when the QDOT MICRO™ Catheter is connected and the QDOT MICRO™ software 
module is enabled. The temperatures recorded by the 6 thermocouples within the QDOT 
MICRO™ Catheter are transmitted to and displayed graphically on the CARTO® 3 
System. The purpose of sending all six (6) temperature readings to the CARTO® 3 System 
is to provide two graphical displays to the physician on the CARTO® 3 System. 
 

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Tip Temperature Display 
The CARTO® 3 System will display the temperature measured by the TX eco Cable in 
colored 2D and 3D imaging format. The image on the left is the temperature distribution 
around the tip electrode.  The image on the right is the “bulls eye” display. 
 
Figure 11.4.5A: Information Displayed on the Carto 3 System 
 
Colored 
catheter 
temperature distribution 3D 
display 
“Bulls eye” 2D display of 
values for each thermocouple 
reading 
 
 
The “bulls eye” display provides temperature information to the physician.  An optional 
numerical value of the temperature from the RF Generator is displayed on the “bulls eye” 
determined by the physician’s preference to display or not to display).  The colored graphic 
of the bull’s eye provides relative tip to tissue interface temperature readings obtained from 
the 6 thermocouples. The colored tip graphic provides the physician with an indication as 
to which part of the catheter tip has contact with the tissue. In addition, it can also provide 
the physician with an indication of the catheter’s tip to tissue stability; if the catheter tip 
slips, the temperatures obtained from the thermocouples will change which will be visually 
displayed on the “bulls eye” as well as on the graphic of the tip of the catheter. The colors 
in the displays change as the temperature of the thermocouples change. The colors range 
from dark blue (minimum temperature) to dark red (maximum temperature) and the 
circular presentation allows the physician to visualize the relative temperatures of distal 
and proximal thermocouples in the tip (viewed from the center outward). The outer halo 
provides the orientation of the catheter tip in 3-dimensional space. 
 
The TX eco Cable is responsible for gathering the QDOT MICRO™ Catheter temperature 
and micro electrode signal information and transferring this data to the Carto 3 System for 
display. The temperature feedback display during ablation is described below. 
 
• Tip Temperature Distribution - monitor the maximum temperature measured and 
verify the proper response of the temperature distribution of the catheter tip during 
the RF session. In the figure below, the six small circles represent the 6 

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thermocouples: 3 distal and 3 proximal. The inner circle represents the tip electrode 
and the outer ring represents the tip sides. 
 
Figure 11.4.5B: Temperature Distribution Display 
 
 
 
Any change in the desired Ablation catheter tip orientation – from a perpendicular 
orientation to the tissue, would result in temperature rise of the corresponding part of the 
catheter tip electrode, as indicated by the red color the tip temperature distribution display 
as shown below. 
 
 
Figure 11.4.5C: Temperature Display for Perpendicular Catheter Tip Orientation 
 
 
 
 
• Any change in the desired Ablation catheter tip orientation – from a parallel 
orientation to the tissue, would result in maximum temperature rise of the 
cylindrical part of the tip that is in contact with the tissue.  This is indicated by the 
red color at the tip temperature distribution display, as shown in Figure 11.4.5D. 
 
Figure 11.4.5D: Temperature display for Parallel Catheter Tip Orientation 
 

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Figure 11.4.5E: CARTO® 3 GUI with RF generator in Unipolar Mode, QDOT 
MIDRO™ Catheter 
 
 
 
 
11.5 
Required Study Devices and Equipment 
The following devices are required for the AF ablation procedure during this study: 
Table 11.5A: Required Study Equipment  
Equipment 
Function or Specifics 

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Investigational Equipment 
QDOT MICRO™ Catheters  
• D-1394-XX-SI  
• D-1395-XX-SI 
Delivers RF energy to the target tissue. 
TX eco EXT Connection Cable  
(D-1357-03-SI) 
Provides a means to interface the QDOT 
MICRO™ catheters with the Dongle  
TX eco Cable (Dongle)  
(EM-5050-055F) 
Provides a means to interface the QDOT 
MICRO™ catheters to the Multi-Channel 
RF Generator 
nMARQ 
Multi-Channel 
RF 
Generator (D-1341-07-I) 
• v3.0.1 – Main Study 
• v3.0.6  – Second (variable 
Flow) Study 
Transmits RF energy to the Ablation 
Catheter 
CARTO 
3 
v6.0.60 
QDOT 
MICRO™ Software Module 
Provides a visual interface for the features of 
the QDOT MICRO™ catheter  
Non-Investigational Equipment 
8.5 F compatible sheath 
Facilitate deployment of catheter into the 
atria.  
 Lasso® or PentaRay® (optional) 
Pre-ablation recording and mapping of the 
atria of the heart with the CARTO® system. 
CoolFlow® Irrigation Pump and 
Tubing Set 
Delivers heparinized saline to the catheter 
for cooling during the RF energy application 
Esophageal 
temperature 
monitoring device 
Esophageal temperature monitoring  
EP lab recording equipment 
Records multiple intracardiac electrograms 
and signals from the RF generator (power, 
temperature, impedance) and performs 
electrical stimulation. 
Adhesive electrical dispersive 
pads / indifferent electrode 
Component of the RF current return path 
(Valley Lab recommended) 
Interface Cables 
Connection of choice 
CARTO® System Junction Box 
Provide the interface to the catheter, 
generator, and the CARTO® System. 
Carto® 3 v 6.0 System 
For mapping and visualization information. 
Version 6.0.60 or higher 
 
 
11.6 
System Components and Set-Up 
 
A connectivity diagram for system set up is depicted in Figure 11.6A. 
 

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Figure 11.6A: System Set Up 
 
12.0 
STUDY MEDICATIONS 
12.1 
Antiarrhythmic Drugs 
12.1.1 
Definitions 
• Antiarrhythmic drugs (AADs)  
The study protocol will classify and analyze the following: 
o Class I drugs (e.g., flecainide, propafenone, disopyramide, etc.) 
o Class III drugs (e.g., amiodarone, dronedarone, dofetilide, etc.) 
• Previously Failed AAD 
Any AAD that a subject has ever taken for the treatment of his/her AF, prior to 
enrollment, is considered a “previously failed AAD” if it meets both of the following 
conditions: 
o prior to enrollment, the AAD was ineffective in controlling the subject’s AF 
or produced intolerable side effects leading to its discontinuation; 
o the AAD is administered for AF 
• New AAD  
ANY AAD that was never taken for the treatment of AF prior to enrollment is 
considered a “new AAD” if the drug is administered to treat an “atrial tachyarrhythmia” 
post-enrollment. 
 
Table 12.1A illustrates the corresponding status of primary effectiveness endpoints based 
on AAD therapy administered in the blanking and post-blanking periods.  

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Table 12.1A: AAD Usage and Impact on Primary Effectiveness Classification  
  
Blanking period  
(≤ 90 days post procedure)  
Post blanking period  
(> 90 days post procedure)  
Class I and/or 
Class 
III AAD  
Can be initiated, continued from 
prior to study enrollment, or 
increased in 
dose as 
long 
as 
the AAD is stopped on or before 
day 90 post procedure and 
subject will not be classified as a 
primary effectiveness failure.   
If initiated for the treatment of AF; 
subject will be classified as a primary 
effectiveness failure.  
If initiated for the treatment of AF during 
the blanking period and continued past 
Day 90; Subject will be classified as a 
primary effectiveness failure  
Can be initiated, 
continued 
from 
blanking period, or increased if drug is 
NOT 
for 
the 
treatment 
of 
atrial 
arrhythmia (e.g. hypertension) other than 
CTI dependent AFL and subject will 
not be 
classified 
as 
a 
primary 
effectiveness failure.  
Class 
II 
and/or Class 
IV AAD  
Can be initiated, continued from 
prior to study enrollment, or 
increased in dose and subject will 
not be classified as a primary 
effectiveness failure.  
Can be initiated, continued from prior to 
study enrollment, or increased in dose and 
subject will not be classified as a primary 
effectiveness failure.  
 
12.2 
Study specific anticoagulation requirements 
• PRIOR to the procedure 
o Uninterrupted anticoagulation therapy should be in place at least 1 month prior 
to ablation procedure. 
 If receiving warfarin/coumadin therapy, subjects must have an 
international normalized ratio (INR) ≥ 2 for at least 3 weeks prior to 
treatment and the subject’s must be confirmed to be ≥ 2 within 48 hours 
pre-procedure. Any INR < 2 within 3 weeks prior to ablation will lead 
to exclusion of the subject or postponement of the study procedure until 
the INR is ≥ 2 for at least 3 weeks prior to treatment. 
o Anticoagulation therapy should not be interrupted or stopped prior to the 
procedure (this means no doses should be missed or omitted) and daily regimen 
should be continued. 
• DURING the procedure 
o Administer a heparin bolus PRIOR to transseptal puncture. 

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o Target an ACT of ≥350 seconds prior to inserting the catheter and throughout 
the procedure. 
o ACT levels MUST be checked every 15 - 30 minutes during the procedure to 
ensure an ACT target of ≥350 seconds. All recordings (ACT level, timing of 
heparin administration and dose) must be documented in the medical records as 
source documentation. 
o Flush all tubing and sheath continuously with heparinized saline. 
• FOLLOWING the procedure 
o Anticoagulation therapy is strongly recommended for at least 2 months 
following ablation. 
13.0 
STUDY 
SCHEDULE, 
PROCEDURES, 
AND 
ASSESSMENTS 
13.1 
Screening and Informed Consent 
13.1.1 
Patient Screening 
All patients considered for RF ablation procedure for drug refractory recurrent 
symptomatic PAF should be evaluated by the investigator or designated member of the 
research team for study eligibility per the protocol inclusion and exclusion criteria.  
 
Subjects are enrolled upon signing the informed consent form. No subject may undergo 
any protocol required tests or examinations falling outside the standard of care without first 
signing the Informed Consent form for this clinical investigation.  
 
Screening for the second (variable flow) study can only begin after enrollment in the main 
study is complete. 
 
13.1.2 
Informed Consent 
Signing of an approved Informed Consent form (ICF) or Patient Information/Informed 
Consent form (PI/ICF) by the study candidate documents the patient’s acceptance and 
enrollment in the study. Prior to signing, the investigator or authorized member of the 
research team should discuss the background, potential risks and benefits, and expectations 
of the study with the candidate. The candidate should have any questions answered to his 
or her satisfaction and should have access to an investigator for technical or medical 
questions as requested. Sufficient time must be given for this process. The subject or legal 
representative must sign the consent form prior to conducting any study-specific exams or 
tests that fall outside of the standard of care. The consent form used must have prior 
approval from a duly-constituted Institutional Review Board, Regional Ethics Board, or 
Ethics Committee. Failure to obtain informed consent renders the subject ineligible for 
participation in the study. 
 
The informed consent will include an authorization for use and disclosure of the subject’s 
protected health information, in accordance with the Health Insurance Portability and 
Accountability Act (HIPAA) or as required per local regulations. Subject confidentiality 

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will be maintained throughout the clinical trial in a way that assures that individual subject 
data can be tracked back to the source data. For this purpose, a unique subject identification 
code will be used that allows identification of all data reported for each subject. Data 
relating to the trial may be made available to third parties, provided the data are treated as 
confidential and that the subject’s privacy is guaranteed. 
 
The informed consent will also request authorization for release of billing information 
specific to the subject’s participation in the study. Specifically, the subject’s UB04 (an 
itemized bill for the study procedure), the explanation of benefits (EOB) and any other 
hospitalizations or ER visits that occur during the study will be requested for each 
procedure and/or hospitalization. 
 
13.2 
Pre-Procedure/Baseline Assessments, Evaluations and Procedures 
Pre-procedure assessments must be performed within 30 days prior to the index AF 
ablation procedure unless otherwise noted. Some assessments (listed below) have a 
shorter window prior to the AF ablation procedure.  
• Demographics (age, gender, etc.) 
• Medical History: including but not limited to arrhythmia, heart disease, 
thromboembolic events, lung/respiratory problems.  
• AF History (first evidence of AF, number of episodes, symptoms, etc.).  
• NYHA Functional Class Scale (for subjects with congestive heart failure).  
• CHA2DS2 VASc Score: Will be used to assess the risk of stroke 
• 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 enrollment but prior to the ablation procedure and should be 
recorded in the eCRF.  
• Anticoagulation Therapy: Uninterrupted anticoagulation management is 
mandatory for each study subject. For subjects on warfarin/coumadin therapy, 
subjects shall be maintained on Warfarin/Coumadin for at least 3 weeks prior 
to treatment with an INR ≥ 2 (to be confirmed maximum 48 hours pre-
procedure). Any INR < 2 within 3 weeks prior to ablation will lead to exclusion 
of the subject or postponement of the study procedure. The results must be 
available prior to start of procedure.  
• Physical Exam including standardized neurological exam done by a physician 
(including cranial nerve, motor and sensory function, and gait assessments), 
must be conducted at the pre-procedure visit  
• NIH Stroke Scale (NIHSS) administered by certified healthcare provider done 
pre-procedure 

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• Vital Signs: height, weight, heart rate, body temperature, blood pressure, pulse 
rate  
• Electrocardiogram: (12-Lead ECG) Data from 12-lead ECG recordings will 
be collected if available.  
• Transthoracic Echocardiogram (TTE): Imaging to determine the atrial size 
prior to the AF procedure. If the subject has undergone an imaging procedure 
within the last 6-months where the atrial size (parasternal long axis view) was 
assessed and documented, the pre-procedure imaging assessment is not 
required. 
• Cardiac Multi Slice Computed Tomography (CT) or Magnetic Resonance 
Angiogram (MRA) image: CT/MRA will be used to evaluate the number, size 
and anatomy of the pulmonary veins and the left atrial anatomy in the CT/MRA 
subset. It is mandatory to conduct the CT/MRA assessment prior to the study 
ablation procedure. For each PV, a core lab will determine the following 
measurements: 
o Major axis (mm) 
o Minor axis (mm) 
o Average diameter (mm) 
• Imaging for detection of LA thrombus: performed within 48 h of the study 
procedure or day of ablation procedure. The following are allowable imaging 
modalities: 
o TEE 
o CT/MRI 
o Intracardiac Echocardiography (ICE) 
• Pregnancy Test: Pre-menopausal women only, performed within 24 hours 
prior to the procedure. 
• Baseline Quality of Life (QOL) Assessment: AFEQT must be collected prior 
to procedure  
• Adverse Events must be collected from the time the subject signs the informed 
consent onwards  
13.3 
Study Ablation Procedure  
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 Study ablation procedure will utilize both QMODE and QMODE+ temperature control 
modes to treat subjects with PAF.  QMODE+ temperature control will be used primarily 
for PVI.  QMODE temperature control will be used primarily for AF application outside 
the PV ostia and for touch-up of the PVI, if necessary.   
 

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Table 13.3A: QMODE and QMODE+ RF and Flow Rate Settings during RF 
applications 
Power 
Target Temp* 
Cut-off Temp 
Nominal 
Irrigation 
Flow 
rate 
Range 
maximum 
allowed 
Range 
Maximum 
allowed 
25-35 W 
40-50ºC 
50ºC 
50-55ºC 
55ºC 
4mL** 
36-50W*** 
40-50ºC 
50ºC 
50-55ºC 
55ºC 
15mL** 
90W† 
40-60ºC 
60ºC 
60-70ºC 
70ºC 
8mL** 
Second study (Variable Flow Rate) 
90W† 
40-60ºC 
60ºC 
60-70ºC 
70ºC 
4-15 mL 
* 
Temperatures displayed on the RF generator do not represent tissue temperature or electrode tissue interface 
temperature. 
** A minimum flow rate of 2mL during mapping is recommended. 
*** RF applications at 36-50W should not exceed 60 sec. 
† 
The study recommends using this power setting for PVI as a primary ablation Strategy.  RF applications at 
this power setting are limited to 4 sec. It is recommended to use lower target temp setting for the posterior 
wall RF applications. 
. 
 
Recommendation for CoolFlow® Irrigation Pump Setting and RF Power-delivery 
 
The CoolFlow® Irrigation Pump will deliver a continuous infusion of 2 ml/min of room 
temperature heparinized saline (1 u heparin/1 ml saline) when not delivering RF energy. 
Increase the irrigation to high flow rate starting minimal 2 seconds before the onset of RF 
energy delivery. 
 
Main Study 
 
• QMODE+ 
For QMODE+ (90W), a flow rate of 8 ml/min will be used.  Do not use this catheter without 
irrigation flow and maintaining this higher flow rate.   
• QMODE 
For QMODE, a high flow rate starting up to minimal 2 seconds before the onset of RF 
energy delivery and maintaining this higher flow rate up to 4 seconds after termination of 
the energy application (refer to Table 13.3A and Section 13.3.5). 
 
Second (Variable Flow) Study 
 
For the second study the flow rate for QMODE+ will incorporate a variable flow rate 
during RF applications.   
 
• QMODE+ 

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For QMODE+ (90W), a flow rate will begin at 4 mL/min and change to 15 mL/min as 
temperature dictates.  Do not use this catheter without irrigation flow and maintaining the 
variable flow rate during RF applications.  
  
• QMODE 
Flow rate remain the same as described above and in Section 13.3.5. 
 
Recommended Contact Force (CF) Settings 
 
When using the study catheter in QMODE and QMODE+, the recommended Contact Force 
working range should be between 5 and 30g.  
Caution: For safety precautions, it’s recommended to not exceed CF values above 30g. 
Note: The QMODE and QMODE+ parameters, presented in Table 13.3A, are user-
adjustable, in case the investigator deems appropriate.  
 
13.3.1 
QMODE+ Recommended Ablation Parameters 
In this study protocol, QMODE+ is to be used as the primary mode for pulmonary vein 
isolation. If the investigator deems QMODE+ unable to achieve PVI, the study catheter in 
QMODE should be used to complete the procedure. (refer to Section 13.3.5 and Appendix 
B for QMODE details) 
 
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. 
 
Main Study 
 
Table 13.3.1A: QMODE+ RF and Flow Rate Settings during RF applications 
Power 
Target Temp* 
Cut-off Temp 
Nominal 
Irrigation 
Flow 
rate 
Range 
Maximum 
allowed 
Range 
Maximum 
allowed 
90W† 
40-60ºC 
60ºC 
60-70ºC 
70ºC 
8mL** 
* 
Temperatures displayed on the RF generator do not represent tissue temperature or electrode tissue interface 
temperature. 
** A minimum flow rate of 2mL during mapping is recommended. 
† 
The study recommends using this power setting for PVI as a primary ablation Strategy.  RF applications at 
this power setting are limited to 4 sec.  It is recommended to use lower target temperature setting for the 
posterior wall RF applications. 
 
Note: The QMODE+ parameters, presented in Table 13.3.1A, 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 catheter 

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movement, initial impedance, impedance drop, electrogram reduction, time of RF 
application, and with consideration of individual patient conditions. 
 
Second (Variable Flow) Study 
 
For the second (variable flow) study the flow rate for QMODE+ will incorporate a variable 
flow rate during QMODE+ RF applications.  At the onset of 90W RF application the flow 
rate will be at 4mL/min.  As the temperature approaches the target temperature the flow 
rate will change to 15 mL/min to maintain the tip temperature within the target range.  If 
the temperature reaches the set cut-off temperature the system will stop RF delivery.  
 
The introduction of the variable flow is the only change to the system.  The catheter should 
be used in QMODE+ as described in the remainder of this section.  
 
Table 13.3.1A: QMODE+ RF and Flow Rate Settings during RF applications 
Power 
Target Temp* 
Cut-off Temp 
Nominal 
Irrigation 
Flow 
rate 
Range 
Maximum 
allowed 
Range 
Maximum 
allowed 
90W† 
40-60ºC 
60ºC 
60-70ºC 
70ºC 
4-15mL** 
*  Temperatures displayed on the RF generator do not represent tissue temperature or electrode tissue 
interface temperature. 
** A minimum flow rate of 2mL during mapping is recommended. 
† 
The study recommends using this power setting for PVI as a primary ablation Strategy.  RF applications 
at this power setting are limited to 4 sec.  It is recommended to use lower target temperature setting for 
the posterior wall RF applications. 
 
Note: The QMODE+ parameters, presented in Table 13.3.1A, 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 catheter 
movement, initial impedance, impedance drop, electrogram reduction, time of RF 
application, and with consideration of individual patient conditions. 
 
 
13.3.2 
General AF Procedure Guidelines for QMODE+ 
The AF ablation procedures for this study should follow the sequence below: 
• Diagnostic catheter placement 
• Electrophysiology study (discretion of investigator) 
• Cardioversion if subject is in AF (discretion of investigator) 
• CARTO® Respiratory Gating Mandatory (unless using Jet Ventilation) 
• Placement of esophageal temperature monitoring device 

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• Confirmation of ACT in ≥ 350 sec. PRIOR to insertion of the QDOT 
MICRO™ Catheter into the left atrium and maintained throughout the 
procedure  
• Transseptal puncture 
• A left atrial anatomical map is required prior to an ablation procedure in the 
LA.  
o An anatomical map is not required of triggers outside of the left atrium e.g. 
SVC/CS etc.  
• Introduction of the QDOT MICRO™ Catheter 
o Use the AUTOTAG feature in Carto to tag each QMODE+ ablation point 
after each application 
o At the new location ensure catheter stability before commencing RF 
application. 
o A pre-ablation flow rate delay of minimal 2 seconds will occur before RF 
application  
o Ablation: RF power application of up to 90W for up to 4 seconds 
(QMODE+)  
o Move the catheter to a new location (~4mm) if clinically effective ablation 
is achieved  
o QMODE+ should be used for full PV encirclement. If the investigator deems 
QMODE+ unable to achieve PVI, the study catheter in QMODE should be 
used to complete the procedure (refer to Appendix B for details). 
o Continue RF applications and catheter movement until the circumferential 
PVI is completed. 
o Precautions: 
 If the temperature increases above the temperature cutoff (default 
65°C), RF application will stop immediately (automatically) 
 The decision to interrupt RF power delivery at any time during 
ablation should be guided by Clinical Investigator judgment and the 
monitoring of ablation effectiveness parameters commonly used 
such as catheter movement, EGM reduction and/or impedance 
changes. 
o For ablation in the region of the right superior PV, precautionary 
measures such as pacing maneuvers are recommended to evaluate 
proximity to the phrenic nerve.  
• Left Atrial ablation and real time PV isolation 
• Post ablation a 20-min waiting period is REQUIRED before pacing 
procedure(s) and/or infusion of cardiac medications to induce AF/reconnection 
(e.g., Adenosine, Isoproterenol 2-20 mcg/min) 

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• Confirmation of entrance block in all targeted PVs by Lasso® or PentaRay®  
• Conduct fluoroscopic (or equivalent) evaluation of the diaphragm  
13.3.3 
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 localization: 
• Use of an esophageal temperature probe, 
• Esophageal visualization with CARTOSOUND® and/or ICE, 
• Esophageal visualization using barium swallow. 
Safety Alert: when esophageal temperature rise observed, please allow necessary time 
for tissue to cool down, and do not apply additional lesion immediately at the same or 
nearby location until the temperature returns to baseline. 
In the event of Esophageal temperature rise: 
1. When esophageal temperature rise observed, please allow necessary time for 
tissue to cool down, and do not apply additional lesion immediately at the same or 
nearby location  
2. Move away from that spot and ablate the other areas first then return to that spot if 
isolation is not attained 
3. At the investigator’s discretion, QMODE may be used with the operator’s usual, 
chosen, posterior wall power and duration, still watching very carefully for 
temperature rise and not starting until esophageal temperature returns to baseline. 
4. Ablate in an area nearby but slightly away from that area if the above 2 steps 
don’t accomplish the task. 
 
Power reduction data and clinical practice associated with posterior wall RF applications 
will be collected in the CRFs and CARTO® data files for analysis. 
 
NOTE 1: The recommendations provided are based on data obtained from animal and 
clinical studies. Use clinical judgment when using this catheter paying careful attention to 
impedance drop, electrogram reduction, time of RF application, and with consideration of 
individual subject conditions when selecting settings.  
NOTE 2: Reduce Power when high contact forces are observed during creation of RF 
lesions in the left atrium. For CF ≥ 20g power should be ≤ 35 watts. 
 
13.3.4 
Ablation Outside the PV Ostia  
The ablation procedure includes PVI, ablation of non-PV triggers and substrate 
modification.  For RF application outside the PV ostia QMODE+ and QMODE may be 
used at the discretion of the Investigator.   

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Study procedure requirements are outlined below: 
• PVI of all PVs are required (acute success) 
• Linear ablation lines are only required to treat documented macro-reentry atrial 
tachycardias and limited to the following targets only: 
o LA roof line 
o MV isthmus line 
o LA floor line 
o CTI  
• A right atrial CTI linear ablation is REQUIRED in cases with documented 
typical atrial flutter either prior to or during the procedure. 
• Ablation of spontaneous non-PV triggers 
• CFAE ablation (left atrial, right atrial and CS) is not recommended 
• Ablation of non-PV triggers induced by adenosine or isoproterenol 
Prophylactic ablation of empirical sites is not allowed. 
All linear lesions require confirmation of bidirectional conduction block by pacing 
and/or mapping maneuvers. 
13.3.5 
QMODE Ablation Parameters and Workflow 
QMODE temperature control mode will be used for PVI once the investigator deems 
QMODE+ unable to complete PVI.  Additionally, QMODE temperature control mode 
will be used for all RF applications outside the PV ostia during the study ablation 
procedure (refer to Section 13.3.4 and Appendix B for additional details).   
 
Table 13.3.5A: QMODE Ablation parameters  
Power 
Target Temp* 
Cut-off Temp 
Nominal 
Irrigation Flow 
rate 
Range 
Recommended 
Range 
Recommended 
25-35 W 
45-50ºC 
50ºC 
50-55ºC 
55ºC 
4mL** 
36-50W*** 
45-50ºC 
50ºC 
50-55ºC 
55ºC 
15mL** 
* 
Temperatures displayed on the RF generator do not represent tissue temperature or electrode tissue interface 
temperature. 
** A minimum flow rate of 2mL during mapping is recommended. 
*** RF applications at 36-50W should not exceed 30 sec. 
 
QMODE Contact Force (CF) Settings 
When using the study catheter in QMODE the recommended Contact Force working 
range should be between 5 and 30g.  
 

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QMODE Ablation Workflow: 
• If the temperature increases rapidly, stop RF application immediately 
• RF power range of 15-50 Watts (W) is recommended for atrial ablation 
• At anatomical locations, not on the LA posterior wall or CS: 
o Maximum allowed power should not exceed 50 W 
o Duration of ablation should not exceed 60 seconds of continuous ablation at a 
given location 
• Move/drag the catheter to a new location when clinically effective ablation is 
achieved (EGM reduction and/or impedance drop). 
• Duration of ablation as well as the decision to interrupt RF power delivery at any 
time during ablation SHOULD be guided by: 
o Clinical Investigator judgment and the monitoring of ablation effectiveness 
parameters commonly used such as EGM reduction and/or impedance 
changes.  
Precautions while ablating on the Posterior wall and Coronary Sinus: 
• LA posterior wall and close to the esophagus:  
o Start ablation using standard workflow for posterior wall.  
o Move/drag the catheter to a new location if clinically effective ablation is 
achieved within 20 seconds (EGM reduction and/or impedance drop). 
o Maximum power used SHOULD NOT exceed 35 W, except when using 
QMODE+. 
o Duration of ablation as well as the decision to interrupt RF power delivery at 
any time during ablation SHOULD be guided by: 
 Clinical Investigator judgment and monitoring of ablation effectiveness 
parameters commonly used such as EGM reduction and/or impedance 
changes 
 Esophageal temperature changes should be monitored by an endo-luminal 
esophageal probe or method used to move esophagus as needed (refer to 
Section 13.3.3) 
 Duration of ablation should not exceed 30 seconds on posterior wall. 
 
13.4 
Post Ablation 
• Verification of entrance block is required for all PVs. 
o A 20-minute waiting period is REQUIRED from the last RF application 
at a PV before verification may be confirmed. If reconduction is noted, 
additional RF applications should be applied and a second 20-minute waiting 
period will be required to recheck for entrance block. If reconduction is still 
noted, additional RF applications may be applied but a third 20-minute 
waiting period is not required prior to recheck for entrance block. 

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• To verify entrance block, analyze electrograms in sinus and/or atrial paced 
rhythm to confirm that no PV potentials are present. 
o Administration of adenosine or isoproterenol after a 20-minute waiting 
period is REQUIRED to rule out dormant conduction.  
• Demonstration of entrance block MUST be confirmed and documented by the 
LASSO® Circular Mapping Catheter or PENTARAY® NAV Catheter.  
• Linear ablation lines may only be performed to treat documented macro-
reentry atrial tachycardias (LA roof line, MV isthmus line, LA floor line, CTI. 
o Bidirectional block must be confirmed and documented 
• The ablation procedure is considered complete when confirmation of block is 
confirmed and documented. 
• In addition to the data collected on the CRFs, a CARTO® backup file 
identified with the subject’s study number must be made for each case and sent 
to the sponsor as part of the data collection. 
13.5 
Data collection During the Study Procedure 
Procedural data collection will be done through anonymized (or de-identified) generator 
files, anonymized (or de-identified) CARTO® data files, procedural worksheets and 
subject medical files. Documentation of procedural data will be kept in the subject’s 
CRF, anonymized (or de-identified) back-up generator files and back-up CARTO® data 
files for study analysis. 
 
The information collected during the procedure will include, but will not be limited to, 
the list below:  
• RF application-mode per lesion (QMODE+/QMODE/other) 
• Number of RF applications with QDOT MICRO™ catheter (total/ 
QMODE+/QMODE) and with non-study catheter 
• Duration of RF applications with QDOT MICRO™ catheter (total/ 
QMODE+/QMODE) 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 

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• 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; fluid output 
and net fluid input 
• Strategy used to minimize risk of esophageal injury 
• Abnormal esophageal temperature rises 
13.5.1 
Collection of Ablation Procedure data for post-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 subject binders, and one fully anonymized copy will be sent to the 
Sponsor. 
13.6 
Repeat Procedures 
Repeat procedures may be performed at the discretion of the investigator. Repeat 
procedures during follow up may be managed per investigator discretion using an 
approved ablation catheter. The follow-up schedule will remain based on the initial 
ablation procedure. 
13.7 
Post Procedure Follow-up Assessments 
The subjects will be required to complete follow up visits through 12 months (365 days) 
post initial ablation procedure.  Follow-up schedules will be based on a 30-day month 
 
Follow-up visits should be scheduled according to the following timeframes: 7 day (7D, 
day 7-10), 1 month ± 7 days (1M, day 23-37), 3 month ± 14 days (3M, day 76-104), 6 
months ± 30 days (6M, day 150-210), and 12 month ± 30 days (12M, day 335-395). 
Follow-up visit schedule will not reset if subject undergoes a repeat AF ablation 
procedure. 
• Prior to hospital discharge: 
o Physical Exam including standardized neurological assessment 
(including cranial nerve, motor and sensory function, and gait 
assessment) conducted by a physician must be performed pre-discharge.  
 If neurological assessment demonstrates new abnormal 
findings as compared to the one performed at baseline, a formal 
neurological consult and examination with appropriate imaging 
(i.e., DW-MRI), needs to be done to confirm any suspected 
diagnosis of stroke. 
o NIH Stroke Scale (NIHSS) must be administered by certified healthcare 
provider done prior to discharge  
o Occurrence of arrhythmias, if any 
o Electrocardiogram (12-Lead ECG) 

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o Transthoracic Echocardiogram (TTE), for evaluation pericardium for 
possible pericardial effusion and/or pericarditis. In the event significant 
pericardial effusion is identified, subjects should be followed until the 
condition resolves. 
o Cardiac-related concomitant medications (such as AADs, anticoagulation 
regimen, etc.) All cardiac-related medications prescribed since the ablation 
procedure till the end of follow-up will be recorded, including the type and 
name of the medication, associated indications, starting and ending dates of 
the prescriptions, etc.  
o Adverse events, if any 
o Collect Subject Hospitalization Billing information (including UB04 and 
EOB) 
• Data will be collected at the 7 day, 1M, 3M, 6M, and 12M follow-up, and at 
any unscheduled visits via in-clinic, telehealth or phone visit. 
o Physical Exam: Exam should be performed at all clinical visits. This 
includes vital signs reported by the patient via telehealth or phone visit.  
o Quality of Life questionnaire: AFEQT™ is to be collected at the 3M, 
6M , and 12M visits via in-clinic, telehealth or phone visit. 
o Electrocardiogram (12-Lead ECG). Data from 12-lead ECG recordings 
will be collected at the 3M and 12M follow-up visit (standard of care are 
acceptable). ECG data will be collected at baseline, pre-discharge, and 
unscheduled visits if completed as standard of care and at 1M and 6M if 
a clinical visit occurs and ECG is completed as standard of care.  
o Transtelephonic Monitoring (TTM): Subjects will be asked to transmit 
any symptom-triggered episode that occurs from the time they receive the 
TTM device through the 12M follow-up visit.  See Section 13.10 for the 
TTM transmission schedule.  A core lab will be used to evaluate and 
assess the TTM tracings.  
o 24 Hour Holter: Holter monitor will be used at the 12M follow-up visit 
to monitor the subjects’ heart rhythm for 24 hours continuously. A core 
lab will be utilized to evaluate and assess the 24-hour Holter recordings.  
o Cardiac Multi Slice CT/MRA Image: CT/MRA will be completed at 
the 3M follow-up visit for subjects in the Main study CT/MRA subset. In 
addition, any subjects who have symptoms suggestive of PV stenosis 
should undergo CT/MRA imaging.  
o Adverse Events: AEs must be collected from the time the subject signs 
the informed consent onwards.  
o AFL/AT/AF recurrence 
o Repeat Ablation: Any ablation procedure performed after the index 
procedure will be recorded at 3M, 6M, and 12M follow-up as well as at 
any unscheduled visits.  

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o Health Economic Data for hospitalizations, ER visits and outpatient 
visits, if any 
 At each follow-up visit, health economic data to be collected 
may include, but is not limited to: hospitalization charge 
(UB04), repeat ablation procedure and/or procedures resulting 
from the ablation procedure, outpatient visits, and ER visits 
o End of Study Report (12-Month) 

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13.8 
Standard Tests and Procedures 
The required schedule for subject treatments and evaluations is summarized in Table 
13.8A.  
Table 13.8A: Schedule of Treatments and Evaluations 
 
Pre- Proced. 
 
 
Phon
e Call 
Follow-Up Visits  
(via in-clinic, telehealth or 
phone visit) 
 
 
Screening / 
Baseline 
Study 
Abl1 
Day 0 
D/C 
7 D 
D7-10 
1 M 
D23-
37 
3 M 
D76-
104 
6M 
D150-
210 
12M 
D335-
395 
U
NS 
Visit no. 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Informed 
consent1 
X 
 
 
 
 
 
 
 
 
 
Inc & Excl 
Criteria 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Vital Signs 
X 
 
 
 
 
 
 
 
 
 
Physical Exam 
 
X17 
 
X17 
 
X 
X 
X15 
X 
X 
NIHSS 
 
X 
 
X 
 
 
 
 
 
 
Med History2  
X 
 
 
 
X2 
X2 
X2 
X2 
X2 
X2 
Arrhythmias 
History 
X 
 
 
 
 
 
 
 
 
 
ECG 
 
X 
 
X 
 
X 
X 
X 
X 
X 
Adverse Events3,4 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CHA2DS2-Vasc 
Score 
X 
 
 
 
 
 
 
 
 
 
NYHA Scale 
 
X 
 
 
 
 
 
 
 
 
QOL Assessment5 
 
X 
 
 
 
 
X 
X 
X 
 
Preg Test6 
 
X 
 
 
 
 
 
 
 
 
LA thrombus 
Imaging7  
 
 
X7 
 
 
 
 
 
 
 
TTE8,9 
 
X8 
 
X9 
 
 
 
 
 
 
Concomitant 
Medications10 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
mRS16 
 
 
 
 
X16 
X16 
X16 
X16 
X16 
X16 
PV CT/MRA 
Subset11 
X 
 
 
 
 
 
X11 
 
 
 
PV Stenosis 
CT/MRA11 
 
 
 
 
X11 
X11 
X11 
X11 
X11 
X11 
Ablation 
Assessments 
 
 
X 
 
 
 
 
 
 
 
Repeat Ablation18 
 
 
 
 
 
X 
X 
X 
X 
X 
Device Deficiency 
 
 
X 
 
 
 
 
 
 
 
Health Economic 
Data Collection12 
 
 
 
X12 
X12 
X12 
X12 
X12 
X12 
X12 
AF/AT/AFL 
recurrence 
 
 
 
X 
X 
X 
X 
X 
X 
X 
TTM13 
 
 
 
 
 
 
X 
X 
X 
X 

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Pre- Proced. 
 
 
Phon
e Call 
Follow-Up Visits  
(via in-clinic, telehealth or 
phone visit) 
 
 
Screening / 
Baseline 
Study 
Abl1 
Day 0 
D/C 
7 D 
D7-10 
1 M 
D23-
37 
3 M 
D76-
104 
6M 
D150-
210 
12M 
D335-
395 
U
NS 
Visit no. 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
24-hour Holter 
 
 
 
 
 
 
 
 
X 
 
Subject 
Completion/ 
discontinuation 
form14 
 
 
 
 
 
 
 
 
X14 
 
 
1 
Initial ablation procedure should be done 
within 30 days of consent.  
2 
Collected to confirm no changes in medical 
history since last visit 
3 
AEs collected once consent has been signed 
Collected to confirm no changes in medical 
history since last visit. 
4 
If AE results in hospitalization, health 
economic data collection is required.  
5 
Quality of life tools (AFEQT). 
6 
Pregnancy test must be done on pre-
menopausal women only, within 24 hours of 
the procedure. 
7 
Subjects should undergo imaging for the 
presence of LA Thrombus.  
8 
Imaging TTE to determine the atrial size (if 
the subject has undergone an imaging 
procedure within the last 6-months where the 
atrial size was assessed, the pre-procedure 
imaging assessment is not required).  
9 
Post procedure all Subjects will undergo a 
TTE procedure to assess the pericardium for 
pericardial effusion and/or pericarditis. 
10 
Concomitant medications: only cardiac 
related (anti-arrhythmia drugs, 
anticoagulation regimen, etc.).  
11 
PV imaging (CT/MRA) for subjects who 
have symptoms suggestive of PV stenosis or 
are in the Main study CT/MRA PV Analysis 
Subset. 
 
 
12 
Health Economic Data for hospitalizations 
(UB04), ER visits and outpatient visits, if 
any.   
13 
TTM: all symptomatic cardiac episodes 
should be recorded and transmitted at the 
time the event occurs.  Asymptomatic 
transmissions should be recorded and 
transmitted as described in Section 13.10. 
14 
12-month visit or last completed visit  
15 
Required only for clinical visit 
16 
In the event of a stroke the Modified 
Rankin Score will assess the degree of 
disability in the subject who suffered the 
stroke.  
17 
A standardized neurological assessment 
(including cranial nerve, motor and sensory 
function, and gait assessment) is to be 
done. If this neurological assessment 
demonstrates new abnormal findings, the 
patient should also have a formal 
neurological consult and examination with 
appropriate imaging (i.e., DW-MRI), used 
to confirm any suspected diagnosis of 
stroke.  
18 
All subjects who undergo a repeat ablation 
procedure during blanking period with the 
QDOT MICRO™ catheter will undergo 
follow-up for Day 7 and 1 month after the 
ablation procedure. 
 
 

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13.9 
Unscheduled visit 
If a subject returns for a potential study related cardiovascular or neurological visit 
outside of the protocol-defined visit schedule provided in Table 13.8A, the visit will be 
considered “unscheduled” (UNS). An Investigator may request an unscheduled visit in 
the presence of a new or worsening 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. 
13.10 
Heart Rhythm Monitoring 
ECG, Transtelephonic monitors (TTM) and Holter Monitors will be used to monitor the 
subjects’ heart rhythm post-treatment.  
Transtelephonic Monitors (TTM): 
Transtelephonic monitors (TTM) will be provided to each subject no later than at the 3-
month follow-up visit for scheduled transmissions of heart rhythm status.  Subjects will 
be instructed to transmit all emergent symptomatic cardiac events and follow a detailed 
schedule if the subject remains asymptomatic post ablation during the Evaluation Period 
(Day 91-365).   
The TTM transmission schedule: 
• Subjects will complete a test transmission upon receipt of the TTM device to 
demonstrate a working understanding of the device.  
• Transmission will be performed once every week during the Evaluation Period, 
starting no later than the month 3 visit through the end of month 5 of the follow-
up period. Starting from month 6, subjects will record and transmit once every 
month until the end of the 12- month follow-up period.  
• All symptomatic cardiac episodes should be recorded and transmitted soon 
after the event occurs during the Evaluation Period (Day 91-365).   
13.11 
Repeat AF Ablation Procedures 
Repeat AF ablations(s) may be performed at the discretion of the physician. The follow-
up schedule (Medication Adjustment and Therapy Consolidation periods and exam 
intervals) will continue based on the initial AF ablation procedure performed, regardless 
of repeat ablations.   
The following assessments should be performed before each procedure: 
• Imaging for detection of LA thrombus – performed within 48 hours prior to 
the procedure (refer to Section 13.2 for details).  
• Pregnancy Test – Pre-menopausal women only, performed within 48 hours 
prior to the procedure. 

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Note: All subjects who undergo a repeat ablation procedure during blanking 
period with the QDOT MICRO™ catheter will undergo follow-up for Day 7 and 
1 month after the ablation procedure. 
13.12 
Core Laboratory  
A core laboratory will be used to review the ECGs, TTMs and Holter Monitors for the 
objective evaluation of recurrence of atrial tachyarrhythmias. Evaluations will be reviewed 
by a physician. AF episodes will be evaluated per the definition included in this protocol. 
A core lab will also be used to review the CT/MRA images. 
 
14.0 
ASSESSMENT OF SAFETY  
14.1 
Adverse Event Recording  
An Adverse Event is any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) occurring during a 
clinical study, whether or not related to the study device or ablation procedure.  
For the purposes of this protocol, adverse events will be reported and recorded (via 
eCRF) if any of the following apply: 
o Event is vascular, cardiovascular, or neurologic in nature 
o The event is a serious adverse event 
o Causality is related to: 
o Investigational device 
o Ablation procedure 
o Unknown in nature 
The following clinical events will not be considered an adverse event for this clinical 
study: 
o Any medical condition that is present at the of screening. Such conditions 
should be added to the medical history, if not previously reported. 
However, if the study subject’s condition deteriorates at any time during 
the study, it should be recorded as an AE. 
o A trace / trivial pericardial effusion that is asymptomatic, requires no 
medical intervention, and does not extend hospitalization will not be 
considered an adverse event 
o Recurrence of pre-existing AF/AT/AFL 
o AF/AFL/AT recurrence requiring pharmacological or direct current 
cardioversion at any time throughout the duration of the study. However, 
new onset of left atrial flutter occurring post-ablation is an AE. 

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o Re-ablation for AF or pre-existing AFL/AT itself is not an AE, however 
any complication associated with the repeat ablation procedures is 
considered an AE and shall be reported within the applicable timelines. 
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. 
The investigator is responsible for ensuring that all reportable AEs, observed by the 
investigator/study staff 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 and whenever the physician 
becomes aware of an event. Investigators will determine, at each encounter, whether 
any adverse events (AE) have occurred, and judge their seriousness and relationship to 
the study device and procedure. Each investigator shall provide source documentation 
as requested by the Sponsor to facilitate reporting and adjudication of these events.  
All adverse events meeting the above definitions, regardless of classification, 
seriousness, intensity, outcome, or causality, must be recorded in the electronic CRF(s) 
in a timely manner throughout the study. Onset date of the event, its treatment, current 
status (resolved, stabilized, or ongoing), and assessment of its seriousness and 
relationship to the device should be provided when available. All AEs will be monitored 
until they are resolved or stabilized (no further changes anticipated).  
14.2 
Classification 
Any of the following events, and any death or hospitalization while on study, is to be 
reported to the sponsor immediately. The Sponsor may request additional information 
after the initial notification. 
14.2.1 
Primary Adverse Event 
A Primary AE is one of the following events occurring within seven (7) days following 
an AF ablation procedure with the QDOT MICRO™ catheter when used with the 
nMARQ™ RF generator, except atrio-esophageal fistula and PV stenosis, which may 
also be considered as primary adverse events if occurring greater than seven (7) days 
and up to 90 days post the ablation procedure:[55, 56] 
Table 14.2.1A: Primary Adverse Events 
PRIMARY ADVERSE 
EVENT 
DESCRIPTION / CRITERIA 
Death 
Patient death directly related to the device or procedure and 
occurs at any time during or after the procedure. 

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PRIMARY ADVERSE 
EVENT 
DESCRIPTION / CRITERIA 
Atrio-Esophageal Fistula 
Is defined as a connection between the atrium and the lumen 
of the esophagus. Evidence supporting this diagnosis includes 
documentation of esophagus erosion combined with evidence 
of a fistulous connection to the atrium such as air emboli, an 
embolic event, or direct observation at the time of surgical 
repair. A CT or MRI scan is the most common method of 
documentation of an atrio-esophageal fistula. 
Cardiac 
Tamponade*+/Perforation+ 
The development of a significant pericardial effusion during or 
within 30 days of undergoing an AF ablation procedure. A 
significant pericardial effusion is one which results in 
hemodynamic compromise, requires elective or urgent 
pericardiocentesis, or results in a 1 cm or more pericardial 
effusion as documented by echocardiography. Cardiac 
tamponade should also be classified as "early” or “late” 
depending on whether it is diagnosed during or following 
initial discharge from the hospital.  
Myocardial Infarction 
The presence of any one of the following criteria: 
• 
Detection of ECG changes indicative of new ischemia 
(new ST-T changes or new LBBB) which persists for 
more than 1 h 
• 
Development of a new pathological Q waves on an 
ECG, and 
• 
Imaging evidence of new loss of viable myocardium or 
new regional wall motion abnormality  

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PRIMARY ADVERSE 
EVENT 
DESCRIPTION / CRITERIA 
Stroke/  
Cerebrovascular Accident 
Rapid onset of a focal or global neurological deficit with at 
least one of the following: change in level of consciousness, 
hemiplegia, hemiparesis, numbness or sensory loss affecting 
one side of the body, dysphasia or aphasia, hemianopia, 
amaurosis fugax, or other neurological signs or symptoms 
consistent with stroke. 
Duration of a focal or global neurological deficit ≥24 h; or <24 
h, if therapeutic intervention(s) were performed (e.g. 
thrombolytic therapy or intracranial angioplasty); OR 
available neuroimaging documents a new hemorrhage or 
infarct; or the neurological deficit results in death. 
No other readily identifiable non-stroke cause for the clinical 
presentation (e.g., brain tumor, trauma, infection, 
hypoglycemia, peripheral lesion, pharmacological influences)†  
Confirmation of the diagnosis by at least one of the following: 
• 
Neurology or neurosurgical specialist   
• 
Neuroimaging procedure (MR or CT scan or cerebral 
angiography) 
• 
Lumbar puncture (i.e., spinal fluid analysis diagnostic 
of intracranial hemorrhage) 
Stroke: (diagnosis as above, preferably with positive 
neuroimaging study)   
• 
Minor—Modified Rankin score <2 at 30 and 90 days††  
• 
Major—Modified Rankin score ≥2 at 30 and 90 days  
Thromboembolism 
Formation of a clot (thrombus) inside a blood vessel causing 
obstruction to blood flow. The thrombus can migrate 
(embolus) and obstruct distal vascular sites. Diagnostic tests to 
help detect thromboembolisms may include but are not limited 
to angiography (pulmonary or distal), ventilation-perfusion 
(V/Q) scans, venography, Doppler ultrasonography, spiral CT, 
and echocardiography. 
Transient Ischemic Attack 
New focal neurological deficit with rapid symptom resolution 
(usually 1 to 2 h), always within 24h.  Neuroimaging without 
tissue injury.  
Phrenic Nerve Injury / 
Diaphragmatic Paralysis 
Absent phrenic nerve function as assessed by a sniff test. A 
phrenic nerve paralysis is considered to be permanent when it 
is documented to be present 12 months or longer following 
ablation. 

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PRIMARY ADVERSE 
EVENT 
DESCRIPTION / CRITERIA 
Heart Block 
Impairment of AV conduction requiring intervention (e.g. 
temporary or permanent pacemaker) due to iatrogenic cause 
(e.g. inappropriate RF application, traumatic maneuvering of 
catheter or other intracardiac devices). 
Pulmonary Vein Stenosis 
A reduction of the diameter of a PV or PV branch. PV stenosis 
can be categorized as mild <50%, moderate 50-70%, and 
severe 70% reduction in the diameter of the PV or PV branch.  
PV stenosis (> 70% PV narrowing) regardless of the presence 
or absence of symptoms and PV stenosis with ≥ 50% PV 
narrowing when accompanied with relevant symptoms that 
cannot be explained by other etiologies will be considered a 
primary adverse event. 
Pulmonary Edema 
(Respiratory Insufficiency) 
Respiratory insufficiency resulting in pulmonary 
complications necessitating intubation or other significant 
intervention (including diuretics administered specifically for 
treating pulmonary edema or ICU hospitalization requiring 
oxygen administration but not intubation) Exclusion criteria 
include: 
• 
Pneumonia – infiltrate, fever and leukocytosis 
• 
Acute Respiratory Distress Syndrome 
Vagal Nerve Injury 
Injury to the vagal nerve that results in esophageal dysmotility 
or gastroparesis. Vagal nerve injury is considered to be a 
major complication if it prolongs hospitalization, requires 
hospitalization, or results in ongoing symptoms for more than 
30 days following an ablation procedure. 
Pericarditis 
Should be considered a major complication following ablation 
if it results in effusion which leads to hemodynamic 
compromise or requires pericardiocentesis, prolongs 
hospitalization by more than 48 h, requires hospitalization, or 
persists for more than 30 days following the ablation 
procedure.  
Major Vascular Access 
Complication / Bleeding 
Major Bleeding: 
A major complication of AF ablation if it requires and/or 
treated with transfusion or results in a 20% or greater fall in 
HCT. 
Major Vascular Access Complication: 
Defined as hematoma, an AV fistula, or a pseudoaneurysm 
which requires intervention such as surgical repair or 
transfusion, prolongs the hospital stay, or requires hospital 
admission.  
* Hemodynamic compromise or instability is defined as Systolic BP < 80 mm Hg. 

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+ Cardiac Tamponade/Perforation occurring within 30 days of the AF ablation 
process will be considered Primary AEs 
† Subjects with non-focal global encephalopathy will not be reported as a stroke 
without unequivocal evidence based upon neuroimaging studies. 
†† Modified Rankin score assessments should be made by certified individuals.  
 
All reported Primary AEs will be monitored until they are adequately resolved or explained. 
14.3 
Serious AEs  
A serious adverse event (SAE) is any event that meets one or more of the following 
criteria: 
• Lead to a death 
• Lead to a serious deterioration in the health of a subject that: 
o Resulted in a life-threatening illness or injury 
o Resulted in a permanent impairment of a body structure or a body 
function; 
o Required in-patient hospitalization or prolongation of existing 
hospitalization* 
o Resulted in medical or surgical intervention to prevent permanent 
impairment to body structure or a body function 
• Lead to fetal distress, fetal death or a congenital abnormality or birth defect. 
“Hospitalization” means the event necessitated an admission to a health care facility 
e.g., with at least an overnight stay. Emergency room visits that do not result in 
admission to the hospital should be evaluated for one of the other serious outcomes. 
*Planned hospitalization for a condition present prior to the participant’s enrollment in 
the study will not meet the definition of an SAE, but should nevertheless be included in 
routine study reporting.  
14.4 
Non-Serious AEs 
A non-serious AE is any event that results in minimal transient impairment of a body 
function or damage to a body structure and does not require any intervention listed under 
the criteria for “Serious Adverse Event.” Non-serious adverse events require routine 
reporting via EDC. 
14.5 
Anticipated AEs 
An anticipated AE is one that has been reported in previous studies of RF ablation and 
can be anticipated in this current study as per the risk analysis. Table 14.5A provides a 
comprehensive list of anticipated AEs. 
 
Table 14.5A: Anticipated Adverse Events 

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Anticipated Adverse Events 
1. Acute Respiratory Distress Syndrome (ARDS) 
2. Air embolism 
3. Allergic reaction  
4. Anaphylactic shock 
5. Anemia 
6. Allergic reaction to Anesthesia (e.g., hair loss) 
7. Apnea - sedation induced 
8. Arrhythmia: bradycardia 
9. Arrhythmia: tachycardia 
10. Arrhythmia: pro-arrhythmias 
11. Arrhythmia: ventricular tachyarrhythmia / pro-arrhythmia 
12. Aspiration pneumonia 
13. Asthmatic attack 
14. Atelectasis 
15. Atrial fibrillation 
16. Exacerbation of pre-existing arrhythmia 
17. Atrio-Esophageal fistula 
18. Typical atrial flutter 
19. Atypical left atrial flutter 
20. Atypical right atrial flutter 
21. AV fistula 
22. Bleeding complications 
23. Bleeding requiring transfusion 
24. Cardiac arrest 
25. Cardiac perforation  
26. Tamponade 
27. Cardiac thrombo-embolism 
28. Cerebro-vascular accident (CVA) / stroke 
29. Chest pain/discomfort 
30. Complete heart block, temporary or permanent 
31. Conduction block: ongoing / resolved 
32. Congestive Heart Failure 
33. Coronary artery dissection 
34. Coronary artery occlusion 
35. Coronary artery spasm 
36. Coronary artery Thrombosis 
37. Death 
38. Deep venous thrombosis 
39. Dislodgement of ICD (Implantable Cardioverter Defibrillator)  
40. Dislodgement of permanent pacing leads 

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Anticipated Adverse Events 
41. Disseminated Intravascular Coagulation 
42. Dyspnoea 
43. Endocarditis 
44. Epistaxis 
45. Expressive aphasia 
46. Fainting 
47. Fatigue 
48. Gastro-intestinal NOS 
49. Gastric reflux 
50. Nausea 
51. Gastrointestinal diverticulosis 
52. Heart Failure 
53. Hematoma (local) /ecchymosis 
54. Hemorrhage  
55. Hemothorax 
56. High / increased creatine phosphokinase (CPK) 
57. Hypotension 
58. Hypertension 
59. Hypoxia 
60. Infection, localized  
61. Infection, systemic 
62. Laceration 
63. Leakage of air or blood into the lungs or other organs due to perforation 
64. Liver toxicity 
65. Mobile strands in Inferior Vena Cava 
66. Myocardial Infarction 
67. Neurological disorders (tremor) 
68. Neurological disorders (poor coordination) 
69. Neurological disorders (headache) 
70. Obstruction to the vascular system 
71. Perforation of the vascular system 
72. Damage to the vascular system 
73. Pericardial effusion resulting in tamponade 
74. Pericardial effusion without tamponade 
75. Minor Pericarditis 
76. Major Pericarditis 
77. Peripheral embolus 
78. Peripheral nerve injury 
79. Peripheral thromboembolism 
80. Phlebitis 

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Anticipated Adverse Events 
81. Phrenic nerve damage  
82. Diaphragmatic paralysis 
83. Pleural effusion 
84. Acute Respiratory Distress Syndrome (ARDS) 
85. Pneumothorax 
86. Pseudoaneurysm 
87. Pulmonary edema 
88. Heart failure 
89. Pulmonary embolism 
90. Pulmonary hypertension 
91. Pulmonary toxicity, like acute pulmonary syndrome 
92. Pulmonary vein dissection 
93. Pulmonary vein Stenosis 
94. Pulmonary vein thrombus 
95. Pump failure 
96. Renal failure 
97. Respiratory depression 
98. Respiratory failure 
99. Retroperitoneal hematoma 
100. Rhabdomyolysis, including produced by body position or propofol 
101. Sedation induced CO2 retention with lethargy and cholecystitis 
102. Seizure 
103. Sepsis 
104. Skin burns (due to cardioversion, tape, etc.) 
105. Skin discoloration 
106. Skin injury / muscle or connective tissue injury due to body position, electrical 
cardioversion 
107. Skin rash 
108. Thrombocytopenia 
109. Thromboembolism 
110. Thrombosis 
111. Thyroid disorders 
112. Transient extremity numbness 
113. Extremity numbness 
114. Transient ischemic attack (TIA) 
115. Unintended complete or incomplete AV, Sinus node, or other heart block or damage 
116. Urinary retention 
117. Urinary tract infection 
118. Urinary tract injury or infection related to the urinary catheter 
119. Vagal Nerve injury 

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Anticipated Adverse Events 
120. Valvular damage/insufficiency 
121. Vasovagal reactions 
122. Vision change 
123. Volume overload 
124. Worsening obstructive, restrictive, or other form of pulmonary disease 
125. X-ray radiation injury of skin, muscle and/or organ 
14.6 
Unanticipated Serious Adverse Device Effect 
A (serious) adverse device effect (SADE) is any (serious) adverse effect on subjects’ 
health, safety, rights, welfare, and life-threatening problems including death, which is 
caused by, or associated with the study device. Accordingly, relationship to device or 
study is crucial assessment by investigators. An unanticipated adverse device effect 
(UADE) or unanticipated serious adverse device effect (USADE) is any ADE or SADE 
that has not been previously identified in nature, severity, or degree of incidence in the 
study plan or risk analysis report. An investigator shall submit to the reviewing IRB/EC 
a report of any unanticipated adverse device effect occurring during an investigation as 
soon as possible, but no later than 10 working days after the investigator first learns of 
the effect, where applicable. 
14.7 
Clinical Investigation Device Failure/Malfunction/Deficiency 
A device has failed if it does not perform according to the instructions for use or fails to 
meet the expectations of the device and/or investigator (i.e., related to appearance of the 
device, performance, durability, safety, effectiveness, quality, reliability, labeling, etc.). 
If a device failure is detected or suspected, it should be documented on the appropriate 
CRF and the device must be promptly returned according to the Sponsor’s 
instructions. If the device failure is associated with an AE, both the device failure and 
AE must be reported to the Sponsor immediately upon awareness (refer to section 
14.8). 
14.8 
Reporting Requirements 
All 
serious 
AEs, 
UADE/SADE/USADE, 
and 
Study 
device 
failure/malfunction/deficiency, whether or not they are related to the device or 
procedure, must be reported by eCRF to the Sponsor (Biosense Webster Clinical 
Operations).  
The sponsor is responsible for reviewing AEs (causality, classification, seriousness…) 
and for ongoing safety evaluations in accordance with the study safety management 
plan. In case of disagreement between the sponsor and the principal investigator(s) that 
remain after query resolution, 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, probably device-

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related, or possibly device-related) in accordance with relevant regulations and current 
company procedures. 
In the case of serious adverse 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 preventive action is required. 
Timing for reporting the different types of AEs is described in Table 14.8A 
 
Table 14.8A Adverse Event Reporting Requirements 
Type of Adverse Event  
Reporting Requirements  
Serious Adverse Events  
Report to Sponsor as soon as possible but no later than 72 
hours upon awareness of the event  
UADE, USADE & SADE  
Report to Sponsor as soon as possible but no later than 72 
hours upon awareness of the event  
Study device deficiency 
associated with an AE  
Report both study device deficiency and AE to Sponsor as 
soon as possible but no later than 72 hours upon awareness 
of the event  
All other Adverse Events  
Routine reporting via eCRF as soon as possible but no later 
than 2 weeks upon awareness of the event  
 
14.9 
Intensity or Severity 
Intensity (or severity) of AEs is defined as follows:  
Table 14.9A: Intensity or Severity Definitions 
Mild 
Events that result in minimal transient impairment of a body 
function or damage to a body structure, and/or does not require 
intervention other than monitoring. 
Moderate 
Events that result in moderate transient impairment of a body 
function or damage to a body structure, or that require 
intervention, such as the administration of medication, to prevent 
permanent impairment of a body function or damage to a body 
structure. 
Severe 
Events that are life threatening and/or result in permanent 
impairment of body functions or damage to body structures, or 
that require significant intervention, such as major surgery, to 
prevent permanent impairment of a body function or damage to a 
body structure. 
Intermittent AEs should be classified according to their greatest severity. A continuous 
AE that changes severity should be reported as a new AE. 

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14.10 
Outcome 
AE outcomes are assessed according to the following classifications: 
Table 14.10A: Adverse Event Outcome Classifications 
Recovered/ Resolved 
without Sequelae 
Subject fully recovered with no observable residual 
effects. 
Recovering/ 
Resolving 
Subject’s condition is improving but residual effects 
remain.  
Recovered/ Resolved 
with Sequelae 
Subject recovered with observable residual effects. 
Not recovered/ 
resolved 
AE is ongoing without improvement in overall 
condition 
Fatal 
Subject died as a result of the adverse event, whether or 
not the AE is related to the device or procedure. Note; 
deaths from any cause occurring on this study are to 
follow expedited reporting. 
Unknown  
AE outcome is unknown (e.g., subject lost to follow-
up) 
14.11 
Causality 
Cause of AEs is defined as follows: 
Table 14.11A: Adverse Event Causality Classifications 
Caused By 
Relation 
Definition of Relation 
Device 
Definitely 
(Causal 
Relationship) 
The event is associated with the investigational device beyond 
reasonable doubt  
Probable 
The relationship with the use of the investigational device 
seems relevant and/or the event cannot reasonably be explained 
by another cause, but additional information may be obtained  
Possibly 
The relationship with the use of the investigational device is 
weak but cannot be ruled out completely  
Unlikely 
The relationship with the use of the investigational device 
seems not relevant and/or the event can be reasonably explained 
by another cause, but additional information may be obtained  
Not related  
Relationship to the investigational device can be excluded  
Study 
Procedure 
Definitely 
(Causal 
Relationship) 
The event is associated with the study procedure beyond 
reasonable doubt  
Probable 
The relationship with the study procedure seems relevant and/or 
the event cannot be reasonably explained by another cause, but 
additional information may be obtained  

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Possibly 
The relationship with the study procedure is weak but cannot be 
ruled out completely  
Unlikely 
The relationship to the study procedure seems not relevant 
and/or the event can be reasonably explained by another cause, 
but additional information may be obtained  
Not related  
Relationship to the procedure can be excluded  
 
14.12 
Documentation 
All AEs must be documented on the appropriate eCRF. All AEs must be monitored until 
they are adequately resolved or stabilized, with follow-up reports submitted to the 
Sponsor or designee as soon as new information becomes available. Additional 
documentation may be requested by the Sponsor or designee, such as a written event 
narrative detailing the clinical course, copies of correspondence with the local IRB/EC, 
hospital records, death certificates, and autopsy reports, if applicable.  Follow-up 
information 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. 
 
14.13 
Safety Oversight 
Safety oversight will be conducted as described in the Safety Management Plan. 
Aggregate safety data will be reviewed regularly throughout the course of the study by 
the study safety lead or designee to promptly identify new issues or trends which may 
have an impact on the conduct of the study and/or subject safety. 
14.14 
Clinical Events Committee (CEC) 
Primary Adverse Events will be submitted to the independent Clinical Events 
Committee (CEC) for review. 
 
15.0 
DEVIATIONS FROM PROTOCOL AND GOOD CLINICAL PRACTICE 
The investigator is responsible for ensuring that the clinical investigation is conducted in 
accordance with the procedures described in this protocol except in medical emergencies. 
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 may require 
reporting to the IRB/EC and/or regulatory authority per IRB/EC/regulatory authority 
requirements.  

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Under emergency circumstances, deviations from the protocol to protect the rights, 
safety and well-being of a subject may proceed. Such deviations shall be documented 
as protocol deviations in the eCRF and reported to the IRB/EC/regulatory authority as 
required. 
In emergencies, prior approval for a protocol deviation will not be required, but the 
Biosense Webster clinical operations personnel should be notified as soon as possible. 
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 IRB/EC requirements, failure to report. IRB/REBs must 
also be notified promptly of significant protocol deviations as they are defined by the 
IRB/REBs.  
 
16.0 
DEVICE ACCOUNTABILITY 
16.1 
Device Accountability 
The Sponsor will keep records of all investigational devices shipped to 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, and disposition information regarding return to the 
Sponsor. The Sponsor will label all devices as “Investigational device” (as applicable for 
the region) in a prominent location. All system installations will be performed by trained 
field services personnel according to internal processes. 
 
The site Device Accountability Log will include the following information: 
• Date of receipt 
• Individual acknowledging receipt 
• Quantity received 
• Packing Slip Verification 
• Catalog number for catheters 
• Serial/lot numbers 
• Expiry Date 
• Dates devices were used 
• Subject IDs for whom devices were used 
• Dates of return (as applicable) 
• Type of disposal (i.e., return to Sponsor for adverse event, complaint, expired, end 
of study, etc.) 
16.2 
Device Returns 
All study devices will be labeled “Investigational Device” and are only to be used for 
subjects enrolled in this clinical study.  

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The allowable equipment for use in the study are those listed in the Study Protocol Section 
11.5.  
 
Devices suspected of deficiency or device associated with a (device related or possibly 
related) adverse event should be returned immediately to BWI and will undergo thorough 
analysis. Device replacement at the site, except for disposable or resterilizable devices 
which are replaced according to the respective IFU’s, will be performed by trained field 
services personnel according to internal processes.  Returned devices must be 
decontaminated per hospital policy and labeled with the following: 
• Subject identification number, or if unused, site number 
• Date of use/event or if applicable, specify “unused” 
• Return type (device deficiency related, AE related, etc.) 
All tracking information must be retained. All study devices must be returned to:  
Complaints Lab 
Biosense Webster, Inc.  
  
17.0 
MONITORING THE STUDY 
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 trained 
Sponsor representative. Monitoring visits may include, but will not be limited to, the 
following: 
• Adherence of the protocol 
• Verification of accuracy of study logs such as the Delegation of Responsibility, etc. 
• Verification that informed consent is obtained for all subjects participating in the 
study in accordance with requirements described in the study protocol 
• Verification of completeness of the Regulatory Binder.  
• Source data verification with the eCRFs.  
• Identification and action to resolve any issues or problems with the study. 
 
Data are to be submitted as soon as possible after collection via e-CRF. Missing or unclear 
data will be corrected as necessary throughout the trial. Biosense Webster may request 
further documentation such as physician and/or cardiac EP lab procedure notes when 
complications or malfunctions are observed and reported. 
 
Monitoring activities will be documented through such means as contact reports and 
follow-up summaries of status and action items. Further details on clinical monitoring are 
provided in the study specific monitoring plan. 
 

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17.1 
Early Termination Monitoring Visit 
If early termination of the study is required, each site will undergo a monitoring visit as 
described in the monitoring plan 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. Subjects will be notified of the termination of the study. Any 
enrolled subjects will continue to be followed per the study protocol requirements until a 
study closeout plan is implemented that outlines alternative follow-up procedures. 
 
18.0 
STATISTICAL ANALYSIS METHODS 
18.1 
Study Design 
Prospective, multicenter, non-randomized, clinical evaluation of the QDOT MICRO™ 
catheter compared to a historical control performance goal.  There are two study arms for 
the treatment; Main Study, QDOT MICRO™ catheter with constant flow rate (8 mL/min) 
during QMODE+ RF application and second (variable flow) study, variable flow rate (4-
15 ml/min) during QMODE+ RF application.  QMODE RF applications will use the same 
flow rates for both studies.   
The tral will enroll 𝟏𝟏𝟏𝟏𝟏𝟏 evaluable subjects in the Main study and 92 subjects in the 
second (variable flow) study for a total of 277 subjects. The analysis for the Main study 
is a standalone analysis and it is not dependent on data from the variable flow study. 
The results from the variable flow study will only be used for additional claims.   
18.2 
Treatment Assignment 
The treatment assigned for both studies is the QDOT MICRO™ catheter.  The 
difference in the 2 studies is the irrigation flow rate during QMODE+ RF application; 
Main study irrigation flow rate is 8 mL/min constant and the second study is variable 
flow of 4-15 mL/min (dependent on catheter tip temperature).   
Enrollment into the two studies will be in a sequential fashion. The first 185 subjects 
will be enrolled in the Main study.  Subjects enrolling after the completion of enrollment 
in the Main study will be enrolled into the second (variable flow) study.  
18.3 
Interval Windows 
Refer to section 13.7 and Table 13.8A.   
18.4 
Primary and Secondary Endpoint(s), and Associated Hypotheses 
 
The primary goal of the trial is to demonstrate safety and effectiveness. For each study to 
be successful, both safety and effectiveness endpoints must be statistically significant 
relative to their respective performance goals.  
 
Study Success 
The study will be considered successful if the primary endpoints are met for main study.  
If the main study is not successful, the data for the second (variable flow) study will not 

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be submitted for labeling. The second (variable flow) study will be considered successful 
if both the primary safety and primary effectiveness performance goals are met.  
 
18.4.1 
Primary Endpoint(s) and Associated Hypotheses 
Acute Safety: The primary safety endpoint is the proportion of subjects with any Primary 
Adverse Event occurring within 7 days of ablation procedure. The PAE rate will be 
compared against an PG of 14%. 
 
The primary safety endpoint will be assessed by testing the hypotheses:  
 
𝐻𝐻0: 𝑝𝑝𝑆𝑆≥0.14  vs.  𝐻𝐻𝐴𝐴: 𝑝𝑝𝑆𝑆< 0.14, 
 
where 𝑝𝑝𝑆𝑆 is the proportion of patients with PAE at early onset (within 7 days of ablation 
procedure). 
 
The primary safety analysis will be performed at the time of the interim analysis for the 
Main study. In the variable flow study, the primary endpoints will be evaluated after full 
12-month follow-up is completed on all subjects.   
 
12-Month Chronic Effectiveness: The primary effectiveness endpoint is the proportion 
of patients that are free from documented atrial arrhythmia (atrial fibrillation (AF), atrial 
tachycardia (AT), or atrial flutter (AFL)) episodes at Month 12 (that is, during the 9-month 
post-blanking period, i.e. Day 91-365).  
 
The primary effectiveness endpoint will be assessed by testing the hypotheses:  
 
𝐻𝐻0: 𝑝𝑝𝐸𝐸≤0.50  vs.  𝐻𝐻𝐴𝐴: 𝑝𝑝𝐸𝐸> 0.50, 
 
where 𝑝𝑝𝐸𝐸 is the proportion of patients that are free from AF, AT, and AFL episodes at 12-
month follow-up (includes a 3-month blanking period).  
 
 
In case early success is achieved, the study will continue to follow up the subjects for the 
full follow-up duration. The primary effectiveness endpoints based on full 12-month 
follow-up data will be descriptively summarized in subjects in the PP population. The 
primary effectiveness endpoint in the variable flow study will be evaluated at the end of 
the study, i.e. completion of 12-month follow-up in all subjects. 
18.4.2 
Secondary Endpoints and Associated Hypotheses 
No formal statistical hypothesis and inferential statistics will be formulated and 
performed for the secondary safety and effectiveness endpoints.  
Refer to Section 8.2.3.1 for secondary safety endpoint, and Section 8.2.3.2 for secondary 
effectiveness endpoints. 

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18.4.3 
Other Endpoints 
No formal statistical hypothesis and inferential statistics will be formulated and 
performed for the additional safety and effectiveness endpoints.  
 
Refer to Section 8.2.3.3 for additional endpoints. 
18.5 
Levels of Significance 
The type I error for the interim and final analyses of the primary endpoints for the main 
study is controlled at one-sided 2.5%. Two-sided 95% confidence intervals will be 
presented around the percentages unless otherwise specified. For the variable flow 
study,  both primary endpoints will be tested at the end of the study at the 2.5% 
significance level, and all confidence intervals will be presented at the 95% confidence 
level unless otherwise specified. 
    
18.6 
Analysis Set  
The treatment for both studies is the QDOT Micro Catheter, there for the analyses sets 
are defined identically for both studies. 
Safety Population (SP) : The Safety population will include all enrolled subjects who 
have the investigational device inserted, regardless if RF energy is delivered. 
 
 
Modified Intent-To-Treat (mITT) Population: the modified Intent-To-Treat (mITT) 
 
population will consist of all enrolled subjects who have the investigational device inserted AND 
 
meet all eligibility criteria.. 
 
Per Protocol (PP) Population: The PP population will include subjects who satisfy 
the following criteria: 
o are enrolled and meet all eligibility criteria 
o have undergone RF ablation 
o are treated with the study catheters, and have been treated for the study-
related arrhythmia  
CT/MRA (CTS) Population:  The CT/MRA set will consist of the first 40 subjects 
who are consecutively enrolled in the main study with 3-month CT/MRA assessment. 
The subject must have readable outcomes at baseline and 3 months.  
18.7 
Sample Size Justification 
The Main study: 
 
The Final analyses for primary safety and effectiveness endpoints will apply Bayesian 
methods and use a beta-binomial model after all subjects complete the 12 months 

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follow-up (assuming early success is not achieved for the primary effectiveness 
endpoint). Non-informative Beta priors will be used for both safety and effectiveness 
endpoints. Trial simulations were performed to estimate the power for the success of 
the safety and effectiveness endpoints. Based on PG of 14% for the primary safety 
endpoint and PG of 50% for the primary effectiveness endpoint, the sample size of 185 
subjects will provide above 80% power to declare success for both endpoints controlling 
the overall type-I error rate at one-sided 2.5% assuming the true PAE rate is 7% and the 
true effectiveness failure-free rate is 65%. It is also assumed that there are 5% and 12% 
dropout rates for the safety and effectiveness endpoints, respectively.   
 
Simulations were also performed to estimate the overall type I error for this study under 
various hypothetical scenarios. The highest type I error rates were reached in the 
following two scenarios, including 1) the true primary safety rate was on the decision 
boundary (i.e. equal to 14%) and the device was assumed to be effective: type I error 
rate was 0.023, and 2) the true primary effectiveness rate was on the decision boundary 
(i.e. equal to 50%) and the devices was assumed to be safe: type I error rate was 0.011. 
As the primary safety or effectiveness moves away from the decision boundary, the 
overall Type-I error decreases. Therefore, considering all scenarios, the overall type I 
error for claiming success for both safety and effectiveness was controlled at 2.5%. 
 
Based on the simulation results, the study is adequately powered to meet the primary 
safety and effectiveness endpoints and Type-I error for the overall trial success is 
controlled at 2.5%.  
 
The Second (variable flow) Study: 
 
The analyses for primary safety and effectiveness endpoints in the variable flow study 
will apply Bayesian methods using a beta-binomial model with data borrowing from the 
Main study using a propensity score-integrated power prior approach. Based on a PG of 
14% for the primary safety endpoint and a PG of 50% for the primary effectiveness 
endpoint, and allowing borrowing up to 91 subjects from QDOT MICRO (IDE # 
G180176) Main study, the sample size of 92 subjects in the variable flow study provides 
close to 80% power at a one-sided signficance level of 2.5% to declare success for both 
the safety and effectiveness endpoints assuming the true PAE rate is 7% and the true 
effectiveness failure-free rate is 65%. Overall power for the variable flow study is 
maintained close to 80% when information from at least 80 subjects in the Main study 
is borrowed. It is also assumed that there are 5% and 12% attrition rates for the safety 
and effectiveness endpoints in the variable flow study, respectively.   
 
 
 
18.8 
Data Monitoring Committee 
Data Monitoring Committee will be formed for this study and will evaluate data from 
both studies. An independent statistician will be responsible for conducting the interim 
analyses and reviewing the results with the designated Data Monitoring Committee 

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(DMC). The DMC charter will document the role and responsibilities of the committee, 
Sponsor and the independent statistician.  
18.9 
Analyses to be Conducted 
18.9.1 
  General Conventions 
In general, descriptive statistics will be provided for all primary and secondary safety and 
effectiveness endpoints and other endpoints as appropriate.  For continuous variables, 
number of subjects/events, mean, standard deviation, median, 25% percentile, 75% 
percentile, minimum, and maximum will be provided.  For categorical variables, frequency 
and percentage will be presented for each category.  
 
Confidence intervals for binary variables, including the primary outcome variables, will be 
computed using the exact binomial distribution.  Categorical variables will be compared 
using Chi-square or Fisher’s exact test.  Continuous variables will be compared using 
ANOVA or Kruskal-Wallis test. 
18.9.2 
  Disposition of Study Subjects 
 Disposition and accountability of the study subjects will be summarized and listed. 
18.9.3 
  Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized and listed. 
18.9.4 
  Analysis of Primary Endpoint Analyses 
The Main study: 
The final analyses for primary safety and effectiveness endpoints in the main study will 
apply Bayesian methods and use a Beta-Binomial model. A vague Beta(1,1) prior will be 
used for both safety and effectiveness endpoints.  
If the primary safety endpoint is met (at the time of the interim analysis) and early success 
is achieved for the primary effectiveness endpoint, then the trial will be declared a success. 
If the safety endpoint is not met the study will be deemed unsuccessful. Under the success 
scenario, the study will continue to follow up the subjects for the full follow-up duration, 
and the primary effectiveness endpoint based on full 12-month follow-up data will then be 
descriptively summarized in subjects in the PP population. If early success is not achieved 
for the primary effectiveness endpoint, then the final effectiveness analysis for the main 
study will be based on complete follow-up data for effectiveness endpoint and will use a 
beta-binomial model. 
Primary safety endpoint will be analyzed in the mITT population and primary effectiveness 
endpoint will be analyzed in the PP population. 
Assuming early effectiveness success is not achieved, the trial will be considered a 
success if BOTH 

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                                                  Pr(𝑝𝑝𝑆𝑆< 0.14|𝑦𝑦, 𝑛𝑛) > 0.975 
AND 
Pr(𝑝𝑝𝐸𝐸> .50| 𝑥𝑥, 𝑛𝑛) > 0.9775. 
These thresholds control the overall Type I error rate for the trial below one-sided 2.5% 
(see appendix C report for additional discussion of Type I error control). 
The Second (variable flow) study: 
The analyses for primary safety and effectiveness endpoints in the variable flow study will 
apply Bayesian methods and use a Beta-Binomial model. A propensity score-integrated 
power prior approach will be used to borrow data from the Main study for establishing 
safety and effectiveness of the variable flow study. The borrowing approach follows the 
method described in Yue, L. et al[59]. The catheter design and the procedure workflow 
with the exception of the flow rate are identical between the Main study and the variable 
flow study. Preclinical and bench testing concluded comparable performance of the 
catheter for constant or variable flow rates. Accordingly, data from up to 91 subjects in the 
Main study will be borrowed for the variable flow study based on similarity in baseline 
characteristics. Details on the borrowing approach are defined in SAP for the variable flow 
study.  
 
The primary safety endpoint will be considered met if                           
Pr(𝑝𝑝𝑆𝑆< 0.14|𝑦𝑦, 𝑛𝑛) > 0.975, 
and the primary effectiveness endpoint will be considered met if                           
Pr(𝑝𝑝𝐸𝐸> .50| 𝑥𝑥, 𝑛𝑛) > 0.975. 
  
18.9.5 
Analyses of Secondary and Additional Endpoints 
Secondary and additional endpoints will be analyzed separately in each study. 
Descriptive statistics will be presented for the secondary safety endpoints in the Safety 
Population.. Descriptive statistics for the secondary effectiveness endpoints will be 
analyzed in the PP population. For the Main Study, descriptive statistics for additional 
endpoints will be analyzed in the Safety Population, particularly, incidence of severe 
PV stenosis will be analyzed in the CMSP population. All of these analyses will be 
performed after the 12 months follow up is complete. No formal statistical hypotheses 
and inferential statistics will be formulated and performed for the secondary and 
additional effectiveness and safety endpoints. Details of analyses methods for secondary 
and additional endpoints will be provided in SAP. 
 

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18.9.6 
  Plans for Interim Analysis 
One (1) interim analysis per arm is planned for early success claim in the Main study. 
The details on the timing of the interim analysis are provided in the simulation report 
and the SAP. For the safety endpoint, the outcome for all patients will be known at the 
time of the interim analysis in each arm, and therefore, the primary safety analyses will 
be performed at the time of the interim analyses. Early success will be declared at the 
interim analysis for the Main study if: 
1. The safety objective has already been met, and 
2. Posterior probability of the effectiveness proportion 𝑝𝑝𝐸𝐸 being greater than 50% is 
greater than 0.9975 
 
 
 
18.9.7 
  Handling of Missing Data 
            Missing data will be queried for reasons and handled on an individual basis.  
 
At the time of early success interim analysis in the Main study (final safety analysis), if a 
subject’s safety follow-up data is missing but a PAE has occurred earlier, then the subject 
will be considered having an event.  If a subject’s follow-up data is missing for the 3-month 
follow-up and the subject has not had a PAE, then that subject will be excluded from the 
early success safety analysis. For each early success interim analysis of the effectiveness 
endpoint, the subjects with incomplete follow-up data will be censored at the time of their 
last follow-up visit, and only their observed partial follow-up time will contribute to 
estimating model parameters.  
 
For the variable flow study, if a subject is missing 3-month follow-up and the subject has 
not had a PAE, the subject will be excluded from the primary safety endpoint analysis. 
Information will not be borrowed from subjects in the Main Study without PAE but were 
missing 3-month follow-up.   
 
For final effectiveness analysis in the Main Study, if a subject has an effectiveness failure 
at any time during the evaluation period, then the subject will be considered having an 
event. Subjects without an effectiveness failure who do not have full 12 months of follow-
up will be excluded from the final effectiveness analysis. 
 
For the primary effectiveness endpoint analysis in the variable flow study, if a subject has 
an effectiveness failure at any time during the evaluation period, then the subject will be 
considered having an event. Subjects without an effectiveness failure who do not have full 
12 months of follow-up will be excluded from the final effectiveness analysis.  No 
information will borrowed from subjects who are failure free in the Main study but do not 
have full 12-month follow-up.       

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18.9.8 
  Sensitivity Analyses 
The Main study:  
The primary safety endpoint will be analyzed in the Safety Population as sensitivity 
analyses. The primary effectiveness endpoint will be analyzed in the Safety Population 
for those subjects who have undergone RF delivery with the study catheter as sensitivity 
analyses. In addition, tipping point analysis[59] will be performed for the primary 
effectiveness endpoint in the PP population and for the primary safety endpoint in the mITT 
population to assess the impact of missing outcomes on study conclusions.  These 
sensitivity analyses will be done after the 12 months follow-up is complete. Additional 
details will be defined in the SAP   for the Main study.  
 
The Variable Flow study: 
Details are defined in the SAP for the variable flow study.   
 
18.9.9 
  Subgroup Analyses 
For the Main study, subgroup analyses for the primary endpoints and acute effectiveness 
endpoints will be performed after the 12 months follow-up is complete, including but not 
limited to: age, gender, ablation mode, individual site, CF and ablation index etc.  PP 
population will be used for primary effectiveness endpoint and Safety population will be 
used for primary safety endpoint for the subgroup analyses. Details of analyses methods 
will be defined in the SAP.  
Ablation mode subgroups:  
• Set 1- QMODE+ alone for PVI, QMODE+ & QMODE for PVI, QMODE alone for 
PVI;  
• Set 2- QMODE+ alone for index procedure, QMODE+ & QMODE for index 
procedure, QMODE alone for index procedure   
18.9.10   Assessment of Site Homogeneity 
For the Main study, there will be up to 30 sites recruiting the approximate 185 subjects in 
US.  
 
Each site should enroll no more than 15% of the total enrollment in each study to minimize 
the possibility that the study results could be highly influenced by a few sites. Sites with 
less than five subjects will be combined according to geographic regions. Using this pre- 
determined criterion, sites with less than five subjects within the same geographic region 
will be combined such that the combined center(s) would have five or more subjects and 
no more than 5 sites combined. 
 
Chi-square test will be used to examine the homogeneity across sites for the primary 
effectiveness and safety endpoints using data from the patients in the Main study. A p-
value less than 0.15 will be considered statistically significant for an assessment of 

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homogeneity across sites. A non-significant result will support pooling of sites for the 
primary analyses. 
 
If the sites are not poolable, logistic regression models treating site as a random effect will 
be fit to examine the impact of site heterogeneity on the primary endpoints. The claim of 
trial success will be based upon the totality of the data. 
19.0 
ETHICS AND PROTECTION OF HUMAN SUBJECTS 
19.1 
Ethics Review 
Study materials including informed consent must be reviewed and approved by an 
appropriately-constituted IRB/IEC/REB before enrollment of subjects. Biosense 
Webster and the IRB must approve in writing any changes to the protocol. 
Proof of IRB/IEC/REB review and approval must be obtained prior to subject 
enrollment. Investigators are responsible for submitting and obtaining initial and 
continuing review (per local regulations) of the study by their IRB/IEC/REB. 
19.2 
Patient Informed Consent 
Biosense Webster and the reviewing IRB/IEC/REB must approve any modifications to 
the ICF or PI/ICF.  The ICF may be translated as appropriate. Certification of accurate 
translation will be required.  
Informed consent is mandatory and must be obtained from all subjects prior to their 
participation in this study. Copies of all signed consents must be retained in the records 
of the study, and an unsigned sample copy of the approved ICF must also be in the study 
file. Subjects must each receive a copy of the ICF. 
19.3 
Confidentiality 
All information and data sent to Biosense Webster concerning subjects or their 
participation in this study will be considered confidential. Only authorized Biosense 
Webster personnel or representatives, or representatives of Health Authorities (HA) or 
Regulatory Authorities (RA) acting in their official capacities will have access to these 
confidential files. No data transmitted to Sponsor for evaluation and reporting will 
contain identifiable references to individual subjects. 
19.4 
Subject Confidentiality/Record 
All representatives of the Sponsor have undergone training for Privacy regulations and 
appropriate conduct for their compliance. For the duration of this study, all 
representatives of the Sponsor will comply with all privacy regulations regarding 
contact with subjects, their medical record information, copying of information, 
protection of the subject identities, and other aspects.  Authorization for limited access 
to Protected Health Information by Sponsor personnel will be obtained as part of subject 
informed consent. 
Site personnel should also be attentive to privacy considerations and should not transmit 
PHI outside of PI control (e.g., via .pdf or FAX) without redaction of patient identifiers.   

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Privacy considerations such as above will also be covered in protocol training for both 
Sponsor representatives and study site personnel.  
20.0 
DATA MANAGEMENT 
The Sponsor will be responsible for all data management activities. These activities 
include development of a database, utilizing validated database software, into which all 
study data will be entered by the clinical sites. The Sponsor will be responsible for 
ensuring the overall integrity of the database. 
20.1 
Electronic Case Report Forms (CRFs) 
Electronic CRFs will be used to collect all subject data during the study.  
Electronic CRFs (eCRFs) have been developed to capture the information outlined in 
this Study Protocol. Data on these eCRFs will be monitored, corrected if necessary, and 
entered into a validated database. All changes made to the data will be tracked in the 
electronic audit trail, recording the current value, previous value, reason for change, 
date timestamp of data entry/change, and the name of the person who changed the data. 
The investigator will electronically sign all subject eCRFs as verification that the data 
have been reviewed and correctly reflects source documentation. Data from these 
eCRFs will be used to provide analysis of this study.  
20.2 
Data Reporting 
The investigator, or a designated individual, is responsible for recording data from the 
trial on the eCRFs supplied by Biosense Webster. The investigator or a delegated 
individual is required to electronically sign eCRFs on the appropriate pages to verify 
that he/she has reviewed and attests to the correctness of the recorded data. Completed 
eCRFs will be reviewed and monitored remotely and at the research site by Biosense 
Webster personnel or designees throughout the trial. To this end, the investigator and 
institution must permit inspection of trial files including original (source) records and 
subject eCRFs by sponsor representatives and responsible government agencies. 
Table 20.2A. Responsibilities for Preparing and Submitting Reports 
Type of Report  
Prepared 
by 
Investigator For  
Time of Notification  
Subject 
withdrawal  
Biosense Webster  
Should report within 5 working days  
Withdrawal 
of 
IRB/EC approval  
Biosense Webster  
Should report within 5 working days  
Final report  
Biosense 
Webster, 
IRB/EC  
Will prepare a final report separately 
for the main study and the variable 
flow 
study 
for 
the 
clinical 
investigation as required per national 
regulations.  

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Informed consent 
not obtained from 
subject  
Biosense 
Webster, 
IRB/EC (per IRB/EC 
requirements)  
Should report within 5 working days  
 
20.3 
Data Review 
Biosense Webster will track the amount of missing data and contact sites as appropriate 
to instruct them on steps to minimize missing data and remain compliant with protocol 
required assessments. Missing or unclear data points will be queried as necessary 
throughout the trial. Biosense Webster may request further documentation such as 
physician and/or cardiac EP lab procedure notes when complications or device 
deficiencies are observed and reported. Biosense Webster will be responsible for 
auditing the database and confirming the overall integrity of the data. 
20.4 
Procedural Data 
It is the responsibility of the investigator to provide timely completion of CRFs to the 
sponsor. 
20.5 
Source Documentation 
Data entered into the eCRFs may be taken from source documentation, such as hospital 
procedure reports, admission and discharge summaries, and other hospital or physician 
office/clinic documents. If no standard hospital or office document exists to capture 
some of the information that may be unique to this study, a worksheet may be developed 
to record this information. Data collection instruments should clearly identify the 
individual collecting the data and the date of collection. The instrument of original 
capture of all study data will serve as the source document for future verification of for 
those data parameters. Privacy regulations will be observed during the use of these 
source documents during monitoring. 
21.0 
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. 

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22.0 
ADMINISTRATIVE RESPONSIBILITIES 
22.1 
Records and Reports 
22.1.1 
Records 
Records to be maintained by the investigator include: 
• Study protocol and all amendments with signature pages 
• Signed clinical study agreement and Statement of Investigator 
• IRB/IEC/REB approval letter, including approved ICF document 
• Evidence of IRB/IEC/REB compliance 
• Other significant IRB/IEC/REB correspondence  
• Significant sponsor correspondence relating to the study 
• CVs for all investigator(s) 
• Financial Disclosure for key study staff 
• Records of protocol and supporting training 
• Site personnel delegation of authority/responsibility 
• Clinical Monitor/Site Visit sign-in log 
• Device accountability log 
• Reports (e.g. annual reports, final reports from investigator and Sponsor) 
The following records must be maintained for each subject enrolled in the study: 
• Signed Patient ICF 
• All completed electronic CRFs and supporting source documentation 
• Supporting documentation of any AEs and/or death  
The investigator must retain copies of procedure reports, procedure nursing notes and 
the results of any interventional procedures that occur while the subject is enrolled in 
the study. Biosense Webster reserves the right to secure data clarification and additional 
medical documentation on subjects enrolled in this study. 
22.1.2 
Record Retention 
Records and reports of the study will remain on file at sites for a minimum of two (2) 
years after its completion/termination. Records for U.S. sites must be maintained in 
accordance with 21 CFR 812.140 [d], and for OUS sites, according to local 
requirements.  
If the principal investigator plans to leave the study site, he/she is responsible for 
identification of another individual at site who will assume the obligation for file 

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maintenance and management of any continuing subjects. Biosense Webster and 
pertinent HA/RA, per its requirements, should be notified of this change.  
Records and reports may be discarded upon notification by Biosense Webster to the 
study site. Site personnel should contact Biosense Webster prior to destruction of any 
study-related records and reports to ensure appropriate record retention. 
22.1.3 
Investigator’s Final Report 
Upon completion or termination of the Biosense Webster study, the principal 
investigator must submit a final written report to the approving Investigational Review 
Board/Ethics Committee (as required by the IRB/IEC/REB) and provide a copy to 
Biosense Webster. The report should contain the information required by the 
IRB/IEC/REB and be submitted in the time frame required by the IRB/IEC/REB. 
23.0 
TERMINATION OF THE STUDY 
The study may be suspended or terminated early at the discretion of the Sponsor, for 
reasons such as incidence of unanticipated serious adverse device effects that may pose 
a risk to other subjects. In any early termination, already enrolled subjects will continue 
to be followed per the study protocol requirements.  
Sponsor may also terminate a site prior to completion if it believes the site is no longer 
capable of participating (e.g., cannot fulfill subject enrollment or protocol compliance 
goals, site suspension by IRB/REB).  
At termination of the investigation, each active site will undergo closeout monitoring to 
conclude any outstanding issues, resolve all data discrepancies and make sure any 
outstanding eCRFs are completed, discuss responsibilities with the Principal 
Investigator, and discuss any other items relevant to the conclusion of the study. The 
termination process will be documented by a written report. 
24.0 
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. 
25.0 
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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26.0 
REFERENCES:  
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January, C.T., et al., 2014 AHA/ACC/HRS guideline for the management of patients with atrial 
fibrillation: a report of the American College of Cardiology/American Heart Association Task 
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e1-76. 
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Cain, M.E., Atrial fibrillation--rhythm or rate control. N Engl J Med, 2002. 347(23): p. 1822-3. 
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Fuster, V., et al., ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial 
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Calkins, H., et al., 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on 
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Jazayeri, M.R., et al., Selective transcatheter ablation of the fast and slow pathways using 
radiofrequency energy in patients with atrioventricular nodal reentrant tachycardia. Circulation, 
1992. 85(4): p. 1318-28. 
6. 
Pappone, C., et al., A randomized trial of circumferential pulmonary vein ablation versus 
antiarrhythmic drug therapy in paroxysmal atrial fibrillation: the APAF Study. J Am Coll Cardiol, 
2006. 48(11): p. 2340-7. 
7. 
Wilber, D.J., et al., Comparison of antiarrhythmic drug therapy and radiofrequency catheter 
ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA, 
2010. 303(4): p. 333-40. 
8. 
Natale, A., et al., Paroxysmal AF catheter ablation with a contact force sensing catheter: results 
of the prospective, multicenter SMART-AF trial. J Am Coll Cardiol, 2014. 64(7): p. 647-56. 
9. 
Ullah, W., et al., Randomized trial comparing pulmonary vein isolation using the SmartTouch 
catheter with or without real-time contact force data. Heart Rhythm, 2016. 13(9): p. 1761-7. 
10. 
Kautzner, J., et al., EFFICAS II: optimization of catheter contact force improves outcome of 
pulmonary vein isolation for paroxysmal atrial fibrillation. Europace, 2015. 17(8): p. 1229-35. 
11. 
Andrade, J.G., et al., Pulmonary vein isolation using "contact force" ablation: the effect on 
dormant conduction and long-term freedom from recurrent atrial fibrillation--a prospective 
study. Heart Rhythm, 2014. 11(11): p. 1919-24. 
12. 
Anter, E., et al., Acute pulmonary vein reconnection is a predictor of atrial fibrillation recurrence 
following pulmonary vein isolation. J Interv Card Electrophysiol, 2014. 39(3): p. 225-32. 
13. 
Haines, D.E., The biophysics of radiofrequency catheter ablation in the heart: the importance of 
temperature monitoring. Pacing Clin Electrophysiol, 1993. 16(3 Pt 2): p. 586-91. 
14. 
Bhaskaran, A., et al., Five seconds of 50-60 W radio frequency atrial ablations were transmural 
and safe: an in vitro mechanistic assessment and force-controlled in vivo validation. Europace, 
2017. 19(5): p. 874-880. 
15. 
Kuck, K.H., et al., A novel radiofrequency ablation catheter using contact force sensing: Toccata 
study. Heart Rhythm, 2012. 9(1): p. 18-23. 
16. 
Ikeda, A.N., H; Sharma, T;  Govari, A; Datta, K; Joshi, H; Lifshitz, A; Wittkampf, F and Jackman, W, 
High Power - Short Radiofrequency Applications Rapidly Produce Shallow Lesions Of Equal 
Diameter Without Increasing Risk Of Thrombus Or Steam Pop, in Heart Rhythm Society. 2018: 
Boston, MA. 
17. 
Rozen, G., et al., Safety and efficacy of delivering high-power short-duration radiofrequency 
ablation lesions utilizing a novel temperature sensing technology. Europace, 2018. 

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18. 
Barkagan, M., et al., High-power and short-duration ablation for pulmonary vein isolation: 
Safety, efficacy, and long-term durability. J Cardiovasc Electrophysiol, 2018. 
19. 
leshem, E., Zilberman I, Tschabrunn C, et al, High-Power and Short-Duration Ablation for 
Pulmonary Vein Isolation Biophysical Characterization. JACC: Clinical Electrophysiology, 2018. In 
Press. 
20. 
Sandhu, R.K., et al., The epidemiology of atrial fibrillation in adults depends on locale of 
diagnosis. Am Heart J, 2011. 161(5): p. 986-992 e1. 
21. 
Lee, G., et al., Low risk of major complications associated with pulmonary vein antral isolation 
for atrial fibrillation: results of 500 consecutive ablation procedures in patients with low 
prevalence of structural heart disease from a single center. J Cardiovasc Electrophysiol, 2011. 
22(2): p. 163-8. 
22. 
Voskoboinik, A., et al., Low Rates of Major Complications for Radiofrequency Ablation of Atrial 
Fibrillation Maintained Over 14 Years: A Single Centre Experience of 2750 Consecutive Cases. 
Heart Lung Circ, 2018. 
23. 
Cappato, R., et al., Updated worldwide survey on the methods, efficacy, and safety of catheter 
ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol, 2010. 3(1): p. 32-8. 
24. 
Bohnen, M., et al., Incidence and predictors of major complications from contemporary catheter 
ablation to treat cardiac arrhythmias. Heart Rhythm, 2011. 8(11): p. 1661-6. 
25. 
Michowitz, Y., et al., Effects of sex on the incidence of cardiac tamponade after catheter ablation 
of atrial fibrillation: results from a worldwide survey in 34 943 atrial fibrillation ablation 
procedures. Circ Arrhythm Electrophysiol, 2014. 7(2): p. 274-80. 
26. 
Muthalaly, R.G., et al., Temporal trends in safety and complication rates of catheter ablation for 
atrial fibrillation. J Cardiovasc Electrophysiol, 2018. 
27. 
Teunissen C, V.B., Hassink, R, et.al, Incidence of Pulmonary Vein Stenosis After Radiofrequency 
Catheter Ablation of Atrial Fibrillation. JACC: Clinical Electrophysiology, 2017. 3(6): p. 589-598. 
28. 
Ha, F.J., et al., Prevalence and prevention of oesophageal injury during atrial fibrillation ablation: 
a systematic review and meta-analysis. Europace, 2018. 
29. 
Knopp, H., et al., Incidental and ablation-induced findings during upper gastrointestinal 
endoscopy in patients after ablation of atrial fibrillation: a retrospective study of 425 patients. 
Heart Rhythm, 2014. 11(4): p. 574-8. 
30. 
Kapur, S., et al., Esophageal Injury and Atrioesophageal Fistula Caused by Ablation for Atrial 
Fibrillation. Circulation, 2017. 136(13): p. 1247-1255. 
31. 
Nair, K.K., et al., Atrioesophageal Fistula: A Review. J Atr Fibrillation, 2015. 8(3): p. 1331. 
32. 
Scanavacca, M.I., How to prevent, recognize and manage complications of AF ablation? Rev Port 
Cardiol, 2017. 36 Suppl 1: p. 43-49. 
33. 
Yong Ji, S., et al., Phrenic nerve injury: An underrecognized and potentially preventable 
complication of pulmonary vein isolation using a wide-area circumferential ablation approach. J 
Cardiovasc Electrophysiol, 2013. 24(10): p. 1086-91. 
34. 
Haegeli, L.M. and H. Calkins, Catheter ablation of atrial fibrillation: an update. Eur Heart J, 2014. 
35(36): p. 2454-9. 
35. 
Cappato, R., et al., Prevalence and causes of fatal outcome in catheter ablation of atrial 
fibrillation. J Am Coll Cardiol, 2009. 53(19): p. 1798-803. 
36. 
Funayama, N., et al., Acute right coronary artery occlusion after radiofrequency catheter 
ablation of cavotricuspid isthmus: Vascular response assessed by optical frequency domain 
imaging. HeartRhythm Case Rep, 2017. 3(10): p. 496-498. 
37. 
Rillig, A., et al., Catheter ablation within the sinus of Valsalva--a safe and effective approach for 
treatment of atrial and ventricular tachycardias. Heart Rhythm, 2008. 5(9): p. 1265-72. 

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38. 
Fujii, S., J.R. Zhou, and A. Dhir, Anesthesia for Cardiac Ablation. J Cardiothorac Vasc Anesth, 
2017. 
39. 
Liu, Y., et al., Incidence and outcomes of cerebrovascular events complicating catheter ablation 
for atrial fibrillation. Europace, 2016. 18(9): p. 1357-65. 
40. 
Housley, B.C., et al., Acute Pulmonary Hemorrhage Following Radiofrequency Ablation of Atrial 
Fibrillation. J Cardiothorac Vasc Anesth, 2017. 31(4): p. 1397-1400. 
41. 
Bessiere, F. and P. Chevalier, Pulmonary vein hematoma after atrial fibrillation cryoablation: a 
new complication. Heart Rhythm, 2013. 10(9): p. 1359. 
42. 
Desimone, C.V., et al., Catheter ablation related mitral valve injury: the importance of early 
recognition and rescue mitral valve repair. J Cardiovasc Electrophysiol, 2014. 25(9): p. 971-975. 
43. 
Scheinman, M.M. and S. Huang, The 1998 NASPE prospective catheter ablation registry. Pacing 
Clin Electrophysiol, 2000. 23(6): p. 1020-8. 
44. 
Lin, A.C. and D. Wilber, Complications associated with radiofrequency catheter ablation, in 
Radiofrequency Catheter Ablation of Cardiac Arrhythmias: Basic Concepts and Clinical 
Applications, S.K.S. Huang and D.J. Wilber, Editors. 2000, Futura Publishing Company, Inc.: 
Grouponk, NY. p. 737-746. 
45. 
Kovoor, P., et al., Risk to patients from radiation associated with radiofrequency ablation for 
supraventricular tachycardia. Circulation, 1998. 98(15): p. 1534-40. 
46. 
Nahass, G.T., Fluoroscopy and the skin: implications for radiofrequency catheter ablation. Am J 
Cardiol, 1995. 76(3): p. 174-6. 
47. 
Calkins, H., et al., Radiation exposure during radiofrequency catheter ablation of accessory 
atrioventricular connections. Circulation, 1991. 84(6): p. 2376-82. 
48. 
Cox, B., M.E. Durieux, and M.A. Marcus, Toxicity of local anaesthetics. Best Pract Res Clin 
Anaesthesiol, 2003. 17(1): p. 111-36. 
49. 
Mertes, P.M. and M.C. Laxenaire, Allergic reactions occurring during anaesthesia. Eur J 
Anaesthesiol, 2002. 19(4): p. 240-62. 
50. 
Morcos, S.K., et al., Prevention of generalized reactions to contrast media: a consensus report 
and guidelines. Eur Radiol, 2001. 11(9): p. 1720-8. 
51. 
Gruchalla, R.S., 10. Drug allergy. J Allergy Clin Immunol, 2003. 111(2 Suppl): p. S548-59. 
52. 
Bick, R.L. and E.P. Frenkel, Clinical aspects of heparin-induced thrombocytopenia and thrombosis 
and other side effects of heparin therapy. Clin Appl Thromb Hemost, 1999. 5 Suppl 1: p. S7-15. 
53. 
Kirchhof, P., et al., 2016 ESC Guidelines for the management of atrial fibrillation developed in 
collaboration with EACTS. Eur Heart J, 2016. 37(38): p. 2893-2962. 
54. 
Liu E, S.E., Belden W, Thosani AJ, High power short duration radiofrequency catheter ablation for 
atrial fibrillation: Safety and acute procedural outcomes.  , in HRS, H.R. Society, Editor. 2017. 
55. 
Holmes, D.R., Jr., K.H. Monahan, and D. Packer, Pulmonary vein stenosis complicating ablation 
for atrial fibrillation: clinical spectrum and interventional considerations. JACC Cardiovasc Interv, 
2009. 2(4): p. 267-76. 
56. 
Oh Jk, S.J., Tajik AJ, The Echo Manual. 2006: Lippincott Williams & Wilkins. 
57. 
Milman, A., et al., Gender Differences in Patients with Brugada Syndrome and Arrhythmic Events: 
Data from a Survey on Arrhythmic Events in 678 Patients. Heart Rhythm, 2018. 
58. 
Leon, M.B., et al., Standardized endpoint definitions for Transcatheter Aortic Valve Implantation 
clinical trials: a consensus report from the Valve Academic Research Consortium. J Am Coll 
Cardiol, 2011. 57(3): p. 253-69. 
59. 
Yan, X., S. Lee, and N. Li, Missing data handling methods in medical device clinical trials. J 
Biopharm Stat, 2009. 19(6): p. 1085-98. 

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27.0 
APPENDIX A: STUDY DEFINITIONS  
Term 
Definition 
Adverse Event (AE) 
Any unfavorable and unintended sign, medical occurrence, disease or 
injury (including abnormal laboratory findings) in subjects, users or 
other persons temporally associated with the use of a medicinal 
product or device whether or not related to the sponsor’s product. 
This definition includes events related to the medical device and/or the 
comparator, and events related to the procedure in which the device 
was used. 
Adverse Device 
Effects (ADE’s) 
Adverse events related to the use of the medical device. This definition 
includes adverse events resulting from insufficient or inadequate 
instructions for use deployment, implantation, installation, or 
operation, or any malfunction of the medical device. This definition 
includes any event resulting from use errors or from intentional misuse 
of the investigation medical device. 
AF/AT/AFL Episode 
An episode of AF/AT/AFL ≥ 30 seconds in duration.  
AF Episode 
An atrial fibrillation episode is defined as AF which is documented by 
ECG monitoring and has a duration of at least 30 seconds, or if less 
than 30 seconds, is present continuously throughout the ECG 
monitoring tracing. The presence of subsequent episodes of AF 
requires that sinus rhythm be documented by ECG monitoring 
between AF episodes 
Anticipated AE 
An effect which by its nature, incidence, severity or outcome has been 
identified as possible complications associated with the medical 
device and/ or intervention procedure.  
Atypical Flutter 
Macro-reentrant circuits within the atria where activation rotates 
around large obstacles that does not meet the criteria for Typical 
Flutter.  

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Term 
Definition 
Bleeding 
Complications (ISTH 
definition): 
Major (ISTH definition):  
Fatal bleeding AND/OR symptomatic bleeding in a critical area or 
organ, such as intracranial, intraspinal, intraocular, retroperitoneal, 
intraarticular, pericardial, or intramuscular with compartment 
syndrome AND/OR bleeding causing a fall in hemoglobin level of 2 
g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more 
units of blood. 
Clinically relevant nonmajor bleed (ISTH definition):  
An acute or subacute clinically overt bleed that does not meet the 
criteria for a major bleed but prompts a clinical response such that it 
leads to one of the following: hospital admission for bleeding; 
physician guided medical or surgical treatment for bleeding; change in 
antithrombotic therapy (including interruption or discontinuation). 
Minor bleeding (ISTH definition): 
All nonmajor bleeds. Minor bleeds are further divided into clinically 
relevant and not. 
Catheter Insertion 
Defined as the QDOT MICRO™ catheter breaching the sheath and 
entering the bloodstream.   
Device Deficiency 
Inadequacy of a medical device related to its identity, quality, 
durability, reliability, safety or performance, such as malfunction 
(failure of a medical device to perform in accordance with its intended 
purpose when used in accordance with the instructions for use or 
protocol), misuse or use error and inadequate labeling.  
Documented 
AF/AT/AFL episode 
An AF/AT/AFL episode documented by an electrocardiographic 
monitoring tool. This may include ILR, ECG, TTM, Holter monitor, 
or telemetry strip.  
Reporting of a symptomatic episode by a patient or in a referral letter 
is not considered a documented AF episode. 
Minor Pericarditis 
Pericarditis will be considered ‘minor if is treated using only 
analgesics and does not extend hospitalization by more than 48 
hours.  
Paroxysmal AF  
Paroxysmal AF is defined as recurrent AF (≥ 2 episodes) that 
terminates spontaneously within 7 days. Episodes of AF of ≤ 48 hours 
duration that are terminated with electrical or pharmacologic 
cardioversion should also be classified as paroxysmal AF episodes. 
Permanent AF  
Not appropriate in the context of patients undergoing catheter ablation 
of AF; refers to a group of patients where a decision has been made 
not to pursue restoration of sinus rhythm by any means, including 
catheter or surgical ablation. 
Persistent AF (PsAF) 
Persistent AF is defined as continuous AF that is sustained beyond 7 
days and less than 1 year.  

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Term 
Definition 
Serious adverse event 
(SAE) 
1. Any adverse event that: 
• Led to a death 
• Led to a serious deterioration in health that either: 
o Resulted in a life-threatening illness or injury, or 
o Resulted in a permanent impairment of a body structure 
or a body function, or 
o Required in-patient hospitalization or prolongation of 
existing hospitalization, or 
o Resulted in medical or surgical intervention to prevent 
life threatening illness or injury or permanent 
impairment to a body structure or a body function 
• Led to fetal distress, fetal death or a congenital abnormality or 
birth defect 
2. Any Device Deficiency that could have led to an SAE  
A planned hospitalization for pre-existing condition, or a procedure 
required by the protocol, without a serious deterioration in health, is 
not considered to be a serious adverse event.  
Medical and scientific judgment should be exercised in deciding 
whether expedited reporting is appropriate in other situations, such 
as important medical events that may not be immediately life-
threatening or result in death or hospitalization but may jeopardize 
the subject or may require intervention to prevent one of the 
outcomes listed in the definition above. 
Serious Adverse 
Device Effects 
(SADE’s) 
Adverse device effects that has resulted in any of the consequences 
characteristic of a serious adverse event. 
Symptomatic 
AF/AT/AFL Episode 
Symptom(s) which is/are exhibited by the subject which made them 
seek medical attention and are concurrent with a documented episode 
of AF/AT/AFL by either ECG, TTM, Holter monitor, or telemetry 
recording. Symptoms may include but are not limited to: palpitations, 
irregular pulse (e.g., rapid, racing, pounding, fluttering, bradycardia), 
dizziness, weakness, chest discomfort, and breathlessness. 
Typical Flutter 
Atrial flutter is caused by a reentrant rhythm in either the right or left 
atrium. Typically initiated by a premature electrical impulse arising in 
the atria, atrial flutter is propagated due to differences in refractory 
periods of atrial tissue. This creates electrical activity that moves in a 
localized self-perpetuating loop. For each cycle around the loop, there 
results an electric impulse that propagates through the atria. 

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Term 
Definition 
Unanticipated 
Serious Adverse 
Device Effect 
(USADE) 
Serious adverse device effect which by its nature, incidence, severity 
or outcome has not been identified in the current version of the risk 
analysis report. 
NOTE: Anticipated SADE: an effect which by its nature, incidence, 
severity or outcome has been previously identified in the risk analysis 
report 
Ventricular 
Tachycardia (VT) 
Ventricular tachycardia: a tachycardia (rate > 100/min) with three or 
more consecutive beats that originates from the ventricles independent 
of atrial or AV nodal conduction. Continuous VT for > 30 s or that 
requires an intervention for termination (such as cardioversion). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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28.0 
APPENDIX B: QMODE 
 
Introduction QMODE Temperature Control Mode 
 
The QDOT MICRO™ catheter with QMODE introduces temperature controlled ablation 
to irrigated catheters.  Temperature controlled ablation allows RF power to be delivered 
safely without tip char or steam pops.  The QMODE temperature control mode utilizes the 
temperature sensing capabilities of the QDOT MICRO™ catheter to optimize power 
delivery ensuring efficient ablation.  When using the QMODE temperature control mode 
the irrigation rate will vary based on temperature to both cool the catheter tip adequately 
and retain temperature sensitivity, ensuring the safety profile. 
 
The QMODE temperature control is designed to maximize RF lesion efficiency by using 
temperature feedback from the tip to adjust power and irrigation flow.  The QMODE 
temperature control mode monitors the temperature rate of change in relationship to the set 
target temperature during RF application.  To maintain a desired power levels at a safe 
temperature, the algorithm applies an accurate correction to control the irrigation flow rate. 
 
• For maximum power settings, 35W or lower: The flow rate starts at low flow (4ml, 
lowest setting) to increase temperature sensitivity.  If the set power is titrated down 
because the temperature exceeds the set target temperature (50°C), the generator 
changes the pump flow rate from low (4mL) to high flow (15 mL) to maintain the 
set maximum power.  Once the temperature decreases the pump irrigation flow rate 
is returned to low (4mL). 
 
• For maximum power settings, greater than 35W: The flow rate starts at high flow 
(15ml) for safety. If the temperature drops below the set maximum low flow 
temperature (45°C), the generator changes the pump from high (15 mL) to low 
(4mL) flow. The change to low flow allows the temperature to rise above the set 
maximum low flow temperature and closer to the target temperature. 
 
28.1 
Use of the QDOT MICRO™ QMODE algorithm 
In the event of spontaneous or induced AF and/or atrial flutter, the placement of additional 
RF lesions outside of the PV ostia in Qmode is at the discretion of the investigator and 
includes the following: 
• Linear lesions between both superior PVs (roof line), the mitral annulus and the left 
inferior PV (mitral isthmus line) or between the LA roof and mitral annulus 
(anterior line) 
• Ablation for any non-PV foci in the LA and/or RA, including isolation of the 
superior vena cava (SVC) 
• Linear lesions in the cavo-tricuspid isthmus 
 
If linear lesions are placed, it is recommended that complete conduction block across the 
ablation line be demonstrated by mapping and/or pacing maneuvers. 

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28.2 
Recommended ablation parameters  
QMODE temperature control mode will be used for PVI once the investigator deems 
QMODE+ unable to complete PVI.  Additionally, QMODE temperature control mode will 
be used for all RF applications outside the PV ostia during the study ablation procedure 
(refer to Sections 13.3.4 and 13.3.5).   
 
The QDOT MICRO™ catheter with QMODE temperature control mode is designed to 
maximize RF lesion efficiency by using temperature feedback from the tip to adjust power 
and irrigation flow.  For power levels from 1-50W, the generator changes the pump 
irrigation flow rate from low (4 mL/min) to high flow (15 mL/min) or from high to low 
flow to reach and maintain the set maximum power without exceeding the set target 
temperature (50°C). The QMODE temperature control mode minimizes the irrigation rate 
thus increasing temperature sensitivity at the catheter tip. 
 
Table 28.2A: QMODE Ablation parameters  
Power 
Target Temp* 
Cut-off Temp 
Nominal 
Irrigation 
Flow 
rate 
Range 
Recommended Range 
Recommended 
25-35 W 
45-50ºC 
50ºC 
50-55ºC 
55ºC 
4mL** 
36-50W*** 
45-50ºC 
50ºC 
50-55ºC 
55ºC 
15mL** 
* 
Temperatures displayed on the RF generator do not represent tissue temperature or electrode tissue interface 
temperature. 
** A minimum flow rate of 2mL during mapping is recommended. 
*** RF applications at 36-50W should not exceed 30 sec. 
 
Note: The default parameters for QMODE temperature control are user-adjustable, in case the 
investigator deems appropriate.  
 
Recommendation for CoolFlow® Irrigation Pump Setting and RF Power-delivery 
The CoolFlow® Irrigation Pump will deliver a continuous infusion of 2 ml/min of room 
temperature heparinized saline (1 u heparin/1 ml saline) when not delivering RF energy. 
Increase the irrigation to high flow rate starting up to minimal 2 seconds before the onset 
of RF energy delivery and maintaining this higher flow rate up to 5 seconds after 
termination of the energy application. 
 
QMODE Contact Force (CF) Settings 
When using the study catheter in QMODE the recommended Contact Force working range 
should be between 5 and 30g.  
 
Visitag Settings (recommendation) 
It is recommended that ACCURESP™ be enabled; Respiratory Gating Mandatory (unless 
using Jet Ventilation) 

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• Stability Settings: 
o Range: 3 mm 
o Time: 3 seconds 
• Filter (FOT) Settings: 
o If an FOT filter is desired, the percentage of time of the chosen gram force is 
recommended to be set on 50% 
 
Recommended Temperature Range and RF Power Settings 
• QMODE Temperature settings 
o Below or equal to 35 W 
 Temperature Cut-Off:  55°C 
 Target Temperature: 50°C 
o Above 35W 
 Temperature Cut-Off:  55°C 
 Target Temperature: 50°C (prevents overheating) 
 
Note: The default parameters are user-adjustable, in case the investigator deems 
appropriate.  
 
QMODE Ablation Workflow: 
• If the temperature increases rapidly, stop RF application immediately 
• RF power range of 15-50 Watts (W) is recommended for atrial ablation 
• At anatomical locations, not on the LA posterior wall or CS: 
o Maximum allowed power should not exceed 50 W 
o Duration of ablation should not exceed 60 seconds of continuous ablation at a 
given location 
• Move/drag the catheter to a new location when clinically effective ablation is 
achieved (EGM reduction and/or impedance drop). 
• Duration of ablation as well as the decision to interrupt RF power delivery at any 
time during ablation SHOULD be guided by: 
o Clinical Investigator judgment and the monitoring of ablation effectiveness 
parameters commonly used such as EGM reduction and/or impedance changes.  

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Precautions while ablating on the Posterior wall and Coronary Sinus: 
• LA posterior wall and close to the esophagus:  
o Start ablation using standard workflow for posterior wall.  
o Move/drag the catheter to a new location if clinically effective ablation is 
achieved within 20 seconds (EGM reduction and/or impedance drop). 
o Maximum power used SHOULD NOT exceed 35 W. 
o Duration of ablation as well as the decision to interrupt RF power delivery at 
any time during ablation SHOULD be guided by: 
 Clinical Investigator judgment and monitoring of ablation effectiveness 
parameters commonly used such as EGM reduction and/or impedance 
changes 
 Esophageal temperature changes should be monitored by an endo-luminal 
esophageal probe or method used to move esophagus as needed (refer to) 
 Duration of ablation should not exceed 30 seconds on posterior wall. 
 
• Ablation within the Coronary Sinus (CS):  
o A maximum of 35 W will be used if ablation is required in the CS  
o Duration of ablation is limited to 20 seconds per ablation location in the CS 
 
 
 

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29.0 
APPENDIX C:  JUSTIFICATION OF SAFETY PERFORMANCE GOAL 
In a recent BWI study (Heliostar), the FDA had recommended using a meta-analysis for 
combining safety rates from relevant studies for deriving a performance goal. For this 
recent study, the agency had agreed to setting the performance goal by allowing a 50% 
increase in risk from the upper bound of the 95% confidence interval for the combined 
safety rate.  
Data from recent clinical trials for devices similar to the device in the current study were 
reviewed as a first step to deriving the performance goal for the safety endpoint. The 
following trials were reviewed: TOCCASTAR, ZERO-AF, and SMART-AF. A meta-
analysis approach was taken to estimate the average composite endpoint rate. Since the 
definition of the safety composite varies across the studies reviewed, individual 
complication rates were reviewed and utilized to derive composite rates from each trial 
that are more closely aligned with the proposed endpoint definition. Table 1 summarizes 
the event rates as observed in each of the trials.  
 
Table 1: Observed event rates 
* Number of events observed if reported. 
 
 
TactiCath™ 
CF 
(n=152) 
TactiCath™ 
TC 
(n=143) 
Zero AF 
Blazer 
Open-
Irrigated 
(n=157) 
Zero AF 
Thermocool 
(n=164) 
Smart AF 
(n=161) 
Design 
RCT 
RCT 
Single 
Device /Procedure Death 
 
 
 
 
 
Atrial esophageal fistula 
 
 
 
 
 
Myocardial Infarction 
 
 
1 (0.6%) 
0 (0.0%) 
 
Cardiac tamponade/ Perforation 
1 (0.66%) 
1 (0.70%) 
4 (2.5%) 
3 (1.8%) 
4 (2.5%) 
Thromboembolism 
 
 
1 (0.6%) 
0 (0.0%) 
 
Stroke/CVA 
 
 
 
 
 
TIA 
 
 
 
 
 
Phrenic nerve paralysis 
 
 
 
 
 
PV Stenosis 
0 (0.0%) 
1 (0.7%) 
1 (0.6%) 
2 (1.2%) 
 
Major Vascular Access/ Bleeding 
Complication 
 
 
2 (1.3%) 
2 (1.2%) 
3 (1.86%) 
Pulmonary or bronchial complication 
 
 
5 (3.2%) 
4 (2.4%) 
 
Pericarditis 
2 (1.3%) 
0 (0.0%) 
1 (0.6%) 
0 (0.0%) 
2 (1.24%) 
Hospitalization 
 
 
 
 
6 (3.72%) 
Heart Block 
 
 
 
 
1 (0.62%) 
Pericardial Effusion 
 
 
 
 
1 (0.62%) 
AF or AFL requiring cardioversion 
(12M) 
 
  
  
  
 
Atrial arrhythmia 
 
 
1 (0.6%) 
1 (0.6%) 
 
All cause death 
 
 
1 (0.6%) 
1 (0.6%) 
 
Events* 
 
 
 
 
17 
Subject level rate 
3 (1.97%) 
2 (1.4%) 
16 (10.2%) 
13 (7.9%) 
16 (9.9%) 

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Table 2 summarizes the event rates consistent with the proposed safety composite 
definition. 
 
Table 2: Observed event rates consistent with the proposed safety composite 
definition (Translated safety rates) 
 
*Number of  subjects with events if reported. 
 
 
Figure 1 Meta-analysis results 
TactiCath™ 
CF 
 (n=152) 
TactiCath™ 
TC 
 (n=143) 
Zero AF 
Blazer Open-
Irrigated 
(n=157) 
Zero AF 
Thermocool 
(n=164) 
Smart AF 
(n=161) 
Design 
RCT 
RCT 
Single 
Device / Procedure Death 
 
 
 
 
 
Atrial esophageal fistula 
 
 
 
 
 
Myocardial Infarction 
 
 
1 (0.6%) 
 
 
Cardiac tamponade/ 
Perforation 
2 (1.3%) 
2 (1.4%) 
4 (2.5%) 
3 (1.8%) 
4 (2.5%) 
Thromboembolism 
 
 
1 (0.6%) 
 
 
Stroke/CVA 
 
 
 
 
 
TIA 
 
 
 
 
 
Phrenic nerve paralysis 
 
 
 
 
 
PV Stenosis 
 
1 (0.7%) 
1 (0.6%) 
2 (1.2%) 
 
Major Vascular 
Access/Bleeding 
Complication 
3 (2.0%) 
3 (2.1%) 
2 (1.3%) 
1 Hematoma 
(Ablation 
procedure) 
1 Sanguineous 
drainage 
2 (1.2%) 
1 AV fistula 
1 Rectus Sheath 
Hematoma 
3 (1.86%) 
Pulmonary or bronchial 
complication 
2 (1.3)  
P. edema 
2 (1.4%) 
P. edema 
5 (3.2%) 
2 Heart failure / 
pulmonary 
edema 
3 Pulmonary 
4 (2.4%) 
Pulmonary 
 
Pericarditis 
2 (1.3%) 
 
1 (0.6%) 
 
3 (1.86%) 
Heart Block 
 
 
 
 
1 (0.62%) 
Event total 
9 (5.9%) 
8 (5.6%) 
14 (8.9%) 
11 (6.7%) 
11 (6.8%) 
Rate * 
7 (4.6%) 
8 (5.6%) 
 
 
11 (6.8%) 

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Figure 1 shows the result of the meta-analysis for combining the safety rates. Based on 
the plot, the upper bound of the 95% confidence interval was estimated to be equal to 9%. 
The proposed performance goal of 14% would reflect an approximately 50% increase in 
risk from the upper bound of the 95% CI. 
 
 
 

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30.0 
APPENDIX D ADAPTIVE DESIGN MAIN STUDY 
Simulation Report for Q-FFICIENCY Study Main Study 
30.1 
Introduction 
This document describes the single-arm trial design for Biosense Webster's pre-market 
clinical evaluation of the QDOT MICRO™ Catheter to demonstrate the acute safety and 
12-months effectiveness. The trial will enroll N=185 subjects. One interim analysis for 
early success will be performed at 6 months after the last patient is enrolled. 
30.1.1 
Endpoints 
30.1.1.1 
Primary Efficacy Endpoint 
The primary effectiveness endpoint is freedom from documented atrial arrhythmia (atrial 
fibrillation (AF), atrial tachycardia (AT) or atrial flutter (AFL)) episodes at Month 12 
(that is, during the 9-month post-blanking period). The proportion of patients that are free 
from failure at Month 12 will be compared against a performance goal (PG) of 50%. 
30.1.1.2 
Primary Safety Endpoint 
The primary safety endpoint is occurrence of primary adverse events(PAE) within 7 days 
of an ablation procedure. The PAE rate will be compared against a PG of 14%. PAE 
includes the following AEs and are defined in the protocol: 
• Death 
• Atrio-Esophageal Fistula 
• Cardiac Tamponade/Perforation 
• Myocardial Infarction 
• Stroke / Cerebrovascular Accident 
• Thromboembolism 
• Transient Ischemic Attack 
• Diaphragmatic Paralysis 
• Pulmonary Vein Stenosis 
• Pericarditis 
• Vagal Nerve Injury 
• Major Vascular Access Complication / Bleeding 
30.2 
Adaptive Design 
30.2.1 
Primary Analysis 
The primary goal of the trial is to demonstrate effectiveness and safety. For the trial to be 
successful, both primary safety and effectiveness endpoints must be statistically 
significant relative to their respective PGs. 
 
The effectiveness endpoint will be assessed by testing the hypotheses (assuming early 
success for effectiveness is not achieved):  
 

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𝐻𝐻0: 𝑝𝑝𝐸𝐸≤0.50  vs.  𝐻𝐻𝐴𝐴: 𝑝𝑝𝐸𝐸> 0.50, 
 
where 𝑝𝑝𝐸𝐸 is the proportion of patients free from effectiveness events. 
 
Let 𝑋𝑋 be the number of patients that are failure-free through 12 months. We model the 
number of patients free from an event as 
 
𝑋𝑋∼Binomial(𝑛𝑛, 𝑝𝑝𝐸𝐸), 
 
where 𝑛𝑛 is the number of patients. We use a vague Beta(1, 1) prior distribution for 𝑝𝑝𝐸𝐸. 
Then the posterior distribution is  
 
(𝑝𝑝𝐸𝐸|𝑥𝑥, 𝑛𝑛) ∼Beta(1 + 𝑥𝑥, 1 + 𝑛𝑛−𝑥𝑥). 
 
Similarly, the hypothesis test for the safety endpoint is:  
 
𝐻𝐻0: 𝑝𝑝𝑆𝑆≥0.14  vs.  𝐻𝐻𝐴𝐴: 𝑝𝑝𝑆𝑆< 0.14, 
 
where 𝑝𝑝𝑆𝑆 is the 7-day PAE. We model the number of patients with PAEs as 
 
𝑌𝑌∼Binomial(𝑛𝑛, 𝑝𝑝𝑆𝑆) 
 
with a vague Beta(1, 1) prior distribution on 𝑝𝑝𝑆𝑆. 
 
Assuming early success for effectiveness is not achieved, the trial will be considered a 
success if BOTH 
1. Pr(𝑝𝑝𝐸𝐸> 0.5|𝑥𝑥, 𝑛𝑛) > 0.9775 AND 
2. Pr(𝑝𝑝𝑆𝑆< 0.14|𝑦𝑦, 𝑛𝑛) > 0.975. 
 
These thresholds control the overall Type I error rate for the trial below one-sided 2.5% 
(see Section 29.5.1 of this report for additional discussion of Type I error control). 
 
30.2.2 
Interim Analyses for Early Success 
One interim analysis is planned for an early success claim. The interim will occur 6 
months after enrollment is complete; that is, 6 months before the final analysis. For the 
safety endpoint, the outcome for all patients will be known at the time of the interim 
analysis and therefore the primary safety analysis will be performed at the time of the 
interim analysis. It should be noted that because these two tests are identical there will 
not be an increase in type-I error.  
 
At the interim analysis, the trial will declare early success if: 
1. The safety objective is met. 

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2. Posterior probability of the effectiveness proportion 𝑝𝑝𝐸𝐸 being greater than 50% is  
greater than 0.9975. 
3. . 
30.2.3 
Longitudinal Modeling for Effectiveness 
 
For effectiveness, the time-to-failure during the 9-month(39 weeks) post-blanking period 
is modeled by using a piecewise exponential model. The model has three distinct time 
intervals: (0, 2], (2, 8], and (8, 39] weeks. Failure times during each interval is 
exponentially distributed, with different hazard rates in each segment. The model is:  
 
 
 
𝑓𝑓(𝑡𝑡) = exp(−𝑡𝑡ℎ(𝑡𝑡)), 
 
 where  
ℎ(𝑡𝑡) = ൝
ℎ1
0 < 𝑡𝑡≤2;
ℎ2
2 < 𝑡𝑡≤8;
ℎ3
8 < 𝑡𝑡≤39.
 
 
These intervals are based on a model used in the ThermoCool Pivotal trial. A vague 
Gamma(1, 1) prior distribution will be used for each ℎ in the model.  
 
Given hazard rates ℎ1, ℎ2 , and ℎ3, the failure-free rate at 12 months 𝑝𝑝𝐸𝐸 can  then be 
estimated 
by 
𝑝𝑝𝐸𝐸= exp(−[2ℎ1 + (8 −2)ℎ2 + (39 −8)ℎ3]). 
 
At the interim, the total number of primary effectiveness events and the total 
subject exposure time will be used to update the vague Gamma prior and obtain the 
posterior Gamma distribution for each segment. Then 10,000 random hazard rates will be 
sampled from the posterior distribution for each segment and each triplet set of hazard 
rates will be used to calculate 𝑝𝑝𝐸𝐸. The distribution of 𝑝𝑝𝐸𝐸 is estimated based on the 10,000 
calculated 𝑝𝑝𝐸𝐸𝑠𝑠. If the probability of 𝑝𝑝𝐸𝐸 being greater than 50% is greater than 
0.9975(99.75%), the trial will declare early success. 
30.3 
Simulation Scenarios 
The operating characteristics of this trial were determined through trial simulation. We 
hypothesized several scenarios for the underlying rates for the effectiveness and safety 
endpoints and simulated the entire trial multiple times under each scenario. In each 
virtual trial, the interim analysis was conducted according to the pre-specified rules, and 
results were tracked for each trial, including whether the trial was successful on each 
endpoint individually and on both endpoints, whether trial success was achieved early, 
etc. This section describes the parameters that were used to simulate subject-level data for 
the virtual trials. 
 
30.3.1 
Effectiveness Profiles 
In order to simulate the effectiveness outcome for a virtual subject, we need to simulate 
whether the subject has a failure and when that failure occurs. As previously discussed in 
section 29.2.3, a piecewise exponential time-to-failure model is assumed and calibrated to 

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have a particular failure rate (1 −𝑝𝑝𝐸𝐸) at the end of follow-up. The profiles are 
constructed by taking advantage of the relationship: 
  
𝑝𝑝𝐸𝐸= exp(−[2ℎ1 + (8 −2)ℎ2 + (39 −8)ℎ3]), 
 
where 𝑝𝑝𝐸𝐸 is the failure-free rate at 12-months. Previous study of catheter is assumed to 
estimate the hazard rates for the three pieces. From ThermoCool SSED, the reported 
hazard rates have the following pattern:  
 
ℎ1 = (38.06)ℎ3; 
ℎ2 = (1.71)ℎ3; 
ℎ3 = (1)ℎ3. 
 
To simulate data, we use the above multiplicative factors from ThermoCool and then find 
a value for ℎ3, such that when multiplied by each of the assumed rates for the three-time 
intervals, the failure-free rate at 12 months (39 weeks following 13weeks blanking 
period) matches the desired scenarios. Table 1 shows the derived hazard rates that were 
used to simulate data for a range of assumed failure-free rates.  
 
Table 1: Parameters to generate failure times 
 
Hazard Rate (h) 
Failure-free Rate 
ℎ1 
ℎ2 
ℎ3 
0.50 
0.2248 
0.0101 
0.0059 
0.55 
0.1938 
0.0087 
0.0051 
0.60 
0.1656 
0.0074 
0.0044 
0.65 
0.1397 
0.0063 
0.0037 
0.70 
0.1157 
0.0052 
0.0030 
0.99 
0.0032 
0.0001 
0.0001 
 
In order to compute the predictive probability of success for the effectiveness endpoint, 
2500 imputations were performed for each subject with missing outcome in the 
simulations 
30.3.2 
Adverse Event Rate Profiles 
The 7-day PAE outcome for each subject is simulated as a Bernoulli random variable, 
with scenarios defined by the rates shown in Table 2. 
 
Table 2: Parameters to generate PAE outcomes 
True AE Rate 
0.01 
0.07 

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0.08 
0.10 
0.12 
0.14 
30.3.3 
Enrollment Rates 
We simulate three scenarios for the enrollment rate. The "expected" scenario assumes 
that full enrollment of N=185 would take approximately 7 months on average. The “fast” 
and "slow" scenarios assume that full enrollment would take, on average, 6 and 8 months 
respectively. Table 3 shows the rates for each scenario. 
 
Table 3: Monthly enrollment rates 
 
30.3.4 
Attrition Rate Profile 
For each subject, a time-to-withdrawal is simulated from an exponential distribution with 
a 5% dropout rate for the safety outcome and a 12% dropout rate for the effectiveness 
outcome. Both dropout rates are per year of follow-up. If a subject experiences a failure 
prior to their withdrawal time, then their outcome is recorded as a failure. A subject is 
censored at the time of withdrawal if the simulated withdrawal time is prior to the 
simulated failure time. 
 
30.4 
Operating Characteristics 
For the scenarios described above, we simulate multiple virtual trials and track the 
behavior of each trial, including the final outcome of the trial, whether success was 
declared early, etc. The results for Type I Error are based on 10,000 simulated virtual 
trials per scenario. For all other scenarios, 5,000 virtual trials were simulated. 
30.4.1 
Type I Error Control 
This section summarizes the probability of a successful trial under the null hypotheses for 
both safety and effectiveness.  Table 4 summarizes Type I error rates for the trial under 
various scenarios; that is, the probability of declaring success on both endpoints under 
two scenarios: (1) Assuming the true failure-free rate is 50% with various range of the 
true PAE rates; and (2) Assuming the true PAE rate is 14% with various range of the true 
failure-free rates.  
 
Month 
Rate(patients/month) 
1 
2 
3 
4 
5 
6 
7 
8 
Expected 
5 
15 
25 
30 
40 
40 
30 
 
Fast 
5 
20 
35 
45 
45 
35 
 
 
Slow 
2 
10 
20 
30 
35 
35 
35 
18 

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The scenario that is expected to have the largest Type I error rate is either when the true 
PAE rate is 14% and the device is assumed to be effective (true failure-free rate is 99%) , 
or when the true failure-free rate is 50% and the device is assumed to be safe (true PAE 
rate is 1%). The table shows the largest Type I error rate for the trial in the simulations 
was 0.023, still below the 2.5% threshold. 
 
In adaptive trials, the enrollment rate to the trial directly impacts the amount of 
information that is available at the time of the interim and may influence the probability 
of stopping at the interim.  In this simulation, however, there is little to no impact of 
different enrollment rates on Type I error, and notably, all values are below 2.5%. 
 
Table 4: Type I error rate 
 
 
                       Pr(Declaring Success) 
 Failure-free 
Rate 
PAE Rate 
Expected     
Fast    
Slow     
0.50 
0.01 
0.011 
0.007 
0.010 
0.50 
0.07 
0.008 
0.009 
0.007 
0.50 
0.08 
0.007 
0.007 
0.006 
0.50 
0.10 
0.004 
0.005 
0.004 
0.50 
0.12 
0.001 
0.001 
0.001 
0.50 
0.14 
0.000 
0.000 
0.000 
0.55 
0.60 
0.14 
0.14 
0.003 
0.012 
0.004 
0.013 
0.003 
0.012 
0.65 
0.14 
0.019 
0.021 
0.019 
0.70 
0.14 
0.021 
0.021 
0.020 
0.99 
0.14 
0.023 
0.021 
0.023 
 
30.4.2 
Probability of Success 
For the full range of effectiveness and safety scenarios, this section summarizes the 
probability of trial success for the expected enrollment rate. Table 5 summarizes the 
probability of success in the following ways: 
 
• Both: the proportion of virtual trials that were successful (on both endpoints) 
either at an interim or at the final analysis 
• Effectiveness: the proportion of trials that were successful on the effectiveness 
endpoint 
• Safety: the proportion of trials that were successful on the safety endpoint 

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• Early: the proportion of trials that met the criteria for success (on both endpoints) 
at the interim analysis 
• Final: the proportion of trials that met the criteria for success (on both endpoints) 
at the final analysis when the early success is not declared.  
 
If the true PAE rate is 7% and the true failure-free rate is 65%, the trial has approximately 
81.7% power. Under this scenario, 64.8% of the simulated trials claimed success at the 
interim and an additional 16.9% of trials achieved success at the final analysis. 
Table 5: Pr(Declaring Success) (Expected Enrollment) 
 
Failure-free 
Rate 
 
Pr(Declaring Success) 
 
PAE Rate 
Both 
Effectiveness 
Safety 
Early 
Final 
0.50 
0.07 
0.008 
0.010 
0.856 
0.002 
0.007 
 
0.08 
0.007 
0.010 
0.696 
0.001 
0.006 
 
0.1 
0.004 
0.009 
0.342 
0.001 
0.003 
 
0.12 
0.001 
0.010 
0.105 
0.000 
0.001 
 
0.14 
0.000 
0.009 
0.021 
0.000 
0.000 
0.55 
0.07 
0.144 
0.169 
0.853 
0.046 
0.098 
 
0.08 
0.114 
0.161 
0.710 
0.035 
0.079 
 
0.1 
0.058 
0.160 
0.352 
0.018 
0.040 
 
0.12 
0.016 
0.148 
0.101 
0.006 
0.010 
 
0.14 
0.003 
0.153 
0.020 
0.001 
0.002 
0.60 
0.07 
0.530 
0.625 
0.847 
0.270 
0.261 
 
0.08 
0.439 
0.613 
0.705 
0.225 
0.214 
 
0.1 
0.209 
0.613 
0.340 
0.104 
0.105 
 
0.12 
0.063 
0.625 
0.104 
0.030 
0.033 
 
0.14 
0.012 
0.617 
0.021 
0.006 
0.006 
0.65 
0.07 
0.817 
0.952 
0.860 
0.648 
0.169 
 
0.08 
0.661 
0.953 
0.696 
0.522 
0.138 
 
0.1 
0.325 
0.951 
0.338 
0.260 
0.064 
 
0.12 
0.099 
0.954 
0.104 
0.078 
0.021 
 
0.14 
0.019 
0.948 
0.021 
0.015 
0.004 
0.70 
0.07 
0.852 
0.999 
0.853 
0.824 
0.028 
 
0.08 
0.699 
0.999 
0.700 
0.680 
0.019 
 
0.1 
0.347 
0.998 
0.347 
0.336 
0.011 
 
0.12 
0.107 
0.999 
0.107 
0.104 
0.003 
 
0.14 
0.021 
0.999 
0.021 
0.020 
0.001 
 

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30.4.3 
Sensitivity to Enrollment Rate 
In this section, we repeat the operating characteristics of the previous section under 
different trial enrollment rates. Table 6 and Table 7 show the probability of success for 
the 5 different categories under the fast and slow enrollment rates respectively. 
 
In this simulation, there is little to no impact from different enrollment rates on overall 
power, and notably, all values are about 81.7% when the true PAE rate is 7% and the true 
failure-free rate is 65%. However, it seems there is some impact on the early success rate 
for different enrollment rates since the amount of information available at the time of the 
interim is changed according to the enrollment rate. If the enrollment is slower than 
expected, the trial has a little higher ability to reach a success decision before the final 
analysis. With the fast enrollment, the trial has a lower ability to reach early success. 
 
Table 6: Pr(Declaring Success) (Fast Enrollment) 
 
 
Failure-free 
Rate 
 
Pr(Declaring Success) 
 
PAE Rate 
Both 
Effectiveness 
Safety 
Early 
Final 
0.50 
0.07 
0.009 
0.010 
0.855 
0.002 
0.007 
 
0.08 
0.007 
0.010 
0.706 
0.001 
0.006 
 
0.1 
0.005 
0.010 
0.342 
0.001 
0.004 
 
0.12 
0.001 
0.010 
0.100 
0.000 
0.001 
 
0.14 
0.000 
0.009 
0.023 
0.000 
0.000 
0.55 
0.07 
0.132 
0.155 
0.861 
0.040 
0.092 
 
0.08 
0.107 
0.151 
0.705 
0.030 
0.077 
 
0.1 
0.054 
0.154 
0.345 
0.016 
0.039 
 
0.12 
0.015 
0.144 
0.102 
0.005 
0.009 
 
0.14 
0.004 
0.153 
0.021 
0.001 
0.003 
0.60 
0.07 
0.539 
0.620 
0.866 
0.237 
0.302 
 
0.08 
0.453 
0.631 
0.712 
0.208 
0.245 
 
0.1 
0.216 
0.629 
0.336 
0.095 
0.121 
 
0.12 
0.063 
0.616 
0.100 
0.026 
0.037 
 
0.14 
0.013 
0.618 
0.022 
0.006 
0.008 
0.65 
0.07 
0.818 
0.951 
0.859 
0.621 
0.196 
 
0.08 
0.669 
0.957 
0.700 
0.503 
0.166 
 
0.1 
0.316 
0.952 
0.330 
0.239 
0.076 
 
0.12 
0.097 
0.953 
0.101 
0.073 
0.024 
 
0.14 
0.021 
0.954 
0.022 
0.016 
0.006 
0.70 
0.07 
0.847 
0.999 
0.848 
0.817 
0.030 

Q-fficiency  
 
 
 
 
 
 
Protocol# BWI_2017_07 
 
Biosense Webster, Inc 
 
Version 5.0 – Feb 3, 2021 
CONFIDENTIAL 
Page 135 of 135 
 
 
0.08 
0.683 
0.999 
0.684 
0.658 
0.025 
 
0.1 
0.347 
0.999 
0.348 
0.334 
0.014 
 
0.12 
0.102 
0.999 
0.102 
0.099 
0.003 
 
0.14 
0.021 
0.999 
0.021 
0.021 
0.000 
 
 
 
 
 Table 7: Pr(Declaring Success) (Slow Enrollment) 
 
Failure-free 
Rate 
 
Pr(Declaring Success) 
 
PAE Rate 
Both 
Effectiveness 
Safety 
Early 
Final 
0.50 
0.07 
0.007 
0.009 
0.862 
0.002 
0.006 
 
0.08 
0.006 
0.008 
0.708 
0.002 
0.004 
 
0.1 
0.004 
0.010 
0.334 
0.002 
0.002 
 
0.12 
0.001 
0.008 
0.101 
0.000 
0.001 
 
0.14 
0.000 
0.008 
0.022 
0.000 
0.000 
0.55 
0.07 
0.136 
0.155 
0.868 
0.051 
0.085 
 
0.08 
0.111 
0.158 
0.694 
0.038 
0.072 
 
0.1 
0.053 
0.155 
0.335 
0.015 
0.038 
 
0.12 
0.015 
0.146 
0.102 
0.005 
0.010 
 
0.14 
0.003 
0.146 
0.023 
0.001 
0.003 
0.60 
0.07 
0.546 
0.632 
0.857 
0.299 
0.247 
 
0.08 
0.434 
0.623 
0.691 
0.238 
0.195 
 
0.1 
0.206 
0.612 
0.337 
0.113 
0.093 
 
0.12 
0.064 
0.610 
0.099 
0.035 
0.029 
 
0.14 
0.012 
0.609 
0.020 
0.007 
0.006 
0.65 
0.07 
0.816 
0.955 
0.855 
0.670 
0.146 
 
0.08 
0.676 
0.961 
0.705 
0.560 
0.116 
 
0.1 
0.327 
0.954 
0.342 
0.262 
0.065 
 
0.12 
0.101 
0.952 
0.104 
0.083 
0.018 
 
0.14 
0.019 
0.948 
0.020 
0.015 
0.004 
0.70 
0.07 
0.850 
1.000 
0.850 
0.834 
0.016 
 
0.08 
0.700 
0.999 
0.700 
0.685 
0.015 
 
0.1 
0.324 
0.999 
0.324 
0.318 
0.007 
 
0.12 
0.097 
0.999 
0.097 
0.095 
0.002 
 
0.14 
0.020 
0.999 
0.020 
0.020 
0.000